144 patients with severe rheumatoid arthritis from six centres were randomised to receive oral cyclosporin or placebo for 6 months. The initial daily dose of cyclosporin was 2.5 mg/kg, which was increased cautiously with monitoring of serum cyclosporin levels and creatinine; the mean stabilisation dose was 3.8 mg/kg. There were significant improvements in the cyclosporin-treated patients compared with the controls in the major outcomes of reduction of active joints (23% improvement), pain (24%), and functional status (16%); global improvement was 27%. In the cyclosporin group serum creatinine increased by a mean of 15.6 mumols/l and mean arterial blood pressure by 6.27 mmHg; these increases were controlled in all but 2 patients by dose adjustment without withdrawal from the study.

To assess the value of autolymphocyte therapy (ALT) in the treatment of metastatic renal-cell carcinoma, 90 patients were randomised to receive every month for six months oral cimetidine plus an infusion of autologous peripheral blood lymphocytes activated in vitro by a previously generated autologous lymphokine mixture, or cimetidine alone. The median follow-up was 15 months. Survival time for the autolymphocyte group was approximately 2.5 times that for the cimetidine group (p = 0.008). Patients who had greater than 500 pg interleukin-1 (IL-1) per ml autologous lymphokine mixture had a six-fold survival advantage over those with less than 500 pg/ml (p less than 0.00005). Men treated with ALT had a four-fold survival advantage (p = 0.001) over men who received cimetidine only. Infusion of the cultured autolymphocytes was accompanied by mild, self-limited fever in 11 of the 45 ALT patients, and by only one instance in which fever was accompanied by tachypnoea and hypotension.

Bilateral simultaneous blood samples were taken from the inferior petrosal sinuses of nine patients with Cushing's disease for measurement of adrenocorticotropin (ACTH), vasopressin (AVP), prolactin, growth hormone, luteinising hormone (LH), and follicle stimulating hormone (FSH). Inter-sinus gradients for ACTH (range 3.3-18.2) and AVP (2.0-375) correctly lateralised the microadenoma in seven of these patients. One additional patient showed an increased gradient for AVP but not ACTH on the side of the tumour. The correlation between the AVP and ACTH concentrations in the petrosal sinus draining the microadenoma was significant. Petrosal sinus plasma concentrations of prolactin and growth hormone were also significantly higher on the side of the tumour than on the non-tumour side. Evidence against a non-specific tumour effect on the secretion of all pituitary hormones was the fact that in most cases the gradients for LH and FSH were not significant. It is proposed that increased delivery of AVP to part of the pituitary may result from an aberrant blood supply, and that AVP may interact with corticotropin releasing factor to promote tumour growth and ACTH release.

59 elderly patients (mean age 82) with femoral neck fractures were randomised into two groups. 27 patients received daily an oral nutrition supplement (250 ml, 20 g protein, 254 kcal) for a mean of 32 days; 32 patients acted as controls. On admission most patients had nutritional deficiencies. Despite being offered adequate quantities, nutritional requirements were not met during the hospital stay. Clinical outcome was significantly better in the supplemented group (56% favourable course vs 13% in controls) during the stay in the convalescent hospital. The rates of complications and deaths were also significantly lower in supplemented patients (44% vs 87%). 6 months after the fracture the rates of complications and mortality were significantly lower in supplemented patients (40% vs 74%). The median duration of hospital stay was significantly shorter in the supplemented group (24 vs 40 days). Thus the clinical outcome of elderly patients with femoral neck fracture can be improved by once daily dietary oral supplementation.

10 patients with frequent and severe bleeding from gastrointestinal vascular malformations took part in a double-blind, placebo-controlled, cross-over trial of a daily dose of 0.05 mg ethinyloestradiol plus 1 mg norethisterone given by mouth. Each arm of the trial lasted 6 months. Oestrogen-progesterone significantly decreased the transfusion need from 10.9 to 1.1 units packed cells (p less than 0.003). While on oestrogen-progesterone 2 of 9 patients required transfusions (mean 1.1 units packed cells per patient over 6 months), whereas all patients had to be transfused while on placebo (mean 10.9 units per patient over 6 months; p = 0.002 for number of patients). No significant excess of side-effects was noted with the active agents. The findings indicate that oestrogen-progesterone is an effective treatment for severely bleeding gastrointestinal vascular malformations.

In a double-blind randomised trial an infusion of doxapram, 2 mg per min for 6 h immediately after surgery and repeated on the first postoperative day, or the same volume of saline, was given to 39 patients who underwent upper abdominal surgery and who were at high risk of postoperative day, or the same volume of saline, was given to 39 patients who underwent upper abdominal surgery and who were at high risk of postoperative pulmonary complications. The patients were assessed pre-operatively and during the first 5 postoperative days by physical examination, spirometry, blood-gas analysis, and chest radiography. Postoperative pulmonary complications were defined as temperature over 38 degrees C for 2 days, abnormal auscultation, pathological radiography, and/or productive cough. Data from 16 patients per group were analysed. Significantly more patients in the placebo group had three criteria of postoperative pulmonary complication compared with the doxapram group (63% vs 19%). The doxapram group also had higher PaO2 postoperatively.

No-scalpel vasectomy was developed to increase acceptability of vasectomy by elimination of the fear of the incision. Although this method has been used for over 8,000,000 men, the technique is largely unknown in developed countries. During the King's birthday vasectomy festival no-scalpel vasectomy was compared with standard incisional vasectomy in 1203 patients. An average of 57 procedures per day could be done by each physician with the no-scalpel method, compared to 33 procedures with the standard method (p less than 0.001). The complication rate was 0.4/100 procedures for no-scalpel vasectomy compared with 3.1/100 for standard vasectomy (p less than 0.001). No-scalpel vasectomy is a rapid and economic alternative to standard vasectomy, with fewer complications and increased patient acceptability.

An infusion of calcitonin-gene-related peptide (CGRP) at progressively increased concentrations was given to 15 patients with neurological deficits after intracranial aneurysm surgery for subarachnoid haemorrhage. In 9 of the patients the deficits, quantified by a modified Glasgow coma scale, improved with no adverse effects; after a placebo infusion only 2 of the 15 patients showed improvement. If CGRP can reverse cerebral ischaemia after early intracranial aneurysm surgery, its use may improve the safety of such early surgery, remove the need for late surgery with its increased risk of death from rebleeding, and reduce overall morbidity and mortality of aneurysmal subarachnoid haemorrhage.

There are 14 unconfounded randomised trials of antihypertensive drugs (chiefly diuretics or beta-blockers): total 37,000 individuals, mean treatment duration 5 years, mean diastolic blood pressure (DBP) difference 5-6 mm Hg. In prospective observational studies, a long-term difference of 5-6 mm Hg in usual DBP is associated with about 35-40% less stroke and 20-25% less coronary heart disease (CHD). For those dying in the trials, the DBP difference had persisted only 2-3 years, yet an overview showed that vascular mortality was significantly reduced (2p less than 0.0002); non-vascular mortality appeared unchanged. Stroke was reduced by 42% SD 6 (95% confidence interval 35-50%; 289 vs 484 events, 2p less than 0.0001), suggesting that virtually all the epidemiologically expected stroke reduction appears rapidly. CHD was reduced by 14% SD 5 (95% CI 4-22%; 671 vs 771 events, 2p less than 0.01), suggesting that just over half the epidemiologically expected CHD reduction appears rapidly. Although this significant CHD reduction could well be worthwhile, its size remains indefinite for most circumstances (though beta-blockers after myocardial infarction are of substantial benefit). At present, therefore, a sufficiently high risk of stroke (perhaps because of age, blood pressure, or, in particular, history of cerebrovascular disease) may be the clearest indication for antihypertensive treatment.

30 patients with active Crohn's disease, mean Crohn's Disease Activity Index 301 (SE 32), who would otherwise have been treated with steroids, were randomised to receive for 4 weeks either an elemental diet ('Vivonex') (n = 16) or a polymeric diet ('Fortison') (n = 14). Assessment on days 10 and 28 showed that clinical remission occurred in 5 (36%) of the 14 patients on fortison compared with 12 (75%) of the 16 patients assigned to vivonex. The difference in remission rate was significant (p less than 0.03). Dietary treatment resulted in little change in the nutritional state and various laboratory indices of activity over a 4 week period despite clinical improvement. Polymeric diets do not seem to offer an effective therapeutic alternative to elemental diets in patients with acute exacerbations of Crohn's disease.