The copper-chelating, immunological, and antifibrotic effects of D-penicillamine indicated that it might be suitable for the treatment of primary biliary cirrhosis (PBC). In a randomised clinical trail, 55 PBC patients received penicillamine (600 mg daily), and 32 received a placebo. Drug reactions developed in 16 patients on penicillamine. All deaths occurred in patients with stage 3 or 4 (late stage) liver histology on entry to the study. 5 (14%) of 37 penicillamine-treated patients and 10 (43%) of 23 placebo patients have died (p less than 0.01). Improvement in survival only became evident after 18 months. Survivors in the penicillamine group demonstrated a significant fall in serum aspartate transaminase, serum immunoglobulins, and liver copper concentrations. On follow-up liver biopsy 12-72 months (median 33) after joining the study, 21% of penicillamine-treated patients had less pronounced inflammation and piecemeal necrosis, whereas there had been no improvement in patients on placebo (p less than 0.02). Penicillamine did not retard the histological evolution of the liver disease from the early prefibrotic stages to the late fibrotic or cirrhotic stages. Both the copper-chelating and immunological effects of penicillamine are probably important in improving survival. The excellent prognosis of patients with PBC in its early histological stages, and the failure of penicillamine to prevent histological progression from early to late stages, suggests that penicillamine treatment should not be given to patients with PBC in the early (stage 1 or 2) histological phase of the disease. Penicillamine treatment is recommended in patients once liver biopsy has demonstrated histological results typical of late stage 3 or 4 PBC.

A randomised, double-blind, placebo controlled study of morbidity and mortality was carried out using heparin, atenolol, and a combination of both drugs, in 214 patients with the intermediate coronary syndrome. During the trial period, transmural myocardial infarction developed in 9 (17%) out of 54 patients on placebo, 8 (13%) out of 60 on atenolol, 1 (2%) out of 51 on heparin, and 2 (4%) out of 49 on heparin and atenolol combined (p = 0.024). The improved prognosis in the heparin-treated patients was was maintained at follow-up. All five deaths occurred among patients who did not receive heparin. These results show that intravenous heparin therapy was of benefit in preventing myocardial infarction in patients with the intermediate coronary syndrome.

In 28 of 53 patients with a palpable abdominal mass computed tomography (CT) was used as the initial imaging technique, and conventional imaging was used in the remaining 25 patients. The diagnosis was established more quickly in the CT group, and the period of inpatient investigation was shorter. The cost of imaging investigations was higher for the CT group, but this difference was small when compared with the difference in cost of inpatient stay. CT seems accurate in the investigation of a palpable abdominal mass and particularly useful in excluding a pathological cause. The need for the latter is emphasised by the fact that no lesion could be found in 23 of the 53 patients.

In a placebo-controlled, cross-over study, thirty-seven puerperal women with inadequate production of breast-milk were treated with 5, 10, or 15 mg of metoclopramide three times a day for 2 weeks. Doses of 10 or 15 mg significantly raised maternal serum prolactin; they also increased breast-milk secretion by 42.5 +/- 34.7 (SD) ml and 50.0 + 35.9 ml per feed, respectively. This effect was unrelated to the phase of the puerperium during which treatment was started. The increase in milk secretion was associated with a decreased need for supplementary feeds, and 33% of the infants of these mothers needed no supplementary feeds during treatment. 5 mg doses did not stimulate prolactin milk secretion. Although placebo had no objective effect on the milk yield, 24% of the women judged its effect to be good, and 89% of women on metoclopramide reported a good effect. Seven women on metoclopramide and three women on the placebo complained of slight side-effects. No adverse effects upon the infants were observed. Metoclopramide therapy may be useful for improving poor lactation.

Four treatments for sciatic symptoms--traction, exercises, manipulation, and corset--were assessed in a randomised controlled trial in 322 outpatients. The design was factorial. There were thus sixteen treatment groups, enabling a comparison of combinations of methods as well as of individual methods. Treatment lasted for four weeks. Patients were reviewed at the end of this period and at four and sixteen months after entry to the trial. Progress was measured by the patient's account of symptomatic improvement or deterioration and by return to work or normal activities. At four weeks each of the treatments was associated with a small degree of benefit over and above the high rate of spontaneous improvement. For manipulation, the benefit was statistically significant on one of the scales used to measure progress. There was a significant increase in symptomatic improvement with increasing numbers of treatments used in combination. This was complemented by a clear tendency for those who had received fewer types of treatment during the trial to have further treatment in the ensuing three months. There were no beneficial effects of treatment detectable at four or sixteen months. In the short-term, active physiotherapy with several treatments appears to be of value in the outpatient management of patients with sciatic symptoms, but it does not seem to confer any longer-term benefit.

30 patients with active classical rheumatoid arthritis affecting the knee took part in a 12-week double-blind trial in which intra-articular injections of orgotein (4 mg/week for 6 weeks) were compared with intra-articular aspirin 4 mg/week for 6 weeks. After 12 weeks clinical and biochemical assessments showed that orgotein was superior to aspirin. Clinical response was measured in terms of the cumulative rheumatoid activity index (RAI) which was based on scores for morning stiffness, range of flexion, pain and 25-foot (7.5 m) walking time. Treatment with orgotein resulted in significant improvement of the RAI; the improvement correlated with findings on knee-joint scanning which showed reduced mean uptake of 99mTc-pyrophosphate. After intra-articular orgotein injections, synovial fluid IgM and IgG rheumatoid factor levels fell significantly; so did prostaglandin E2 formation and lactate dehydrogenase activity. The changes in the synovial fluid suggest that the anti-inflammatory properties of orgotein may lie in its effect on proliferating synovia.

In a multicentre trial to compare the ability of a combination of acetylsalicylic acid and dipyridamole (1050 mg + 150 mg/day, group A) to prevent recurrence of transient ischaemic attacks (TIA) with that of pentoxifylline (1200 mg/day, group B), 36 patients received the combination and 30 pentoxifylline. There was no statistically significant difference between the groups as regards age, sex, blood pressure, site of origin of TIA, and incidence of other risk factors. The incidence of recurrent TIAs during 1 year of follow-up was 28% in group A and 10% in group B; this difference was significant (p less than 0.05). The incidence of permanent strokes was similar in the two groups but distinctly lower (4.5%) than that usually reported after untreated TIA.

Placebo or propranolol was given randomly of two groups of 12 adults with cirrhosis who had recently held from oesophageal or gastric varices or from acute gastric erosions. During three months' follow-up 5 patients in the placebo and none in the propranolol group had recurrent gastrointestinal bleeding.

The effect of oxygen on breathlessness and exercise tolerance was examined in "pink and puffing" patients with fixed airways obstruction. When breathing oxygen, patients were less breathless and walked further. This was true whether the cylinder was carried by the patient or by an assistant. It was not possible to identify those patients who would benefit most. The best method of assessing improvement was by comparing breathlessness on a standardised progressive exercise test on a treadmill. Four patients had a greater than 30% reduction in breathlessness on submaximum exercise when breathing oxygen. Breathing oxygen for five or fifteen minutes before exercise but not during exercise (predose) resulted in a similar improvement in exercise tolerance. For short periods of exercise predosing with oxygen provides a convenient alternative to continuous oxygen. For longer periods of exercise the benefits of portable oxygen in selected patients have been previously underestimated.

In a double-blind trial prostacyclin was given to 12 of 23 patients undergoing coronary vein grafting. The treatment group showed a preservation of platelet number and function, with a halving of blood loss in the first 18 h postoperatively. The heparin sparing effect of prostacyclin was confirmed, as were the vasodilator effects which were not troublesome.

A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in 138 haemodialysis patients in a placebo-controlled randomised double-blind trial. In an interim analysis, hepatitis B infections were observed in 21% of the vaccine group and 45% of the placebo group (p less than 0.02). 2 of the infections in the vaccine group and 12 of the infections in the placebo group occurred after the third injection. 60% of the vaccine recipients had an immune response. 4 months after the first injection the mean titre of anti-HBs was 120 mlU/ml.

The effect of five days of antibiotic prophylaxis with cefazolin injections (beginning just before surgery) on postoperative infections (beginning just before surgery) on postoperative infectious complications was evaluated in a double-blind, randomised, placebo-controlled trial in nine centres on 2137 patients undergoing hip replacement. Antibiotic prophylaxis reduced the number of hip infections significantly from 3.3% (placebo) to 0.9% (cefazolin). Positive peroperative blood samples and positive bacteriological examination of the drain were risk factors for hip infection but the prognostic value of obesity, diabetes, or previous hip surgery was not confirmed. Development of a urinary infection was not related to hip infection. Hip infections were less common in the four centres with hypersterile operating theatres, and the benefits of prophylactic antibiotics were restricted to patients having hip replacement operations in conventional theatres.

The effects of intrarectal metronidazole and intraincisional povidone iodine on sepsis after emergency appendicectomy were compared in a double-blind randomised controlled trial in 496 patients. Wound sepsis occurred in 12.3% of metronidazole-treated patients compared with 24% in the povidone-iodine group and 23.5% in an untreated control group. The metronidazole-treated patients left hospital approximately 2 days earlier than patients in the other two groups. They returned to work sooner and receiver fewer visits from the district nursing service. A short six-dose course of metronidazole significantly reduces the wound-infection rate in patients over the age of 12 undergoing emergency appendicectomy. If the clinical and economic benefits of metronidazole shown by this study are confirmed, the drug should be considered for routine use in emergency appendicectomy.

Intravenous administration of nicotinic acid (25 mg), resulted in a readily reproducible facial flush. The development of this flush was inhibited by two prostaglandin synthetase inhibitors, indomethacin and benorylate, but was not affected by the administration of the opiate receptor antagonist naloxone. Indomethacin, the agent with the greater anti-prostaglandin activity, was markedly more effective than benorylate in inhibiting the nicotinic-acid-induced rise in facial temperature. These findings will be useful in the in vivo assessment of the activity of prostaglandin inhibitors.

The effects of single-donor (SD) and multiple-donor (MD) platelet transfusions in 34 cancer patients with severe thrombocytopenia and haemorrhages were compared in a randomised study. Platelet recovery values in both groups were similar after the first transfusion. After the second transfusion platelet recovery values were significantly better in those receiving SD transfusions. Platelet recovery values gradually declined with subsequent MD transfusions. These results suggest early alloimmunisation in the MD transfused patients only. MD transfusions were estimated to be no longer effective after about nine transfusions. Platelet recovery values were better indicators of early sensitisation than was the lymphocytotoxicity test. Restriction of the number of donors per transfusion may postpone the development of refractoriness to random-donor platelet transfusions in thrombocytopenic patients.

Ninety-eight patients with advanced ovarian cancer took part in a prospective, randomised trial comparing low-dose cisplatin and chlorambucil with low-dose cisplatin, chlorambucil, and doxorubicin. After 4 years response rates (greater than 50%) and proportion of complete remissions (28%) were similar in both groups. Median duration of remission was longest in the complete remitters, being 31 months in those having cisplatin and chlorambucil, and 24 months in those having doxorubicin as well.