The prognostic value of the aminoterminal propeptide of type III procollagen (P3NP) was investigated in 63 patients with primary biliary cirrhosis (PBC) followed for up to 87 months. No patient with an initially normal serum P3NP level died during the study; survival was significantly worse with increasing serum P3NP levels. Cox multivariate analysis confirmed that serum P3NP was an independent prognostic variable. Positive correlations were found between serum P3NP and histological stage, pericellular fibrosis, piecemeal necrosis, and serum concentrations of alanine aminotransferase and aspartate aminotransferase. Raised P3NP levels also correlated with the degree of cholestasis as evaluated by serum bilirubin, serum alkaline phosphatase, and copper binding protein deposition in the liver. Serum P3NP is of prognostic value because it reflects the major pathophysiological features of PBC.

22 patients with amyotrophic lateral sclerosis were entered into a double-blind, randomised, placebo-controlled trial of treatment with branched-chain aminoacids. 11 received daily 12 g L-leucine, 8 g L-isoleucine, and 6.4 g L-valine, by mouth, and the remainder received placebo. During the one-year trial, patients in the placebo group showed a linear decline in functional status consistent with the natural history of the disease. Those treated with aminoacids showed significant benefit in terms of maintenance of extremity muscle strength and continued ability to walk.

16 chronic haemodialysis patients (group I), with non-microcytic anaemia (mean haemoglobin 7.2 g/dl, SD 1.0, range 5.8-9.8), moderate aluminium overload (serum aluminium 44 micrograms/l, SD 16, range 21-74), and normal or high iron stores (ferritin 800 micrograms/l SD 464, range 34-2013) were treated with intravenous desferrioxamine 1 g at the end of each dialysis for six months. 8 patients with similar characteristics served as controls (group II). After six months group I showed a rise in haemoglobin to 9.1 (SD 2.5) g/dl and a decrease in blood transfusion requirements, both significant, whereas group II showed no changes. Other significant changes observed in group I, but not group II, were a rise in reticulocytes and in red cell creatine and a fall in red cell protoporphyrin and serum ferritin. Ferritin decreased more in the patients whose anaemia improved. Minor increases in serum aluminium in group I did not differ from those in the control group. Desferrioxamine may benefit the anaemia of chronic haemodialysis patients through improvement of erythropoiesis. The effect seems not to be related to chelation of a heavy aluminium overload.

Small-scale trials of the Edmonston-Zagreb (E-Z) measles vaccine were undertaken to determine the dose necessary to immunise 4-6-month-old infants. Antibody responses, measured 16 weeks after vaccination, were dose dependent: 40,000 plaque forming units given subcutaneously resulted in positive responses in all infants and higher antibody levels than doses of 20,000 or 10,000 units (10,000 units gave a failure rate of 25%). In further trials the E-Z vaccine was compared with the Schwarz vaccine, both being given in subcutaneous doses of 40,000 plaque forming units. In infants aged 20 weeks the E-Z vaccine produced higher levels of measles antibody and in those aged 18 weeks its superiority showed in a lower proportion failing to respond (3 of 39 versus 19 of 35).

3801 children aged 5-11 months were entered into a blind placebo-controlled trial of pertussis vaccine. 954 were randomised to receive placebo (vaccine solvent), 1419 to receive a two-component vaccine containing formaldehyde detoxified lymphocytosis promoting factor (LPF) and filamentous haemagglutinin, and 1428 to receive an LPF-toxoid vaccine. After 7-13 weeks 3724 infants received a second dose. Immediate side-effects were mild. Small local reactions occurred more often in the vaccinated infants than in those who received placebo, especially after the second dose of the two-component vaccine. During 15 months of follow-up from 30 days after the second dose, culture-confirmed whooping cough (cough and a positive culture of Bordetella pertussis) occurred in 40 placebo, 27 LPF-toxoid vaccine, and 18 two-component vaccine recipients. The point estimate of protective efficacy was 54% (95% confidence intervals 26-72%) for the LPF-toxoid vaccine and 69% (47-82) for the two-component vaccine; protection against culture-confirmed whooping cough of over 30 days duration was 80% (59-91%) and 79% (57-90%), respectively.

131 patients with frequently recurring genital herpes were treated for 1 year with reducing doses of oral acyclovir. The time to first recurrence in patients who commenced therapy on 400 mg twice a day was statistically significantly shorter than those on 200 mg four times a day (p less than 0.02) and as the total daily dose and frequency of therapy were lowered so the time to first recurrence was shortened. By the end of 60 days on 200 mg once a day (the lowest daily dose) 56% of patients had recurrences. Patients showed a marked reduction in the frequency of recurrence during therapy (from a mean of 1.1 per 28 days before to 0.11 during treatment, p = 0.0001). After stopping treatment the frequency of recurrences (0.71 per 28 days) was significantly less than the pre-treatment period (p = 0.001). No important side-effects were seen. It is concluded that long-term suppression with acyclovir is safe and effective for patients with recurrent genital herpes.

In a large randomised trial of early beta-blockade in acute myocardial infarction (ISIS-1), almost all the reduction in mortality associated with the use of atenolol occurred on the day of admission or on the subsequent day. To help determine the mechanisms that might be responsible for this retrospective observation, case notes were obtained for British, Irish, and Scandinavian patients who died during this early period. Of 217 early deaths adequate records were available for 193 (79 allocated atenolol and 114 allocated control). In the atenolol group, necropsy had shown cardiac rupture in 5 patients, and a further 15 in whom necropsy had not been done had had electro-mechanical dissociation (total, 20 early deaths from these causes); among control patients the corresponding numbers were 17 and 37 (total, 54 such deaths). Electro-mechanical dissociation was probably a manifestation of acute rupture, and the observed difference in the numbers with this complication was responsible for much of the difference in early mortality. There was a slightly higher incidence of fatal ventricular fibrillation and aortic dissection in the control group, and of bradycardia/asystole in the atenolol group. The data did not indicate any substantial contribution from mechanisms such as limitation of infarct size or prevention of reinfarction or cardiac arrest.

A 2-year randomised pilot study was conducted in 70 patients to see whether the osteoclast-inhibiting effect of calcitonin would reduce postmenopausal vertebral bone loss. An oestradiol-treated group was included in the study as a positive control since oestrogens are known to be effective. Calcitonin reduced vertebral bone loss in doses above 250 micrograms human calcitonin (50 international units) a week, and at this dose was as effective as oestradiol.

Agreement between 24 physicians on the presence or absence of respiratory signs was investigated. The physicians were divided into six sets of 4; each set examined 4 patients with well-defined chest signs. There was generally poor agreement about particular signs. Overall, the 4 physicians in a set were in complete agreement only 55% of the time. Some signs such as wheezing seemed to be more reliably elicited than others such as whispering pectoriloquy. Comparison of diagnoses based on the clinical findings with the correct diagnoses supported by investigations showed that 28% of physicians' diagnoses were incorrect. The more often the examiners differed from the majority on the presence or absence of a sign, the more likely they were to make an incorrect diagnosis. A ranked order of the reliability with which chest signs are elicited would improve the teaching of chest medicine.

To examine whether anticoagulants given after autologous saphenous bypass surgery influenced patient survival 119 patients who received such a graft for obliterative arterial disease were recruited for a controlled clinical trial. Patients were randomly assigned to start, in the second postoperative week, phenprocoumon (60 patients) or no treatment (59 patients). The median duration of survival for all patients was greater than 60 months, and the 75%-quartile was 39.0 (SE of the median 3.9) months. 10 patients died in the treated group and 20 in the control group. The treated group had a greater probability of survival (p less than 0.023, Breslow; p less than 0.043, Mantel). Graft occlusions occurred in 11 patients in the treatment group and in 17 controls. When these patients were excluded from the analysis, the difference in probability of survival between the two groups remained significant (p less than 0.009, Breslow; p less than 0.013, Mantel).

116 patients aged 70 or over who were judged to have surgically resectable cancer of the breast were prospectively randomised to tamoxifen 20 mg daily or surgical resection. At a median follow-up of three years, local relapse or progression was seen in 15 (25%) of 60 patients in the tamoxifen group and 21 (37.5%) of 56 in the surgical arm. Distant metastases occurred in 8 (13%) in the tamoxifen group and in 10 (18%) in the surgical arm. There were 13 deaths in the tamoxifen group and 11 in the surgical arm, of which 8 and 9, respectively, were attributable to breast cancer. Disease-free survival did not differ between the groups.

To examine the anti-leprosy effect of deoxyfructoserotonin the drug was given in a dose of 10 mg/kg for 6 months to 6 patients with active lepromatous leprosy, in accordance with the WHO-THELEP protocol. Clinical and histological assessment and mouse foot-pad studies suggest that the drug has some anti-leprosy effect.

The ability of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, to lower lipid levels in 16 patients with primary hypercholesterolaemia was compared with that of bezafibrate in a 16-week, double-blind, parallel, placebo-controlled trial that was continued in an open crossover fashion. Simvastatin was better than bezafibrate at lowering total and low-density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations (30.4% [p less than 0.001], 37.3% [p less than 0.001], and 37.8% [p less than 0.001] vs 17.0%, 19.6%, and 24.0%, respectively). Both drugs increased the high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I, but this change was significant only with bezafibrate (p less than 0.05). Bezafibrate and simvastatin reduced triglycerides by 25.6% (p less than 0.001) and 13.7% (p less than 0.05), respectively. Very low-density lipoprotein (VLDL)-cholesterol was significantly reduced only by bezafibrate (44.3%, p less than 0.001). Both drugs were tolerated well and no serious side-effects were noted. The results show that simvastatin was more effective than bezafibrate in lowering total-cholesterol, LDL-cholesterol, and apolipoprotein B, while bezafibrate was better at lowering triglycerides and VLDL-cholesterol and at raising HDL-cholesterol and apolipoprotein A-I.