Five consecutive patients with cryofibrinogenaemia in association with painful leg ulcers and intravascular dermal thrombi were treated with stanozolol, an androgenic steroid with fibrinolytic properties. In all patients treatment was followed by rapid and striking pain relief and healing of the ulcers. Cryofibrinogenaemia was not detected on subsequent laboratory evaluation, and dermal intravascular thrombi had resolved on repeat histological examination.

Although used widely, the effectiveness of zidovudine therapy and primary prophylaxis for Pneumocystis carinii pneumonia (PCP) in HIV-1-infected individuals, has not been assessed in a large cohort. We have done an observational study between October, 1986, and October, 1990, of a cohort of 2145 HIV-1-seropositive men and 371 who seroconverted during the study. A Markov chain transitional analysis was used to examine the effect of zidovudine and PCP prophylaxis on the probability of progression of HIV-1 infection to AIDS (after 6, 12, 18, and 24 months) after follow-up visits categorised into one of six disease states. The six starting states were based on CD4+ lymphocyte counts and the presence of HIV-related symptoms. Use of pre-AIDS zidovudine and PCP prophylaxis was associated with significant reductions in rates of progression to AIDS at 6, 12, 18, and 24 months for participants starting with less than 350 CD4+ lymphocytes/microliter. For those starting with 350 or more CD4+ lymphocytes/microliter, non-significant protective trends were seen during 12, 18, and 24 month intervals. In multivariate log-linear models virtually all the treatment effect was due to zidovudine. However, after adjusting for the effects of zidovudine, PCP prophylaxis reduced significantly the probability of progression to a first episode of PCP during 6, 12, 18, and 24 month intervals. This study suggests that early primary PCP prophylaxis is effective in preventing first episodes of PCP, and that the efficacy of zidovudine demonstrated in clinical trials can be translated to the population level.

Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results. To resolve the question, a randomised, double-masked, placebo-controlled community trial of 28,630 children aged 6-72 months was carried out in rural Nepal, an area representative of the Gangetic flood plain of South Asia. Randomisation was carried out by administrative ward; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents. After 12 months, the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 (95% confidence interval 0.56-0.88), equivalent to a 30% reduction in mortality. The trial, which had been planned to last 2 years, was discontinued. The reduction in mortality was present in both sexes (relative risk for boys 0.77; for girls 0.65), at all ages (range of relative risks 0.83-0.50), and throughout the year (0.76-0.67). The reduction in mortality risk was not affected by acute nutritional status, as measured by arm circumference. Thus, periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries.

Hyperbilirubinaemia in newborn infants is generally regarded as a problem, and bilirubin itself as toxic metabolic waste, but the high frequency in newborn infants suggests that the excess of neonatal bilirubin may have a positive function. To investigate the hypothesis that bilirubin has a role as a free-radical scavenger, the rate of rise in serum bilirubin in the first few days of life was measured in 44 infants with five illnesses thought to enhance free-radical production and in 58 control infants. The infants were selected from 2700 consecutive births by exclusion of those with factors known to affect bilirubin metabolism, including enteral feeding. The control infants were those who seemed to be ill and received treatment, including restriction of enteral feeds, but in whom no illness, or disorders not related to free-radical production, were found. The mean serum bilirubin rise was significantly lower in the combined illness group than in the control group (36.1 [95% Cl 26.9-45.3] vs 66.7 [55.9-77.5] mumol.l-1.day-1; p less than 0.0001). In subgroup analyses the mean rises in infants with circulatory failure, neonatal depression/asphyxia, aspiration syndromes, and proven sepsis were significantly lower than in controls matched for gestational age and birthweight, but rises in infants with respiratory distress and their matched controls did not differ. These findings are consistent with the hypothesis that bilirubin is consumed in vivo as an antioxidant. Such consumption may operate in vivo in addition to the standard pathways for bilirubin metabolism (production, isomerisation, and excretion).

For 18 years treatment with lindane or crotamiton products has failed to stem the epidemic of scabies among the Kuna Indians in the San Blas islands of the Republic of Panama. Permethrin 5% cream was introduced as the only treatment in a programme to control scabies on an island of 756 inhabitants and involving workers recruited locally. Prevalence fell from 33% to less than 1% after every person was treated. As long as continued surveillance and treatment of newly introduced cases was maintained, prevalence of scabies remained below 1.5% for over 3 years. When supply of medication was interrupted for 3 weeks, prevalence rose to 3.6%. When control was lost after the US invasion of Panama, prevalence rose to 12% within 3 months. Bacterial skin infections decreased dramatically when scabies was controlled. Permethrin is safe and effective even in areas where this disease has become resistant to lindane.

Syncytium formation, a feature of HIV-1-induced cytopathology, allows the virus to propagate through cell-to-cell spread. An assay has been developed to measure antibodies (syncytium inhibition, SI) that inhibit this process. Two cell lines were used: the indicator cells, which are not HIV-1 infected, bear CD4 receptors on their surface; the fusogenic HIV-1 infected cells, which do not release virus but are responsible for initiating syncytium formation, are free of CD4 receptors. Co-cultivation of about 10(5) of each of these cells induces the emergence of 70-100 multinucleated giant cells within 48 h. Sera from 34 children born to HIV-1-infected mothers were tested by western blot (WB) and SI assay. SI antibodies were detected in the blood of 15 (65%) of 23 WB-positive children and in none of 11 WB-negative children. There were striking differences in prevalence and titre of SI antibodies in children with lymphocytic interstitial pneumonitis (LIP) compared with those with opportunistic infections (OI). All 8 children with LIP had SI antibodies ranging in titre from 40 to greater than 320. By contrast, only 2 of 7 with OI had SI antibodies, in both of whom the SI titre was 20 (p less than 0.05). No sera from children who had seroreverted contained SI antibodies. The findings point to the need to identify the specific HIV-I peptides or epitopes responsible for syncytium formation since SI antibodies correlate with clinical outcome in children.

A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation.

In a retrospective survey, 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987, were studied for evidence of publication bias. As of May, 1990, 285 of the studies had been analysed by the investigators, and 52% of these had been published. Studies with statistically significant results were more likely to be published than those finding no difference between the study groups (adjusted odds ratio [OR] 2.32; 95% confidence interval [Cl] 1.25-4.28). Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor. An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results, and with increasing sample size. The tendency towards publication bias was greater with observational and laboratory-based experimental studies (OR = 3.79; 95% Cl = 1.47-9.76) than with randomised clinical trials (OR = 0.84; 95% Cl = 0.34-2.09). We have confirmed the presence of publication bias in a cohort of clinical research studies. These findings suggest that conclusions based only on a review of published data should be interpreted cautiously, especially for observational studies. Improved strategies are needed to identify the results of unpublished as well as published studies.

The presence of recipient lymphocytes in grafts is thought to equate with rejection. Thus, we wished to follow the fate of lymphocytes after transplant of the small bowel. Three complete small-bowel transplants, two with the liver from the same donor also transplanted, were done successfully. Patients were immunosuppressed with FK 506. 5 to 11% of lymphocytes in the recipients' peripheral blood were of donor origin during the early postoperative period when there were no clinical signs of graft-versus-host disease. However, donor cells were no longer detectable after 12 to 54 days. Serial biopsy specimens of the grafted small bowel showed progressive replacement of lymphocytes in the lamina propria by those of the recipient's HLA phenotype. Lymphoid repopulation was complete after 10 to 12 weeks but the epithelial cells of the intestine remained those of the donor. The patients are on enteral alimentation after 5, 6, and 8 months with histopathologically normal or nearly normal intestines. Re-examination of assumptions about the rejection of intestinal grafts and strategies for its prevention are required following these observations.

In the absence of evidence for pneumonia or pulmonary embolus, primary pulmonary infarction has been assumed to be the cause of the syndrome of chest pain, fever, and pulmonary infiltrate on chest X-ray that commonly complicates sickle cell anaemia. To find out whether the syndrome might be due to rib infarction, 99mTc-diphosphonate bone scans were done. In the eleven episodes thus investigated (10 patients) the scans showed segmental areas of increased radionuclide uptake in ribs, indicative of bone infarction. A possible sequence of events is that the rib infarcts are primary and cause bone pain, followed by soft tissue reaction, pleuritis, and splinting. The resultant hypoventilation leads to atelectasis and subsequent development of the radiographic changes of the acute chest syndrome. Prevention of hypoventilation and treatment of bone pain are important therapeutic goals.

Guidelines in most developed countries for testing pregnant women for HIV infection recommend that screening should be directed to groups with acknowledged risk factors for infection. Our prospective study of HIV seroprevalence among 2724 pregnant women in an inner-city area of Baltimore, USA, showed that if these guidelines had been applied only 57% of HIV-seropositive women would have been detected. By offering counselling and HIV testing to all pregnant women, the detection rate was raised to 87%. We conclude that screening directed at women who admit risk factors is not effective in identifying HIV-infected women and that routine HIV screening should be offered to all pregnant women.