Observational studies have suggested that the prevalence of trachoma is lower in children with clean faces than in those with ocular or nasal discharge or flies on the face. We carried out a community-based randomised trial in three pairs of villages to assess the impact on trachoma of a face-washing intervention programme following a mass topical antibiotic treatment campaign. Six villages in Kongwa, Tanzania, were randomly assigned mass treatment plus the face-washing programme or treatment only. 1417 children aged 1-7 years in these villages were randomly selected and followed up for trachoma status and observations of facial cleanliness at baseline and 2, 6, and 12 months. At 12 months, children in the intervention villages were 60% more likely to have had clean faces at two or more follow-up visits than children in the control villages. The odds of having severe trachoma in the intervention villages were 0.62 (95% Cl 0.40-0.97) compared with control villages. A clean face at two or more follow-up visits was protective for any trachoma (odds ratio 0.58 [0.47-0.72]) and severe trachoma (0.35 [0.21-0.59]). This community-based participatory approach to face-washing intervention had variable penetration rates in the villages and was labour intensive. However, we found that, combined with topical treatment, community-based strategies for improving hygiene in children in trachoma-endemic villages can reduce the prevalence of trachoma.

The UK Medical Research Council trial MRC UKALL X was designed to investigate the benefit of one or two courses of additional intensification therapy in children with acute lymphoblastic leukaemia receiving standard treatment. From 1985 to 1990 1612 children, comprising more than 90% of eligible cases in the UK, were treated with intensive induction therapy, central nervous system directed therapy with cranial irradiation and intrathecal methotrexate, and continuing treatment for 2 years. 1171 children were randomised to receive additional intensification therapy at 5 weeks, 20 weeks, both, or neither. At follow-up of at least 3 years disease-free survival for all children at 5 years was 62% (95% confidence interval [Cl] 60.0-64.4), a significant improvement over the 56% (53.0-59.6) found in the preceding MRC UKALL trial. The 5-year disease-free survival was 71% (65.5-76.1) for children randomised to two blocks of intensification therapy, this being significantly better than the 62% (56.6-68.0), 61% (55.7-67.1), and 57% (50.9-62.7) rates for the groups randomised to one intensification block at 5 weeks, one at 20 weeks, and no intensification, respectively. The benefits of intensification therapy were seen irrespective of clinical factors known to influence outcome such as age, sex, and initial leucocyte count. We conclude that the addition of two courses of intensification therapy has produced a 14% improvement in disease-free survival and an 11% improvement in overall survival for the randomised patients. This additional treatment is of benefit to all children with acute lymphoblastic leukaemia, even those traditionally deemed at lower risk of relapse.

Approximately 15% of registered pregnancies end in spontaneous abortion, and for 50 years or so dilatation and curettage (D&C) has been the usual management. In a prospective randomised trial we compared the clinical results after either expectant management or D&C, for miscarriages of less than 13 weeks' gestation in which transvaginal ultrasound examination showed intrauterine tissue and/or blood clots with a diameter 15-50 mm. 103 patients were randomised to expectant management and spontaneous resolution of pregnancy occurred within 3 days in 81 cases (79%). 52 patients were randomised to D&C. 3 infections were diagnosed among patients who underwent expectant management (3%); 5 infections and 1 case of postoperative anaemia were observed among patients randomised to D&C (11%). The duration of vaginal bleeding was a mean of 1.3 days longer in the expectant management group (p < 0.02). Convalescence time, time during which patients experienced pain, and packed-cell volume 3 and 14 days after inclusion did not differ significantly between the groups. This study shows that expectant management of selected cases of spontaneous abortion has a similar outcome to D&C.

Laparoscopic hysterectomy (LH) is a way to avoid laparotomy. However, there is evidence that most women treated by abdominal hysterectomy are suitable for vaginal surgery. To test this hypothesis, and to determine the relative merits of laparoscopic and vaginal hysterectomy (VH) and the best technique for LH, we prospectively studied 98 women who had relative contraindications for vaginal surgery by traditional criteria. 75 underwent LH and 23 VH. The LH group included 22 women who had been assigned to this route of surgery as part of a prospective randomised controlled comparison with VH (23 women). Surgery was completed with the intended technique in 93.9% of cases. 5 women in the LH group (6.7%) and 2 in the VH group required laparotomy or additional procedures. In the prospective randomised study LH took longer than VH (mean duration 131 vs 77 min). VH was the faster procedure, irrespective of uterine size and need for oophorectomy. With LH, the operative time increased as more of the hysterectomy was carried out with laparoscopic rather than vaginal dissection. Complication rates, blood loss, analgesia requirements, and recovery were similar for the two techniques. Our study confirms that most hysterectomies could be performed vaginally, and that LH is a much slower procedure. If LH is done, it should be converted to a vaginal procedure as early as possible to reduce the overall operating time. LH does seem to be a waste of time for most patients.

We treated 19 patients with advanced breast cancer resistant to tamoxifen with a new specific antioestrogen (ICI 182780) which, in animal studies, has no agonist activity. 13 (69%) patients responded (7 had partial responses and 6 showed no change) to monthly intramuscular injections of ICI 182780 after progression on tamoxifen, for a median duration of 18 months with minimum side effects. Preliminary evidence suggests that the agent is without effects on the liver or the hypothalamic-pituitary axis. ICI 182780 appears to be a promising new agent for treatment of advanced and early breast cancer.

Cough is a frequent side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the effects of inhaled sodium cromoglycate in 10 patients with ACE-inhibitor cough in a double-blind crossover study. After a 2-week run-in, patients were randomised to either 2 weeks' inhaled sodium cromoglycate or placebo followed by a further 2 weeks on the other treatment. Patients kept a cough diary during each study period. Cough severity was recorded on a scale from 0 to 12. At the end of each study period the cough threshold to inhaled capsaicin was measured. 9 patients reported a reduction in cough after sodium cromoglycate. Median (range) daily cough scores during run-in and placebo periods were 3.6 (1.9-6.4) and 4.1 (0.6-8.1), respectively (p > 0.05). Median daily cough score after sodium cromoglycate was 1.8 (0.4-3; p < 0.01). There was a significant relation between initial cough severity and benefit from sodium cromoglycate; and cough-reflex sensitivity to inhaled capsaicin was significantly reduced. Inhaled sodium cromoglycate is an effective treatment for ACE-inhibitor cough. Its effect may be due to suppression of afferent vagal activity.

Canada has not introduced the non-A, non-B (NANB) surrogate marker tests (antibodies to hepatitis B core antigen and alanine aminotransferase) to screen donated blood. We evaluated the effect of NANB surrogate markers in reducing post-transfusion hepatitis in a prospective randomised intervention study. From 1988 to 1992, 4588 subjects were enrolled into two study groups that received allogeneic blood from which units positive for NANB surrogate markers were either withheld (n = 2311) or not withheld (n = 2277). We also assessed a simultaneous non-randomised cohort (n = 650) of subjects who received only syngeneic blood. All subjects were followed up for 6 months and assessed for the presence of post-transfusion hepatitis due to hepatitis A, B, C, non ABC, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Withholding of blood containing NANB surrogate positive units reduced the overall post-transfusion hepatitis rate by 40% (p = 0.065) and the hepatitis C rate by 70% (p = 0.05). Most of the benefit of NANB surrogate testing was due to reduced frequency of hepatitis C virus after transfusion before all donor blood was screened for anti-HCV. During this time the overall post-transfusion hepatitis rate per 1000 transfusion recipients was 20.2 in the no-withhold group compared with 5.0 in the withhold group (p = 0.05), and the HCV hepatitis rate was 12.6 and 0 respectively (p = 0.06). After the introduction of HCV screening, the overall post-transfusion hepatitis rates were 8.6 and 6.8 per 1000 (p = 0.55) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrogen dioxide is a common indoor pollutant. In the light of suggestions that outdoor air pollution can harm people with asthma, we investigated the effect of 1 h exposures to domestic concentrations of nitrogen dioxide on the airway response to house-dust mite (HDM) allergen in ten patients with mild asthma. Each subject breathed air, 100 ppb nitrogen dioxide, or 400 ppb nitrogen dioxide for 1 h, in double-blind, random order, then immediately underwent a fixed-dose HDM challenge. Baseline forced expiratory volume in 1 s (FEV1) was not affected by any of the gas mixtures. The mean early asthmatic response (maximum percentage change in FEV1 during first 2 h after challenge) was -14.62% (SD 8.03) after air, -14.41% (7.86) after 100 ppb nitrogen dioxide, and -18.64% (7.28) after 400 ppb nitrogen dioxide. The difference between air and 400 ppb (-4.01%) was significant (95% CI -1.34 to -6.69%, p < 0.009), but those between air and 100 ppb and between 100 and 400 ppb were not (0.21 [-3.10 to 3.53]% and -4.23 [-8.75 to 0.29]%). The mean late asthmatic response (maximum percentage change in FEV1) to challenge after air was -2.85% (3.95), after 100 ppb nitrogen dioxide -7.76% (6.92), and after 400 ppb -8.13% (6.64). The difference in means between the air and 400 ppb exposures was significant (-5.28 [-0.73 to -9.83]%, p < 0.02) but those between air and 100 ppb (-4.90 [-10.60 to 0.78]%) and 100 and 400 ppb (0.37 [3.06 to 3.80]%) were not. These findings suggest that nitrogen dioxide, at concentrations encountered in the home environment, can potentiate the specific airway response of patients with mild asthma to inhaled HDM allergen, although the effect is small.

Domiciliary treatment of severely malnourished children could have economic and practical advantages over other methods. We compared three approaches in a controlled trial. 437 children in Dhaka (< 60% weight-for-height, and/or oedema) aged 12-60 months were sequentially allocated to treatment as inpatients, to day-care, or to care at home after one week of day-care. Institutional and parental costs incurred to reach 80% weight-for-height were compared. Costs for inpatient, day-care, and at-home groups averaged 6363, 2517, and 1552 taka (60 taka = UK pound 1). Mortality was low (< 5%) in all three groups. Day-care treatment approached inpatient care for speed of recovery at less than half the cost, but it was unpopular with parents. The at-home group took significantly longer to attain 80% weight-for-height than the other groups, but did so at the lowest average cost. Parental costs were highest for the at-home group as no food supplements were provided; nevertheless this was the most popular option. We conclude that at-home management of severely malnourished children after 1 week of inpatient care is a cost-effective strategy.

Anecdotal reports have suggested that reduced efficacy of pediculicides against Pediculus humanus capitis could be related to resistance to treatments. Ovicidal and pediculicidal activities of 0.5% malathion and 0.3% d-phenothrin lotions were tested in an experimental model of P humanus capitis grown on rabbits to ensure that the two treatments were pharmacologically equipotent. We then did a randomised controlled trial in which the lotions were administered to 193 P humanus capitis-infested schoolchildren (malathion, 95; d-phenothrin, 98). Success rate was defined as the absence of both live lice and viable nits. Before treatment, live lice were collected and subjected to a pediculicidal test. Pharmacological tests showed 100% killing of the rabbit-grown nits and lice after exposure to both pediculicides. On day 1 of the controlled trial, the success rate was 92% in the malathion group (95% CI, 0.86-0.97) and 40% in the d-phenothrin group (0.30-0.49) (p < 0.0001); on day 7, it was 95% in the malathion group (0.90-0.99) and 39% in the d-phenothrin group (0.29-0.48, p < 0.0001). Malathion was also significantly more active in the pediculicidal tests compared to d-phenothrin and control. These results suggest an acquired resistance to d-phenothrin in the schoolchildren tested, since all other conditions of the administration of insecticides were standardised.

The development of intravenous enzyme-replacement treatment for Gaucher's disease has changed life expectancy in cases without neurological involvement (type 1). The effects in patients with neurological involvement are unknown. We treated 12 Italian patients, types 1 (9) and 3 (3), with intravenous alglucerase: 70-120 IU/kg per month for type 3 and 30-60 IU/kg per month for type 1. Maintenance infusions were biweekly in patients without neurological symptoms, whereas in one symptomatic type 3 patient, infusion was weekly. All patients improved; a resumption of growth in children with growth retardation was observed and spleen and liver reduced in size. In one type 3 patient, a bone callus formed during treatment and enabled the patient to walk. Laboratory tests showed rapid increase of haemoglobin in anaemic patients, and a slower response in patients with thrombocytopaenia. In 4 patients there was temporary hypocalcaemia immediately after the beginning of treatment. Neurological symptoms were present in 1 of the type 3 patients, and electroencephalogram was abnormal in another. After 2 years of treatment, the patient with symptoms showed an improvement of psychomotor skills and of IQ from 50 to 60. Genotype analysis showed a high frequency of the 1448C mutation (54.5%). The 9 patients carrying this allele came from Italian regions which in the past had been invaded from north Europe and Scandinavia. Enzyme replacement in Gaucher's type 1 can also be effective at low doses and even with a 2-week interval between infusions. This makes treatment cheaper, and reduces hospital stay for patients.

Air pollution may enhance the airway response of asthmatic subjects to allergen inhalation. To test the hypothesis that sulphur dioxide and nitrogen dioxide alone or in combination could have a contributory role, we have studied the effect of 6 h exposure to air, 200 parts per billion (ppb) sulphur dioxide, 400 ppb nitrogen dioxide, and the two gases together on the airway response to inhaled allergen in ten volunteers with mild atopic asthma. The subjects were exposed to the gases in random order at weekly visits, then challenged with pre-determined concentrations of Dermatophagoides pteronyssinus allergen 10 min after each exposure. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and cumulative breath units (CBU) of D pteronyssinus allergen required to produce a 20% fall in FEV1 (PD20FEV1) were measured after each exposure. Compared with air, neither sulphur dioxide nor nitrogen dioxide nor the combination significantly altered FEV1 or FVC. Although the decreases in PD20FEV1 after exposure to each agent alone were not significant (41.2%, p = 0.125 after nitrogen dioxide; 32.2%, p = 0.506 after sulphur dioxide) the decrease after exposure to the combination was significant (60.5 [SE 8.1]%, p = 0.015). Exposure to a combination of sulphur dioxide and nitrogen dioxide in concentrations that could be encountered in heavy traffic enhances the airway response to inhaled allergen, possibly as a result of previous airway inflammation.

The development of non-surgical techniques for the relief of malignant low bileduct obstruction has cast doubt on the best way of relieving jaundice, particularly in patients fit for surgery whose life expectancy is more than a few weeks. We did a randomised prospective controlled trial comparing endoscopic stent insertion and surgical biliary bypass in patients with malignant low bileduct obstruction. 204 patients were randomised (surgery 103, stent 101); 3 subsequently proved to have benign disease and were excluded, leaving 101 surgical and 100 stented patients for assessment. Technical success was achieved in 94 surgical and 95 stented patients, with functional biliary decompression obtained in 92 patients in both groups. In stented patients, there was a lower procedure-related mortality (3% vs 14%, p = 0.01), major complication rate (11% vs 29%, p = 0.02), and median total hospital stay (20 vs 26 days, p = 0.001). Recurrent jaundice occurred in 36 stented patients and 2 surgical patients. Late gastric outlet obstruction occurred in 17% of stented patients and 7% of the surgical group. Despite the early benefits of stenting there was no significant difference in overall survival between the two groups (median survival: surgical 26 weeks; stented 21 weeks; p = 0.065). Endoscopic stenting and surgery are effective palliative treatments with the former having fewer early treatment-related complications and the latter fewer late complications.