To test the validity of the generally held belief that moderate consumption of alcohol during convalescence from acute viral hepatitis adversely affects outcome, 87 adults recovering from acute viral hepatitis (hepatitis A in 36, hepatitis B in 34, hepatitis non-A, non-B in 17) were studied. Criteria for entry to the study attempted to ensure that no patient was a chronic hepatitis B carrier. Patients were randomised either to a moderate alcohol intake, or to continued complete abstention. Drinkers consumed 26 g alcohol daily (mean) and none remained abstinent. At 3 months all patients were well, with normal liver function tests. There were no significant differences between the two groups at anytime. The findings suggest that moderate alcohol intake during convalescence from acute viral hepatitis does not seem to be harmful.

In a double-blind study ten asthmatic patients with impaired lung function received the cysteinyl-leukotriene receptor antagonist ICI 204,219 (40 mg by mouth) and placebo in random order on 2 days at least 1 week apart. The increase in forced expiratory volume in 1 s (FEV1) above baseline was significantly greater after ICI 204,219 than after placebo. This effect persisted after nebulised salbutamol. These findings suggest that cysteinyl-leukotrienes are one of the causes of persistent bronchoconstriction in chronic asthma.

We evaluated oral ribavirin as therapy for chronic hepatitis C infection in a pilot study including 10 patients. Patients (7 men, 3 women; mean age 40 years, range 23-54) all had biopsy-proven chronic non-A, non-B hepatitis and were repeatedly positive for antibodies to hepatitis C virus. Treatment was with oral ribavirin 1000-1200 mg per day in two divided doses for 12 weeks. The median serum alanine aminotransferase concentration for all patients at enrollment was 3.15 mu kat/l (range 1.22-7.79) and decreased significantly (p less than 0.005) to 1.25 mu kat/l (0.78-2.04) after 12 weeks of treatment. Within 6 weeks of the end of treatment the median serum alanine aminotransferase concentration was not significantly different from that before treatment. Side-effects were mild and fully reversible after cessation of therapy. We conclude that ribavirin is the first drug to offer a potentially effective oral treatment for chronic hepatitis C. It should be further evaluated in controlled trials, possibly in combination with interferon alpha.

Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) is most common in adults and is associated with poor prognosis. Since karyotypic identification of the Philadelphia translocation has been hampered by technical difficulties, we used the polymerase chain reaction (PCR) to look for the BCR-ABL rearrangement in stored samples from a selected group of 314 German ALL patients. BCR-ABL transcripts were found in 77 of 179 adults and were restricted to those with B-precursor leukaemias. 55% of adult common ALL patients had BCR-ABL and its presence correlated with poor overall survival and remission duration. Of 135 children with common ALL, 5 (6%) primary cases and 8 (17%) with recurrent neoplasias were PCR-positive. We recommend prospective evaluation of BCR-ABL analysis with PCR in patients with a B-precursor leukaemia.

HLA typing contributes to the delays that occur in the search for HLA-matched unrelated marrow donors, and that result in poor patient survival. A new DNA technique for testing DR match between patient and unrelated marrow donors has been assessed. The technique is based on the formation of heteroduplexes between heterologous amplified coding and non-coding DNA sequences during the final annealing stage of the polymerase chain reaction (PCR), and different HLA-DR/Dw types give unique banding patterns ("PCR fingerprints") on non-denaturing polyacrylamide gel electrophoresis. HLA-DR matching is by visual comparison of patients' with donors' fingerprints. Identity can be confirmed by mixing donor and recipient DNA before the final stage of the PCR ("DNA crossmatching"). In an assessment of the technique in 53 unrelated HLA-A and HLA-B matched patient-donor pairs, 42 pairs gave the same results with PCR fingerprinting as with DNA-RFLP analysis. In the 11 other pairs DR/Dw mismatches were detected by PCR fingerprinting but not by the standard DNA-RFLP method; PCR-SSO typing with selected sequence-specific oligonucleotides (SSO) confirmed that mismatches were due to different subtypes of DR4. PCR fingerprinting might thus accelerate the selection of unrelated marrow donors by simplifying the logistics of the donor search.

The effect of control of houseflies on the incidence of diarrhoea and shigellosis was evaluated in a prospective crossover intervention study at two military field bases several kilometers apart. In early summer, 1988, intensive fly control measures (mainly bait and trap strategy) were introduced on one base, while the other served as a control. After 11 weeks, as new cohorts arrived, the intervention was abruptly discontinued in the first base and instituted in the second for the next 11 weeks. The study was repeated the next summer. Overall, fly counts were 64% lower on the bases exposed to fly control measures (p = 0.024). Concomitantly, clinic visits dropped by 42% (p = 0.146) for diarrhoeal diseases and by 85% for shigellosis (p = 0.015), as did rates of seroconversion, by 76% (p = 0.024) for antibodies to Shigella and by 57% (p = 0.006) for antibodies to enterotoxigenic Escherichia coli. The findings indicate that houseflies, acting as mechanical vectors, transmit Shigella (and possibly enterotoxigenic E coli) diarrhoeal infections.

The efficacy and safety of tacrine (tetrahydroaminoacridine) plus lecithin were studied in a randomised, double-blind, placebo-controlled, crossover study. Patients with probable Alzheimer's disease were selected from those attending the memory clinic at a psychiatric hospital. Of the 89 patients included, 24 were withdrawn, 19 because of side-effects, 4 with other illnesses, and 1 for non-compliance. The active treatment was the maximum tolerated dose of tacrine up to 150 mg daily plus 10.8 g lecithin daily. Patients were randomly assigned to active or placebo treatment and crossed over after 13 weeks' treatment and 4 weeks' washout to the other treatment. The main outcome measures were the mini mental state examination (MMSE), the abbreviated mental test score (AMTS), and the carer's rating of the activities of daily living scale. Analysis for the 65 patients who completed the trial showed a significant beneficial effect of tacrine over placebo in the MMSE score (p less than 0.0001; 95% confidence interval for group change on tacrine over that on placebo 1.67-3.71); 29 (45%) patients showed an improvement of 3 or more points on tacrine compared with 7 (11%) during placebo. The findings with the AMTS were similar (p = 0.0001; 95% CI 0.36-1.38) but the ADL score showed no significant treatment effect. There was substantial variation in response among the subjects. Dose-dependent rises in serum liver enzymes were common but reversible. Tacrine produced an improvement in key outcome measures roughly equivalent to the deterioration which might have occurred over 6-12 months. The clinical relevance of the findings is a matter for individual judgment.

We entered 876 patients into a clinical trial aimed at preventing pulmonary complications after abdominal surgery. Patients either received conventional chest physiotherapy or were encouraged to perform maximal inspiratory manoeuvres for 5 min during each hour while awake, using an incentive spirometer. The incidence of pulmonary complications did not differ significantly between the groups: incentive spirometry 68 of 431 (15.8%, 95% CI 14.0-17.6%), and chest physiotherapy 68 of 445 (15.3%, CI 13.6-17.0%). Nor was there a difference between the groups in the incidence of positive clinical signs, pyrexia, abnormal chest radiographs, pathogens in sputum, respiratory failure (PO2 less than 60 mm Hg), or length of stay in hospital. We conclude that prophylactic incentive spirometry and chest physiotherapy are of equivalent clinical efficacy in the general management of patients undergoing abdominal surgery.

The absorption of high and low molecular fractions of heparin from the subcutaneous compartment was evaluated in eight healthy males. They were given an intravenous infusion of 4000 U calcium heparin in 4 hours and on another occasion a subcutaneous injection of 12,500 U calcium heparin (washout period of 1 week). Anticoagulation was monitored by anti-Xa, antithrombin activity, and activated partial thromboplastin time. To evaluate factors that might influence absorption, body weight, body fat, and abdominal skinfold thickness were recorded. There was a pronounced inter-individual variability in absorption but the absorption of the two fractions of heparin was similar. The highly variable absorption was related to the abdominal skinfold thickness, and this could have implications for therapeutic and prophylactic heparin regimens.

We studied the interaction of platelets with the wall of human internal mammary arteries and saphenous veins, suspended in organ chambers for measurement of isometric tension. Vessels were obtained during coronary bypass surgery and cut into 5 mm rings; in some the endothelium was chemically removed. Rings from several patients were randomly chosen for each experiment, and in each ring six concentrations of platelets (from healthy blood donors; 1-75 x 10(3)/microliters) were tested consecutively and concentration-response curves constructed; the areas under these curves were used for statistical comparisons. In rings of internal mammary artery contracted in response to noradrenaline, aggregating platelets induced endothelium-dependent relaxation which was prevented by apyrase (0.67 U/ml ADPase activity) and L-NG-monomethylarginine (1 mmol/l). By contrast, in saphenous vein rings contracted in response to noradrenaline, aggregating platelets induced only a further increase in tension. In quiescent vessels, the platelet-induced contraction did not occur in arteries with endothelium but that in veins was greater and facilitated by endothelium. Preincubation of platelets with aspirin (10 mumol/l) reduced the contraction in both vessels, but contraction was abolished only in the presence of both the thromboxane receptor antagonist SQ-30741 and the serotoninergic (5HT2) receptor antagonist ketanserin. These findings show that platelet-derived ADP causes release of nitric oxide by the endothelium of internal mammary artery but not of saphenous vein; thromboxane A2 and serotonin mediate contraction in vein but not artery with endothelium. These differences may contribute to differences in graft function and the clinical efficacy of antiplatelet drugs.

To investigate whether reperfusion after myocardial ischaemia leads to free-radical-mediated peroxidation of membrane lipids and cell damage, we measured pentane, a product of lipid peroxidation, in the breath of 10 healthy control subjects and in 20 consecutive patients with suspected acute myocardial infarction. 10 of these patients showed no myocardial damage on electrocardiography (patient control group) and 10 satisfied standard diagnostic criteria for acute myocardial infarction. The three groups were well matched for age, sex, underlying disease, and smoking habits. The time from onset of chest pain to breath collection was similar in the patient control and acute myocardial infarction groups. The breath pentane concentration was higher (p less than 0.0001) in the acute myocardial infarction group (4.96 [1.15] nmol/l) than in the patient control (1.96 [1.04] nmol/l) and healthy control groups (1.71 [0.87] nmol/l). Lipid peroxidation during acute myocardial infarction reflects action of oxygen radicals and their potential for contribution to the pathogenesis of tissue damage.

This study was designed to determine the need for water supplementation to maintain water homoeostasis in exclusively breastfed infants during summer in a tropical country. A prestudy questionnaire revealed that 97% of 34 nurses and 63% of 70 doctors advocated such supplementation. 45 healthy, male, exclusively breastfed babies, aged 1-4 months, were recruited from a well-baby clinic. 9 who had never received supplemental water plus a random selection of 14 others were allocated to group I (breastmilk only); the remaining 22 infants were allocated to group II (breastmilk plus supplemental fluid according to the mother's usual practice). The babies were studied at the hospital for 8 h; breastmilk intake was measured by weighing the infant before and after each feed, water intake by calibrated bottles, and urine output by accurate collection and measurement. The maximum room temperatures were 34-41 degrees C and relative humidities 9-60% (below 50% in all but 3 infants). In group II the mean water intake was 11% (95% confidence interval 7-16%) of the total fluid intake. Both breastmilk intake (274 vs 210 ml) and total fluid intake (274 vs 233 ml) were higher in group I than in group II (p = 0.003, p = 0.073, respectively), after adjustment for age, weight, length, room temperature, and humidity. However, there were no significant differences between the groups in urine output, urine or serum osmolality, weight change, or rectal temperature whether or not the factors adjusted for included total fluid intake. Thus, exclusively breastfed infants do not need supplemental water to maintain water homoeostasis; a reduced breastmilk intake is a potential disadvantage of this practice.