Antagonism of the effects of platelet activating factor (PAF) by the ginkgolide mixture BN 52063 was assessed in a double-blind, placebo-controlled, crossover study in 6 normal subjects. Weal and flare responses to 400 ng PAF, examined 2 h after ingestion of BN 52063 (80 mg, 120 mg) were inhibited in a dose-related manner. After 120 mg the flare area was reduced by a mean 62.4% (p less than 0.005) and the weal volume by a mean 60% (p less than 0.05). Both doses of BN 52063 significantly inhibited PAF-induced platelet aggregation in platelet-rich plasma (p less than 0.001). In vitro, BN 52063 inhibited PAF-induced but not ADP-induced platelet aggregation. Thus BN 52063 seems to be an antagonist of PAF in man.

40 adult patients with cystic fibrosis (CF) were admitted to hospital with acute exacerbations of infection associated with isolation of Pseudomonas aeruginosa from sputum. The patients were randomly allocated (20 per group) to receive intravenous azlocillin 5 g and gentamicin 80 mg, or oral ciprofloxacin 500 mg. Both treatments were given three times a day for 10 days. The patients were assessed on days 1 and 10, and at 6 weeks. There was a significant improvement in lung function between days 1 and 10 in both groups (p less than 0.001). Significant improvement was maintained at 6 weeks after ciprofloxacin but not in the intravenous group. Improvement after ciprofloxacin was superior at day 10. Sputum weight decreased in both groups (p less than 0.001). Patient-recorded symptoms also improved in both groups. There was no serious toxicity or side-effects. Drug resistant organisms were isolated no more frequently after ciprofloxacin than after intravenous therapy. 17 of the ciprofloxacin-treated patients said they preferred oral treatment to intravenous therapy. Oral ciprofloxacin is a useful short-term treatment for patients with CF who are infected with Ps aeruginosa.

300 patients at high fetal risk (mean gestational age 34 wk) were randomised to a group for antenatal doppler umbilical artery waveform studies and a control group. The timing of delivery was similar in the control and doppler-report-available groups overall. However, in the report group obstetricians allowed the pregnancies of those not selected for elective delivery to continue longer. There was no difference in the rates for elective delivery (induction of labour or caesarean section) in the two groups, whereas among those who went into labour (induced or spontaneous) emergency caesarean section was more frequent in the control group (23%) than in the report group (13%). Fetal distress in labour was also more common in the control group. Babies from the control group spent longer in neonatal intensive care (level 3) and needed more respiratory support than did those in the report group. The findings indicate that the availability of doppler studies leads to better obstetrical decision making.

After treatment with chloroquine and pyrimethamine/sulfadoxine, 118 school children aged 6 to 10 years living near the Kenyan coast were enrolled in a malaria chemoprophylaxis study and followed up for 20 weeks. Children were randomly assigned to receive either chlorproguanil 20 mg weekly (n = 78) or placebo (n = 37). The attack rate of Plasmodium falciparum infection was 42% in chlorproguanil recipients (39.8 episodes per 1000 person-weeks of prophylaxis) and 73% in placebo recipients (69.2 episodes per 1000 person-weeks, p less than 0.02). Sensitivity tests on 36 isolates successfully cultured in vitro showed that all 21 isolates from chloroproguanil recipients were resistant to dihydrofolate-reductase inhibitors, whereas only 3 of 15 isolates from the placebo group were resistant (p less than 10(-6)). Chlorproguanil in a weekly adult dose of 40 mg does not provide adequate prophylaxis against P falciparum in Kenya, probably because drug levels between doses fall below those required to suppress parasites resistant to dihydrofolate-reductase inhibitors.

In a randomised controlled trial, preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine, with (n = 8) or without (n = 8) the addition of fentanyl (10 micrograms/kg intravenously) to the anaesthetic regimen. Major hormonal responses to surgery, as indicated by changes in plasma adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol levels, in the insulin/glucagon, molar ratio, and in blood glucose, lactate, and pyruvate concentrations were significantly greater in the non-fentanyl than in the fentanyl group. The urinary 3-methylhistidine/creatinine ratios were significantly greater in the non-fentanyl group on the second and third postoperative days. Compared with the fentanyl group, the non-fentanyl group had circulatory and metabolic complications postoperatively. The findings indicate that preterm babies mount a substantial stress response to surgery under anaesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anaesthesia may be associated with an improved postoperative outcome.

Three 1 microgram or 2 micrograms doses of Merck, Sharp and Dohme plasma vaccine were given to 119 infants of mothers negative for antibody to hepatitis B surface antigen (anti-HBs). Anti-HBs antibodies developed in 25/29 (86%) infants given 1 microgram and in 86/90 (96%) given 2 micrograms doses. Levels of anti-HBs achieved by three 2 micrograms doses were similar to those that have been reported for conventional 10 micrograms doses. Similar levels were recorded from infants of anti-HBs-positive mothers, which suggests that maternal antibody does not interfere with the infant's immune response to low doses of vaccine. Three 2 micrograms doses of vaccine in infancy produce satisfactory immunogenicity and make possible economic control of hepatitis B in endemic areas.

A prospective randomised single-blind study of the effects of real and sham acupuncture on exercise-induced asthma was conducted in nineteen children. Forced expiratory flow in 1st second (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) were measured throughout acupuncture and after treadmill exercise. Neither real nor sham acupuncture affected the basal bronchomotor tone but both, when applied 20 min before exercise, attenuated exercise induced asthma: mean maximum percentage falls in FEV1, FVC, and PEFR were 44.4%, 33.3%, and 49.5% without acupuncture; 23.8%, 15.8%, and 25.9% after real acupuncture; and 32.6%, 26.1%, and 34.3% after sham acupuncture. Real acupuncture provided better protection against exercise-induced asthma than did sham acupuncture (p less than 0.05).

In a randomised controlled trial, twelve matched pairs of patients with chronic obstructive pulmonary disease received traditional Chinese acupuncture or placebo acupuncture. After three weeks' treatment the traditional-acupuncture group showed significantly greater benefit in terms of subjective scores of breathlessness and six-minute walking distance. Objective measures of lung function were unchanged in either group. Whether these differences are mediated by endogenous opiate and/or peptide release remains speculative.

In this randomised, double-blind, placebo-controlled, 2-year multicentre study intrathecally administered natural human fibroblast interferon (IFN-B) was effective in reducing exacerbations of multiple sclerosis (MS) in patients with exacerbating/remitting disease. The mean reduction in exacerbation rate of 34 patients who received IFN-B (recipients) was significantly greater during the study than that of 35 patients who received placebo (p less than 0.04). The prestudy exacerbation rates were comparable in recipients and controls, but the rate at the end of the study was significantly lower in recipients than in controls (p less than 0.001). IFN-B was given by nine or ten lumbar punctures over the first 6 months of the study, and patient observations continued for 2 years. IFN-B was well tolerated in 95% of the recipients, and the side-effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin reduced the toxicity of IFN-B and played an important role in successful double-blinding.

36 patients with insulin-dependent diabetes mellitus who had 'Albustix'-negative urine but raised urinary albumin excretion (30 to 300 mg/24 h) were randomly assigned to either remaining on conventional insulin treatment or continuous subcutaneous insulin infusion and followed up for 2 years. The insulin-infusion group showed a significant, sustained improvement in metabolic control, with a median glycosylated haemoglobin of 7.2% (range 5.9-8.8), but there was no change in the conventional-treatment group (median 8.6%, range 7.2-13.4) (p less than 0.001). Clinical diabetic nephropathy (a urinary albumin excretion rate above 300 mg/24 h in at least two of three 24 h urine collections) developed in 5 patients in the conventional-treatment group, but not in the insulin-infusion group (p less than 0.05, two-tailed). Fractional albumin clearance (mean and range X 10(7] increased in the conventional-treatment group from 160 (35-468) to 360 (29-1580) and was unchanged in the insulin-infusion group (170 [31-608] before to 160 [26-460] after) (p less than 0.05). Insulin infusion had an overall beneficial effect on the annual increase in urinary albumin excretion (p less than 0.05), and the mean glycosylated haemoglobin values correlated positively with annual change in albumin excretion (r = 0.57, p less than 0.0001). The diastolic blood pressure rose significantly in the conventional-treatment group (p less than 0.001), and annual change in mean blood pressure correlated with change in urinary albumin excretion (r = 0.49, p less than 0.001).

The effectiveness of ethamsylate in the prevention of periventricular haemorrhage (PVH) in very low birthweight infants was evaluated by means of a multicentre, placebo-controlled, double-blind trial. In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage, but intraventricular and parenchymal haemorrhages developed in 30/162 infants (18.5%) in the treated group, compared with 50/168 (29.8%) in the control group (p less than 0.02). The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 (14.6%) in the ethamsylate group and 37/146 (25.3%) in the controls (p less than 0.05). In 30 infants with evidence of PVH on the initial scan, ethamsylate treatment seemed to limit parenchymal extension. Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grades of severity of PVH was recorded during the trial was lower in the treated than in the placebo group (p less than 0.01). No adverse effects were attributed to ethamsylate therapy. The reported incidence of patent ductus arterious was lower in the treated than in the placebo group (p less than 0.02). Mortality was similar in the two groups.

Two anticoagulant regimens, similar except for the timing of warfarin therapy, were compared in patients with clinically submassive venous thromboembolism (VTE). Warfarin was begun after 7 days of continuous intravenous heparin infusion in group L (127 patients) or within 3 days (average 1 day) of starting heparin in group S (139 patients), with similar outcomes. The frequency of symptomatic VTE recurrence during the hospital stay was 4.7% in group L and 3.6% in group S, and that of symptomless new perfusion defects 8.5% in group L and 3.9% in group S. On routine iodine-125-fibrinogen leg scanning of patients presenting with distal thrombosis (in the calf, popliteal, or distal femoral veins) 3.6% of group S but no group L patients had symptomless proximal extension. The incidence of bleeding was similar with both regimens. Outpatient follow-up showed no excess recurrent VTE in either treatment group. Early warfarin treatment significantly shortened hospital stay by an average of 3.9 days (30%) in patients admitted solely because of VTE.

The effect of a synthetic analogue of atrial natriuretic peptide (Ileu-ANP) on haemodynamic, hormonal, and electrolyte excretion indices was studied in 7 patients with chronic congestive heart failure. Patients received in random order placebo or Ileu-ANP infusions (5 micrograms/min) for 4 h on 2 separate occasions, at least 1 week apart. Compared with placebo, Ileu-ANP caused significant reductions in mean systemic arterial pressure, mean pulmonary artery pressure, pulmonary diastolic pressure, and right atrial pressure. These changes were sustained for at least 2 h after infusion. Cardiac output increased from 6.2 to 7.4 l/min at 60 min, then returned to pre-infusion levels. Despite considerable falls in systemic pressure there was no significant increase in heart rate or plasma noradrenaline. With Ileu-ANP infusion, plasma renin activity, angiotensin, arginine vasopressin, aldosterone, and cortisol values were not significantly different from placebo values. Plasma cortisol and aldosterone increased after stopping Ileu-ANP. Neither urine volume nor sodium excretion rate was significantly increased by Ileu-ANP.

Between 1978 and 1983, 1127 patients with de-novo acute myeloid leukaemia (AML) were entered into the Medical Research Council (MRC)'s 8th AML trial. All received the same induction therapy consisting of daunorubicin, cytarabine, and 6-thioguanine--DAT (1 + 5). The 67% who entered complete remission were randomised to consolidation with two or six further courses of DAT. Adults under the age of 55 were randomised for central nervous system (CNS) prophylaxis with intrathecal cytarabine and methotrexate. Finally, those still in remission after 1 year of cytarabine and 6-thioguanine (AT) maintenance were randomised to receive either late intensification with cyclophosphamide, vincristine, cytarabine, and prednisolone (COAP) or continued AT. The median survival for the whole group was 12 months; the median duration of first remission was 15 months, with relapse-free survival at 5 years estimated at 18%. The factors most strongly associated with poor survival were performance status and age at presentation, but even among those over 60 years of age, half went into remission. Six courses of DAT consolidation gave a small advantage over two courses in reducing the number of late relapses but no significant survival advantage. Late intensification showed a marginally significant advantage over continued AT maintenance. The incidence of CNS relapse was low and unaffected by prophylaxis. The second remission rate varied from 10% when the first remission was shorter than 6 months to 61% when it had continued for more than 2 years. 40 patients received histocompatible allogeneic bone-marrow transplants in first remission. There was a high procedure-related death rate, particularly among patients over 30 years of age. Thus, initially at least, the transplanted group had shorter survival than a comparable group of chemotherapy-treated patients. Treatment specifications remained unchanged throughout the trial but those enrolled in the later half of the trial had a better (p = 0.003) survival.

The preliminary results are presented from a study in which 85 serious tibial fractures were treated with external skeletal fixation. In group I patients were treated with highly rigid fixation. In group II the same fixation was used but axial micromovement was applied across the fracture site for 30 min per day, starting 1-3 weeks after injury and continuing until partial weight-bearing, which leads to self-induced movement. The overall mean time to independent weight-bearing was longer in group I than group II (p = 0.02); delayed union occurred in more group I patients. Objective measurement of fracture stiffness was made by means of strain gauges placed on the fixation frame for 49 fractures treated consecutively. The time to reach stiffness levels equivalent to clinical union was significantly longer in group I than in group II. The fractures in the treatment groups were of comparable severity. It seems that the fracture healing process is susceptible to small changes in mechanical environment.