Food intolerance seems to be an important cause of the hyperkinetic syndrome, but restricted diets are expensive, socially disruptive, and often nutritionally inadequate. Enzyme-potentiated desensitisation (EPD) may overcome some of these difficulties. EPD was tested in a double-blind placebo-controlled trial among 40 children with food-induced hyperkinetic behaviour disorder. A total of 185 children with established hyperkinetic syndrome underwent oligoantigenic dietary treatment for four weeks. 116 whose behaviour responded had provoking foods identified by sequential reintroduction. Foods that reproducibly provoked overactivity were avoided. 40 patients who were then invited to take part in the hyposensitisation trial were randomly assigned to treated and control groups. Treated patients received three doses of EPD (beta-glucuronidase and small quantities of food antigens) intradermally at two-monthly intervals. Controls received buffer only. Thereafter, patients were allowed to eat known provoking foods. Of 20 patients who received active treatment, 16 became tolerant towards provoking foods compared with 4 of 20 who received placebo (p less than 0.001). Our results show that EPD permits children with food-induced hyperkinetic syndrome to eat foods that had previously been identified as responsible for their symptoms. These results also support the notion that food allergy is a possible mechanism of the hyperkinetic syndrome.

Prompt treatment with empirical antibiotics in neutropenic febrile patients reduces morbidity and mortality. Most patients have been treated with parenteral combination antibiotics, but newer antibiotics with broad-spectrum bactericidal activity have made monotherapy feasible. Ofloxacin, a broad-spectrum fluoroquinolone, has the additional advantage that bactericidal concentrations can be achieved with oral administration. We have compared ofloxacin as an oral single agent with standard parenteral combination antibiotics for the management of neutropenic febrile patients in a prospective, randomised trial. Patients with severe neutropenia (absolute neutrophil count less than or equal to 0.5 x 10(9)/l), fever above 38 degrees C, and ability to take drugs by mouth were eligible for the study. After initial investigations, 60 patients were randomly assigned to oral ofloxacin 400 mg twice daily and 62 to parenteral combination antibiotic therapy (amikacin 15 mg/kg daily, plus, at various times in the trial, carbenicillin, cloxacillin, or piperacillin). Patients were examined 72 h and 7 days after the start of treatment and when neutropenia resolved. 24 (40%) ofloxacin-treated and 26 (42%) combination-treated patients had pyrexia of unknown origin (PUO). In both treatment groups, the treatment success rate was higher for such patients than for those with clinically or microbiologically documented infections (92% vs 67% [p less than 0.05] for ofloxacin; 85% vs 64% for combination). There were no significant differences in success rates of ofloxacin and combination treatment for these subgroups or overall (77% vs 73%). Patients with neutropenia for less than 1 week had better responses to both treatments than patients with longer-lasting neutropenia. There were 4 (7%) deaths in the ofloxacin group and 6 (10%) in the combination group. Both regimens were well tolerated. We conclude that oral single-agent ofloxacin is as effective as parenteral combination antibiotic therapy in neutropenic febrile patients, especially those expected to have short durations of neutropenia.

A home-based exercise programme has been found to be as useful as a hospital-based one in improving cardiovascular fitness after an acute myocardial infarction. To find out whether a comprehensive home-based programme would reduce psychological distress, 176 patients with an acute myocardial infarction were randomly allocated to a self-help rehabilitation programme based on a heart manual or to receive standard care plus a placebo package of information and informal counselling. Psychological adjustment, as assessed by the Hospital Anxiety and Depression Scale, was better in the rehabilitation group at 1 year. They also had significantly less contact with their general practitioners during the following year and significantly fewer were readmitted to hospital in the first 6 months. The improvement was greatest among patients who were clinically anxious or depressed at discharge from hospital. The cost-effectiveness of the home-based programme has yet to be compared with that of a hospital-based programme, but the findings of this study indicate that it might be worth offering such a package to all patients with acute myocardial infarction.

The high birthweights and long duration of pregnancy in the Faroe Islands led us to suggest that a high intake of marine-fat-derived n-3 fatty acids might prolong pregnancy by shifting the balance of production of prostaglandins involved in parturition. We have compared the effects on pregnancy duration, birthweight, and birth length of a fish-oil supplement, a control olive-oil supplement, and no supplementation. 533 healthy Danish women in week 30 of pregnancy were randomly assigned in a ratio of 2/1/1 to fish oil (four 1 g Pikasol capsules [containing 2.7 g n-3 fatty acids] per day), olive oil (four 1 g capsules per day), or no supplement. The three groups differed in mean length of gestation (p = 0.006), which was highest in the fish-oil group and lowest in the olive-oil group; the result was similar when the analysis was restricted to women with an estimate of gestation length based on early ultrasound findings (443 women). Pregnancies in the fish-oil group were on average 4.0 (95% confidence interval 1.5-6.4) days longer than those in the olive-oil group; the difference in birthweight was 107 (1-214) g. The effect of supplementation on length of gestation was influenced by intake of fish and of fish oil: the difference between fish-oil and other groups was increased by a low fish intake at baseline. Fish-oil supplementation in the third trimester seems to prolong pregnancy without detrimental effects on the growth of the fetus or on the course of labour.

Controlled trials have shown that bleeding peptic ulcers can be successfully treated by endoscopy and injection of adrenaline, with or without sclerosant. However, these trials have been done in major research centres, and endoscopic treatment of upper gastrointestinal bleeding has not yet become routine in general hospitals. We have done a prospective, randomised, controlled trial of injection treatment for bleeding peptic ulcers in a district general hospital. Between April, 1989, and June, 1991, all patients with acute upper gastrointestinal bleeding (n = 555) underwent endoscopy by an experienced endoscopist within 24 h of admission. 98 patients were found to have an ulcer with a visible vessel, of whom 93 were randomised to injection (n = 48) or standard treatment alone (n = 45). Injection treatment consisted of 1-2 ml of 1 in 10,000 adrenaline injected at four to six sites around the ulcer. Adrenaline and 5% ethanolamine oleate (1-2 ml) were then injected directly into the vessel. The medical team managing the patient was unaware of the endoscopic treatment given. The two groups were similar for age, initial haemoglobin concentration, shock, and ulcer site. Rebleeding (injected 8 [16.7%] vs control 21 [46.7%], p = 0.011) was significantly reduced in treated patients. The treated group also had lower mortality (4 [8.3%] vs 9 [20%]), requirement for surgery (4 [8.3%] vs 8 [17.8%]), and mean blood-transfusion requirement (5 vs 7.5 units). Endoscopic injection treatment in our patients significantly reduced rebleeding rate and may have other benefits. This cheap and widely applicable treatment can be used routinely in the management of patients with bleeding peptic ulcers who are at high risk of rebleeding.

Patients receiving antibiotics during bladder drainage have a lower incidence of urinary-tract infections compared with similar patients not on antibiotics. However, antibiotic prophylaxis in patients with a urinary catheter is opposed because of the fear of inducing resistant bacterial strains. We have done a double-blind, placebo-controlled trial of prophylactic ciprofloxacin in selected groups of surgical patients who had postoperative bladder drainage scheduled to last for 3 to 14 days. Patients were randomly assigned to receive placebo (n = 61), 250 mg ciprofloxacin per day (n = 59), or 500 mg ciprofloxacin twice daily (n = 64) from postoperative day 2 until catheter removal. 75% of placebo patients were bacteriuric at catheter removal compared with 16% of ciprofloxacin-treated patients (relative risk [RR] [95% CI] 4.7 [3.0-7.4]). The prevalence of pyuria among placebo patients increased from 11% to 42% while the catheter was in place; by contrast, the rate of pyuria was 11% or less in patients receiving ciprofloxacin (RR 4.0 [2.1-7.3]). 20% of placebo patients had symptomatic urinary-tract infections, including 3 with septicaemia, compared with 5% of the ciprofloxacin groups (RR 4.0 [1.6-10.2]). Bacteria isolated from urines of placebo patients at catheter removal were mostly species of enterobacteriaceae (37%), staphylococci (26%), and Enterococcus faecalis (20%), whereas species isolated from urines of ciprofloxacin patients were virtually all gram-positive. Ciprofloxacin-resistant mutants of normally sensitive gram-negative bacteria were not observed. Ciprofloxacin prophylaxis is effective and safe in the prevention of catheter-associated urinary tract infection and related morbidity in selected groups of patients requiring 3 to 14 days of bladder drainage.

Exercise capacity in patients with stable heart failure may be influenced by prolonged drug treatment or exercise training, but acute interventions are generally thought to have little effect. Cardiorespiratory responses to exercise were studied in 12 consecutive patients with chronic congestive heart failure who underwent serial submaximal and maximal exercise tests at inspired oxygen concentrations of 21% (room air), 30%, and 50%. Mean (SD) exercise duration during progressive testing to maximum exercise capacity was prolonged from 548 (276) s on room air to 632 (285) s on 50% oxygen (p = 0.012). During steady-state exercise at 45 W, oxygen enrichment to 50% was associated with significantly increased arterial oxygen saturation (94.6 [1.9]% to 97.5 [1.3]%), and significantly reduced minute ventilation (36.1 [8.6] l/min to 28.1 [5.9] l/min), cardiac output (7.5 [2.3] l/min to 6.5 [1.9] l/min), and subjective scores for fatigue and breathlessness (13.9 [3.1] to 11.5 [3.5]) compared with room air intermediate changes were observed with 30% inspired oxygen. Increased inspired oxygen concentrations can improve exercise performance acutely and modify the ventilatory response to exercise in patients with heart failure. Hyperoxia reduces ventilatory response and circulatory demand while maintaining oxygen delivery at a given workload. The potential benefits of increased inspired oxygen concentrations in the treatment of chronic heart failure merit further assessment.

The finding that the carotid vascular beds are sensitive to the potent vasodilator calcitonin-gene-related peptide (CGRP) suggested that the drug might help to prevent ischaemic deterioration after surgery for aneurysmal subarachnoid haemorrhage (SAH). The results of a preliminary study were encouraging, so we have carried out a randomised multicentre single-blind comparison of CGRP and standard best management in patients with ischaemic deficits after surgery for ruptured intracranial aneurysms. Patients aged 18-70 years in whom a focal neurological deficit developed or who had a reduction of 2 or more points on the Glasgow coma scale (GCS) after surgery entered the study after computed tomography had excluded non-ischaemic causes for the neurological deficit. 62 patients were randomly assigned an infusion of 0.6 micrograms/min CGRP for 4 h, then up to a maximum of 10 days, and 55 patients standard best management (controls). GCS and haemodynamic variables were assessed during the hospital stay, and all patients were followed up at 3 months by an independent investigator, who was unaware of their treatment. Outcome, measured on the Glasgow outcome scale, at 3 months was good in 66% of those treated with CGRP and 60% in the controls; the relative risk of a poor outcome in CGRP-treated patients was 0.88 (95% confidence interval 0.60 to 1.28). Hypotension was a common side-effect of the CGRP infusion. 66% of the CGRP group did not complete treatment because of adverse events (19 patients), lack of improvement at 4 h (17 patients) or later (4 patients), or patient's request (1 patient). Although we could not show a significant beneficial effect of CGRP in this trial, the wide confidence interval for the risk of a poor outcome and the fact that only a third of patients completed treatment mean that a clinically useful benefit cannot yet be ruled out.

The increasing frequency of therapeutic failures in falciparum malaria in Thailand shows an urgent need for effective drugs or drug combinations. Artesunate, a qinghaosu derivative, is effective in clearing parasitaemia rapidly, but the recrudescence rate can be as high as 50%. We have compared artesunate followed by mefloquine with each drug alone in acute, uncomplicated falciparum malaria. 127 patients were randomly assigned treatment with artesunate (600 mg over 5 days), mefloquine (750 mg then 500 mg 6 h later), or artesunate followed by mefloquine. All patients were admitted to hospital for 28 days to exclude reinfection. Cure was defined as no recrudescence during the 28 days' follow-up. The cure rates for mefloquine and artesunate alone were 81% (30/37 patients) and 88% (35/40); the combination was effective in all of 39 patients. Fever and parasite clearance times were significantly shorter in the groups that received artesunate than in the mefloquine-only group. The frequency of nausea and vomiting was slightly, but not significantly, higher among patients who received both drugs than in the other groups. The combination of artesunate followed by mefloquine is highly effective and well tolerated in patients with acute, uncomplicated falciparum malaria in Thailand.

The risk of pelvic inflammatory disease (PID) associated with use of an intrauterine device (IUD) has been an important concern that has dominated decisions on its use throughout the world, especially in the USA. Early research that suggested such an association led to both a dramatic decline in use of the method and its withdrawal from the US market by two manufacturers. However, factors other than use of an IUD are now thought to be major determinants of PID risk. To address these concerns, we have reviewed the World Health Organisation's IUD clinical trial data to explore the incidence and patterns of PID risk with use of an IUD. The overall rate of PID among 22,908 IUD insertions and during 51,399 woman-years of follow-up was 1.6 cases per 1000 woman-years of use. After adjustment for confounding factors, PID risk was more than six times higher during the 20 days after insertion than during later times (unadjusted rates, 9.7 vs 1.4 per 1000 woman-years, respectively); the risk was low and constant for up to eight years of follow-up. Rates varied according to geographical area (highest in Africa and lowest in China) and were inversely associated with age. PID rates were lower among women who had IUDs inserted more recently. Our findings indicate that PID among IUD users is most strongly related to the insertion process and to background risk of sexually transmissible disease. PID is an infrequent event beyond the first 20 days after insertion. Because of this increased risk with insertion, IUDs should be left in place up to their maximum lifespan and should not routinely be replaced earlier, provided there are no contraindications to continued use and the woman wishes to continue with the device.

To speed collection of blood for autologous transfusion during elective surgery, patients may be given recombinant human erythropoietin (r-HuEPO). In a controlled trial, we evaluated the effects of r-HuEPO on perioperative red-blood-cell and serum erythropoietin (s-EPO) production in patients donating blood before elective orthopaedic surgery. Patients were assigned randomly to receive no r-HuEPO (12 patients), or 3000 U (4), 6000 U (5), or 9000 U (4) of r-HuEPO intravenously twice a week from the time of the first blood donation. All patients received iron sulphate. 1200 ml blood was collected from each patient in three weekly donations of 400 ml. The 3000, 6000, and 9000 U treatment groups produced 284, 350, and 383 ml, respectively, of red cells during donation, and the untreated controls produced 211 ml. s-EPO concentrations were within the normal range during donation. After surgery, s-EPO concentrations peaked on postoperative day 1 in untreated patients and on day 7 in treated patients; therefore, r-HuEPO may suppress endogenous erythropoietin secretion. Although administration of r-HuEPO increases production of red blood cells, the preoperative anaemia induced by repeated phlebotomy without r-HuEPO may accelerate the postoperative secretion of endogenous erythropoietin.

41,299 patients entering 914 hospitals up to 24 h (median 4 h) after the onset of suspected acute myocardial infarction were randomised between streptokinase (SK: 1.5 MU infused over about 1 h), tissue plasminogen activator (tPA, duteplase: 0.60 MU/kg infused over about 4 h), or anisoylated plasminogen-streptokinase activator complex (APSAC), anistreplase: 30 U over about 3 min). All patients were to receive aspirin (162 mg/day enteric-coated), with the first tablet chewed for rapid and full antiplatelet effect. Half of all patients were randomly allocated subcutaneous calcium heparin (12,500 IU starting at 4 h and given twice daily for 7 days or until prior discharge) in addition to aspirin, and the other half were to receive aspirin alone. ASPIRIN PLUS HEPARIN VERSUS ASPIRIN ALONE--The addition of heparin to aspirin was associated with an excess of transfused or other major non-cerebral bleeds (1.0% aspirin plus heparin vs 0.8% aspirin alone; 2p < 0.01) and of definite or probable cerebral haemorrhage (0.56% vs 0.40%; 2p < 0.05), but with no significnat differences in total stroke (1.28% vs 1.18%). Reinfarctions were slightly less common among those allocated aspirin plus heparin (3.16% vs 3.47%; 2p = 0.09). There was no signficant difference in the pre-specified endpoint of 35-day mortality (2132 [10.3%] aspirin plus heparin vs 2189 [10.6%] aspirin alone). During the scheduled heparin treatment period there were slightly fewer deaths in the aspirin plus heparin group (days 0-7 in hospital: 1534 [7.4%] vs 1633 [7.9%]; 2 p = 0.06), with a slight convergence by day 35 (598 further deaths [3.1% of survivors] vs 556 [2.9%]). The pattern was similar to that observed in the GISSI-2 trial, so that in both trials combined there was a significant reduction in mortality during the scheduled treatment period (2071 [6.8%] vs 2239 [7.3%]; 2p < 0.01). This indicates avoidance of 5 deaths (SD 2) per 1000 patients allocated this high-dose subcutaneous heparin regimen in addition to aspirin, but some of any early benefit may be lost after heparin ceases, with no significant mortality advantage in days 0-35 (both trials: 3100 [10.0%] vs 3172 [10.2%]) or during follow-up to 6 months. SK VERSUS APSAC--APSAC was associated with significantly more reports of allergy causing persistent symptoms and of non-cerebral bleeds, but not of transfused bleeds or of reinfarctions. There was a slight excess of strokes with APSAC (1.04% SK vs 1.26% APSAC; 2p = 0.08), much of it appearing soon after treatment started (strokes during days 0-1: 0.50% SK vs 0.73% APSAC; 2p < 0.02) and being attributed to cerebral haemorrhage (0.24% SK vs 0.55% APSAC; 2p < 0.0001). No significant difference was observed in reinfarction (3.47% SK vs 3.55% APSAC). There was no significant mortality difference during days 0-35, either among all randomised patients (1455 [10.6%] SK vs 1448 [10.5%] APSAC) or among the pre-specified subset presenting within 0-6 h of pain onset and with ST elevation on the electrocardiogram in whom fibrinolytic treatment may have most to offer (861 [10.0%] SK vs 855 [9.9%] APSAC). No significant difference in 6-month survival was apparent overall or in the subset.(ABSTRACT TRUNCATED AT 400 WORDS)

Although exercise may be beneficial in cystic fibrosis (CF), patients' low tolerance to climatic heat stress means that physical exertion can increase morbidity and mortality. We postulated that the high salt content of CF patients' sweat and the consequent absence of body-fluid hyperosmolality during a long episode of sweating might deprive such patients of a thirst stimulus. Eight children with CF (four boys, four girls; aged 9.5-14.1 years) and eight controls, matched for age and sex, attended two randomly ordered sessions of exercise (cycling) in a chamber at 31-33 degrees C, relative humidity 43-47%. 20 min bouts of exercise (at 45% of predetermined maximum oxygen uptake) were interspersed with 25 min rest periods. At one session, chilled water was given every 15-20 min to replace fluid lost; at the other, drinking was guided by the child's thirst. At the thirst-guided session, CF patients drank much less than the controls did (0.80% vs 1.73% initial body weight) and lost twice as much fluid (1.57% vs 0.78% initial body weight). The recovery of heart rate after exercise was slower in CF patients, but there were no other signs of heat strain. The groups did not differ in any variable during the forced drinking session. We conclude that children with CF underestimate their fluid needs and undergo excessive dehydration during extended exposure to hot conditions.

Attempts to prevent peritoneal carcinomatosis after surgery for gastric cancer by intraperitoneal administration of anticancer drugs have not been successful, largely because the drugs are not retained in the peritoneal cavity. We have assessed the prophylactic efficacy of a delayed-release preparation--mitomycin adsorbed onto activated charcoal (M-CH). 50 patients with gastric cancer and serosal infiltration were randomly assigned intraperitoneal treatment with M-CH (50 mg mitomycin intraoperatively) or no anticancer prophylaxis (control). Survival rates for the 3 years of follow-up were significantly higher among the 24 M-CH recipients (1 was lost to follow-up) than among the 25 controls (p less than 0.01). There were significant differences in survival between the groups at 1.5 years after randomisation (difference 34.6% [95% confidence interval 8.5-60.8%]; p less than 0.01) and at 2.0, 2.5, and 3.0 years (41.7% [14.2-69.1%]; p less than 0.005). The concentration of mitomycin was significantly higher in peritoneal exudate than in plasma for 24 h after drug administration. Side-effects were slight and well tolerated. Thus, peroperative intraperitoneal treatment with M-CH seems to improve survival after gastrectomy for gastric cancer, presumably by a prophylactic effect on peritoneal recurrence.