In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.

In a prospective randomised study, 31 patients with an unruptured tubal pregnancy were treated either with local and systemic prostaglandins or with local instillation of a hyperosmolar glucose solution. Prostaglandin therapy was successful in 13 of 15 patients and glucose therapy in 16 of 16. 9 women treated with prostaglandins had cramping abdominal pains postoperatively. No side-effects were noted in those treated with glucose. At subsequent hysterosalpingography 5 of 6 patients treated with prostaglandins and 7 of 8 treated with glucose had normal tubal configuration and patency. 3 patients treated with glucose later had a normal intrauterine pregnancy, demonstrably through the affected tube in 1 case. These results suggest that local instillation of hyperosmolar glucose solution is an option in the laparoscopic management of unruptured tubal pregnancies.

In a study with 2 x 2 factorial design, 20,891 patients with suspected acute myocardial infarction of less than 6 h duration (12,490 from the GISSI-2 trial and 8401 recruited elsewhere) were randomly allocated to alteplase (recombinant tissue plasminogen activator, tPA) or streptokinase (SK) and to subcutaneous heparin, beginning 12 h after the start of thrombolytic therapy or no heparin. The protocol recommended that, in the absence of specific contraindications, all patients should receive aspirin and intravenous beta-blockade as soon as possible. No significant differences in hospital mortality were found between tPA and SK (8.9% versus 8.5%) or between heparin and no heparin (8.5% versus 8.9%). The incidence of major cardiac complications was also very similar in the different groups. For non-cardiac complications significant differences between the treatment groups were observed: more strokes were reported with tPA than with SK (1.3% versus 1%) while more major bleeds occurred with SK than with tPA (0.6% versus 0.9%). Subcutaneous heparin was likewise associated with an excess of major bleeds (1.0% with heparin versus 0.5% without heparin) but did not affect the incidence of stroke or reinfarction.

A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1.5 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12,500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12,490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23.1%; SK 22.5%; relative risk 1.04, 95% Cl 0.95-1.13), nor after the addition of heparin to the aspirin treatment (hep 22.7%, no hep 22.9%; RR 0.99, 95% Cl 0.91-1.08). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0.5%, SK 1.0%, RR 0.57, 95% Cl 0.38-0.85; hep 1.0%, no hep 0.6%, RR 1.64, 95% Cl 1.09-2.45), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8.8% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI.

516 patients with New York Heart Association class III and IV heart failure despite treatment with diuretics and angiotensin converting enzyme inhibitors were randomised in a double-blind between-group comparison to xamoterol 200 mg (352) or placebo (164) twice daily for 13 weeks. There was no difference between the treatments in loss of clinical signs. Visual analogue scale and Likert scores indicated that breathlessness was less severe with xamoterol, but there was no difference in exercise duration or total work done. Xamoterol reduced maximum exercise heart rate and systolic blood pressure, did not affect the number of ventricular premature beats after exercise, showed no arrhythmogenic activity, and had variable (agonist and antagonist) effects on 24 h heart rate. On intention-to-treat analysis 32 (9.1%) patients in the xamoterol group and 6 (3.7%) patients in the placebo group died within 100 days of randomisation (p = 0.02).

Serial sectioning of ipsilateral axillary lymph nodes judged to be disease-free after routine histological examination revealed micrometastases in 83 (9%) of 921 breast cancer subjects. These patients had a poorer disease-free (p = 0.003) and overall (p = 0.002) survival after 5 years' median follow-up than did patients whose nodes remained negative on serial sectioning. The presence of axillary lymph node micrometastases correlated with the presence of vascular invasion and tumour size (p less than 0.0001 and p = 0.02, respectively). The presence of occult micrometastases remained statistically significant after adjusting for other prognostic factors. The detection of these micrometastases in lymph nodes may identify a high risk "node-negative" population and should be considered as part of the routine pathology examination.

Screening of 1226 nulliparous women by means of doppler uteroplacental flow-velocity waveforms in early pregnancy identified 148 (12%) as being at high risk of pregnancy-induced hypertension. After exclusions and refusals, 100 women were randomly allocated to groups receiving either low-dose aspirin (75 mg daily; 48 patients) or identical placebo (52 patients) for the remainder of the pregnancy. The difference between the aspirin and placebo groups in the frequency of pregnancy-induced hypertension (13% vs 25%) did not achieve significance, but there were significant differences in the frequencies of proteinuric hypertension (2% vs 19%) and hypertension occurring before 37 weeks' gestation (0% vs 17%). Fewer aspirin-treated than placebo-treated women had low birthweight babies (15% vs 25%), but this difference was not significant. The only perinatal death in the aspirin group followed a cord accident during labour, whereas the 3 perinatal deaths in the placebo group were all due to severe hypertensive disease. No maternal or neonatal side-effects were observed in either group.

424 preterm infants were randomly assigned a standard "term" formula or a nutrient-enriched "preterm" formula as sole diets (trial A) or as supplements to mother's own expressed milk (trial B) for a median of 4 weeks postnatally. 18 months post term, blind evaluation of 377 survivors showed that those previously fed preterm rather than term formula had major developmental advantages, more so in motor than mental function; the advantages, in both mental and motor scores, were especially striking in small-for-gestational-age infants and in males. For motor development index in trial A, this advantage was 15 points; in infants born small for gestation, it was 23 points (nearly 1.5 SD). Moderate developmental impairment (developmental index less than 85), notably motor impairment, was considerably more common in the group fed term formula. Infants fed preterm formula also had a small benefit in social maturity quotient. Thus, a short period of early dietary manipulation in preterm infants had major consequences for later development, which suggests that the first weeks may be critical for nutrition.

Heavy chronic consumption of kava (Piper methysticum) is associated with a pellagroid dermopathy that has been attributed to niacin deficiency. Over 200 male kava drinkers in the Tonga Islands were interviewed and examined regarding the characteristic skin changes. A scaly rash suggestive of ichthyosis and eye irritation were present in some heavy kava drinkers. 29 kava drinkers with prominent skin changes were randomised to receive either 100 mg oral nicotinamide or placebo daily for three weeks. Skin examinations and photographs showed clinical improvement in 5/15 of the nicotinamide group and 5/14 of the placebo group. These data, along with history and physical examination findings, suggest that niacin deficiency is not responsible for the rash, which is more characteristic of an acquired ichthyosis.

40 patients (24 male, 16 female, aged 21-59 years) of American Society of Anesthesiologists class I or II who were undergoing routine surgery took part in a randomised, double-blind comparison of the anaesthetic efficacy and potency of xenon and nitrous oxide and their effects on the circulatory and respiratory systems. During anaesthesia, for each rise in blood pressure of more than 20% of the preanaesthetic (baseline) value, the patient received 0.1 mg fentanyl. The total amount of fentanyl required per patient was used as an index of the anaesthetic potency of the study gases. Patients in the xenon group required on average only 0.05 mg fentanyl, whereas those in the nitrous oxide group required 0.24 mg fentanyl; the duration of anaesthesia was similar in the two groups. Changes in blood pressure were significantly greater throughout the study in the nitrous oxide than in the xenon group. Thorax-lung compliance fell during the study period in the nitrous oxide group but not in the xenon group. Thus, xenon is a potent and effective anaesthetic which can be safely used under routine conditions.

The effects of two pranayama yoga breathing exercises on airway reactivity, airway calibre, symptom scores, and medication use in patients with mild asthma were assessed in a randomised, double-blind, placebo-controlled, crossover trial. After baseline assessment over 1 week, 18 patients with mild asthma practised slow deep breathing for 15 min twice a day for two consecutive 2-week periods. During the active period, subjects were asked to breathe through a Pink City lung (PCL) exerciser--a device which imposes slowing of breathing and a 1:2 inspiration:expiration duration ratio equivalent to pranayama breathing methods; during the control period, subjects breathed through a matched placebo device. Mean forced expiratory volume in 1 s (FEV1), peak expiratory flow rate, symptom score, and inhaler use over the last 3 days of each treatment period were assessed in comparison with the baseline assessment period; all improved more with the PCL exerciser than with the placebo device, but the differences were not significant. There was a statistically significant increase in the dose of histamine needed to provoke a 20% reduction in FEV1 (PD20) during pranayama breathing but not with the placebo device. The usefulness of controlled ventilation exercises in the control of asthma should be further investigated.

The effect of the progesterone antagonist mifepristone on the cervix was investigated in two randomised double-blind placebo-controlled trials, the first in 30 women undergoing first trimester surgical termination of pregnancy and the second in 30 non-pregnant premenopausal women. 600 mg mifepristone, given orally 48 h before surgery, increased the mean preoperative cervical dilatation in both pregnant and non-pregnant treatment groups and also reduced the force required to dilate the pregnant and non-pregnant cervix.

50 patients with intractable duodenal ulcer were randomly assigned to 4 weeks of treatment with colloidal bismuth subcitrate (CBS) alone (26 patients) or with amoxicillin and metronidazole (24 patients). 5 patients (all on triple therapy) withdrew because of side-effects. In 17 of the 45 patients who completed the treatment, Helicobacter pylori was eradicated, and there was no ulcer relapse during the first 12 months of follow-up. The ulcer relapse rate was significantly higher (17 of 21 [89%]) among patients who remained positive for H pylori. 9 patients who remained positive for H pylori and had ulcer relapses within 6 months of treatment with CBS alone, were subsequently given triple therapy. 7 of the 9 showed H pylori eradication and no relapses within the next 12 months. The 2 patients still H pylori-positive after triple therapy had further ulcer relapses. H pylori eradication, without altering acid output, will become the mainstay of duodenal ulcer treatment because it cures the disease.

In a randomised, controlled trial 2514 patients with suspected acute myocardial infarction received 100 mg intravenous alteplase (recombinant tissue plasminogen activator [rt-PA]) plus heparin within 5 h of onset of symptoms, and 2499 similar controls received placebo plus heparin. At 1 month the overall mortality rates were 7.2% and 9.8%, respectively, a relative reduction of 26% (95% confidence interval [CI] 11-39%). At 6 months the mortality rates were 10.4% (alteplase) and 13.1% (placebo), a relative reduction of 21% (95% Cl 8%-32%, p = 0.0026). 6-month mortality rates in patients with proven myocardial infarction were 12.6% and 17.1%, respectively (relative reduction 26%; 95% Cl 14-37%); this effect was similar for anterior (15.6% vs 21.2%) and inferior (7.7% vs 12.8%) myocardial infarction. 6-month mortality rates were lower in those treated with alteplase irrespective of other recognised cardiac risk factors. However, treatment with alteplase made no difference to subsequent cardiac events after one month (readmissions, reinfarctions, death) nor to treatment for angina or heart failure. Product limit estimates of one year mortality are 13.2% with alteplase and 15.1% with placebo. The corresponding figures for patients with an index diagnosis of myocardial infarction are 15.7% and 18.9%, a relative reduction of 16.9%.