Although it is well established that cervical priming before surgically induced abortion reduces the incidence of complications, its use is infrequent and confined to groups perceived to be at high risk. We compared the effect of prostaglandin E1 analogues, gemeprost and misoprostol, on the cervix. Both induced clinical and histochemical changes that were significantly different from controls and were likely to have therapeutic value. Misoprostol, however, is cheap, easily stored, and associated with few side-effects. Cervical pre-dilation with misoprostol may be considered in all women having surgically induced abortions.

Over the past decade various clinical trials have used monoclonal antibodies as therapeutic agents against solid tumours. No consistent pattern of response or improved survival has yet emerged although antigenic heterogeneity and insufficient accessibility of cells in advanced tumours have been offered as explanations for these failures. We designed a study in which a monoclonal antibody was used to target minimal residual disease in an early stage of tumour cell dissemination in patients with colorectal cancer. Only patients in Dukes' stage C who had undergone curative surgery and were free of manifest residual tumour were admitted. 189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved by dynamic randomisation procedure. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% (Cox's proportional hazard, p = 0.04, log-rank p = 0.05) and decreased the recurrence rate by 27% (p = 0.03, p = 0.05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p = 0.0014, p = 0.002), an effect that was not seen for local relapses (p = 0.74, p = 0.67). Toxic effects of 17-1A antibody were infrequent, consisting mainly of mild constitutional and gastrointestinal symptoms. During 371 infusions four anaphylactic reactions were seen, all controllable by intravenous steroids and none necessitated admission to hospital. Adjuvant therapy with 17-1A antibody extends life and prolongs remission in patients with colorectal cancer of Dukes' stage C.

Compression ultrasonography is regarded as the non-invasive gold-standard to detect deep vein thrombosis (DVT) in patients presenting with symptoms. However, its use as a screening method in symptom-free postoperative patients at high risk of developing DVT remains controversial. In 100 consecutive patients who had undergone craniotomy, we compared the results of bilateral compression ultrasonic measurements of the results of bilateral compression ultrasonic measurements of the entire legs with the outcomes of contrast venography. Proximal DVT was detected in 13 patients, 5 of whom also had an abnormal ultrasonic result (sensitivity 38%, 95% CI 8-69%). Only 5 of the 9 patients with an abnormal ultrasound result for the proximal veins had proximal DVT (positive predictive value, 56%, 18-94%). Calf sonograms were evaluable in 71 of the 91 patients with bilaterally normal ultrasound results for the proximal veins. Of the 16 patients with calf DVT, ultrasound was abnormal in 8 (sensitivity 50%, 25-75%). Overall, ultrasound detected 13 of the 26 patients with proximal or isolated calf DVT (sensitivity 50%, 29-71%). The positive predictive value for the whole leg examination was 41% (24-60%). Most thrombi missed by ultrasound were non-occlusive and smaller than 5 cm. We conclude that compression ultrasound is not useful for screening for DVT in symptom-free postoperative high-risk patients.

Two sources of artifactual pulse-oximetry estimation were investigated in 20 neonates. Increased pressure on tissue due to inappropriate sensor fixation was mimicked with a blood pressure cuff. The error in arterial oxygen saturation (pSO2) exceeded 2 SD (> 3%) in 25% subjects at 50 mm Hg which in an ancillary experiment was produced by 11 of 26 nurses fixing the sensor. Venous congestion at 30 and 40 mm Hg permitted normal detection of pulse rate but induced errors in pSO2 over 2 SD in 15% and 30% of subjects, respectively. Pulse-oximeter values need to be scrutinised for these common errors.

We did a population study to identify the prevalence of reactions to eight foods commonly perceived to cause sensitivity in the UK. A cross-sectional survey of 7500 households in the Wycombe Health Authority area and the same number of randomly-selected households nationwide was followed up by interviews of positive respondents from the Wycombe Health Authority area. Those who agreed entered a double-blind, placebo-controlled food challenge study to confirm food intolerance. 20.4% of the nationwide sample and 19.9% of the High Wycombe sample complained of food intolerance. Of the 93 subjects who entered the double-blind, placebo-controlled food challenge, 19.4% (95% confidence interval 11.4%-27.4%) had a positive reaction. The estimated prevalence of reactions to the eight foods tested in the population varied from 1.4% to 1.8% according to the definition used. Women perceived food intolerance more frequently and showed a higher rate of positive results to food challenge. There is a discrepancy between perception of food intolerance and the results of the double-blind placebo-controlled food challenges. The consequences of mistaken perception of food intolerance may be considerable in financial, nutritional, and health terms.

In Japan the standard adjuvant treatment after resection of gastric cancer is intravenous mitomycin plus oral fluorouracil. We have assessed the efficacy of protein-bound polysaccharide (PSK) in addition to standard chemotherapy in patients who had undergone curative gastrectomy at 46 institutions in central Japan. 262 patients were randomly assigned standard treatment alone or with PSK. The minimum follow-up time was 5 years (range 5-7 years). PSK improved both the 5-year disease-free rate (70.7 vs 59.4% in standard treatment group, p = 0.047) and 5-year survival (73.0 vs 60.0%, p = 0.044). The two regimens had only slight toxic effects, consisting of nausea, leucopenia, and liver function impairment, and there were no significant differences between the groups. The treatments were clinically well tolerated and compliance was good. Addition of PSK to adjuvant chemotherapy with mitomycin and fluorouracil is beneficial as treatment after curative gastrectomy.

GISSI-3 is a multicentre randomised clinical trial to assess the efficacy of lisinopril, transdermal glyceryl trinitrate (GTN), and their combination in improving survival and ventricular function after acute myocardial infarction (AMI). Between June, 1991, and July, 1993, 19,394 patients were randomised from 200 coronary care units in Italy. Eligible patients presented within 24 h of symptom onset and had no clear indications for or against the study treatments. In a factorial design patients were randomly assigned 6 weeks of oral lisinopril (5 mg initial dose and then 10 mg daily) or open control as well as nitrates (intravenous for the first 24 h followed by transdermal GTN 10 mg daily) or open control. Complete clinical data and 6-week follow-up were available for 18,895 (97.4%) patients randomised. Two-dimensional echocardiographic data were available for 14,209 patients. Overall 6-week mortality was 6.7%. Lisinopril, started within 24 h from AMI symptoms, produced significant reductions in overall mortality (odds ratio 0.88 [95% CI 0.79-0.99]) and in the combined outcome measure of mortality and severe ventricular dysfunction (0.90 [0.84-0.98]). In the same trial the systematic administration of transdermal GTN did not show any independent effect on the same outcome measures (0.94 [0.84-1.05] and 0.94 [0.87-1.02]). Systematic combined administration of lisinopril and GTN also produced significant reductions in overall mortality (0.83 [0.70-0.97]) and in the combined endpoint (0.85 [0.76-0.94]). The favourable effect of lisinopril alone or with GTN was clear also in the predefined high-risk populations (elderly patients and women) for the combined endpoint. These findings were obtained in a population intensively exposed to recommended treatments (thrombolysis 72%, beta-blockade 31%, and aspirin 84%); non-protocol treatment with angiotensin-converting-enzyme inhibitors and nitrates was allowed for specific clinical indications. No excess of unfavourable clinically relevant events in the treated groups was reported.

Patients with plateau-phase multiple myeloma have an increased risk of life-threatening bacterial infections and polyclonal humoral immune suppression. We conducted a randomised, double-blind, placebo-controlled, multicentre trial of intravenous immunoglobulin (IVIg) as prophylaxis against infection. 82 patients with stable multiple myeloma received monthly infusions of IVIg at 0.4 g/kg body weight or an equivalent volume of placebo (0.4% albumin) intravenously for 1 year. Other interventions, including chemotherapy, were not affected; no patient received prophylactic antibiotics. There were no differences at entry or on study in clinical or laboratory variables between patients in the two groups. There were no episodes of septicaemia or pneumonia in patients receiving IVIg compared with 10 in placebo patients (p = 0.002). There were 57 serious infections; 38 occurred in 470 patient-months on placebo, compared with 19 in 449 patient-months on IVIg (p = 0.019). IVIg also protected against recurrent infections (p = 0.021) in 60 patients who completed a year. Before treatment, 54 patients were immunised with Pneumovax and specific IgG responses were measured. A poor pneumococcal IgG antibody response (less than 2-fold increase) identified patients who had maximum benefit from IVIg. Mild adverse reactions were noted in 12% of IVIg infusions and 5% of placebo infusions. IVIg can be given safely to plateau-phase myeloma patients. It protects against life-threatening infections and significantly reduces the risk of recurrent infections. The individuals who benefit most can be identified prospectively by measuring IgG antibody responses to pneumococcal immunisation.

When a patient resuscitated from cardiac arrest remains unconscious the clinician would like to have a reliable early method for predicting the outcome. The objective of our study was to predict cerebral outcome after cardiac arrest by clinical neurological examination. The data were drawn from an international multicentre controlled clinical trial of thiopentone. Twelve hospitals in nine countries took part. 262 comatose cardiac arrest survivors were followed up for one year. These patients were given advanced life support (American Heart Association guidelines) followed by intensive care to a standardised protocol. Glasgow and Glasgow-Pittsburgh coma scores and their constituent signs were recorded at fixed times. Outcome was taken to be the best cerebral performance at any time during follow-up, and for that purpose we used cerebral performance categories (CPC 1-5) of the Glasgow outcome categories. A poor outcome (CPC 3-5) could be predicted immediately after reperfusion (at entry into the study) with an accuracy ranging from 52% to 84% for various signs and scores. On the third day it was possible to identify severely disabled or permanently comatose survivors without false predictions using both coma scores and several of their constituent variables. The best predictor was absence of motor response to pain. This modelling exercise now needs to be repeated on a new series of patients but the results do suggest that, after 3 days, stringent ethical criteria can be met and used in decision-making about termination of care in comatose cardiac arrest survivors.

Theophylline, in addition to its bronchodilator effect, may attenuate inflammation in asthma. We did a double-blind placebo-controlled study of the effect of oral theophylline on the inflammatory response of the bronchial mucosa to inhalation of allergen in 19 atopic asthmatic subjects. Bronchoscopy and bronchial biopsy were done 24 hours after allergen inhalation before and after six weeks of treatment with oral slow-release theophylline, 200 mg 12 hourly. The mean serum concentration was 36.6 mumol/L, which is below the currently-accepted therapeutic range. After treatment with theophylline there was a significant reduction in the number of EG2-positive activated eosinophils (5.9 before and 2.1 after treatment, Wilcoxon signed rank p < 0.05) and total eosinophils (16.7 before and 7.6 after treatment, p < 0.05) beneath the epithelial basement membrane. We conclude that low-dose oral theophylline attenuates airway inflammatory response to allergen inhalation in atopic asthma.

Although histamine release is recognised as a common event during anaesthesia and surgery, few clinicians judge the resultant cardiorespiratory disturbances serious enough to warrant prophylaxis with antihistamines. We have assessed the incidence and importance of histamine release in a randomised 2 x 2 factorial study. 240 patients representing a routine throughput of major general surgery were studied during a standardised induction of anaesthesia and preoperative loading of the circulation with either Ringer solution or Haemaccel-35, with or without antihistamine prophylaxis with dimetindene (H1) plus cimetidine (H2). Cardiorespiratory disturbances were graded as detectable, clinically relevant, or life-threatening from observers' records of the anaesthesia and the actions taken by the anaesthetists. Disturbances that were accompanied by significant rises in plasma histamine were further designated histamine-related, and those that were not were designated histamine-unrelated. Anaesthetists, observers, and designators were blinded to whether or not the patients had received antihistamines and to which solution was used for circulatory volume loading. Clinically relevant or life-threatening histamine-related disturbances occurred in 8% of the patients who after induction of anaesthesia received Ringer without antihistamines, in 26% of those who received Haemaccel without antihistamines, and in 2% or less of those who received antihistamines (p < or = 0.0001). There were 4 life-threatening histamine-related disturbances, all in patients who received Haemaccel without antihistamines (p < 0.01). Histamine-unrelated disturbances occurred in 16% overall, with no obvious effect of Haemaccel or antihistamines. The histamine-related disturbances under anaesthesia were remarkable for their severity (even with small rises in histamine concentrations), for the prevalence of bradycardia, and for the absence of skin signs. Their likelihood and severity were increased in patients with tumours. The results of the trial make a case for routine prophylaxis with antihistamines as part of anaesthetic management.