A double-blind, placebo-controlled, crossover study on the effects of 4 months' growth hormone (GH) treatment was carried out in 22 GH-deficient adults (8 women, 14 men; mean [SEM] age 23.8 [1.2] years). 1 patient was withdrawn because of oedema. Mean total body weight of the other 21 did not change, whereas mean muscle volume of the thigh, estimated by computerised tomography (CT), was significantly higher after GH than after placebo (70.0 [3.7] vs 66.3 [3.1] ml/0.8 cm cross-sectional slice). The mean adipose tissue volume of the thigh and subscapular skinfold thickness fell significantly during GH treatment. Growth hormone caused a small increase in the isometric strength of the quadriceps muscles and a significant rise in exercise capacity (60.8 [7.2] vs 54.2 [6.6] kJ). The heart rate both at rest and after maximum exercise was low during the placebo period and increased significantly during GH treatment. Blood pressure and echocardiographic wall mass of the left ventricle did not change during the study. Growth hormone increased both mean glomerular filtration rate and renal plasma flow from a subnormal level on placebo to a level comparable with that of an age-matched control group. The filtration fraction did not change. Urinary albumin excretion was in the low normal range and was not affected by GH treatment. Finally, GH treatment normalised mean circulating levels of insulin-like growth factor 1 (IGF-1), which were low after the placebo period (96 [9] micrograms/l placebo; 224 [28] micrograms/l GH). These findings suggest that GH, in a conventional replacement dose, has several potentially beneficial effects in GH-deficient adults and therefore encourage future long-term trials.

The Canadian American Ticlopidine Study (CATS) is a randomised, double-blind, placebo-controlled trial to assess the effect of ticlopidine (250 mg twice daily) in reducing the rate of subsequent occurrence of stroke, myocardial infarction, or vascular death in patients who have had a recent thromboembolic stroke. Twenty-five centres entered 1072 patients into the study between 1 week and 4 months after their qualifying stroke. The patients were treated and followed for up to 3 years (mean 24 months). In the efficacy analysis, the event rate per year for stroke, myocardial infarction or vascular death, considered together, was 15.3% in the placebo group and 10.8% in the ticlopidine group, representing a relative risk reduction with ticlopidine of 30.2% (95% confidence interval 7.5-48.3%; p = 0.006). Ticlopidine was beneficial for both men and women (relative risk reductions 28.1%, p = 0.037, and 34.2%, p = 0.045, respectively). Analysis by intention-to-treat gave a smaller estimate of risk reduction (23.3%, p = 0.020) for stroke, myocardial infarction, or vascular death. Adverse experiences associated with ticlopidine included neutropenia (severe in about 1% of cases) and skin rash and diarrhoea (severe in 2% of cases each); all were reversible. This study provides evidence of a beneficial effect of ticlopidine in both men and women with a recent thromboembolic stroke.

392 patients were examined by endoscopy for acute upper gastrointestinal bleeding; 140 had ulcers containing an actively bleeding visible vessel or a non-bleeding visible vessel and were enrolled in a randomised trial of three endoscopic methods of haemostasis--adrenaline (1/10(4] alone, adrenaline plus polidocanol 1%, and adrenaline followed by yttrium-aluminium-garnet (YAG) laser photocoagulation. For patients with non-bleeding visible vessels sham treatment was significantly less effective in achieving haemostasis (8 of 20 patients) than were adrenaline plus polidocanol (18 of 20; p = 0.002) and adrenaline plus laser (16 of 20; p = 0.012). All three treatments significantly reduced total transfusion needs compared with sham treatment. For the whole group of patients, adrenaline plus polidocanol was significantly more effective than adrenaline alone in achieving permanent haemostasis; adrenaline plus laser was also more effective than adrenaline alone, but not significantly so. The efficacy of the three treatments was enhanced by repeated application on recurrence of bleeding. Since injection therapy with adrenaline and polidocanol was at least as effective as adrenaline plus laser therapy, it should be preferred over laser therapy because it is cheaper, easier to use, and perhaps also safer.

To assess the effectiveness of screening by faecal occult blood tests, 107,349 people without symptoms of colorectal disease identified from general practitioner records have been randomly allocated to test and control groups. 53,464 test subjects were invited to carry out the screening test; 27,651 (53%) of the 52,258 who received the tests did so. Further investigation of the 618 (2.3%) with positive tests showed 63 cancers (52% stage A) and 367 adenomas (266 subjects). Rescreening of subjects with negative results every 2 years (9510 first rescreen, 3639 second) has shown a significant fall in the rate of positive results (1.7% of 7344; 0.3% of 2906). Cancers have also been diagnosed in 20 subjects presenting in the interval between a negative test and rescreening, and in 83 non-responders. The incidence of cancer in the control group (123 subjects; 10.6% stage A) was 0.72 per 1000 person-years. Cancers detected by screening were at a less advanced pathological stage, but it is too early to show any effect of screening on mortality from colorectal cancer.

Four screening tests for bacteriuria were assessed at ward level in 418 elderly subjects and were compared with standard methods of bacterial culture. The tests were visual appearance; microscopy; dipstick for nitrite, leucocyte esterase, protein, and blood; and dipstick for nitrite and organisms. The sensitivity of the tests varied from 85.6% to 98.3%, and the specificity from 18.4% to 82.9%. A combination of visual appearance and dipstick testing for nitrite and leucocyte esterase gave a sensitivity of 96.1% with a specificity of 50.6%, and could have reduced by almost one-third the number of urine samples submitted to the laboratory for processing.

The efficacy and safety of oral cyclosporin 10 mg/kg per day in Behçet's disease were compared in a randomised double-masked study with those of colchicine, 1 mg orally per day, and were also investigated in a long-term open study. The double-masked study showed that cyclosporin was effective in treating not only the ocular manifestations of Behçet's disease but also oral aphthous ulcer, dermal lesions, and genital ulceration. Efficacy did not weaken during long-term treatment.

Combined therapy with clindamycin and primaquine was used in twenty-eight episodes of Pneumocystis carinii pneumonia in 25 patients, of whom 17 had been unresponsive or intolerant to conventional treatment and 8 were being treated for the first time. The treatment was effective in all but two episodes, the main adverse reaction being a generalised maculopapular rash.

32 subjects with long-term insulin-dependent diabetes mellitus (IDDM) were entered into a double-blind, randomised crossover trial with human and porcine insulin. They were treated during both periods with regular insulin and with protamine (NPH) insulin. 18 subjects started with human and 14 with porcine insulin; the two insulin periods each lasted twelve weeks; the insulin doses were much the same in the two periods (mean 23 [SD 9] U daily NPH; 14 [7] U daily regular insulin), as were blood glucose profiles and HbA1c values. There were 171 episodes of hypoglycaemia during human and 150 episodes during porcine insulin. Patients completed questionnaires after each hypoglycaemic episodes and at the end of the trial. Hunger and sweating without concomitant neuroglycopenic symptoms were significantly more frequent as initial warning symptoms during porcine than during human insulin (41% vs 20%), whereas neuroglycopenic symptoms were more frequent during human insulin. At the end of the trial 18 of 32 subjects reported diminished awareness of hypoglycaemia during human insulin compared with 6 of 32 during porcine insulin. Hypoglycaemia developed faster during human than during porcine insulin administration. The transfer of IDDM subjects from porcine to human insulin seems to alter warning symptoms of low blood glucose concentration, with consequent impairment of its early recognition.

32 volunteers who lacked antibody to hepatitis A virus (HAV) received, at intervals of one month, three injections of a killed vaccine made from HAV propagated in diploid human fibroblast cell cultures. In 16 the vaccine was coupled with aluminium hydroxide as adjuvant. The serconversion rates measured by radioimmunoassay, with and without adjuvant respectively, were 13% and 25% at four weeks, 81% and 89% at eight weeks, and 94% and 100% at twelve weeks. Four weeks after the third injection all volunteers had high neutralising antibody titres. Twelve weeks later the titres of anti-HAV and anti-HAV neutralising antibodies had not declined.

The effects of hydroxychloroquine and sulphasalazine on progression of joint damage shown by X-rays were compared in a double-blind, randomised trial in 60 patients with rheumatoid arthritis not previously treated with slow-acting antirheumatic drugs. X-rays of the hands and feet at the start and after 24 and 48 weeks of treatment were available for 28 patients treated with hydroxychloroquine and 22 treated with sulphasalazine. Erosions and joint space narrowing were scored by a single observer unaware of treatment. At baseline there were no significant differences in demographic, clinical, or radiographic characteristics between the treatment groups. Patients withdrawn because of lack of effect were included in the analysis. The median number of erosions was lower in the sulphasalazine than the hydroxychloroquine group at 24 weeks of treatment (2.5 vs 10) and the difference was significant at 48 weeks (5 vs 16; p less than 0.02). The difference in median total score of joint damage was significant at 24 weeks (6.5 vs 17; p less than 0.02) and at 48 weeks (8 vs 33; p less than 0.02). The increase in number of erosions and total score was significantly greater in the hydroxychloroquine than the sulphasalazine group, both after 24 weeks and after 48 weeks of treatment.

The effects of brief warming of stored platelet concentrates were assessed in 15 children undergoing transfusion for stable thrombocytopenia due to chemotherapy (n = 13) or aplastic anaemia. Half of a pool of platelet concentrates stored at 22 degrees C was incubated at 37 degrees C for 1 hour and the other half at room temperature. Each patient received one bag of warmed and one of unwarmed cells transfused in random order 2 h apart. Platelet warming improved transfusion efficacy, as assessed on the basis of corrected platelet count increments (CCIs) and platelet morphology. Compared with unwarmed bags, warmed bags had a higher morphology score (p = 0.0001) and a higher CCI (adjusted for the transfusion order) at 1 h (n = 11; p = 0.014) and at 2 h (n = 15, p = 0.006) post transfusion. Thus, with platelets stored at room temperature bags warmed before transfusion to 37 degrees C for 1 h provide a larger number of circulating platelets after transfusion than do unwarmed bags.

The relation between hemispheric lateralisation of intracerebral lesion and duration of impaired consciousness was investigated in 43 survivors of severe closed head injury. Duration of impaired consciousness, defined as the time from injury until the obeying of commands, was significantly longer in patients with left hemisphere than right hemisphere lesions. However, the side of intracerebral lesion had no effect on duration of impaired consciousness defined as time from injury until localisation to pain. Use of verbal methods to assess level of consciousness may be responsible for the observation that lesions of the language dominant hemisphere produce greater disturbance of consciousness than similar insults to the right hemisphere.

In a prospective, double-blind, randomised trial, 401 patients with a first acute myocardial infarction were treated within 4 h of onset of symptoms with 80 mg recombinant pro-urokinase or single-chain urokinase plasminogen activator (rscu-PA; proposed INN saruplase) intravenously given as a 20 mg bolus followed by 60 mg infusion for 60 min (198 patients), or 1.5 million IU streptokinase infused over 60 min (203 patients). The first two angiograms were taken at 60 min and at 90 min. Angiography was repeated at 24-36 h. Patency rates at 60 min were 71.8% for rscu-PA and 48.0% for streptokinase (p less than 0.001) and at 90 min they were 71.2% and 63.9%, respectively (p = 0.15). At 24-36 h 6/121 patients treated with rscu-PA and 5/114 patients treated with streptokinase showed reocclusion of the vessel. At the end of the thrombolytic infusion (60 min) fibrinogen concentration had decreased to 0.44 (0.23-1.27) g/l (median, 1st and 3rd quartile) in patients treated with rscu-PA and to 0.17 (0.06-0.27) g/l in patients treated with streptokinase (p less than 0.001). Concentrations of fibrin(ogen) degradation products rose to 96 (24-240) mg/l after rscu-PA and to 240 (192-360) mg/l after streptokinase (p less than 0.001). Bleeding complications were less common in the rscu-PA than in the streptokinase group (p less than 0.01). Thus intravenous rscu-PA led to higher patency rate, earlier reperfusion, less disturbance of haemostasis, and fewer bleeding complications than did intravenous administration of streptokinase.

12 adult patients with perennial asthma and chronic skin infection were found to have immediate hypersensitivity to Trichophyton spp. 10 patients were tested by bronchial provocation and gave immediate bronchial reactions to an extract of T tonsurans. Double-blind, placebo-controlled nasal challenge of 8 patients demonstrated that the upper airways of these patients were also sensitive to this dermatophyte antigen. In addition to perennial asthma most of the patients had persistent eosinophilia and chronic rhinosinusitis. The results suggest that absorption of fungal antigen can give rise to IgE antibody production, sensitisation of the airways, and symptomatic asthma and rhinosinusitis. Several patients had many of the features of late onset or "intrinsic" asthma.