4801. An experiment to determine the active therapeutic moiety of sulphasalazine.
Sulphasalazine (S.A.S.P.) is of proven value in the treatment of ulcerative colitis, but its mode of action is unknown. When it is taken by mouth, nearly all the dose reaches the colon intact, where it is split by bacteria into sulphapyridine (S.P.) and 5-aminosalicylic acid (5-A.S.A.). An experiment was devised to determine whether the therapeutic property of S.A.S.P. is a function of the parent molecule or of these two principal metabolites. Retention enemas of S.A.S.P., S.P., and 5-A.S.A. were administered to volunteer patients with sigmoidoscopic evidence of active ulcerative colitis. The experiment was conducted as a blind controlled therapeutic trial, each patient having one of the test enemas daily for two weeks. Pronounced histological improvement was observed in approximately 30% of the patients receiving S.A.S.P. or 5-A.S.A., and in only 5% of those receiving S.P. It is concluded that the active therapeutic moiety of S.A.S.P. IS 5-A.S.A. and that the S.P. functions as a carrier ensuring that the 5-A.S.A. is liberated within the colon.
4802. Oral disopyramide for the prevention of arrhythmias in patients with acute myocardial infarction admitted to open wards.
作者: N Zainal.;D J Carmichael.;J W Griffiths.;E M Besterman.;P H Kidner.;A D Gillham.;G D Summers.
来源: Lancet. 1977年2卷8044期887-9页
Patients with acute myocardial infarction admitted to open wards of three hospitals were given either oral disopyramide (100 mg four times daily) or matching placebo, prophylactically, for seven days. The drug was associated with a significant reduction in mortality (p = 0-0025) and in incidence of extension of infarction (p = 0-01), ventricular fibrillation (p = 0-05), and ventricular tachycardia (p = 0-01). Disopyramide was not associated with any particular complication or side-effect. Unitl information is available to the contrary, oral disopyramide should be given for the first seven days after myocardial infarction to all patients not managed in an intensive-care unit.
4803. Oral non-absorbed antibiotics prevent infection in acute non-lymphoblastic leukaemia.
113 patients being treated for acute non-lymphoblastic leukaemia were investigated to determine the effect of suppression of body microbial flora on prevention of infection. They were randomly allocated to a control group or a group which received non-absorbed antibiotics by mouth and topical applications of cutaneous and mucosal antiseptic preparations. The group receiving oral non-absorbed antibiotics had significantly few infections, fewer deaths from infection, fewer pyrexial episodes, and consequently received less systemic antibiotic therapy than the controls.
4804. Low-dose heparin as a prophylaxis against deep-vein thrombosis after acute stroke.
A trial of subcutaneous low-dose heparin in the prevention of deep-vein thrombosis was carried out in elderly patients admitted to hospital after an acute stroke. A statistically significant reduction was observed in deep-vein thrombosis as assessed by isotope leg scanning.
4805. Intravenous lignocaine in prevention of deep venous thrombosis after elective hip surgery.
Intravenous lignocaine is a possible means of preventing deep venous thrombosis (D.V.T.) after elective hip surgery. In 14 control patients the total incidence of D.V.T. was 78%, with a 57% incidence of thigh-vein thrombosis. In 14 patients treated at random with intravenous lignocaine during the first 6 postoperative days, there were only 2 calf-vein thrombi (14%; P less than 0-005). In a further 14 cases treated consecutively there were 4 unilateral calf-vein thrombi. No thrombi originated in the thigh veins (P less than 0-001). After intravenous lignocaine was stopped the total incidence of D.V.T. in the 28 patients rose to 53% with a 21% incidence of thigh-vein thrombi between the 7th and 14th postoperative days. There was no significant difference in postoperative coagulation and fibrinolytic activity between control and treated patients, and blood loss and transfusion requirements were similar. Immediate or delayed hypersensitivity reactions to lignocaine were not observed. The results support the view that damage to the vessel wall may be the initial event in the formation of a venous thrombus.
4806. Depletion and disruption of dietary fibre. Effects on satiety, plasma-glucose, and serum-insulin.
Ten normal subjects ingested test meals based on apples, each containing 60 g available carbohydrate. Fibre-free juice could be consumed eleven times faster than intact apples and four times faster than fibre-disrupted purée. Satiety was assessed numerically. With the rate of ingestion equalised, juice was significantly less satisfying than purée, and purée than apples. Plasma-glucose rose to similar levels after all three meals. However, there was a striking rebound fall after juice, and to a lesser extent after purée, which was not seen after apples. Serum-insulin rose to higher levels after juice and purée than after apples. The removal of fibre from food, and also its physical disruption, can result in faster and easier ingestion, decreased satiety, and disturbed glucose homoeostasis which is probably due to inappropriate insulin release. These effects favour overnutrition and, if often repeated, might lead to diabetes mellitus.
4807. Effect of antilyphocyte-globulin potency on survival of cadaver renal transplants. Prospective randomised double-blind trial.
71 recipients of cadaver primary and secondary renal transplants were investigated in a prospective randomised double-blind study. Patients were given one of two rabbit antilymphocyte globulin (A.L.G.) preparations made by similar techniques but differing in potency as measured by skin-graft prolongation in rhesus monkeys. Patient selection and management were otherwise similar. A statistically significant difference (P less than 0-05) in graft survival (78% vs. 42%) developed between the two groups at a mean follow-up of 18-4 months and patient entry into the study was terminated. After a 3-5 year interval from the start of the trial the double-blind code was broken. It was found that the high-potency-A.L.G. group had better graft survival and fewer rejection episodes (P less than 0-05) than the moderate-potency group. The results suggest that preclinical testing of A.L.G. by the primate skin graft test can be a valid indicator of the potential efficacy of an A.L.G. preparation in renal-transplant recipients. It is suggested that quality-control standards may improve the clinical results of A.L.G. therapy.
4809. Death from acute pancreatitis. M.R.C. multicentre trial of glucagon and aprotinin.
来源: Lancet. 1977年2卷8039期632-5页
The influence of glucagon and aprotinin ('Trasylol') on the death-rate of acute pancreatitis has been studied in a randomised double-blind multicentre trial. The death-rate in 257 patients was 11%. In the doses used neither drug was found to diminish the risk of death.
4810. Propranolol as an adjunct to the treatment of schizophrenia.
作者: N J Yorkston.;S A Zaki.;D R Pitcher.;J H Gruzelier.;D Hollander.;H G Sergeant.
来源: Lancet. 1977年2卷8038期575-8页
Propranolol contributed usefully to the practical management of patients with chronic schizophrenia whose florid symptoms had not remitted with major tranquillisers. 14 patients who had received an average equivalent of 954 mg per day of chlorpromazine for 10 years were given, in addition, either propranolol or a placebo for 12 weeks. Both groups had improved by the twelfth week, but the propranolol group had improved significantly more.
4811. Treatment of cryptorchidism by intranasal synthetic luteinising-hormone releasing hormone. Results of a collaborative double-blind study.
作者: R Illig.;G U Exner.;F Kollmann.;K Kellerer.;M Borkenstein.;L Lunglmayr.;W Kuber.;A Prader.
来源: Lancet. 1977年2卷8037期518-20页
The effect of intranasal luteinising-hormone releasing hormone (L.H.R.H.) in 84 boys with unilateral or bilateral cryptorchidism was evaluated in a double-blind controlled trial. Boys with retractile testes were not studied. L.H.R.H. caused no side-effects; plasma antibodies to L.H.R.H. were never demonstrated. Four weeks' therapy with intranasal L.H.R.H. administered in six doses daily (1.2 mg/day) led to complete descent in 38% of a total of 61 testes, an improved position in 28%, and no response in 19%; 15% of testes were never palpated. After placebo the position of 25% of testes was improved; there was no response in 75% of a total of 51 testes. The success-rate seemed to be independent of age, but was related to the initial testicular position, with complete descent in only 11% of testes not previously palpated compared with 48% of testes found in the inguinal region.
4812. Minoxidil in resistant hypertension.
Minoxidil in combination with propranolol and diuretics controlled the blood-pressure in a group of hypertensive patients who were resistant to treatment with large doses of standard drugs. The main problem was fluid retention but subjective side-effects were fewer than in a comparable group on other drugs.
4814. Wheat fibre and irritable bowel syndrome. A controlled trial.
Twenty-six patients with irritable bowel syndrome entered a controlled trial of diets with a high or low wheat-fibre content. After 6 weeks on the high-wheat fibre regimen there was significant improvement in symptoms and an objective change in colonic motor activity. No such improvement occurred on the low-fibre regimen. Patients with irritable bowel syndrome should be encouraged to increase their daily intake of wheat fibre.
4817. Dissolution of cholesterol gallstones by ursodeoxycholic acid.
44 patients with radiolucent gallstones in gallbladders visible on cholecystography were randomly alloted to three treatment groups: ursodeoxycholic acid (600 mg/day), ursodeoxycholic acid (150 mg/day), a placebo. At the end of six months' treatment, cholecystograms of all the patients were interpreted by radiologists who were not aware of the treatment. Dissolution of gallstones occurred in 8 (26%) of the 31 patients treated with ursodeoxycholic acid, but not in the placebo group. Ursodeoxycholic acid had no hepatotoxicity, as assessed by standard liver-function tests. These results indicate that ursodeoxycholic acid, the 7beta epimer of chenodeoxycholic acid, is effective in the dissolution of cholesterol gallstones.
4819. Levamisole-induced immunostimulation in spondylarthropathies.
The term "seronegative spondylarthritis" (S.S.A.) has been assigned to rheumatic disorders with closely related clinical features, defined by seronegativity and HLA-B27 phenotype. Its pathogenesis may be linked with a genetically controlled defective immune response. Therefore, 37 men with S.S.A. were treated with levamisole (150 mg/day, 3 days/wk) to stimulate the immune reactions. In a randomised controlled crossover study these patients also received a placebo; each period ran for 12 wk. Symptomatic therapy was continued through the entire 6 mo. Serious side-effects led to withdrawal of the active drug in 9 patients. Clinical response was measured in terms of a cumulative joint index, spondylometry, morning stiffness, and a pain scale. Treatment with levamisole resulted in a significant improvement in these parameters. Radiological evidence of sacroiliitis was present in 48.6% before and after levamisole, and joint scanning with 99Tc-pyrophosphate also revealed no progress in the disease. After levamisole treatment, IgM levels fell significantly (P less than 0-014). Likewise, the previously high percentage of antibodies with weak cytotoxic activity against lymphocytes was reduced after levamisole (P less than 0-049), and an increased rate of leucocyte-migration inhibition (L.M.I) was found in the levamisole-treated group. Thus, the immunostimulating properties of levamisole may interfere with defective immunoregulation in S.S.A. and, by improving the clinical conditions, lead to a change in the course of this disease.
4820. Radiotherapy and hyperbaric oxygen in head and neck cancer. Interim report of second clinical trial.
A controlled clinical trial is in progress to assess the value of hyperbaric oxygen and radiotherapy in the management of head and neck cancer. An established dose-fractionation schedule in hyperbaric oxygen is being compared with a widely used conventional schedule in air. Survival and local recurrence-free rates are significantly higher in the oxygen group, and the effects on normal tissue are similar in both groups. These findings suggest a genuine therapeutic advantage. There was a distinct improvement in the results of treating advanced laryngeal carcinoma, where there was a high survival rate, without resort to laryngectomy.
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