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TITLE: Simvastatin in the treatment of hypercholesterolaemia in patients with essential hypertension.ABSTRACT: Mortality from coronary artery disease is a common problem in treated hypertensive patients, and these people have a high prevalence of elevated cholesterol levels. A study was undertaken to determine whether cholesterol could be lowered effectively without major side effects in patients with treated hypertension. Forty-nine patients (mean age 67.6 years) with cholesterol greater than 5.5 mmol/l were placed on a reduced-fat (less than 30% of calories from fat with a ratio of polyunsaturated to saturated fats of less than 1) diet for 3 months. If the cholesterol was between 5.5 and 7.5 mmol/l and total cholesterol divided by high-density lipoprotein cholesterol was greater than 4.5, the patients were randomly allocated either to the simvastatin (24 patients) or the placebo group (25 patients). Diet and placebo caused minor and insignificant falls in cholesterol and no change in triglycerides or lipids. Treatment with simvastatin reduced cholesterol levels from 6.85 to 4.75 mmol/l (P less than 0.001), triglycerides from 2.7 to 2.1 mmol/l (P less than 0.01), low-density lipoproteins from 4.6 to 2.6 mmol/l (P less than 0.001) and high-density lipoproteins rose from 1.09 to 1.18 mmol/l (P less than 0.01). Total cholesterol divided by high-density lipoprotein cholesterol fell from 6.3 to 4.0 (P less than 0.001). The drug was well tolerated and the side-effect profile did not differ from the placebo in clinical or biochemical events. The active drug was stopped in one patient (abdominal pain, dizziness, headache, tiredness) and in two patients taking the placebo (elevated creatine phosphokinase, cardiovascular collapse). Simvastatin effectively lowered total cholesterol and improved the lipoprotein profile. The dose required in most patients was 40 mg/day. Simvastatin may be an acceptable drug to improve the lipoprotein profile in order to determine whether this improves the prognosis in patients treated for hypertension.

TITLE: Blood coagulation findings and the efficacy of factor XIII concentrate in premature infants with intracranial hemorrhages.ABSTRACT: Coagulation findings were examined in 55 cases of neonatal intracranial hemorrhages (ICH). Marked decreases of the platelet count, fibrinogen, factor XIII (F XIII) activity, were observed in these cases. However, the relatively mild increases in the alpha 2-plasmin inhibitor activity, alpha 2-plasmin inhibitor.plasmin complex and fibrin/fibrinogen degradation products level were observed and only about one third of the cases showed abnormal values. In consideration of these coagulation findings, fifty-eight cases of premature infants were randomly divided into a treated group with a F XIII concentrate and a non-treated group. Thirty cases were administered within 6 hours after delivery to investigate the preventive effects against intraventricular hemorrhages (IVH). Compared in frequencies between both groups limited to the cases with a high risk of IVH, the frequency in the treated group was two out of 13 (15.4%), significantly low (p less than 0.05), while it was six out of eight cases (75.0%) in the non-treated group. From these results it was concluded that a F XIII concentrate is effective in the prophylaxis of IVH in premature infants.

TITLE: A clinical comparison of central and peripheral argon laser panretinal photocoagulation for proliferative diabetic retinopathy.ABSTRACT: Fifty eyes with three or four diabetic retinopathy risk factors received argon laser panretinal photocoagulation (PRP) with treatment randomly assigned to either central or peripheral distribution. Six months after treatment, two or more acuity lines had been lost by 24% of the central PRP, and by only 8% of the peripheral PRP eyes. Mean visual field constriction with the I-4e isopter was 39% for the central and 29% for the peripheral PRP eyes; for the IV-4e isopter, it was 12 and 7%. Pretreatment macular thickening increased in 19% of the central PRP eyes, but decreased in 19% of the peripheral PRP eyes (P less than 0.05). There was complete disc neovascular regression in 38% of the central and 47% of the peripheral PRP eyes. Partial regression was obtained in 31% centrally and 33% peripherally treated eyes.

TITLE: Thrombosis prophylaxis with low molecular weight heparin in total hip replacement.ABSTRACT: In a randomized prospective trial, the efficacy of low molecular weight heparin (LMWH) (Fragmin) and dextran 70 (Macrodex) in preventing deep vein thrombosis (DVT) in the legs was evaluated in 98 consecutive patients undergoing elective total hip replacement. The patients were randomly allocated to receive either 2500 anti-factor Xa units LMWH twice daily for 7 days, with the first dose given 2 h before surgery; or 500 ml dextran 70 twice during the day of operation, followed by a single infusion of 500 ml on the first and again on the third postoperative day. DVT was assessed by 125I-fibrinogen test for 2 weeks postoperatively, a positive test being followed by phlebography. DVT developed in 22 (45 per cent) of 49 patients receiving dextran 70 and in 10 (20 per cent) of 49 patients in the LMWH group (P less than 0.01). LMWH was thus statistically significantly better than dextran 70 in preventing DVT in the legs. It was not firmly established whether this benefit was also valid in the high ileofemoral region. Two patients with non-fatal pulmonary embolism were found in each group. Per- and postoperative blood loss and blood transfusion requirements were significantly lower in the LMWH group.

TITLE: Response of thromboxane B2, malondialdehyde and platelet sensitivity to 3 weeks low-dose aspirin (ASA) in healthy volunteers.ABSTRACT: To examine the effects of low-dose aspirin thromboxane B2 (TXB2), malondialdehyde (MDA) and platelet sensitivity to prostaglandin I2 (PGI2) have been measured in a total of 18 healthy volunteers. They were randomly assigned to 3 groups, 6 volunteers each, receiving either 1, 10 or 20 mg ASA orally a day for 3 weeks in a double-blind fashion. In order to assess the time course of ASA-induced changes, blood was drawn before, 1 hour and 2, 3, 5, 7, 9, 12, 14, 16 and 21 days after the first drug-intake. Serum-TXB2 was depressed time- and dose-dependently, after 1 mg daily to about 60%, after 10 mg to about 30%, after 20 mg to about 5% of controls. MDA-formation and conversion of exogenously added arachidonic acid (AA) to TXB2 also dropped significantly, (p less than 0.01), the extent depending on the ASA-dosage administered. The drop in MDA- and TXB2-values in the 3 groups correlated with r = 0.98, 0.94, 0.98, respectively. The platelet sensitivity during 20 and 10 mg ASA-administration did not change at all, whereas a significant increase (p less than 0.01) in platelet sensitivity during treatment with 1 mg ASA was observed.

TITLE: Metabolic effects of biosynthetic human proinsulin in type 2 diabetes mellitus.ABSTRACT: Due to a longer plasma half-life and half-time of action on glucose metabolism biosynthetic human proinsulin was thought to be an alternative to long-acting insulin preparations. To test this hypothesis we studied 23 type 2 diabetic patients who could no longer be treated sufficiently with oral hypoglycaemic agents. After an initial 1 week phase during which all patients received protamine bound insulin twice daily, the patients either continued on NPH insulin (Group A, n = 11) or were randomly switched to human proinsulin (Group B, n = 12). Glucose profiles and peripheral and hepatic insulin sensitivity (euglycaemic clamp: 120 mU m-2 min-1) were measured at the end of the initial period (Time 1) and 1 week later (Time 2). The insulin-mediated glucose disposal (RD) was not changed after either treatment (group A: 176 +/- 18 vs. 192 +/- 19 mg m-2 min-1; group B: 175 +/- 15 vs. 174 +/- 12 mg m-2 min-1 for times 1 and 2, respectively, NS). Suppression of hepatic glucose output (HGO) was complete in both groups at both times. Fasting blood glucose levels (FBG) and basal HGO were equally low at times 1 and 2 (group A: FBG 118 vs. 123 mg dl-1, BHGO 81 vs. 79 mg m-2 min-1; group B: FBG 118 vs. 106 mg dl-1, BHGO 87 vs. 84 mg m-2 min-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Comparison of continuous and intermittent bolus infusions of metoclopramide during 5-day continuous intravenous infusion with cisplatin.ABSTRACT: In order to decide the administration method of metoclopramide for prevention or control of chemotherapy-induced nausea and vomiting in multidrug chemotherapy, with cisplatin 5-day continuous intravenous infusion (25 mg/m2/day) for patients with advanced lung cancer, a randomised crossover study of intermittent bolus infusion (1 mg/kg, 30 min, every 8 h, day 1-5) and continuous infusion (3 mg/kg/24 h, 120 h) of metoclopramide was performed. Both regimens included methylprednisolone and diphenhydramine given concurrently. The acute and delayed antiemetic effects were examined. 21 cases could be evaluated. There were 6 and 10 cases (P = 0.048), respectively, of no nausea and no vomiting; 14 and 18 cases (P = 0.048), respectively, of no vomiting; and vomiting episodes were seen 27 and 9 times, respectively (P = 0.042). Thus, metoclopramide continuous infusion was significantly superior in antiemetic effect compared to bolus infusion. Neither method had any serious side-effects and both were safe.

TITLE: Influence of beta-blockade on circulating plasma levels of 3-methoxy-4-hydroxy phenylethylene glycol (MHPG) during exercise in moderate hypertension.ABSTRACT: 1. The effect of exercise testing and beta-blockade on plasma norepinephrine (PNE), and secretion of its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), was assessed in 28 mild-to-moderate hypertensives before and after the administration of dilevalol, a new beta-blocker with beta 2-agonism. 2. This double blind, placebo-controlled study consisted of two successive submaximal exercise tests before and after the administration of a single oral dose of dilevalol (200 mg, 400 mg or 600 mg). Plasma norepinephrine levels were determined at rest, at 100 watts step of exercise and at maximal effort (Emax). 3. During the control test, mean PNE levels increased from 1.73 +/- 0.52 nmol/L (resting value) to 8.01 +/- 4.01 nmol/L at Emax (P less than 0.01) as MHPG levels increased from 11.18 +/- 1.33 nmol/L (rest) to 17.50 +/- 1.15 nmol/L (Emax, P less than 0.01). After dilevalol, PNE increased significantly as compared to controls (P less than 0.05), from 2.32 +/- 0.99 to 12.42 +/- 5.97 nmol/L (P less than 0.01). PNE and MHPG levels were correlated, both at rest and during exercise. PNE levels after beta-blockade were linearly related to the dose of beta-blocker administered. MHPG levels were unaltered by the administration of dilevalol, both before and after exercise. 4. The increase in MHPG that occurs during bicycle exercise is largely generated from an increase in central nervous system noradrenergic activity. While dilevalol increases the peripheral sympathetic nervous system, both at rest and during exercise (which is reflected by increases in PNE levels) the drug does not alter resting central nervous system noradrenergic activity nor amplify the increase in central noradrenergic activity that occurs during exercise.

TITLE: Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study.ABSTRACT: To investigate in the prospective Helsinki Heart Study, whether chronic Chlamydia pneumoniae infection, indicated by elevated antibody titers against the pathogen, chlamydial lipopolysaccharide-containing immune complexes, or both, is a risk factor for coronary heart disease.The Helsinki Heart Study was a randomized, double-blind, 5-year clinical trial to test the efficacy of gemfibrozil in reducing the risk for coronary heart disease. Participants were randomized to receive either gemfibrozil (2046 patients) or placebo (2035 patients). Fatal and nonfatal myocardial infarction and sudden cardiac death were the main study end points. Serum samples were collected at 3-month intervals from all patients.One hundred forty cardiac events occurred during the follow-up period. Serum samples from 103 case patients obtained 3 to 6 months before a cardiac end point were matched with those from controls for time point, locality, and treatment. Samples were tested for markers of chronic chlamydial infection.Immunoglobulin A (IgA) and G (IgG) antibodies to C. pneumoniae were measured using the microimmunofluorescence method. Lipopolysaccharide-containing immune complexes were measured using two antigen-specific enzyme immunoassays, the lipopolysaccharide-capture and immunoglobulin M (IgM)-capture methods.Using a conditional logistic regression model, odds ratios for the development of coronary heart disease were 2.7 (95% CI, 1.1 to 6.5) for elevated IgA titers, 2.1 (CI, 1.1 to 3.9) for the presence of immune complexes, and 2.9 (CI, 1.5 to 5.4) for the presence of both factors. If we adjusted for other coronary heart disease risk factors such as age, hypertension, and smoking, the corresponding values would be 2.3 (CI, 0.9 to 6.2), 1.8 (CI, 0.9 to 3.6), and 2.6 (CI, 1.3 to 5.2), respectively.The results suggest that chronic C. pneumoniae infection may be a significant risk factor for the development of coronary heart disease.

TITLE: The predictive value of silent ischemia at an exercise test before discharge after an episode of unstable coronary artery disease. RISC Study Group.ABSTRACT: The prognostic value of silent ischemia during a symptom-limited predischarge exercise test (ET) was evaluated in 740 men after an episode of unstable angina or non-Q wave myocardial infarction. The 51% of patients with ST depression at the ET had a higher rate of myocardial infarction or death after 1 year (18%) compared with those without ST depression (9%; p less than 0.01). This increased risk was not influenced by the presence or absence of pain at the ET: 18.3% in patients with painful ischemia compared with 18.1% in patients with silent ischemia. However, ST depression combined with pain at the ET predicted a higher incidence of class III or IV angina at follow-up (43.9% compared with 16.7% in the group with asymptomatic ST depression; p less than 0.001). Because revascularization in addition to alleviating symptoms also enhances the prognosis in certain groups of patients, selections for coronary angiography and possible revascularization should not be made only on the basis of symptoms but also on the presence of myocardial ischemia, whether symptomatic or not.

TITLE: Efficacy of orally administered ondansetron in the prevention of postoperative nausea and vomiting: a dose ranging study.ABSTRACT: In a placebo-controlled, double-blind study, we have compared the efficacy of ondansetron 16 mg, 8 mg and 1 mg administered 8-hourly for prevention of postoperative nausea and vomiting. We studied 995 patients undergoing major gynaecological surgery; 982 were included in the analysis. Study medication was administered 1 h before induction of anaesthesia and second and third doses were given 8 and 16 h after the first. The treatment groups were similar for patient characteristics, surgical procedures, anaesthetics administered and opioids given. The frequency of nausea was 75%, 70%, 56% and 55% after placebo and ondansetron 1 mg, 8 mg and 16 mg, respectively; the corresponding frequencies of vomiting were 60%, 55%, 37% and 37%. Ondansetron 8 mg was as effective as 16 mg and both resulted in significant reductions in nausea and vomiting compared with placebo and ondansetron 1 mg (P less than 0.001).

TITLE: Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial.ABSTRACT: Neurohormonal activation has major impact on the pathophysiology of congestive heart failure. The Munich Mild Heart Failure Trial was designed to test the hypothesis that interference with the renin-angiotensin system by angiotensin converting enzyme inhibition favourably influences the natural history of heart failure.170 patients, median New York Heart Association (NYHA) class II, were randomised to double blind treatment with 25 mg captopril twice a day or placebo in addition to standard treatment for a median observation period of 2.7 years.Progression of heart failure to NYHA class IV on an optimally adjusted standard treatment, death due to progressive heart failure, and sudden death.Heart failure progressed to class IV in nine patients (10.8%) treated with captopril and in 23 patients (26.4%) treated with placebo (p = 0.01). The mean survival time until this end point was 223 days longer in the captopril group (Kaplan-Meier life table analysis; p = 0.02). Also, progressive deterioration to severe heart failure was a powerful predictor of total mortality and death from heart failure; 80% of deaths due to progressive heart failure occurred after this end point. There were fewer deaths caused by progressive heart failure in the captopril group than in the placebo group (4 v 11; p = 0.10) but similar numbers of sudden deaths (11 v 10). Progressive heart failure was the cause of death in 18.2% of all deaths in the captopril group and 50% in the placebo group. Total heart failure events (the end point on which power calculation was based) were also more common in the placebo group (19 v 32 events) but not significantly so. Total mortality was similar to both groups (22 of 83 v 22 of 87).Angiotensin converting enzyme inhibition in conjunction with standard therapy early in the course of congestive heart failure slowed the progress of heart failure and thus favourably altered the natural history of the disease.

TITLE: Paroxetine in the treatment of elderly depressed patients in general practice: a double-blind comparison with amitriptyline.ABSTRACT: A total of 101 patients entered a double-blind, parallel-group study in general practice, comparing the efficacy and tolerability of paroxetine and amitriptyline in elderly depressed patients. All patients received placebo for 1 week followed by active therapy for a total of 6 weeks. Medication was randomly allocated, two-thirds of the patients took paroxetine (20 mg daily) and one-third received amitriptyline (50 mg daily); this dose was increased to 30 mg and 100 mg, respectively, after 1 week. Of the patients who entered the placebo run-in, 90 took active treatment and were evaluable on an intention-to-treat basis (56 paroxetine, 32 amitriptyline). The mean age of the patients was 72 years. Significant reductions in Hamilton Depression Rating Scale (HAMD) from baseline to the end of treatment were seen for both groups (p < 0.01), with no difference between treatments. The HAMD score was reduced by half, or more, for 76% of patients taking paroxetine and 86% taking amitriptyline. Significant improvement was observed in the investigators' Clinical Global Impression (CGI) score for 57% of patients taking paroxetine and 52% on amitriptyline. Improvements after treatment were also observed in the Leeds Sleep Evaluation Questionnaire (LSEQ) scores. Significantly fewer patients taking paroxetine reported adverse events (34% vs 63% taking amitriptyline, p = 0.02). Those taking paroxetine experienced significantly fewer anticholinergic side effects (7% vs 25% taking amitriptyline, p = 0.04). Overall, this study confirmed the effectiveness of paroxetine as an antidepressant drug.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Sodium fluoride prevents bone loss in primary biliary cirrhosis.ABSTRACT: Low-bone-turnover osteoporosis is a common complication of primary biliary cirrhosis (PBC). Since sodium fluoride stimulates bone formation we assessed the effect of this drug on bone mass in a 2-year, prospective, double-blind trial including 22 women with PBC who were randomly assigned to receive sodium fluoride (50 mg/day) or placebo. All received calcium supplements and low doses of vitamin D. Bone mineral density of the lumbar spine was measured by dual-photon absorptiometry initially and every 6 months. Vertebral fractures were evaluated in thoracic and lumbar spine initially, and after 1 and 2 years. Seven patients in the fluoride group and eight in the placebo group completed the trial. In the fluoride group, bone mineral density did not change after 2 years (initial 1.05 +/- 0.07, final 1.07 +/- 0.06 g/cm2; p = n.s.). In the placebo group, however, bone mineral density decreased significantly (initial 1.00 +/- 0.07, final 0.93 +/- 0.06 g/cm2; p = 0.03). Moreover, in the fluoride group bone mineral density increased by 2.9 +/- 3.6%, and in the placebo group decreased by 6.6 +/- 2.6% (p = 0.04). None of the patients developed new vertebral or non-vertebral fractures. Treatment with sodium fluoride did not impair liver function or cholestasis in PBC. These results indicate that sodium fluoride prevents bone loss in PBC and therefore might be considered as a possible therapeutic agent for osteoporosis associated with this liver disease. Since a small number of patients completed the trial, further studies are required.

TITLE: Growth hormone stimulates galactopoiesis in healthy lactating women.ABSTRACT: Sixteen normally lactating women underwent a double-blind randomized placebo-controlled trial of recombinant human growth hormone (hGH) to assess the effect of hGH on milk production in early lactation. Milk volumes were measured by test weighing procedures of the infants and removal of residual milk on a control day and after 7 days of treatment with recombinant hGH (0.1 IU.kg-1 body weight.d-1) or placebo treatment. Although all women were lactating normally before the study commenced, milk volume in 8 hGH treated mothers was increased (p < 0.02) by 18.5 +/- 1.4% (mean +/- SEM) compared to 11.6 +/- 2.0% in the placebo-treated group (N = 8). No adverse effects were seen with hGH treatment and no major changes noted in milk constituents. The hGH concentrations in milk were low and did not change with therapy. Plasma concentrations of IGF-1 increased significantly within 24 h of hGH treatment and increased further towards the end of the trial to values of 2.6-fold above the pretreatment values. The concentration of IGF-1 in milk was approximately 100-fold lower than those observed in plasma and could only be reliably measured after size exclusion chromatography to remove the interfering influence of IGF binding proteins in the radioimmunoassay. All women treated with hGH showed a small increase in milk IGF-1 concentrations but the values remained within the range of values observed in women receiving the placebo treatment (1.2-4.4 micrograms/l). Growth hormone treatment increased milk volume in normal lactating women during early lactation.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Thrombolysis with recombinant human tissue-type plasminogen activator during instability in coronary artery disease: effect on myocardial ischemia and need for coronary revascularization. TRIC Study Group.ABSTRACT: Two hundred five men, 40 to 70 years of age, admitted to the coronary care unit with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarction), were randomized to double-blind placebo-controlled treatment with an intravenous infusion of recombinant tissue-type plasminogen activator (rTPA), 1 mg/kg body weight (maximum 100 mg) during 4 hours, in addition to aspirin, heparin, and beta-blockade. No severe complications occurred. Myocardial ischemia, defined as myocardial infarction, incapacitating angina despite medication, or signs of ischemia at the exercise test, was reduced by treatment with rTPA compared with placebo both at discharge, 53% compared with 70% (p = 0.02), and at 1 month, 61% compared with 80% (p = 0.005). Signs of myocardial ischemia during the exercise test were reduced at discharge 51.0% compared with 68% (p = 0.03) and at 1 month 48% compared with 62% (p = 0.09). Coronary angiography after 1 month showed no difference in major coronary lesions between the groups, nor was there any reduction in the number of performed coronary revascularization procedures. In conclusion, treatment with rTPA in unstable coronary artery disease in men reduced myocardial ischemia but did not significantly reduce the need for revascularization in long-term follow-up.

TITLE: Epidural lidocaine with sufentanil and epinephrine for abdominal hysterectomy under general anaesthesia: respiratory depression and postoperative analgesia.ABSTRACT: The purpose of this investigation was to compare the analgesic actions and side-effects of a 50 micrograms epidural bolus of sufentanil and 50 micrograms epinephrine, with a control group receiving saline and epinephrine. The method employed was a prospective, randomised, double-blind trial involving 40 ASA I or II patients for total abdominal hysterectomy. All received 1.5% lidocaine with 1/200,000 epinephrine epidurally before operation, until a block to T4 was established. Patients were anaesthetised, their tracheas were intubated, and they were allowed to breathe spontaneously before administration of the test drug. Results showed that sufentanil prolonged the duration of local anaesthesia (198 +/- 35 min vs 174 +/- 29 min; P less than 0.05), and of analgesia (288 +/- 85 min vs 188 +/- 42 min; P less than 0.01). There was an increase in somnolence in the sufentanil group (9/20 vs 2/20; P less than 0.05). Glycopyrollate was given to 11/20 patients in the sufentanil group vs 1/20 in the control group (P less than 0.01) following bradycardia and hypotension. Clinical respiratory depression occurred in the sufentanil group; 5/20 patients required controlled ventilation following apnoea greater than 20 sec. It is concluded that epidural sufentanil causes considerable cardiorespiratory depression in the setting of general anaesthesia, and should be used with caution in the spontaneously breathing, anaesthetised patient.

TITLE: Prevention of lower extremity venous thrombosis by early mobilization. Confirmation in patients with acute myocardial infarction by 125I-fibrinogen uptake and venography.ABSTRACT: To determine the effects of early ambulation on peripheral venous thrombosis in the coronary care unit, 29 patients with acute myocardial infarction had daily 125I-fibrinogen point counting of both legs using a standard portable technique in the first 3 to 7 days after admission. Twenty-one patients underwent early ambulation during the initial 3 days, while 8 remained at complete bed rest for 5 days. Only 2 of 21 early ambulated patients had positive fibrinogen point counts, in contrast to 5 of 8 nonambulated patients (P less than 0.01). With heart failure, only 2 of 9 ambulated patients had positive point counts, compared with 4 of 5 nonambulated patients (P less than 0.05). In 16 patients undergoing venography, point counts were confirmed in 6 positive and 10 negative findings. These results show that the high frequency of peripheral venous thrombosis in immobilized acute myocardial infarction patients, particularly those with heart failure, can be effectively reduced by early ambulation.

TITLE: Effects of coronary artery bypass grafting on resting and exercise hemodynamics in patients with stable angina pectoris: a prospective, randomized study.ABSTRACT: In this prospective randomized study, resting and exercise hemodynamics were determined in the nonmedicated state before ("entry") and 1 year after coronary bypass surgery in 38 patients, and at entry and 1 year in 40 patients treated medically. The surgical group showed a significant decrease in mean pulmonary arterial wedge pressure during exercise (entry 23.5 +/- 6.1 [standard error of the mean] mm Hg, 1 year 18.9 +/- 1.0, P less than 0.02); an increase in cardiac index during exercise (entry 4.3 +/- 0.1 liter/min per m2, 1 year 4.6 +/- 0.1, P less than 0.05); an increase in resting mean arterial pressure (entry 94.5 +/- 2.2 mm Hg, 1 year 100.2 +/- 2.2, P less than 0.02); and an increase in resting heart rate (entry 68.5 +/- 1.9 beats/min, 1 year: 76.0 +/- 2.0, P less than 0.01). Maximal treadmill exercise performance also improved significantly in the surgical group of patients (entry 285 +/- 24 seconds, 1 year 382 +/- 24, P less than 0.002). There were no significant changes in these variables in the medically treated "control" group. The improvement in pulmonary arterial wedge pressure during exercise and in maximal treadmill exercise time in the surgical group as a whole was due to striking improvement in these variables in a subgroup of 16 surgical patients who had a more than 10 mm Hg increase in pulmonary arterial wedge pressure during exercise in their entry study. In this subgoup, considered to contain those patients with marked "ischemicdysfunction," pulmonary arterial wedge pressure during exercise fell from 31.4 +/- 1.5 mm Hg (entry) to 19.l +/- 1.8 (1 year) (P less than 0.0001) and treadmill time increased from 217 +/- 24 seconds (entry) to 357 +/- 37 (1 year) (P less than 0.001). Thus, hemodynamic evidence of ischemic left ventricular dysfunction during stress may identify those patients who will show objective improvement in ventricular performance after bypass graft surgery.

TITLE: Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment.ABSTRACT: In 30 patients who developed atrial fibrillation after open-heart surgery the efficacy of intravenous procainamide was evaluated and compared with standard acute digoxin digitalisation. The patients were randomized to two groups of 15. One group received procainamide intravenously at a rate of 25 mg/min and with maximum dose 15 mg/kg. In the other group digoxin 0.75-1.0 mg was given intravenously according to renal function and body weight. Conversion to sinus rhythm occurred during or immediately after the infusion in 87% of the procainamide group, but only in 60% of the digoxin group (p < 0.05). The mean time from start of treatment to conversion was 40 min in the procainamide vs. 540 min in the digoxin group (p < 0.002). There were no serious complications of the procainamide treatment. Intravenous procainamide conversion of postoperative atrial fibrillation is concluded to be effective and safe and can be recommended as the treatment of first choice in awake and nonintubated postoperative cardiac patients.

TITLE: Randomised comparison of olsalazine and mesalazine in prevention of relapses in ulcerative colitis.ABSTRACT: Sulphasalazine extends remissions and lessens disease activity during relapses of ulcerative colitis, but it also causes many adverse side-effects. The adverse reactions are mostly attributable to the sulphapyridine carrier moiety rather than the active principle 5-aminosalicylic acid (5-ASA), so agents to deliver 5-ASA to the colon by other means have been designed. We have compared the efficacy and tolerability of two such agents, olsalazine and mesalazine, in maintenance therapy of ulcerative colitis. 100 patients with ulcerative colitis in remission were recruited at one centre and assigned randomly to treatment with olsalazine (Dipentum; 1.0 g daily) or mesalazine (Asacol, with Eudragit-S coating; 1.2 g daily). Compliance, biochemical and haematological variables, and clinical evidence of disease activity were assessed every 3 months for 12 months by observers unaware of treatment allocation. In intention-to-treat analysis, which included as treatment failures patients withdrawn for protocol violations, adverse reactions, intercurrent illness, or non-compliance as well as those with relapses of ulcerative colitis, the olsalazine group had a significantly lower rate of treatment failure than the mesalazine group (12/49 [24%] vs 23/50 [46%]; p = 0.025). Analysis restricted to 64 patients still in remission at 1 year and 18 with relapses also showed a significant difference in relapse rate (olsalazine 5/42 [12%] vs mesalazine 13/40 [33%]; p = 0.024). Both drugs were well tolerated; only 9 patients reported substantial side-effects. Olsalazine was clearly superior to mesalazine in prevention of relapses in ulcerative colitis, especially in patients with left-sided disease.

TITLE: Determinants of the need for early acute intervention in patients treated conservatively after thrombolytic therapy for acute myocardial infarction. TAMI-5 Study Group.ABSTRACT: This study sought to determine whether clinical variables can be used to identify patients at high risk of recurrent spontaneous myocardial ischemia or hemodynamic compromise during the 1st 4 days after intravenous thrombolysis for acute myocardial infarction. Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission. Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21% for each agent alone, p = 0.30). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 +/- 11% (vs. 54.3 +/- 10.8%, p = 0.12) and regional infarct zone wall motion was -2.68 +/- 1.07 SD/chord (vs. -2.46 +/- 1.19 SD/chord; p = 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Late streptokinase infusion and antithrombotic treatment in myocardial infarction reduce subsequent myocardial ischemia.ABSTRACT: Of 255 consecutive patients with acute myocardial infarction, 111 were eligible for attempted late thrombolysis. They were randomly assigned to either thrombolytic and antithrombotic treatment (treatment group) or routine treatment (control group). Patients in the treatment group received streptokinase initiated late (mean 32 hours; range 12 to 49) after the onset of symptoms, followed by heparin infusion for at least 5 days and warfarin and dipyridamole for at least 3 months. Patients were examined clinically and by bicycle ergometry on discharge from the hospital and after 3 and 12 months. The two groups did not differ with respect to deaths or reinfarctions. There was a trend toward a lower incidence of angina pectoris in the treatment group. Exercise tolerance in this group was significantly higher than in the control group (at 3 months 124 +/- 39 W vs 107 +/- 41 W; p less than 0.05). The difference was entirely accounted for by patients with no previous history of infarction or angina pectoris (at 3 months 142 +/- 37 W vs 112 +/- 45 W; p = 0.01). ECG signs of myocardial ischemia, silent or symptomatic, occurred at significantly lower levels of exercise among patients in the control group compared with patients in the treatment group. The results support the notion that thrombolytic therapy given as late as 12 to 49 hours after the onset of symptoms may reduce the incidence of residual ischemia during the postinfarction period.

TITLE: Thiazide for the postponement of postmenopausal bone loss.ABSTRACT: The effect of thiazide on bone mineral loss in normal postmenopausal women was examined during a 3 yr placebo-controlled clinical trial. Sixty-three healthy women in their early menopause were randomized to treatment with bendroflumethiazide 5 mg/day or placebo for 2 yr, while both groups received placebo for the third year of the trial. Calcium supplement 0.5 g/day was given throughout the 36 mo to all participants. Bone mineral content (BMC) determined by 125I-photon absorptiometry of the forearms decreased 2% per year in the placebo group (p less than 0.001). In the thiazide group no fall in BMC was seen during the first 6 mo. whereafter BMC declined with the same rats as in the placebo group. At the end of the 3 yr trial BMC averaged 94.1% in the placebo group and 95.2% in the thiazide group (p greater than 0.05). Despite a daily supplement of 0.5 g calcium, thiazide induced a persistent fall in the urinary calcium excretion of 25% (p less than 0.001), whereas the calcium supplement in the placebo group caused a significant increase in mean urine calcium of 10%-20% (p less than .001). At stop of thiazide medication a rebound effect caused a marked rise in urine calcium. One month after withdrawal of the calcium supplement the urinary calcium excretion had returned to the initial level in both groups. It is concluded that despite a sustained urine calcium lowering action the effect of thiazide upon postmenopausal bone loss is shortlived.

TITLE: Cotrimoxazole prophylaxis in patients with leukemia and prolonged granulocytopenia.ABSTRACT: Sixty-three patients with acute nonlymphoid leukemia (ANLL) under cytostatic treatment were investigated in a randomized trial to determine whether oral administration of cotrimoxazole (TMP/STX) would reduce the rate of infection. Four significant differences were observed between the group given TMP/STX (30 patients) and the control group (33 patients): 1) the mean duration of severe granulocytopenia (less than or equal to 500 PMN/mm3) before the first febrile episode was longer in prophylaxis group, 14.26 days versus four in the control group (p less than 0.001); 2) the number of febrile episodes was 37 in TMP/STX group and 69 in control group (p less than 0.01); 3) 23 patients on prophylaxis presented at least one febrile episode versus 33 in the control group (p less than 0.01); 4) deaths due to infection were two in the TMP/STX group versus 11 in control group (p less than 0.05). Prophylaxis with TMP/STX appears to be useful since by reducing the number of febrile episodes and deaths due to infection, it increases the survival of leukemia patients under cytostatic drugs. Nevertheless, further studies on a larger number of patients are necessary in order to confirm the true efficacy of the drug in the reduction of sepsis and death due to infection.

TITLE: Are bile bacteria relevant to septic complications following biliary surgery?ABSTRACT: Bile bacteriology, wound sepsis and the effect of prophylactic antibiotics have been studied in a controlled prospective double blind randomized trial on 375 patients undergoing elective cholecystectomy at a district general hospital. We have examined the overall prevalence of bacteria in bile and have identified several factors associated with an increased incidence. The identity of organisms isolated from a total of 21 patients with infected wound swabs was compared with isolates from the bile at operation, and in only two instances was there a correlation. Cephazolin, given either pre-operatively, or into the wound, reduced wound infection rates compared with a control group (from 11.8 to 2.4 per cent, P less than 0.005). We conclude that the majority of wound infections in this series were caused by organisms from the patients' skin or exogenous sources, rather than by bacteria from the biliary system.

TITLE: Effect of postoperative total parenteral nutrition (TPN) as an adjunct to gastrectomy for advanced gastric carcinoma.ABSTRACT: Clinical staging and immune reactivity were correlated in 39 patients who underwent gastrectomy for primary gastric cancer. Cellular immunity was depressed as the stage of cancer advanced, whereas humoral immunity was unaffected. Gastrectomy for advanced cancer in stage 3 and 4 suppressed cellular immunity. The cellular and humoral immune systems in relation to total parenteral nutrition (TPN) versus non-TPN were evaluated in 57 patients who underwent gastrectomy for stage 3 and 4 advanced cancer. Cell-mediated immunocompetence was restored in all 29 patients who received postoperative TPN, while serum immunoglobulins were unaffected by TPN. Improvement of impaired cell-mediated immunity was also obtained in patients treated with a TPN-5-FU combination as an adjunct to surgery. Treatment with TPN during 5-FU administration restored immunocompetence, increased tolerance for 5-FU and gave a satisfactory 3-year survival rate. There were significant differences in the 3-year survival rates of patients who underwent non-curative gastrectomy (54 per cent for TPN-5-FU v. 0 per cent for non-TPN-5-FU; P less than 0.05). It is concluded that TPN during chemotherapy as an adjunct to surgery leads to diminished morbidity, and possibly to prolonged survival time, in patients undergoing gastrectomy for gastric cancer. A possible mechanism responsible for the gratifying results of TPN treatment may be the increased tolerance for 5-FU resulting from improved nutrition and increased cell-mediated immunity.

TITLE: Larvicidal activity of albendazole against Necator americanus in human volunteers.ABSTRACT: This study evaluated the efficacy and tolerance of a single oral 400-mg dose of albendazole on Necator americanus larvae, and compared its efficacy when administered between meals or with a meal. Twenty-nine healthy and hookworm-free male volunteers were exposed on the forearm to approximately 45 8-day-old N. americanus larvae. All subjects developed discrete maculopapular eruptions at the site of larval application. Following a random double-blind study design, each subject received at the end of the 6th post-infection day either the investigational drug or a placebo as follows: Group I (n = 8)-placebo; Group II (n = 11)-400 mg albendazole with a meal; Group III (n = 10)-400 mg albendazole 3 or more hours after or before a meal. On day 56 post-infection, the stools of all subjects who received placebo were positive for N. americanus eggs (by zinc sulfate flotation technique), compared with 48% positivity (10/21) in those who received albendazole (P = 0.01). By day 63 post-infection, an additional three subjects in the treatment group became positive, for an overall 62% rate of positivity (13/21), i.e., albendazole prevented patent infection in 38%. Administration of albendazole with a meal did not alter drug efficacy. In those subjects in whom patent infections were not prevented, egg output was one-fourth that of the placebo group. There was no difference in viability of eggs appearing in feces of treated and untreated subjects as judged by larval development in Harada-Mori cultures. Our data indicate that albendazole is active against pre-intestinal stages of N. americanus in human infections.

TITLE: Effects of two energy: nitrogen ratios in patients with gastroenterological disease and malnutrition.ABSTRACT: In 10 patients with active gastroenterological disease and protein-malnutrition (weight: 77.3 +/- 2.6 (mean +/- SEM) percent of ideal body weight, serum-albumin levels: 2.59 +/- 0.17 mg/100 ml) a randomized crossover study was performed to assess the effects of two energy:nitrogen ratios on body cell replenishment. After at least 3 days for equilibration, the total parenteral nutrition (TPN) study carried out with 354 +/- 5 mg of casein hydrolysate-nitrogen/kg/day, divided in two 7-day periods during which two nonprotein calorie supplies of 47 +/- 1 kcal/kg/day and 81 +/- 4 kcal/kg/day were given. The same 50 +/- 5% dextrose and fat emulsion energy sources were used in the two periods. Nitrogen (Kjeldahl method) and potassium retention, and weight and serum albumin concentration gains were all significantly better (Student t test) during the hypercaloric regimen than during the normocaloric regimen. In the 10 patients, the protein-sparing effect of nonprotein calories "added" during the hypercaloric regimen was demonstrated and represented 17% of the constant infused nitrogen. The more catabolic patient was prior to TPN, the more energy-dependent was the protein-sparing effect observed (r = +0.638). Preliminary data obtained with 3-methylhistidine urine determination suggests that the protein-sparing effect of "added" calories was due to an increased protein synthesis. Finally, body cell replenishment was better with the higher 230 +/- 6 energy:nitrogen ratio than with the lower 132 +/- 4 energy:nitrogen ratio, which suggests that the hypercaloric TPN regimen was useful in such patients.

TITLE: Effects of the estrogenicity of levonorgestrel/ethinylestradiol combinations of the lipoprotein status.ABSTRACT: Ninety-eight women seeking contraceptive advice were randomly allocated to 6 months of treatment with one of the following four combinations of ethinylestradiol (EE) and levonorgestrel (NG): 20/250, 30/250, 30/150, and the so-called triphasic drug. The EE/NG ratios were 0.08, 0.12, 0.20 and 0.36 respectively. Blood lipids, HDL-cholesterol and sex hormone binding globulin (SHBG) were determined twice before treatment and after 1, 3 and 6 months of medication. Plasma triglyceride levels were moderately elevated in all groups, with the highest increase in the women taking the triphasic drug. The HDL-cholesterol and HDL-cholesterol to cholesterol ratios were both markedly reduced, by 20/250 and 30/250, while 30/150 and the triphasic drug caused only minor reductions. The mean change in HDL-cholesterol showed a good correlation with the mean changes of SHBG (r = 0.916) and with the EE/NG ratios (r = 0.979). It is concluded that both SHBG and the EE/NG ratio may be used as an index of the estrogenicity of a combined oral contraceptive drug. As reduced HDL-cholestrol levels and HDL-cholesterol to cholesterol ratios have been shown to be directly correlated to the risk of developing ischemic cardiovascular disease it would seem important that the estrogenicity of such a drug should be sufficiently high.

TITLE: Effects of dexfenfluramine on free fatty acid turnover and oxidation in obese patients with type 2 diabetes mellitus.ABSTRACT: To test the potential effects of dexfenfluramine (dF) on enhancing free fatty acid (FFA) turnover and oxidation rates, 11 obese female non-insulin-dependent diabetes mellitus (NIDDM) outpatients (age, 52.5 +/- 1.5 years; weight, 81.3 +/- 3.2 kg; height, 158 +/- 3.04 cm; body mass index, 32.4 +/- 0.7 kg/m2) received a primed-constant infusion of 1-14C-palmitate. The waist to hip ratio (WHR) was 0.91 +/- 0.04. Fat body mass and lean body mass, assessed by dual-energy x-ray densitometry, were 32.0 +/- 1.5 and 49.30 +/- 2.67 kg, respectively. All patients had an average hemoglobin A1 of 6.3% +/- 0.3% in the month preceding the study and had not received oral hypoglycemic agents. Gas exchange was measured both basally and during a ventilated-hood system, indirect-calorimetry session. The protocol was a randomized, placebo-controlled, single-blind design. Subjects received dF 30 mg acutely (n = 6) or a placebo (n = 5). A dose of dF 15 mg twice daily or placebo was then administered over 15 days (chronic). To obtain serum peak level of the drug, dF was administered 2 hours before starting palmitate infusion. A free diet was allowed throughout the study, and the group treated with dF lost approximately 0.5 kg body weight. Acute and chronic dF administration resulted in a significant increase in FFA oxidation, expressed as a percentage of the dose of radiocarbon (respectively, 11.47% +/- 0.46% v 9.50% +/- 0.46% [P < .01] and 12.06% +/- 0.71% v 9.88% +/- 0.62% [P < .01]). FFA turnover rate was higher after both acute and chronic dF administration (respectively, 10.71 +/- 2.18 v 7.79 +/- 1.48 mumol/kg/min [P < .05] and 11.92 +/- 2.74 v 8.43 +/- 1.86 mumol/kg/min [P < .05]). Serum FFA concentration during both acute and chronic dF administration increased, but not significantly. Mean serum glucose level decreased after acute dF from 114.3 +/- 8.6 to 86.5 +/- 5.1 mg/dL (P < .001) and after chronic dF from 120.3 +/- 7.3 to 89.8 +/- 5.8 mg/dL (P < .001). Serum insulin was not affected by dF administration. In conclusion, oral acute and chronic dF administration increase FFA turnover and oxidation rates in NIDDM obese patients. This may play an important role in weight reduction. In addition, dF shows a weight-independent effect on glucose metabolism, reducing serum glucose levels without acting on insulin secretion.

TITLE: Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group.ABSTRACT: Several small studies have suggested beneficial effects of long-term beta-blocker treatment in idiopathic dilated cardiomyopathy. Our large multicentre study aimed to find out whether metoprolol improves overall survival and morbidity in this disorder. 383 subjects with heart failure from idiopathic dilated cardiomyopathy (ejection fraction < 0.40) were randomly assigned placebo or metoprolol. 94% were in New York Heart Association functional classes II and III, and 80% were receiving background treatment. A test dose of metoprolol (5 mg twice daily) was given for 2-7 days; those tolerating this dose (96%) entered randomisation. Study medication was increased slowly from 10 mg to 100-150 mg daily. There were 34% (95% CI -6 to 62%, p = 0.058) fewer primary endpoints in the metoprolol than the placebo group; 2 and 19 patients, respectively, deteriorated to the point of needing transplantation and 23 and 19 died. The change in ejection fraction from baseline to 12 months was significantly greater with metoprolol than with placebo (0.13 vs 0.06, p < 0.0001). Pulmonary capillary wedge pressure decreased more from baseline to 12 months with metoprolol than with placebo (5 vs 2 mm Hg, p = 0.06). Exercise time at 12 months was significantly greater (p = 0.046) in metoprolol-treated than in placebo-treated patients. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol prevented clinical deterioration, improved symptoms and cardiac function, and was well tolerated.

TITLE: Vitamin A supplementation and childhood malaria in northern Ghana.ABSTRACT: Two companion, randomized, placebo-controlled trials of prophylactic vitamin A supplementation provided the opportunity to assess the impact of supplementation on malaria parasitemia, morbidity, and mortality in young children in northern Ghana. In the mortality study, 21,906 children were visited every 4 mo over 2 y, and in the morbidity study 1455 children were visited weekly for 1 y. There was no difference between children supplemented with vitamin A and those given placebo in malaria mortality rates (rate ratio = 1.03; 95% CI 0.74, 1.43) or fever incidence based on reported symptoms. Malaria parasitemia rates, parasite densities in children with a positive blood smear, and rates of probable malaria illness also did not differ between treatment groups. There was no correlation between serum retinol at the beginning of the trial and subsequent malaria parasitemia in children who received placebo (r = 0.01). It is concluded that vitamin A supplementation had no impact on malaria in this population.

TITLE: Correcting respiratory rate for the presence of fever.ABSTRACT: This study defines what degree of respiratory rate (RR) elevation can be attributed to fever using a double blind randomized pre- and post-acetaminophen comparison of vital signs of febrile children presenting to an outpatient clinic. Inclusion criteria were aged between 6 weeks and 24 months, fever between 38.5 and 40.1 degrees C, no serious illness such as sepsis, and no recent receipt of antipyretics or antibiotics. RRs counted over 1 min and rectal temperatures were recorded by a trained observer before, and 1 and 1.5 hours (hr) after receipt of 10-15 mg/kg/dose of either acetaminophen (A) or placebo (P). Randomization produced groups A (n = 54), and P (n = 50) with similar mean age (12.3 vs 12.8 mo.), gender distribution (57 vs 54% female), baseline temperature (39.1 vs 39.1 degrees C), baseline RR (44 vs 45), and hours of fever prior to visit (42 vs 37 hr). The most common diagnoses were otitis media (49%), viral syndrome (18%), upper respiratory infection (16%) or gastroenteritis (7%). The mean temperature decrement of group A was 0.4 degrees C at 1 hr and 0.9 degrees C at 1.5 hr compared to slight increases in fever of 0.3 degrees C at 1 hr and 1.5 hr in group P. Significant decreases in RR occurred in group A compared to group P at 1 hr (7.0 vs 1.9, p = 0.009) and 1.5 hr (10.8 vs 4.0, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: The effect of raw potato starch on energy expenditure and substrate oxidation.ABSTRACT: Because resistant starch (RS) is not absorbed as glucose in the small intestine of healthy humans, postprandial thermogenesis should be lower after the intake of RS as compared with digestible starch. To evaluate this hypothesis, we measured 5-h postprandial thermogenesis and substrate oxidation by indirect calorimetry after ingestion of 50 g pregelatinized (0% RS) and 50 g raw potato starch (54% type II RS) in 15 healthy, normal-weight young males. The subjects consumed each starch (mixed in diluted fruit syrup) twice on separate days and in random order. RS intake was followed by lower thermogenesis (46.5 +/- 13.1 compared with 115.4 +/- 10.4 kJ/5 h; P = 0.008), lower glucose oxidation (P < 0.0005), and greater fat oxidation (P = 0.013) than was pregelatinized starch consumption. Our results suggest that RS has no thermogenic effect and that its presence does not influence the size of the thermic response to digestible starch.

TITLE: One-year acarbose treatment raises fasting serum acetate in diabetic patients.ABSTRACT: alpha-Glucosidase inhibitors such as acarbose improve blood glucose control in diabetes by delaying or reducing carbohydrate absorption. The fermentation of malabsorbed carbohydrate in the colon is associated with the production of gas, leading to flatulence, and short chain fatty acids such as acetate, which may have systemic effects. To see if acarbose raised fasting serum acetate in diabetic patients, we studied 85 subjects selected from the 267 who had completed a 1-year, double-blind, placebo-controlled, parallel design study of the effects of acarbose in the treatment of diabetes. At baseline, there was no significant difference between the 44 subjects subsequently randomized to placebo and the 41 randomized to acarbose, respectively, in fasting serum acetate (80 +/- 5 vs 71 +/- 4 mumoll-1) or glycosylated haemoglobin (HbA1C; 7.2 +/- 0.3 vs 7.4 +/- 0.3%). Compared to placebo, acarbose treatment significantly increased fasting serum acetate by 11 +/- 4 vs 2 +/- 3 mumoll-1 (p < 0.02) and reduced HbA1C by -0.59 +/- 0.16 vs -0.13 +/- 0.20% (p < 0.02). Acarbose treatment had no significant effect on serum cholesterol or non-esterified fatty acids, but was associated with a significant increase in flatulence. There was no relationship between changes in serum acetate and changes in HbA1C, serum cholesterol or symptoms. We conclude, in subjects with diabetes who tolerate therapy for a 1-year period, that acarbose treatment increases serum acetate. The magnitude of change in acetate was unrelated to side-effects or changes in blood glucose control or serum lipids.

TITLE: Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT).ABSTRACT: We examined the results of the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) to determine the characteristics and consequences of creatine kinase (CK) and creatine kinase, MB myocardial isoenzyme fraction (CK-MB) elevations after percutaneous coronary intervention.Enzyme elevations after interventional procedures have usually been thought to be without long-term clinical consequences. However, recent preliminary reports have suggested that there are important long-term clinical sequelae in patients with even mild enzyme elevations after coronary procedures.Patients with new native lesions undergoing coronary intervention at 35 clinical sites were randomized to undergo percutaneous coronary angioplasty (n = 500) or directional coronary atherectomy (n = 512). Cardiac enzyme levels were measured 12 and 24 h after the interventional procedure and when clinically indicated for recurrent myocardial ischemia. Enzyme profiles were analyzed using a ratio that compared the peak enzyme level and the local laboratory upper limit of normal. Standard 12-lead electrocardiograms (ECGs) recorded before and after the procedure were interpreted by two independent readers who had no knowledge of the randomization data. Postprocedural myocardial infarction was defined as the appearance of new Q waves on the ECG, CK-MB levels three or more times the upper limit of normal or a total CK concentration two or more times the upper limit of normal when CK-MB levels were unavailable. Regression models were used to evaluate the predictive significance of a postintervention myocardial infarction with respect to clinical outcomes at 30 days and 1 year.There were 78 myocardial infarctions in the atherectomy group and 34 in the angioplasty group (15.2% vs. 6.8%, p = 0.001). Patients with a myocardial infarction more often had a repeat intervention or emergency coronary artery bypass surgery. Hospital length of stay was increased among patients with an infarction, as were mean hospital costs ($17,340.65 vs. $11,308.47, p = 0.0003). Postprocedural myocardial infarction was highly predictive of mortality, bypass surgery or repeat intervention within 30 days (p < 0.0001).Myocardial infarction occurred commonly after coronary intervention in CAVEAT and was associated with a worse clinical outcome. Although the incidence of myocardial infarction was higher with atherectomy than with angioplasty, the baseline characteristics and consequences of the infarctions were similar between the treatments with regard to 30-day outcome. Myocardial enzyme elevations after an otherwise successful interventional procedure may identify a population at risk for a future cardiac event.

TITLE: Impact of surgical stress on the haemodynamic profile of isoflurane-induced hypotension.ABSTRACT: It has been suggested that stimulation of adrenoreceptors could be responsible for some of the haemodynamic effects of isoflurane. But there are no solid data demonstrating the role of sympatho-adrenal stimulation induced by pain during isoflurane administration. The impact of surgical stress on the haemodynamic profile of isoflurane-induced hypotension has been investigated in 28 patients (47-76 years), scheduled for total hip arthroplasty. After premedication with morphine hydrochloride (0.1 mg/kg), patients were randomly assigned to receive either no fentanyl (control group) or fentanyl (5 micrograms/kg before tracheal intubation, 5 micrograms/kg before skin incision, and 2 micrograms/kg each 15 min during the 1st hour). Isoflurane was given to maintain mean arterial blood pressure in the range 6.7-8 kPa in both groups. Haemodynamic data and blood samples for determination of plasma renin activity (PRA) and epinephrine (E) and norepinephrine (NE) levels were collected before and during hypotension. The fentanyl group and the control group differed significantly during hypotension: heart rate, cardiac index, oxygen consumption and E, NE and PRA were lower (P less than 0.01) in the fentanyl group than in control group. Fentanyl lowered the required concentration of isoflurane to achieve the same degree of hypotension (end-tidal concentration: 0.8 +/- 0.2% in the fentanyl group and 1.4 +/- 0.15% in the control group; P less than 0.001). Our results demonstrate that the cardiovascular effects of higher isoflurane concentrations in the absence of narcotic analgesia are counterbalanced by adrenergic stress stimulation of released epinephrine and norepinephrine. Among the likely reasons for catecholamine release during isoflurane administration, inadequate analgesia may be considered.

TITLE: Prognostic value of serum lactic dehydrogenase (S-LDH) in multiple myeloma.ABSTRACT: Serum lactic dehydrogenase (S-LDH) was analysed at diagnosis in ninety-three patients with multiple myeloma. The patients were then followed up after a mean observation period of 39 months (SD 29). Serum lactic dehydrogenase was elevated in twenty-seven out of ninety-three patients and found to correlate with the serum concentrations of beta 2-microglobuline, creatinine, and thymidine kinase. In discriminant analysis of pretreatment S-LDH levels in relation to survival, the best discrimination level was 7.0 mukat 1(-1). Patients with values below 7 microkat 1(-1) ahd a median survival time of 45 months compared to 14 months for those with levels above 7 mukat 1(-1) (P less than 0.001). Serum lactic dehydrogenase at diagnosis, thus, has prognostic information in multiple myeloma.

TITLE: The effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia.ABSTRACT: To assess the effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia, six healthy male volunteers each underwent two insulin tolerance tests in random order, separated by at least 1 week with and without atropine. ACTH levels were significantly greater at +45 min (mean +/- SEM, 223 +/- 21 pg/ml vs 148 +/- 15 pg/ml, P less than 0.01) and at +120 min (54 +/- 11 pg/ml vs 29 +/- 10 pg/ml, P less than 0.05). beta-endorphin levels were significantly greater at +30 min (170 +/- 45 pg/ml vs 96 +/- 32 pg/ml, P less than 0.05) and at +105 min (81 +/- 14 pg/ml vs 54 +/- 7 pg/ml, P less than 0.01). Cholinergic blockade had no effect on plasma glucose or cortisol concentrations. This study demonstrates that cholinergic blockade with atropine facilitates the ACTH and beta-endorphin responses to insulin-induced hypoglycaemia without altering the cortisol responses.

TITLE: Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event.ABSTRACT: Fifty three of the 5778 patients included in the MIAMI (Metoprolol in Acute Myocardial Infarction) trial were investigated with long-term ECG recordings in order to evaluate the effect of acute beta-blockade on premature ventricular complexes in and after acute myocardial infarction. Twenty five patients were given placebo and 28 metoprolol in a double-blind randomized fashion for 15 days. After this period the patients were put on open beta-blockade without breaking individual study codes. The mean number of premature ventricular complexes during the inclusion day (day 0) was the same in the two groups. The median numbers were also similar in the two groups: 190 and 154 in the placebo and metoprolol groups, respectively. Metoprolol significantly reduced the median number of premature ventricular complexes in the randomized period. The median numbers on days 1, 2 and 15 were 146, 101, 84 in the placebo group and 73, 59 and 10 in the metoprolol group, respectively (P less than 0.05). Also during the further follow-up, when investigated 1, 3 and 6 months after the infarction, the median number of premature ventricular complexes was lower in the metoprolol group (74, 257, 142 in the placebo group and 7, 5 and 11 in the metoprolol group, P less than 0.05). This indicates that metoprolol treatment in the acute phase of myocardial infarction reduces ventricular arrhythmias both in the early stage and also after the acute event.

TITLE: Enalapril maleate versus captopril. A comparison of the hormonal and antihypertensive effects.ABSTRACT: 24 hypertensive patients were randomised into 2 groups to compare the antihypertensive effects of enalapril and captopril over a 10-week period. In the hydrochlorothiazide run-in period, blood pressure was reduced from 171 +/- 4/109 +/- 1mm Hg to 160 +/- 4/103 +/- 1mm Hg (p less than 0.05). Angiotensin-converting enzyme (ACE) inhibition decreased blood pressure to 132 +/- 3/87 +/- 2mm Hg. Captopril decreased diastolic blood pressure significantly more after 3 hours than enalapril (-24 versus -17mm Hg, p less than 0.05). After 10 weeks of therapy, this antihypertensive response was maintained at 134 +/- 3/83 +/- 1mm Hg. There was no difference between the captopril and enalapril treated groups. Acute and chronic responses of plasma renin activity, plasma aldosterone and ACE were determined. There was an acute positive correlation between the rise in plasma renin activity and the fall in blood pressures with captopril but not with enalapril. With chronic treatment there was no difference in the ability of either of the 2 drugs to reduce blood pressure, inhibit ACE, reduce aldosterone or stimulate plasma renin activity.

TITLE: Efficacy of indobufen in the treatment of intermittent claudication.ABSTRACT: The aim of this trial was to assess the activity of indobufen compared with placebo in peripheral occlusive arterial disease of the lower limbs of atherosclerotic or diabetic origin. Fifty-two outpatients were admitted to the randomized, double-blind study and were given either an indobufen 200-mg tablet (28 subjects) or placebo (24) for six months. Painfree walking distance on a treadmill at a constant speed (4 km/h) and slope (10 degrees) was assessed before and after three and six months' treatment. The painfree walking distance before treatment with indobufen or placebo averaged 153 +/- 23.02 (mean +/- SE) and 199 +/- 30.58 (mean +/- SE) meters respectively. After six months' treatment with active drug or placebo, this parameter reached 610 +/- 115.36 (p less than 0.01) and 243 +/- 32.49 (p greater than 0.05) meters respectively. The difference between the two treatments was statistically significant in favor of indobufen (p less than 0.01 Dunn's test).

TITLE: A randomized trial comparing cyclosporine with antilymphoblast-globulin-azathioprine for renal allograft recipients. Results at 2 1/2-6 years.ABSTRACT: Between September 1980 and June 1984, 246 splenectomized, transfused renal allograft recipients were stratified according to presence of diabetes and donor source, and randomized to treatment with either cyclosporine (CsA)-prednisone (pred) or antilymphoblast-globulin (ALG--azathioprine (AZA)--prednisone. As of August 1986, mean follow-up is 47 months. Over all, actuarial patient survival is 84% and 83%, respectively at 4 years. Corresponding graft survival is 70% and 63% for CsA-treated and ALG-AZA-treated patients (NS). Within the subgroup of diabetic recipients of cadaver grafts, graft survival is 70% for CsA-treated and 53% for ALG-AZA-treated recipients (P = .035). In the CsA group, 71% required either a significant reduction in CsA dosage with the addition of azathioprine or a complete switch to azathioprine, mainly because of CsA-associated nephrotoxicity. Of those CsA patients switched at a mean time of 21.3 +/- 16.4 months posttransplant with mean serum creatinine of 2.40 +/- .67, current serum creatinine is 1.79 +/- .63. Current mean serum creatinine values are significantly greater for patients randomized to CsA-pred (1.73 +/- .60) vs. ALG-AZA-pred (1.49 +/- .59), P = .014, even though most CsA-treated patients were eventually switched. The causes of graft loss are not different between CsA and ALG-AZA randomized patients. In nondiabetics, rejection is the most common cause of graft loss (17/33), whereas in diabetics loss due to complications from overimmunosuppression or death from cardiovascular events is significantly more common (27/44) than corresponding losses in nondiabetics (6/33, P less than .05). Switching does not seem to influence the incidence or cause of graft loss. Since most patients started on CsA-prednisone are ultimately switched to triple drug therapy, the latter is now the preferred initial treatment modality.

TITLE: A randomized double-blind comparison of diltiazem and nifedipine in stable angina.ABSTRACT: A double-blind crossover trial comparing diltiazem (360 mg/day) and nifedipine (120 mg/day) for treatment of stable angina was conducted in 21 of 27 patients with proven coronary artery disease who completed the trial. All patients started with a 2 week placebo period followed by a random assignment to either drug treatment for 3 weeks and subsequent crossover to the other treatment. The two drug treatment periods were separated by a 1 week placebo washout phase and the study was completed with a 1 week placebo phase. There were no significant differences between patients' responses to diltiazem and nifedipine in relation to time to onset of angina, ST depression responses to exercise, heart rate or systolic or diastolic blood pressure. A total of 37 adverse effects were reported with nifedipine compared with 9 with diltiazem in the 22 patients in whom drug safety was analyzed. Additionally, two patients treated with nifedipine were withdrawn from study participation before crossover. There was a significant (p less than 0.05) difference with respect to incidence of edema (7 of 22 patients taking nifedipine, 1 of 22 taking diltiazem) and dizziness (7 of 22 patients taking nifedipine, 0 of 22 taking diltiazem). The most frequent adverse effect reported with diltiazem was rash (3 of 22 patients). Severe adverse effects were reported in four patients: in one with diltiazem (rash) and in three with nifedipine (palpitation in two and headache in one). A reduction in prescribed dosage was required in 37% of nifedipine-treated compared with 6% of diltiazem-treated patients. Efficacy measures were significantly improved above placebo levels by both diltiazem and nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Acute coronary artery obstruction in myocardial infarction: overview of thrombolytic therapy.ABSTRACT: Pump failure, ranging from ventricular dysfunction to acute cardiogenic shock, is now the leading cause of cardiac death. Efforts at temporary mechanical or pharmacologic support of the heart have been largely unsuccessful so that attention is now directed toward prevention of ventricular failure and limitation of myocardial infarct size or even outright prevention of infarction itself. In particular, attention has been refocused on earlier reperfusion efforts with streptokinase. The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function and early mortality was studied in subsets of patients in a randomized trial (Netherlands Interuniversity Cardiology Institute). Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. Of the patients eligible for this detailed analysis, 245 were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiography was preformed in 212 of the 245 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 versus 1,179 U/liter in control subjects, p = 0.0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% versus 43% in control subjects, p = 0.0001). Twelve month mortality was lower in patients allocated to thrombolytic therapy (8% versus 16% in the control group, p less than 0.01). In multivariate regression analysis infarct size limitation, improvement of left ventricular ejection fraction and 3 month mortality were predicted by sigma ST, time from onset of symptoms to admission and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with a sigma ST segment of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function or mortality were observed in the subset of patients with sigma ST less than 1.2 mV, admitted 2 to 4 hours after onset of symptoms.

TITLE: Effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responsiveness to leukotriene D4 in normal and asthmatic subjects.ABSTRACT: Cysteinyl leukotrienes are potent inflammatory mediators that are considered to play a role in the pathophysiology of asthma. It can be postulated that leukotrienes exert their bronchoconstricting effects, in part, through secondary release of endogenous neuropeptides. We examined the effect of inhaled thiorphan, an inhibitor of a neuropeptide degrading enzyme, on the concentration-response curve to leukotriene D4 (LTD4) in a two-period, double-blind, cross-over and placebo-controlled study, in 16 nonasthmatic and 12 asthmatic subjects. Thiorphan or placebo were aerosolized and administered in two 0.5 ml doses of 1.25 mg.ml-1 each, 10 min prior to LTD4 inhalation. The airway response was measured by forced expiratory volume in one second (FEV1) and partial expiratory flow-volume curves (expiratory flow at 40% of forced vital capacity; V40p), and expressed as % fall from baseline. Complete concentration-response curves to inhaled LTD4 were recorded and characterized by their position (provocative concentration producing a 20% fall in FEV1 and a 40% fall in V40p; PC20FEV1 and PC40 V40p) and, in the nonasthmatics, also by the maximal-response plateau (MFEV1, MV40p). Post-pretreatment baseline values of FEV1 and V40p were not different between thiorphan and placebo pretreatment. In both groups of subjects, there was no significant difference in lnPC40V40p or lnPC20FEV1 to LTD4 between the two pretreatments mean difference +/- SD (in doubling concentrations): 0.12 +/- 0.73 and -0.19 +/- 1.23, respectively, in asthmatics; and 0.17 +/- 0.95 and -0.99 +/- 1.95, respectively, in nonasthmatics. The maximal-response plateau could not be obtained in the majority of the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Active compression-decompression resuscitation: effect on resuscitation success after in-hospital cardiac arrest.ABSTRACT: The purpose of this study was to test the hypothesis that active compression-decompression would improve resuscitation success in human subjects after cardiac arrest.Active compression-decompression cardiopulmonary resuscitation is a new method that improves cardiopulmonary hemodynamic function in animal models and humans after cardiac arrest.We conducted a prospective randomized clinical trial in patients with in-hospital cardiac arrest. Patients were assigned to receive standard manual or active compression-decompression cardiopulmonary resuscitation. The primary study end points were spontaneous return of circulation, 24-h survival and survival to hospital discharge.Fifty-three consecutive patients after cardiac arrest undergoing 64 resuscitation attempts were studied (30 women, 23 men; mean [+/- SD] age 71 +/- 13 years, range 38 to 96). Spontaneous return of circulation was observed in 24 (47%) of 53 patients and was increased in patients receiving active compression-decompression compared with those receiving standard manual cardiopulmonary resuscitation (15 [60%] of 25 vs. 9 [32%] of 28, respectively, p = 0.042); 24-h survival was increased (12 [48%] of 25 vs. 6 [21%] of 28, respectively, p = 0.041); and there was a trend toward improved survival to hospital discharge (6 [24%] of 25 vs. 3 [11%] of 28, respectively, p = 0.198) when active compression-decompression was compared with standard manual cardiopulmonary resuscitation.Active compression-decompression cardiopulmonary resuscitation improves return of spontaneous circulation and 24-h survival after in-hospital cardiac arrest. Active compression-decompression cardiopulmonary resuscitation appears to be a beneficial adjunct to standard manual cardiopulmonary resuscitation.

TITLE: Perioperative chemotherapy in patients with oral cancer.ABSTRACT: In the final report of a prospective, randomized controlled clinical trial, we report the results of using adjuvant perioperative chemotherapy in patients with oral cancer. Our study is based on the hypothesis of Goldie and Coldman. A total of 135 patients with alveolobuccal carcinoma, classified as clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The patients in the test arm of the study received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The patients in the control arm underwent observation. This analysis at 24 months showed a disease-free survival rate of 61% in the test arm versus 37% in the control arm, which is statistically highly significant (P < 0.01). Analysis of the recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P = 0.002). Our study provided further clinical evidence in support of the concepts of Goldie and Coldman that the timing of chemotherapeutic drugs is critical for a successful end result.

TITLE: Laparoscopic salpingostomy versus laparoscopic local methotrexate injection in the management of unruptured ectopic gestation.ABSTRACT: Our goal was to determine whether laparoscopic salpingostomy is preferable to laparoscopic methotrexate injection in the management of unruptured tubal gestation.Forty-eight patients with unruptured tubal pregnancy were prospectively randomized to either laparoscopic salpingostomy or laparoscopic local methotrexate injection in a university medical center. Operation time, duration of hospital stay, decrease in levels of beta-human chorionic gonadotropin, and fertility outcome were compared between the two groups.The salpingostomy group had a longer operative time (p < 0.0001) but a shorter hospital stay (p < 0.01) and a lower incidence of persistent trophoblastic activity (5% vs 14%), although this difference did not reach statistical significance. The time interval until beta-human chorionic gonadotropin disappearance was similar (13.9 and 13.7 days), and the subsequent intrauterine pregnancy rate was similar in the two groups (83.5% and 81%). One repeat tubal pregnancy occurred in the salpingostomy group.Both these methods of conservative management are equally effective and each one has its merits.

TITLE: Hypophosphataemia after renal transplantation: relationship to immunosuppressive drug therapy and effects on muscle detected by 31P nuclear magnetic resonance spectroscopy.ABSTRACT: Plasma phosphate values were examined in 72 renal transplant patients in a randomised trial of immunosuppression with azathioprine and prednisolone versus cyclosporin alone. From 21 to 77 days after transplantation, in patients with plasma creatinine concentrations of 75-150 mumol/l, mean plasma phosphate was 0.98 (SEM 0.04) mmol/l in cyclosporin-treated patients, compared with 0.65 (SEM 0.12) mmol/l in cyclosporin-treated patients receiving pulse methylprednisolone for rejection (P less than 0.003), and 0.68 (SEM 0.02) mmol/l in patients treated with azathioprine and prednisolone (P less than 0.001). There was no difference between the mean plasma creatinine of these groups of patients. A preliminary study by nuclear magnetic resonance spectroscopy of four patients with asymptomatic chronic hypophosphataemia showed reduced concentrations of intracellular phosphate in resting muscle, and further abnormalities developed on exercise. Thus, exogenous steroid administration is a major contributing factor of hypophosphataemia in the early post-transplant period. In addition chronic hypophosphataemia may be associated with reduced intracellular inorganic phosphate concentrations detectable by nuclear magnetic resonance spectroscopy, although these changes are not apparently associated with any clinical symptoms.

TITLE: Lack of effects of angiotensin-converting enzyme (ACE)-inhibitors on glucose metabolism in type 1 diabetes.ABSTRACT: To evaluate the impact of ACE-inhibitors on insulin-mediated glucose uptake, glucose-induced glucose uptake, and hepatic glucose production, a sequential glucose clamp was performed in eight normotensive Type 1 diabetic patients after 3 weeks of enalapril therapy 20 mg day-1 and during control conditions. The experiments were carried out in random order. Mean arterial blood pressure was significantly reduced during ACE-inhibition (95 +/- 3 (+/- SE) vs 84 +/- 3 mmHg; p less than 0.02), while blood glucose control as assessed by HbA1c was unaltered (7.9 +/- 0.5 vs 7.6 +/- 0.5%). The night prior to the study normoglycaemia was maintained by a Biostator. A two-step hyperinsulinaemic euglycaemic clamp (insulin infusion rate 0.3 and 0.8 mU kg-1 min-1) was followed by a hyperinsulinaemic and hyperglycaemic clamp (insulin infusion rate 0.8 mU kg-1 min-1, plasma glucose 11 mmol l-1). Insulin concentrations were comparable with and without enalapril treatment. During the hyperinsulinaemic clamps isotopically determined glucose disposal was unchanged (low dose 2.5 +/- 0.3, high dose 4.3 +/- 0.7 vs 2.6 +/- 0.3 and 4.3 +/- 0.7 mg kg-1 min-1, enalapril vs control). Glucose-induced glucose disposal (9.2 +/- 1.2 vs 9.1 +/- 1.2 mg kg-1 min-1) was also similar, as were non-protein respiratory exchange ratios (indirect calorimetry). Glucose production was not changed by enalapril. In conclusion, treatment with enalapril has no significant effect on glucose metabolism in Type 1 diabetes.

TITLE: The long-term effects of nedocromil sodium and beclomethasone dipropionate on bronchial responsiveness to methacholine in nonatopic asthmatic subjects.ABSTRACT: We investigated the effects of long-term treatment with two anti-inflammatory drugs, nedocromil sodium and beclomethasone dipropionate, on airway hyperresponsiveness to methacholine (PC20), on baseline FEV1 and on the bronchodilating effect of a deep breath in 25 nonsteroid-dependent nonatopic asthmatic adults. In all subjects the prestudy PC20 was less than 8 mg/ml, the postbronchodilator FEV1 was greater than 75% predicted, and skin prick tests and RAST to 13 common allergens were negative. After 2 months run-in, the subjects were randomly allocated into 3 parallel treatment groups to inhale double-blind either 4 mg nedocromil (n = 9) or 100 micrograms beclomethasone (n = 8) or placebo (n = 8) 4 times daily for 4 months. PC20 was measured using the 2-min tidal breathing method. The effect of a deep breath was measured during methacholine-induced bronchoconstriction by standardized maximal and partial expiratory flow-volume curves and was expressed as a flow ratio (M/P ratio). Pretreatment values of FEV1, PC20, and M/P ratio were not different between the 3 groups. PC20 did not change in the placebo group, but increased significantly by a factor of 3 after 8 wk of treatment with beclomethasone or nedocromil (p less than 0.001). FEV1 did not change after treatment with placebo or nedocromil (p greater than 0.2), but increased (mean change 0.2 L, SD 0.2) after 4 wk of treatment with beclomethasone (p less than 0.05). Geometric mean M/P ratio increased from 1.98 to 2.66 after 4 wk of beclomethasone (p less than 0.01), but not after nedocromil or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Evaluation of the clinical pharmacology of nilvadipine in patients with mild to moderate essential hypertension.ABSTRACT: Eighty-four patients with diastolic blood pressure ranging from 100-115 mm Hg were randomized into a multicenter, parallel, double-blind, placebo-controlled, dose response study with nilvadipine (6 mg, 8 mg, 10 mg tid for 28 days). The hypotensive response pattern to nilvadipine was similar with all three doses although duration of response was dose dependent. Maximal decreases in diastolic blood pressure occurred at 1 hour when assessed on days 1 and 15 (16.0, 17.4, and 15.8 mm Hg, vs 17.2, 18.7, and 17.5 mm Hg, respectively). The hypotensive effect remained significant compared to placebo for at least 4 hours after dosing. The increase in heart rate associated with the maximal hypotensive response was minimal and not clinically significant (day 1: 7.6, 5.2, and 4.0 beats/min with 6, 8, and 10 mg; day 15: 4.0, 5.1, 2.6 beats/min with 6, 8, 9, and 10 mg, respectively). Finally, a correlation between plasma drug concentrations and nilvadipine-induced hypotensive response was observed (r = 0.48). Black and white hypertensive patients had similar hypotensive responses. Plasma nilvadipine concentrations on day 15 were similar to those on day 1 suggesting no accumulation of drug with a tid regimen. The most common drug related side effect was headache; less frequently seen were dizziness, edema, palpitations, and abdominal pain. Nilvadipine was well tolerated (only three patients were discontinued due to side effects). The efficacy, lack of tachycardia, and side effect profile observed in this study suggest that nilvadipine may be an important addition to the treatment of hypertension.

TITLE: Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients. A multicenter, randomized, double-blind placebo-controlled trial.ABSTRACT: To assess the preventive effect of Saccharomyces boulardii on diarrhea in critically ill tube-fed patients and to evaluate risk factors for diarrhea.Prospective, multicenter, randomized, double-blind placebo-controlled study.Eleven intensive care units in teaching and general hospitals.Critically ill patients whose need for enteral nutrition was expected to exceed 6 days.S. boulardii 500 mg four times a day versus placebo.Diarrhea was defined by a semiquantitative score based on the volume and consistency of stools. A total of 128 patients were studied, 64 in each group. Treatment with S. boulardii reduced the mean percentage of days with diarrhea per feeding days from 18.9 to 14.2% [odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.50-0.90, P = 0.0069]. In the control group, nine risk factors were significantly associated with diarrhea: nonsterile administration of nutrients in open containers, previous suspension of oral feeding, malnutrition, hypoalbuminemia, sepsis syndrome, multiple organ failure, presence of an infection site, fever or hypothermia, and use of antibiotics. Five independent factors were associated with diarrhea in a multivariate analysis: fever or hypothermia, malnutrition, hypoalbuminemia, previous suspension of oral feeding, and presence of an infection site. After adjustment for these factors, the preventive effect of S. boulardii on diarrhea was even more significant (OR = 0.61, 95% CI = 0.44-0.84, P < 0.0023).S. boulardii prevents diarrhea in critically ill tube-fed patients, especially in patients with risk factors for diarrhea.

TITLE: Comparison of a lifestyle modification program with propranolol use in the management of diastolic hypertension.ABSTRACT: To compare the management of mild diastolic hypertension (90 to 104 mm Hg) using a nonpharmacologic intervention with that using propranolol or placebo.Randomized, placebo-controlled trial with a 2 x 2 factorial design.University-based ambulatory care center.Two hundred seven men and 105 women, 22 to 59 years of age, 73% white, who had mild diastolic hypertension untreated for at least eight weeks.1) a multicomponent lifestyle modification intervention (lifestyle focus group, or LFG) administered in eight weekly meetings + placebo, 2) LFG + propranolol, 3) propranolol alone, and 4) placebo alone, followed for 12 months.Systolic blood pressure (SBP), diastolic blood pressure (DBP), and self-reported adverse effects at each of nine follow-up visits; fasting total cholesterol, triglycerides, and glucose at baseline and 12 months; 24-hour urine sodium (Na+) and potassium (K+), three-day food records and physical activity questionnaire at three and 12 months; and a quality of life questionnaire at 12 months.The mean decreases in DBP at 12 months were: 8.5 mm Hg in the LFG + propranolol group; 7.7 mm Hg in the propranolol-only group; 5.9 mm Hg in the placebo-only group; and 5.4 mm Hg in the LFG + placebo group. Repeated-measures analysis of covariance showed that level of baseline DBP (p < 0.0001), time of follow-up (p < 0.0001), and propranolol use (p < 0.0001) were significantly associated with a decrease in DBP at 12 months. Despite reductions in urinary Na+ (-35 mEq; 95% CI = -50, -19), dietary Na+ (-521 mg; 95% CI = -710, -332), total calories ingested (-238; 95% CI = -335, -140), and weight (-1.4 lb; 95% CI = -3.7, +0.8), and significant increases in dietary K+ (+294 mg; 95% CI = +107, +480) and in mets-minutes of exercise (+43; 95% CI = +20, +67) at three months, assignment to the LFG intervention had no effect on DBP at three or 12 months. The subjects assigned to take propranolol more frequently reported fatigue during ordinary activities, sleep disturbance, decrease in sexual activity, and depressed feelings, when compared with the subjects taking placebo, but the numbers of study withdrawals did not differ by drug assignment. No significant difference in total cholesterol and glucose levels was observed by group assignment. Triglycerides increased significantly in the subjects assigned to propranolol (mean difference = +20 mg/dL; 95% CI of difference +1.5, +39). There was no difference in the responses to 21 quality of life items between the subjects assigned to propranolol and those assigned to placebo.This multicomponent lifestyle modification intervention was unable to promote persistent behavior changes and thus was inferior to propranolol therapy for the treatment for mild diastolic hypertension. Future research should focus on single modifiable factors to lower blood pressure.

TITLE: Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B.ABSTRACT: To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia.A randomized, controlled, multicenter trial.30 hematologic units in tertiary care or university hospitals.820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia.Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours.An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B.Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01).Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.

TITLE: Cow's milk versus soy-based formula in mild and moderate diarrhea: a randomized, controlled trial.ABSTRACT: We determined the efficacy of a soy-based formula compared with a cow's milk formula in infant refeeding after acute diarrhea in a randomized controlled double-blind clinical trial. Infants 2-12 months of age with diarrhea of less than one week's duration and mild or moderate dehydration admitted to a pediatric hospital or in the practice of a participating primary care pediatrician were investigated. Seventy-six patients were enrolled and 73 completed the study; 39 infants received a soy-based formula (Isomil) and 34 received a cow's milk formula (SMA). Hospitalized patients were rehydrated with an oral glucose-electrolyte solution or an iv dextrose-sodium solution. Outpatients received oral glucose-electrolyte solution. In all patients, the study formula was commenced ad libitum during the first 24 h as determined by the attending pediatrician. The primary outcome measure was duration of diarrhea, defined as time to first normal stool, when subsequent stools were normal for a 24-h period. In addition, a predetermined secondary outcome was proportion of treatment failures, defined as the need to reinstitute clear fluids because of emesis, refusal to accept study formula, need for iv fluids due to negative fluid balance or diarrhea persisting beyond 7 days after enrollment. Total duration of diarrhea was significantly longer (p = 0.03) in those receiving cow's milk (mean +/- SD 6.6 +/- 4.2 days) than in those receiving soy-based formula (4.5 +/- 3.6 days). Volume of formula intake and weight gain at 14 days were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Hemodynamic effects of morphine and nalbuphine in acute myocardial infarction.ABSTRACT: Hemodynamic effects of morphine and the new narcotic analgesic, nalbuphine, were compared in a randomized, double-blind study in 15 patients with acute myocardial infarction (11 men and four women, average age 56.2 yr) and normal group mean hemodynamic function. During a 1-hr evaluation the hemodynamic effects were small but there were changes in several parameters. Morphine reduced heart rate (78 to 72 bpm, p less than 0.01) and diastolic and mean arterial pressures (69 to 64 mm Hg, p less than 0.05; and 91 to 84 mm Hg, p less than 0.05); nalbuphine was associated with a decrease in heart rate (82 to 72 bpm, p less than 0.01), decrease in cardiac index, which remained within the normal range (3.16 to 2.75 l/min/m(2), p less than 0.01), and an increase in systemic vascular resistance (1,204 to 1,461 dynes . sec . cm(-5), p less than 0.05). Neither drug altered systolic arterial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, stroke index, stroke work index, or pulmonary vascular resistance. Echocardiographic assessment revealed diminution of left ventricular mean velocity of circumferential fiber shortening after nalbuphine (1.26 to 1.08 circ/sec, p less than 0.05). Both drugs induced small reductions in respiratory rate and arterial pH and increases in PAO2. There were no changes in PaO2. Because of the absence of clinically important deleterious effects on cardiac pump function, nalbuphine merits further investigation as an analgesic in acute myocardial infarction.

TITLE: Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma.ABSTRACT: This prospective, randomized, controlled trial from the University of Hong Kong evaluated the efficacy of perioperative parenteral nutrition (PN) in patients requiring hepatectomy for primary hepatocellular carcinoma. From September 1990 through June 1993, 150 consecutive patients with resectable hepatocellular carcinoma were randomly assigned to receive either perioperative PN (n = 75), in addition to usual oral diet, or to no additional therapy (oral diet alone without PN; n = 75). Excluding patients with metastatic disease, a total of 64 patients in the perioperative PN group (39 with associated cirrhosis, 18 with chronic active hepatitis, and 7 without associated liver disease) were compared to 60 control patients (33 with cirrhosis, 12 with chronic active hepatitis and 15 with no associated liver disease). PN was started 7 days before hepatic resection and continued for 7 days after operation in the experimental patients. The PN consisted of standard micronutrients, dextrose, lipid emulsion (containing 50 percent of lipid as medium-chain triglycerides, MCT) and amino acids enriched in branched-chain amino acids (BCAA, 35 percent of PN protein intake), and provided = 1.5 g protein/kg/day and 30 kcal/kg/day. PN was administered via a superior vena cava Broviac catheter cycled over 12 hours each evening preoperatively, and as a 24 hour infusion during the postoperative week. Control patients received only 5 percent dextrose in normal saline postoperatively, with volume and sodium content similar to the experimental PN-treated patients. All patients studied (experimental and control) received 25 grams of albumin intravenously for 5 days postoperatively, and all were allowed to consume enteral diet as tolerated throughout the entire study period. Preoperative assessment included standard anthropometric indices, serum chemistries and proteins, indocyanine green clearance (an index of hepatic function), hand grip strength, and immune function tests (serum immunoglobulin concentrations and peripheral lymphocyte stimulation by phytohemagglutinin). Postoperative assessment included the same preoperative indices (chemistries measured from days 1 to 8 post-operatively), and overall postoperative mortality and morbidity during the hospitalization. Morbidity indices included both infectious complications and non-infectious complications (eg, pleural effusion, ascites, renal failure, hepatic coma). The two groups of patients were similar in age, sex, total and percent weight loss, hepatic carcinoma stage, incidence of cirrhosis, and other preoperative indices. However, a higher percentage of patients in the PN group had abnormal preoperative hepatic function by indocyanine green clearance (67 vs 47%, p = 0.03). The proportion undergoing major hepatectomy and other important intraoperative factors were similar between groups. No significant difference in postoperative hospital mortality occurred between groups (PN 8% vs control 15%; p = 0.30), and PN use did not change hand-grip strength, skin-fold thickness or midarm circumference. However, a significant beneficial effect of PN on hospital morbidity was observed Perioperative PN use was associated with a significant reduction in the overall postoperative morbidity rate (PN group 34% vs control group 55%; p = 0.02). This difference was mainly due to a significant reduction in infectious complications (PN 17% vs control 37%; p = 0.01), and in the need for diuretic drugs to control ascites (PN 25% vs control 50%; p = 0.004). There were no differences between groups in serum immunoglobulins or lymphocyte response to mitogens. There was less deterioration of liver function with PN as measured by the change in the rate of indocyanine green clearance (PN group -2.8% loss vs control group -4.8% loss; p = 0.05). The attenuation of hepatic function loss with PN occurred despite a significant rise in serum transaminase values from days 5 to 8 postoperatively. PN therapy was also associated with le

TITLE: Obese patients with type 2 diabetes poorly controlled by insulin and metformin: effects of adjunctive dexfenfluramine therapy on glycaemic control.ABSTRACT: Dexfenfluramine is well known for its weight reducing action and has been reported to improve glycaemic control in obese Type 2 diabetic patients not adequately controlled on conventional oral hypoglycaemic therapy. In this double-blind placebo-controlled study, 20 obese Type 2 diabetic patients with mean HbA1c of 8.8 +/- 0.5% (normal range 3.5-6.0%), and mean body mass index (BMI) of 34.4 +/- 1.0 kg m-2, who were poorly controlled on insulin (mean dosage 58.0 +/- 6.1 units day-1) were randomized to receive either additional dexfenfluramine or placebo for 12 weeks. Seventeen of these patients were already taking maximum tolerated metformin therapy (mean dosage 1.6 +/- 0.2 g day-1) and the other three were unable to tolerate any at all. At baseline, the dexfenfluramine and placebo groups were similar in all parameters studied. After the 12-week treatment period, median HbA1c had fallen in dexfenfluramine treated patients from 8.5 (interquartile range (IR): 7.5-10.3) to 7.1% (IR: 6.7-7.5; p < 0.02). The fall in HbA1c in individual patients after treatment with dexfenfluramine was strongly associated with weight loss (r = 0.69; p < 0.04), although as a group the changes in weight and BMI were not statistically significant. Placebo was without effect. These results show that in the obese patient with Type 2 diabetes who is poorly controlled despite large daily doses of insulin and metformin, adjunctive dexfenfluramine can improve glycaemic control without exacerbating weight gain.

TITLE: Treatment of Candida-infected denture stomatitis with a miconazole lacquer.ABSTRACT: The efficacy of a topically administered miconazole denture lacquer was compared with that of a placebo lacquer in the treatment of Candida-infected denture stomatitis. The study was a double-blind, randomized, controlled clinical trial with two parallel treatment groups. The lacquer was applied once on the fitting denture surface. Follow-up examinations took place on days 3, 7, 14, 21, 28, and 35. On day 14 the effect of the treatment was assessed. Thirty-six patients were included in the statistical analysis. Eighteen received miconazole and 18 received placebo lacquer. Primary efficacy endpoints were the number of colonies cultured from the palatal mucosa and denture surface on day 14. Thirteen of 16 patients in the miconazole group A showed < 10 colonies on culture medium on day 14 in the specimens from the palatal mucosa as did 5 of 18 patients in the placebo group B (p < 0.05). Corresponding results for the denture surface were 6 of 17 and 3 of 18, respectively (p < 0.05). Reapplication of lacquer was considered necessary (> 100 colonies in at least one sampling site within 14 days) in 35% of the patients from group A and in 83% of the patients from group B. The results indicate that a single application of a miconazole denture lacquer considerably reduces the number of Candida yeasts for a substantial period of time.

TITLE: Jogging or walking--comparison of health effects.ABSTRACT: The present study compared the different health effects of 6 months' endurance training at two exercise intensities. Seventy-five nonsmoking, sedentary men were randomly assigned to either a home-based, unsupervised exercise program of 4 x 30 min/wk jogging at an intensity of 75% VO2max (n = 28), or of 6 x 30 min/wk walking at an intensity of 50% VO2max (n = 28), or to an inactive control group (n = 19). Exercise adherence and injuries related to exercise training as well as changes in endurance capacity, body fat, and serum lipids were assessed. After 6 months, joggers and walkers showed a similar increase in VO2max as measured by a maximal bicycle ergometer test (2.9 +/- 4.1 ml/kg min, P < 0.01 and 2.5 +/- 5.7 ml/kg min, P < 0.5, respectively). There were no significant changes in blood lipids in either group, although results revealed a significant association between the amount of training (i.e., kilometers exercised) and the increase in high-density lipoprotein-cholesterol (HDL-C) in joggers (Pearson's r = 0.42, P < 0.05). In walkers, a significant association between the amount of exercise and the decrease in sum of skinfolds and the waist-hip ratio was observed (Pearson's r = -0.48 and -0.45, P < 0.05 for both). The adherence rate was similar for both training groups with respect to the prescribed intervention goal with an average of 90 +/- 41 min/wk (joggers) and 121 +/- 72 min/wk (walkers) spent on endurance training.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Inhibition of 5-hydroxytryptamine re-uptake impairs human gall-bladder emptying.ABSTRACT: 5-Hydroxytryptamine (5-HT) is an important neurotransmitter in the enteric nervous system. The intrinsic neural plexus of the gall-bladder resembles the enteric nervous system and similarly contains 5-HT neurones. The action of 5-HT on gallbladder motility has been investigated in animals but its effect on the human gall-bladder in vivo is unknown.The effect of indirect 5-HT agonism using paroxetine, a specific inhibitor of neuronal 5-HT reuptake, on gall-bladder motility was investigated in 12 healthy volunteers. In a randomized double-blind crossover design, gall-bladder motility was assessed after administration of 30 mg paroxetine daily for two days and after placebo. Ultrasonography was used to determine gall-bladder volumes while fasting and at 5 min intervals following a 250 kcal mixed liquid meal.Fasting gall-bladder volumes of 21.8 +/- 3.2 ml on placebo and 28.0 +/- 3.5 ml on paroxetine were similar. Paroxetine impaired postprandial gall-bladder emptying. Residual gall-bladder volume was 10.2 +/- 2.7 ml with placebo and 17.1 +/- 2.7 ml with paroxetine (P < 0.05). Ejection fraction was 57.3 +/- 7.7% on placebo and 40.9 +/- 4.7% on paroxetine (P < 0.05).5-HT pathways may participate in the regulation of biliary motility, and this study demonstrates an inhibitory role of 5-HT in the control of human gall-bladder emptying.

TITLE: The effects of single oral doses of 17 beta-oestradiol and progesterone on finger skin circulation in healthy women and in women with primary Raynaud's phenomenon.ABSTRACT: The effects of sex, the menstrual cycle, oral contraceptives, pregnancy, and the menopause on skin perfusion in healthy women and in patients with Raynaud's phenomenon suggest a role of female sex hormones. However, no clear relation between skin blood flow and circulating concentrations of oestrogens or progestogens has yet been found. The aim of this study was to investigate the effect of orally administered 17 beta-oestradiol and progesterone on finger skin blood flow before and during heat and cold challenge in 17 healthy normotensive women and in 12 women with Raynaud's phenomenon. In each subject standardized finger heating (45 degrees C water bath, 10 min) and cooling tests (15 degrees C water bath, 5 min and 20 min recovery) were performed twice on the second (or third) day of two consecutive menstrual cycles. 17 beta-Oestradiol (9 mg) or progesterone (300 mg) were given before the second test, after a first test with placebo. Both hormonal doses resulted in (high) physiological concentrations. Fingertip skin temperature and laser Doppler flux were measured. There were no significant differences in the test results after placebo and after progesterone. Although values of fingertip skin temperature and laser Doppler flux after 17 beta-oestradiol tended to be higher only the precooling values in the healthy subjects reached significance: fingertip skin temperature respectively with placebo and with oestradiol (mean (SD)): 32.7 (1.0) and 33.1 (0.8) degrees C; laser Doppler flux with placebo and with oestradiol: 33.6 (11.7) and 42.2 (9.5) perfusion units; both P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Effects of oral ranitidine, famotidine and omeprazole on gastric volume and pH at induction and recovery from general anaesthesia.ABSTRACT: We have studied, in 150 patients undergoing elective general surgery, the effect on gastric content of omeprazole 40 mg, ranitidine 300 mg and famotidine 40 mg, given orally the night and the morning before surgery. Volume and pH of gastric content were measured at induction and recovery from anaesthesia. Gastric volumes did not differ between groups. The median gastric pH was lower with omeprazole compared with ranitidine and famotidine at intubation (5.11, 7.05 and 6.99, respectively) (P < 0.001) and extubation (6.41, 6.98 and 6.96) (P < 0.001). The proportion of patients with gastric pH < 2.5 at induction was 40% for omeprazole, 12% for famotidine and 10% for ranitidine (P < 0.02); the proportion did not differ significantly at extubation.

TITLE: Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study.ABSTRACT: Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice.We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks. Otherwise, their medical therapy for heart failure was not changed.Worsening heart failure necessitating withdrawal from the study developed in 23 patients switched to placebo, but in only 4 patients who continued to receive digoxin (P < 0.001). The relative risk of worsening heart failure in the placebo group as compared with the digoxin group was 5.9 (95 percent confidence interval, 2.1 to 17.2). All measures of functional capacity deteriorated in the patients receiving placebo as compared with those continuing to receive digoxin (P = 0.033 for maximal exercise tolerance, P = 0.01 for submaximal exercise endurance, and P = 0.019 for New York Heart Association class). In addition, the patients switched from digoxin to placebo had lower quality-of-life scores (P = 0.04), decreased ejection fractions (P = 0.001), and increases in heart rate (P = 0.001) and body weight (P < 0.001).These findings indicate that the withdrawal of digoxin carries considerable risks for patients with chronic heart failure and impaired systolic function who have remained clinically stable while receiving digoxin and angiotensin-converting-enzyme inhibitors.

TITLE: Effectiveness of a nicotine patch in helping people stop smoking: results of a randomised trial in general practice. Imperial Cancer Research Fund General Practice Research Group.ABSTRACT: To assess the effectiveness of 12 weeks' treatment with a 24 hour transdermal nicotine patch in helping heavy smokers to stop smoking; also to assess the value of a specially written support booklet about smoking cessation and patch use compared with a simple advice pamphlet.Double blind placebo controlled randomised trial with a 2 x 2 factorial design.19 general practices in Oxfordshire.1686 heavy smokers aged 25-64 (mean cigarette consumption 24/day; mean duration of smoking 25 years).Sustained cessation for the last four weeks of the 12 week treatment period, confirmed by saliva cotinine estimation (226/262 cases; 86.3%) or expired carbon monoxide concentration (36/262; 13.7%). Patients lost to follow up (155/1686; 9%) were assumed to have continued to smoke.Cessation was confirmed in 163 patients (19.4%) using the nicotine patch and 99 patients (11.7%) using the placebo patch (difference 7.6% (95% confidence interval 4.2% to 11.1%); p < 0.0001). There was no significant advantage in using the more detailed written support material. The most important adverse effect of the patch was local skin irritation, which occurred in 15.8% (133/842) and 5.1% (43/844) of patients using the nicotine and placebo patches respectively, was graded as severe in 4.8% (40) and 1.1% (nine), and was stated as a reason for withdrawal from the trial in 9.5% (80) and 2.8% (24).Nicotine patches are effective in a general practice setting with nursing support, but the extent to which this effect is sustained cannot be assessed until the results of longer term follow up are known.

TITLE: Five years of physical exercise and low fat diet: effects on progression of coronary artery disease.ABSTRACT: This study was designed to assess the long-term effects of low-fat diet and intensive physical exercise.Long-term efficacy of exercise and diet was assessed in 18 nonselected, fully employed patients with symptomatic coronary artery disease. Results were compared to 18 patients on usual care.In the intervention group at 1 year, serum lipoproteins were brought to ideal levels, exercise-induced myocardial ischemia was significantly reduced, and progression in coronary atherosclerosis was retarded. After more than 5 years, patients in the intervention group showed a significant reduction in lipoprotein levels (total cholesterol, 248 [179-299] vs 214 [173-272] mg/dL, P < .01; low density lipoprotein, 146 [83-216], vs 152 [121-197] mg/dL, P < .005 vs control; triglycerides; 151 [80-303] mg/dl, vs 98 [46-182] mg/dL; P < .005) and body mass index (26 +/- 2.9 vs 25.4 +/- 3.3 kg/m2; P < .05). Exercise induced myocardial ischemia, measured by 201thallium scintigraphy, decreased by 29% (41 degrees +/- 36 degrees vs 29 degrees +/- 29 degrees, P = NS) and coronary atherosclerosis, assessed by angiography and digital image processing, progressed at a slower pace in light of a 21% increase in physical work capacity (169 +/- 40 vs 205 +/- 50, P < .01) and a 28% increase in maximal rate pressure product (25 +/- 6 vs 32 +/- 4, P < .004). In contrast, patients in the control group showed only poorly controlled coronary risk factors (total cholesterol, 243 [179-306] vs 26 [178-304] mg/dL, P = NS; low density lipoprotein, 151 [79-229] vs 196 [107-238] mg/dL, P < .0005 vs intervention; body mass index 25.7 +/- 2.5 vs 27.5 +/- 3.5 kg/m2, P < .01), whereas their physical work capacity tended to deteriorate (165 +/- 45 vs 142 +/- 62 Watts, P = not significant).These data demonstrate that current usual care is insufficient in controlling risk factors of coronary artery disease. However, intensive physical exercise and low-fat diet remain an effective form of treatment after more than 5 years.

TITLE: Increase of birth weight following chloroquine chemoprophylaxis during the first pregnancy: results of a randomized trial in Cameroon.ABSTRACT: A randomized trial was carried out from 1991 to 1993 among women attending an antenatal clinic in Ebolowa, Cameroon where malaria is hyperendemic and transmission occurs at a high level all year round. All pregnant women attending the clinic for their first prenatal visit between October 1991 and November 1992 were alternately assigned to chloroquine (CQ) or control (CT) groups. Chloroquine was given under observation at a weekly oral dose of 300 mg. At delivery, smears from maternal, cord, and placental blood were made and stained with Giemsa for parasites. An in vivo chloroquine sensitivity investigation was carried out on women attending the postnatal consultation to evaluate the level of chloroquine resistance in the target population. The efficacy of chloroquine was moderate in placental infection (39.2% infected in the CQ group versus 57.8% in the CT group: P = 0.05), probably because of a resistance to chloroquine estimated to be 10.9%. In the CQ group, the mean birth weight was significantly higher (P = 0.02) and the proportion of low birth weight newborns was lower (10.5% versus 27.7%; P = 0.02). A strong correlation between placental infection and birth weight was observed: the mean birth weight difference between infected and noninfected placentae was 359 g (P < 0.0001) and the proportion of low birth weight new born babies was 35.6% versus 5.9% (P = 0.0001). In Cameroon, in spite of a moderate resistance to chloroquine, this drug proved to be highly effective in increasing birth weight when administered to primigravidae. We therefore think such a prophylaxis should be recommended only to primigravidae in high transmission areas.

TITLE: A controlled trial of verapamil in patients after acute myocardial infarction: results of the calcium antagonist reinfarction Italian study (CRIS)ABSTRACT: A multicenter, double-blind, randomized, placebo-controlled trial was conducted to assess the effects of verapamil on total mortality, cardiac mortality, reinfarction, and angina after an acute myocardial infarction. All patients, aged 30 to 75 years, consecutively admitted for acute myocardial infarction between 1985 and 1987 to the participating centers, and without contraindications to verapamil or history of severe heart failure were enrolled. Seven to 21 days (mean 13.8) after myocardial infarction, 531 patients were randomized to verapamil retard 360 mg/day, and 542 patients to placebo. At baseline, the 2 groups of patients had similar characteristics. Mean age was 55.5 years and 91% were men. During a mean follow-up of 23.5 months, 5.5% of the patients died. No differences between verapamil and placebo were observed in total mortality (n = 30 and 29, respectively) and cardiac death (n = 21 and 22, respectively). The verapamil group had nonsignificant lower reinfarction rates (n = 39 vs 49). The number of patients developing angina was significantly less in the verapamil group (n = 100 vs 132, RR = 0.8, 95% confidence interval 0.5 to 0.9). There were no differences in discontinuation of therapy caused by adverse reactions. This trial showed no effect of verapamil on mortality. The lower reinfarction rates found in the verapamil group are in agreement with the results of other studies.

TITLE: Single- versus multiple-dose mezlocillin prophylaxis in emergency cesarean section.ABSTRACT: 163 patients undergoing emergency cesarean section were prospectively and randomized evaluated to determine the effect of mezlocillin in reducing postoperative morbidity. We compared a single 5-gram preoperative dose and a perioperative 3-dose regimen, each of 2 g, with a placebo. Postoperative morbidity was reduced from 65% in the placebo group to 20% in the groups receiving mezlocillin (p less than 0.005). The incidences of febrile morbidity, endometritis and urinary tract infection were all significantly lower in both groups given mezlocillin. There was no difference in the reduction of morbidity between the two groups receiving mezlocillin. The main advantages of the prophylaxis included a shorter hospitalization and the absence of serious infections in the treated groups.

TITLE: Intravenous propafenone for termination of reentrant supraventricular tachycardia. A placebo-controlled, randomized, double-blind, crossover study.ABSTRACT: To assess the antiarrhythmic efficacy of intravenous propafenone, 20 patients with inducible sustained supraventricular tachycardia received propafenone, 2 mg/kg body weight, or placebo in a double-blind, randomized, crossover study. Three patients had intra-atrial reentrant tachycardia, 3 had atrioventricular nodal reentrant tachycardia, and 14 had atrioventricular reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. Termination of supraventricular tachycardia occurred in 15 of the 20 patients receiving propafenone but 0 of the 11 patients receiving placebo (p less than 0.01). Propafenone prolonged refractoriness and slowed conduction of the atrium, the atrioventricular node, and accessory atrioventricular bypass tracts, and these effects provided antiarrhythmic action to halt tachycardia. No adverse effects were observed in any patient. We conclude that intravenous propafenone is safe and effective in the acute treatment of various forms of reentrant supraventricular tachycardia.

TITLE: Comparison of spectinomycin hydrochloride and aqueous procaine penicillin G in the treatment of uncomplicated gonorrhea.ABSTRACT: Men and women with uncomplicated gonorrhea were randomly assigned to receive aqueous procaine penicillin G (2,400,000 U for men; 2,400,000 U daily for 2 days for women) or spectinomycin hydrochloride (2.0 g for men; 4.0 g for women). Among men who returned for post-treatment evaluation within 10 days, treatment failures were noted among 16 (20.3%) of 79 men who received penicillin and 8 (9.5%) of 84 men who received spectinomycin (P < 0.1). Similarly, 6 (13.3%) of 45 women who received penicillin and 3 (6.5%) of 46 women who received spectinomycin had positive endocervical cultures for Neisseria gonorrhoeae at the time of the post-treatment examination (P = not significant).

TITLE: Angiotensin converting enzyme during acute and chronic enalapril therapy in essential hypertension.ABSTRACT: The acute and chronic effects of enalapril (MK421) were assessed in a double-blind randomized trial in subjects with essential hypertension. In acute studies, twelve subjects received enalapril (10 mg p.o.), following which there was a fall in blood pressure, maximal at 6 h and lasting for 24 h. Serum MK422 (enalaprilic acid, the bioactive form of enalapril) and serum angiotensin converting enzyme (ACE) inhibition had a similar time course with good correlation between drug levels and ACE inhibition (P less than 0.001, r = 0.98, n = 16) and between ACE inhibition and the hypotensive effect (P less than 0.001, r = 0.84, n = 16). In chronic studies enalapril was titrated from 5 mg to 20 mg twice a day in eleven hypertensive patients to achieve a diastolic blood pressure less than 90 mmHg. Treatment continued for 3-12 months. Increasing serum MK422 was correlated with reducing serum ACE activity (P less than 0.001, r = 0.8, n = 104). The fall in blood pressure correlated both with serum MK422 level (P less than 0.05, r = 0.37, n = 39) as well as ACE inhibition (P less than 0.01, r = 0.45, n = 42). The drug level:ACE inhibition curve was shifted to the right during chronic enalapril treatment. ID50 for serum ACE was 32 ng MK422/ml following the single 10 mg dose of MK421 and 70 ng MK422/ml during chronic treatment. Blood pressure falls during acute and chronic treatment were similar over the range of serum MK422 levels achieved. The shift in the drug level:ACE inhibition curve suggests induction of ACE during chronic treatment with enalapril in man.

TITLE: Desflurane analgesia for vaginal delivery.ABSTRACT: The use of subanaesthetic concentration of inhalational anaesthetic for vaginal delivery offers many advantages to the mother and newborn. Desflurane, with the characteristics of rapid onset and minimal metabolism, may provide better analgesia and safety for labour pain control. Eighty healthy parturients were randomly assigned to receive either desflurane 1.0-4.5% and oxygen (n = 40) or nitrous oxide 30-60% in oxygen (n = 40). Analgesia was assessed using a score from 0 (no relief) to 4+ (excellent analgesia), amnesia for the delivery, blood loss were recorded. Neonates were evaluated by Apgar scores and neurologic and adaptive capacity scores (NACS). Data were analyzed for statistical significance using Student's t-test or Chi-square when appropriate. Analgesia scores were similar for both groups with more amnesia in desflurane group (23% vs 0% P < 0.05). Blood loss did not differ significantly, 364 ml for the desflurane group and 335 ml for the nitrous oxide group. There were no significant differences for neonatal Apgar score at 1 min or at 5 min or the NACS at 2 hr or 24 hr between the two groups. We conclude that desflurane in subanaesthetic doses is safe and effective inhalation agent for normal delivery but might be associated with amnesia.

TITLE: Human immunodeficiency virus type 1 quantitative cell microculture as a measure of antiviral efficacy in a multicenter clinical trial.ABSTRACT: A quantitative cell microculture assay (QMC) was used to measure the human immunodeficiency virus type 1 (HIV-1) peripheral blood mononuclear cell (PBMC)-associated titer in 109 subjects rolled in an open-label phase I/II study of didanosine monotherapy or combination therapy with zidovudine. The titer was inversely correlated with CD4+ cell count at baseline (r = .37, P = .001). After 12 weeks of therapy, subjects showed a significant decreases in virus titer and those with the highest baseline virus titers had the greatest increase in CD4+ cell number (r = .430, P = .002). The QMC assay was more sensitive (98%) for assessing the antiretroviral effect of therapy than was immune complex-dissociated HIV p24 antigen (32%) or plasma culture (3.4%). Estimated sample sizes for phase I/II clinical trials were derived using the within-subject QMC SD of .72 log10 infectious units per 10(6) PMBC.

TITLE: Inhibition of steroid 5 alpha-reductase with finasteride: sleep-related erections, potency, and libido in healthy men.ABSTRACT: To objectively measure the effects of a 5 alpha-reductase inhibitor on erectile function, we studied 20 sexually active men (aged 41-64 yr) during double blind, randomized administration of 5 mg/day finasteride (F) or placebo (P). Serum testosterone and dihydrotestosterone (DHT) were measured every 4 weeks. Sleep-related erections were assessed with comprehensive polysomnography for 2 nights before randomization (session 1) and at week 12 (session 2). Sexual function questionnaires were administered weekly. Serum DHT levels at week 0 were 1.47 +/- 0.11 and 1.16 +/- 0.27 nmol/L (P > 0.05) in the P and F groups, respectively. F group levels fell to 31% and 28% of control values at week 4 and 12. Penile tip peak tumescence time increased on second nights more in the P than the F group at 12 weeks, producing a session main effect (P < 0.02) and a group X session interaction (P < 0.05). No significant group X session interactions were found for any sleep erection measures in a best night analysis or for self-reported sexual activity. Thus, F did not consistently suppress sleep-related erections compared to P. F primarily inhibits type 2 5 alpha-reductase activity; however, type 1 5 alpha-reductase is the major enzyme in the central nervous system. Therefore, DHT involvement in the maintenance of libido and potency is not excluded. Nonetheless, these data support the feasibility of using a type 2 inhibitor to treat benign prostatic hyperplasia without impairing erectile function.

TITLE: Endothelin-1 in pulmonary hypertension associated with high-altitude exposure.ABSTRACT: Endothelin-1 is involved in chronic pulmonary hypertension. Its role in acute pulmonary hypertension due to hypoxia in humans is not clear. We therefore studied the influence of hypoxia caused by exposure to high altitude on plasma endothelin-1 levels, arterial blood gases, and pulmonary arterial pressure in subjects taking nifedipine or placebo.Twenty-two healthy volunteers were investigated at low altitude (490 m) and high altitude (4559 m). Arterial blood gases were analyzed immediately, endothelin-1 was measured by radioimmunoassay, and pulmonary artery pressure was assessed by Doppler echocardiography. After baseline investigations, the mountaineers were allocated in a randomized double-blind fashion to receive either placebo or nifedipine (20 mg TID) during rapid ascent to high altitude within 22 hours. Tests were repeated at the high-altitude research laboratories located in the Capanna "Regina Margherita" (Italy, 4559 m). Plasma endothelin-1 was increased twofold at high altitude (5.9 +/- 2.2 pg/mL compared with 2.9 +/- 1.1 pg/mL, P < .05), was inversely related to arterial PO2 (r = -.46, P < .001), and correlated with pulmonary artery pressure (r = .52, P < .002). At high altitude, arterial endothelin-1 was lower (4.3 +/- 1.6 pg/mL) than venous endothelin-1 (5.9 +/= 2.2 pg/mL, P < .001), indicating either predominant production in the venous vasculature or pronounced clearance in the pulmonary circulation. The calcium antagonist nifedipine, which lowered pulmonary artery pressure at high altitude (32 +/- 5 versus 42 +/- 11 mm Hg, P < .05), had no influence on plasma endothelin-1 levels. The administration of 35% O2 at high altitude normalized arterial PO2, tended to decrease endothelin-1, and decreased pulmonary artery pressure accordingly.We conclude that plasma endothelin-1 is increased at high altitude, but whether or not it represents an important pathogenetic factor for pulmonary hypertension remains to be investigated.

TITLE: Indomethacin but not metoprolol reduces exercise-induced albumin excretion rate in type 1 diabetic patients with microalbuminuria.ABSTRACT: The effects of a single oral dose of indomethacin (1 mg kg-1) metoprolol (1.5 mg kg-1) and placebo on exercise-induced albumin excretion rate (AER) were compared in a randomized, crossover design in 14 normotensive, young Type 1 diabetes patients, nine of them with microalbuminuria (AER > 15 micrograms min-1) and five without microalbuminuria at rest. The albumin excretion rate, blood pressure, heart rate, blood glucose, and plasma concentrations of indomethacin and metoprolol were determined before and after 30 min submaximal physical exercise. In microalbuminuric patients the rise in albumin excretion rate after exercise on indomethacin (7 micrograms min-1) was lower than after placebo (29 micrograms min-1, p < 0.001) whereas the rise in albumin excretion rate with metoprolol during exercise (18 micrograms min-1) did not differ from placebo (p = 0.48), in spite of the expected less marked increase in blood pressure. In normoalbuminuric patients no significant increase in albumin excretion rate was noted by exercise in any of the treatment periods. A tendency to a linear correlation (r = -0.54, p = 0.07) was seen between the plasma concentration of indomethacin and the inhibition of exercise-induced increase in albumin excretion rate. No correlations were observed between exercise-induced changes in albumin excretion rate and systolic blood pressure, heart rate or blood glucose. In conclusion, acute indomethacin treatment, presumably through inhibition of renal prostaglandin synthesis, reduces the exercise-induced rise in albumin excretion rate in Type 1 diabetic patients with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity.ABSTRACT: This two-arm, double-blind, randomized trial was conducted to determine the effects of lenograstim, a glycosylated recombinant human granulocyte colony-stimulating factor (rHu-G-CSF), on the hematologic tolerance of patients with sarcoma treated with mesna, doxorubicin, ifosfamide, and doxorubicin (MAID) chemotherapy.Forty-eight patients with metastatic or locally advanced soft tissue sarcoma were, following the first cycle of a combination with doxorubicin 60 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2, ifosfamide 7.5 g/m2, and dacarbazine 900 mg/m2 given on days 1 to 3, randomized to receive either lenograstim 5 micrograms/kg/d by once-daily injection from day 4 to day 13, or its vehicle. For subsequent cycles, 28 patients continued on the same chemotherapy and lenograstim was systematically given as prophylactic treatment in an open manner.Following the first cycle of MAID, the duration of neutropenia was reduced in patients who received lenograstim as compared with those who received placebo, with a median duration of neutropenia ( < 0.5 x 10(9)/L neutrophils) of 0 days (range, 0 to 3) and 5 days (range, 0 to 10), respectively (P < .001). All patients who received lenograstim had recovered at least 1 x 10(9)/L neutrophils (polymorphonuclear lymphocytes [PMN]) on day 14, compared with only one of 26 in the placebo group (P < .001). The median time to recover this neutrophil level was 12 days (range, 10 to 13) and 17 days (range, 14 to 21), respectively (P < .001). Neutropenic fever occurred in five (23%) and 15 (58%) patients respectively (P = .02). Twenty-eight patients received at least two cycles (median, four) of MAID at the same dose. Toxicity remained constant across all treatment cycles. A progressive increase in thrombocytopenia was noted, with median platelet nadirs of 102 x 10(9)/L at cycle 2 and 19.5 x 10(9)/L at cycle 6, but did not result in significant treatment modifications. Consequently, median relative dose-intensities remained greater than 0.95 for up to six consecutive MAID cycles.Lenograstim significantly improved hematologic tolerance in patients treated with the MAID chemotherapy regimen and, therefore, allowed optimal adhesion to the theoretic doses planned for up to six cycles. Whether such an optimization in relative dose-intensity will result in an improvement of treatment efficacy remains to be determined.

TITLE: Open-label study to assess the efficacy, safety, and tolerability of fluvastatin versus bezafibrate for hypercholesterolemia.ABSTRACT: Increased levels of total cholesterol and low density lipoprotein cholesterol (LDL-C) are associated with the development of coronary artery disease, which has become a worldwide public health problem. Clinical trials show that, in the long term, effective lowering of total cholesterol and raising of high density lipoprotein cholesterol (HDL-C) can slow atherosclerosis progression and reduce coronary artery disease risk. This study evaluated the efficacy, safety, and tolerability of fluvastatin versus bezafibrate (slow release) in patients with cholesterol > 241 mg/dL (6.2 mmol/liter) not responding to dietary treatment alone (cholesterol < 300 mg/day for 8 weeks). Patients were divided into 2 groups: group A (13 women, 7 men; mean age, 47.8 +/- 9.7 years; range, 30-70) received 40 mg fluvastatin once daily with their evening meal; group B (14 women, 6 men; mean age, 45 +/- 11 years, range, 25-68) received 400 mg bezafibrate once daily with either breakfast or their evening meal. After 12 weeks of treatment, the mean cholesterol decrease in group A was 27% (from 271 +/- 51.4 to 197.4 +/- 24.3 mg/dL; p < 0.001) versus 8% (from 278.6 +/- 33.2 to 255.8 +/- 20.3 mg/dL; p < 0.005) in group B. At the same time point, LDL-C was significantly decreased in group A (from 197.9 +/- 49 to 107.5 +/- 27.6 mg/dL; p < 0.001) but not in group B (from 181.6 +/- 39.6 to 173.3 +/- 24.3 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Hemodynamic responses to intravascular injection of epinephrine-containing epidural test doses in adults during general anesthesia.ABSTRACT: Epidural anesthesia is sometimes initiated during general anesthesia, yet few data exist concerning efficacy of epinephrine-containing test doses.Thirty-six patients were randomized to receive either 0.5 MAC isoflurane, 1 MAC isoflurane, or 0.5 MAC each (1 MAC total) of isoflurane and nitrous oxide. Each subject received intravenous saline followed by three test doses containing 45 mg lidocaine with 7.5, 15, and 30 micrograms epinephrine in a randomized, double-blind fashion. Heart rate and systolic, diastolic, and mean blood pressures were measured for 5 min after injection. Positive hemodynamic criteria identifying intravascular injection were determined from peak increases in hemodynamics during administration of saline. Dose-effect relationships between epinephrine and peak increases in hemodynamics were assessed with linear regression. Minimum required doses of epinephrine to produce peak positive hemodynamic increases on average were determined from linear regression.Positive hemodynamic criteria were identified as increases in heart rate > or = 8 beats/min, systolic blood pressure > or = 13 mmHg, diastolic blood pressure > or = 7 mmHg, and mean blood pressure > or = 9 mmHg. Significant dose-effect relationships were observed for epinephrine and peak increases in hemodynamics (correlation coefficients ranged from 0.61-0.91). Minimum required doses of epinephrine ranged from 6 to 19 micrograms depending on hemodynamic measurement and anesthetic group.Hemodynamic responses to intravascular injection of test doses vary with dose of epinephrine and depth and type of general anesthetic used. Thus, the 15 micrograms epinephrine contained in the standard test dose may not be sufficient during all anesthetic conditions.

TITLE: Effects of nedocromil sodium in steroid-resistant asthma: a randomized controlled trial.ABSTRACT: Some patients with asthma respond poorly to corticosteroids and have persistent airway inflammation and daily clinical symptoms. The aim of this study was to investigate the effects of nedocromil sodium (NS), a nonsteroidal antinflamatory drug, in the treatment of steroid-resistant asthma.Steroid-resistant asthma as diagnosed in any patient who demonstrated 20% improvement in FEV1 after treatment with inhaled salbutamol with failure of FEV1 to improve by at least 15% after a 2-week trial of prednisolone, 30 mg daily. In a double-blind placebo-controlled trial, the patients received either 4 mg of inhaled NS (n = 13) or placebo (n = 13), 4 times daily for 3 months.NS but not placebo resulted in a mean increase in FEV1 of 11.4% after 12 weeks of therapy (p = 0.05) and of 12.4% (p = 0.04) and 15% (0.02) in morning peak expiratory flow after 8 and 12 weeks of treatment, respectively. Changes in FEV1 at 4 and 8 weeks and in peak expiratory flow at 4 weeks of NS therapy were not significant. NS was also effective in reducing variability of peak expiratory flow (p = 0.02) and use of salbutamol (p = 0.005) and in improving quality of life (p = 0.007) by the trial end. Six of the 12 patients treated with NS who completed the treatment period showed a "good response," defined by a reduction in salbutamol use of more than 50% and an increase in morning peak expiratory flow of more than 20% from baseline; there were no clinical predictors of this response. Two patients were withdrawn from the study because of severe asthma exacerbation (one from each treatment group).Inhaled NS improved pulmonary function and decreased asthma severity in steroid-resistant asthma, but its effectiveness is not homogeneous and cannot be predicted from baseline clinical data.

TITLE: Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure.ABSTRACT: The aim of this study was to determine the impact of nasal nocturnal oxygen therapy on respiration, sleep, exercise capacity, cognitive function and daytime symptoms in patients with congestive heart failure and Cheyne-Stokes respiration.Cheyne-Stokes respiration is common in patients with congestive heart failure and is associated with significant nocturnal oxygen desaturation and sleep disruption with arousals. Oxygen desaturations and arousals cause an increase in pulmonary artery pressure and sympathoneural activity and therefore may reduce exercise capacity. Oxygen is an effective treatment of Cheyne-Stokes respiration and should improve exercise capacity in these patients.The study was designed as a randomized crossover, double-blind, placebo-controlled trial: 22 patients were assigned to 1 week each of nocturnal oxygen and room air. After each week, polysomnography, maximal bicycle exercise with expiratory gas analysis and trail-making test were performed, and a health assessment chart was completed.Nocturnal oxygen significantly reduced the duration of Cheyne-Stokes respiration (162 +/- 142 vs. 88 +/- 105 min [mean +/- SD]; p < 0.005). Sleep improved as evidenced by less stage 1 sleep and fewer arousals (20 +/- 13 vs. 15 +/- 9/h total sleep time; p < 0.05) as well as more stage 2 and slow-wave sleep; nocturnal oxygen saturation also improved. Peak oxygen consumption during exercise testing increased after oxygen treatment (835 +/- 395 vs. 960 +/- 389 ml/min; p < 0.05). Cognitive function evaluated by the trail-making test improved, but daytime symptoms in the health assessment chart did not improve significantly.Successful treatment of Cheyne-Stokes respiration with nocturnal nasal oxygen improves not only sleep, but also exercise tolerance and cognitive function in patients with congestive heart failure.

TITLE: Risks for sensorimotor peripheral neuropathy and autonomic neuropathy in non-insulin-dependent diabetes mellitus (NIDDM).ABSTRACT: Identification of risk factors for development of diabetic sensorimotor peripheral neuropathy (DSPN) and diabetic autonomic neuropathy (DNA) may help to prevent or modify these complications. The ABCD Trial, a prospective study of diabetic complications, has identified risk factors of the presence and staging of peripheral neuropathy based on neurological symptom scores, neurological disability scores, autonomic function testing and quantitative sensory examination. DSPN is independently associated with diabetes duration [odds ratio (OR) = 1.5 per 10 years], body weight (OR = 1.1 per 5 kg), age (OR = 1.8 per 10 years), retinopathy (OR = 2.3), overt albuminuria (OR = 2.5), height (OR = 1.2 per 10 cm), duration of hypertension (OR = 1.1 per 10 years), insulin use (OR = 1.4), and race/ethnicity [African American vs. non-Hispanic white (OR = 0.4) and Hispanic vs. non-Hispanic white (OR = 0.8)]. DAN is independently associated with diabetes duration (OR = 1.2 per 10 years), body weight (OR = 1.1 per 5 kg), glycosylated hemoglobin (OR = 1.1 per 2.5%), overt albuminuria (OR = 1.6), and retinopathy (OR = 1.8).

TITLE: Healing and recurrence of active duodenal ulcer with nizatidine.ABSTRACT: Nizatidine, a new H2-receptor antagonist for treatment of duodenal ulcer disease, was evaluated in a unique two-phase, placebo-controlled, randomized, double-blind, multicenter clinical trial. Patients received either 150 mg nizatidine twice daily or placebo for 4 weeks (phase I). If ulcer healing did not occur during phase I, patients were randomly reallocated to receive either 150 mg nizatidine twice daily or placebo for an additional 4 weeks (phase II). Patients with a healed ulcer continued on the same therapy. All patients were endoscoped at week 8. Healing rates at week 2 were 93 of 265 (35%) nizatidine-treated patients and 55 of 260 (21%) placebo-treated patients (p less than 0.001); at week 4, healing rates were 198 of 259 (76%) nizatidine-treated patients and 95 of 243 (39%) placebo-treated patients (p less than 0.001). In phase II, ulcer healing occurred in 46 of 86 (53%) nizatidine-treated patients and in 23 of 90 (26%) placebo-treated patients (p = 0.002). In patients who had a healed ulcer at previous endoscopies, 18 of 178 (10%) nizatidine-treated patients and 10 of 81 (12%) placebo-treated patients had a recurrence of duodenal ulcer. Smokers who had histories of previous ulcers were more likely to have an early recurrence.

TITLE: A pilot study of piracetam in cuprophan hemodialysis.ABSTRACT: Twelve patients, 8 male and 4 female, aged from 26 to 70 years were studied. They were on hemodialysis (HD) 4 h three times weekly with cuprophan hollow fiber dialyzers (Gambro 120M) and dialysate containing 35 mEq/L of acetate. The study compares two random HD sessions on each patient. Sixty minutes prior to one random session a placebo was administered orally, and prior to another random session piracetam was given at a dose of 8 g. Heparin dosage was not reduced during HD using QB 200 ml, QD 500 ml, and no ultrafiltration. Blood samples for leukocyte and platelet counts, serum C3, arterial paO2 and paCO2, thromboxane-B2 (TxB2), and beta-thromboglobulin (beta-TG) were taken from the arterial line before and at 15, 60, and 240 min during HD. Leukopenia at 15 min of HD was found to be less severe (p less than 0.01) in the piracetam study than in the placebo, whereas platelet count did not change. Serum C3 was slightly increased in both studies. Arterial oxygen was preserved close to the initial levels by piracetam (91.66 mm Hg versus 81.08, p less than 0.01 at 60 min, and 93.08 versus 80.17 mm Hg, p less than 0.01 at 240 min of HD sessions) but paCO2 did not change significantly. TxB2 increased less with piracetam in comparison to placebo (p less than 0.01 or p less than 0.001), but beta-TG was reduced significantly by piracetam at any time during HD (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Experience with terazosin administered in combination with other antihypertensive agents.ABSTRACT: In a randomized, double-blind, placebo-controlled, multicenter trial, the efficacy and safety of terazosin in combination with other antihypertensive agents were assessed using patients with inadequately controlled essential hypertension (supine diastolic blood pressure 95 mm Hg or greater). Of 138 evaluable patients, the terazosin-treated group (n = 84) achieved a significant (p less than 0.05) mean reduction of 7.3 mm Hg in supine diastolic blood pressure when compared with the placebo-treated group (n = 54) who achieved a reduction of 0.6 mm Hg. Analysis of patients by background therapeutic categories (beta blocker, beta blocker plus diuretic, or "other") revealed that terazosin caused a significantly greater decrease in supine diastolic blood pressure than did placebo when added to the combination of beta blocker plus diuretic (decrease of 7.2 mm Hg for the terazosin group versus a decrease of 1.5 mm Hg for the placebo group) and to other antihypertensive drugs (decrease of 7.9 mm Hg for the terazosin group versus a decrease of 1.0 mm Hg for the placebo group). Significant differences between treatment groups were also observed for supine systolic and for standing systolic and diastolic blood pressure variables in select subgroups. The addition of terazosin did not cause significant changes in physical examinations or electrocardiograms. Changes in pulse rates and body weight did not differ significantly between treatment groups for any background therapeutic category. The overall incidence of adverse experiences was only somewhat greater for terazosin-treated than placebo-treated patients. These results suggest that terazosin is safe and effective when administered in combination with other antihypertensive drugs.

TITLE: A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri.ABSTRACT: A randomized, double-blind study was performed on 16 women to compare the efficacy of daily subcutaneous (SC) injections of leuprolide acetate (LA; TAP Pharmaceuticals, North Chicago, IL) plus oral placebo tablets (group A, n = 7) with SC LA plus oral medroxyprogesterone acetate (The Upjohn Company, Kalamazoo, MI; group B, n = 9) in the treatment of leiomyomata uteri. Patients in group A had a significant reduction in uterine size from a pretreatment volume of 601 +/- 62 cm3 (mean +/- standard error) to a mean uterine volume of 294 +/- 46 cm3 at 24 weeks of therapy (P less than 0.01). Group B patients had a reduction in uterine volume from 811 +/- 174 cm3 to 688 +/- 154 cm3, which was not statistically significant. However, only one patient in group B experienced hot flashes, whereas six patients in group A had this symptom (P less than 0.01). Both groups demonstrated significant increases in mean hemoglobin concentrations, hematocrits, and serum iron levels at 24 weeks of therapy compared with pretreatment levels.

TITLE: Effects of infant nutrition on cholesterol synthesis rates.ABSTRACT: Nutrient effects on cholesterol fractional synthesis rates (FSR) in infancy by stable isotope determination have not been studied. We hypothesized that FSR is significantly reduced with high dietary cholesterol and phytoestrogen intake and increased with low dietary cholesterol and phytoestrogen intake. We prospectively studied 33 term male infants exclusively fed human milk (high cholesterol, low phytoestrogen, n = 12), cow milk-based formula (low cholesterol, low phytoestrogen, n = 8), soy milk-based formula (zero cholesterol, high phytoestrogen, n = 7), or soy milk-based formula modified to contain cholesterol (low cholesterol, high phytoestrogen, n = 6) during the first 4 mo of life. Cholesterol FSR was determined from rate of incorporation of deuterium into erythrocyte membrane cholesterol, and urinary isoflavone excretion (an index of dietary phytoestrogen exposure) was measured by gas chromatography-mass spectrometry. Significant differences in cholesterol FSR were found. FSR (%/d) was lowest in human milk (2.62 +/- 0.38), highest in soy milk-based formula (9.40 +/- 0.51), and intermediate in cow milk-based and modified soy milk-based formula (6.90 +/- 0.48 and 8.03 +/- 0.28, respectively), p < 0.0001. Cholesterol FSR was significantly lower in modified soy milk-based compared with soy milk-based formula, p < 0.05. We also show for the first time that dietary phytoestrogens are absorbed and excreted by the infant fed soy protein-based formula. Urinary isoflavone excretion was inversely related to cholesterol FSR, but it was not significantly related to serum cholesterol concentration. We conclude that the type of infant nutrition and dietary cholesterol are major factors influencing cholesterol fractional synthesis rates in infancy.

TITLE: Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol.ABSTRACT: Do the benefits of intensive lipid-lowering therapy extend to patients with only borderline or moderately elevated levels of low density lipoprotein (LDL) cholesterol?The merits of the present LDL cholesterol treatment goal of < or = 100 mg/dl need to be clarified for patients without high levels of LDL cholesterol, particularly for those patients previously classified as having only borderline high (130 to 159 mg/dl) or desirable (101 to 130 mg/dl) levels.Disease change and clinical events were examined in LDL cholesterol subgroups in the Familial Atherosclerosis Treatment Study (FATS) trial, a randomized, blinded, quantitative arteriographic comparison of one conventional and two intensive lipid-lowering strategies in men with coronary artery disease, a positive family history and apolipoprotein B > or = 125 mg/dl. The primary end point, disease change per patient, was measured as the mean change in severity of stenosis (delta %SProx) among nine standard proximal segments.Of the 120 patients completing the 30-month protocol, 60 had a baseline LDL cholesterol < 90th percentile (mean LDL cholesterol 152 mg/dl) and 60 > 90th percentile (mean LDL cholesterol 221 mg/dl). Thirty-one patients had levels < 160 mg/dl (mean LDL cholesterol 134 mg/dl) and 89 > 160 mg/dl (mean LDL cholesterol 205 mg/dl). Patients with LDL cholesterol < 90th percentile benefited angiographically from therapy (delta %SProx = -1.5% diameter stenosis [regression] during intensive therapy vs. +2.3% diameter stenosis [progression] during conventional therapy, p < 0.01), as did patients with LDL cholesterol < 160 mg/dl (delta %SProx = -4.2% vs. +3.3% diameter stenosis, p = 0.0001). By comparison, angiographic benefit was less pronounced among those entering with very high LDL cholesterol (delta %SProx = -0.2% vs. +1.9% diameter stenosis, p = 0.07) or with LDL cholesterol > or = 160 mg/dl (delta %SProx = +0.2% vs. +1.6% diameter stenosis, p = 0.13). Intensive therapy resulted in a statistically significant reduction in clinical events only in the subgroup with baseline LDL cholesterol < 90th percentile (2 of 42 vs. 8 of 29 patients initially enrolled, p = 0.01) and a trend toward fewer events in patients with LDL cholesterol < 160 mg/dl (2 of 20 vs. 6 of 15 patients, p = 0.05). No such difference was seen in the higher LDL cholesterol subgroups.Treatment benefit in the FATS trial was not confined to patients with very high levels of LDL cholesterol and was in fact particularly evident in those patients with levels < 160 mg/dl. Such patients should be considered more likely, not less, to benefit from intensive lipid-lowering therapy.

TITLE: Propofol anaesthesia in paediatric ambulatory patients: a comparison with thiopentone and halothane.ABSTRACT: The purpose of this study was to evaluate the haemodynamic changes during induction, as well as the speed and quality of recovery when propofol (vs thiopentone and/or halothane) was used for induction and maintenance of anaesthesia in paediatric outpatients. One hundred unmedicated children, 3-12-yr-old, scheduled for ambulatory surgery were studied. The most common surgical procedures performed were eye muscle surgery (42%), plastic surgery (21%), dental restoration (15%), and urological procedures (15%). The children were randomized to an anaesthetic regimen for induction/maintenance as follows: propofol/propofol infusion; propofol/halothane; thiopentone/halothane; halothane for both induction and maintenance. Succinylcholine 1.5 mg.kg-1 was used to facilitate tracheal intubation and N2O/O2 were used as the carrier gases in each case. All maintenance drugs were titrated according to the clinical response of the patient to prevent movement and/or maintain BP +/- 20% of baseline. Two patients (4%) who received propofol expressed discomfort during injection. The mean propofol dose required to prevent movement was 267 +/- 83 micrograms.kg-1.min-1. The overall pattern of haemodynamic changes, as well as awakening (extubation) times were not different among the four groups. Children who received propofol recovered faster (22 vs 29-36 min) (P < 0.05), were discharged home sooner (101 vs 127-144 min) (P < 0.05), and had less postoperative vomiting (4 vs 24-48%) (P < 0.05) than all others.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients.ABSTRACT: To examine the effects of caloric restriction, independent of differences in weight loss, on improvements in glycemic control, fasting insulin, and insulin sensitivity.We randomized 93 obese type II diabetic patients to two different degrees of calorie restriction (1,674 or 4,185 kJ/day; 400 or 1,000 kcal/day) and compared the changes in fasting glucose, fasting insulin, and insulin sensitivity that resulted from a comparable reduction in body weight (11% of initial body weight). Insulin sensitivity was assessed using the minimal model analysis of frequently sampled intravenous glucose tolerance tests.Despite equal weight losses, subjects in the 1,674 kJ/day (400 kcal) condition had lower fasting glucose levels (7.61 vs. 10.13 mM, P = 0.03) and greater insulin sensitivity (1.79 vs. 1.13, P = 0.04) after weight loss than did subjects in the 4,185 kJ/day (1,000 calorie) condition. Subjects were restudied 15 weeks later when both groups were consuming a 4,185 kJ/day (1,000 kcal/day) diet. Subjects who increased from 1,674 to 4,185 kJ (400 to 1,000 calories) had worse fasting glycemic control in spite of continued weight loss, whereas subjects who remained on 4,185 kJ (1,000 calories) throughout had further improvements in both blood glucose and insulin sensitivity with increased weight loss.Both degree of calorie restriction and magnitude of weight loss have independent effects on improvements in glycemic control and insulin sensitivity.

TITLE: Clinical evaluation of topical isotretinoin in the treatment of actinic keratoses.ABSTRACT: Retinoids have been shown to improve the manifestations of skin photodamage, including actinic keratoses.The efficacy and tolerability of isotretinoin 0.1% cream in the treatment of actinic keratoses were evaluated in a randomized, double-blind, placebo-controlled, parallel-group study.One hundred patients were randomly assigned to treatment with 0.1% cream or vehicle twice daily for 24 weeks to the face, the scalp, and the upper extremities. Patients were assessed every 4 weeks by the investigators, who counted and recorded the number of lesions in each treatment area. The 93 patients who had at least one postbaseline assessment were included for efficacy analysis. Local tolerability was evaluated at each study visit.On the face, the reduction in number of actinic keratoses (mean +/- SEM) at the end of treatment was greater for patients treated with isotretinoin (3.9 +/- 0.6, i.e., 66% of patients with a reduction > 30%) than with placebo (1.7 +/- 0.5, i.e., 45% of patients with a reduction > 30%); this difference was statistically significant (p = 0.001). No significant drug effect was seen for lesions on the scalp or upper extremities. Mild to moderate local reactions with isotretinoin abated with reduced treatment frequency.Our results suggest that isotretinoin 0.1% cream cannot compete with more rapid treatments of actinic keratoses. However, its effect on facial lesions may be beneficial during long-term treatment of associated sun-damaged skin.

TITLE: Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group.ABSTRACT: Bone metastases are a major cause of morbidity in breast cancer, resulting in complications that include pain, loss of mobility, pathologic fracture, and tumor-induced hypercalcemia (TIH). Inhibition of osteoclast-mediated bone destruction using bisphosphonates represents a promising new management approach.Breast cancer patients with bone metastases were randomly allocated to receive chemotherapy alone (152 patients) or chemotherapy plus pamidronate 45 mg in 250 mL of saline as a 1-hour intravenous infusion every 3 weeks (143 patients). Whenever possible, treatment continued until progression of disease (PD) in bone appeared on radiographs or bone scan. Time to PD in bone and pain reduction according to a self-assessment six-point scale were selected as primary end points. PD in bone was verified during extramural review (EMR) of all imaging studies by blinded observers, and these data were used as the main efficacy criterion. Analgesic intake, World Health Organization (WHO) performance status, and complications of bone metastases (radiotherapy, TIH, fractures, orthopedic surgery) were also compared in the two groups.At EMR, median time to PD in bone was increased by 48% in patients who received pamidronate (249 v 168 days; P = .02, Wilcoxon test). Marked pain relief, defined as a two-point decrease lasting for > or = 6 weeks, was reported by 44% of pamidronate patients and by 30% of controls (P = .025, chi 2 test). The infusions (median, nine per patient; range, 0 to 39) were well tolerated, with no major toxicities reported. Pamidronate by repeated infusion can significantly slow the progression of bone metastases and reduce attendant morbidity.

TITLE: Effect of aprotinin on insulin sensitivity in non-insulin-dependent diabetes mellitus.ABSTRACT: It has been suggested that kallikrein-kinin system may influence carbohydrate metabolism via a kinin-mediated increment of insulin-mediated glucose uptake. To evaluate the effect of acute inhibition of the kallikrein-kinin system on insulin sensitivity, a randomized, placebo-controlled, double-blind study was performed in 15 male non-insulin-dependent diabetic patients. After basal evaluation of insulin sensitivity with a 2-h euglycaemic hyperinsulinaemic clamp (40 mU m-2 min-1), patients were infused either with aprotinin (200,000 U.I.C. as intravenous bolus injection) or placebo (10 ml isotonic saline) in a cross-over fashion, at 1 week intervals. After both saline and aprotinin infusions, insulin sensitivity was reassessed by continuing the euglycaemic hyperinsulinaemic clamp for a further 1 h. Resulting data showed that aprotinin significantly improved total glucose uptake (from 16.2 +/- 2.9 mumol kg min-1 to 20.6 +/- 4.9 mumol kg min-1 p < 0.01), and decreased metabolic clearance rate of insulin (from 586 +/- 57 ml m-2 min-1 to 442 +/- 155 ml m-2 min-1, p < 0.05). Thus, in spite of the suggested positive effects of kinins on insulin-mediated glucose uptake, acute inhibition of the kallikrein-kinins system resulted in a paradoxical increment of insulin sensitivity, which was probably mediated by the reduced metabolic clearance rate of insulin.

TITLE: Failure of cefonicid prophylaxis for infectious complications related to endoscopic retrograde cholangiopancreatography.ABSTRACT: We performed a controlled study to evaluate the role of cefonicid in preventing infectious complications related to retrograde cholangiopancreatography (ERCP). Consecutive patients were randomized to receive prophylaxis with cefonicid (1 g intravenously) 1 hour before the procedure or to be untreated controls. During a 26-month period, 179 ERCPs, including 93 therapeutic procedures, were performed on 164 patients. Prophylaxis was administered before 88 procedures (49%). The rate of bacteremia among treated patients was similar to that among controls (3% vs. 2%, respectively; P = .4). The rate of cholangitis was also similar among both groups (8% vs. 2%, respectively; P = .07). There were no episodes of sepsis, and none of the patients died. The rate of bacteremia was also similar among patients undergoing diagnostic procedures and patients undergoing therapeutic procedures, but all cases of cholangitis occurred in the latter group (0 vs. 10%, respectively; P = .002). Nevertheless, the rate of cholangitis was not significantly changed by the use of prophylaxis (14% among treated patients vs. 5% among controls, P = .12). Therefore, infectious complications could not be prevented by cefonicid prophylaxis.

TITLE: Bupivacaine decreases epidural meperidine requirements after abdominal surgery.ABSTRACT: The purpose of this study was to determine the optimal of three concentrations of bupivacaine (0.0%, 0.05%, 0.10%) to add to an epidural infusion of meperidine (1 mg.ml-1) for postoperative pain relief.In this prospective, double blind study, 60 patients undergoing abdominal surgery with general anaesthesia were randomized into three groups to receive for postoperative epidural analgesia: 1) 1 mg.ml-1 meperidine (0% group), 2) bupivacaine 0.05% and 1 mg.ml-1 meperidine (0.05% group), 3) bupivacaine 0.10% and 1 mg.ml-1 meperidine (0.10% group). Postoperatively, the epidural infusion rate was titrated to produce adequate analgesia and pain was assessed at rest and on movement.There were no differences in demographic data, average pain scores or side effects among the three groups. However, there was improvement of pain relief at rest over time in the three groups (P < 0.05). Postoperative epidural analgesic infusion rates increased over time for the three groups (P < 0.05) and were lower in the 0.10% group (mean of 10.0 ml.hr-1) than in the 0% group (mean of 12.6 ml.hr-1) (P < 0.05). More than half of the 0% group had serum meperidine concentrations > 400 g.L-1 to control moderate postoperative pain.Although analgesia was identical among groups, the lower serum concentrations of meperidine support the addition of bupivacaine 0.10% to meperidine when administered as a continuous infusion following abdominal surgery.

TITLE: The role of the hypothalamic-pituitary-adrenal (HPA) axis in the regulation of blood pressure.ABSTRACT: The role of the HPA axis in blood pressure regulation was examined in 6 normal male volunteers by comparing haemodynamic and hormonal effects of placebo, captopril, and dexamethasone given in random order for two days. The average 24-hour systolic and mean arterial pressures on placebo (135 +/- 6 and 93 +/- 2 mmHg respectively) were significantly higher than on captopril (118 +/- 1 and 85 +/- 1 mmHg respectively, p < 0.05) but there were no significant changes on dexamethasone compared with placebo (128 +/- 3 and 89 +/- 3 mmHg respectively). There were no differences in the average 24-hour diastolic blood pressures or heart rates, nor the day-night differences, night:day ratios or percentage changes in blood pressure and heart rate between treatments. Captopril significantly increased active plasma renin concentration, whilst dexamethasone decreased cortisol concentration. These results confirm the role of the renin-angiotensin system in the regulation of blood pressure in normal subjects but suggest that the HPA axis does not play a major role in determining ambulatory blood pressure or day-night variability in the short term.