Effects of flecainide on the electrophysiological properties of atrial vulnerability in humans.

The aims of this study were to evaluate the changes in the electrophysiological characteristics of the right atrium after the administration of flecainide and to clarify whether flecainide has a selective effect on human atrial tissue. Electrophysiological measurements were made in 38 patients, before and after intravenous administration of flecainide (2 mg/kg per 10 min). The effective refractory period of the right atrium (ERP-A), maximum conduction delay (Max.CD), repetitive atrial firing zone (RAFZ), fragmented atrial activity zone (FAAZ), and conduction delay zone (CDZ) were studied in the patients who were divided into 2 groups based on whether repetitive atrial firing (RAF) was induced in the baseline study. Flecainide significantly prolonged the ERP-A (202+/-22 to 238+/-33 ms, p<0.001) and shortened Max.CD (77+/-17 to 63+/-32 ms, p<0.05) in the patients with RAF, but not in those without RAF in the baseline study. After flecainide administration, there were significant reductions in the RAFZ (43+/-22 to 13+/-19 ms, p<0.0001), FAAZ (51+/-22 to 28+/-26 ms, p<0.001) and CDZ (70+/-21 to 48+/-30 ms, p<0.01) in the patients with RAF. However, atrial fibrillation (AF) was induced by stimulation after flecainide in 2 patients without RAF in the baseline study. There was a significant negative correlation between the ERP-A in the baseline study and the change in the ERP-A upon flecainide administration (r=0.45, p<0.01). Flecainide may preferentially activate the substrate for AF and RAF, but that action is mainly based on the electrophysiological characteristics found in the baseline study.     

Combination therapy of ecabet sodium and cimetidine compared with cimetidine alone for gastric ulcer: prospective randomized multicenter study

BACKGROUND AND AIM: Little is known about the clinical efficacy of co-therapy of ecabet sodium, a mucoprotective agent, and a histamine H2-receptor antagonist. The aim of the present study was to assess its additive benefit in combination with cimetidine for gastric ulcer. METHODS: In this prospective randomized study, after gastric ulcer was confirmed by endoscopy, 200 patients in 47 hospitals received either ecabet sodium 1 g b.i.d and cimetidine 400 mg b.i.d. (EC), or cimetidine 400 mg b.i.d. alone (C) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks. RESULTS: Of the intention-to-treat (ITT) population (EC, 103; C, 97), 181 patients comprised the per protocol (PP) analysis (EC, 93; C, 88). At 4 weeks, healing rates were significantly higher in the EC group (60%) than in the C group (36%) ( p < 0.01). At 8 weeks, those by the ITT and PP analyses were 82% (EC) versus 58% (C), and 90% (EC) versus 64% (C), respectively ( p < 0.01 and p < 0.001). Symptom relief rates (EC vs C) at 2, 4 and 8 weeks were 73%versus 47% ( p < 0.01), 89%versus 66% ( p < 0.001), and 97%versus 73% ( p < 0.001), respectively. Significant additive effects of ecabet sodium were observed in patients aged 60 years or older, with solitary and medium to large ulcer, and without smoking or drinking habits. No adverse effects were critical. CONCLUSION: Ecabet sodium significantly augmented gastric ulcer healing and symptom relief by cimetidine, especially in the elderly.     

Genetically determined interferon-gamma production influences the histological phenotype of lupus nephritis

OBJECTIVE: To clarify whether the interferon-gamma (IFN-gamma) gene (IFNG) is associated with the histological phenotype of lupus nephritis. METHOD: We analysed microsatellite polymorphisms located within the first intron of the IFNG gene to determine the genotypes of patients with lupus nephritis WHO class IV (n=24), patients with WHO class V (n=12) and healthy controls (n=61). We used flow cytometric detection of intracellular cytokines to identify CD4(+) T cells producing IFN-gamma. Production of IFN-gamma by peripheral blood mononuclear cells after stimulation with phytohaemagglutinin was evaluated with an enzyme-linked immunosorbent assay. RESULT: The frequency of the IFNG allele 114 was significantly greater in WHO class V patients than in WHO class IV patients. Furthermore, the IFNG 114 +/+ genotype was more frequent in WHO class V than in WHO class IV patients. The level of IFN-gamma and the percentage of IFN-gamma-producing CD4(+) T cells were lower in individuals with genotype 114 +/+ than in individuals with genotype 114 -/-. CONCLUSION: The IFN-gamma gene is associated with the histological phenotype in lupus nephritis.     

Noninvasive positive pressure ventilation in patients with acute exacerbations of pulmonary tuberculosis sequelae]

To clarify whether noninvasive positive pressure ventilation (NPPV) is effective in patients with acute exacerbations of pulmonary tuberculosis sequelae (PTS), 50 PTS patients (66 episodes) without long-term domiciliary noninvasive ventilation were studied, retrospectively. The average values (SD) of their pulmonary function tests and arterial blood gases were as follows; %predicted VC = 31.4 (8.4)%, pH = 7.29 (0.06), PaCO2 = 91.8 (19.7) mmHg, and PaO2 = 64.2 (20.3) mmHg. The probability of avoiding endotracheal intubation and recovering from an acute exacerbation with NPPV (NPPV success rate) was 92% as a whole. NPPV success rates according to the causes of deterioration were as follows; 96% in 26 episodes with only a simple right heart failure, 93% in 29 episodes with airway infectious diseases, 75% in eight episodes with pneumonia and/or acute respiratory distress syndrome. Moreover, the NPPV success rate of eight episodes in coma or semicoma was 88%. Most patients were treated in respiratory wards rather than intensive care units. Out of 46 patients who recovered from an acute exacerbation, 41 finally received domiciliary NPPV. In facilities where staff are well-trained for an acute NPPV, patients with exacerbations of PTS can be treated as successfully with NPPV as patients with COPD.     

Brief episode of myocardial ischemia before prolonged ischemia attenuates cardiac sympathetic nerve injury.

BACKGROUND: The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown. METHODS AND RESULTS: Sympathetic neural function was assessed using 123I-metaiodobenzylguanidine (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days prior to acute myocardial infarction. In the rat experiment, cardiac interstitial NE (iNE) with or without pretreatment of 5-min coronary ligation was determined during a 30-min occlusion. Differences between MIBG and Thallium-201 for the total defect score were significantly greater in Group II than in Group I (6.1 +/- 4.0 vs 0.4 +/- 4.4). Levels of iNE were less in rats with a 5-min pretreatment (7.3 +/- 2.3 vs 18.6 +/- 5.9 x 10(3) pg/ml, p < 0.01) and MIBG uptake of ischemic region was greater (0.061 +/- 0.029 vs 0.031 +/- 0.011 %kg dose/g, p < 0.05) compared with rats without the pretreatment. CONCLUSION: A brief episode of ischemia attenuates the sympathetic neural injury caused by subsequent prolonged ischemia and this protective effect is associated with attenuation of NE release during the prolonged ischemia.     

Intragastric nicotine protects against 40% ethanol-induced gastric mucosal injury despite pretreatment with propranolol orN-ethylmaleimide in rats

We tested the hypotheses that the protective effect of intragastric nicotine against ethanol-induced gastric mucosal injury is dependent on propranolol- orN-ethylmaleimide-sensitive mechanisms. Propranolol was administered in doses (2 and 20 mg/kg) that provided dose-related blockade of -adrenoceptors (significant decreases in heart rate).N-Ethylmaleimide was administered in doses that previously had been shown to increase gastric vascular permeability (10 mg/kg) or inhibit gastric mucosal sulfhydryl compounds (50 mg/kg). At 0.5 hr after these or control subcutaneous pretreatments, the rats received intragastric nicotine (4 mg/kg) or vehicle. One hour later 40% ethanol was given intragastrically. The gastric corpus mucosal lesions were recorded by polaroid photographs after another hour, and their areas measured unbiasedly by computerized image analysis. The results showed thatN-ethylmaleimide, but not propranolol, aggravated ethanol-induced gastric mucosal injury. The protective effect of intragastric nicotine was not modified by either pretreatment. We conclude that the mechanism mediating intragastric nicotine protection against 40% ethanol-induced gastric mucosal injury is independent of propranolol- orN-ethylmaleimide-sensitive mechanisms.Supported by Veterans Administration Medical Research Funds, and in part by research grants (0162-01, 02 and 0291-01) from the Smokeless Tobacco Research Council, Inc., and by funds (1RT 80) provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco-Related Disease Research Program of the University of California to FWL. Dr. Endoh is a recipient of the University of California Tobacco-Related Disease Research Program Research Fellowship Award (FT 37).     

Age-related decrease in plasma growth hormone: response to growth hormone-releasing hormone, arginine, and L-dopa in obesity

Aging is associated with a reduction in plasma growth hormone (GH) secretion in non-obese subjects. To determine whether or not age-related changes in plasma GH secretion exist in obese subjects, we measured (a) plasma GH response to growth hormone-releasing hormone (GRH; 1 microgram/kg body wt), arginine (0.5 g/kg body wt), L-dopa (500 mg), and (b) plasma glucose, insulin, and free fatty acids (FFAs) in 26 fasted obese subjects of various ages ranging from 16 to 71 years. Only subjects with a body mass index (BMI; kg/m2) between 30.0 and 39.0 were studied. Six subjects were adolescents, 9 were in their 20s, and 11 were 30 years or older. The mean peak levels of plasma GH in response to GRH, arginine, and L-dopa in obese subjects were 11.3 +/- 2.1, 21.9 +/- 4.4, and 5.2 +/- 0.3 ng/mL in adolescents, 8.2 +/- 1.6, 9.1 +/- 1.5, and 3.1 +/- 0.6 ng/mL in those in their 20s, and 4.5 +/- 0.4, 7.3 +/- 1.4, and 2.8 +/- 0.3 ng/mL in those 30 years or older, respectively, showing a significant decrease in peak GH level with advancing age (P less than .05 to P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of late potentials in myocardial infarction

To clarify factors which have an influence on late potentials (LPs), signal averaged electrocardiogram, echocardiogram, cardiac catheterization and Holter monitoring were studied in 86 patients with previous myocardial infarction (MI). Group 1 consisted of 27 patients with LPs (LP duration greater than or equal to 20 msec) and Group 2 consisted of 59 patients without them. Twelve percent of anterior MI and 35% of inferior MI had LPs. Left ventricular (LV) diastolic dimension was larger and % fractional shortening was lower in group 1 than those in group 2. LV end-diastolic volume index and LV end-systolic volume index were larger and LV ejection fraction was lower in group 1 than those in group 2. Aneurysm was noted in 37% in group 1 and 17% in group 2 (p less than 0.05), and mean number of involved coronary vessels was 2.3 +/- 0.8 in group 1 and 1.7 +/- 0.8 in group 2 (p less than 0.05). No significant difference was found in other clinical and hemodynamic parameters. The incidence of patients with 100 or more ventricular premature contractions per hours and that with ventricular tachycardia (VT) were significantly higher in group 1 than in group 2 (26% vs 7%, p less than 0.05, 33% vs 7%, p less than 0.01, respectively). Multiple regression analysis and the method of quantification demonstrated that ventricular arrhythmia was most strongly associated with LP duration.