Metoprolol reverses left ventricular remodeling in patients with asymptomatic systolic dysfunction: the REversal of VEntricular Remodeling with Toprol-XL (REVERT) trial.

Background: There are no randomized, controlled trial data to support the benefit of beta-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether beta-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Method And Results: Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months.

Efficacy and safety of extended release metoprolol succinate in hypertensive children 6 to 16 years of age: a clinical trial experience.

Objective: To evaluate the efficacy, tolerability, and blood pressure (BP) lowering effect of extended release metoprolol succinate (ER metoprolol) in children 6 to 16 years of age with established hypertension.

Study Design: Patients were randomized to one of four treatment arms: placebo or ER metoprolol (0.2 mg/kg, 1.

Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF.

Background: The objective of the current study was to examine the efficacy and tolerability of the beta-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).

Methods: The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI).

Results: The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%).

Metoprolol CR/XL in postmyocardial infarction patients with chronic heart failure: experiences from MERIT-HF.

Background: The benefit of beta-blockers post-myocardial infarction (MI) was established in the late 1970s. Major advances in the treatment of MI have since occurred. However, patients with chronic heart failure (CHF) were excluded from those trials.

Clinical trial of extended-release felodipine in pediatric essential hypertension.

Essential hypertension in pediatric patients may require pharmacological treatment. There is a need for efficacious, safe, and well-tolerated antihypertensive agents with a once-a-day dosing regimen in children and adolescents. The aim of the trial was to evaluate the dose-response and tolerability of the dihydropyridine calcium channel blocker, felodipine extended-release tablets (felodipine ER), given once daily to pediatric patients with essential hypertension.

Pharmacokinetic considerations of formulation: extended-release metoprolol succinate in the treatment of heart failure.

Extended-release (ER) metoprolol succinate is a controlled-release formulation designed to deliver metoprolol succinate at a near constant rate for approximately 20 h, independent of food intake and gastrointestinal pH. Once-daily dosing of ER metoprolol succinate 12.5-200 mg produces even plasma concentrations over a 24-h period, without the marked peaks and troughs characteristically observed with the immediate-release (IR) formulation.

One-year study of felodipine or placebo for stage 1 isolated systolic hypertension.

Asubstantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure <90 mm Hg), but there are currently no data showing that drug treatment is effective, safe, and/or beneficial. To compare the effects of active treatment compared with placebo on blood pressure, left ventricular hypertrophy, and quality of life among older stage 1 isolated systolic hypertensive patients, a randomized, double-blind, parallel-group, multicenter clinical trial comparing felodipine (2.5, 5, or 10 mg once daily) and matching placebo was performed in 171 patients (49% male, average age 66+/-7 years, with 49% white and 30% Hispanic) with a baseline blood pressure of 149+/-7/83+/-6 mm Hg.

Comparison of two strategies for intensifying antihypertensive treatment: low-dose combination (enalapril + felodipine ER) versus increased dose of monotherapy (enalapril). LEVEL (Lexxel vs Enalapril) Study Group.

To compare two popular strategies for intensifying treatment for hypertension, a double-blind, randomized, prospective, parallel-group, and partial crossover study was done. After 2 weeks of placebo run-in (baseline) and 3 weeks of 5 mg enalapril once daily, 217 patients were randomized to 6 weeks of treatment with either a low-dose combination therapy (5 mg enalapril + 5 mg felodipine ER once daily, Lexxel, Astra Merck, Inc.), or a higher dose of monotherapy (10 mg enalapril once daily, Vasotec, Merck & Co.

Baseline clinical and angiographic data in the Quinapril Ischemic Event (QUIET) Trial.

The QUinapril Ischemic Event Trial (QUIET) is the first prospective, double-blind, placebo-controlled trial to investigate the long-term antiatherosclerotic effects of angiotensin-converting enzyme inhibition. Normotensive, nonhyperlipidemic subjects (1,750) with normal left ventricular systolic function were randomly assigned to treatment or placebo at percutaneous transluminal coronary angioplasty (PTCA). The primary end point is time to first cardiac ischemic event.

Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study.

Background: Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized.

Methods And Results: Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography.

Effect of food on the relative bioavailability of a hypolipidemic agent (CGP 43371) in healthy subjects.

The relative bioavailability of a capsule formulation and the effects of food on the pharmacokinetics of a hypolipidemic agent (CGP 43371) in 12 healthy subjects were examined. Each subject randomly received a single dose of 800 mg of CGP 43371, either as a dispersion formulation under fasting conditions or as a capsule formulation under fasting and fed conditions in a three-way crossover design with a washout period of 2 weeks between each treatment. Serial blood samples were collected at frequent intervals up to 96 h after each treatment.

GM1 ganglioside protection against ethanol-induced gastric mucosal injury.

The gastroprotective properties of GM1-ganglioside, an indigenous component of epithelial cell membrane, was investigated. The experiments were conducted with groups of rats with and without indomethacin pretreatment. The animals received intragastrically either a dose of GM1 as emulsion in 5% gum arabic or vehicle alone, followed by ethanol given at various time intervals up to 3 h after the GM1.

Delayed fatal pulmonary hemorrhage complicating use of a balloon flotation catheter.

A case of delayed fatal pulmonary hemorrhage caused by a balloon flotation catheter is described. The catheter was inserted preoperatively. The patient died on the 14th postoperative day from massive hemorrhage in the right pleural space after 12 days without any clinical symptoms.

Signet ring carcinoma of the pancreas, a rare variant with very high CEA values. Immunohistologic comparison with adenocarcinoma.

Signet ring carcinoma of the pancreas is rare. We report a case which was remarkable for (1) diffuse, infiltrating growth which suggested chronic pancreatitis at laparotomy, and (2) an associated very high circulating carcinoembryonic antigen (CEA) level of 6400 ng/ml. The case report and autopsy are presented.

Tuberculous abscess of the pancreas.

A patient who presented with a prolonged febrile course was found to have a pancreatic abscess. Routine bacterial cultures of the abscess obtained at laparotomy were negative. The patient was treated with surgical drainage and antibiotics but did poorly.

[Adaptation and disadaptation of the myocardium of rats trained to hypoxia].

Adaptation to oxygen deficit resulted from training of rats to hypoxia (8--9% O2) at the normal atmospheric pressure, during 3 weeks. Subsequent 2-week training decreased the resistance to hypoxia (disadaptation). Perfusion of the isolated hearts of adapted and disadapted animals at anoxic regimen together with the recording of the systolic pressure in the left ventricle, the rhythm, glucose uptake, lactate excretion, coronary blood flow, and the histochemical data on SDH, MDH, LDH, and hydroxibutyric DH, as well as the electron microscopy of the left ventricle mitochondria, indicate that the range of compensation reactions increases in adapted rats and decreases in disadapted ones.

[Damage to the isolated heart due to adrenaline perfused with a saline solution].

Perfusion of the isolated heart with Krebs solution containing 5 and 20 microgram/ml of adrenaline induced cardiocyte micronecrosis. Perfusion with 0.5 microgram/ml of adrenaline induced no micronecrosis.

[Myocardial resistance to adrenaline in rats adapted to hypoxia].

Expression of the damaging effect of adrenalin on the myocardium of rats adapted to hypoxia was studied under condition of adrenalin being injected into the integral body or in perfusion of an isolated heart. The damage was tested by the histoenzymatic reaction for the succinic dehydrogenase activity and staining for lipids. When the cardiotoxic dose (2.

[Metabolic disorders and plasmorrhagia in myocardial cells following adrenalin damage].

The authors examined serial sections of the myocardium of rats sacrificed at periods of from 1 to 24 hours after adrenalin administration. The results of histoenzymatic reaction to succinic dehydrogenase (a test for cell injury) were compared with the data obtained in fibrin detection by Coons' method. Plasmorrhagia into the irreversibly injured muscle cells had a characteristic appearance in the test with nitro-BT; there proved to be no fibrin in the fibers with fatty dystrophy marked by macrogranular depositions of formazan.

[Enzymatic heterogeneity of the rat myocardium].

The histoenzymatic method was applied to the study of distribution of the activity of the redox enzymes in the myocardium of the ventricles in rats; distribution of the activity of lactic and malic dehydrogenase and of alpha-glycerophosphate proved to be the most manifest near the apex of the heart and was expressed in the presence of "spotty" areas of increased activity against the general homogeneous background of formazan deposits. The activity of mitochondrial upsilon-glycerophoric dehydrogenase was seen in all the portions of the ventricles and was characterized by an uneven distribution in the sarcoplasm with increase in the direction from the interdisc to the nucleus. Unevenness of distribution of the beta-oxybutyric dehydrogenase activity was detected in some of the animals and was pronounced in all the portions of the myocardium.

[Histoenzymatic characteristics of fibroblasts during organization of myocardial micronecroses].

The activity of dehydrogenase of succinate, lactate, glutamate, malate (NAD- and NADP dependent), alpha-glycerophosphate (NAD-dependent), glucoso-6-phosphate, NAD- and NADP-dyaphorase was studied in adult and old rats with the help of histoenzymatic methods in normal cardiac fibroblasts and under conditions of reparative regeneration developing in the places of foci of myocardial micronecroses caused by administration of adrenaline. Analysis of the activity of enzymes in normal fibroblasts revealed the predominance therein of an anaerobic way of metabolism. In the process of reparative regeneration the level of metabolism of fibroblasts rose with inclusion of the acitvity of pentose shunt and Krebs' cycle.