Short- and long-term changes of flow-mediated vasodilation in patients under statin therapy.

Background: Flow-mediated vasodilation (FMD) of the brachial artery (BA) has been shown to improve in response to lipid-lowering therapy and other therapeutic interventions, usually within 1 to 2 months. Whether FMD remains improved under therapy in the longer term is unknown.

Hypothesis: The aim of this study was to examine the short- and long-term changes of FMD under statin therapy.

Heme oxygenase activity modulates vascular endothelial growth factor synthesis in vascular smooth muscle cells.

Hypoxia, cytokines, and nitric oxide (NO) stimulate the generation of vascular endothelial growth factor (VEGF) and induce heme oxygenase-1 (HO-1) expression in vascular tissue. HO-1 degrades heme to carbon monoxide (CO), iron, and biliverdin, the latter being reduced to bilirubin by biliverdin reductase. In the present study, we investigated the role of HO-1 in the modulation of VEGF synthesis in rat vascular smooth muscle cells (VSMC).

Association of wall thickness of the brachial artery measured with high-resolution ultrasound with risk factors and coronary artery disease.

Intima-media thickness of the carotid and femoral arteries has been associated with coronary atherosclerosis and its clinical sequelae. The brachial artery (BA) is widely used for the assessment of flow-mediated vasodilation. The aim of this study was to examine whether BA wall thickness (WT) is associated with coronary artery disease (CAD) and risk factors.

Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease.

Background: Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of genes involved in lipid metabolism and inflammation, making it a candidate gene for atherosclerosis and ischemic heart disease (IHD).

Methods And Results: We investigated the association between the leucine 162 to valine (L162V) polymorphism and a G to C transversion in intron 7 of the PPARalpha gene and progression of atherosclerosis in the Lopid Coronary Angiography Trial (LOCAT), a trial examining the effect of gemfibrozil treatment on progression of atherosclerosis after bypass surgery and on risk of IHD in the second Northwick Park Heart Study (NPHS2), a prospective study of healthy middle-aged men in the United Kingdom. There was no association with plasma lipid concentrations in either study.

Asymptomatic versus symptomatic persistent atrial fibrillation: clinical and noninvasive characteristics.

Objective: This prospective study was designed to investigate the differences between asymptomatic versus symptomatic arrhythmia as well as left ventricular dysfunction in a consecutive population of patients with persistent atrial fibrillation.

Design: A total of 282 consecutive outpatients referred with persistent atrial fibrillation formed the study population. A structured medical history was obtained.

Oral immunization of mice with ricin toxoid vaccine encapsulated in polymeric microspheres against aerosol challenge.

Mucosal (oral) immunization of mice with carrier-delivered ricin toxoid (RT) vaccine was accomplished by one long (7 weeks) or two short (4 weeks) immunization schedules. For the long and short immunization schedule two lots of vaccine were administered prepared with the same procedure but at different occasions. The long schedule consisted of a total of seven doses of 50 microg of vaccine in microencapsulated (lot #108) or aqueous form administered on days 1, 2, 3, 28, 29, 30 and 49.

Fusion pore expansion is a slow, discontinuous, and Ca2+-dependent process regulating secretion from alveolar type II cells.

In alveolar type II cells, the release of surfactant is considerably delayed after the formation of exocytotic fusion pores, suggesting that content dispersal may be limited by fusion pore diameter and subject to regulation at a postfusion level. To address this issue, we used confocal FRAP and N-(3-triethylammoniumpropyl)-4-(4-[dibutylamino]styryl) pyridinium dibromide (FM 1-43), a dye yielding intense localized fluorescence of surfactant when entering the vesicle lumen through the fusion pore (Haller, T., J.

Secretion in alveolar type II cells at the interface of constitutive and regulated exocytosis.

Long-term, simultaneous, measurements of cytoplasmic free Ca(2+) concentrations and single exocytotic fusion events in surfactant-secreting type II cells were performed. All fusion (constitutive, phorbol ester-induced, and agonist-induced) was Ca(2+)-dependent. Kinetic analysis revealed that agonist (adenosine triphosphate [ATP])-induced fusion exhibited a kinetic pattern that correlated well with the Ca(2+) signal.

Mechanisms of surfactant exocytosis in alveolar type II cells in vitro and in vivo.

Surfactant secretion must be regulated to maintain a low surface tension in the lung during various conditions such as exercise. In vitro studies reveal a slow, unique exocytotic process at the interface of stimulated and constitutive exocytosis. The exocytotic mechanisms and sites of regulation in vivo, however, are still poorly understood.

Spontaneous delayed recovery of perfusion after thrombolyzed acute myocardial infarction: is it predictable before discharge?

In patients with thrombolyzed acute myocardial infarction, early assessment of the final infarct size is difficult because spontaneous recovery of perfusion and function of the left ventricle may be delayed. This study was undertaken to evaluate the ability of predischarge low-dose dobutamine echocardiography to predict late spontaneous recovery of perfusion assessed by single-photon emission computed tomography after acute myocardial infarction. We prospectively studied 53 consecutive patients with myocardial infarction treated with thrombolysis.

Remnant-like lipoprotein particle cholesterol concentration and progression of coronary and vein-graft atherosclerosis in response to gemfibrozil treatment.

Remnant lipoproteins such as chylomicron and very low density lipoprotein (VLDL) remnants have been implicated in the progression of coronary atherosclerosis. Recently, a novel method for the determination of the remnant-like lipoprotein particle cholesterol (RLP-C) concentration was developed based on immunoaffinity-separation of plasma. The compositional characteristics of RLP are strikingly similar to those of postprandially modified VLDL.

Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients.

The relationship between the dose of tacrolimus, trough tacrolimus blood concentration, and selected clinical endpoints (acute rejection, nephrotoxicity, and other toxicities) were examined in a prospective, multicenter clinical trial to validate the use of an enzyme-linked immunosorbent assay (ELISA) for monitoring whole-blood concentrations of tacrolimus in liver transplant patients. A total of 111 subjects from six transplant centers were evaluated over 12 weeks posttransplantation. In addition to trough tacrolimus blood concentrations, hematocrit, ALT, AST, GGTP, alkaline phosphatase, total bilirubin, serum creatinine, BUN, serum potassium, serum magnesium, blood glucose, and serum albumin were also measured.

Inhibition of ATP-induced surfactant exocytosis by dihydropyridine (DHP) derivatives: a non-stereospecific, photoactivated effect and independent of L-type Ca2+ channels.

Purinergic stimulation of surfactant secretion via exocytosis of lamellar bodies is mediated by an elevation of the intracellular Ca2+ concentration ([Ca2+](i)). We tested the dihydropyridine (DHP) analogues isradipine (+/-enantiomers), nifedipine and Bay K 8644 (racemic forms) on ATP-induced surfactant secretion and [Ca2+](i) in single type II cells, using FM1-43 and fura-2 fluorescence. None of the DHPs (2 microM) had an effect on ATP-induced surfactant secretion in the dark.

Factors predicting success rate and recurrence of atrial fibrillation after first electrical cardioversion in patients with persistent atrial fibrillation.

Background: The recurrence rate of atrial fibrillation (AF) after elective cardioversion is high.

Hypothesis: The study aimed to identify clinical predictors for successful electrical cardioversion and maintenance of sinus rhythm after a first electrical cardioversion in patients with persistent AF without concomitant antiarrhythmic drugs of class I and III.

Methods: Consecutive outpatients (n = 166) with persistent AF for > 1 month, scheduled for elective cardioversion, were prospectively included in the study.

The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation.

Aims: To determine whether magnesium given orally decreases the recurrence rate of atrial fibrillation after elective direct current cardioversion of persistent atrial fibrillation.

Methods And Results: Consecutive outpatients were randomized to treatment with oral magnesium (10.3 mmol) or placebo twice daily in a double-blind fashion.

Prospective evaluation of Roux-en-Y gastric bypass as primary operation for medically complicated obesity.

Objective: To determine prospectively the results of Roux-en-Y gastric bypass (RYGB) used as the primary weight-reducing operation in patients with medically complicated ("morbid") obesity. The RYGB procedure combines the advantages of a restrictive physiology (pouch of 10 mL) and a "dumping physiology" for high-energy liquids without requiring an externally reinforced (banded) stoma.

Patients And Methods: Between April 1987 and December 1998, a total of 191 consecutive patients with morbid obesity (median weight, 138 kg [range, 91-240 kg]; median body mass index, 49 kg/m2 [range, 36-74 kg/m2]), all of whom had directly weight-related morbidity, underwent RYGB and prospective follow-up.

Development of a PCR marker for rapid identification of the Bt-10 gene for common bunt resistance in wheat.

In western Canada, the Bt-10 resistance gene in wheat (Triticum aestivum) is effective against all the known races of common bunt caused by Tilletia tritici and T laevis. The genotypes of 199 F2 plants, originated from a cross between BW553 containing Bt-10 and the susceptible spring wheat cultivar 'Neepawa,' were established in greenhouse and field inoculation studies. A ratio of 1:2:1 resistant : heterozygous : susceptible was observed for bunt reaction, indicating that Bt-10 was expressed in a partially dominant fashion.

Fibrinolytic proteins and progression of coronary artery disease in relation to gemfibrozil therapy.

Impaired fibrinolytic function, mainly due to increased plasma plasminogen activator inhibitor-1 (PAI-1) activity, is common in patients with manifest coronary artery disease (CAD) and a predictor of recurrent cardiovascular events. We investigated the relationships of plasma tissue-type plasminogen activator (tPA) and PAI-1 antigen levels, plasma PAI-1 activity and PAI 4/5-guanosine (4G/5G) genotype to CAD progression in 203 middle-aged men participating in the Lopid Coronary Angiography Trial (LOCAT). A higher tPA antigen concentration, whether baseline or on-trial, was associated with a more severe global angiographic response (p < 0.

Cardioversion of atrial fibrillation and its effect on right ventricular function as assessed by tricuspid annular motion.

In patients with atrial fibrillation, the reduced right ventricular function determined by tricuspid annular motion before cardioversion returns to normal 1 month after successful cardioversion to sinus rhythm. The simplicity of recording the tricuspid annular motion provides an easy opportunity to assess right ventricular function following electroconversion of atrial fibrillation to sinus rhythm.

Threshold calcium levels for lamellar body exocytosis in type II pneumocytes.

Pulmonary surfactant is secreted via exocytosis of lamellar bodies (LBs) by alveolar type II cells. Here we analyzed the dependence of LB exocytosis on intracellular Ca(2+) concentration ([Ca(2+)](i)). In fura 2-loaded cells, [Ca(2+)](i) was selectively elevated by flash photolysis of a cell-permeant caged Ca(2+) compound (o-nitrophenyl EGTA-AM) or by gradually enhancing cellular Ca(2+) influx.

Factors influencing G-CSF-mediated mobilization of hematopoietic progenitor cells during steady-state hematopoiesis in patients with malignant lymphoma and multiple myeloma.

We retrospectively analyzed factors influencing PBPC mobilization during steady-state hematopoiesis in 52 patients with malignant lymphoma (n=35) or multiple myeloma (n=17) who received 77 cycles of G-CSF (12.5-50 microg G-CSF/kg/day). For 15 of these patients, the first mobilization cycle (12.

Heart rate variability and progression of coronary atherosclerosis.

Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (<1.

Effect of intravenous magnesium on heart rate and heart rate variability in patients with chronic atrial fibrillation.

The present double-blind, placebo-controlled study investigated the effects of intravenous magnesium on heart rate and rate variability in 30 patients with chronic atrial fibrillation. During standardized conditions, intraindividual variation in heart rate and rate variability was low in patients with chronic atrial fibrillation and magnesium had no effect on heart rate or rate variability.