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Denis Roy

Publications and source records attributed to Denis Roy.

30 records · Page 2Linked to original sources

Rationale for the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial.

Congestive heart failure and atrial fibrillation (AF) are two important and growing problems in medicine and cardiology. Both conditions often coexist and complicate each other's management. Two therapeutic strategies are available for patients with AF and congestive heart failure: the first aims at restoring and maintaining sinus rhythm, whereas the second focuses exclusively on optimizing ventricular rate. Prior studies of AF and congestive heart failure were not randomized and most were retrospective. Although some studies suggested that AF had no effect on survival, in most recent large congestive heart failure trials, AF was reported to be an independent risk factor for mortality or major morbidity. The primary objective of the Atrial Fibrillation in Congestive Heart Failure (AF-CHF) trial is to compare the two widely used treatment strategies with respect to cardiovascular mortality. AF-CHF is a prospective, multicenter trial that will randomize 1450 CHF patients with left ventricular ejection fraction (LVEF) < or =35% and a documented recent episode of atrial fibrillation to either a rhythm control or a rate control strategy. From recent trial data, we anticipate an 18.75% 2-year cardiovascular mortality in the rate control arm and a 25% event reduction in the rhythm control group. As of December 2003, 960 patients have been randomized. Enrollment is expected to be completed in September 2004 with a minimum follow-up of 2 years.

Atrial Fibrillation↗

Cost evaluation of rhythm control methods for atrial fibrillation: evidence from CTAF.

Atrial fibrillation (AF) is a highly prevalent arrhythmia that is difficult to treat and generates important health care costs. One consideration in the selection of various therapeutic options is the cost of a given treatment compared to that of alternatives. The Canadian Trial of Atrial Fibrillation (CTAF) evaluated the effectiveness of sinus rhythm maintenance with amiodarone compared to propafenone or sotalol in a prospective, randomized fashion. A subsequent CTAF substudy of the medical costs associated with amiodarone vs. propafenone/sotalol found that amiodarone decreased AF-related costs. This paper reviews the results of the CTAF cost-analysis substudy in the context of other analyses in the literature of the cost effectiveness of amiodarone in AF. The costs associated with amiodarone therapy are no greater than for other sinus rhythm maintenance drugs, and for some cost categories and some patient subgroups are likely to be less, despite amiodarone's greater therapeutic efficacy. However, additional considerations are important in evaluating the clinical place of amiodarone, including its adverse effect and pharmacokinetic profile. As well, the results of recent randomized clinical trials have highlighted the limitations of sinus rhythm maintenance as a primary therapeutic objective in AF. The decision about whether and at what point to use amiodarone in a given patient requires a careful analysis of the individual case, in terms of symptomatology during AF, the response to previous treatment regimes, and risk factors for various forms of adverse drug reactions.

Amiodarone↗

Consensus-degenerate hybrid oligonucleotide primers for amplification of priming glycosyltransferase genes of the exopolysaccharide locus in strains of the Lactobacillus casei group.

A primer design strategy named CODEHOP (consensus-degenerate hybrid oligonucleotide primer) for amplification of distantly related sequences was used to detect the priming glycosyltransferase (GT) gene in strains of the Lactobacillus casei group. Each hybrid primer consisted of a short 3' degenerate core based on four highly conserved amino acids and a longer 5' consensus clamp region based on six sequences of the priming GT gene products from exopolysaccharide (EPS)-producing bacteria. The hybrid primers were used to detect the priming GT gene of 44 commercial isolates and reference strains of Lactobacillus rhamnosus, L. casei, Lactobacillus zeae, and Streptococcus thermophilus. The priming GT gene was detected in the genome of both non-EPS-producing (EPS(-)) and EPS-producing (EPS(+)) strains of L. rhamnosus. The sequences of the cloned PCR products were similar to those of the priming GT gene of various gram-negative and gram-positive EPS(+) bacteria. Specific primers designed from the L. rhamnosus RW-9595M GT gene were used to sequence the end of the priming GT gene in selected EPS(+) strains of L. rhamnosus. Phylogenetic analysis revealed that Lactobacillus spp. form a distinctive group apart from other lactic acid bacteria for which GT genes have been characterized to date. Moreover, the sequences show a divergence existing among strains of L. rhamnosus with respect to the terminal region of the priming GT gene. Thus, the PCR approach with consensus-degenerate hybrid primers designed with CODEHOP is a practical approach for the detection of similar genes containing conserved motifs in different bacterial genomes.

Amino Acid Sequence↗

Phosphorylation of Streptococcus salivarius lactose permease (LacS) by HPr(His ~ P) and HPr(Ser-P)(His ~ P) and effects on growth.

The oral bacterium Streptococcus salivarius takes up lactose via a transporter called LacS that shares 95% identity with the LacS from Streptococcus thermophilus, a phylogenetically closely related organism. S. thermophilus releases galactose into the medium during growth on lactose. Expulsion of galactose is mediated via LacS and stimulated by phosphorylation of the transporter by HPr(His approximately P), a phosphocarrier of the phosphoenolpyruvate:sugar phosphotransferase transport system (PTS). Unlike S. thermophilus, S. salivarius grew on lactose without expelling galactose and took up galactose and lactose concomitantly when it is grown in a medium containing both sugars. Analysis of the C-terminal end of S. salivarius LacS revealed a IIA-like domain (IIA(LacS)) almost identical to the IIA domain of S. thermophilus LacS. Experiments performed with purified proteins showed that S. salivarius IIA(LacS) was reversibly phosphorylated on a histidine residue at position 552 not only by HPr(His approximately P) but also by HPr(Ser-P)(His approximately P), a doubly phosphorylated form of HPr present in large amounts in rapidly growing S. salivarius cells. Two other major S. salivarius PTS proteins, IIAB(L)(Man) and IIAB(H)(Man), were unable to phosphorylate IIA(LacS). The effect of LacS phosphorylation on growth was studied with strain G71, an S. salivarius enzyme I-negative mutant that cannot synthesize HPr(His approximately P) or HPr(Ser-P)(His approximately P). These results indicated that (i) the wild-type and mutant strains had identical generation times on lactose, (ii) neither strain expelled galactose during growth on lactose, (iii) both strains metabolized lactose and galactose concomitantly when grown in a medium containing both sugars, and (iv) the growth of the mutant was slightly reduced on galactose.

Autoradiography↗

Prognostic significance of ventricular arrhythmias post-myocardial infarction.

Despite improvements in management strategies, ventricular arrhythmias remain important markers of electrical instability and contribute to the identification of patients at increased risk of sudden cardiac death post-myocardial infarction (MI). Over the past 20 years, understanding of pathophysiological mechanisms and implications of various types of ventricular arrhythmias has evolved remarkably. This systematic review details the prognostic significance of ventricular arrhythmias classified by type and time of onset post-MI. Subacute and late premature ventricular complexes are associated with increased mortality independent of left ventricular function. Although nonsustained ventricular tachycardia (VT) in the acute phase post-MI is of questionable significance, later onset heralds poorer prognosis. Sustained monomorphic VT in the acute post-MI phase is associated with infarct extension, heart failure and increased mortality. Extensive wall motion abnormalities, left ventricular dysfunction and aneurysm formation correlate with later postinfarct sustained VT. Inhospital mortality is higher when ventricular fibrillation presents in the acute phase but long term prognosis is not adversely affected.

Anti-Arrhythmia Agents↗

Structure determination of the exopolysaccharide produced by Lactobacillus rhamnosus strains RW-9595M and R.

Exopolysaccharides (EPSs) were isolated and purified from Lactobacillus rhamnosus strains RW-9595M, which has been shown to possess cytokine-stimulating activity, and R grown under various fermentation conditions (carbon source, incubation temperature and duration). Identical (1)H NMR spectra were obtained in all cases. Molecular masses were determined by gel permeation chromatography. The primary structure was elucidated using chemical and spectroscopic techniques. Organic acid, monosaccharide and absolute configuration analyses gave the following composition: pyruvate, 1; D-glucose, 2; D-galactose, 1; and l-rhamnose, 4. Methylation analysis indicated the presence of three residues of 3-linked rhamnose, and one residue each of 2,3-linked rhamnose, 2-linked glucose, 3-linked glucose and 4,6-linked galactose. The EPS was submitted to periodate oxidation followed by borohydride reduction. Monosaccharide analysis of the resulting polysaccharide gave the new composition: rhamnose, 4; and glucose, 1. Methylation analysis confirmed the loss of the 2-linked glucose and 4,6-linked galactose residues. On the basis of one- and two-dimensional (1)H and (13)C NMR data, the structure of the native EPS was consistent with the following heptasaccharide repeating unit: [3Rha alpha-3Glc beta-3[Gal4,6(R)Py alpha-2]Rha alpha-3Rha alpha-3Rha alpha-2Glc alpha-](n) where Rha corresponds to rhamnose (6-deoxymannose) and Py corresponds to pyruvate acetal. Complete (1)H and (13)C assignments are reported for the native and the corresponding pyruvate-hydrolysed polysaccharide. Electrospray MS and MS/MS data are given for the oligosaccharide produced by Smith degradation.

Carbohydrate Sequence↗

Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation.

BACKGROUND: The impact of atrial fibrillation (AF) and its treatment on health-related quality of life (QOL) is not well understood. We assessed QOL in patients with symptomatic AF participating in the Canadian Trial of Atrial Fibrillation. METHODS: Self-report QOL questionnaires including the Short-Form-36 (SF-36), symptom checklist (SCL) and AF Severity Scale (AFSS) were completed at baseline and 3, and 12 months after randomization. RESULTS: The study group was aged 65 +/- 10 years and 59% were male. By design, 50% of patients were randomized to amiodarone (n = 132), 25% to sotalol (n = 66), and 25% to propafenone (n = 66). Most patients had normal left ventricular function (89%). Physical (41.9 +/- 9.3 to 43.7 +/- 9.2, P =.001) and mental health (47.5 +/- 10.5 to 49.0 +/- 9.8, P =.023) summary measures from the SF-36 improved significantly from baseline to 3 months. Arrhythmia symptom frequency and severity (SCL) also improved markedly from baseline to 3 months (symptom frequency 20.4 +/- 9.4 to 16.2 +/- 9.5 and symptom severity 16.7 +/- 8.2 to 12.9 +/- 7.4, both P <.001). QOL improvements were not significantly different among the groups randomized to amiodarone, sotalol, or propafenone. However, patients with no symptomatic recurrences of AF had higher scores at 3 months on measures of global well-being than those with recurrences in the first 3 months (7.4 +/- 1.8 vs 6.9 +/- 1.8, P <.05). There were no significant QOL changes from the 3 to 12 month assessment. CONCLUSION: In patients with symptomatic AF, QOL improves after treatment, independent of the specific drug used for treatment. This is especially true for patients in whom treatment prevents AF recurrence.

Aged↗

New approaches to atrial fibrillation management: a critical review of a rapidly evolving field.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, the prevalence of which is increasing with the aging of the population. Because of its clinical importance and the lack of highly satisfactory management approaches, AF is the subject of active clinical and research efforts. This paper reviews recent and on-going developments in pharmacological and non-drug management of AF. The ideal therapeutic goal for AF is the production and maintenance of sinus rhythm. Comparative studies suggest that available class I and III drugs have comparable and modest efficacy for sinus rhythm maintenance. Amiodarone, with actions of all antiarrhythmic classes, has recently been shown to have clearly superior efficacy compared with other available drugs. Newer agents are in development, but their advantages are as yet unclear and appear limited. A potentially interesting approach is the prescription of drugs upon the occurrence of an attack, rather than on a continuous basis. Recent insights into AF mechanisms may permit therapy to prevent development of the AF substrate. An alternative to sinus rhythm maintenance is a rate control approach, with no attempt to prevent AF. Drugs to effect rate control include digitalis, beta-blockers and calcium channel antagonists. Digitalis has limited value for control of exercise heart rate and for paroxysmal AF, but is particularly well suited for patients with concomitant AF and congestive heart failure. AV-nodal ablation and pacing is an effective alternative for rate control but leaves the patient pacemaker dependent. The relative merits of rate versus rhythm control are being evaluated in ongoing trials, preliminary results of which indicate no statistically significant differences in primary endpoints but highlight the risks of rhythm control therapy. In patients requiring pacemakers, physiological pacing (dual chamber devices or atrial pacing) has an advantage over purely ventricular pacemakers in AF prevention. Newer pacing modalities that produce more synchronised atrial activation, as well as pacemakers that prevent excessive atrial rate swings, show promise in AF prevention and may soon see wider use. The usefulness of automatic atrial defibrillators is presently limited by discomfort during shocks. Targeted destruction of pulmonary vein foci by radiofrequency catheter ablation suppresses paroxysmal AF. Efficacy in persistent AF is lower and still under study. Problems include potential recurrence in other veins and a small but nontrivial risk of pulmonary vein stenosis. Surgical division of the atria into zones with limited electrical connection, the MAZE procedure, is highly effective in AF prevention but is a major intervention that is not applicable to most patients. In conclusion, significant advances are being made in the management of patients with AF but much more work remains to be done.

Anti-Arrhythmia Agents↗

Evidence for Escherichia coli O157:H7 attachment to water distribution pipe materials by scanning electron microscopy.

Scanning electron microscopy observation was used to investigate the adhesion of Escherichia coli O157:H7 on water distribution pipe surfaces such as copper and polyethylene plastic at different contact times and storage temperatures. Our results indicated that E. coli cells could easily attach to both surface types after exposures as short as 1 or 4 h at ambient (20 degrees C) and refrigeration temperatures (4 degrees C). Also, we found that copper surfaces have a higher number of attached E. coli cells than plastic surfaces. The number of cells attached to each type of material depended on the nature of the water distribution pipe surfaces and the length of contact time. In addition, the surface energy value of each surface estimated by contact angle measurements using water, alpha-bromonaphthalene, and dimethyl sulfoxide as wetting agents showed that both copper (41.2 megajoules [MJ] m(-2)) and plastic (45.8 MJ x m(-2)) have a low energy surface. In no cases could evidence of extracellular material be observed on surfaces with either exposure condition.

Bacterial Adhesion↗

Attachment of Arcobacter butzleri, a new waterborne pathogen, to water distribution pipe surfaces.

The capability of Arcobacter butzleri to attach to various water distribution pipe surfaces, such as stainless steel, copper, and plastic, was evaluated using scanning electron microscopy. Our results indicated that Arcobacter cells could easily attach to all surface types and the number of attached cells depended on the length of exposure and temperatures (4 and 20 degrees C). Extracellular fibrils were also observed on the stainless steel surface, especially after 72 h of contact times at both refrigeration and ambient temperatures. In addition, the surface energy value of each material was estimated by contact angle measurements using water, alpha-bromonaphthalene, and dimethylsulfoxide. The surface energy of A. butzleri was 58.6 mJ x m(-2) and the surface energy values of the three surfaces studied showed that plastic had a low energy surface (26.1 mJ x m(-2)) as did copper (45.8 mJ x m(-2)) and stainless steel (65.7 mJ x m(-2)).

Arcobacter↗

Management of atrial fibrillation in patients with congestive heart failure.

An increase in the prevalence of both atrial fibrillation and congestive heart failure is occurring in part because of the demographic shift toward an aging population. These two clinical entities often coexist in the same patient, resulting in the worsening of symptoms and prognosis, rendering their management even more challenging. A large clinical trial is currently examining whether a rhythm-control strategy is superior to a rate-control strategy in patients with congestive heart failure. New nonpharmacologic therapies such as pulmonary vein isolation are undergoing clinical investigation and may also alter the management of these patients. At present, therapy for atrial fibrillation in patients with congestive heart failure should aim first at controlling heart rate to provide symptomatic relief; then sinus rhythm should be restored if symptoms persist or if congestive heart failure worsens. For a more definitive approach in managing these patients, the authors await further clinical trial data.

Aged↗