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Biomedical subjects

P Chevalier

Publications and source records attributed to P Chevalier.

At least 37 records · Page 2Linked to original sources
PubMed1999

Splicing mutations in KCNQ1: a mutation hot spot at codon 344 that produces in frame transcripts.

BACKGROUND: Long-QT syndrome is a monogenic disorder that produces cardiac arrhythmias and can lead to sudden death. At least 5 loci and 4 known genes exist in which mutations have been shown to be responsible for the disease. The potassium channel gene KCNQ1, previously named KVLQT1, on chromosome 11p15.5 is one of these. METHODS AND RESULTS: We initially analyzed one family using microsatellite markers and found linkage to KCNQ1. Mutation detection showed a G to C change in the last base of exon 6 (1032 G-->C) that does not alter the coded alanine. Restriction digest analysis in the family showed that only affected individuals carried the mutation. A previous report suggested that a G to A substitution at the same position may act as a splice mutation in KCNQ1, but no data was given to support this hypothesis nor was the transcription product identified. We have shown by reverse-transcription polymerase chain reaction that 2 smaller bands were produced for the KCNQ1 gene transcripts in addition to the normal-sized transcripts when lymphocytes of affected individuals were analyzed. Sequencing these transcripts showed a loss of exon 7 in one and exons 6 and 7 in the other, but an in-frame transcript was left in each instance. We examined other families in whom long-QT syndrome was diagnosed and found another unreported splice-site mutation, 922-1 G-->C, in the acceptor site of intron 5, and 2 of the previously reported 1032 G-->A mutations. All these showed a loss of exons 6 and 7 in the mutant transcripts, validating the proposal that a consensus sequence is affected in the exonic mutations and that the integrity of the base at position 1032 is essential for correct processing of the transcript. CONCLUSIONS: The 6 cases already reported in the literature with the 1032 G-->A transition, the novel 1032 G-->C transversion, and a recent G-->T transversion at the same base show that codon 344 is the second most frequently mutated after codon 341, suggesting at least two hotspots for mutations in KCNQ1.

Child, Preschool↗
PubMed1999

Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome.

The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT interval, ventricular arrhythmias, and sudden death. The autosomal recessive form, the Jervell and Lange-Nielsen syndrome, also includes bilateral deafness. In the present study, we report the entire genomic structure of KCNQ1, which consists of 19 exons spanning 400 kb on chromosome 11p15.5. We describe the sequences of exon-intron boundaries and oligonucleotide primers that allow polymerase chain reaction (PCR) amplification of exons from genomic DNA. Two new (CA)n repeat microsatellites were found in introns 10 and 14. The present study provides helpful tools for the linkage analysis and mutation screening of the complete KCNQ1 gene. By use of these tools, five novel mutations were identified in LQTS patients by PCR-single-strand conformational polymorphism (SSCP) analysis in the C-terminal part of KCNQ1: two missense mutations, a 20-bp and 1-bp deletions, and a 1-bp insertion. Such mutations in the C-terminal domain of the gene may be more frequent than previously expected, because this region has not been analyzed so far. This could explain the low percentage of mutations found in large LQTS cohorts.

Base Sequence↗
PubMed1999

Single breath exhaled nitric oxide in lung transplant patients: a preliminary clinical study.

Exhaled nitric oxide is considered as a marker of airway inflammation. We report here our preliminary experience with single-breath exhaled nitric oxide measured in lung transplant patients with and without bronchiolitis obliterans syndrome and in cardiac transplant patients. Peak and end-expiratory nitric oxide concentrations did not differ between groups, but single-breath exhaled nitric oxide recordings were strikingly different in patients suffering from bronchiolitis obliterans syndrome, with a slower decrease from peak to end-expiratory nitric oxide concentration. Further studies are required in order to determine whether theses abnormalities reflect the inflammatory process of bronchiolitis obliterans syndrome.

Adult↗
PubMed1999

Thoracoscopic epicardial radiofrequency ablation for vagal atrial fibrillation in dogs.

Epicardial radiofrequency catheter ablation of the atria in the open-chest dog has been shown to reduce inducibility of atrial fibrillation. Video-assisted endoscopic techniques decrease the operative trauma in adult thoracic surgery. We report our results of video-assisted thoracoscopic radiofrequency catheter ablation of the atria for the prevention of atrial fibrillation induction in canines. In 12 consecutive anesthetized dogs, induction of sustained atrial fibrillation was reproducibly obtained by burst pacing and cervical vagal stimulation. In six dogs, biatrial ablation was performed through right and left minithoracotomies and guided by video-assisted endoscopic techniques. The remaining six dogs underwent a video-guided left atrial procedure. Long continuous and transmural lesions were produced using epicardial temperature controlled radiofrequency energy delivery according to a simplified maze approach. Transmural lesions were demonstrated at the end of the study by examination of the heart. Sustained atrial fibrillation was still inducible after the right atrial ablation but sustained atrial fibrillation could not be induced following left atrial ablation. In acute canine studies: (1) epicardial radiofrequency catheter ablation of the atria is feasible using video-assisted endoscopic techniques; (2) ablation extended or confined to the left atrium appears to be effective in preventing the inducibility of sustained vagal atrial fibrillation; and (3) ablation of the right atrium alone had no antiarrhythmic effect.

Animals↗
PubMed1999

Accuracy and limitations of published algorithms using the twelve-lead electrocardiogram to localize overt atrioventricular accessory pathways.

INTRODUCTION: The purpose of this study was to evaluate the accuracy and limitations of published algorithms using the 12-lead ECG to localize AV accessory pathways (APs). METHODS AND RESULTS: The 11 relevant algorithms found in the literature (MEDLINE database and major scientific sessions) were tested on a series of 266 consecutive patients who successfully underwent radiofrequency catheter ablation of a single overt AV AP. The positive predictive values (PPV) of the algorithms in applicable patients were significantly lower for algorithms with > 6 accessory location sites (40.6% +/- 10.9% vs 61.2% +/- 8.0%; P < 0.03) and show a tendency for algorithms not relying on delta wave polarity but on QRS polarity only (36.6% +/- 11.2% vs 52.3% +/- 13.1%; P = 0.09). The PPV in applicable patients is related to the AP location (P < 0.001) and ranked from the highest to the lowest as follows: left lateral (mean PPV = 86.3%), posteroseptal (mean PPV = 65.2%), right anteroseptal (mean PPV = 45.2%), and right posterolateral (mean PPV = 23.4%). CONCLUSION: Our study suggests that the accuracy of algorithms relying on the 12-lead ECG depends on AP locations as defined in the algorithms and on the number of AP sites. The accuracy tends to be lower when delta wave polarity is not included in the algorithm's architecture. This should be considered when using these algorithms or when building new ones.

Adolescent↗
PubMed1999

Pharmacokinetics of quinupristin-dalfopristin in continuous ambulatory peritoneal dialysis patients.

Quinupristin-dalfopristin may be useful for treatment of organisms causing peritoneal dialysis-related peritonitis, including methicillin-resistant coagulase-negative staphylococci, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. The pharmacokinetic profiles of single intravenous doses of this combination streptogramin antibiotic of 7.5 mg/kg of body weight were characterized for eight noninfected patients receiving continuous ambulatory peritoneal dialysis. Comparison was made to pharmacokinetic profiles determined for eight healthy volunteers matched by age, sex, and race. Drug was measured in dialysate up to 6 h following the dose. Plasma and dialysate were assayed for parent compounds and metabolites. Mean pharmacokinetic parameters were compared between groups. No statistically significant differences were observed between groups for maximal concentrations in plasma, times to maximal concentration, areas under the curve, distribution volumes, rates of total body clearance, or half-lives in plasma for quinupristin and dalfopristin. No statistically significant differences were observed in maximal concentrations in plasma, times to maximal concentration, areas under the curve, or half-lives for cysteine, the glutathione conjugates of quinupristin, or the pristinamycin IIA metabolite of dalfopristin. The measurements in dialysate of the parent and most metabolites were below the expected MICs. Dialysis clearance was insignificant. Quinupristin-dalfopristin was well tolerated in both groups, causing only mild adverse events that resolved prior to discharge from the study. The disposition of quinupristin, dalfopristin, or their primary metabolites following a single dose was unaltered in patients receiving peritoneal dialysis. Intravenous dosing of this antibiotic combination is unlikely to be adequate for the treatment of peritonitis associated with peritoneal dialysis.

Adolescent↗
PubMed1999

[Idiopathic ventricular fibrillation].

In 1 to 8% of survivors of syncopal ventricular fibrillation, it is impossible to identify a structural cardiac abnormality. Idiopathic ventricular fibrillation, a diagnosis of exclusion, is a term which includes a variety of diseases. This article describes several well defined electro-clinical entities: Brugada's syndrome, torsades de pointes with a short coupling interval, catecholinergic polymorphic ventricular tachycardia and the acquired long QT syndrome. In the majority of these cases, despite the fact that their physiopathology is not fully understood, the management is clear-cut. However, in a large number of patients, the choice between pharmacological treatment and the implantation of an automatic defibrillator remains difficult. Molecular biological studies and strict clinical investigation, standardised with the help of networks, should provide a rational approach to the treatment of idiopathic ventricular fibrillation.

Adult↗
PubMed1999

[Stenotrophomonas maltophilia endocarditis following mitral valve prosthesis implantation. Report of a case].

The authors report the first case of early postoperative endocarditis after mitral valvuloplasty due to Stenotrophomonas Maltophilia, a Gram negative organism, in a 37 year old man with no special risk factors. Pyrexia and mitral valve vegetations were the main features, and, in the absence of complications or of embolism, the patient was treated initially with triple antibiotherapy (ceftazidime, amikacine, ciprofloxacine). Relapse two weeks after withdrawal of treatment due to two variants of Stenotrophomas Maltophilia, one of which was resistant to ciprofloxacine, and the presence of a large vegetation, required repeat mitral valvuloplasty and a change in antibiotic therapy (ticarcilline with clavulanic acid, trimethoprim sulphamethoxazole, colistine). This time, the outcome was good. The little known Stenotrophomonas Maltophilia infectious endocarditis is a serious complication and, in the absence of standardised management, the authors suggest that, in view of the multi-resistant character of the organism and in the light of this case, surgery should be considered in association with prolonged antibiotic therapy.

Adult↗
PubMed1999

[Study of the incidence of giardiasis in Quebec (Canada) and association with drinking water source and quality].

BACKGROUND: We analyzed data from the notifiable diseases data base in Québec to document the incidence of giardiasis. The objectives were to perform a descriptive analysis of the cases of giardiasis and to verify the relation between their incidence and the quality of drinking water. METHODS: The Québec notifiable diseases data-base contained 4273 cases of giardiasis declared between January 1st, 1990 and December 31st, 1995. Incidence rates were adjusted for age and calculated monthly. The sources and kinds of treatment of drinking water permitted to elaborate a vulnerability scale for classifying contamination by Giardia sp. into four categories. Incidence of giardiasis was examined in relation with this vulnerability scale. Other socioeconomic indicators possibly associated with the incidence of giardiasis were also analyzed. RESULTS: Analysis showed that there were few annual variations in the incidence of giardiasis and that there were no epidemic peaks during the study period. According to age, the incidence follows a bimodal pattern with a peak for young children and young adults. The incidence rates showed an increase of the cases at the end of summer and at the beginning of fall, with a higher relative risk for males. Even if no relation was found between the incidence of giardiasis and the vulnerability of the drinking water source, incidence rates were lower for people living in communities that use the St. Lawrence River as a drinking water source than for those using other sources of surface water. CONCLUSION: This study allowed us to obtain a good description of the cases of giardiasis declared in Québec and to formulate hypothesis about their causes. The lower incidence of giardiasis in communities that use the St. Lawrence river as their drinking water source is possibly related to a lower contamination of this source. However, considering the limits of this work, case-control studies should be considered to understand variables, which influence the incidence of giardiasis in Québec.

Adolescent↗
PubMed1998

Safety and tolerability of intravenous cibenzoline for acute termination of spontaneous sustained ventricular tachycardia. Cibenzoline and spontaneous VT.

STUDY OBJECTIVES: To evaluate prospectively, the tolerability and safety of intravenous cibenzoline therapy, for the cardioversion of spontaneous monomorphic ventricular tachycardia (VT). SETTING AND PATIENTS: Between February 1990 and December 1996, fifty-eight patients aged 59+/-10 years old (fifty-three males, five females), with spontaneous VT not causing cardiac arrest, received intravenous cibenzoline. Their underlying heart conditions were: ischemic heart disease [35], dilated cardiomyopathy [14], right ventricular dysplasia [3], hypertrophic cardiomyopathy [1], valvulopathy [2], Fallot's Tetralogy [1] and primary arrhythmogenic disease [2]. The left ventricular ejection fraction was 42+/-13% (range 20%-76%). RESULTS: The mean dose of cibenzoline was 70+/-12 mg. The tachycardia stopped within 6+/-3 min in 47 (81%) patients. Side effects from cibenzoline occurred in two patients. The hemodynamic complications were limited to hypotension, that required vasopressor therapy in one patient. The only apparent proarrhythmic effect consisted of an isolated change in the morphology of the VT, that resolved spontaneously on withdrawal of the drug. No mortality occurred at the hospital. CONCLUSION: With appropriate rules for its administration, intravenous cibenzoline has the potential to become one of the first-line antiarrhythmic drugs, to be used for cardioversion of patients with spontaneous VT.

Analysis of Variance↗
PubMed1998

Role of the preaxillary flora in pacemaker infections: a prospective study.

BACKGROUND: Infection remains a severe complication after pacemaker implantation. The purpose of our prospective study was to evaluate the role of the local bacteriologic flora in its occurrence. METHODS AND RESULTS: Specimens were collected at the site of implantation for culture from the skin and the pocket before and after insertion in a consecutive series of patients who underwent elective permanent pacemaker implantation. Microorganisms isolated both at the time of insertion and of any potentially infective complication were compared by using conventional speciation and ribotyping. There were 103 patients (67 men and 36 women) whose age ranged from 16 to 93 years (mean+/-SD, 67+/-15). At the time of pacemaker implantation, a total of 267 isolates were identified. The majority (85%) were staphylococci. During a mean follow-up of 16.5 months (range, 1 to 24), infection occurred in four patients (3.9%). In two of them, an isolate of Staphylococcus schleiferi was recognized by molecular method as identical to the one previously found in the pacemaker pocket. In one patient, Staphylococcus aureus, an organism that was absent at the time of pacemaker insertion, was isolated. In another patient, a Staphylococcus epidermidis was identified both at the time of pacemaker insertion and when erosion occurred; however, their antibiotic resistance profiles were different. CONCLUSIONS: This study strongly supports the hypothesis that pacemaker-related infections are mainly due to local contamination during implantation. S schleiferi appears to play an underestimated role in infectious colonization of implanted biomaterials and should be regarded as an important opportunistic pathogen.

Abscess↗
PubMed1998

Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis.

BACKGROUND: Infection remains a serious complication after permanent pacemaker implantation. Antibiotic prophylaxis is frequently prescribed at the time of insertion to reduce its incidence, although results of well-designed, controlled studies are lacking. METHODS AND RESULTS: We performed a meta-analysis of all available randomized trials to evaluate the effectiveness of antibiotic prophylaxis to reduce infection rates after permanent pacemaker implantation. Reports of trials were identified through a Medline, Embase, Current Contents, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, open or blind trials; (2) patients assigned to a systemic antibiotic group or a control group; (3) end point events related to any infection after pacemaker implantation: wound infection, septicemia, pocket abscess, purulent secretion, right infective endocarditis, inflammatory signs, a positive culture, septic pulmonary embolism, or repeat operation for an infective complication. Seven trials met the inclusion criteria. They included 2023 patients with established permanent pacemaker implantation (new implants or replacements). The incidence of end point events in control groups ranged from 0% to 12%. The meta-analysis suggested a consistent protective effect of antibiotic pretreatment (P=.0046; common odds ratio: 0.256, 95% confidence interval: 0.10 to 0.656). CONCLUSIONS: Results of the present meta-analysis suggest that systemic antibiotic prophylaxis significantly reduces the incidence of potentially serious infective complications after permanent pacemaker implantation. They support the use of prophylactic antibiotics at the time of pacemaker insertion to prevent short-term pocket infection, skin erosion or septicemia.

Adult↗
PubMed1998

Arrhythmic cardiac arrest due to isolated coronary artery spasm: long-term outcome of seven resuscitated patients.

OBJECTIVES: Our aim was to look at the clinical features and long-term follow-up of seven patients without coronary artery disease, who had a history of life-threatening ventricular arrhythmias due to coronary spasm. BACKGROUND: Arrhythmic cardiac arrest due to isolated coronary spasm is rare, and there is limited information on the patients affected by this entity alone. METHODS: The seven patients were recruited retrospectively from a cohort of survivors of cardiac arrest. None had a history of angina pectoris, structural heart disease or significantly narrowed coronary segments. All had a positive ergonovine provocation test result. RESULTS: The patients' mean age was 44 years; three were male and four female. All were habitual cigarette smokers. No arrhythmias were induced on programmed ventricular stimulation; corrected QT interval (QTc) and corrected JT interval (JTc) dispersion were within normal ranges. After the ergonovine provocation test, treatment with calcium channel blocking agents (diltiazem, verapamil, nifedipine or amlodipine) was initiated at a dose determined by titration until a negative test result was obtained. At a mean follow-up interval of 58 months for the total group, six patients remained free of symptoms, whereas the one patient who did not stop smoking had a new cardiac arrest despite treatment for coronary spasm. CONCLUSIONS: A favorable long-term outcome may be expected in survivors of cardiac arrest due to coronary spasm, in the absence of significant coronary artery disease. Calcium channel blockers are the most appropriate therapy in these patients. These observations provide further evidence for the role of silent ischemia in cardiovascular death.

Adult↗
PubMed1998

Immune recovery of malnourished children takes longer than nutritional recovery: implications for treatment and discharge.

Protein-energy malnutrition decreases cellular immunity yet immune recovery has rarely been investigated during nutritional rehabilitation. Malnourished children from low income families of Cochabamba (Bolivia) were hospitalized for 2 months in the Center for Immune and Nutritional Rehabilitation (CRIN), of the German Urquidi Materno-Infantil Hospital. They received a special four-step diet. Nutritional status was determined by a daily clinical examination and weekly anthropometric measurements. Immune status was assessed by weekly ultrasonography of the thymus. The classical criterion for discharge (90 per cent of median reference weight for height) was reached after the first month, whereas a 2-month period was required for complete immunologic recovery. The children belonged to disadvantaged population groups with high exposure to disease. In such an environment, discharge based only on nutritional status after 1 month of treatment could explain frequent relapses because the children were still immunodepressed.

Anthropometry↗
PubMed1998

Interaction between alpha-1 adrenergic and vagal effects on cardiac rate and repolarization.

Alpha-1 adrenergic stimulation modulates ventricular automaticity via an alpha-1 adrenoceptor (AR) subtype blocked by the alpha-1B antagonist chloroethylclonidine (CEC) and alters repolarization via receptor subtype(s) (alpha-1A and alpha-1D) blocked by WB4101. Our objective was to determine alpha-1 AR subtype specific effects and vagal interactions on heart rate and ventricular repolarization. We studied right vagally innervated Langendorff-perfused guinea pig hearts, beta-blocked with propranolol, 5 x 10(-7) M. Heart rate and QT interval were measured from bipolar epicardial electrodes. In some experiments rate corrected QT interval (QTc) (Bazett formula) was calculated, as well. Phenylephrine (PE) alone, 10(-8) M, reduced sinus rate significantly (P < .05) in 8 of 13 preparations. A decrement in rate occurred in all preparations in the presence of WB4101 and was blocked by CEC. Vagal stimulation, at 1 to 20 Hz slowed heart rate (P < .05) in a frequency-dependent fashion. Addition of PE alone or in the presence of WB4101 further reduced rate (P < .05). However, with vagal stimulation + PE + CEC, rate did not differ from that in the presence of vagal stimulation, alone (P > .05). In studies of repolarization, QTc shortening was elicited by PE alone (P < .05) and CEC + PE (P < .05). In the presence of WB4101, no QTc shortening occurred (P > .05). QTc shortening induced by vagal stimulation was attributable to the heart rate change rather than to a direct effect on ventricular repolarization. In conclusion, in the setting of beta adrenergic blockade, an alpha-1B receptor appears responsible for the alpha-1 adrenergic decrease in heart rate and facilitation of vagal responsiveness. A receptor subtype blocked by WB4101 (alpha-1A or alpha-1D) is responsible for the QT and QTc shortening. Whereas right vagal stimulation shortens the QTc interval, this action reflects the change in sinus rate rather than an effect on the ventricle.

Animals↗
PubMed1998

[Infections secondary to implantation of cardiac pacemakers].

Infectious complications of pacemaker implantation are not common but may be particularly severe. Localised wound infections at the site of implantation have been reported in 0.5% of cases in the most recent series with an average of about 2%. The incidence of septicaemia and infectious endocarditis is lower, about 0.5% of cases. The operator's experience, the duration of the procedure and repeat procedures are considered to be predisposing factors. The main cause of these infections is though to be local contamination during the implantation. The commonest causal organism is the staphylococcus (75 to 92%), the staphylococcus aureus being the cause of acute infections whereas the staphylococcus epidermis is associated with cases of secondary infection. The usual clinical presentation is infection at the site of the pacemaker but other forms such as abscess, endocarditis, rejection of the implanted material, septic emboli and septic phlebitis have been described. The diagnosis is confirmed by local and systemic biological investigations and by echocardiography (especially transoesophageal echocardiography) in cases of right heart endocarditis. There are two axes of treatment: bactericidal double antibiotherapy and surgical ablation of the infected material either percutaneously or by cardiotomy. Though controversial, and unsupported by scientific evidence, the role of systematic, preoperative, prophylactic antibiotic therapy in the prevention of these complications seems to be increasing.

Abscess↗
PubMed1998

[QT interval and drugs. Recommendation for drug prescription for patients with long QT syndrome. Clinical Research Group of INSERM 4940 12: Diagnostic Clinic of Congenital Long QT Syndrome].

The genetics of the long QT syndrome are now better understood. However, there is much heterogeneity as three different genes have already been identified affecting the function of sodium and potassium channels. The aim of these recommendations is to draw up a list of drugs which are contraindicated or not recommended in patients with congenital long QT syndromes. The conraindicated drugs are those with which torsades de pointe have already been described. Drugs not recommended are substances which are not electrohysiologically neutral and for which, in view of their modes of action, their metabolism or belonging to a particular therapeutic class, make them very difficult to use in those patients. It is therefore better not to prescribe them whenever possible in this condition. These substances belong mainly to cardiovascular (especially antiarrhythmic), psychotropic, anti-infectious and antiallergic groups of drugs.

Anti-Allergic Agents↗