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Biomedical subjects

P Chevalier

Publications and source records attributed to P Chevalier.

At least 19 recordsLinked to original sources

[Voriconazole photosensitivity: 7 cases].

BACKGROUND: Voriconazole is a new second-generation fluconazole-derived triazole. With greater potency against susceptible species and a broader spectrum of activity than fluconazole, it is the treatment of choice for invasive pulmonary aspergillosis and other fungal infections (Fusarium, Scedosporium/Pseudalleschezria) is indicated in a visit Candida infections refractory to fluconazole. We describe 7 cases of photosensitivity during treatment with voriconazole in a setting of immunodepression. CASE REPORTS: The patients comprised 5 women and 2 men with a mean age of 38 years (17-67 years). Five had undergone pulmonary transplantation for mucoviscidosis, one had undergone kidney transplantation for lupus nephroangiosclerosis and one was on long-term systemic steroid treatment for Sjögren's syndrome. All patients had very severe immunosuppression and were receiving voriconazole for pulmonary aspergillosis (6 cases) or Scedosporium infection (1 case). Photosensitization appeared within 5 weeks to 14 months after the start of treatment, and in all cases followed exposure to sun, occasionally at low levels. In all cases, cutaneous lesions rapidly disappeared on discontinuation of treatment. DISCUSSION: There have been reports in the literature, although rare, of photosensitivity with voriconazole. Patients must be informed of the possibility of this adverse effect and sun protection must be recommended when voriconazole is prescribed, particularly during periods of intensive exposure.

Adolescent↗

Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.

Long QT syndrome (LQTS) is a rare and clinically heterogeneous inherited disorder characterized by a long QT interval on the electrocardiogram, increased risk of syncope and sudden death caused by arrhythmias. This syndrome is mostly caused by mutations in genes encoding various cardiac ion channels. The clinical heterogeneity is usually attributed to variable penetrance. One of the reasons for this variability in expression could be the coexistence of common single nucleotide polymorphisms (SNPs) on LQTS-causing genes and/or unknown genes. Some synonymous and nonsynonymous exonic SNPs identified in LQTS-causing genes may have an effect on the cardiac repolarization process and modulate the clinical expression of a latent LQTS pathogenic mutation. We report the molecular pattern of 44 unrelated patients with LQTS using denaturing high-performance liquid chromatography analysis of the KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes. Forty-five disease-causing mutations (including 24 novel ones) were identified in this cohort. Most of our patients (84%) showed complex molecular pattern with one mutation (and even two for four patients) associated with several SNPs located in several LQTS genes.

Adolescent↗

[Long QT syndrome in children: analysis of the Lyon series].

Congenital long QT syndrome is a rare and serious disorder in children. In addition to the clinical and electrocardiographical diagnostic criteria, molecular biochemistry has identified six genes which are implicated in this pathology. Our study involved a retrospective analysis of 23 patients aged less than 21 with congenital long QT syndrome, followed up for an average of two years. Genotypes were obtained for all of the patients. There were unfortunately two deaths, one of which had a mutation in the SCN5A gene. The other patient had a double mutation of the SCN5A and KCNE2 genes. Symptomatic patients had QT and QTc intervals noticeably longer than the asymptomatic patients, although this difference was not shown to be significant. LQT3 patients as well as those with a double mutation were affected more severely because two of the three LQT3 patients and one of the two patients with a double mutation suffered a cardiac arrest. Three patients in our study showed no mutation. Nevertheless, two of them suffered a severe cardiac event. This confirms the limits of genetic diagnosis, which could be envisaged in all cases. All of the clinical and ECG data should be combined with the genetic analysis in order to confirm the diagnosis.

Adolescent↗

[Systemic validation of clinical practice guidelines: the AGREE network].

INTRODUCTION: Over recent decades, the number of available clinical practice guidelines has enormously grown. Guidelines should meet specific quality criteria to ensure good quality. There is a growing need for the developement of a set of criteria to ensure that potential biases inherent in guideline development have been properly addressed and that the recommendations for practice are valid and reliable. AIM: The AGREE-collaboration is an international network that developed an instrument to critically appraise the methodological quality of guidelines. AGREE promotes a clear strategy to produce, disseminate and evaluate guidelines of high quality. METHOD: In the first phase of the international project the AGREE-instrument was tested in 11 different countries. Based on this experience the instrument was refined and optimised. In the second phase it was disseminated, promoted and evaluated in 18 participating countries. Belgium was one of them. RESULTS: The Belgian partner in the AGREE-project developed 3 workshops and established 13 validation committees to validate guidelines from Belgian developer groups. We collected 33 questionnaires from participants of the workshops and the validation committees, in which we asked for primary experiences and information on the usefulness and applicability of the instrument. We were also interested in the shortcomings of the instrument and potential strategies to bridge them. DISCUSSION: More efforts should be made to train methodological experts to gain certain skills for a critical appraisal of clinical practice guidelines. Promoting the AGREE-instrument will lead to a broader knowledge and use of quality criteria in guideline development and appraisal. CONCLUSION: The development and dissemination of an international list of criteria to appraise the quality of guidelines will stimulate the development of methodologically sound guidelines. International comparisons between existing guidelines will lead to a better collaboration between guideline developers throughout the world.

Canada↗

[EBM: otitis media in children: how to formulate a PICO question].

This series of articles begins with a problem frequently encountered in children: acute otitis media. Under the insistence of parents, antibiotics are frequently prescribed. The physician knows that the value of that therapy is debatable, but what for a child of 6 years of age? The physician whishes to compare his/her opinion with what is published in the litterature or available on the web. How to start his/her research? In this first article the physician will find out how to translate his/her practical question into a question which leads to a practical answer, and then to a PICO question. This will allow the physician to find sources of directly usable and relevant data which will offer a rational and wellfounded answer to his/her clinical question.

Child↗

Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia.

BACKGROUND: Sudden death is a possible consequence of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Prevalence of ARVC/D in unexpected sudden cardiac death (USCD), however, remains imprecise, as do circumstances of death and ARVC/D-associated gross and microscopic findings, especially His bundle anomalies. METHODS AND RESULTS: We reviewed 14 000 forensic autopsies required by judicial authorities from January 1980 to January 1999 in a 2 000 000-resident area. Age, gender, and circumstances of death were recorded. Hearts were examined macroscopically and microscopically. In this series, the ARVC/D group accounted for 200 consecutive cases (10.4%) of USCD, including 108 males and 92 females (average age 32.5 and 34.5 years, respectively). Nearly one third of deaths occurred during the fourth decade of life. Circumstances of death were various, but 75.6% occurred during everyday life events (at home, 63.1%; in the street, 6.6%; or at work, 6.1%); only 7 cases (3.5%) occurred during sports activity. Nineteen cases (9.5%) happened during the perioperative period. Adipose infiltration of the right ventricle was either isolated (20%) or associated with fibrosis (74.5%) and lymphocytes (5.5%). A total of 14.5% of cases had cardiac hypertrophy, assessed by an increase in heart weight and/or left ventricular wall thickness. In most cases, the His bundle and its branches were abnormal either because of infiltration of adipose tissue (8.1%), fibrosis (54.3%), or both (5.6%). CONCLUSIONS: In ARVC/D, both sexes are equally affected, and there is a peak of risk during the fourth decade. Death most frequently occurs during sedentary activity. His abnormalities and left ventricular hypertrophy may be associated with ARVC/D.

Adolescent↗

Bridge to transplantation with the DeBakey VAD axial pump: a single center report.

AIMS: To report our experience with a left ventricular assist device axial pump as a bridge to transplantation: the DeBakey Ventricular Assist Device (VAD). METHODS: From February 1999 to February 2002, nine patients (among which eight males), with a mean age of 47 years, all in NYHA functional class IV, were proposed for a bridge to transplantation with the DeBakey VAD. Five patients had primary dilated cardiomyopathy, four had ischemic cardiomyopathy. All the patients had inotropic support prior to the intervention (dobutamine with a mean dose of 12 mcg/kg per min), six had an intra-aortic counterpulsation, four presented ventricular rhythm disorders. Interventions were performed through sternotomy alone (no need for an abdominal pocket) under extra-corporeal circulation on beating heart (except in one patient suffering from an apical thrombosis for which cardioplegic arrest was performed) as followed: implantation of the apical inflow cannula, tunneling of the percutaneous cable, implantation of the outflow graft under aortic side clamping, starting of the DeBakey VAD during CPB weaning-off. RESULTS: Mean support duration was 81+/-62 days (16-224 days). Eight reoperations were required (three for bleeding or cardiac tamponade, one for haemoperitoneum, one for aortic bifurcation thrombectomy, one for right ventricular assist device implantation, two for iterative replacements of the DeBakey VAD). A significant hemolysis was observed in two patients. No device infection or dysfunction were observed. Secondary recovery of a pulsed flow was observed either clinically or by Echo-Doppler in six patients. Five patients were transplanted, four died prior to transplantation (three from multi-organ failure on post-operative day 35, 16 and 50, respectively, and the last patient was found disconnected at day 109). CONCLUSIONS: The DeBakey VAD is at the origin of renewed interest for continuous flow assist devices. Still under evaluation, the advantages of miniaturization and facility of implantation of this new device seem to be promising.

Adult↗

[Humanitarian action: its requirements, its stakes].

Humanitarian action is developing in an increasingly changing and troubled world context. Organizations are subject to more and more complex requirements due to ethical, legal, technical, financial, media-related, and political considerations. They must deal with higher and higher stakes such as the emergency-development trade-off, the need for professionalization, and the revival of governmental humanitarian action. The articles in this special issue deal with all these topics and more. In most cases the authors are players in the field of humanitarian action from non-governmental, intergovernmental, international and national organizations. There are also academics, politicians, and civilians.

Altruism↗

Non-invasive testing of acquired long QT syndrome: evidence for multiple arrhythmogenic substrates.

BACKGROUND: Although well-defined clinically and electrocardiographically, Acquired Long QT Syndrome (LQTS) remains elusive from a pathophysiologic point of view. An increasingly accepted hypothesis is that it represents an attenuated form of Congenital Long QT Syndrome. To test this hypothesis further, we investigated patients with Acquired LQTS, using various investigations that are known to give information in patients with Congenital LQTS. METHODS: All the investigations were performed in patients with a history of Acquired Long QT Syndrome, defined by marked transient QT lengthening (QT>600 ms) and/or torsades de pointes. Measurement of the QT interval dispersion, the interlead difference for the QT interval on a 12-lead ECG, was performed in 18 patients and compared with 18 controls, matched for age and sex. To assess sympathetic myocardial innervation, I-123 Meta-iodobenzylguanidine (I-123-MIBG) scintigraphy was performed in 12 patients, together with Thallium scintigraphy, to rule out abnormal myocardial perfusion. Time-frequency analysis of a high-resolution ECG using a wavelet technique, was made for nine patients and compared with 38 healthy controls. Finally, genetic studies were performed prospectively in 16 consecutive patients, to look for HERG, KCNE1, KCNE2 and KCNQ1 mutations. The functional profile of a mutated HERG protein was performed using the patch-clamp technique. RESULTS: Compared with the control group, a significant increase in QT dispersion was observed in the patients with a history of Acquired LQTS (55+/-15 vs. 33+/-9 ms, P<0.001). In another group of patients with Acquired LQTS, 123 I-MIBG tomoscintigraphy demonstrated a decrease in the sympathetic myocardial innervation. Time--frequency analysis using wavelet transform, demonstrated an abnormal frequency content within the QRS complexes, in the patients with Acquired LQTS, similar to that found in Congenital LQTS patients. Molecular screening in 16 consecutive patients, identified one patient with a missense mutation on HERG, one of the LQTS genes. Expression of the mutated HERG protein led to altered K(+) channel function. CONCLUSION: Our results suggest that Acquired and Congenital Long QT Syndromes have some common features. They allow the mechanism of the clinical heterogeneity, found in both syndromes, to be understood. Further multi-facet approaches are needed to decipher the complex interplay between the main determinants of these arrhythmogenic diseases.

Aged↗

Influence of atrial flutter ablation on right to left inter-atrial conduction.

AIMS: Ablation of the atrial isthmus between the tricuspid annulus and the inferior vena cava changes P-wave morphology during low lateral right atrial pacing. For better understanding of the mechanism of this alteration, the sequence of activation of the inter-atrial septum and the left atrium were compared before and after ablation of the isthmus between the inferior vena cava and the tricuspid annulus. METHODS AND RESULTS: In 13 patients, left atrial mapping was performed using a duodecapolar electrode catheter advanced to the far distal coronary sinus. The inter-atrial septum was mapped using a right atrial duodecapolar electrode catheter. Conduction times were measured during low lateral right atrial pacing from the pacing artefact and during sinus rhythm from the earliest right atrial electrogram to every intra-cardiac electrogram before and after the ablation. During low lateral right atrial pacing, isthmus ablation resulted in a significant delay in every left atrial lead. Changes were maximal at the posterior aspect of the left atrium and minimal at its anterior aspect. No significant change was discernible on the inter-atrial septum. During sinus rhythm, atrial activations remained unchanged. CONCLUSION: Electrocardiographic changes of P-wave morphology result from alteration in the sequence of left atrial activation rather than that of the inter-atrial septum.

Atrial Flutter↗

Multiple-dose pharmacokinetics and safety of two regimens of quinupristin/dalfopristin (Synercid) in healthy volunteers.

Quinupristin/dalfopristin (Q/D) is a novel streptogramin antibiotic for the treatment of severe gram-positive infections. The purpose of this open, nonrandomized, parallel-group, phase I trial was to evaluate Q/D pharmacokinetics after single and repeated doses under the two different dosing regimens corresponding to the effective doses and to evaluate tolerability. Two groups of 10 healthy volunteers received multiple 1-hour intravenous infusions of 7.5 mg/kg Q/D either every 8 or 12 hours for 4 or 5 days, respectively. Plasma concentrations of Q, D, and metabolites were determined using high-performance liquid chromatography and selective microbiological assays. The two regimens q8h and q12h lead to the same disposition profile after single and repeated administration. Single-dose data confirmed the high plasma clearances of Q and D (about 0.90 l/h/kg) obtained previously. Unchanged drugs were the main components in plasma, with each of the three metabolites representing about 20% (in terms of the AUC ratio) of the parent drugs. Comparable steady-state concentrations were reached from day 2 of both regimens. A similar moderate increase in Cmax and AUC (about 20%) of parent drugs was observed between the first and last day of treatment. This phenomenon, which was also observed for the metabolites, was not expected considering the short terminal disposition half-lives of the parent drugs and trough plasma concentrations of all components mostly below the limits of quantitation at steady state, whatever the dosing regimen. The clearances of parent drugs at steady state were about 20% lower as compared with that observed following the first drug administration (statistically significant difference). No trend suggesting a treatment effect on any laboratory parameter, vital signs, or electrocardiographic parameters was identified. However, 80% of subjects reported venous adverse events probably related to treatment.

Adolescent↗

Serum cardiac troponin I and ST-segment elevation in patients with acute pericarditis.

OBJECTIVE: ST-segment elevation in acute pericarditis is believed to be caused by superficial myocardial inflammation or epicardial injury. We used cardiac troponin I, a sensitive and specific marker of myocardial injury, to assess myocardial lesions in idiopathic acute pericarditis and its relationship to ST-segment elevation. PATIENTS AND METHODS: Sixty-nine consecutive patients (53 men, 48+/-17 years) with idiopathic acute pericarditis were included. We used an enzymoimmunoflurometric method to measure serum cardiac troponin I on admission (myocardial infarction threshold was 1.5 ng. ml(-1)). RESULTS: Cardiac troponin I was detectable in 34 patients (49%) and was beyond the 1.5 ng. ml(-1)threshold in 15 (22%). Coronary angiography performed in seven of these 15 patients was normal in all of them. ST-segment elevation was observed in 93% of the patients with cardiac troponin I >1.5 ng. ml(-1)vs 57% of those without (P<0.01). Sensitivity of ST-segment elevation to detect myocardial injury was 93% and specificity 43%. Patients with a cardiac troponin I increase higher than 1.5 ng. ml(-1)were more likely to have had a recent infection (66% vs 31%;P=0.01) and were younger (37+/-14 vs 52+/-16 years;P=0.002). There was no significant relationship with other parameters such as pericardial friction rub, fever, PR segment abnormalities, echocardiographic findings or C-reactive protein. CONCLUSION: In patients with idiopathic acute pericarditis, an increase in cardiac troponin I is frequently observed, especially in younger patients and those with a recent infection. Although ST-segment elevation does not reliably indicate myocardial injury, a significant cardiac troponin I increase is only seen in these patients.

Acute Disease↗

Identification of post-myocardial infarction patients prone to ventricular tachycardia using time-frequency analysis of QRS and ST segments.

BACKGROUND: Late potentials (LPs) in the terminal portion of the QRS complex are commonly sought to identify post-myocardial infarction patients prone to ventricular tachyarrthythmias (VT) or sudden death. More recent time frequency signal processing tools have been shown to provide new parameters for the quantification of LPs and abnormal activities buried within the QRS complex. METHODS AND RESULTS: The study population comprised 23 myocardial infarction patients with documented sustained VT (MI+VT), 40 myocardial infarction patients without VT (MI - VT) and 31 normal subjects. The reproducibility of the method was tested in an additional set of 66 patients. The signal-averaged high-resolution electrocardiograms (HRECGs) were quantified by deconstructing the unfiltered X, Y and Z leads using a 511-orthogonal wavelet network. Using receiver operating characteristics (ROC) curves and discriminant analysis applied to the wavelet coefficients, we extracted the most significant wavelets to classify the post MI patients. These wavelets detected time-frequency alterations both in the ST segment and within the QRS complex, characterizing patients prone to VTs. The same statistical methods were applied to the conventional time-domain measurements. The combined application in our population of the orthogonal wavelet deconstruction method and discriminant analysis had 91% sensitivity and 95% specificity, an improvement of 22% and 25%, respectively, compared with the conventional time domain method. Reproducibility was 82%. CONCLUSIONS: In post-myocardial infarction patients, orthogonal wavelet transforms can detect alterations in high-frequency components within the QRS and ST segment. Our findings support the view that wavelet-related parameters are more relevant than those of the time domain method in predicting subsequent malignant tachyarrhythmias.

Adult↗

Pharmacokinetics of quinupristin/ dalfopristin in patients with severe chronic renal insufficiency.

OBJECTIVE: To compare the pharmacokinetic profile of a single intravenous injection of quinupristin/dalfopristin, a new injectable streptogramin, in healthy young individuals and patients with severe chronic renal insufficiency. A secondary objective was to assess the relative tolerability of this dose in these patients compared with healthy individuals. PATIENTS AND PARTICIPANTS: 13 patients with severe chronic renal insufficiency (creatinine clearance 6 to 28 ml/min/1.73m2) were individually matched for gender, bodyweight and age to a healthy volunteer. METHODS: Participants received a single dose of quinupristin/dalfopristin 7.5 mg/kg bodyweight as a continuous 1-hour intravenous infusion, followed by serial blood sampling. RESULTS: The disposition profile of unchanged quinupristin was similar in the 2 groups. However, the elimination of quinupristin derivatives in patients with renal impairment tended to be decreased: mean peak plasma drug concentration (Cmax) and area under the concentration-time curve from zero to infinity (AUCinfinity) of quinupristin plus its active derivatives were about 1.4 times higher in the patients with renal impairment compared with healthy volunteers. The mean Cmax and AUCinfinity of both unchanged dalfopristin and dalfopristin plus its active derivatives were about 1.3 times higher in renally impaired patients than in healthy volunteers. Adverse events were generally mild and transient. No severe or serious adverse events were reported and no participants prematurely discontinued the study. Venous tolerability tended to be better in healthy volunteers than in the patients with renal impairment. CONCLUSION: These results suggest that no formal reduction in the dosage of quinupristin/dalfopristin is necessary in patients with severe chronic renal impairment.

Adult↗

[Ocular manifestations associated with vitamin A deficiency in a rural area of Burkina Faso].

Vitamin A deficiency can cause nyctalopia, hemeralopia, xerophthalmia, and even blindness. Studies have demonstrated the extent of this problem in various regions of Burkina Faso but extrapolation of these findings to other countries is difficult because of methodological problems. In the initial phase of study, signs of hemeralopia were noted in 14 of 466 children between the ages of 6 and 14, indicating an incidence of 3 p. 100 in this age group. In the second phase, examination of 281 subjects of all ages from 30 randomly selected families in the same village indicated that the incidence of hemeralopia was 3.9 p. 100 (6 p. 100 in children between 2 and 5 years old). Clinical examination demonstrated evidence of xerophthalmia in 7 p. 100 of subjects. The incidence fell to 50 p. 100 after the mango season and to 0 p. 100 after administration of 200,000 IU of vitamin A. Of the 8 cases of blindness observed in this study, 5 were due to onchocerciasis and 2 to vitamin A deficiency. These findings document the role of vitamin A deficiency in the occurrence of severe ocular manifestations in Burkina Faso and underline the need for preventive action.

Adolescent↗

Gated blood-pool SPECT evaluation of changes after radiofrequency catheter ablation of accessory pathways: evidence for persistent ventricular preexcitation despite successful therapy.

OBJECTIVES: This study was designed to prospectively evaluate the effects of radiofrequency ablation in Wolff-Parkinson-White (WPW) syndrome by scintigraphic analysis. BACKGROUND: The functional changes triggered by radiofrequency current ablation of atrioventricular accessory pathways are not fully known. METHODS: Forty-four patients with WPW syndrome were consecutively investigated before and 48 h after radiofrequency therapy. Fourteen patients had right sided atrioventricular pathways and 30 patients had left sided bypass-tracts. Planar gated imaging and gated blood pool tomography were performed in all of these patients. RESULTS: A significant increase in the left ventricular ejection fraction (LVEF) was demonstrated in patients with left preexcitation (62.2+/-7.9% before ablation against 64.4+/-6.3% after ablation, p = 0.02) but not for those with right sided anomalous pathway. Phase analysis only gave significant differences following ablation of right sided pathways (left-to-right phase difference = 14.4+/-13.8 degrees before ablation versus 7.5+/-7.2 degrees after ablation, p<0.05). Early abnormal ventricular contraction persisted in 12 patients with right accessory pathways and in 8 patients with left accessory pathways despite the complete disappearance of any abnormal conduction as proven electrophysiologically. CONCLUSIONS: Following catheter ablation of atrioventricular accessory pathways: 1) an improvement of left ventricular function may be seen, particularly in patients with left sided accessory pathways, and 2) unexpected persistence of local ventricular preexcitation at the site of successful ablation may be detected.

Adult↗