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Biomedical subjects

G Fontaine

Publications and source records attributed to G Fontaine.

At least 19 recordsLinked to original sources
PubMed1992

Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences.

Ornithine delta-aminotransferase is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the reversible interconversion of ornithine and alpha-ketoglutarate to glutamate semialdehyde and glutamate. Inherited deficiency of ornithine delta-aminotransferase results in ornithine accumulation and a characteristic chorioretinal degeneration, gyrate atrophy of the choroid and retina. We have surveyed the ornithine delta-aminotransferase genes of gyrate atrophy patients for mutations. Using a variety of techniques, we discovered and molecularly characterized 21 newly recognized ornithine delta-aminotransferase alleles. We determined the consequences of these and three previously described mutations on ornithine delta-aminotransferase mRNA, antigen, and enzyme activity in cultured fibroblasts. The majority (20/24) of these alleles produce normal amounts of normally sized ornithine delta-aminotransferase mRNA. By contrast, only 2/24 had normal amounts of ornithine delta-aminotransferase antigen. Reproducing these mutations by site-directed mutagenesis and expressing the mutant ornithine delta-aminotransferase in Chinese hamster ovary cells confirms that several of these mutations inactivate ornithine delta-aminotransferase and cause gyrate atrophy in these patients.

Alleles↗
PubMed1992

Strand-separating conformational polymorphism analysis: efficacy of detection of point mutations in the human ornithine delta-aminotransferase gene.

We tested the use of a modified method of single-strand conformational polymorphism (SSCP) analysis for the detection of point mutations in the human ornithine-delta-aminotransferase gene. Using a combination of three different electrophoretic conditions, we detected 20/20 known mutations. In a prospective study of 24 previously uncharacterized mutant OAT genes, we found 13 different mutations accounting for 19 (79%) of the 24. We conclude that SSCP is an efficient technique with high sensitivity and specificity.

Base Sequence↗
PubMed1992

Comparison of DDD and 'VVI-R like' pacing during moderate exercise: echo-Doppler study.

The non-invasive haemodynamic comparisons of DDD and 'VVI-R like' pacing at rest and during moderate exercise by echo Doppler are reported. Twelve patients (six males, six females, mean age 48.2 years) with a dual chamber pacemaker were submitted to a series of two exercise tests in a semi-supine position, the first test in DDD mode and the second test in a 'VVI-R like' mode: VVT mode, during which pacing rate was externally increased by chest wall stimulation. During the second test, the workload profile was matched to that of the first test (66 watts and same exercise stages) and ventricular pacing rate was incremented via chest wall stimulation and reproduced exactly the heart rate profile of the first test in DDD mode. The heart rate averaged 81 beats.min-1 at rest and reached 116 beats.min-1 during exercise. At rest and throughout exercise tests, aortic blood flow velocity spectra were continuously recorded on video tape and analysed with the calculation program of the echocardiograph. At rest, ejection time, flow velocity integral, flow acceleration and stroke volume differed between DDD and 'VVI-R like' mode while other parameters did not. During exercise all but two parameters differed. DDD mode especially was associated with a larger stroke volume (81.9 vs 70.9 ml; P less than 0.001) and cardiac output (9.24 vs 8.011.min-1; P less than 0.001) than VVI-R mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Factors predicting success in DC catheter ablation of accessory pathways.

In a series of 33 patients with accessory pathways, 26 had successful catheter ablation (fulguration [23 patients] or modification [3 patients]) of their accessory pathway conduction, and could be considered as a clinical success. One hundred thirteen single discharge or double discharge shocks were delivered, and each shock was studied to reveal which parameters were important to predict the success or failure of catheter ablation. Double discharge shocks resulted in successful accessory pathway modification or ablation twice as often as single discharge shocks (32% vs 16%). This effect was more pronounced in left lateral accessory pathways (48% vs 4%). Shocks in the electrophysiologically defined ventricular zone were more likely to be successful (33%) than shocks delivered in the atrial zone (14%), irrespective of accessory pathway location. The presence of a probable Kent potential was the parameter most strongly associated with success. The parameter most strongly associated with failure, with a 100% negative predictive value, was the absence of earliest activation recorded on the ablating catheter prior to shock delivery. An AV interval of < 60 msec significantly divided the successful from the unsuccessful shocks (P = 0.01). The VA interval during orthodromic reciprocating tachycardia or right ventricular stimulation did not allow for significant division into successful and unsuccessful attempts in this relatively short series. VA intervals, when longer, were predictive of failure but, when shorter, had low positive predictive value. Mean follow-up in 25 successful patients was 15 +/- 6 months. All patients did well in the follow-up period. Neither those patients with ablation nor modification of the accessory pathway had recurrent episodes of tachycardia or required pharmacological treatment for control of arrhythmias.

Adult↗
PubMed1992

[Right ventricular dysplasia].

Arrhythmogenic right ventricular dysplasia is responsible for ventricular tachycardia affecting an apparently healthy heart. It can sometimes lead to sudden death, which may be the presenting symptomatology of the disease. It results from fibro-adipose infiltration of the free wall of the right ventricle, and sometimes of the septum, possibly secondary to myocarditis. The prognosis depends upon the quality of the left ventricle. If it is healthy, the only risk is that of arrhythmia. Treatment using anti-arrhythmic drugs is most often effective and, with proper management, the prognosis is good and the risk of sudden death eliminated. If the left ventricle is abnormal, there is the risk that dysplasia associated with arrhythmia will progress to right then congestive cardiac failure in the context of a dilated idiopathic cardiomyopathy with ventricular tachycardias originating on the right side. Arrhythmogenic right ventricular dysplasia is a notable cause of sudden death in athletes. Routine screening of such individuals is justified, as is that of those with high risk occupations (locomotive and vehicle drivers, etc.).

Adolescent↗
PubMed1992

[Ventricular anti-arrhythmic treatments during postinfarction].

Antiarrhythmic agents may be prescribed in the post-infarction period either as systematic therapy to prevent sudden death or as prophylactic treatment against recurrences of documented life-threatening arrhythmias. Systematic therapy or even the treatment of symptomatic ventricular extrasystoles by Class IC anti-arrhythmics is associated with an increased risk, especially in patients with a low risk of sudden death at the outset. Betablockers are effective on symptoms: they are not always effective on the arrhythmia but at least they do not aggravate the mortality of these patients. However, for high risk patients with post-infarction left ventricular dysfunction, betablockers are the only drugs which have a proven efficacy: they should therefore be prescribed, especially those whose efficacy has been demonstrated, at the same dosages as those used in clinical trials. Preventive treatment of sustained ventricular tachycardia should be chosen with respect to the patient's hemodynamic status. When the ejection fraction is under 40%, amiodarone and betablockers are the drugs of first intention, with controls of their efficacy by the inability to induce or the slowing of the tachycardia rhythm during endocavitary electrophysiological studies.

Adrenergic beta-Antagonists↗
PubMed1992

[Experimental study of fulguration on a healthy ventricle. I. Acute lesions].

The effect of fulguration shocks applied to the healthy ventricular myocardium in 6 pigs weighing between 63 and 100 kg showed that for shocks with the same energy level as those used in clinical practice, the immediate effects of fulguration result in a hemorrhagic zone with a diameter of up to 15 mm. Histopathological examination revealed tearing of the cardiomyocytes which is probably related to barotraumatic phenomena. Deflagrating shocks of 90 Joules, with a short development time (non-self-inductive circuit) can lead to perforation of the myocardium in both the right and left ventricles. In this animal model, arrhythmia was rare and did not lead to sudden death in any case. No vascular damage was observed.

Acute Disease↗
PubMed1992

[Experimental study of fulguration of healthy ventricle. II. Chronic lesions].

The effect of fulguration shocks was studied using healthy ventricular myocardium of 12 pigs weighing between 63 and 100 kg. With shocks of equal energy to those used clinically, lesions seen 24 hours after the session in two pigs showed the formation of loose fibrosis and of marked cellular infiltration as well as zones of hypercontraction with calcium precipitation. The size of chronic lesions seen during periods ranging from one week to 2 months was studied in 4 pigs. Transmural plaques with a diameter of 1.5 to 2 cm were seen in the right ventricle. For the same energy levels of 240 Joules delivered to left ventricular tissue, lesions were of the same size but were never transmural. Under certain conditions, lesions were disposed in the direction of the neutral electrode.

Acute Disease↗
PubMed1991

Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation.

In studies of mutations causing deficiency of ornithine delta-aminotransferase (EC 2.6.1.13), we found an allele whose mature mRNA has a 142-nucleotide insertion at the junction of sequences from exons 3 and 4. The insert derives from an Alu element in ornithine delta-aminotransferase intron 3 oriented in the direction opposite to transcription (an "antisense Alu"). A guanine----cytosine transversion creates a donor splice site in this Alu, activating a cryptic acceptor splice site at its 5' end and causing splice-mediated insertion of an Alu fragment into the mature ornithine-delta-aminotransferase mRNA. We note that the complement of the Alu consensus sequence has at least two cryptic acceptor sites and several potential donor sequences and predict that similar mutations will be found in other genes.

Amino Acid Sequence↗
PubMed1991

Predictors of in-hospital mortality after DC catheter ablation of atrioventricular junction. Results of a prospective, international, multicenter study.

BACKGROUND: The Catheter Ablation Registry was the first international, multicenter, prospective study of the safety and efficacy of catheter ablation. METHODS AND RESULTS: From August 1987 through March 1990, the study comprised 136 patients in whom only DC energy was used in attempted production of third-degree atrioventricular block to treat uncontrollable supraventricular tachycardias. Eight patients died during hospitalization for ablation. In seven (5.1%), the ablation may have contributed to their deaths. Causes of death included ventricular fibrillation (five patients, three with polymorphic ventricular tachycardia), progressive heart failure (one patient), and respiratory failure (two patients, one dying after resuscitation from ventricular fibrillation). Compared with survivors, patients who died were more likely to have had prior aborted sudden death (38% versus 2%, p less than 0.05), congestive heart failure (88% versus 22%, p less than 0.001), cardiomyopathy (50% versus 16%, p less than 0.05), lower baseline systolic blood pressure (106 versus 138 mm Hg, p less than 0.001), prolonged baseline and postablation corrected QT interval (p less than 0.01), and markedly reduced ejection fraction (27% versus 52%, p less than 0.001). Ablation successfully produced third-degree atrioventricular block in 88% of the patients who died and in 83% of survivors. CONCLUSIONS: Catheter ablation of the atrioventricular junction with DC energy carries a significant, previously unrecognized risk of death (5.1%), particularly from lethal arrhythmias, when applied to patients with severe left ventricular dysfunction. Great care should be taken in these seriously ill patients to guard against postablation ventricular arrhythmias.

Bundle of His↗
PubMed1991

[The role of Holter monitoring and electrophysiological studies in the evaluation of ventricular anti-arrhythmia agents].

The roles of Holter monitoring and electrophysiological studies (EPS) in the evaluation of antiarrhythmic drugs for ventricular arrhythmias are to record their effects on ventricular extrasystoles (VES) and ventricular tachycardia (VT), and to search for undesirable rhythmological effects. The usual protocol is to perform baseline studies and then repeat them after a certain period of treatment using a number of modalities, comparison with placebo, control group, in acute or oral administration. Holter monitoring is an economical non-invasive method which carries no risk. Spontaneous arrhythmias of sufficient frequency to be recorded during the monitoring period can be studied. When applied to VES, it provides quantitative rather than qualitative information despite classifications such as Lown's. The results should be analysed taking spontaneous variations of the arrhythmia into consideration. Holter monitoring may also reveal proarrhythmic drug effects (bradycardia, torsades de pointe). However, there are no absolute criteria of efficacy except total suppression of VES, unexplainable by spontaneous variability. Holter antiarrhythmic studies require stable VES which creates a bias in the evaluation of results due to the special selection of patients. Electrophysiological studies are costly, invasive and uncomfortable but they are the only way of assessing paroxysmal VT apart from clinical follow-up. This method is only applicable to inducible VT, which is the commonest form. The investigating protocols are specific and reproducible: a tachycardia which is non-inducible does not recur in 90% of cases, which enables prediction of the antiarrhythmic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1991

[Physical and biophysical aspects of high energy intracardial electrical discharges. 4. Effects of fulguration beads in an isotropic diphasic medium].

Study of the effects of fulgurating electric shocks on an isotropic protein gel more supple than ordinary myocardium provides better understanding of the mechanical effects of fulguration on biological tissues. With a shock and energy level of the type used clinically, a central crater is produced measuring 4 to 6 mm in diameter and a few millimetres deep, surrounded by a crown 30 mm in diameter. Damage due to the mechanical effects of fulgurating shocks is thus 3 to 15 times greater than the size of the electrode. The size of lesions is generally proportional to the energy level and is greater at the anode than cathode. It is also greater with impulses having a short rise time. When the electrode is almost parallel to the wall, the surface area of mechanical lesions is larger and more irregular and it is less deep than when the electrode is perpendicular to the gel.

Biophysical Phenomena↗
PubMed1991

[Doppler echocardiography of the effect of atrioventricular delay on transmitral flow in dual chamber pacing. Role of associated cardiopathy].

Doppler echocardiography was used to analyse transmitral blood flow in 23 patients undergoing DDD pacing under basal conditions at a pacing rate of 70/min. Changes in the atrioventricular delay led to changes in Doppler parameters corresponding to the different phases of ventricular filing. When the atrioventricular interval was increased, the maximum velocity, the velocity time integral and the duration of the E wave decreased and the maximum velocity, the velocity time integral and duration of the A wave increased. The atrial contribution to left ventricular filing increased by 15 to 46% (p less than 0.001). The changes of the Doppler parameters with respect to the duration of the atrioventricular interval varied according to the patient group studied. Patients without ventricular dilatation with or without hypertrophy had greater maximum velocities and velocity time integrals of the A wave than patients with left ventricular dilatation. However, for the same changes in atrioventricular delay, the A wave and atrial contribution to left ventricular filing were more variable in patients without left ventricular dilatation than those with left ventricular dilatation confirming the greater sensitivity of patients without left ventricular dilatation to the setting of the atrioventricular interval. These results confirm the great variability of transmitral flow with changes in atrioventricular delay. They illustrate the need for appropriate programming of the atrioventricular delay especially in patients in whom the mitral flow is most sensitive to this adjustment.

Aged↗
PubMed1991

[Nosologic frontiers of arrhythmogenic dysplasia. Quantitative variations of normal adipose tissue of the right heart ventricle].

The increasing number of arrhythmogenic idiopathic cardiomyopathies with available histological studies by biopsy or peroperative sampling has prompted the need for data about the normal structure of the right ventricle. A retrospective study of right ventricular tissues was undertaken in 148 autopsies. The quantity of adipose tissue was scored 0 (only epicardial fat visible) to 4 (total replacement of the myocardium by adipose tissue). The topography of the adipocytes was also coded 0 to 4 according to the degree of intermyocytic penetration, irrespective of the total quantify of fat. The amount and extension of adipose tissue in the right ventricular wall was striking. Fifty called "normal" appearances with a myocytic wall of normal thickness and a separate layer of epicardial fat, were only present in 61 of the 148 cases. Adipocytes were present in variable numbers, often unexpectedly high in the majority of cases, with no relationship to the age or gender of the patient with frequent individualization of the myocardial bundles. These surprising findings in normal right ventricles should be born in mind when considering the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). The histopathological appearances of ARVD are very similar but also differ very significantly, at least in typical cases. The adipocytes are often present in large numbers but this is banal and non-specific. On the other hand, the bundles which penetrate the epicardial fat are usually fibro-muscular and not purely myocytic. In addition, arterioles suggesting segmental diversions are present within the fatty layer with non-specific inflammatory cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗