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Biomedical subjects

B Thiel

Publications and source records attributed to B Thiel.

At least 37 records · Page 2Linked to original sources

[Syncopes associated with mitral valve prolapse. Mechanisms].

Prolapsed mitral valve prolapse (PMV) is classically associated with disorders of ventricular excitability whose significance is unclear. However, syncope can suggest the possibility of a serious ventricular arrhythmia. The objective of this study was to try to identify the mechanisms of dizziness and syncope associated with PMV. We report the results of programmed atrial and ventricular stimulation performed under baseline conditions and after administration of Isuprel in 56 patients with PMV: 27 patients had a history of presyncope or syncope (group I), 14 had spontaneous atrial or supraventricular tachycardias without dizziness or syncope (group II) and 15 were asymptomatic and investigated for VEBs or conduction disorders (group III). The following results were obtained: In group I, 6 patients experienced sustained inducible ventricular tachycardia (VT); an atrial tachycardia (atrial tachycardia and/or atrial fibrillation) (AT) was also induced in 5 of them. In another 19 patients, a supraventricular tachycardia (SVT) and/or AT was induced. A total of 24 atrial or junctional tachycardias were triggered in this group. In group II, AT and/or SVT were reproduced in 13 out of 14 cases (93%). In group III, AT was triggered in 3 patients (20%). SVT were induced by Isuprel while AT were triggered prior to administration of Isuprel, under baseline conditions, and 3 of them were reproduced during vagal manoeuvres. A ventricular arrhythmogenic effect was observed in two cases in group II while taking class I antiarrhythmics. In conclusion, spontaneous AT and SVT of PMV are easily inducible with a sensitivity of 93%, but are difficult to induce in asymptomatic subjects. The high incidence of TA and SVT in the case of unexplained presyncope in subjects without documented tachycardia therefore appears to be suggestive of a relationship between these presyncopes and AT or SVT. However, the search for VT should take precedence. SVT appear to be catecholaminergic while AT tend to be vagal.

Adolescent↗

Programmed ventricular stimulation in survivors of acute myocardial infarction: long-term follow-up.

The prognostic significance of ventricular tachyarrhythmias induced by programmed ventricular stimulation was evaluated in 492 consecutive survivors of acute myocardial infarction (AMI). Holter monitoring, signal-averaged electrocardiogram (ECG) and measurement of left ventricular ejection fraction (EF) were also performed. The protocol used up to 3 extrastimuli. Sustained monomorphic ventricular tachycardia (VT) < 270 beats/min, > 270 beats/min (ventricular flutter) (VFI), and ventricular fibrillation (VF) were induced in 99, 66 and 52 patients, respectively. Long term follow-up (mean 3.7 +/- 2.2 years) showed that most episodes of VT occurred during the first months following AMI (n = 14), but some patients (n = 6) could develop VT as late as 4 years after AMI. Sudden death (SD) (n = 22) always occurred during the first year following AMI. Multivariate analysis demonstrated that EF < 30% and induction of a VT < 270 beats/min were the only predictors for total cardiac death (P < 0.001). EF < 30%, induction of a VT < 270 beats/min and also of VFI (P < 0.05) were predictors for VT and SD: the risk was 4% in patients without inducible VT, 12% in those with inducible VF1, and 21% in those with inducible VT < 270 beats/min. In conclusion, induction of a sustained monomorphic VT < 270 beats/min or > 270 beats/min is a predictor of arrhythmic events during the first year as well as 4 years after myocardial infarction. However the risk of arrhythmic sudden death decreases after the first year, while the risk of VT persists. Because of the low positive predictive value of programmed stimulation (respectively 21% and 12% for the induction of a sustained VT and VFI), we recommended the indication of programmed stimulation in only the patients with one abnormal non-invasive investigation.

Actuarial Analysis↗

Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease.

Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most common cause of congenital bowel obstruction with an incidence of 1 in 5000 live births. Recently, linkage of an incompletely penetrant, dominant form of HSCR was reported, followed by identification of mutations in the RET receptor tyrosine kinase. To determine the frequency of RET mutations in HSCR and correlate genotype with phenotype, we have screened for mutations among 80 HSCR probands representing a wide range of phenotypes and family structures. Polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis of RET's 20 exons for mutations among probands revealed eight putative mutations (10%). Sequence changes, which included missense, frameshift and complex mutations, were detected in both familial and isolated cases, among patients with both long- and short-segment HSCR and in three kindreds with other phenotypes (maternal deafness, talipes and malrotation of the gut, respectively). Two mutations (C609Y and C620R) we identified have previously been associated with multiple endocrine neoplasia type 2A (MEN2A), medullary thyroid carcinoma (MTC) and, on rare occasions, HSCR. Thus, while HSCR family members may be at risk for developing neuroendocrine tumors, it follows that identical mutations in RET may be able to participate in the pathogenesis of distinct phenotypes. Our data suggest that: (i) the overall frequency of RET mutations in HSCR patients is low and therefore, other genetic and/or environmental determinants contribute to the majority of HSCR susceptibility, and (ii) at present, there is no obvious relationship between RET genotype and HSCR phenotype.

Base Sequence↗

[Ablation of the bundle of His through a patent foramen ovale, by approach from the left side].

The authors report the case of a 60-year-old male patient in whom resection of the bundle of His via a right-sided approach to treat permanent very rapid atrial fibrillation was attempted, but failed. The bundle of His tissue was resected very easily on the left side due to the presence of a patent foramen ovale, which also avoided the risks of the left catheterism in this patient.

Atrial Fibrillation↗

[Should a signal-averaged electrocardiogram be requested in the evaluation of malaise and syncope?].

In order to determine whether signal-averaged electrocardiography was useful in the diagnosis of syncopal ventricular tachycardia, 244 subjects with malaise or unexplained syncope without documented ventricular tachycardia underwent endocavitary electrophysiological study and signal-averaged electrocardiography with a 25 Hz bandpass filter. Ninety-three patients had no apparent cardiac disease whereas 151 patients had cardiac problems. ventricular tachycardia was induced in 91 patients. Fifty-two of them (57%) had ventricular late potentials. Twenty-two patients without inducible ventricular tachycardia also had late potentials (14%). The diagnostic value of signal-averaged electrocardiography depended on the cardiac disease: in the absence of cardiac disease, its sensitivity was poor (31%) but the specificity was excellent (96%). In the presence of cardiac disease, the sensitivity improved (63%) but the specificity was not as good (67%). The lack of sensitivity in the group with cardiac disease generally concerned subjects with inducible rapid ventricular tachycardia. The authors conclude that signal-averaged electrocardiography should not be requested in the investigation of unexplained syncope in subjects without cardiac disease to demonstrate abnormal ventricular excitability which is very rate in these subjects. On the other hand it is more valuable in those with underlying cardiac disease although inducible rapid ventricular tachycardia may still escape detection.

Adolescent↗

[Changes in heart rate after ventricular stimulation; correlations with vagal tone].

The authors report a new method of studying the autonomic nervous system, especially vagal tone, during endocavitary electrophysiological studies. After termination of fixed ventricular pacing at incremental rates to 200/min, an initial acceleration of the heart rate is observed followed about 5 seconds later by a sudden slowing. This phenomenon was studied in 278 patients. Ninety seven patients had no cardiac disease: the variation in heart rate was 33 +/- 18%. In the 181 other patients with cardiac disease (ejection fraction 35 +/- 16%) the variation was only 21 +/- 16% (p < 0.01). When the ejection fraction was less than 30%, the variation was only 13 +/- 4%. When the heart rate variation was less than 10%, the prognosis was poor because, of the 48 patients with this sign, 13 died, whereas there were only 2 deaths in the 133 other patients with cardiac disease and preserved adaptation. In 14 patients without cardiac disease the injection of 2 mg of atropine suppressed all adaptation of the heart rate, whilst in 18 other patients, oral betablockers reduced the variation but it persisted to a significant degree. The authors conclude that the adaptation of the heart rate after rapid ventricular stimulation is probably a reflection of vagal tone and may be used to assess the prognosis of subjects undergoing electrophysiological investigations.

Adolescent↗

Synergistic cooperation between T cell lymphokines for induction of the nitric oxide synthase gene in murine peritoneal macrophages.

The ability of T cell-derived cytokines to induce the expression of the nitric oxide synthase (NOS) gene in murine peritoneal macrophages was examined. IL-2 or TNF-alpha alone had no effect either on gene expression or enzyme activity, whereas IFN-gamma had only modest activity. When IL-2 or TNF-alpha were used in combination with IFN-gamma, there was a marked cooperative induction of both mRNA and enzyme activity. The cooperative effects were truly synergistic, as the consequences of combined cytokine treatment were many times greater than was seen with any of the agents acting independently. The expression of NOS mRNA and enzyme activity in response to combined lymphokine treatments was a continuous process reaching optimal levels between 24 and 48 h after stimulation. Concentration dependency for both IL-2 and TNF-alpha suggested that their effects were mediated through interaction with the corresponding defined cell surface receptors. Human rTNF-alpha was as effective a stimulus as murine TNF-alpha; because human TNF-alpha is recognized only by the p55 Type II TNF receptor, this structure appears to mediate the response to TNF-alpha. When IL-2 and TNF-alpha were added at saturating doses in the presence of IFN-gamma, there was an additive effect on NOS mRNA expression suggesting that IL-2 and TNF-alpha cooperate with IFN-gamma through at least partially distinct intracellular signaling pathways. Expression of NOS mRNA in response to IFN-gamma/IL-2 or IFN-gamma/TNF-alpha treatment required protein synthesis, suggesting that cooperative cytokine induction of NOS involves the intermediate expression of new gene products. Such molecular controls for regulation of inducible macrophage gene expression can be contrasted with regulatory control of other inflammatory genes such as IP-10 and TNF-alpha.

Amino Acid Oxidoreductases↗

Clinical significance of rapid ventricular tachycardia (> 270 beats per minute) provoked at programmed stimulation in patients without confirmed rapid ventricular arrhythmias.

Rapid uniform ventricular tachycardia (VT) (> 270 beats/min) or ventricular flutter induced during electrophysiological studies is thought not to be clinically significant in patients without cardiac arrest or documented rapid VT. The purpose of the study was to follow up 73 patients with inducible ventricular flutter but without confirmed rapid spontaneous VT. A long follow up (mean 3.5 years) identified two groups of patients. The first group had an excellent outcome and was characterised by a normal 24 hour Holter monitoring. In the second group, however, the risk of cardiac mortality was high (35%) and spontaneous VT was < 270 beats/min (26%) and was characterised by couplets or salvos of extrasystoles on Holter monitoring. In this group the history of syncope and decreased left ejection fraction increased the risk of mortality and VT. The presence of late potentials increased the risk of spontaneous VT. Electrophysiologically guided antiarrhythmic therapy reduced the risk of VT. Ventricular flutter was a non-specific finding in patients with normal Holter monitoring. In contrast, in patients with salvos of extrasystoles, ventricular flutter was associated with a high risk of cardiac mortality and VT.

Adult↗

[Results of systematic programmed ventricular stimulation after myocardial infarction. Which protocol should be recommended?].

The authors report the prognostic value of ventricular arrhythmias induced by routine programmed ventricular stimulation after the acute phase of myocardial infarction. The protocol consisted of two extrastimuli in the first 185 patients and 3 extrastimuli in 308 patients. The use of 3 extrastimuli increased the incidence of inducible sustained monomorphic ventricular tachycardia (VT) < 270/mn, from 17 to 22% and, more importantly, that of ventricular fibrillation from 4 to 17%. Induction of ventricular flutter (monomorphic VT > 270/mn) was not increased. A long follow-up period (average 4 +/- 2 years) showed that the risk of VT was increased during the first months after infarction (n = 14), and that, 4 years later, other patients develop VT (n = 6). The risk of serious arrhythmias (VT and sudden death) was significantly higher in patients with inducible VT < 270/mn (20%) than in patients without inducible VT, but it was also higher in patients with inducible ventricular flutter (12.5%). The use of a third extrastimulus has a low positive predictive value for arrhythmic events (10%). This study confirms that the induction of sustained monomorphic VT after myocardial infarction is associated with an increased risk of arrhythmic events but the positive predictive value is relatively low (17%). In view of the risk of inducing non-specific ventricular fibrillation, the authors recommended using a stimulation protocol with only 2 ventricular extrastimuli.

Arrhythmias, Cardiac↗

[Results of high amplification electrocardiogram in primary dilated cardiomyopathy].

Idiopathic dilated cardiomyopathy carries a high risk of sudden death. It is also associated with sustained ventricular tachycardia. A complex ventricular arrhythmia is recorded in 3/4 of cases on Holter monitoring which has a low specificity. The aim of the study was to determine whether signal-averaged electrocardiography could provide a better evaluation of the prognosis of this condition. The results of signal-averaged electrocardiography were compared with those of 24 hour Holter monitoring and of systematic programmed ventricular stimulation in 58 patients with idiopathic dilated cardiomyopathy. Late ventricular potentials were recorded in 13 of the 14 subjects with inducible and usually spontaneous sustained ventricular tachycardia. The sensitivity of the technique for evaluating the risk of sustained VT was therefore good (93%). Late potentials were also recorded in 9 patients with induced ventricular flutter or fibrillation, these patients being symptomatic (dizzy spells). Late potentials were also demonstrated in 14 of the 35 asymptomatic patients without inducible VT, indicating that this non-invasive investigation had a limited specificity (60%). In addition, during follow-up of the patients, the risk of sudden death was difficult to demonstrate. Late potentials were only found in subjects with inducible sustained VT but no in the other cases. In conclusion, signal-averaged electrocardiography seems to be valuable for evaluating the risk of sustained VT in subjects with idiopathic dilated cardiomyopathy and complex ventricular arrhythmias. The detection of the risk of sudden death is probably impossible by this technique.

Adult↗

[Cardiac arrest reversed: causes and treatments].

The aim of this study was to report the probable mechanism of resuscitated cardiac arrest without acute myocardial infarction. Fifty-seven cases were recensed but the arrest was only documented in 44 subjects. Systematic non-invasive investigations and programmed stimulation showed that the diagnosis of cardiac arrest was probably false in 5 patients and, in the others, that a ventricular arrhythmia was probably the cause (63%). The occurrence of cardiac arrest under antiarrhythmic therapy may reveal an underlying abnormality requiring specific therapy (3/8). The absence of cardiac disease did not exclude the risk of VF (3 cases). When reproducible, ventricular arrhythmias were present during programmed stimulation, the prognosis was good if the arrhythmia could not be induced under antiarrhythmic therapy. It was easier to find an effective treatment for inducible ventricular fibrillation-flutter (13/17) than for inducible ventricular tachycardia (7/17). The prognosis was poor if the arrhythmia was unchanged during programmed stimulation under antiarrhythmic therapy and non-pharmacological treatment was required.

Adolescent↗

[Incidence of inducible supraventricular tachycardia in dysplasia of the right ventricle].

Arrhythmogenic right ventricular dysplasia (ARVD) is classically associated with ventricular tachycardia and the prevalence of supraventricular tachycardia in this condition is not well known. The aim of this study was to observe the response of 20 patients with ARVD to programmed atrial stimulation and compare it with 150 subjects without cardiac disease or spontaneous supraventricular tachycardia. The protocol used 2 atrial extra-stimuli delivered on 3 paced cycles. Programmed atrial stimulation with 1 extrastimulus was repeated after infusion of 20 to 30 micrograms of Isoproterenol. Sustained supraventricular tachycardia could be induced in 13 patients with ARVD (65%) and 17 control subjects (11%) (p < 0.001). It was not possible to distinguish patients with inducible supraventricular tachycardia from those without inducible arrhythmias by electrophysiologic parameters. Isoproterenol facilitated the induction of VT but not supraventricular tachycardia. Three patients with inducible supraventricular tachycardia developed spontaneous atrial fibrillation. In conclusion, there is a relatively high incidence of inducible supraventricular tachycardia in ARVD: Isoproterenol does not facilitate this tachycardia, contrary to ventricular tachycardia.

Adult↗

[Programmed ventricular stimulation in unexplained syncope: risk factors for induction of ventricular tachycardia].

The aim of this study was to identify the factors associated with the induction of ventricular tachycardia (TV) by programmed ventricular stimulation in patients with unexplained syncope. Sustained VT was induced in 71 out of 619 patients (11.5%) with syncope. A comparison of subjects with inducible VT and those without inducible VT showed underlying cardiac disease to be more common (89% versus 16%), more Holter abnormalities (Grade IVa ventricular extrasystoles) (60.5% versus 10%) in the first group but that signal-averaged ECG, recorded in 51 cases, was not sufficiently specific to differentiate the two groups (delayed potentials in 57% versus 43%). When syncope occurred in a subject without apparent cardiac disease with a normal Holter recording, inducible VT was rare (1%). On the other hand, when syncope was associated with cardiac disease and/or an abnormal Holter recording, VT could be induced in 45 to 64% of cases. In addition, as inducible VT was associated with severe infrahisian conduction defects in 3 cases, the following strategy is suggested in patients with unexplained syncope: programmed ventricular stimulation should be performed systematically during endocavitary electrophysiological investigation of AV conduction in patients with cardiac disease and if the non-invasive investigations, Holter monitoring or echocardiography, are abnormal.

Cardiac Pacing, Artificial↗

[Results of programmed ventricular stimulation in induced non-sustained polymorphic ventricular tachycardia and maintenance of stimulation].

Programmed ventricular stimulation risks inducing non-pathological ventricular fibrillo-flutter. The aim of this study was to determine if the induction of a non-sustained polymorphic ventricular tachycardia (over 5 intraventricular reentries) could prevent this incident. One hundred and thirty-three non-sustained polymorphic tachycardias were induced by 2 or 3 extrastimuli during 1450 programmed ventricular stimulation studies. Ventricular stimulation was continued and led to ventricular fibrillo-flutter in 46 cases (Group I); to induction of sustained ventricular tachycardia in 26 cases (Group II) or to no other arrhythmias excepting the non-sustained tachycardia in 61 cases (Group III). The duration of the salvo was similar in all 3 groups. The rate of the induced arrhythmia was significantly lower in Group II (234 vs 290/min). The essential difference between the three groups was the clinical context. Only patients in Group II had previously documented sustained ventricular tachycardia and only patients in Group III had no apparent underlying cardiac disease. These results suggest that the decision to stop programmed ventricular stimulation should be based on the clinical indications of the study. In patients with previously documented or probable sustained ventricular tachycardia, it would seem to be necessary to continue ventricular stimulation irrespective to the rate and duration of the induced non-sustained ventricular tachycardia.

Cardiac Pacing, Artificial↗

Deletion of cytoplasmic sequences of the nerve growth factor receptor leads to loss of high affinity ligand binding.

The nerve growth factor (NGF) receptor is a glycosylated transmembrane protein present on the cell surface as both high and low affinity forms, but biological responsiveness requires interactions of NGF with the high affinity site. We have tested the effects of mutations in the intracellular domain of the receptor upon its cell surface expression and equilibrium binding of 125I-NGF. Although mutant receptors lacking the entire cytoplasmic domain are processed and expressed at the cell surface and are capable of binding to NGF, the absence of cytoplasmic sequences leads to a loss of high affinity binding and to a lack of an appropriate cross-linking pattern as assessed by N-hydroxysuccinimidyl 4-azidobenzoate photoaffinity cross-linking. These results, taken together with the highly conserved nature of these cytoplasmic sequences, implies that the interaction of the receptor with an accessory molecule is necessary to form the high affinity receptor.

Base Sequence↗

[Detection of IgG antibodies against rubella virus using the "Rubella-IgG-EIA SSW" test kit].

A new commercial ELISA test kit "Rubella-IgG-EIA SSW" is described for the determination of IgG antibodies to rubella virus. A panel of 99 sera was tested by "Rubella-IgG-EIA SSW" and by hemagglutination-inhibition (HI test). The results of enzyme-immunoassay (EIA) and of HI test correlate well; the coefficient of correlation is 0.95, the specificity is 90.9% and the sensitivity is 100%. A coefficient of correlation was found out of 0.92 between EIA and HI test in the evaluation of the quantitative procedure. The test kit can be used for determination of immune status to rubella virus and for quantitative detection of rubella-IgG antibodies.

Enzyme-Linked Immunosorbent Assay↗