Introduction of permanent cardiac stimulation/defibrillation leads via the retro-pectoral veins.

When the cephalic vein route is not easily accessible for the introduction of permanent stimulation/defibrillation leads, retro-pectoral veins can be looked for, which are usually present and suitable in most patients. As with the cephalic vein route, it is a safer approach than direct subclavian vein puncture. Moreover, using a guidewire and a split introducer increases the rate of successful cannulation.

[Atrial lead placement in the right atrial appendage during recent or chronic arrhythmia]. / Implantation de la sonde atriale dans l'auricule droit chez des patients en arythmie atriale récente ou chronique en vue d'une régularisation différée du rythme. Performance de la sonde à 6 mois.

An atrial arrhythmia could be encountered during the atrial lead implantation. The lead placement must subsequently be delayed after restitution of the sinus rhythm or completely abandoned. The authors investigate the atrial lead placement during atrial arrhythmia and the lead performance at 6-month follow-up. The study population was 65 patients aged 78.5 years, 42 males and 28 structural heart diseases. They were implanted for sick sinus syndrome (n=14), atrioventricular block (n=44), infra-hisian conduction abnormality (n=7) in association with an atrial fibrillation (63.1%), an atrial flutter (24.6%) or an atrial tachycardia (12.3%). The onset of the arrhythmia was < or = 7 days (47.7%) or > 7 days (52.3%). An atrial lead was placed in the right atrial appendage under fluoroscopic control. If the sinus rhythm was not restored at 1 month, an electrical cardioversion was performed. The per-implantation atrial signal amplitude was 2.2+/-1.5 mV (range 0.5 mV to 7 mV). Sinus rhythm was restored in 54 patients. At 1 month, one patient was in an incessant atrial fibrillation. The 53 patients in sinus rhythm had a good atrial lead performance. Out of 46 patients who completed the 6-month follow-up, 4 had an arrhythmia recurrence. The 42 patients in sinus rhythm had a good atrial lead performance. At 1 and 6-month follow-up, the atrial pacing threshold (1.1+/-0.7 V vs 1.2+/-1.0 V, ns) and the atrial signal amplitude (2.1+/-1.0 mV and 2.1+/-0.9 mV, ns) were stable. Comparing the patients with a recent or a chronic arrhythmia, the pacing thresholds (1.2+/-1.1 V vs 1.14+/-0.8 V, ns), the atrial signal amplitudes (2.17+/-0.9 mV vs 2.05+/-0.9 mV, ns) and the proportion of satisfactory pacemaker performance in DDD(R) mode for the patients in sinus rhythm (100% vs 100%, ns) did not statistically differ between the two groups at 6 months. In conclusion, the placement of an atrial lead in the right atrial appendage during an atrial arrhythmia is feasible with a good lead performance at 6 months in sinus rhythm regardless the onset time of the arrhythmia and provides a satisfactory atrial-based pacing with the preservation of the atrioventricular synchrony.

Pseudofracture of an ICD lead.

A proximal pseudofracture of a Medtronic 6936 defibrillating lead adjacent to the ICD pulse generator was found on X ray. At this site, the multifilar metallic connector joins the stimulating lead before coiling around it. Conventional X ray of the abdomen does not visualize this connection. During ICD replacement, lead impedance should be routinely measured.

[Transformation of left bundle branch block into simulated bundle branch block after ablation of the right bundle in a patient with branch-to-branch reentry ventricular tachycardia]. / Transformation d'un bloc de branche gauche en bloc de branche déguisé après ablation de la branche droite chez un patient présentant des tachycardies ventriculaires par réentrée de branche à branche.

Masquerading bundle branch block associates left bundle branch block in the standard lead and right bundle branch block in the precordial leads. Mr R., 67 year old, was referred for investigation of syncope. He had a history of idiopathic dilated cardiomyopathy (normal coronary arteries; EF: 14%, CI: 2.2 l/min/m2 at later investigations). The ECG showed LBBB with left axis deviation, a PR interval at the upper limits of normal and ventricular premature beats. During observation, he had another syncopal episode and the ECG showed wide complex tachycardia (160 bpm) reduced by external cardioversion. Electrophysiological investigations showed inducible VT due to bundle branch reentry. The HV interval in sinus rhythm was 80 ms. Radiofrequency ablation of the right bundle led to first degree AVB with masquerading bundle branch block with an increased HV interval of 120 ms. The usual facility of ablation of the right bundle branch block is an argument in favour of the hypothesis whereby masquerading bundle branch block is a variety of RBBB with severe conduction defects of the two branches.

[Therapeutic possibilities for the management of vasovagal syncopes]. / Possibilités thérapeutiques pour la prise en charge des syncopes vasovagales.

Since the advent of the tilt test, our understanding of the pathogenesis of vasovagal syncope has progressed greatly. Two mechanisms lead to the sudden fall in blood pressure: on one hand a series of interrelated neuroreflexes, and on the other, neuroendocrine effects. Although our understanding is not complete, new therapeutic measures can be proposed beyond simple empiric prescriptions of vagolytic agents. The efficacy of different treatments is yet to be proven due to the need for long controlled trials with large numbers of subjects. In the early studies versus placebo, no significant evidence of a preventive effect against recurrent malaise could be distinguished from the placebo effect. Complementary investigations such as the tilt test also act as a placebo. While firm recommendations for effective prevention cannot be established until the results of controlled trials are available, it is nevertheless possible to propose a reasonable approach to management.

[Comparative data of tilt test with or without isoproterenol in investigation of unexplained unconsciousness and syncope]. / Données comparatives du test d'inclinaison avec ou sans isoprotérénol dans l'exploration des syncopes et lipothymies inexpliquées.

The tilt test is a widely used diagnostic tool for the investigation of syncope of suspected vasovagal origin. Some workers suggest that the sensitivity should be increased at the price of the loss of some specificity. Passive (non-sensitised) or isoproterenol (sensitised) protocols have not been widely studied on a large scale. The authors report the respective results of two protocols (passive and sensitised with isoproterenol proposed by Benditt et al.) applied to the same subject at 24 hours' interval in a random order in a series of 108 patients (age 56 +/- 19.3 years, 72 men) with unexplained syncope or malaise. After 30 minutes in decubitus, an 80 degrees tilt was maintained for 45 minutes for the passive test and for 25 minutes for the sensitised test, followed by a continuous infusion of isoproterenol in 10 minutes intervals of decubitus and inclination at successive doses of 1.3 and 5 micrograms/min. One or both tests were positive in 62 patients (57.4%). The overall concordance of the two tests (both positive or both negative) was 53.7%. In a subgroup of 60 subjects with clinically suggestive vasovagal attacks, the sensitivity of the passive test was 25% compared with 73.3% with the isoproterenol test (p < 0.001). Based on this difference of sensitivity between the two protocols, and knowing the good specificity of the isoproterenol test, the authors recommended the isoproterenol test as being of great practical value.

Relationship between interatrial conduction times and left atrial dimension in patients undergoing atrioventricular stimulation.

Interatrial conduction time (IACT) and left atrial dimension (LAD) were determined in 75 patients (41 males, 34 females, mean age 78.2 +/- 7.9 years) undergoing atrioventricular (AV) stimulation. The LAD was measured by M mode echocardiography as the distance between the posterior aortic wall and the posterior left atrial wall. The IACT was determined during a transvenous dual chamber pacemaker implant done under local anesthesia (lidocaine). The spontaneous interatrial conduction time (SIACT) was measured from the intrinsic deflection (ID) of the right atrium recorded in a unipolar mode (unipolar J-shaped lead positioned in the right appendage) to the ID of the left atrium (bipolar esophageal lead, left atrial positive deflection equal to the negative one) during sinus rhythm. The right atrium then was paced at a rate slightly greater than the spontaneous one. The paced interatrial conduction time (PIACT) was measured from the stimulus artifact to the left atrial ID. The PIACT was also measured during incremental right atrial pacing (10 beats/min step increase to 180 beats/min) and, from these measurements, the maximum increase of PIACT (MIPIACT) was deduced. The LAD was measured at 39.5 +/- 8.7 mm, SIACT at 70.3 +/- 24.8 msec, PIACT at 118.8 +/- 27.9 msec, and MIPIACT at 16.5 +/- 16.4 msec. We found highly significant relationships between SIACT and LAD (P = 0.0006, r = 0.39), PIACT and LAD (P = 0.0001, r = 0.45), and MIPIACT and LAD (P = 0.0006, r = 0.38). We also noted that the LAD was greater in patients in whom MIPIACT was > 10 msec than in patients in whom the MIPIACT was negligible (P < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of the behaviour pattern on the nocebo response of healthy volunteers.

The occurrence of a nocebo effect after placebo administration to healthy volunteers in a Phase I trial was analysed according to their type of personality (Bortner Rating Scale). More subjects with a behaviour pattern A (competitive and aggressive) (50%) described subjective side effects of the placebo than type B subjects (17%, P = 0.03). The volunteers who had nocebo effect had a higher Bortner score (BS) than did placebo non-responsive subjects (P = 0.05). The BS was 205 for paramedical staff, 189 for medical and dentistry students, 173 for non-science students and 161 for science students (P < 0.04). The nocebo response was not statistically correlated with professional status. These results suggest that volunteer's type of personality might influence the reporting of subjective symptoms after placebo, and therefore impair the evaluation of new drugs in Phase I clinical trials.

[Severe arrhythmia in the elderly: a prospective hospital study]. / Troubles du rythme graves du sujet âgé; étude prospective hospitalière.

The prevalence of arrhythmia increases with age. Considered as an "ordinary" event in elderly patients, these arrhythmias may nevertheless have serious consequences. This study was undertaken to determine the clinical, aetiological and prognostic features of serious arrhythmias in a population of elderly subjects (> or = 70 years) hospitalised over a 20 months period and comprising 202 patients (103 women, 99 men, mean age 79.6 +/- 5.9 years). Supraventricular arrhythmias are the most common by far (84.2%): 51.4% of patients had atrial fibrillation, 15.3% had atrial flutter; 12.9% had focal atrial tachycardia, 4.5% had junctional tachycardia. Of the ventricular arrhythmias (15.8%), there were 12 sustained ventricular tachycardias, 4 torsades de pointes and 1 ventricular fibrillation. The increased duration of hospital stay (10 +/- 6 days on average) is related not to age but to the type of arrhythmia (longer for ventricular arrhythmias) and to left ventricular dysfunction. The main complications of arrhythmias were cardiac failure (52.4%), neurological deficits (37.4%) and angina (18.6%). Electrocardiographic signs of atrioventricular block were present in 62% of cases and QRS changes in 47.3% of cases. Ventricular arrhythmias were more commonly associated with intraventricular conduction defects, signs of myocardial necrosis and prolongation of the QT interval; they were also common in patients with left ventricular dysfunction and when the left ventricle was dilated. The aetiology of ventricular arrhythmias was mainly iatrogenic (50%) and ischaemic (21.8%), whereas the aetiologies of the supraventricular arrhythmias were varied, 14.7% of cases being idiopathic. Conversion to stable sinus rhythm was obtained in half the patients. A pacemaker was implanted in 10.8% of cases. The hospital mortality was 4.9%.(ABSTRACT TRUNCATED AT 250 WORDS)

Interatrial conduction in patients undergoing AV stimulation: effects of increasing right atrial stimulation rate.

To evaluate the frequency of spontaneous or rate dependent interatrial blocks, the interatrial conduction time (IACT) was studied on 100 consecutive patients (mean age 78.3 +/- 7.8 years) during a transvenous dual chamber pacemaker implant. The spontaneous interatrial conduction time (SIACT) was measured from the intrinsic deflection (ID) of the unipolar right atrial signal to the ID of the left atrial signal recorded in a bipolar way by an esophageal lead. The paced interatrial conduction time (PIACT) was measured from the stimulus artifact to the left atrial ID, when the atrium was paced at a slightly higher rate than the spontaneous rate and during incremental atrial pacing. From these measurements, the maximum increase of PIACT (MIPIACT) was deduced. In this elderly population, the PIACT was similar (117 +/- 26.9 msec) to the data in the literature. However, there were large interindividual variations that were also found in SIACT. We found a close correlation between SIACT and PIACT (P < 0.0001). PIACT was on average 50 msec longer than SIACT. SIACT increased with age (P < 0.03). The MIPIACT was 15.3 +/- 15.2 msec. In the majority of patients, the MIPIACT was > 10 msec, and even reached 90 msec in one patient. MIPIACT was longer in patients with a PIACT exceeding 110 msec (P < 0.004). Based on IACT alone, the AV interval must be lengthened on average by 50 msec when changing from atrial tracking-ventricular pacing to atrial pacing-ventricular pacing, but large individual differences must be kept in mind. Elderly people should probably have a longer AV delay.

Structure, chromosome mapping and expression of the murine Fgf-6 gene.

The sixth member of the fibroblast growth factor gene family was cloned and analysed in the mouse. It is composed of three coding exons and encodes a putative growth protein of 198 amino acids, possessing a potential signal peptide, and presenting 79% and 93.5% sequence similarity with the mouse Hst/K-fgf and human FGF-6 genes products, respectively. The murine Fgf-6 gene is located in a region distinct from the Int-41 locus and belongs to a linkage group conserved between chromosome 12 in man and chromosome 6 in mouse. It presents an intrinsic oncogenic capacity since it is able to transform cultured fibroblasts. Fgf-6 mRNA levels are developmentally regulated with a peak of expression in the developing fetus at day 15.5 of gestation, moderate levels during late gestation and in the neonate. In the adult, Fgf-6 mRNA can be detected in testis, heart and skeletal muscle.

Characterization of the HST-related FGF.6 gene, a new member of the fibroblast growth factor gene family.

By screening a mouse cosmid library with a human HST probe under reduced conditions of stringency, we isolated several positive clones. One of them was identified as a new member of the fibroblast growth factor gene family, and called FGF.6. The human FGF.6 gene was subsequently isolated and sequenced. The deduced amino-acid sequence exhibited 70% identity with the HST gene product over the C-terminal two-thirds of the putative protein. FGF.6 was mapped to chromosome 12 at band p13 by in situ hybridization. The cloned normal human gene was able to transform mouse NIH3T3 fibroblasts using both focus- and tumorigenicity-assays.

[Research on the molecular basis of neoplasms: malignant melanoma as an example]. / Recherche d'une base moléculaire des cancers: l'exemple des mélanomemalins.

Knowledge about genetic alterations occurring in human tumors has dramatically increased following the development of cytogenetic and molecular techniques. Various alterations have been characterized: chromosomal damages, oncogene activations, loss of genetic material. Some of those alterations, such as c-abl rearrangements in certain leukemias, are characteristic of a certain type of malignancy. However, in most tumors, no such correlation has been demonstrated. We review here the genetic alterations discovered in human malignant melanomas.

Chromosomal localization of the hst oncogene and its co-amplification with the int.2 oncogene in a human melanoma.

In this report we described the linkage between two oncogenes of the fibroblast growth factor family. Using in situ hybridization to human metaphase chromosomes we mapped the hst gene to chromosome 11 at band q13. This is also the location of the int.2 gene. Furthermore, the two genes are co-amplified in a human melanoma, raising the possibility that amplification in human tumors may be a mechanism of activation of genes of the FGF family.

Detection of a low frequency of activated ras genes in human melanomas using a tumorigenicity assay.

We have used an assay combining DNA-mediated gene transfer and tumorigenicity in Swiss athymic mice to look for activated ras genes in solid human sporadic melanomas. This assay can detect ras oncogenes mutated at codons 12, 13, or 61. We examined a panel of 13 independent surgical specimens of primary tumors and metastases. No H- or K-ras oncogenes were detected; an N-ras oncogene, mutated at codon 61, was identified in one of the 13 samples. No N-ras genes mutated at codon 13 were detected. Thus, the tumorigenicity assay detects a low frequency of ras gene activation in melanomas.

Detection of transforming sequences in human melanomas and leukemias.

DNA extracted from fresh solid human melanoma tumors and untreated acute myeloid leukemic cells was used in two assays designed to detect oncogenes, based on the transfection of murine NIH 3T3 fibroblasts followed by selection of transformed cells in low serum concentration or induction of tumors in athymic mice. Ras and non-ras oncogenes were detected.

Magnetic resonance imaging of gadolinium-labeled monoclonal antibody polymers directed at human T lymphocytes implanted in canine brain.

Two different murine monoclonal anti-human T cell antibodies, that were coupled to gadolinium (Gd), bind specifically to human T lymphocyte cells implanted in canine brain. This binding was at a concentration of Gd sufficient to detect the implanted cells and to distinguish them from the surrounding brain tissue with magnetic resonance imaging (MRI) at a field strength of 1.5 Tesla. These Gd-labeled immunoglobulin preparations did not bind bovine T cells at a concentration sufficient to be detected on MRI. A protein solution containing the immunoglobulins (100 micrograms), gelatin (2 mg), and bovine serum albumin (2.5 mg) was reacted with the dianhydride of diethylenetriaminepentaacetic acid (DTPA); the DTPA serves as a metal chelator and as a protein crosslinking agent. The DTPA-protein complex was reacted with Gd chloride. There were approximately 10 DTPA residues per protein molecule in the modified protein mixture. Isolated human or bovine monocytes (approximately 12 million cells) were implanted in the brains of anesthetized dogs in a volume of 40 microliters. The blood-brain barrier was then disrupted by the intra-arterial injection of hyperosmotic mannitol, and the Gd-labeled antibodies were injected through a catheter placed at the branch of the internal and external carotid arteries. The brains were imaged 48 to 72 hours later. The MRI scans revealed a markedly decreased T1 relaxation time with a high signal intensity (TE = 25 msec, TR = 200 msec) related to the human T cell implants. There was no evidence of decreased T1 at the site of the bovine T cells. Neither control murine gamma globulin coupled to Gd-DTPA nor anti-human T cell antibodies uncoupled to Gd modified the MRI contrast of the human T cells in the brain.

[Activated oncogenes in human tumors]. / Les oncogènes ras activés dans les tumeurs humaines.

ras oncogenes are cellular genes altered by point mutation in 10 to 30% of human tumors. Under this mutated form they play a role in the malignant process, probably in association with other oncogenes. The different ras genes identified in human cancers, the point mutations that activate the ras genes and the properties of the ras proteins are described.