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Biomedical subjects

P Chatelain

Publications and source records attributed to P Chatelain.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Immediate results of coronary endoprosthesis in threatening or occlusive dissections complicating angioplasty; the Geneva experience].

Between April 1988 and September 1993, 123 patients (average age 60.4 +/- 8.9 years) underwent coronary stenting for threatening or occlusive dissection complicating angioplasty. The anterograde coronary flow was disturbed in 51% of cases (TIMI-0-2). The artery concerned was the left anterior descending in 59% of cases, the right coronary in 28% of cases, the circumflex in 12% and a coronary bypass graft in 1% of cases. Technically, the stenting was successful in 118 cases (98%) and, in 21 cases, complete stenting of the dissection required the insertion of several stents. The minimal coronary diameter after expansion of the stent was 3.1 +/- 0.6 mm. During hospital follow-up, 3 deaths (3%) and 7 Q-wave infarcts were observed. Twenty-eight patients (23%) developed a haemorrhagic complication, including 2 retroperitoneal and 2 intracerebral bleeds. Eight patients (6%) underwent coronary bypass grafting, as an emergency in 4 cases and semi-electively in another 4 cases. One hundred and five patients (89%) survived the intra-hospital period without major complications (death, Q-wave infarction, emergency coronary bypass surgery or severe haemorrhage). Coronary stenting for threatening or occlusive dissection complicating angioplasty seems to be a reasonable solution and a usually definitive one. The frequency of haemorrhagic complications underlines the need for strict clinical and biological surveillance.

Aged↗
PubMed1993

Characterization of cardiac angiotensin AT1 receptors by [3H]SR 47436.

[3H]SR 47436, a selective and potent novel non-peptide antagonist of angiotensin receptors, was used to characterize the cardiac angiotensin AT1 receptors. In neonatal rat heart cells, Scatchard analysis showed a single class of high affinity binding sites (Kd = 0.24 nM, Bmax = 28 fmol/mg protein). The binding was saturable, reversible and prevented by angiotensin II and the AT1 subtype receptor antagonist DuP 753 whilst unaffected by the AT2 receptor antagonist PD123177. In the same cells, angiotensin II induced a twofold increase in the intracellular free Ca2+ concentration ([Ca2+]i), with a half-maximal effect (EC50) at 14 nM. This increase was prevented by SR 47436 (IC50 = 1.03 nM) and by the AT1 receptor antagonist DuP 753, but at higher concentrations (IC50 = 15.6 nM) and was unaffected by PD123177. These data directly demonstrate the presence of cardiac AT1 receptors in rat neonatal cardiomyocytes and confirm the involvement of AT1 receptors in cardiac Ca2+ homeostasis.

Angiotensin I↗
PubMed1993

Genetic and molecular analysis of familial isolated growth hormone deficiency.

Familial isolated growth hormone deficiency (IGHD) has been associated with complete deletions of the hGH-N gene encoding the pituitary growth hormone (GH) in a large number of cases. However, there is still no alternative empirical explanation for the remaining familial or non-familial IGHD cases. We studied a large kindred including five IGHD-affected first cousins to determine possible IGHD inheritance and whether the hGH-N gene was the cause of IGHD in this pedigree. Sex-linked and autosomal recessive transmission of IGHD in this kindred was rejected. Autosomal dominant inheritance was the most probable explanation according to a model of one locus with two alleles, one being dominant for IGHD, under genetic modifiers or epistasis. Southern blotting analysis (BamHI and HindIII digestions) was used to determine whether the hGH-N gene was present in the patients and their family members. Because we found that the hGH-N gene was present, five restriction fragment length polymorphisms (RFLPs; HincII, MspI-A and B, and BglII-A and B) linked to the hGH-N gene were used to try to identify the possible RFLP haplotypes in the pedigree that could be markers or associated with the abnormal hGH-N alleles responsible for IGHD. From the haplotype analysis, it appeared that other genes not linked to the hGH-N gene cluster were the cause of the IGHD phenotype in this kindred. An alternative conclusion could be that the hGH-N gene was responsible for IGHD in this kindred, if a mutation (gene conversion) at the MspI-B site or a reciprocal recombination event between the HincII and MspI-B sites occurred from generation P to F1 and a similar event took place from generation F1 to F2. The non-significant GH responses of patients to the growth releasing factor test confirmed that the hGH-N gene structural product or some step in its regulation was responsible for causing IGHD in this kindred. We suggest that genetic micromutations in the hGH-N gene are present and are responsible for IGHD. We developed a method using the polymerase chain reaction to amplify a 790-bp fragment of the hGH-N gene. The fragment spanned from the second part of the dyad symmetry region in the non-transcribed 5' end of the hGH-N gene to 9 bp before the alternative splice-acceptor site in exon 3. The expected fragment was verified by its digestion with seven diagnostic restriction endonucleases (BamHI, FspI, PstI, NdeI, BssHII, BglII and HincII).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

In vitro characterization of a novel Ca2+ entry blocker: SR 33805.

In this study, SR 33805 was shown to inhibit competitively [3H]fantofarone binding to cardiac sarcolemmal membranes. In contrast, SR 33805 was shown to inhibit allosterically [3H](+)-PN200-110, [3H](-)-D888 and cis-(+)-[3H]diltiazem binding. In isolated rabbit atrial preparations, SR 33805 was shown to be the least potent of fantofarone, nifedipine, verapamil and diltiazem in terms of both negative chronotropic and inotropic responses (IC50's 6 and 12 microM, respectively). In superfused rat aortic strips, SR 33805 like other Ca2+ channel antagonists, caused a significant inhibition of both K(+)-induced 45Ca2+ influx and contractile responses. In addition this agent was shown to antagonize Ca(2+)-induced contractions in K(+)-depolarized aorta with a pA2, value of 8.39 +/- 0.02. In femoral, renal and basilar arteries, SR 33805 was equiactive to the other Ca2+ channel antagonists studied in antagonizing K(+)-induced contractions (IC50 approximately 40 nM), but unlike the reference Ca2+ channel antagonists, was equiactive in antagonizing serotonin-induced contractions (IC50 approximately 250 nM). This suggests that the effects of SR 33805 depend mainly on membrane potential. In conclusion, SR 33805 is a potent Ca2+ channel antagonist which, unlike fantofarone, verapamil and diltiazem, is highly selective for vascular smooth muscle and devoid of any potent negative inotropic actions.

Animals↗
PubMed1993

Physiological pulmonary branch stenosis in newborns: 2D-echocardiographic and Doppler characteristics and follow up.

Transient systolic murmurs in neonates and premature infants due to mild left (LPA) and right (RPA) pulmonary branch stenosis is recognized but follow up studies are lacking. We studied echocardiographically 21 neonates with murmur and 10 controls. Diameters of the main pulmonary artery (MPA), LPA and RPA were smaller in patients with murmur. Colour-coded Doppler showed turbulent flow in LPA and RPA in 20/21 (95%) patients and flow velocities of both pulmonary branches were significantly higher than in controls. The follow up study at 3 months in 14/21 (67%) patients showed absent or decreased murmur in 9 (64%). Echographically, absolute and relative diameters of LPA and RPA increased whereas the ratio of MPA/aorta did not change suggesting accelerated growth or dilatation of the pulmonary branches. Flow velocities decreased significantly in the branches. Thus, transient systolic murmurs in neonates are associated with temporary relative hypoplasia of the pulmonary branches which showed increased growth leading to disappearance of the murmur in most cases within 3 months of life.

Arterial Occlusive Diseases↗
PubMed1993

Cine gradient-echo MR imaging in the evaluation of cardiovascular diseases.

The contributions of cine gradient-echo (GRE) magnetic resonance imaging were compared with those of spin-echo (SE) imaging for the evaluation of morphologic, functional, and flow alterations in 78 cases of congenital and acquired cardiac diseases. High temporal and spatial resolution cine GRE images (256 phase-encoding steps, 256 x 256 acquisition matrix interpolated to 512 x 512 for display, 16-64 frames per cycle) and SE images were acquired in each case. Cine GRE images provided a better diagnostic evaluation than SE images in several cases: (a) both masses and thrombi could be differentiated from flow artifacts; (b) abnormalities in cardiac function, such as infarction, abnormal wall motion, and ventricular dysfunction, could be evaluated; (c) small defects, shunts, and abnormal communications could be clearly seen; and (d) valvular regurgitations, poststenotic flow alterations, and aortic coarctation could be assessed. Cine GRE imaging was also valuable for postoperative evaluations. The authors believe that cine GRE imaging is a useful addition to SE sequences, especially for the assessment of blood flow and cardiac function.

Adolescent↗
PubMed1993

Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy, and deafness (Wolfram syndrome, MIM 222300).

The Wolfram syndrome (MIM 222300) is a disease of unknown origin consisting of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. Here we report on a generalized deficiency of the mitochondrial respiratory enzyme activities in skeletal muscle and lymphocyte homogenate of a girl suffering from the Wolfram syndrome. In addition, we provide evidence for a 7.6-kilobase pair heteroplasmic deletion (spanning nucleotides 6465-14135) of the mitochondrial DNA in the two tissues and show that directly repeated sequences (11 bp) were present in the wild-type mitochondrial genome at the boundaries of the deletion. Neither of the patient's parents was found to bear rearranged molecules. This study supports the view that a respiratory chain defect can present with insulin-dependent diabetes mellitus as the onset symptom. It also suggests that a defect of oxidative phosphorylation should be considered when investigating other cases of Wolfram syndrome, especially because this syndrome fulfills the criteria for a genetic defect of the mitochondrial energy supply: (a) an unexplained association of symptoms (b) with early onset and rapidly progressive course, (c) involving seemingly unrelated organs and tissues.

Adolescent↗
PubMed1993

[Breaking the isolation. Telecommunication in the service of schooling of sick children].

We describe here a two-way teleconferencing system which links the sterile and pediatric units of the Center for Cancer Treatment in Lyon to a secondary school and the pediatric unit of the University Hospital Edouard-Herriot where primary teaching is given. Léon-Bérard Center and Edouard-Herriot Hospital are 300 m apart. Elie-Vignal secondary school is 6 km from the first site; all three institutes are connected through hyperfrequency aerials. With the help of this system, communication (voice and image) between children in hospital and pupils or teachers in school is instantaneous. Children in bed can listen to the lesson, break in on the conversation in school, ask questions or answer those of teachers. After school time, the system can also be used to organize games between children, or friendly contacts between children in each institute, children in the college, brothers, sisters or friends who may have access to one of those institutes. The system aims are: 1) to improve the education delivered to children and teenagers who spend long periods in hospital; 2) to establish a relationship between both worlds of healthy or sick children through teaching and playing in common; 3) finally, to facilitate the social insertion of sick children at leaving hospital.

Adolescent↗
PubMed1992

Modulation of subcellular distribution of doxorubicin in multidrug-resistant P388/ADR mouse leukemia cells by the chemosensitizer ((2-isopropyl-1-(4-[3-N-methyl-N-(3,4-dimethoxy-beta- phenethyl)amino]propyloxy)-benzenesulfonyl))indolizine.

The impact of the novel chemosensitizer ((2-isopropyl-1-(4-[3-N-methyl-N-(3,4-dimethoxy-beta- phenethyl)amino]propyloxy)benzenesulfonyl))indolizine (SR33557) on the intracellular distribution of doxorubicin (DOX) within the multidrug-resistant murine P388/ADR leukemia cell line was studied by fluorescence microscopy. We found that under conditions which modulated multidrug-resistant (30 microM SR33557 for 1 h), P388/ADR cells presented an original sequestration of DOX in large intracellular vesicles, where SR33557 is itself sequestered, as seen by colocalization studies. Colocalization experiments with lysosomal and mitochondrial probes suggest that these vesicles are neither mitochondrial in nature nor functional lysosomes. To investigate the biochemical basis for this effect, we studied the impact of SR33557 on the sphingolipid metabolism of P388/ADR cells. We observed that although P388/ADR cells normally catabolized exogenous [3H]sphingomyelin, when pretreated with SR33557 they showed almost complete inhibition of sphingomyelin breakdown. Finally, in order to demonstrate that the inability of P388/ADR cells to degrade sphingomyelin in the presence of SR33557 (which is a potent inhibitor of acid lysosomal sphingomyelinase) leads to phospholipid accumulation, we performed electron microscopy where we observed laminated inclusions. These morphological modifications are similar to those observed in Niemann-Pick disease lymphoblastoid cell lines which are inherently deficient in acid sphingomyelinase activity. The observation that, in the absence of SR33557, these Niemann-Pick disease cell lines presented similar DOX sequestration to that of SR33557-treated P388/ADR cells strongly suggests that DOX accumulates in SR33557-induced myeloid bodies. The redistribution of DOX within these vesicles, perhaps by preventing its expulsion by P-glycoprotein, may be a key in discovering the mechanism of action of SR33557.

Animals↗
PubMed1992

Success with coronary angioplasty as seen at demonstrations of procedure.

To assess the real-life results of coronary angioplasty, unidentified participants made notes on 104 cases demonstrated live at twelve international angioplasty courses in 1991. The initially planned procedure was successful in 73% with crossover to another device in 20% for an ultimate success rate of 93%. Interventions lasted an hour on average and two devices on average were used per artery tackled. Rates of success and of complication necessitating reintervention were, for balloon angioplasty (57 cases) 81% and 19%, for directional atherectomy (16 cases) 75% and 0%, for the Rotablator (12 cases) 42% and 42%, for stent implantation (10 cases) 100% and 0%, for excimer laser angioplasty (6 cases) 17% and 33%, and for Rotacs recanalisation (3 cases) 67% and 0%, respectively. The complications were occlusions (threatened, acute, or delayed) and they were usually treated by balloon angioplasty or a stent. No death or myocardial infarction was reported. The observer attending the demonstration tended to take a less favourable view of the outcome than the clinician doing the procedure and in general the results of coronary angioplasty seemed inferior to those reported in journals. Interventions done before an audience will be unusually stressful but this will be outweighed by the fact that difficult cases with a low probability of success are rarely tackled during live courses. This survey suggests that conventional balloon angioplasty, complemented by stent implantation in selected cases, is the treatment of choice.

Adult↗
PubMed1992

Fantofarone (SR 33557): effect on post-ischaemic functional recovery in perfused rat hearts.

Fantofarone (SR 33557) is a novel, highly potent calcium channel antagonist representative of a new class of slow channel blockers. In this study, we have assessed its ability to influence cardiac function in two, isolated, perfused heart models and then assessed its ability to modify post-ischaemic functional recovery. In isolated, rat hearts perfused in the Langendorff mode, fantofarone increased coronary flow by 25% at 100 and 1000 nM with no effect on left ventricular pressure or heart rate below 100 nM. In working hearts, fantofarone again increased coronary flow within a similar concentration range. A significant reduction (approximately 40%) was observed in peak systolic pressure and dP/dtmax when hearts were perfused with 1000 nM fantofarone. Working rat hearts were also subjected to a 30 min period of global, low-flow (0.1 ml/min) ischaemia, followed by a 30 min period of reperfusion. Perfusion with 1 or 10 nM fantofarone, began 20 min prior to the onset of ischaemia and continued throughout the ischaemic and reperfusion periods. The addition of 1 nM fantofarone did not cause a significant increase in the recovery of cardiac function during the reperfusion phase. In contrast, perfusion with 10 nM fantofarone resulted in a substantial increase in the recovery of several indices of cardiac function such as aortic output, dP/dtmax and peak systolic pressure. Thus, in the working rat heart, at concentrations which cause minimal alterations to normal cardiac function, fantofarone can improve significantly functional recovery following an ischaemic insult.

Animals↗
PubMed1992

Fluorescent studies on the interaction between a novel Ca2+ antagonist, SR 33557, and membrane lipids.

The fluorescent properties of SR 33557, a novel calcium entry blocker, have been characterized in solution and when interacting with phospholipid vesicles and natural membranes. The intensity and lifetime of fluorescence emission increased directly as a function of the decrease in the solvent dielectric constant (epsilon) with no change in the emission wavelength maxima. The quantum yield and the fluorescence lifetime in dioxane were 0.90 and 11.1 nsec, respectively. In various vesicles and in erythrocyte ghosts, SR 33557 was shown to be located in a lipidic environment corresponding to an epsilon of 30 congruent to 40. At 25 degrees, the dissociation constant (Kd) was 1.1-7.3 x 10(-6) M with a maximum of 15 SR 33557 molecules bound per 100 phospholipid molecules. When interacting with phospholipids, SR 33557 exhibited two fluorescence lifetimes (approximately 13 and 4 nsec) with the fractional contribution of 81 and 19% of the total decay, respectively. Binding of SR 33557 was enthalpy-driven. Both intensity of fluorescence emission and of fluorescence polarization of SR 33557 were indices of phase transitions in phospholipid vesicles. Thus, SR 33557 has fluorescent properties which may be of use in the study of its mode of action in biological media.

Animals↗
PubMed1992

A novel class of calcium-entry blockers: the 1[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines.

The synthesis and initial biological evaluation of a series of 1-sulfonylindolizines is described. These compounds have been shown to be representatives of a novel class of potent, slow-channel calcium antagonists. All compounds were found to be at least as active as the reference calcium antagonists verapamil and cis-(+)-diltiazem. Structure-activity relationship studies have shown that all compounds possessing an aralkyl group in the amine moiety and an isopropyl or cyclopropyl group at the 2 position of the indolizine are among the most potent calcium antagonists known outside the 1,4-dihydropyridine series. The IC50 values for the inhibition of [3H]nitrendipine binding vary between 0.19 and 4.5 nM whereas the IC50 value for nifedipine is 2.5 nM. One of the compounds in this group (9ab) has now been selected for clinical development.

Animals↗