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Biomedical subjects

M Vincent

Publications and source records attributed to M Vincent.

At least 109 records · Page 6Linked to original sources
PubMed1996

Dobutamine-induced wall motion abnormalities: correlations with myocardial fractional flow reserve and quantitative coronary angiography.

OBJECTIVES: This study evaluated both the relation between dobutamine-induced wall motion abnormalities and the physiologic and morphologic features of epicardial coronary artery stenoses and the impact of the extent of the area at risk on the sensitivity of dobutamine echocardiography. BACKGROUND: The accuracy of dobutamine echocardiography has traditionally been assessed by comparing results with stenosis geometry. Myocardial fractional flow reserve is a functional index of coronary stenosis severity that takes into account both antero-grade and collateral flow and may therefore be a more appropriate standard for comparison. METHODS: Seventy-five patients with normal left ventricular function, good echocardiographic images and an isolated coronary stenosis underwent, within 6 h, dobutamine echocardiography, quantitative coronary angiography and intracoronary pressure measurements. Myocardial fractional flow reserve was calculated as the ratio of mean hyperemic distal coronary to aortic pressure. RESULTS: The degree of dobutamine-induced dyssynergy correlated significantly with percent diameter stenosis (r = 0.68), area stenosis (r = 0.68) and minimal lumen diameter (r = -0.60) and markedly better with myocardial fractional flow reserve (r = -0.77). However, marked dispersion of the individual data was observed. The sensitivity of dobutamine echocardiography in detecting lesions with a minimal lumen diameter < or = 1 mm and diameter stenosis > or = 50% was 83% and 80%, respectively. All but one patient with a myocardial fractional flow reserve >0.75 had a normal stress test result. Among patients with a myocardial fractional flow reserve < or = 0.75, the sensitivity of dobutamine echocardiography was significantly lower for lesions in vessels with a reference diameter < or = 2.6 mm than for lesions in larger vessels (58% vs. 90%, p = 0.008). CONCLUSIONS: 1) The magnitude of wall motion abnormalities induced by dobutamine infusion correlates with angiographic and, more closely, with functional indexes of stenosis severity, even though a wide scatter is observed. 2) In patients with a functionally significant stenosis, the amount of myocardium at risk is a critical determinant of the accuracy of dobutamine echocardiography.

Coronary Angiography↗
PubMed1996

Phase II study of ZD1694 in patients with advanced gastric cancer.

ZD1694 (Tomudex), a quinazoline folate analogue, is a potent and selective thymidylate synthase inhibitor. A phase II trial was undertaken to determine the efficacy and toxicity of ZD1694 in patients with advanced, measurable gastric adenocarcinoma. ZD1694, 3.0 mg/m2, was administered as a 15 min intravenous infusion every three weeks. Tumor measurements were obtained for response assessment every six weeks. Clinical examinations, adverse event assessments, and clinical laboratory tests were performed every three weeks. Thirty-three patients were enrolled. There were no objective responses to ZD1694. In general, treatment was well-tolerated. Grade 3 and 4 toxicities were infrequent, and included mucositis, nausea and vomiting, leukopenia, thrombocytopenia, and elevations of liver enzymes. Mild to moderate asthenia was common. Toxicities with ZD1694 were reversible and manageable. In conclusion, ZD1694 has an acceptable toxicity profile but shows no antitumor activity in patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed1996

Left ventricular weight but not blood pressure is associated with sex chromosomes in Lyon rats.

OBJECTIVE: To investigate, by studying reciprocal back-crosses to Lyon hypertensive (LH) rats, the involvement of sex chromosome loci in high blood pressure and heart weight in LH rats. METHODS: Reciprocal F1 and F'1 generation male rats obtained from male LH x female Lyon normotensive (LN) and male LN x female LH crosses respectively, male back-cross rats obtained from male LH x female F1 or F'1 and from male F1 or F'1 x female LH crosses, and parental LH and LN male rats were studied at 29-31 weeks of age. Systolic, diastolic, mean and pulse pressures were measured beat to beat in unrestrained rats for 1 h. In addition, relative left and right ventricular weights were measured. RESULTS: The average blood pressures did not differ between F1 and F'1 rats or between the four populations of back-cross rats. On the contrary, the relative left ventricular weight was higher in F'1 than in F1 rats. As a role for loci on the Y chromosome could be discarded by comparison of the two populations of back-cross rats, which differ only in the origin of their Y chromosome, this increase in the relative left ventricular weight of F'1 rats was consistent with an effect of a locus on the LH X chromosome. This was supported by findings in the back-cross populations, those populations in which 100% of the rats carried an LH X chromosome having a significantly higher left ventricular weight than those in which only 50% of the rats carried such a chromosome. The estimate of the genetic determination was higher for left ventricular weight (41%) than for mean arterial pressure (19%). Although these two parameters were associated in the back-cross population, the origin of the X chromosome had no influence on this association. CONCLUSIONS: These findings indicate that, against the genetic background provided by the cross studied and at the age studied, the sex chromosomes of LH and LN rats do not contain loci at which alleles differentially influence blood pressure. They do, however, suggest that relative left ventricular weight in this model has a specific genetic determination, partly contributed by a locus on the X chromosome.

Animals↗
PubMed1996

Elevated epidermal growth factor receptor levels in hypertensive Lyon rat kidney and aorta.

1. The adult spontaneously hypertensive Lyon rats (LH strain) exhibited increased maximal epidermal growth factor (EGF) binding in freshly prepared kidney and aortic tissue membranes compared with age-matched normotensive (LN) or hypotensive (LL) strains. However, the binding affinity of the receptors to EGF was the same in all the three strains studied. These findings indicate an increased number of EGF receptors (EGFR) in the hypertensive LH strain. 2. Protein tyrosine kinase activity associated with the EGFR was also elevated in the LH strain compared with LN or LL strains, indicating that these receptors are functionally active. 3. There was a correlation between maximal EGF binding by aortic membranes and blood pressure in individual animals (r = 0.55; P < 0.001). 4. Taken together with previously reported similar findings in other models of genetic hypertension, the present results suggest a possible role for increased levels of EGFR in the development and maintenance of genetic hypertension.

Analysis of Variance↗
PubMed1996

Renin secretion in conscious Lyon hypertensive rats.

To characterize the renin secretory profile in Lyon hypertensive (LH) rats, renin responses to reductions of arterial pressure and beta-adrenoceptor stimulation were assessed in conscious unrestrained LH (n = 13) and Lyon normotensive (LN, n = 14) rats under normal-salt diet. Mean arterial pressure (MAP) in the infrarenal aorta was recorded beat to beat for 3 h. Then, plasma renin concentration (PRC) was measured 1) in basal conditions, 2) during 10-mmHg stepwise reductions of MAP down to 60 mmHg using a chronically implanted aortic inflatable cuff, and 3) during isoprenaline infusion (62.5, 125, and 250 ng.kg-1.min-1 iv). Compared with LN, LH rats had an elevated MAP (146 +/- 3 vs. 111 +/- 1 mmHg, P < 0.001) and decreased PRC [4.2 +/- 0.6 vs. 8.2 +/- 0.8 ng angiotensin (ANG) I.ml-1.h-1, P < 0.001] and kidney renin content (216 +/- 14 vs. 1,149 +/- 103 micrograms ANG I.h-1.g-1, P < 0.001). Pressure-dependent renin release occurred below 90 mmHg in LN rats and below 80 mmHg in LH rats, and its sensitivity in the low-pressure range did not differ between strains. Isoprenaline-induced increases in PRC were weaker (P < 0.01) in LH than in LN rats. In additional LH and LN rats (n = 6-8), acute ANG II AT1-receptor blockade with losartan (20 mg/kg, followed by 10 mg.kg-1.h-1 iv for 2 h) induced lesser (P < 0.001) PRC increases in LH than in LN rats. Renin responses to isoprenaline remained blunted (P < 0.01) during losartan infusion in LH rats. We conclude that, in LH rats, renin secretion is independent of MAP in the range of its spontaneous variations and is poorly responsive to beta-adrenoceptor stimulation, the alteration of which cannot be explained by an enhanced feedback inhibition by ANG II.

Adrenergic beta-Agonists↗
PubMed1996

Analysis of quantitative trait loci for blood pressure on rat chromosomes 2 and 13. Age-related differences in effect.

Previous studies have suggested the presence of quantitative trait loci (QTLs) influencing blood pressure on rat chromosomes 2 and 13. In this study, we mapped the QTLs in F2 rats derived from a cross of the spontaneously hypertensive rat and the Wistar-Kyoto rat and analyzed the effect of the QTLs on blood pressures measured longitudinally between 12 and 25 weeks of age. We analyzed 16 polymorphic markers spanning 147.3 cM on chromosome 2 and 13 markers spanning 91.6 cM on chromosome 13. Both chromosomes contained QTLs with highly significant effects on blood pressure (peak logarithm of the odds [LOD] scores, 5.64 and 5.75, respectively). On chromosome 2, the peak was localized to a position at anonymous marker D2Wox7, 2.9 cM away from the gene for the sodium-potassium ATPase alpha 1-subunit. On chromosome 13, the major peak coincided with the marker D13Mit2, 21.7 cM away from the renin gene, but there was a suggestion of multiple peaks. The effect of the QTL on chromosome 2 was seen throughout from 12 to 25 weeks of age, whereas interestingly, the effect for the QTL on chromosome 13 was maximal at 20 weeks of age but disappeared at 25 weeks of age, presumably because of the effect of either epistatic factors or environmental influences. The findings provide important information on QTLs influencing blood pressure on rat chromosomes 2 and 13 that will be useful in localizing and identifying the causative genes and emphasize the importance of age being taken into account when the effects of individual QTLs on a trait that shows significant age-related changes are being analyzed.

Aging↗
PubMed1996

Connective tissue disease due to intentional inhalation of scouring powder.

There have been reports in the literature of acute and chronic silicosis and connective tissue disease induced by occupational exposure to silica in factories producing scouring powder. Reports of connective tissue diseases induced by intentional inhalation of such a powder are rare and perhaps underestimated. We report the case of a young woman who developed Sharp's syndrome 5 yrs after diagnosis of acute silicosis due to scouring powder inhalation. The frequency of diseases from scouring powder as well as physiopathological and therapeutical issues of the association of pneumoconiosis and connective tissue disease are discussed.

Administration, Inhalation↗
PubMed1996

Major cardiovascular risk factors in Lyon hypertensive rats. A correlation analysis in a segregating population.

OBJECTIVE: To investigate the association of blood pressure with the other major cardiovascular risk factors in a large population of back-cross to Lyon hypertensive (LH) rats. METHODS: Mean arterial pressure was recorded in male freely moving Lyon normotensive (LN), LH, F1 and backcross to LH rats aged 30 weeks. Plasma cholesterol, triglycerides, insulin, creatinine, urea, fibrinogen and haematocrit levels, and the insulin: glucose ratio were measured in 31-week-old rats and 24h albuminuria in 6-week-old rats. RESULTS: Adult LH rats exhibited a significant increase in plasma lipids, insulin, fibrinogen, creatinine, urea and haematocrit levels compared with LN rats. In young LH rats, at an age at which blood pressure is slightly increased, albuminuria was increased to a greater extent than expected from their blood pressure levels. In the adult back-cross to LH rats, only the plasma cholesterol level was associated with blood pressure. Moreover, the plasma cholesterol level was related to fibrinogen and haematocrit levels. Finally, in the same rats, albuminuria developed early in life was positively related to hypercholinesterolaemia measured later in life. CONCLUSION: Plasma cholesterol, fibrinogen, haematocrit levels and early albuminuria could act synergistically in the enhancement or the development, or both, of vascular and kidney damage in the LH rat. Most interestingly, the association between plasma cholesterol level and blood pressure indicates that, as in essential hypertension, hypercholesterolaemia is a major phenotype associated with hypertension in the LH rat.

Albuminuria↗
PubMed1996

[Two strains of genetically hypertensive rats, LH and SRH, have distinct profiles of postnatal expression of tropoelastin and type III collagen in the aortic wall].

Experimental pharmacology and studies on hypertension frequently use genetically hypertensive animal models like the SHR or the Lyon hypertensive rat LH. In order to further characterize these two models we measured the expression levels of three major extracellular matrix components in the aortic wall, tropoelastin (TE) and type I and type III collagen, during postnatal development. The type I collagen expression decreases progressively during the first twelve weeks of postnatal development without significant differences between SHR and LH, or their normotensive controls, WKY or LN respectively. No differences were detected either for the expression levels of TE and type III collagen between the hypertensive strains and their respective controls. However, direct comparison of the two hypertensive strains SHR and LH, revealed a specific, strong increase of TE and type III expression for the LH at 5 and 12 weeks (p < 0.001 and 0.005 respectively). The evolution of the ratios of expression levels between the two collagens (type III/type I) on one side and of TE and collagen type I (TE/type I) on the other side were similar for the hypertensive strains and their respective controls, but diverged significantly for LH and SHR animals (up to p < 0.001 depending on the age group). Both indicators, III/I and TE/I, are considerably higher in LH compared to SHR from 5 weeks of postnatal development onwards. Our results indicate that the genes for TE and type I and III collagen are regulated during postnatal development of LH and SHR. It is however not possible at this point to establish a link between mRNA levels and hypertension in these animals. Nevertheless, the ratios III/I and TE/I seem to be good phenotypic markers for the characterisation of LH and SHR strains.

Animals↗
PubMed1996

HSP27 locus cosegregates with left ventricular mass independently of blood pressure.

Left ventricular hypertrophy remains a significant clinical problem and a predictor of fatal outcome in hypertension. Blood pressure per se and environmental modifiers including stress affect cardiac mass. Heat shock proteins are involved in the stress response as well as in the regulation of cardiac growth and cytoprotection. The present study evaluates heat shock protein 27 as a locus marker or candidate gene of cardiac hypertrophy in hypertension. The spontaneously hypertensive rat allele of heat shock protein 27 was associated with about a 6% increase in relative left ventricular weight (P = .0112) in 30 recombinant inbred strains from crosses of Brown Norway and spontaneously hypertensive rats. In 336 F2 crosses of spontaneously hypertensive and Wistar-Kyoto rats, the hypertensive allele was dominant and cosegregated with a similar 6% increase in the ratio of left ventricular weight to body weight (P = .0058) in rats fed a normal salt diet, but its contribution to left ventricular weight decreased in rats kept on a high salt diet. The contribution of the heat shock protein 27 allele was independent of blood pressure. We suggest that heat shock protein 27 represents a candidate gene/locus marker of cardiac hypertrophy in hypertension.

Alleles↗
PubMed1995

The nuclear matrix phosphoprotein p255 associates with splicing complexes as part of the [U4/U6.U5] tri-snRNP particle.

The monoclonal antibody CC3 recognizes a phosphorylated epitope present on an interphase protein of 255 kDa. Previous work has shown that p255 is localized mainly to nuclear speckles and remains associated with the nuclear matrix scaffold following extraction with non-ionic detergents, nucleases and high salt. The association of p255 with splicing complexes is suggested by the finding that mAb CC3 can inhibit in vitro splicing and immunoprecipitate pre-messenger RNA and splicing products. Small nuclear RNA immunoprecipitation assays show that p255 is a component of the U5 small nuclear ribonucleoprotein (snRNP) and the [U4/U6.U5] tri-snRNP complex. In RNase protection assays, mAb CC3 immunoprecipitates fragments containing branch site and 3' splice site sequences. As predicted for a [U4/U6.U5]-associated component, the recovery of the branch site-protected fragment requires binding of U2 snRNP and is inhibited by EDTA. p255 may correspond to the previously identified p220 protein, the mammalian analogue of the yeast PRP8 protein. Our results suggest that changes in the phosphorylation of p255 may be part of control mechanisms that interface splicing activity with nuclear organization.

Animals↗
PubMed1995

Arrest at the G2/M transition of the cell cycle by protein-tyrosine phosphatase inhibition: studies on a neuronal and a glial cell line.

The addition of the peroxovanadium (pV) derivatives potassium bisperoxo(1,10-phenanthroline)oxovanadate(v) (bpV[phen]) or potassium bisperoxo(pyridine-2-carboxylato) oxovanadate(v) (bpV[pic]), both of which are potent inhibitors of protein tyrosine phosphatases (PTPs) [Posner et al. (1994): J Biol Chem 269:4596-4604], to the culture medium of neuroblastoma NB 41 and glioma C6 cells resulted in a marked decrease in their proliferation rates and a progressive accumulation at the G2/M transition of the cell cycle. The effect was dependent on dose, cell type, and a pV compound employed. Mean values of the RNA-to-DNA and RNA-to-protein ratios in NB cells treated for 48 h with increased doses of bpV[phen] showed that general synthetic functions were not altered, nor did we observe oxidative damage to DNA using a sensitive DNA-nick detection assay. No changes in the expression and localization of vimentin, a component of the intermediate filament cytoskeleton, were observed by indirect immunofluorescence, showing that treatment did not disturb the cytoskeleton network. Measurements of BrdU incorporation into newly synthesized DNA showed that cells treated were not totally arrested. Furthermore, cells arrested G2/M were able to reenter the cycle rapidly after the release of inhibition. This progressive accumulation of G2/M coincided with the detection of tyrosine-phosphorylated p34cdc2 and a dramatic reduction in its kinase activity toward histone H1 by 48 h of culture. Both compounds were equally potent in inhibiting the catalytic activity of a yeast and the structurally distant mouse cdc25B in vitro, suggesting that augmented tyrosine phosphorylation of p34cdc2 derived from the in vivo inhibition of cdc25. Their equal in vitro potency contrasted with the considerably greater potency of bpV[phen] in vivo, in vivo suggesting that factors regulating the intracellular access of these compounds to cdc25 might be critical in determining in vivo specificity. In conclusion the final consequence of long-term exposure to potent and structurally defined PTP inhibitors on two highly proliferative nerve cell lines is to restrict cell growth. The corresponding hyperphosphorylation and reduced activity of p34cdc2 likely reflects the unusual sensitivity of cdc25 as an in vivo target for peroxovanadium compounds.

CDC2 Protein Kinase↗
PubMed1995

Alterations of cytosolic calcium in platelets and erythrocytes of Lyon hypertensive rats.

Platelet cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pHi) (including their responses to thrombin), as well as erythrocyte [Ca2+]i and 45Ca2+ influx, were studied in Lyon hypertensive (LH) and normotensive (LN) rats aged 3 months. Platelets of LH rats were characterized by substantially elevated basal [Ca2+]i values, higher [Ca2+]i levels after thrombin stimulation, and enhanced initial rate of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels. Basal platelet pHi values were not significantly different in LH and LN animals but thrombin elicited a significant alkalinization only in LH platelets. Erythrocytes of LH rats had an enhanced initial rate of 45Ca2+ and tended to elevated [Ca2+]i levels. Our data indicate profound alterations in cell Ca2+ handling in platelets and erythrocytes of LH rats, similar to those previously described in spontaneously hypertensive rats of the Okamoto-Aoki strain. The analysis of the relations between blood pressure, plasma lipids, and cell Ca2+ handling suggested that triglycerides, but not cholesterol, might be involved in altered platelet Ca2+ handling in LH rats.

Animals↗
PubMed1995

Photophysics of the fluorescent Ca2+ indicator Fura-2.

The photophysics of the complex forming reaction of Ca2+ and Fura-2 are investigated using steady-state and time-resolved fluorescence measurements. The fluorescence decay traces were analyzed with global compartmental analysis yielding the following values for the rate constants at room temperature in aqueous solution with BAPTA as Ca2+ buffer: k01 = 1.2 x 10(9)s-1, k21 = 1.0 x 10(11) M-1 s-1, k02 = 5.5 x 10(8) s-1, k12 = 2.2 x 10(7) s-1, and with EGTA as Ca2+ buffer: k01 = 1.4 x 10(9) s-1, k21 = 5.0 x 10(10) M-1 s-1, k02 = 5.5 x 10(8) s-1, k12 = 3.2 x 10(7) s-1. k01 and k02 denote the respective deactivation rate constants of the Ca2+ free and bound forms of Fura-2 in the excited state. k21 represents the second-order rate constant of binding of Ca2+ and Fura-2 in the excited state, whereas k12 is the first-order rate constant of dissociation of the excited Ca2+:Fura-2 complex. The ionic strength of the solution was shown not to influence the recovered values of the rate constants. From the estimated values of k12 and k21, the dissociation constant K*d in the excited state was calculated. It was found that in EGTA Ca2+ buffer pK*d (3.2) is smaller than pKd (6.9) and that there is negligible interference of the excited-state reaction with the determination of Kd and [Ca2+] from fluorimetric titration curves. Hence, Fura-2 can be safely used as an Ca2+ indicator. From the obtained fluorescence decay parameters and the steady-state excitation spectra, the species-associated excitation spectra of the Ca2+ free and bound forms of Fura-2 were calculated at intermediate Ca2+ concentrations.

Biophysical Phenomena↗
PubMed1995

Photophysics of the fluorescent K+ indicator PBFI.

The fluorescent indicator PBFI is widely used for the determination of intracellular concentrations of K+. To investigate the binding reaction of K+ to PBFI in the ground and excited states, steady-state and time-resolved measurements were performed. The fluorescence decay surface was analyzed with global compartmental analysis yielding the following values for the rate constants at room temperature in aqueous solution at pH 7.2: k01 = 1.1 x 10(9) s-1, k21 = 2.7 x 10(8) M-1s-1, k02 = 1.8 x 10(9) s-1, and k12 = 1.4 x 10(9) s-1. k01 and k02 denote the respective deactivation rate constants of the K+ free and bound forms of PBFI in the excited state. k21 represents the second-order rate constant of binding of K+ to the indicator in the excited state whereas k12 is the first-order rate constant of dissociation of the excited K(+)-PBFI complex. From the estimated values of k12 and k21, the dissociation constant Kd* in the excited state was calculated. It was found that pKd* (-0.7) is smaller than pKd (2.2). The effect of the excited-state reaction can be neglected in the determination of Kd and/or the K+ concentration. Therefore, intracellular K+ concentrations can be accurately determined from fluorimetric measurements by using PBFI as K+ indicator.

Benzofurans↗
PubMed1995

Survey of carer satisfaction with the quality of care delivered to in-patients suffering from dementia.

Quality assurance in British National Health Service provision stresses the importance of taking account of the consumer's viewpoint. Elderly patients with dementia are not always able to contribute usefully to satisfaction surveys. Therefore, their careers' views were sought in order to assess the quality of services offered to this client group. Forty-one careers of patients discharged from the eight wards for the elderly mentally ill in Leicestershire, England, were randomly selected. Individual focused interviews were conducted in careers' own homes. Both quantitative and qualitative data were obtained by use of a questionnaire designed to tap the patients'/careers' experiences from pre-admission, through hospital stay to post-discharge. Interviews were asked to describe their favorable/unfavorable impressions of, and reactions to, all aspects of hospital care. These interviews were tape-recorded. Analysis of the data included quantitative measurements of scale ratings. Grounded theory was used to analyse qualitative data. A wealth of information was uncovered using this research technique. Much that was positive about the service was elicited. However, careers highlighted areas where they felt the quality of care could be improved within all the foci discussed. Twenty-two recommendations for quality improvements in service provision were made in the report as a result of this survey.

Aged↗
PubMed1995

Inferior vena cava thrombosis following percutaneous filter insertion: an unusual cause of haemodynamic compromise.

Inferior vena cava thrombosis is a well-recognized complication of filter insertion. We report on two patients who presented with progressive exertion dyspnoea and lipothymia revealing a complete inferior vena cava thrombosis below the filter. Haemodynamic exploration demonstrated that cardiac output could not adapt during upright exercise owing to inappropriate cardiac preload. Since these general manifestations can precede any symptom of lower limb venous stasis, thrombosis of inferior vena cava has to be carefully searched in this setting. The pathogenesis of this unusual complication is reviewed in the light of experimental models of vena cava ligation.

Aged↗