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Publications and source records attributed to E Page.

At least 19 recordsLinked to original sources

[Exertional hypertension and sport].

Defining the normal range of blood pressure during exertion is not easy. Each type of exercise induces increased blood pressure that responds to a particular curve, and adaptation modes differ according to age, gender, physical condition, basal blood pressure, etc. The best studied is blood pressure measured on the arm using a cycloergometre. Classical publications established blood pressure curves according to heart rate during exercise. It appears that the best scale of reference for power developed occurs in individuals who can provide a very high degree of effort and in particular, athletes who are in very good training. According to some authors, hypertension on exertion would entail a poor prognosis, even in the absence of resting hypertension. Nevertheless, there is presently no well established therapeutic recommendation concerning exertion hypertension. This approach could depend on resting blood pressure and on the existence of other risk factors. For an athlete, pursuing physical activity is most often encouraged, sometimes after treatment or adjustment of its level.

Blood Pressure↗

Efficacy of a hepatitis C virus core antigen enzyme-linked immunosorbent assay for the identification of 'window-phase' blood donations.

BACKGROUND AND OBJECTIVES: Recent studies have suggested that potentially infectious donations provided during the antibody-negative 'window' phase of hepatitis C virus (HCV) infection may be identified by testing for viral RNA or HCV core protein. We therefore evaluated the performance of an HCV antigen enzyme-linked immunosorbent assay (ELISA) for identification of window-phase donations and for prospective screening of blood donors. MATERIALS AND METHODS: One-hundred and twenty-eight archived plasma donations containing HCV RNA, but lacking antibody to HCV (anti-HCV), were tested by using the HCV antigen ELISA, together with 9951 freshly collected serum and plasma specimens from blood donors. RESULTS: HCV core antigen was detected in 94% (120/128) of window-phase plasma donations. Overall specificity in freshly collected blood donor specimens was 99.74%. Two putative window-phase donations containing HCV core protein and viral RNA were identified from paid plasma donors by prospective testing with the HCV antigen ELISA. CONCLUSION: These results indicate that an HCV antigen ELISA can identify almost all (94%) of viraemic donations given during the seronegative window phase of infection. The performance of the HCV antigen ELISA appears to be suitable for large-scale screening of blood donations.

Antibodies, Viral↗

[Cardiac metastasis from a Merkel cell skin carcinoma. A case report].

The authors report the case of a cardiac metastasis of a Market cell skin tumour in a 72 year old woman, presenting with chest pain and infero-lateral myocardial ischaemia simulating an acute coronary syndrome. The diagnosis, suspected on echocardiography, was confirmed by thoracic CT scan. Markel cell carcinoma is a rare skin tumour classified among the malignant neuroendocrine tumours. It has a high metastatic potential, especially to the gastrointestinal tract and the lung. On the other hand, cardiac metastases are quite exceptionally rare.

Aged↗

Dystrophin associates with caveolae of rat cardiac myocytes: relationship to dystroglycan.

The possibility of an interaction between the cytoskeletal protein dystrophin and cell surface caveolae in the mammalian myocardium was investigated by several techniques. Caveolin (cav)-3-enriched, detergent-insoluble membranes isolated from purified ventricular sarcolemma by density-gradient fractionation were found to contain dystrophin and dystroglycan. Further purification of cav-3-containing membranes by immunoprecipitation using anti-cav-3-coated magnetic beads yielded dystrophin but not always dystroglycan. Electron microscopic analysis of precipitated material revealed caveola-sized vesicular profiles that could be double-labeled with anti-dystrophin and anti-cav-3 antibodies. In contrast, immunoprecipitation of membranes with anti-dystrophin-coated beads yielded both cav-3 and dystroglycan. Electron microscopic analysis of this material showed heterogeneous membrane profiles, some of which could be decorated with anti-cav-3 antibodies. To confirm that dystrophin and cav-3 were closely associated in cardiac myocytes, we verified that dystrophin was also present in immunoprecipitated cav-3-containing membranes from detergent extracts, as well as in sonicated extracts of purified ventricular myocytes. Confocal immunofluorescence microscopy of ventricular and atrial cardiac myocytes showed that the cellular distributions of cav-3 and dystrophin partially overlapped. Immuno-electron micrographs of thin sections of rat atrial myocytes revealed a fraction of dystrophin molecules that are in apparently close apposition to caveolae. These results suggest that a subpopulation of dystrophin molecules interacts with cardiac myocyte caveolae in vivo and that some of the dystrophin is engaged in linking cav-3 with the dystroglycan complex.

Animals↗

Comparative effects of bisoprolol and nitrendipine on exercise capacity in hypertensive patients with regular physical activity.

The aim of this study was to evaluate the long-term effects of administering bisoprolol compared with nitrendipine on the duration of the exercise tolerated by male and female patients, aged 18-65 years, having mild to moderate hypertension and taking regular exercise. In this double-blind, randomized prospective study, 96 patients (85 men and 11 women, 48+/-10 years) formed two groups: 49 in the bisoprolol group, and 47 in the nitrendipine group. After a washout period of 14 days, either 10 mg of bisoprolol or 20 mg of nitrendipine was given daily over a treatment period of 12 weeks. During the treatment period, the stability of the physical training was monitored weekly by using a questionnaire. The results of two maximal triangular exercise tolerance tests (ETTs) on an ergometric bicycle performed at D0 under placebo and at D84 under active treatment were compared. No statistical difference was observed between both groups, concerning age, gender, morphologic characteristics, resting cardiovascular parameters, or physical training. Both groups maintained the same training level throughout the study. No significant differences between the groups were noted for duration of ETT [D0 892+/-284 s, D84, 919+/-267 s (NS) vs. D0 929+/-290 s, D84 904+/-324 s (NS)], or maximal work load [D0 190+/-49 W, D84 197+/-48 W (NS) vs. D0 198+/-49 W, D84 196+/-55 W (NS)]. On the other hand, both groups differed in maximal systolic blood pressure [D0 239+/-24 mm Hg, D84 215+/-22 mm Hg (p<0.001) vs. D0 237+/-24 mm Hg, D84 222+/-27 mm Hg (p<0.05)] (p = 0.05), and maximal pulse rate during exercise [141+/-18 vs. 163+/-17] (p<0.001), albeit not in maximal diastolic blood pressure [D0 113+/-13 mm Hg, D84 106+/-17 mm Hg (p<0.05) vs. D0 112+/-13 mm Hg, D84 104+/-15 mm Hg (p<0.05)]. The patient's own perception of the maximal effort (Borg scale) was not significantly different in either of the groups (placebo vs. treatment). Overall, in a population of hypertensive patients taking regular exercise, long-term treatment with bisoprolol produced no significant changes in the duration of peak effort, maximal workload, or the effort perceived by the patients themselves. The effects of regular exercise were comparable in both groups (bisoprolol or nitrendipine). Because previous studies have shown that dihydropyridines do not modify exercise performance in hypertensive patients, it may be concluded that the antihypertensive therapy with bisoprolol is well tolerated in a population of active hypertensive patients during dynamic exercise.

Adolescent↗

Comparison of metabolic expenditure during CAEP versus a test adapted to aerobic capacity (Harbor test) in elderly healthy individuals.

Cardiopulmonary exercise tests are frequently used to test rate responsive pacemakers. The chronotropic assessment exercise protocol (CAEP) has been specifically proposed for the evaluation of rate responsive pacing systems. A mathematical method, based on CAEP measurements, was developed with a view of normalizing the exercise induced metabolic response. CAEP was compared to a tailored protocol (Harbor), adapted to the metabolic capacity of each patient. Harbor was set to keep the exercise duration within 10 minutes and achieve a workload as linear as possible. Metabolic parameters were continuously recorded by a cardiopulmonary system. Those data were used in the construction of slopes by the normalization method. The results of the tests performed in 16 elderly healthy patients showed no differences in metabolic or functional parameters. Slopes of the mathematical model were comparable (1.09 +/- 0.16 for CAEP vs 1.07 +/- 0.17 for Harbor), though both were higher than the value of 1, defined as normal. In both cases, linearity was confirmed by the coefficient of correlation (0.98 +/- 0.02 for CAEP and Harbor). In conclusion, no significant differences were found in the outcomes of the two protocols. Higher values of the slopes with the normalization method can be explained by the definition of the maximal predicted heart rate as 220--age, which is probably not appropriate for elderly, healthy, active subjects.

Aged↗

T-cadherin is a major glycophosphoinositol-anchored protein associated with noncaveolar detergent-insoluble domains of the cardiac sarcolemma.

Sucrose-density flotation analysis of Triton-insoluble membrane domains isolated from highly purified sheep ventricular sarcolemma revealed the presence of two major 120- and 100-kDa proteins. Both species migrated in two-dimensional isoelectric focussing/SDS gels with an apparent pI of approximately 4.3, suggesting that they might be related. Microsequence analysis of peptides derived from the 100-kDa protein yielded amino acid sequences with high homology to T-cadherin, a truncated cadherin lacking a cytoplasmic domain. The similarity was confirmed using antibodies to chicken T-cadherin that reacted with both proteins on immunoblots. T-cadherin was released from the detergent-insoluble sarcolemmal fraction by phospholipase C treatment indicating that it is linked to the membrane by a glycophosphoinositol anchor. T-cadherin could be ADP-ribosylated by a transferase that was also present in the caveolin-enriched Triton-insoluble fraction. T-cadherin-containing membrane fragments cofractionated on sucrose gradients with caveolin-3, a marker protein for myocyte caveolae. However, immunopurified caveolin-3-containing membranes contained no associated T-cadherin. Immunocytochemical analysis of cultured rat atrial myocytes revealed that T-cadherin and caveolin have related but nonoverlapping staining patterns. These results suggest that T-cadherin is a major glycophosphoinositol-linked protein in cardiac myocytes and that it may be located in plasma membrane "rafts" distinct from but possibly adjacent to caveolae.

Amino Acid Sequence↗

Effects of indomethacin and polyunsaturated fatty acid diet on exercise-induced hypoxaemia in master athletes.

We have previously reported a reduction in exercise-induced hypoxaemia following polyunsaturated fatty acid supplementation (PUFA). Although this might have been explained by increases in membrane fluidity, a clear explanation could not be provided due to potentially confounding influences of series-2 prosta- glandin mediated effects resulting from PUFA. In this investigation, ten master athletes [mean age 48.1 (SEM 6) years, maximal oxygen uptake (VO2max) 3.39 (SEM 0.21) l x min(-1)] completed a maximal cycling test (Ctrl) which was repeated after the administration of 150 mg of indomethacin to inhibit prostaglandin synthesis, both before and after 6 weeks of 3.66-g PUFA x day(-1). Cardiorespiratory parameters were obtained simultaneously with brachial arterial blood sampling for partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), pH, oxygen saturation in arterial blood and lactate concentration determinations. A significant decrease in PaO2 (mmHg) from rest [93 (SEM 1.5)] was observed for exercise intensities of more than 40% VO2max in Ctrl reaching 75.9 (SEM 2.1) at VO2max. PUFA resulted in a 5.0 (SEM 0.68) mmHg upward shift (P < 0.05) in the PaO2-oxygen uptake relationship, reducing the difference in partial pressure of oxygen between alveolar air and arterial blood (P(A-a)O2) at VO2max [Ctrl 36 (SEM 1.6) vs PUFA 33 (SEM 2.2) mmHg] while PaCO2, remained unchanged. Indomethacin had no effect on either PaO2, ideal partial pressure of oxygen in alveolar gas or P(A-a)O2 in either Ctrl or after PUFA. In contrast, the fall in pH was significantly reduced after indomethacin while VCO2, PaCO2 and lactacidaemia remained unchanged. These observations confirm an effect of PUFA on exercise PaO2 behaviour which does not appear to be mediated by the influence of a series-2 prostaglandin.

Adult↗

Water channel proteins in rat cardiac myocyte caveolae: osmolarity-dependent reversible internalization.

We show by confocal immunofluorescence microscopy that the water channel protein aquaporin-1, not previously identified within cardiomyocytes, localizes at 20 and 37 degrees C to rat cardiomyocyte sarcolemmal caveolar membrane and subsarcolemmal cytoplasm of primary atrial myocyte cultures, dissociated atrial and ventricular myocytes, and in situ cardiomyocytes of atrial and ventricular frozen sections. Confocal immunofluorescence microscopy shows that the normal in situ colocalization of the quasi-muscle-specific caveolar coating protein caveolin-3 with aquaporin-1 is reversibly disrupted by exposing in situ atrial or ventricular myocytes to physiological saline made hypertonic by adding 150 mM sucrose or 75 mM NaCl to isotonic physiological saline. This causes caveolae to close off from the interstitium and swell, while aquaporin-1 is internalized reversibly. At 4 degrees C aquaporin-1 does not colocalize with caveolin-3. We suggest that 1) in vivo, under near-isotonic conditions, caveolae may alternate frequently between brief open and closed-off states; 2) aquaporin-1-caveolin-3 colocalization may be energy dependent; and 3) while closed off from the interstitium, each caveola transiently functions as an osmometer that experiences, monitors, and reacts to net water flow from or into the subcaveolar cytosol of the myocyte.

Animals↗

[Diagnostic use of oxygen consumption and gas exchange in exercise testing].

The interpretation of cardio-pulmonary exercise testing is usually performed on successive decisional organigrams which are based on the normality of two initial main branchpoints i.e., Vo2max and ventilatory threshold (VThr). This didactic approach leads however to a simplistic approach of exercise pathophysiology because the answer to the two original branchpoints (Vo2max and VThr) is mainly binary whereas the physiological meaning of these two parameters is multifactorial. Thus, we propose a methodic analytical approach which allows to integrate step by step the various informations concerning aerobic capacity, ventilatory and cardiocirculatory responses, and acidobasic status. After a purely descriptive analysis of data , a first synthesis describes the physiopathological behaviour during exercise and states the specificity of these informations excluding usual confounding factors. The comparison between the functional data and the clinical informations allows to propose some physiopathological hypothesis by confronting several complementary approaches: physiological, physiopathological and clinical ones. This method seems to be more adapted to the clinical diagnostic use of such a physiological investigation because it is sensitive, reproducible but not specific.

Data Interpretation, Statistical↗

Type B atrial natriuretic peptide receptor in cardiac myocyte caveolae.

We have previously shown that atrial natriuretic peptide (ANP) is present in caveolae of in situ rat atrial myocytes. To investigate whether intracaveolar ANP of rat atrial myocytes exists within caveolae bound to type B ANP receptors (ANP-RB, a guanylyl cyclase), we have used confocal immunofluorescence microscopy applied to primary cultures of atrial myocytes from adult rats and to freshly dissociated rat atrial myocytes (not cultured). These experimental designs tested whether atrial myocyte ANP-RB colocalizes at the plasmalemma and elsewhere in the cell with the muscle-specific isoform of the caveolar coating protein caveolin-3, and with a fraction of cellular ANP. The experiments showed that cellular caveolin-3, a fraction of cellular ANP-RB, and a fraction of cellular ANP colocalize at the plasmalemma of cultured atrial myocytes and of freshly dissociated atrial myocytes. The observations support the hypothesis that in rat atrial myocytes, intracaveolar ANP is bound to ANP-RB, a protein whose cytosolic amino acid sequences are known to encode guanylyl cyclase activity. We suggest that among the (probably multiple) effects of the cGMP thus generated in the cytoplasmic microdomain underlying atrial myocyte caveolae may be the activation of cGMP-dependent protein kinase, which would thereby inhibit plasma membrane Ca2+ channel activity and contribute to a negative inotropic effect of ANP.

Animals↗

Quality control for qualitative assays: quantitative QC procedure designed to assure analytical quality required for an ELISA of hepatitis B surface antigen.

An assay for hepatitis B surface antigen (HBsAg) should reliably detect 0.2 microgram/L, the lowest reported concentration in an asymptomatic blood donor. The difference between this concentration and the assay cutoff defines the analytical quality requirement in a total error format. The design of a statistical QC procedure is critically dependent on the precision of the assay. The precision of a developmental ELISA of HBsAg under study ranged from 17.5% to 9.6% for controls containing 0.07 to 1.50 micrograms/L, respectively. Use of one positive control with the 1(3s), QC rule provided an 85% chance of detecting a critical loss of assay sensitivity; use of two positive controls increased the chance of detecting critical loss of assay sensitivity to nearly 100%. These rules are based on the precision of this developmental assay, and must be developed individually for other assays. The development of the proposed QC procedures illustrates how quantitative QC can be provided for qualitative assays.

Blood Donors↗

Cardiac output response to dynamic exercise after atrial switch repair for transposition of the great arteries.

Results from this study showed that patients who underwent successful operation for transposition of the great arteries had no appropriate increase in stroke volume in response to exercise of a nature similar to common recreational activities. The impairment, most likely due to disturbances in both venous return and ventricular systolic function, is compensated for by an increase in peripheral oxygen extraction; however, this increase may not be adequate with maturation or during prolonged exercise when cardiovascular constraints are more important.

Cardiac Output↗