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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 163 records · Page 9Linked to original sources
PubMed1994

[Physical activity, blood pressure and hypertension].

Both dynamic predominantly isotonic and static or isometric exercise increase blood pressure, but pressure reaches higher levels during static effort. One should be aware, however, that blood pressure may rise considerably when hypertensive patients perform dynamic exercise. The response of blood pressure to exercise is rather variable from patient to patient, but this variability does not provide independent prognostic precision when pressure at rest is taken into account. Blood pressure per se adversely affects maximal aerobic power, which is related to an impaired maximal stroke volume that can be ascribed to the high afterload or to impaired ventricular filling at high heart rate. Dynamic, relatively intense physical training, performed at least 3 times 30 minutes per week for 1 to 8 months, has been shown to reduce blood pressure, particularly in hypertensive patients. After training, blood pressure was also reduced when measured during exercise and during daytime ambulatory monitoring. Physical training can therefore be advocated in the management of the hypertensive patient. Finally, when prescribing antihypertensive medication to exercising patients, one should be aware that some drugs, particularly beta-blockers and diuretics, may reduce exercise performance or even impair the conditioning response.

Adolescent↗
PubMed1994

Efficacy and safety of pravastatin in hypertensive hypercholesterolaemic patients on antihypertensive drug therapy.

This double-blind, placebo-controlled, six month trial evaluated the efficacy and safety of pravastatin in hypercholesterolaemic, hypertensive patients on antihypertensive treatment, who on a standard lipid-lowering diet maintained a plasma total cholesterol level of at least 250 mg%. Fifty hypertensive patients were randomised to placebo or pravastatin treatment. Once daily dosing consisted of 10 mg pravastatin during the first month, 20 mg during the second month and 40 mg during an additional 4 months or matching placebos. Compared with placebo, pravastatin reduced (P < 0.001) the plasma level of total cholesterol, LDL-cholesterol and phospholipids during the six month study period whereas plasma HDL-cholesterol and triglycerides did not change significantly. These changes in plasma lipids were independent of age and of the nature of the concomitant antihypertensive treatment. No serious side-effects were observed and pravastatin was generally well tolerated. In conclusion, pravastatin 10-40 mg once daily reduced plasma total and LDL-cholesterol in hypercholesterolaemic, hypertensive patients, independent of age and concurrent antihypertensive drug therapy.

Adolescent↗
PubMed1994

Number of measurements required for the analysis of diurnal blood pressure profile.

The aim of this study was to investigate how frequent blood pressure (BP) readings need to be obtained to reproduce the diurnal BP profile without loss or distortion of information. The subjects were 97 normotensives aged 23-84 years. Noninvasive ambulatory BP readings were programmed with an interval of 7.5 minutes during the day (from 8 am to 8 pm) and at 15 minutes intervals at night. Readings were stepwise omitted from the original recordings. For each step the diurnal BP profile was modelled with five different techniques. The concordance between original and reduced recordings was quantified using the repeatability coefficient, i.e. twice the standard deviation of the differences between these recordings (expressed as a percentage of the 5th to 95th percentile range of the parameter under investigation). The concordance between original and reduced recordings tended to be better for the level of pressure than for the parameters of the diurnal profile. If the sampling frequency was two readings per hour, concordance for SBP was < 10% for the BP level, 19% for the 24h standard deviation, 12% for the nocturnal fall in BP, 23% for the amplitude of the Fourier curve and 17% for the cusum derived circadian alteration magnitude. Concordance worsened to > 25% for most parameters of the diurnal BP curve when the interval between consecutive measurements exceeded 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A consistent reference frame for ambulatory blood pressure monitoring is found in different populations.

This study investigated the consistency of a reference frame for ambulatory pressure monitoring, which using various approaches was determined in two different populations. The two reference groups were 718 subjects randomly selected from the population and 895 bank employees. The reference values derived in these two groups were subsequently tested in 591 untreated hypertensive patients. The ambulatory pressures equivalent to a conventional pressure of 140 mmHg systolic and 90 mmHg diastolic were calculated by regression analysis in all subjects. In addition, in subjects who were normotensive by conventional sphygmomanometry, the mean +2 and +3 standard deviations and the 90th, 95th and 99th percentiles of the ambulatory measurements were determined. The distributions of the ambulatory measurements were similar in the two reference groups and the aforementioned parameters therefore agreed within 4 mmHg in the two populations. There was considerable overlap in the ambulatory pressures between the two reference groups and the hypertensive patients. Classification of the patients according to the means +3 standard deviations and the regression limits gave the same results because in both reference groups these boundaries approximated to each other within 1 mmHg. For the 24 h pressures in the population sample these boundaries were 140 mmHg systolic and 88 mmHg diastolic. Of the patients with systolic hypertension (> or = 160 mmHg on conventional measurement), 39% had a 24 h systolic pressure of < 140 mmHg and of those with diastolic hypertension (> or = 95 mmHg), 44% had a 24 h diastolic pressure of < 88 mmHg; if the corresponding boundaries derived in the bank employees (143/90 mmHg) were applied, these proportions were 47% and 44%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Influence of cholesterol lowering on plasma membrane lipids and cationic transport systems.

BACKGROUND: In order to determine whether alterations in membrane lipids affect transmembrane cationic transport systems in erythrocytes and platelets, cationic fluxes and intracellular cationic concentrations were measured in hypercholesterolaemic patients before and during administration of an inhibitor of 3-hydroxy-3-methlglutaryl coenzyme A reductase. METHODS: After a 1-month run-in placebo period on a lipid-lowering diet the patients were treated, in a double-blind manner, with either placebo (n = 25) or pravastatin (n = 25) for 6 months. Placebo or pravastatin (10 mg during the first month, 20 mg during the second month and 40 mg during the remaining 4 months) was administered once a day in the evening. RESULTS: Compared with the placebo group, the erythrocyte and platelet membrane cholesterol content was reduced in the patients treated with pravastatin. The intra-erythrocyte and intraplatelet Na+ concentration was reduced during pravastatin administration, whereas the activity of the erythrocyte and platelet Na(+)-K+ pump was increased. However, the intra-erythrocyte and intraplatelet K+, Mg2+ and cytosolic Ca2+ concentrations, and water content, as well as the activities of the erythrocyte Na(+)-Li+ countertransporter and Na+,K+ cotransporter, and Na+ and K+ leakage, were not changed during pravastatin treatment. CONCLUSIONS: The present data show that cholesterol lowering in hypercholesterolaemic patients may result in a significant decrease in erythrocyte and platelet membrane cholesterol content. These changes in membrane cholesterol are accompanied by an increase in activity of the Na(+)-K+ pump and a decrease in intra-erythrocyte and intraplatelet Na+ concentrations.

Biological Transport↗
PubMed1994

Mechanical and other factors relating to left ventricular hypertrophy.

Although the development of left ventricular hypertrophy in hypertension is explained as a response to increases in pressure load and wall tension, the relationship between left ventricular mass and conventional blood pressure is usually weak. This may be due to the lack of standardization and the small number of blood pressure measurements in some studies. However, even 24-h blood pressure monitoring can explain only around 25% of the variation in left ventricular mass, and repeated blood pressure measurements over 30 years have not proved better in this respect. Therefore, other factors have been considered, including anthropometric and demographic characteristics; genetic influences; differences in salt intake, physical activity and alcohol consumption; neurohumoral factors; duration of hypertension; and previous antihypertensive treatment. Antihypertensive treatment may reduce left ventricular mass and a number of prospective, randomized, comparative studies have assessed whether some (classes of) drugs are more effective than others. A meta-analysis of such studies, comparing diuretics, beta-blockers, calcium antagonists and/or angiotensin-converting enzyme (ACE) inhibitors, suggests that the reduction of left ventricular mass with each of these classes is similar to the reduction obtained with the other three classes statistically combined. Of particular interest is the observation that the four studies which specifically compared an ACE inhibitor and a calcium antagonist concluded that their effects on left ventricular mass did not significantly differ. Furthermore, that agents such as minoxidil and hydralazine do not reduce left ventricular mass.

Antihypertensive Agents↗
PubMed1993

Anti-CD3 and phorbol ester induce distinct phosphorylated sites in the SH2 domain of p56lck.

P56lck is a protein tyrosine kinase of the Src family specifically expressed in T lymphocytes. Triggering of T cells with anti-CD3 or with phorbol 12-myristate 13-acetate (PMA) results in the appearance of slower migrating forms (shift) of p56lck. To investigate the phosphorylation sites on the shifted forms of p56lck and to assess the role of protein kinase C in this phosphorylation, Jurkat cells were treated with a selective inhibitor of this kinase (GF 109203X). This inhibitor completely reversed the shift induced by PMA but only partially reversed the one induced after triggering with anti-CD3. To analyze the shift further, p56lck was immunoprecipitated from in vivo labeled cells treated either with anti-CD3 or with PMA. Tryptic phosphopeptides were generated and analyzed by using a combination of thin layer chromatography, high reticulation polyacrylamide gel electrophoresis, reverse phase chromatography, and phosphopeptide sequencing. We identified serine 158 as a newly phosphorylated site after PMA treatment and tyrosine 192 and serine 194 in the major tryptic phosphopeptide obtained after anti-CD3 triggering. The three sites identified are located in the SH2 domain of p56lck; this suggests that their phosphorylation may regulate the interaction with other proteins or with other internal domains in p56lck.

Amino Acid Sequence↗
PubMed1993

Coupling of GTP-binding to the T cell receptor (TCR) zeta-chain with TCR-mediated signal transduction.

The zeta-subunit of the TCR binds GTP and is a well characterized substrate for a TCR-activated tyrosine kinase. To examine the possible coupling of GTP-binding to zeta with TCR-mediated signal transduction, a mutant (termed J32-3.2) of the T cell line Jurkat (J32) was used. Anti-TCR/CD3 stimulation of the TCR/CD3+ J32-3.2 cells resulted in a weak stimulation of both the phosphatidyl inositol and tyrosine kinase signal transduction pathways, as measured by changes in the level of free intracellular calcium, tyrosine phosphorylation of TCR-zeta, CD3-epsilon and ZAP-70, p56lck, or p59fyn tyrosine kinase activity and IL-2 gene activation. The impaired responsiveness of J32-3.2 cells to anti-TCR/CD3 mAb correlated with a low basal level of GTP-binding to zeta. Furthermore, in J32-3.2 cells TCR activation by antibody ligation caused a weaker increase in GTP-binding to the zeta-chain, as compared with that of wild-type J32 cells, which indicates for the first time that GTP-binding to zeta can be modulated by extracellular signals and suggest that the role of GTP-binding to zeta is to couple the TCR to intracellular signal transduction mechanisms.

Amino Acid Sequence↗
PubMed1993

Human immunodeficiency virus gp120 and derived peptides activate protein tyrosine kinase p56lck in human CD4 T lymphocytes.

Human immunodeficiency virus binds to CD4 T lymphocytes by interaction between its envelope glycoprotein gp120 and the CD4 molecule. The latter is non-covalently associated with a src-related tyrosine kinase, p56lck. CD4 cross-linking increases the activity of p56lck, leading to phosphorylation of several cellular substrates. We report here that gp160/120 increases both the autophosphorylation of p56lck and its enzymatic activity (reflected by phosphorylation of an exogenous substrate) in normal T cells and the HUT78 CD4+ T cell line. This effect was detectable 5 min after activation and persisted for 40 min in normal T cells. It did not require gp120 cross-linking and was associated with phosphorylation of tyrosine residue on several proteins, as shown by phosphotyrosine Western blot analysis. The pattern of proteins phosphorylated on tyrosine residues in response to gp120 activation was distinct from that induced by anti-CD4 antibodies. p56lck activation required its association with CD4, since p56lck activity was not modified in HUT78 T cell lines expressing a truncated or mutated form of CD4 unable to associate with p56lck. Peptides mimicking residues 418 to 434 and 449 to 464 of HIV-1 Bru gp120, regions known to participate in gp120 binding to CD4, also increased p56lck activity and triggered phosphorylation of similar substrates. Taken together, these results show that gp160/120 and derived peptides can transiently increase p56lck activity without the need for CD4 cross-linking. This activation led to a specific pattern of tyrosine phosphorylation on cellular proteins that may be of significance in the biological effects of the gp120/CD4 interaction, e.g. syncytium formation and inhibition of T cell activation.

Amino Acid Sequence↗
PubMed1993

Fourier analysis of blood pressure profiles.

This short review deals with the use of the Fourier technique to analyze diurnal blood pressure (BP) profiles obtained by noninvasive ambulatory monitoring. A Fourier series with four harmonics strikes an acceptable balance between the accuracy and complexity required to model the diurnal profile accurately in most subjects. A weighting procedure makes it possible to allow for the varying time intervals between consecutive pressure readings. Studies based on a single recording are insufficient to characterize an individual with respect to the statistical parameters describing the diurnal BP profile, regardless of whether they are obtained by Fourier analysis or by other methods. The Fourier approach provides the means to translate 24 h BP profiles into interpretable statistical parameters, such as the amplitude and acrophase of the overall model and the harmonics. These parameters can subsequently be used in further statistical analyses. In conclusion, the Fourier approach makes the description of complex, asymmetrical, and multiphasic BP profiles possible. By using the procedures of linear multiple regression, commonly provided by software packages, the calculations can be readily implemented on microcomputers without requiring advanced skills in mathematics or programming techniques.

Blood Pressure↗
PubMed1993

Response of ambulatory blood pressure to antihypertensive therapy guided by clinic pressure.

The objective of this prospective study was to define the limits below which ambulatory blood pressure (BP) does not decrease in patients with essential hypertension, when the decision to institute and intensify drug treatment is based on conventional blood pressure measurements. After a 1 month placebo run-in period, 30 patients were treated for 1 year with the converting enzyme inhibitor lisinopril or the calcium antagonist isradipine; dose adjustments and the decision to add hydrochlorothiazide were based on conventional blood pressure measurements in the clinic. Ambulatory blood pressure was recorded during 24 h in the run-in period and after 16, 24, and 52 weeks of active therapy. The baseline ambulatory blood pressure below which pressure does, on average, not decrease during active treatment was defined as the pressure at which the regression line between the on-treatment pressure and blood pressure in the run-in period intersects the line of identity. The systolic/diastolic blood pressure limits were similar for the three assessments during active treatment and averaged 128/88 mm Hg for daytime, 106/73 mm Hg for nighttime pressure, and 119/81 mm Hg for the whole 24 h, with upper 95% confidence limits of 137/93, 115/78, and 127/86 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Transcriptional and post-transcriptional mechanisms are involved in the absence of CD4 surface expression in two HIV-1 chronically infected T cell lines.

In vivo infection of human T cell lymphocytes by HIV-1 is mediated by the specific binding of the HIV-1 envelope glycoprotein gp120 to the T cell CD4 receptor. One of the post-infection events observed in vivo is the progressive loss of CD4+ T cells. One possible mechanism is the production of infected T cells which are lacking in surface expression of the CD4 receptor protein. We have analysed this possibility utilizing the two HIV-1 chronically-infected CD4- cell lines, 8E5 and ACH-2, both of which are derived from a CD4+ parental strain (A3.01) after HIV-1 infection. In each cell (8E5 and ACH-2) the loss of CD4 surface expression was found to occur by different mechanisms. In ACH-2 cells, neither CD4 protein nor the 3 kb CD4 RNA transcript could be detected. However, treatment of ACH-2 cells with cycloheximide elicited production of the 3 kb transcript suggesting the possibility for a repressor protein(s) to act at the level of transcription and/or stability of the 3 kb mRNA. In contrast, in 8E5 cells the level of the 3 kb CD4 RNA was comparable with that found in the CD4+ A3.01 parental strain. Analysis of the 8E5 strain revealed the presence of a CD4- gp160 bimolecular protein complex sequestered internally in the rough endoplasmic reticulum (RER). Finally, the protein tyrosine kinase p56lck, normally associated with the cellular membrane, appeared to be linked to the RER and bound to the CD4- gp160 proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Relationship between blood pressure measured in the clinic and by ambulatory monitoring and left ventricular size as measured by electrocardiogram in elderly patients with isolated systolic hypertension.

OBJECTIVE: To assess the additional diagnostic precision conferred by ambulatory blood pressure monitoring on clinic blood pressure measurement in evaluating the severity of isolated systolic hypertension. METHODS: The association between left ventricular size as determined by ECG voltages [R-wave voltages in lead V5 (RV5) and S-wave voltages in lead V1 (SV1)] and blood pressure as assessed by clinic measurements and ambulatory blood pressure monitoring was studied in 97 elderly patients included in the placebo run-in phase of the Syst-Eur trial. The additional diagnostic precision conferred by ambulatory monitoring on clinic blood pressure measurements was assessed by relating the residual ambulatory blood pressure level to the ECG-left ventricular size. The residual ambulatory blood pressure level was calculated by subtracting the predicted ambulatory blood pressure level for each patient (using the linear regression equation relating both techniques for the group) from the observed ambulatory blood pressure. RESULTS: Clinic systolic blood pressure was on average 20 mmHg higher (P < 0.001) than daytime ambulatory blood pressure while diastolic blood pressure was similar with both techniques. The sum of SV1 + RV5 was significantly related to clinic systolic pressure (r = 0.25), and 24-h (systolic, r = 0.37; diastolic, r = 0.29), daytime (systolic, r = 0.30; diastolic, r = 0.19) and night-time (systolic, r = 0.33; diastolic, r = 0.28) ambulatory blood pressure levels. These findings were not affected by adjustment for gender, age and the body mass index. The sum of SV1 + RV5 was significantly related to the residual 24-h (systolic, r = 0.30; diastolic, r = 0.31), daytime systolic (r = 0.20) and night-time (systolic, r = 0.31; diastolic, r = 0.29) ambulatory blood pressure monitoring levels. CONCLUSION: Ambulatory blood pressure monitoring adds to the diagnostic precision of clinic blood pressure measurement in assessing the severity of hypertension in this population. The ongoing side project on ambulatory blood pressure monitoring in the Syst-Eur study should establish whether these findings hold true for morbidity and mortality.

Aged↗
PubMed1993

The relationship between blood pressure and sodium and potassium excretion during the day and at night.

OBJECTIVE: The relationships between blood pressure and the urinary excretion rates of sodium and potassium during the day and at night were investigated. METHODS: A total of 160 participants (135 normotensive subjects and 25 untreated patients with essential hypertension) were examined using ambulatory blood pressure monitoring and timed urine collections during waking and sleeping hours. RESULTS: Blood pressure averaged 126/79 mmHg during waking hours and 107/62 mmHg during sleep. More sodium, potassium and aldosterone were excreted during the daytime, but the natriuretic substance kallikrein was excreted at a fixed rate throughout the 24 h. During waking hours there was poor correlation between blood pressure and urinary sodium and potassium excretion. By contrast, at night when the aldosterone: kallikrein ratio fell, the sodium and potassium excretion rates were positively correlated with blood pressure. CONCLUSIONS: Pressure natriuresis, not apparent during waking hours, may be unmasked at night when the balance between sodium-retaining and sodium-losing mechanisms favours natriuresis. Thus, the relationship between blood pressure and 24-h sodium excretion, usually considered to show the influence of salt intake on blood pressure, may also reflect pressure-induced natriuresis, if urine is more completely collected at night than during the day, and in circumstances favouring sodium retention during the day and sodium loss during sleep.

Adult↗
PubMed1993

Does isradipine modified release 5 mg once daily reduce blood pressure for 24 hours?

Twelve patients with essential hypertension were randomized in a double-blind cross-over study to investigate the blood pressure BP-lowering activity of isradipine regular formulation (RF) 2.5 mg twice daily (between 7 and 8 a.m. and at approximately 6 p.m.), and isradipine modified release (MR), 5 mg once daily (between 7 and 8 a.m.). The two randomized treatment periods were separated by a placebo period. Patient compliance was similar between placebo and isradipine RF and MR treatment. As compared with placebo, isradipine RF decreased daytime BP by 10 mm Hg systolic (SBP, p < 0.001) and by 6 mm Hg diastolic (DBP, p < 0.01), and night SBP and DBP by 7 (p < 0.05) and 3 mm Hg (P = NS), respectively. Isradipine MR reduced the daytime SBP 8 mm Hg (p < 0.05) and DBP by 3 mm Hg (p = NS), and the night SBP by 1 mm Hg (p = NS) and DBP by < 1 mm Hg (P = NS). Analysis of variance showed that the interaction terms between the effects of treatment and time of day were not significant for SBP (F = 1.56, p = 0.24) or DBP (F = 1.40, p = 0.26) with isradipine RF treatment, but they were significant for SBP (F = 6.33, p = 0.03) and DBP (F = 5.12, p = 0.04) with isradipine MR treatment. Therefore, the BP-lowering effect of isradipine MR 5 mg once daily appears to weaken as the day progresses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of antihypertensive drugs on exercise capacity.

Both single dose and short term diuretic treatment adversely affect maximal exercise capacity and the duration of prolonged submaximal exercise. However, insufficient data are available to establish the effect of long term diuretic treatment on exercise capacity. beta-Blockade reduces maximal aerobic power by approximately 7%. In addition, the capacity for prolonged submaximal exercise appears to be markedly impaired in normotensive and hypertensive patients, particularly when nonselective beta-blockers are prescribed. Fewer data are available for other drugs, but, whatever the mechanism of vasodilation, drugs that reduce systemic vascular resistance do not seem to have any effect on exercise capacity.

Antihypertensive Agents↗