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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

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

The Lck tyrosine kinase is expressed in brain neurons.

The lck gene product, p56lck, is a member of the src-related family of protein tyrosine kinases. It is known as lymphocyte specific and involved in thymocyte development and in the immune response mediated by the T cell receptor. We report that the lck gene is also expressed in adult mouse CNS and that brain p56lck is similar to the thymus protein. In situ hybridization and immunohistochemistry show that the lck gene is expressed in neurons throughout the brain in distinct regions, including hippocampus and cerebellum. In primary cultures from fetal mouse brain, neuronal cells are immunoreactive to Lck antiserum. This suggests that the lck gene product might be involved in a new signal transduction pathway in mouse brain.

Animals↗
PubMed1996

Expression of a novel form of the p56lck protooncogene in rat cerebellar granular neurons.

The src family protein tyrosine kinases (PTKs) are nonreceptor kinases. Some PTKs of this family are ubiquitously expressed, whereas others have a more restricted expression, as in neurons. Lymphoid cell kinase (lck) p56lck is highly expressed in tissues of lymphoid origin and believed to be specific for hematopoietic cells. Reports suggesting that CD4 is expressed in neurons prompted us to analyze the possibility that p56lck is also expressed in these cells. By western blot and immunoprecipitations using anti-lck antibody, an lck-like protein was detected in lysates from primary cultures of rat cerebellar granular neurons. This 56-kDa phosphoprotein was autophosphorylated in vitro and also phosphorylated enolase, similarly to p56lck. It was shown to be located actually in the neurons by immunocytofluorescence. Partial proteolysis mapping showed that the 56-kDa phosphoprotein had a peptide pattern very similar to the p56lck protein. Retrotranscription-PCR allowed the detection of an lck RNA in the neurons. The lck kinase domain was completely identical to the lymphocyte lck kinase domain, but the 5' end was modified in the neurons. These results show that p56lck is not lymphoid specific as is widely believed; its expression in neurons might underlie the toxicity of the HIV glycoprotein gp120 to neurons.

3T3 Cells↗
PubMed1996

Power spectral analysis of RR interval and blood pressure short-term variability at rest and during dynamic exercise: comparison between cyclists and controls.

To determine the adaptations of the autonomic nervous system in the control of heart rate and blood pressure induced by endurance training, 10 competitive cyclists aged 27 +/- 7 years and 10 age-, weight- and height-matched sedentary controls were subjected to Power Spectral Analysis of the RR interval and of blood pressure at supine rest and during submaximal cycloergometric exercise test in the supine position at 20% and 40% of maximal workload. At rest, the high-frequency (HF) power of the RR interval was higher in cyclists (p < 0.05) compared to controls, whereas the power spectrum of both systolic and diastolic blood pressure did not differ between cyclists and controls. During exercise the variance, the low-frequency (LF) and the HF power of the RR interval decreased significantly (p < 0.005) and similarly in cyclists and controls. The LF/HF ratio of the RR interval increased (p < 0.001) and the alfa index of baroreflex sensitivity decreased (p < 0.05) without differences between cyclists and controls. The variance of both systolic and diastolic blood pressure increased (p < 0.001 and p < 0.005, respectively) as well as the HF power of systolic blood pressure (p < 0.001) similarly in cyclists and in controls. In conclusion, the data of the present study suggest that competitive cycling causes an enhanced vagal drive to the sinus node, whereas the neural control of blood pressure is not affected. During exercise a vagal withdrawal and a sympathetic activation in the neural control of heart rate, together with a reduction of baroreflex sensitivity are operative. These changes are similar in cyclists and controls.

Adaptation, Physiological↗
PubMed1996

Effect of strength training on blood pressure measured in various conditions in sedentary men.

To examine the effect of long term strength training on heart rate and blood pressure, measured in different conditions, and on their variability, thirty healthy, previously sedentary men were randomized into a training and a control group. The strength training program consisted of 48 training sessions on a multigym apparatus at a frequency of 3 sessions each week, involving leg press, bench press, leg curl, shoulder press, leg extension and sit ups. The control group was asked not to change their sedentary lifestyle. In the subjects of the training group the load could be increased significantly for all exercises (p < 0.01). Heart rate and blood pressure were measured at rest in the supine and sitting position, during 24 hours with a non-invasive ambulatory device and during an exercise test on a cycloergometer. Repeated measures analysis of variance did not show an effect of strength training on heart rate or on blood pressure. In addition, power spectral analysis of the RR interval (ECG) and of the beat-to-beat blood pressure in the supine subject revealed similar total, low frequency and high frequency power before and after training, indicating that the neural control of both heart rate and blood pressure was not affected by a 16-week program of strength training.

Blood Pressure↗
PubMed1996

Prediction of the actual awake and asleep blood pressures by various methods of 24 h pressure analysis.

OBJECTIVE: To assess the relationships of daytime and night-time blood pressures and the day-night pressure differences, obtained by various analytical methods, with the actual awake and asleep pressures and the awake-asleep pressure difference. METHODS: Ambulatory blood pressure was successfully monitored by use of the SpaceLabs 90202 device in 91 healthy young men during a weekend, when they went to bed and awoke at variable and often unusual times. The actual 'awake' and 'asleep' blood pressures were calculated on the basis of these times, noted by the subjects. The 24 h recordings were further analysed by use of two clock time-independent methods (square-wave fitting; cumulative sum analysis) and by one 'wide' (A) and one 'narrow' (B) fixed-time method (daytime: 0700-2200 h or 1000-2000 h; night-time: 2200-0700 h or 0000-0600 h, for methods A and B, respectively). RESULTS: In the total study population, square-wave fitting (+1.1 +/- 1.5 mmHg, mean +/- SD) and cumulative sum analysis (2.4 +/- 1.9 mmHg) overestimated the actual awake systolic blood pressure and underestimated the asleep pressure (-0.7 +/- 1.7 and -1.8 +/- 1.8 mmHg, respectively). The fixed-time techniques underestimated the awake pressure (-2.6 +/- 3.1 and -0.2 +/- 3.2 mmHg for methods A and B, respectively) and overestimated the asleep pressure by +4.9 +/- 5.5 and +2.7 +/- 6.1 mmHg, respectively. The actual awake-asleep pressure difference was overestimated by square-wave fitting (+1.8 +/- 1.9 mmHg) and more so by cumulative sum analysis (+4.2 +/- 2.5 mmHg); the underestimation by the fixed time approach averaged -3.0 +/- 8.4 mmHg with method B and amounted to -7.5 +/- 8.3 mmHg with method A. Overall, the SD of the various differences between the estimated and the actual awake and asleep pressures, and consequently the limits of agreement, were larger for the fixed-time methods than for the clock time-independent techniques. In the 47 subjects who went to bed before 2400 h and awoke between 0600 and 1000 h, the results of the clock time-independent methods were similar to the results in the total study population, whereas the deviations of the fixed time pressures from the actual awake and asleep blood pressures were considerably reduced. The results were similar for diastolic blood pressure. CONCLUSIONS: Clock time-independent methods, particularly square-wave fitting, can predict the actual awake and asleep blood pressures and the awake-asleep pressure differences with reasonable accuracy and the results are independent of the awake-asleep pattern of the subjects. However, fixed-time methods are only reliable when the subjects go to bed and arise within well-defined periods, and yield more accurate results when the morning and evening phases are excluded from the daytime and night-time periods.

Adult↗
PubMed1996

Prognostic significance of peak oxygen uptake in hypertension.

The aim of this study was to investigate the prognostic value of cardiopulmonary fitness in hypertension. From 1972 to 1982 oxygen uptake and heart rate were recorded during an exercise test to exhaustion in 216 patients (143 men). Their outcome was ascertained in 1994. During 3,411 patient years of follow-up, 53 patients suffered at least one fatal or nonfatal cardiovascular event and 25 patients died. After adjustment for age, gender, and weight, the relative hazard rates (RHR; Cox regression) of peak oxygen uptake (l.min-1) amounted to 0.44 (P = 0.01) for the first occurring cardiovascular events and 0.35 (P = 0.05) for all-cause mortality. These RHR remained significant after additional adjustment for traditional cardiovascular risk factors (RHR = 0.45 and 0.28, respectively; P < 0.05). Heart rate at 50 W did not predict outcome after adjustment for age and gender (P = 0.94 and 0.14, respectively), nor after additional adjustment for heart rate at rest (P = 0.86 and 0.61, respectively). In conclusion, a lower peak oxygen uptake, but not a higher submaximal heart rate, is significantly and independently associated with a higher incidence of cardiovascular events and a higher total mortality in hypertensive patients.

Cardiovascular Diseases↗
PubMed1996

Geographical and temporal differences in the urinary excretion of inorganic arsenic: a Belgian population study.

OBJECTIVE: This Belgian study assessed the geographical and temporal differences in the exposure of the population to inorganic arsenic, a known carcinogen. METHODS: In the CadmiBel study (1985-9) the 24 h urinary arsenic excretion was measured, as an index of recent exposure, in industrialised cities (Liège: n = 664, Charleroi: n = 291), in a rural control area (Hechtel-Eksel: n = 397), and in rural districts in which the population had possibly been exposed through the drinking water or the emissions of nonferrous smelters (Wezel: n = 93, Lommel: n = 111, and Pelt: n = 133). In the PheeCad study, in 1991-5, the rural areas (n = 609) were re-examined together with an urban control area (Leuven: n = 152). RESULTS: The CadmiBel results showed that after adjustment for sex, age, and body mass index, the 24 h arsenic excretion was on average low in Liège (91 nmol), Charleroi (155 nmol), Hechtel-Eksel (144 nmol), and Wezel (158 nmol), whereas the highest excretions were found in Lommel (570 nmol) and Pelt (373 nmol). During the PheeCad study, the mean 24 h arsenic excretion in the rural areas ranged from 81 to 111 nmol. This was lower than six years earlier and similar to the excretion in the control town (108 nmol). Longitudinal studies in 529 people living in the rural areas confirmed that their 24 h arsenic excretion had decreased (P < 0.001) from 222 to 100 nmol. As well as the drinking water, industry was likely to be a source of the increased exposure in Lommel and Pelt in 1985-9, because at that time the urinary arsenic excretion did not follow the regional differences in the arsenic content of the drinking water, because the fall in the arsenic excretion over time coincided with the implementation by industry of stricter environmental regulations, because in individual subjects the urinary arsenic excretion was inversely correlated with the distance to the nearest smelter, and because an increased arsenic excretion was only found downwind from the main smelter. The official network that monitors the arsenic concentration in airborne and fall out dust did not detect the high exposure in Lommel and Pelt between 1985 and 1989. CONCLUSION: This study highlights the necessity to validate environmental monitoring programmes by directly estimating the internal exposure of the population.

Adult↗
PubMed1996

Ambulatory monitoring uncorrected for placebo overestimates long-term antihypertensive action. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement. Older patients (> or = 60 years, n=337) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were randomized to placebo or active treatment consisting of nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8/1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration.

Aged↗
PubMed1996

Life style as a blood pressure determinant.

In Belgium, an affluent Western European country, participation in sports, alcohol intake, and living in a working class area were identified as the life style factors with the closest associations with the blood pressure level. Obesity was another important blood pressure correlate. Sodium intake, determined from the 24 h urinary output, and smoking were not associated with blood pressure. Controlled intervention studies have proven that weight reduction, endurance training and alcohol abstinence effectively reduce blood pressure. In the light of these intervention studies, the Belgian findings and the published work highlight the potential of preventive strategies aimed at these major life style factors.

Ethanol↗
PubMed1996

Abnormal signal transduction through CD4 leads to altered tyrosine phosphorylation in T cells derived from MRL-lpr/lpr mice.

CD4+ T cells play a crucial role in the development of lupus in MRL-lpr/lpr mice: incomplete deletion/silencing of self-reactive CD4+ T cells leads to T cell activation, which causes both polyclonal B cell activation and T cell infiltration of multiple organs. Furthermore, anti-CD4 antibody therapy ameliorates disease and prolongs survival. Because CD4 is normally involved in both tolerance induction and T cell activation, we questioned whether signaling through CD4 was normal among T cells in this strain. For this purpose, signal transduction in CD4+ T cells derived from MRL-lpr/lpr and normal mice were compared, using an autoreactive CD4+ T cell clone and freshly isolated CD4+ T cells derived from mice of varying ages. Tyrosine phosphorylation was similar among MRL and normal CD4+ T cells after cross-linking with either anti-TCR antibody or anti-CD3 antibody, and following co-culture with Con A. In constrast, cross-linking of surface CD4 resulted in deficient tyrosine phosphorylation of cellular proteins in MRL T cells. By comparison, lck protein expression in MRL CD4+ T cells was found to be lower than normal. However, following stimulation with Con A, lck enzyme activity, as detected by autophosphorylation of lck, was comparable in MRL and normal T cells. The observed differences were present in the autoreactive T cell clone as well as in T cells isolated from both pre-diseased and diseased mice, and they could not be explained by variation in surface density of CD4. These results raise the possibility that abnormal signaling through CD4 may contribute to impaired tolerance and expansion of autoreactive T cells exhibited in MRL-lpr/lpr mice.

Animals↗
PubMed1996

An epidemiological approach to ambulatory blood pressure monitoring:the Belgian Population Study.

BACKGROUND: In order to determine reference values for ambulatory blood pressure, a random population sample of 1057 persons, 20-88 years old, was investigated in a geographically defined area of Belgium. This article is the final report on the cross-sectional phase of this population survey. METHODS:Twenty-four-hour ambulatory pressure was recorded at 20 min intervals from 0800 to 2200 h and at 45 min intervals from 2200 to 0800 h. Conventional blood pressure was measured by trained nurses at the participants' homes and also in a subgroup of 532 persons at a locally organized clinic. A conventional blood pressure exceeding 140 mmHg systolic or 90 mmHg diastolic and the taking of antihypertensive drugs were the criteria used to distinguish between normotensive and hypertensive persons. RESULTS: In the 1057 patients, of whom 328 were hypertensive, 24 h, daytime (2200 to 0800 h) and night-time (0000 to 0600 h) pressures averaged 119/71, 125/77 and 108/62 mmHg, respectively. Compared with daytime values, blood pressures at home were 3.5/1.5 mmHg lower in 729 normotensive people but 11.6/4.5 mmHg higher in 328 hypertensive patients. In the normotensive subgroup the 95th percentiles of the 24 h, daytime and night-time pressures were 129/80, 137/88 and 121/72 mmHg, respectively. These boundaries were not materially altered when we considered only the 275 participants who had been normotensive both at home and at the clinic (127/79, 135/87 and 118/72 mmHg, respectively). When, in addition to the Belgian data, other reports on large cohorts were also analysed, the transition from normotension to hypertension on ambulatory measurement was likely to be within the ranges of 130-135/80-85, 135-140/85-90 and 120-125/70-75 mmHg for 24 h, daytime and night-time pressures, respectively. CONCLUSION: In comparison with other population surveys and with the earlier interim reports on the Belgian study, the present analysis produced remarkably consistent results with respect to the distributions of the ambulatory measurements. The working definitions of normality based on the 95th percentiles of the ambulatory measurements in the normotensive participants in the present survey and various other studies need further validation in terms of the incidence of cardiovascular complications. For this purpose, the Belgian participants as well as other cohorts are being prospectively followed.

Journal Article↗
PubMed1996

Conventional and ambulatory blood pressure measurement in older patients with isolated systolic hypertension:second progress report on the ambulatory blood pressure monitoring project in the Syst-Eur trial.

OBJECTIVES: To compare clinic and ambulatory blood pressure measurement and the reproducibility of these measurements in older patients with isolated systolic hypertension.PATIENTS: A total of 477 patients aged >/= 60 years with isolated systolic hypertension on clinic measurement were monitored during the placebo run-in phase of the Syst-Eur trial. METHODS: The time-weighted 24 h blood pressure, clock time day and night blood pressure, the cumulative sum-derived crest and trough blood pressure and the high and low blood pressure levels of the square-wave model were computed. The daily alteration between the high and low blood pressure spans was quantified using the clock time day-night difference, the cumulative sum-derived circadian alteration magnitude, the Fourier amplitude and the difference between the high and low blood pressure levels of the square-wave model. RESULTS: The daytime ambulatory systolic blood pressure was, on average, 21 mmHg lower than the clinic blood pressure, whereasthe diastolic blood pressure was, on average, similar with both techniques of measurement. In the 132 patients who underwent repeat measurements, clinic blood pressure levels and the parameters describing the difference betgween the daily high and low blood pressure spans were equally reproducible. However, both were less reproducible than the ambulatory blood pressure levels. The repeatability coefficients, expressed as percentages of near maximum variation, were 50 and 51% for the clinic systolic and diastolic blood pressures, 30 and 33% for the mean 24 h systolic and diastolic blood pressures and between 44 and 54% for the parameters describing the daily alteration between the high and low blood pressure spans. CONCLUSION: In older patients with isolated systolic hypertension, clinic and ambulatory systolic blood pressure may differ greatly; the prognostic significance of this difference remains to be elucidated. Furthermore, the level of blood pressure in these patients is more reproducible by ambulatory measurement than it is by clinic measurement.

Journal Article↗
PubMed1996

Ambulatory blood pressure monitoring in clinical trials.

Ambulatory blood pressure monitoring is increasingly being used in clinical trials. Trials with ambulatory monitoring, just like clinical experiments based on conventional sphygmomanometry, need to be controlled properly, because ambulatory blood pressure measurements are not completely devoid of placebo-like effects. The trough: peak ratio might be a useful instrument for assessment of the durations of action of antihypertensive drugs. However, its error term and confidence interval need to be reported and its determination in clinical trials requires further standardization. Ambulatory compared with conventional blood pressure measurements are characterized by a higher reproducibility. This property makes a reduction in sample size possible in cross-over but not in parallel group trials, if instead of the conventional blood pressure the 24 h or daytime blood pressures are compared. Trials focusing on the full course of the blood pressure through the day need a larger sample size than do those just concerning the conventional blood pressure level.

Journal Article↗
PubMed1996

Ambulatory blood pressure during antihypertensive therapy guided by conventional pressure.

Subjects with elevated conventional clinic or office blood pressure (CBP) may have normal ambulatory blood pressure (ABP). The purpose of this review is to summarize studies in which ABP was monitored while the initiation or intensification of antihypertensive therapy was guided by CBP. These studies show that ABP does not decrease or decreases only slightly in response to treatment in subjects with elevated CBP and low ABP, whereas the CBP is significantly reduced in such patients.

Journal Article↗
PubMed1996

Antihypertensive therapy in older patients with isolated systolic hypertension: the Syst-Eur experience in general practice

Background and objective. This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practices. Methods. In the Syst-Eur trial elderly patients (60 years or older) with isolated systolic hypertension were randomized to either active or placebo treatment. Active treatment consisted of nitrendipine combined with enalapril and/or hydrochlorothiazide to reduce systolic pressure to Results. This analysis was restricted to patients of general practitioners who had been followed for at least 12 months. The placebo (N = 204) and active treatment (N = 217) groups had similar characteristics at randomization. At one year, the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic. Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier. Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment (P Conclusions. A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners. Whether this blood pressure reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation. Keywords. Antihypertensive treatment, general practice, isolated systolic hypertension, randomized clinical trial.

Journal Article↗
PubMed1996

Antihypertensive therapy in older patients with isolated systolic hypertension: the Syst-Eur experience in general practice. The Syst-Eur Investigators.

BACKGROUND AND OBJECTIVE: This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practices. METHODS: In the Syst-Eur trial elderly patients (60 years or older) with isolated systolic hypertension were randomized to either active or placebo treatment. Active treatment consisted of nitrendipine combined with enalapril and/or hydrochlorothiazide to reduce systolic pressure to < 150 mmHg and by > or = 20 mmHg. Matching placebos were used in the control group. RESULTS: This analysis was restricted to patients of general practitioners who had been followed for at least 12 months. The placebo (N = 204) and active treatment (N = 217) groups had similar characteristics at randomization. At one year, the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic. Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier. Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment (P < 0.001 for all comparisons). CONCLUSIONS: A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners. Whether this blood pressure reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation.

Aged↗