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Biomedical subjects

W R de Vries

Publications and source records attributed to W R de Vries.

At least 19 recordsLinked to original sources
PubMed2004

Age-related differences in growth hormone (GH) regulation during strenuous exercise.

This study was designed to investigate the central neuroendocrine mechanisms by which exercise (EX) stimulates growth hormone (GH) release as a function of age. Twelve male subjects, six in their early-to-mid twenties and six in their late sixties or seventies, received a strong GH stimulus either as incremental EX until volitional exhaustion or by administration of GHRH alone or Hex alone two hours after a presumed maximal GH response to combined administration of GHRH plus hexarelin (Hex). Total GH availability was calculated as area under the curve (AUC) over time periods 0 - 120 and 120 - 240 min. The mean AUC in micro g/l x 120 min to GHRH+Hex in the younger group was approximately twice that in the older group (11,260, range 3,947 - 19,007 vs. 5,366, range 2,262 - 8,654). In younger males, the mean AUC to EX (509, range 0 - 1,151) was larger than to GHRH (119, range 0 - 543), but less than that to Hex (919, range 0 - 1,892). In the older group, GH responses to EX and GHRH were abolished (mean AUC: 112, range 0 - 285, and 156, range 30 - 493), respectively) in contrast to the response to Hex (1,077, range 189 - 1,780). These data indicate that maximal GH stimulation by GHRH+Hex results in greater desensitization of GHRH compared to Hex, irrespective of age. We postulate that the abolished responsiveness of GH to EX in older group is due to insufficient disinhibition of hypothalamic somatostatin activity and desensitization of GHRH, while the preserved activity of a central Hex-related pathway is not involved. The GH response to EX in younger males is due to complete inhibition of somatostatin activity and stimulation of a central Hex-related pathway in spite of GHRH desensitization. We conclude that a central Hex-related pathway is the primary factor for EX-induced GH release only in younger males.

Adult↗
PubMed2004

Acromegaly and heart failure: revisions of the growth hormone/insulin-like growth factor axis and its relation to the cardiovascular system.

Cardiomyopathy is a major cause of death in overt acromegaly. Recent progress in research has increasingly revealed the molecular mechanisms concerning growth hormone and insulin-like growth factor in the development of heart failure. In this article, we propose mechanisms according to which heart failure occurs, and we aim to extrapolate this knowledge to more general processes involved in heart failure.

Acromegaly↗
PubMed2003

Somatotropic-axis deficiency affects brain substrates of selective attention in childhood-onset growth hormone deficient patients.

Reduced levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are associated with deteriorated cognitive performance in senescence. Little work has been done on the effect of GH and IGF-1 on a crucial aspect of cognition, selective attention. This study investigated the effect of GH/IGF-1 on performance and brain potentials (EEG) during a selective-attention task in patients with low levels of GH and IGF-1 (childhood-onset growth hormone deficiency) compared to healthy controls. Detection of occasional visual target patterns was impaired in patients. This was paralleled by a reduction in an attention-related brain potential, which has been associated previously with anterior cingulate cortex functioning.

Adolescent↗
PubMed2003

Involvement of endogenous growth hormone-releasing hormone (GHRH) in the exercise-related response of growth hormone.

The aim of this study was to investigate the involvement of endogenous growth hormone-releasing hormone (GHRH) in the growth hormone (GH) release during strenuous exercise (EX). Eight healthy male subjects (age: 22.1 +/- 0.8 yr, body mass index: 22.2 +/- 0.9 kg/m 2, .VO 2 max: 52.2 +/- 0.5 ml/min/kg [mean +/- SEM]) were exposed to incremental EX until volitional exhaustion (cycle ergometry), and in random order to a maximally stimulating bolus injection of 100 microg GHRH, or to combined administration of 100 microg GHRH and EX (GHRH+EX). Serial blood samples in the fasted state were taken immediately before the start of each trial, and at appropriate intervals over 2 h. Total GH availability was calculated as area under the response curve (AUC), corrected for differences in baseline values. The results showed that peak serum GH levels to GHRH alone and EX alone were not significantly different: 41.5 +/- 9.0 microg/l and 64.1 +/- 8.1(mean +/- SEM). Peak GH level to GHRH+EX was 156.1 +/- 19.9 microg/l, which was significantly greater than to either stimulus alone (p < 0.02) or additively (105.6 +/- 17.1 microg/l, p < 0.02). AUC's to GHRH alone and EX alone were not significantly different (3242 +/- 839 vs. 2472 +/- 408 microg/l x 120 min). AUC to GHRH+EX (7807 +/- 1221 microg/l x 120 min) was greater than to either stimulus alone (p < 0.02) or additively (5714 +/- 1247 microg/l x 120 min, p < 0.02). This indicates a potentiating (synergistic) effect between GHRH and EX. We postulate that GH responses to strenuous EX are only partially due to maximal GHRH activation. Next to complete inhibition of hypothalamic somatostatin activity, which is achieved by strenuous exercise, activation of endogenous GH-releasing peptides, such as Ghrelin, must be operative.

Adult↗
PubMed2003

Induction of postprandial inflammatory response in adult onset growth hormone deficiency is related to plasma remnant-like particle-cholesterol concentration.

Increased cardiovascular mortality due to premature atherosclerosis is a clinical feature in the adult-onset GH deficiency (AGHD) syndrome. Inflammation is a key feature in atherogenesis and may be triggered by postprandial lipoprotein remnants. We hypothesized that increased postprandial lipoprotein remnant levels in AGHD may be associated with an inflammatory response. In this case-control study, 10 AGHD patients [6 males and 4 females; age, 48 +/- 9 yr; body mass index (BMI), 26.9 +/- 2.6 kg/m(2)] and 10 healthy control subjects (matched for age, BMI, gender, baseline lipid levels, and apolipoprotein E genotype) were included. They all ingested an oral fat load. Fasting and postprandial levels of plasma remnant-like particle-cholesterol (RLP-C; 0.31 +/- 0.13 mmol/liter and 4.14 +/- 1.37 mmol/liter.h in GHD; 0.18 +/- 0.06 mmol/liter and 2.56 +/- 1.02 mmol/liter.h in controls, respectively) were significantly increased in AGHD patients compared with control subjects. The median inflammatory cytokines, IL-6 and TNF-alpha, were higher in the fasting [3.9 (range, 3.1-11.9) pg/ml and 6.8 (range, 2.5-27.6) pg/ml, respectively] and postprandial [151.7 (range, 87.0-294.3) pg/ml.24 h and 289.9 (range, 87.5-617.6) pg/ml.24 h, respectively] states in AGHD than in controls [fasting, 0.9 (range, 0.2-5.2) pg/ml and 2.8 (range, 2.5-5.7) pg/ml; and postprandial, 54.5 (range, 11.50-126.5) pg/ml.24 h and 118.3 (range, 81.2-243.1) pg/ml.24 h, respectively]. In addition, postprandial profile of RLP-C and IL-6 in AGHD and in the total group were significantly associated (r(2) = 0.44, P < 0.05; and r(2) = 0.38, P < 0.01, respectively). In conclusion, the increased postprandial RLP-C level in GHD is associated with an inflammatory response that may result in increased susceptibility for premature atherosclerosis.

Adult↗
PubMed2002

Detection and treatment of claudication due to functional iliac obstruction in top endurance athletes: a prospective study.

BACKGROUND: Endurance athletes often have restrictions in flow in their iliac arteries during exercise. Such restrictions have previously been ascribed solely to intravascular lesions. We postulate that flow could also be restricted by functional kinking in the arteries, and that surgical release of these kinks might be an effective treatment. METHODS: We prospectively studied 80 endurance athletes who had complaints suggestive of flow restriction in the iliac arteries of one (n=74) or both (6) legs (total 92 legs). Using vascular diagnostic tools, we examined athletes while they were doing activities that often provoke flow restrictions. Restrictions were determined by measurement of systolic pressure in the ankle after exercise; peak systolic velocities were measured with echo-doppler. Kinks were detected with echo-doppler and magnetic-resonance angiography. When functional kinking was diagnosed as the cause of the restriction, the athlete was offered surgery to release the iliac arteries, as part of our prospective study. FINDINGS: We recorded flow restrictions in the iliac arteries of 58 of 92 (63%) legs. In 40 of these legs (69%), kinks were the most important cause of the restriction, making these legs suitable for surgical release. We operated on 23 of 58 (40%) legs. All athletes who had an operation subjectively improved. Maximum workload in a cycling test and ankle pressure significantly improved after the operation. 20 (87%) athletes were able to successfully return to their desired high level of competition. INTERPRETATION: Our sports-specific protocol is effective in detecting kinking of the iliac arteries as a cause for flow restriction in athletes who have few intravascular abnormalities when investigated with conventional vascular diagnostic tools. Surgical treatment directed at the kinking was less invasive and therefore a better alternative to vascular reconstruction in these athletes.

Adult↗
PubMed2001

Reproducibility of ultrasound blood flow measurement of the superior mesenteric artery before and after exercise.

This study examines the reproducibility of gastro-intestinal blood flow measurements in the superior mesenteric artery (SMA) both before and immediately after exercise with Doppler ultrasound measurements. Twelve well-trained males (mean +/- SD: age 25.9 +/- 3.8 yr; VO2max 4.8 +/- 0.91 x min(-1)) were measured twice (trial 1 and 2) with a 1 week interval before and immediately after 1 hr cycling at 70% VO2max. Duplex scanning was performed with the athletes in supine position immediately after transition from a chair (before exercise) or bicycle (after exercise). The variability of three measurements before exercise was studied within both trials (short-term reproducibility) and the mean pre-exercise values were compared between the trials (long-term reproducibility). In addition, post-exercise measurements were compared in the same way. Reproducibility was tested using the coefficient of variation and Cronbach's alpha. Mean pre-exercise blood flow was 424 +/- 66 ml/min (n = 12) in trial 1 and 375 +/- 38 ml/min (n = 11) in trial 2. Immediately after exercise blood flow had decreased by 49% to 214 +/- 36 ml/min (p <0.01) in trial 1 and by 38% to 234 +/- 36 ml/min (p < 0.01) in trial 2. Blood flow before and after exercise was not significantly different between trials (paired t-test) and therefore reproducible at the group level. Before exercise a good to fair reproducibility was observed both at the short-term (Cronbach's alpha: 0.88 in trial 1, 0.73 in trial 2, n = 11), and at the long-term (alpha = 0.80, n= 11). In contrast, long-term reproducibility immediately after exercise was poor (alpha = -0.99, n = 8 and alpha = 0.36, n = 7 after the first and second cycling period, respectively). In conclusion, duplex scanning of SMA after a sitting-supine transition in well-trained subjects is not a reproducible method at the individual level for intestinal blood flow measurements immediately after exercise.

Adult↗
PubMed2000

Cardiopulmonary exercise parameters in relation to all-cause mortality in patients with chronic heart failure.

In this study we analysed the all-cause mortality over a period of maximal 6 years in 60 male patients (age: 63.4+/-8.3 years, mean+/-S.D.), suffering from chronic heart failure with resting left ventricular ejection fraction and E/O2 slope as independent factors. We assessed functional NYHA class (II: n=36, III: n=24), radionuclide left ventricular ejection fraction (29.2+/-10.4%) and peak values of heart rate, O2, CO2, E, anaerobic threshold and exercise duration with an incremental work load test on the treadmill. O2 relative to E was based on the individual slopes of the regression of O2 on E during the first 6 min of exercise. These slopes with other exercise-related variables and factors such as etiology, medication, and NYHA class were analysed with a Cox's Regression Method. A survival time analysis (Kaplan-Meier survival curve) was done to establish the influence of E/O2 slope and left ventricular ejection fraction (both split into above and below median values), as well as their interaction, on survival. From all investigated exercise-related variables. E/O2 slope is the most powerful variable regarding prediction of all-cause mortality in our group of chronic heart failure patients. Concerning risk stratification, the subgroup (n=18) with a relatively high left ventricular ejection fraction (>28%) and flat E/O2 slope (<27.6) had most survivors (77.8%) after about 3 years, while the subgroup (n=12) with a relatively high left ventricular ejection fraction (>28%), but a steep E/O2 slope (>27.6) had least survivors (33.3%). This difference in percentage is highly significant (P=0.0025). The fact that E/O2 slope and left ventricular ejection fraction show comparable main and interaction effects between measures of exercise tolerance (e.g., anaerobic threshold, peak O2, exercise duration) on the one hand, and all-cause mortality on the other, suggests the existence of common sources of variance. Based on our analysis, it is unlikely that effects on all-cause mortality are mediated through phenomena related to exercise tolerance. Therefore, we hypothesize that the effects on exercise tolerance and all-cause mortality both depend on common factors, which cause both cardiac and peripheral organ (c.q. muscular) dysfunctions. Moreover, this study clearly shows that E/O2 slope during incremental exercise is an important prognostic marker for risk stratification in chronic heart failure patients, NYHA class II and III.

Exercise Test↗
PubMed2000

Growth hormone, insulin-like growth factor I and cognitive function in adults.

This review focuses on the possible contribution of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis to cognitive function. Binding sites for GH and IGF-I are found in various areas of the brain. Their distribution suggests that GH and IGF-I contribute to the function of the hippocampus, a brain structure important for the maintenance of cognitive functions such as learning and memory. Evidence for cognitive deficits in GH-deficient individuals has been found in various studies, some of which have shown that these deficits can be reversed by GH substitution therapy. In addition to examining conditions of GH deficiency, this article reviews studies evaluating the correlation between the cognitive deficits associated with ageing and age-related decreases in GH or IGF-I secretion. Based on the available data, one might hypothesize that relative GH or IGF-I deficiency could contribute to the deterioration of cognitive functions observed in the elderly.

Adult↗
PubMed2000

The effect of a sports drink on gastroesophageal reflux during a run-bike-run test.

The effects of different modes of prolonged exercise and different drinks on gastroesophageal reflux and reflux-related symptoms were examined. In a cross-over design seven male triathletes performed two tests at one week intervals (50 min periods of alternately running, cycling and running at 70-75% VO2max), with supplementation of either a conventional sports drink (7% carbohydrates) or tap water. Gastroesophageal reflux (percentage time and number of periods esophageal pH < 4) was measured with an ambulant pH system before, during and after exercise. Percentage reflux time (+/- SEM) during running, cycling, running and recovery was 24.0 +/- 4.6, 8.2 +/- 4.8, 17.6 +/- 8.4 and 11.8 +/- 4.0 with carbohydrates and 7.4 +/- 2.9, 0 +/- 0, 2.4 +/- 1.4 and 0.2 +/- 0.2 with water, respectively. Reflux lasted longer during exercise as compared to the rest situation (5.6 + 1.4%), especially with carbohydrates, and lasted longer with carbohydrates than with water (P < 0.05; Wilcoxon signed rank test). In general, reflux lasted longer during running than during cycling (P < 0.05). Data on the number of reflux periods are concordant to these results. Chest pain was reported by one subject during running with carbohydrates. Heartburn during running was reported by two subjects with water and by one with carbohydrates. In conclusion, physical exercise increases gastroesophageal reflux, dependent on the mode of exercise and beverage used.

Adult↗
PubMed2000

Gastrointestinal mucosal integrity after prolonged exercise with fluid supplementation.

PURPOSE: Studies on the effect of exercise on gastrointestinal (GI) mucosal integrity have been limited to occult-blood tests, which were often nonspecific for human blood. The aim of our study was to investigate more aspects of this integrity. METHODS: We examined the effect of prolonged exercise and carbohydrate (CHO) supplementation on mucosal integrity in 22 male triathletes by measuring fecal lysozyme, alpha1-antitrypsin, and occult-blood loss, which was examined by two tests specific for human blood (Colon-Albumin and Monohaem test). Exercise consisted of two 150-min tests (alternately running, cycling, and running at 70-75% VO2max), either with a 7.0% CHO drink or water (W). Furthermore, GI symptoms during exercise were registered by questionnaire. RESULTS: Three subjects showed human albumin only in the first stool after exercise: twice with W and once with CHO. However, human hemoglobin (Hb) could not be detected in these samples. Four other subjects showed an elevated lysozyme concentration after exercise with CHO but not with W. Elevated alpha1-antitrypsin values were found in three of seven specimens in which either positive albumin tests and/or an elevated lysozyme concentration were demonstrated. Twenty-one subjects (95%) reported one or more GI symptoms during exercise. Incidence rates of different GI symptoms varied from 5 to 68%. Most symptoms were more frequent and lasted longer during running than during cycling but did not differ significantly between supplements and were not related to any mucosal integrity parameter. CONCLUSIONS: GI blood loss during exercise is of no clinical importance, at least in our study design with a group of well-trained male subjects who consumed a relatively high amount of fluid (up to 2.3 L). Nevertheless, an increased alpha1-antitrypsin and lysozyme concentration may indicate a transient local mucosal damage with an inflammatory response.

Adult↗
PubMed2000

Growth hormone responses during strenuous exercise: the role of GH-releasing hormone and GH-releasing peptide-2.

PURPOSE AND METHODS: This study was designed to investigate the role of two effective releasers of growth hormone (GH): GHRH and GHRP-2 during exercise (EX). Eight healthy male subjects (ages: 22 +/- 1.2 (mean +/- SD) yr, BMI: 22.5 +/- 2.2 kg x m(-2)) were exposed to maximally stimulating dose of 100 microg GHRH iv, and 200 microg GHRP-2 iv, during incremental EX on a cycle ergometer to exhaustion. GH responses after EX alone were compared with the responses after the combined administration of the same EX plus GHRH, EX plus GHRP-2, and EX plus GHRH plus GHRP-2. Blood samples were obtained in the fasted state at intervals for 2 h postexercise and the area under the GH response curve (AUC) was calculated by trapezoidal integration. RESULTS: Significant differences (P < 0.003) were observed between the AUCs after administration of EX alone (mean +/- SEM): 2,324 +/- 312 microg x L(-1) 120 min, after EX plus GHRH: 6,952 +/- 1,083, after EX plus GHRP-2: 14,674 +/- 2,210, and after the combination EX plus GHRH plus GHRP-2: 17,673 +/- 1,670. However, AUCs after each combination did not differ significantly from those after arithmetical addition of each separate stimulus, indicating that the mechanisms of the respective stimuli do not interact. Linear regression analysis on mean GH responses between 20 and 30 min after the start of EX showed that EX alone and GHRH alone explain about 59% (adj. R2) of the GH response to the combination EX plus GHRH. The ratio of the respective regression coefficients (GHRH vs EX) was about 2:1 (instead of 1:1), indicating that EX seems to potentiate the activity of GHRH. GHRH alone and EX alone also explained about 74% of the response to the combination EX plus GHRP-2. In the latter response, a synergistic action of GHRP-2 on GHRH could be observed. CONCLUSIONS: The data indicate that under strenuous EX conditions, endogenous GHRH activity causes a further increase of GH release. A GHRP-2 mediated mechanism in the central neuroendocrine regulation acts as a "booster," possibly by stimulating the effects of GHRH and/or an unknown hypothalamic factor, as well as by stimulating the pituitary GH release directly.

Adult↗
PubMed2000

Age-sensitive cognitive function, growth hormone and insulin-like growth factor 1 plasma levels in healthy older men.

Circulating levels of growth hormone (GH) change during the process of aging. Decline of cognitive functioning with aging is also well established. In this study, we investigated whether insulin-like growth factor 1 (IGF-1) and the GH response to a challenge of GH-releasing hormone and GH-releasing peptide 6 were associated with age-sensitive cognitive functions, but not with functions that do not decline with aging, in 17 healthy male subjects aged between 66 and 76 years. In addition, relations with anthropometric measures were examined. Neuropsychological performance was scored on tests of variables not sensitive to aging (general knowledge, vocabulary, basic visual perception and reading ability), and of variables sensitive to aging (visuoconstructive ability, perceptual motor and mental processing speed, and verbal long-term memory). After correcting for education, the serum GH response was significantly associated with two age-sensitive cognitive tests (measures of mental processing speed), but with none of the tests not sensitive to aging. However, the direction of the association was opposite to the relation between IGF-1 and these cognitive tests: higher levels of GH response were associated with poorer cognitive performance, whereas higher levels of IGF-1 were associated with better performance. GH response, but not IGF-1, was inversely correlated with body mass index. The results are in accordance with previous research suggesting a disruption of the relation between IGF-1 and GH secretion in older age.

Aged↗
PubMed2000

Reduction of free fatty acids by acipimox enhances the growth hormone (GH) responses to GH-releasing peptide 2 in elderly men.

GH release is increased by reducing circulating free fatty acids (FFAs). Aging is associated with decreased plasma GH concentrations. We evaluated GH releasing capacity in nine healthy elderly men after administration of GH-releasing peptide 2 (GHRP-2), with or without pretreatment with the antilipolytic drug acipimox, and compared the GHRP-2-induced GH release with the response to GHRH. The area under the curve (AUC) of the GH response after GHRP-2 alone was 4.8 times higher compared with GHRH alone (1834 +/- 255 vs. 382 +/- 78 microg/L.60 min, P: < 0.001). Acipimox, which reduced FFAs from 607 micromol/L to 180 micromol/L, increased the GH AUC to 1087 after GHRH and to 2956 microg/L.60 min after GHRP-2 (P: < 0.01). The AUC after acipimox/GHRP-2 were positively correlated with the AUC after GHRP-2 alone (r = 0.93, P: < 0.01); this was also observed between acipimox/GHRH and GHRH alone (r = 0.73, P: = 0.03). Significant negative correlations were observed between basal FFAs and AUC after GHRH or GHRP-2 after combining the data with and without acipimox (r = 0.58, P: = 0.01 and r = 0.48, P: = 0.04, respectively), and between basal FFAs and GH at t = 0 (r = -0.44, P: = 0.001). Interestingly, GHRP-2 administration was followed by a significant early rise in plasma FFAs by 60% (P = 0.01), indicating an acute lipolytic effect. In conclusion, reduction of circulating FFAs strongly enhances GHRP-2-stimulated GH release in elderly men. The data indicate that the decreased GH release associated with aging can be reversed by acipimox and that the pituitary GH secretory capacity in elderly men is still sufficient.

Aged↗
PubMed1999

High-affinity growth hormone (GH)-binding protein (GHBP), body fat mass, and insulin-like growth factor-binding protein-3 predict the GHBP response to GH therapy in adult GH deficiency syndrome.

The study objective was to investigate which baseline factors can accurately predict plasma high-affinity growth hormone (GH)-binding protein (GHBP) levels after GH replacement therapy in patients with GH deficiency (GHD). The study group consisted of 36 GHD patients (22 men and 14 women; mean age, 43.1 years; (range, 21 to 60) known to have adult-onset GHD for many years (range, 4 to 22). They were randomly divided into a GH-treated group (n = 19) and a placebo group (n = 17). Body composition (assessed by bioelectrical impendance analysis [BIA]), plasma GHBP (fast protein liquid chromatography [FPLC] size-exclusion gel chromatography), insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 ([IGFBP-3] radioimmunoassays) were measured before and after 6 months. A stepwise multiple linear regression analysis with the plasma GHBP level after 6 months as the dependent variable was used to unravel significant explanatory (or predictor) variables. In contrast to placebo therapy, GH replacement therapy increased the mean plasma levels of IGF-I and IGFBP-3 to the normal range, whereas a small but statistically significant increase in plasma GHBP was observed. The combination of baseline plasma GHBP, body fat mass, and IGFBP-3 predicts posttreatment GHBP levels accurately (adjusted R2 = .97), indicating that baseline variables such as age, gender, fat-free mass, and IGF-I have no contribution. Furthermore, reliability analysis showed that the observed and predicted values for GHBP fit a strict parallel model. These findings indicate that the variations in body fat mass and IGFBP-3 among adult GHD subjects explain the reported variable response of GHBP to GH replacement therapy.

Adipose Tissue↗