Biomedical subjects

P Sytze van Dam

Publications and source records attributed to P Sytze van Dam.

12 recordsLinked to original sources

PubMed2006

Effects of growth hormone substitution therapy on cognitive functioning in growth hormone deficient patients: a functional MRI study.

Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 +/- 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.

Adolescent↗

PubMed2006

Neurocognitive function in adults with growth hormone deficiency.

The clinical condition of growth hormone deficiency (GHD) as a consequence of pituitary or hypothalamic disease has been associated with reduced cognitive performance. In several studies, neuropsychological assessment has been performed in adults with GHD both before and after growth hormone (GH) replacement therapy. Interpretation of the available data is complicated by the variation in patient selection as well as the neuropsychological tests used in such studies. Most of the available studies indicate that GHD can lead to small, but clinically relevant changes in memory, processing speed and attention. Some of these changes may be reversed by GH replacement, although the number of reliable intervention studies is limited. In addition to the possible clinical relevance of neuropsychological improvement following GH replacement in patients with GHD, the observed findings may be of interest for studies in neurocognitive performance in other conditions associated with changes in the activity of the somatotrophic axis, and in the understanding of underlying pathophysiological mechanisms.

Adult↗

PubMed2005

Growth hormone deficiency and memory functioning in adults visualized by functional magnetic resonance imaging.

Cognitive functioning, especially memory performance, is known to be impaired in patients with childhood-onset growth hormone deficiency (CO-GHD), and growth hormone substitution has been found to counteract this memory impairment. Neuropsychological and functional magnetic resonance imagining (fMRI) data acquired during a working memory task in 13 childhood-onset GH-deficient patients were compared with 13 age, sex and education level matched healthy controls. Results demonstrated that there is no difference in the quality of the performance in the working memory task between GH-deficient patients and control subjects. However, memory speed was found to be subnormal in patients. Concerning mood, patients reported more complaints of fatigue, and less vigor. Imaging data showed that patients had increased activity in dorsolateral/ventrolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, supplementary motor and motor cortex, as well as in the thalamus and precuneus area. Increasing task load was also associated with an increase in brain activity in similar areas in patients compared to control subjects. In conclusion, this fMRI study shows that GH-deficient patients have a subnormal memory speed, but no impaired quality of memory performance, which may be due to compensatory recruitment of dorsal prefrontal brain regions. These findings indicate that the GH-IGF-1 axis contributes to prefrontal functioning in patients with CO-GHD.

Adolescent↗

PubMed2005

Childhood-onset growth hormone deficiency, cognitive function and brain N-acetylaspartate.

Cognitive deficits have been reported in adults with childhood-onset growth hormone (GH) deficiency. We evaluated cognitive deficits simultaneously with parameters for neuronal integrity using (1)H magnetic resonance spectroscopy (MRS) in a cross-sectional design. We studied 11 adults (mean age 24.5 years) with childhood-onset GH deficiency, which persisted after reaching final height. All subjects were evaluated after interruption of GH supplementation for at least 3 months. We performed neuropsychological assessment (NPA) using tests evaluating memory, mental processing speed, reading ability and executive functioning. MRS was used to assess brain N-acetylaspartate (NAA)/choline ratios. Data were compared with an age-, sex- and education-matched control group (n=9, mean age 27.3 years). NPA demonstrated attenuated performance of the patients in the delayed verbal memory recall score (P<0.05) and the trail making A test (P<0.05), a measure of planning of behavior, processing speed and attention. Other neuropsychological tests were not affected. NAA/choline ratios were significantly reduced (P<0.01) in GH deficient subjects. Specific cognitive defects indicating affected memory and attention were found in patients with childhood-onset GH deficiency. These defects occur simultaneously with reduced neuronal integrity.

Adolescent↗

PubMed2005

The GHRH/GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men.

OBJECTIVE AND DESIGN: Ageing and obesity result in decreased activity of the GH/IGF-I axis and concomitant impaired GH responses to secretory stimuli. We therefore determined the validity of the GH cut-off value of 15.0 microg/l in the GH-releasing hormone (GHRH)/GH releasing peptide-6 (GHRP-6) test for the diagnosis of GH deficiency in elderly or severely obese men. METHODS: We performed a combined GHRH/GHRP-6 test in ten elderly men (mean age 74 years; mean body mass index (BMI) 24.6 kg/m(2)), nine obese men (mean age 47 years; mean BMI 40.6 kg/m(2)) and seven healthy male controls (mean age 51 years, mean BMI 24.3 kg/m(2)). After assessment of fasting plasma GH, IGF-I and IGF-binding protein-3 (IGFBP-3), GHRH (100 microg) and GHRP-6 (93 microg) were given intravenously as a bolus injection. Repeated GH measurements were performed for two hours. RESULTS: Both peak GH levels and areas under the curve (AUC) were significantly lower in the obese than in the controls (peak 13.2 vs 53.4 microg/l, P = 0.001; AUC 707 vs 3250 microg/l x 120 min; P = 0.001). Mean GH response in the elderly was lower than in the controls (peak 35.0 microg/l; AUC 2274 microg/l x 120 min), but this was not statistically significant. In contrast, GH peak levels in seven obese men remained below the cut-off level of 15.0 microg/l associated with severe GH deficiency. All others had GH peak levels exceeding this threshold. IGFBP-3 levels were significantly lower in the elderly than in the controls (1.35 vs 2.05 mg/l, P = 0.001). Baseline GH or IGF-I did not differ significantly between groups. CONCLUSIONS: GH responses following GHRH/GHRP-6 administration were significantly reduced in severely obese men, but were not significantly reduced in elderly men, despite a negative trend. Our data indicate that the cut-off GH level of 15.0 microg/l after GHRH + GHRP-6 administration for the diagnosis of severe GH deficiency cannot be used in severely obese men.

Aged↗

PubMed2004

Insulin-like growth factor-I, cognition and brain aging.

Aging is associated with a decline in the activity of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. As aging also coincides with a decline in specific cognitive functions and as some of these dysfunctions are also observed in subjects with GH deficiency, it has been hypothesised that a causal relationship exists between the reduction in circulating GH and/or IGF-I and the observed cognitive deficits in the elderly. The present review summarises the available data concerning the possible relation between GH, IGF-I and cognitive performance, and regarding possible underlying pathophysiological mechanisms.

Adult↗

PubMed2004

The role of the somatotropic system in cognition and other cerebral functions.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) receptors can be found in several areas of the brain. GH receptors are mainly found in the choroid plexus, thalamus, hypothalamus, pituitary, putamen, and hippocampus, whereas IGF-1 receptors are mainly concentrated in the hippocampus and parahippocampal areas. In early life, GH and IGF-1 have an important role in the development and differentiation of the central nervous system. In the more developed central nervous system, GH and IGF-1 are thought to have a variety of functions such as a neuroprotective function, an appetite increasing function, various cognitive functions, and perhaps a blood flow-regulating function. In GH-deficient children and adults, improvement of cognitive functions was observed after the administration of GH. Furthermore, specific cognitive functions in healthy older subjects may improve after increasing GH or IGF-1 levels.

Affect↗

PubMed2004

Upper gastrointestinal responses to intraduodenal nutrient in type 1 diabetes mellitus.

BACKGROUND: Abnormal nutrient-related small-intestinal feedback may contribute to disordered gastric motility and upper gastrointestinal symptoms in patients with diabetes. AIM: To evaluate the motor, sensory and incretin responses to intraduodenal nutrients in patients with type 1 diabetes and in controls. METHODS: Eight type 1 diabetes patients (two with autonomic neuropathy) and nine controls were studied during euglycaemia. A manometric catheter was positioned across the pylorus, and nutrient was infused intraduodenally (90 kcal over 30 min). Blood glucose and plasma glucagon-like peptide 1 and gastric inhibitory polypeptide were measured, and sensations were assessed with visual analogue questionnaires. RESULTS: During nutrient infusion, neither the number of antral waves nor the stimulation of phasic or basal pyloric pressures differed between patients and controls. Upper gut sensations and areas under the plasma incretin peptide curves did not differ between the groups. CONCLUSIONS: During euglycaemia, the upper gastrointestinal motor, sensory and incretin peptide responses to small-intestinal nutrient are comparable in patients with relatively uncomplicated type 1 diabetes and in healthy subjects.

Adult↗

PubMed2003

Diagnosis of growth hormone deficiency after pituitary surgery: the combined acipimox/GH-releasing hormone test.

OBJECTIVE: Reduction of plasma free fatty acids leads to enhanced GH response after stimulation by GH-releasing hormone (GHRH). We studied the clinical usefulness of combined administration of acipimox and GHRH for the diagnosis of GH deficiency. DESIGN: We evaluated 35 patients [mean age 53.0 years; mean body mass index (BMI) 26.7 kg/m2] after pituitary surgery. We compared GH responses after acipimox and GHRH with the GH response during an insulin tolerance test (ITT) and, in a subgroup of 12 patients, with the GHRH/arginine test. The acipimox/GHRH test was additionally performed in 21 control subjects (mean age 53.8 years; mean BMI 24.7 kg/m2). RESULTS: In the patients, the mean (+/- SEM) peak GH was almost four-fold higher after acipimox/GHRH (6.94 +/- 1.07 microg/l, range 0.46-23.1; P < 0.001) and after GHRH/arginine (8.32 +/- 1.23 microg/l, range 1.1-49.2; P < 0.001) than after ITT (1.84 +/- 0.46 microg/l, range 0.01-11.9). According to the ITT, 29 patients were severely GH deficient (peak GH < 3.0 microg/l). Peak GH levels after acipimox/GHRH in controls ranged from 7.5 to 78.4 microg/l (mean 29.3 +/- 3.5). GH peak values during the acipimox/GHRH test were significantly correlated with values from the ITT (r = 0.63, P < 0.01) and GHRH/arginine test (r = 0.87, P < 0.001). Areas under the curve were also correlated. According to generally accepted cut-off peak GH levels for the ITT and GHRH/arginine test, a GH peak exceeding 11.2 micro g/l excludes severe GH deficiency after acipimox/GHRH. Our control data indicate that the cut-off level is lower at older age. CONCLUSIONS: The acipimox/GHRH test leads to GH responses similar to those of the GHRH/arginine test, and to higher peak GH values if compared with the ITT. The acipimox/GHRH test is a potential additional tool to detect GH deficiency in patients with pituitary disease, in particular in patients with a perturbation of fatty acid metabolism.

Adenoma↗

PubMed2003

High prevalence of fatigue in quiescent inflammatory bowel disease is not related to adrenocortical insufficiency.

OBJECTIVES: Inflammatory bowel disease (IBD) patients, with active as well as quiescent disease, frequently complain of fatigue. This often has consequences for patients' work and daily lives. The primary aim of this study was to assess the prevalence and severity of fatigue in IBD patients in remission. Furthermore, we studied the correlation between fatigue and disease activity, quality of life, and biochemical and hematological test results, and the role of (secondary) hypocortisolism. METHODS: Eighty subjects with proven IBD were included. Disease activity was assessed using the Clinical Activity Index for Ulcerative Colitis and the Crohn's Disease Activity Index. Quality of life was measured by the Inflammatory Bowel Disease Questionnaire, and fatigue was assessed using the Multidimensional Fatigue Inventory (MFI). Routine biochemical and hematological tests were performed, and basal cortisol was determined. To evaluate adrenocortical reserve in subjects with a cortisol level of <0.4 micromol/L, a low dose adrenocorticotrophin hormone test was performed. Healthy age- and sex-matched subjects (n = 67) served as controls. RESULTS: More than 40% of the IBD patients in remission suffered from fatigue. Mean MFI scores of the IBD patients were comparable to mean MFI scores reported in cancer patients. The Inflammatory Bowel Disease Questionnaire showed a negative correlation with the MFI (r = -0.735; p < 0.001). No correlation was found between fatigue and basal cortisol levels or other laboratory parameters. CONCLUSION: Fatigue is an important feature in IBD in remission, adversely affecting the quality of life. It does not, however, affect all patients, nor does it seem to be the result of hypocortisolism.

Adrenal Insufficiency↗

PubMed2002

Sequential ACTH and catecholamine secretion in a phaeochromocytoma.

OBJECTIVE: We describe a patient with an ACTH-producing phaeochromocytoma who initially presented with hypercortisolism and normal catecholamine concentrations, followed by near-normalisation of ACTH secretion and massive catecholamine secretion. In vitro studies were carried out on the tumour to evaluate the interaction between the tumour cells and normal adrenal cortex. METHODS AND RESULTS: A 30-year-old man initially presented with severe hypercortisolism, biochemical evidence of ectopic ACTH production, a tumour in the right adrenal gland without a hyperintense signal on the T2-weighted images at magnetic resonance imaging (MRI) scanning, and normal urinary metanephrine concentrations. After 6 months, ACTH production had almost completely resolved, but the patient developed severe hypertension and excess catecholamines. At repeated MRI-scanning, the T2-weighted images showed a hyperintense signal, in agreement with the diagnosis of phaeochromocytoma. Although the initial T1-weighted images suggested bleeding in the adrenal tumour, no signs of bleeding were observed after surgical removal. The diagnosis of ACTH-producing phaeochromocytoma was histologically and immunohistochemically confirmed. Cultured cell suspensions of the tumour secreted ACTH, which stimulated cortisol production in the ipsilateral adrenocortical cells. CONCLUSION: This case demonstrates that the biological activity of an ACTH-producing phaeochromocytoma can vary significantly in time, which may be the consequence of different stages of tumour differentiation.

3-Iodobenzylguanidine↗

PubMedDate not supplied

Oxidative stress and diabetic neuropathy: pathophysiological mechanisms and treatment perspectives.

Increased oxidative stress is a mechanism that probably plays a major role in the development of diabetic complications, including peripheral neuropathy. This review summarises recent data from in vitro and in vivo studies that have been performed both to understand this aspect of the pathophysiology of diabetic neuropathy and to develop therapeutic modalities for its prevention or treatment. Extensive animal studies have demonstrated that oxidative stress may be a final common pathway in the development of diabetic neuropathy, and that antioxidants can prevent or reverse hyperglycaemia-induced nerve dysfunction. Most probably, the effects of antioxidants are mediated by correction of nutritive blood flow, although direct effects on endoneurial oxidative state are not excluded. In a limited number of clinical studies, antioxidant drugs including alpha-lipoic acid and vitamin E were found to reduce neuropathic symptoms or to correct nerve conduction velocity. These data are promising, and additional larger studies with alpha-lipoic acid are currently being performed.

Animals↗