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Biomedical subjects

Anton Luger

Publications and source records attributed to Anton Luger.

At least 19 recordsLinked to original sources
PubMed2007

Endocrine function is not impaired in patients with a continuous MicroMed-DeBakey axial flow pump.

OBJECTIVES: Pulsatile blood flow has been regarded to be of importance for the regulation of endocrine organs. A new generation of continuous flow mechanical blood pumps is now available for clinical application. Patients with implanted MicroMed-DeBakey axial pumps show nonphysiologic low-pulsatile blood flow profiles, and therefore it appeared to be of interest to evaluate their possible effect on the endocrine system. METHODS: Eight male patients and 1 female patients (mean age, 51 +/- 10 years) with end-stage left-sided heart failure were implanted with a MicroMed-DeBakey axial pump. After a mean period of 67 +/- 19 days, basal pituitary hormone concentrations and their responses to a bolus injection of hypothalamic releasing hormones were tested. In addition, thyroid hormones, testosterone, and plasma and urinary catecholamine levels were measured at baseline. RESULTS: Administration of the hypothalamic releasing hormones revealed normal responses of all pituitary hormones (adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, and prolactin), except for growth hormone, the response of which was slightly impaired (10.2 +/- 6.8 vs 19.9 +/- 6.5 ng/L, P < .05). Also, the cortisol response to the corticotropin-releasing hormone-stimulated adrenocorticotropic hormone release was normal, as were basal concentrations of thyroid hormones (triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine), testosterone, and urinary catecholamines. CONCLUSIONS: Implantation of a continuous flow axial pump with low-pulsatile blood flow profile appears to have no major effect on the hypothalamic-pituitary-endorgan system and sympathoadrenal functions. This finding is reassuring for the growing number of patients treated with this convenient new pump and could contribute considerably to their prognosis and quality of life.

Catecholamines↗
PubMed2006

Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects.

CONTEXT: Administration of retinol-binding protein 4 (RBP-4) impairs insulin sensitivity in animals, and elevated serum concentrations have been associated with insulin resistance in humans. OBJECTIVE: We have studied whether weight loss influences RBP-4. PATIENTS AND METHODS: Fasting serum concentrations of RBP-4 were measured before and 6 months after gastric banding surgery in 33 morbidly obese patients aged 40 +/- 11 yr with a body mass index (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI less than 25 kg/m(2) served as controls. To characterize the association of weight loss with central and peripheral appetite regulation, the signaling protein agouti-related protein (AGRP), the orexigenic hormone ghrelin, and its recently identified antagonist obestatin were determined. RESULTS: At baseline, RBP-4 levels were markedly higher in obese than in lean subjects (2.7 +/- 0.5 vs. 0.9 +/- 0.5 microg/ml; P < 0.001). In contrast, AGRP and obestatin were lower in obese subjects compared with lean controls (all P < 0.001). Six months after gastric banding, BMI was reduced to 40 +/- 5 kg/m(2), RBP-4 was reduced to 2.0 +/- 0.7 microg/ml, AGRP increased from 1.8 +/- 1.1 to 3.4 +/- 1.1 ng/ml, ghrelin increased from 93 +/- 58 to 131 +/- 70 pg/ml, and obestatin increased from 131 +/- 52 to 173 +/- 35 pg/ml (all P < 0.05). Individual changes of RBP-4 were associated with changes of BMI (r = 0.72), the homeostasis model assessment insulin resistance-index (r = 0.53), and total cholesterol (r = 0.42, for all P < 0.05). CONCLUSION: Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss. This is accompanied by favorable changes in appetite-regulating hormones, which might support the sustained weight loss after obesity surgery.

Adult↗
PubMed2006

Long-term in vitro growth of human insulin-secreting insulinoma cells.

OBJECTIVE: Long-term in vitro maintenance of human insulin-secreting insulinoma cells. METHODS: (1) Cell culture of ex vivo-derived insulinoma cell suspensions from 8 individual human donors, using various cell culture medium supplementations; (2) determination of insulin synthesis and secretion using immunocytochemistry and insulin and pro-insulin radioimmunoassays; (3) nestin-immunostaining of long-term in vitro grown insulinoma cell suspensions, and (4) phase-contrast light microscopy for analyzing the in vitro growth characteristics of the insulinoma cells. RESULTS: (1) Parallel persistence of in vitro insulinoma cell proliferation as well as insulin-synthesizing and -secreting capacity depended on both the co-culture of insulinoma cells with human fibroblasts and the supplementation of the cell culture medium with tissue culture supernatant derived from the rodent pituitary adenoma cell line GH-3; (2) immunostaining for insulin and secretagogin confirmed the neuroendocrine origin of the insulinoma cells grown in vitro; (3) insulin secretion capability persisted up to an observation period of 25 weeks; (4) insulin secretion rates after 6 weeks of in vitro growth ranged from 3.5 to 83.3 muU/ml/h/60,000 cells plated, and (5) after long-term in vitro growth of insulinoma-derived cell suspensions with persistent insulin-secreting capacity, nestin staining was observed predominantly in co-cultured fibroblasts. CONCLUSION: Our data describe for the first time the long-term in vitro culture of insulin-secreting human insulinomas and highlight the importance of beta-cell trophic factors for insulinoma cell growth.

Adult↗
PubMed2006

Long term control of hypercortisolism with fluconazole: case report and in vitro studies.

OBJECTIVES: To evaluate the efficacy of fluconazole as an alternative treatment for controlling hypercortisolism in Cushing's syndrome and to determine its effect on glucocorticoid production in vitro. DESIGN: Case report and in vitro study in a University Clinic. CASE: An 83 year old patient presented with recurrence of Cushing's syndrome due to pulmonary metastases three years after unilateral adrenalectomy. During a near fatal episode of sepsis she was started on fluconazole 200 mg/day intravenously which normalised cortisol excretion. The therapy was continued orally for 18 months. Upon temporary discontinuation and reintroduction of treatment, cortisol levels increased and normalized, respectively. At month 16, fluconazole had to be increased to a dose of 400 mg/day to keep cortisol excretion in the normal range. Disease progression was slow and no side effects occurred. IN VITRO RESULTS: Fluconazole in a concentration of 500 microM nearly abolished corticosterone production over 24 h from the adrenal adenoma cell line Y-1 (8.6 +/- 0.5% compared with control, P < 0.0001) and significantly reduced corticosterone production in concentrations of 50 microM (48.3 +/- 1.9% vs. control, P < 0.0001) and 5 microM (80.5 +/- 8.5% vs. control, P < 0.05). CONCLUSION: These results demonstrate for the first time that fluconazole normalises cortisol concentrations in vivo in a patient with Cushing's syndrome with adrenal carcinoma and inhibit glucocorticoid production in vitro in a cell line. Thus, fluconazole might be useful in controlling glucocorticoid excess in Cushing's syndrome and because of its lower toxicity might be preferable to ketoconazole.

Adenoma↗
PubMed2005

G-protein-coupled glucocorticoid receptors on the pituitary cell membrane.

Rapid, nongenomic actions of glucocorticoids (GCs) have been well documented, but information about putative membrane receptors that mediate them is scarce. We used fluorescence correlation spectroscopy to search for membrane GC-binding on the mouse pituitary cell line AtT-20. A slowly diffusing fraction (tau3; diffusion constant 3x10(-10) cm2 s-1) of fluorescein-labeled dexamethasone on the cell membrane corresponds to fluorescein-dexamethasone binding. Preincubation experiments were performed to test binding specificity: a 500-fold excess of unlabeled dexamethasone abolished subsequent fluorescein-dexamethasone membrane binding from 58+/-2 (control) to 8+/-1 (% of tau3, mean+/-s.e.m.), the natural ligand corticosterone prevented it partially (29+/-2), while the sex steroids estradiol (56+/-4) and progesterone (50+/-4) and the GC-receptor antagonist RU486 (56+/-2) had no effect. Preincubation with pertussis toxin resulted in disappearance of the slowest diffusion component (11+/-4) suggesting association of the receptor with a G-protein. Varying the concentration of fluorescein-dexamethasone showed that membrane binding is highly cooperative with an apparent Kd of 180 nM and Bmax of 230 nM. Taken together, these results demonstrate high-affinity GC-binding on the cell membrane of AtT-20 cells with characteristics distinct from intracellular binding.

Animals↗
PubMed2005

Osteoprotegerin plasma concentrations correlate with severity of peripheral artery disease.

OBJECTIVE: Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, is involved in the process of bone turnover and also in the pathogenesis of osteoporosis and premature calcification of the vascular system. In the present study on patients with peripheral artery disease (PAD), we correlated plasma OPG concentrations with severity of disease and the presence of cardiovascular risk factors. PATIENTS AND METHODS: Sixty-seven consecutive inpatients (26 females; mean age 70 years (S.D.: 12), undergoing percutaneous transluminal angioplasty (PTA) because of advanced symptomatic PAD of the lower extremities were studied. Severity grade of disease (clinical stage after "Fontaine", functional measurements in terms of the ankle brachial index (ABI) and "Bollinger score" of angiographies), biochemical parameters and a detailed cardiovascular risk profile were documented. Fasting plasma concentrations of OPG were measured by a commercial sandwich enzyme immunoassay. MAIN RESULTS: The mean plasma concentrations of OPG were 5.3 pmol/l (S.D.: 3.3). Plasma OPG concentrations in subjects with PAD, clinical stages III-IV (n=15) were 7.9 pmol/l (S.D.: 5.3) and were significantly higher than in patients without ischemic ulcerations (n=52; 4.6 pmol/l; S.D.: 2.0; p<0.01). The mean value of Bollinger score was 29.1 (S.D.: 19.8). OPG was positively correlated with Bollinger score of disease (r=0.31; p<0.02), age (r=0.58; p<0.01) and creatinine-values (r=0.32; p<0.01) and negatively correlated with ABI (r=-0.39; p<0.03). CONCLUSION: In patients with PAD, plasma OPG concentrations were significantly higher in subjects with ischemic ulcerations than in those without and were positively correlated with higher severity grade of disease, age and creatinine-values. Further studies are required to analyze the role of OPG as a diagnostic marker for severity of atherosclerotic disease and to assess a possible therapeutic potential as "vasculoprotegerin".

Aged↗
PubMed2005

[Schilddrüse und polyendokrinopathien].

The thyroid gland can be affected in the course of several polyendocrinopathy syndromes either by impairment of physiological function or thyroid carcinoma. The various syndromes -- polyglandular autoimmune syndrome, autoimmune hypophysitis, multiple pituitary hormone deficiency, multiple endocrine neoplasia, and Carney complex -- are discussed. Therapy of thyroid dysfunction is identical whether it is part of a specific syndrome or not. Genetic testing for mutations, however, has had an enormous impact on screening procedures and therapeutic consequences.

Chromosome Aberrations↗
PubMed2004

Normal regulation of elevated plasma ghrelin concentrations in dialysis patients.

BACKGROUND: Chronic renal failure is often associated with malnutrition, and malnourished patients are subject to increased morbidity and mortality. Therefore plasma concentrations of the stomach-derived peptide hormone ghrelin, which has been shown to exert potent GH-releasing and appetite-stimulating effects, were determined and correlated with nutritional parameters. METHODS: Twenty-four patients (15 male, 9 female) undergoing hemodialysis (HD) were studied. In addition, six patients were studied before and one hour after ingestion of a meal and five were studied immediately before and at the end of the dialysis session. RESULTS: Chronic renal insufficiency was associated with significantly elevated ghrelin levels (320.1 +/- 57 fmol/mL vs. 75.6 +/- 12.4 fmol/mL in controls; p < 0.007). Plasma ghrelin concentrations were also significantly higher in the 16 normal-weight patients than in the eight overweight or obese patients (399.6 +/- 76.3 fmol/mL vs. 161.1 +/- 41.3 fmol/mL; p < 0.03). Ingestion of food induced a decrease in five out of six patients tested (mean 242.3 +/- 66.5 fmol/mL vs. 186 +/- 30.7 fmol/mL; n.s.). HD also resulted in a significant decrease of elevated ghrelin concentrations: ghrelin was in the normal range at the end of HD in four of the five patients tested. Plasma ghrelin concentrations did not correlate with nutritional parameters except for cholinesterase which was negatively correlated to ghrelin. CONCLUSION: Plasma ghrelin concentrations are elevated in HD. The fact that ghrelin concentrations are higher in normal-weight than in overweight or obese HD patients and suppressed after ingestion of a meal suggests that the regulation of ghrelin release is retained in HD patients, albeit shifted to a higher level.

Adult↗
PubMed2004

[Surgical treatment of obesity].

At the beginning of the 21st century, obesity has become an epidemic with the greatest prevalence in the western world. For morbidly obese patients, conservative treatment has yielded disappointing results: On the other hand, bariatric surgery offers a sustained substantial weight loss for these patients. Common bariatric procedures including results and complications are described. Different Bariatric procedures including Gastric Banding, Vertical Banded Gastroplasty, Gastric Bypass, Duodenal Switch and Gastric Pacing are introduced. Bariatric procedures can result in permanent excessive weight loss ranging from 25 to 78% and thus are an effective treatment for morbidly obese patients. Efficacy, morbidity and late term complications, however, should be considered in choosing the most effective bariatric approach.

Biliopancreatic Diversion↗
PubMed2004

Dynamic contrast-enhanced MR imaging of the stimulated pituitary gland.

Apoplexy due to infarction and/or hemorrhage is a frequent complication of pituitary adenoma, occurring either spontaneously or precipitated by several factors, among them pituitary function test with hypothalamic releasing hormones. The mechanism by which releasing hormones cause pituitary apoplexy is unclear. It has been proposed that increase in pituitary size and/or alterations in blood flow could be responsible. The aim of this study was to explore the effects of intravenous administration of hypothalamic releasing hormones on pituitary size and hemodynamics in healthy subjects. Gadolinium-DTPA-enhanced dynamic magnetic resonance imaging (MRI) was performed in eight healthy volunteers under basal conditions and 20 min after injection of releasing hormones. Mean upslopes of Gadolinium-DTPA enhancement curves showed good correlation between basal and stimulated conditions (R = 0.89) and were significantly steeper after stimulation (P = 0.017). In contrast, pituitary height, width and length did not differ significantly between basal and stimulated conditions. In conclusion, the pituitary does not swell in healthy subjects in response to stimulation with hypothalamic releasing hormones, whereas transfer of contrast agent to tissue (blood flow and/or vessel permeability) is enhanced.

Adenoma↗
PubMed2004

The cholinergic system controls ghrelin release and ghrelin-induced growth hormone release in humans.

The stomach-derived peptide hormone ghrelin induces appetite and GH release. Several ghrelin actions are possibly mediated and modulated by the central cholinergic system. The aim of this study was to investigate the influence of the unspecific cholinergic antagonist atropine and the acetylcholine esterase inhibitor pyridostigmine, a cholinergic enhancer on ghrelin plasma concentrations and ghrelin-induced GH release. We investigated plasma ghrelin concentrations, ghrelin-induced GH release, and glucose and insulin concentrations after administration of atropine or pyridostigmine, and ghrelin (in two different doses, 0.25 and 1 microg/kg body weight), alone and in combination in a randomized, double-blind, placebo-controlled, crossover study design on 12 young, healthy male volunteers. Atropine alone significantly reduced fasting ghrelin levels by 25%, whereas under pyridostigmine alone ghrelin levels were unaltered. Ghrelin in combination with atropine induced significantly reduced GH concentrations compared with ghrelin administration alone for both ghrelin doses, whereas ghrelin-induced GH peak concentrations and areas under the curve were not enhanced by pyridostigmine treatment. These results suggest that, in humans, fasting ghrelin concentrations might be under cholinergic control and that the cholinergic system appears to modulate ghrelin-induced GH release.

Adult↗
PubMed2004

[Endocrinologie and obesity].

The endocrine system plays a central role in the regulation of body weight and fat distribution. The influence of thyroid hormones, growth hormone, cortisol und sex steroids on body weight are described with a focus on hyper- and hypofunction of these systems. In addition, sequelae of therapeutic interventions aiming to restore homeostasis in dysfunction are discussed. Finally, neuroendocrine control of appetite and syndromes that are consequences of disturbed neuroendocrine control of food intake are described.

Adipose Tissue↗
PubMed2003

Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.

Adult↗
PubMed2003

Effects of glimepiride on HbA(1c) and body weight in Type 2 diabetes: results of a 1.5-year follow-up study.

Sulphonylureas are effective and well tolerated in patients with Type 2 diabetes, but may be associated with weight gain, and lack of compliance due to multiple daily dosing. This open, uncontrolled surveillance study examined the efficacy and safety of glimepiride, a new sulphonylurea, administered once daily in patients with Type 2 diabetes. A total of 1,770 patients were enrolled in the study, and 284 patients were selected for follow-up. Patients received 0.5 to >4 mg glimepiride once daily for 1.5 years. HbA(1c) was reduced from 8.4% at baseline to 7.1% after 4 months and 6.9% after 1 and 1.5 years (median intra-individual change from baseline: -1.4, -1.5, and -1.7%, respectively; P<0.0001). Treatment with glimepiride also resulted in significant and stable weight loss relative to baseline, with the exception of patients with a body mass index of <25 kg/m(2). Mean body weight was reduced from 79.8 kg at baseline to 77.9 kg after 4 months, 77.2 kg after 1 year, and 76.9 kg after 1.5 years (mean intra-individual change from baseline: -1.9 kg, P<0.0001; -2.9 kg, P<0.05; -3.0 kg, P<0.005, respectively). Therefore, once daily glimepiride provides effective glycaemic control, and may have advantages over other sulphonylureas, because it exhibits weight neutralizing/reducing effects in patients with Type 2 diabetes.

Adult↗
PubMed2003

One-year growth hormone therapy improves granulocyte function without major effects on nutritional and anthropometric parameters in malnourished hemodialysis patients.

BACKGROUND/AIMS: Growth hormone (GH) resistance leads to enhanced protein catabolism and contributes to the malnutrition of patients with chronic renal failure (CRF). In short-term trials anabolic effects of rhGH therapy have been demonstrated in patients on chronic hemodialysis. METHODS: This study was initiated to determine the effects of 12 months of rhGH therapy on polymorphonuclear leukocyte (PMNL) function as well as on nutritional and anthropometric parameters. 0.125 IU/kg rhGH was given 3 times a week during the first 4 weeks and 0.25 IU/kg thereafter to 19 malnourished hemodialysis patients with a mean age of 59.3 +/- 13.4 years. RESULTS: Insulin-like growth factor I (IGF-I) concentrations rose significantly from 169.2 +/- 95.6 to 262.9 +/- 144.4 ng/ml (p < 0.01) in the first 3 months, but declined thereafter. Phagocytic activity of PMNLs also increased significantly in response to rhGH therapy and this activation remained stable over the whole 12-month period. Other parameters of PMNL function were not influenced by rhGH therapy. In addition, nutritional parameters such as albumin, prealbumin, transferrin, cholesterol, HDL-cholesterol, cholinesterase, predialytic creatinine and blood urea nitrogen were not affected by rhGH therapy. A decline of total body fat (TBF) was observed after 3 and 9 months of rhGH therapy (17.5 +/- 10 vs. 16.7 +/- 10% after 3 months, p < 0.017 and 16.8 +/- 8.7% after 9 months, p < 0.049), whereas lean body mass remained stable. CONCLUSIONS: Twelve months of rhGH therapy caused a significant increase in IGF-I levels, stimulated phagocytic activity of PMNLs and induced a decline of TBF. Other anthropometric and nutritional parameters were not affected, which might be related to the persistence of GH resistance.

Anthropometry↗
PubMed2003

Plasma ghrelin concentrations are not regulated by glucose or insulin: a double-blind, placebo-controlled crossover clamp study.

Ghrelin plasma concentrations increase during fasting and fall rapidly after nutrient ingestion. We hypothesized that insulin or glucose could regulate ghrelin secretion by a feedback mechanism. In this randomized, double-blind, placebo-controlled crossover study, three different study days were carried out in nine healthy volunteers (age 26 +/- 6 years). On each day, stepwise increasing systemic glucose concentrations of 5.0, 8.3, and 11.1 mmol/l were attained by intravenous infusion of glucose, representing fasting and postprandial conditions. Ghrelin plasma concentration was studied during concomitant exogenous hyperinsulinemia, inhibition of endogenous insulin production by somatostatin infusion, and placebo time control, respectively. Elevated glucose concentrations increased circulating insulin to 612 +/- 85 pmol/l (P < 0.01), but they did not affect ghrelin concentrations. Prolonged hyperinsulinemia by exogenous infusion resulted in circulating insulin of 1,602 +/- 261 pmol/l (P < 0.01) and suppressed plasma ghrelin to 49.6% of baseline (P < 0.01). During administration of somatostatin, insulin concentration remained constant, but an even greater decrease in ghrelin to 39.5% of baseline was noted (P < 0.01). Hyperglycemia does not decrease ghrelin, and a reduction in ghrelin is only seen at supraphysiological insulin concentrations. In contrast, systemic ghrelin concentrations are decreased by somatostatin. The meal-related suppression of ghrelin appears not directly regulated by glucose or insulin.

Adult↗
PubMed2003

[Diseases of the pituitary gland: clinical aspects and biochemical evaluation].

Endocrine inactive and prolactin-secreting adenomas are the most commonly observed forms of pituitary tumors counting for more than 50 percent of diseases. In most cases first clinical symptoms can be attributed to insufficiency of the adenohypophysis which is also true for gonadotropin and thyroid stimulating hormone (TSH) producing adenomas. Clinical signs and symptoms of secondary insufficiency and primary forms of endocrine deficits do not differ significantly and the diagnosis may be hampered by involvement of more than one organ system. In contrast, symptoms and signs of ACTH or GH producing tumors are more impressive leading to diagnosis at an earlier stage. In case of corticotropic and somatotropic dysfunction dynamic tests are necessary for diagnosis. Close cooperation of endocrinologists, radiologists, and neurosurgeons is necessary for the effective workup of pituitary gland diseases.

Adenoma↗