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H Vierhapper

Publications and source records attributed to H Vierhapper.

At least 73 records · Page 4Linked to original sources

Unchanged testosterone production rates in growth hormone-treated healthy men.

The effect of biosynthetic human GH on the production rates of testosterone was determined in healthy men (n = 7) using the stable isotope dilution technique and mass spectrometry. 1Alpha,2alpha-d-testosterone (20 microg/h) was infused for 10 h (0800-1800 h). Blood samples obtained at 20-min intervals from 1400-1800 h were pooled during two 2-h periods. Subsequently, each volunteer received a daily dose of biosynthetic human GH (4 IU/day sc) for 7 days. This resulted in a rise in plasma concentrations of somatomedin-C from, basal, 0.67+/-0.13 U/mL to 1.20+/-0.2 U/mL on day 7 (P < 0.0001). Testosterone production rates (basal: 209.9+/-31.0 microg/h) were unchanged by treatment with GH (day 7: 192.2+/-30.1 microg/h). In healthy men, short-term treatment with sc GH does not influence endogenous testosterone production rates.

Adult↗

Glycoxidation, and protein and DNA oxidation in patients with diabetes mellitus.

1. The role of oxidative stress in the pathogenesis of the diabetic state is being investigated extensively. Although oxidative stress has been reported in terms of glycoxidation, protein oxidation and DNA oxidation in diabetes mellitus, oxidation parameters have not been determined in parallel on the same study population.2. We studied 24 patients with diabetes mellitus (14 patients with Type I diabetes with a mean age of 62.3+/-6.3 years and 10 patients with Type II diabetes aged 67.3+/-5.9 years) and compared them with age-matched non-diabetic controls. Urinary o-tyrosine, 8-hydroxy-2'-deoxyguanosine and pentosidine measurements by HPLC were made on two occasions (t1 and t2).3.A clear statistical difference was found between diabetic patients and controls at t1 or t2 for 8-hydroxy-2'-deoxyguanosine and pentosidine, but not for o-tyrosine. No significant correlations were found between clinical and other laboratory parameters except high-density lipoprotein and uric acid. We revealed significantly increased glycoxidation and DNA oxidation in patients with Type I and Type II diabetes, but protein oxidation was not different from controls.4. The finding of increased glycoxidation reflects increased oxidation of the carbohydrate moiety, whereas the increased levels of oxidized DNA may also be interpreted as due to increased DNA repair. The increased 8-hydroxy-2'-deoxyguanosine does not indicate the generation of an individual active oxygen species, but DNA could have been oxidized simply by alkenals from lipid peroxidation, as e.g. malondialdehyde. As no difference in protein oxidation (i.e. o-tyrosine) between diabetics and controls could be revealed, the oxidation of DNA by hydroxyl radical attack is unlikely, as o-tyrosine was proposed as a marker for hydroxyl radical attack. Therefore, the message is that increased glycoxidation can be confirmed, protein oxidation does not appear to take place and increased DNA oxidation is still not proven, as increased 8-hydroxy-2'-deoxyguanosine may simply reflect repair.

8-Hydroxy-2'-Deoxyguanosine↗

[The "cold" nodule of the thyroid gland: 20 years experience with 2,071 patients and diagnostic limits of fine needle biopsy].

The files of 2071 patients with (Tc99m)-scintigraphically "cold" thyroid nodules (CTN) attending a teaching hospital were analysed retrospectively. Between 1975 and 1995 altogether 49 endocrinologists with varying degrees of experience carried out the clinical evaluation as well as fine needle aspiration biopsy (FNAB), and 33 pathologists undertook the cytological interpretation. By clinical criteria the CTN of 1272 patients were deemed benign, whilst malignancy was suspected in 301 patients (81% and 19% of evaluable cases, respectively). A cytological diagnosis was made in 47.3% of all FNAB performed ("benign" in 611 patients, "follicular neoplasia" in 86, and "malignant" in 39 patients; 39.3%, 5.5% and 2.5%, respectively). 36.5% of the clinically suspect CTN and all nodules with a cytological diagnosis of either "follicular neoplasia" or "malignant" in patients who could be followed up after the FNAB procedure were treated surgically, leading to a total of 420 histological diagnoses. 76% and 35% of the CTN classified as being suspicious of malignancy in the preoperative clinical and cytological evaluation, respectively, were found to be malignant on histology. A clinical assessment of "no abnormality" and "normal" cytology missed a malignant lesion in 16.3% and 15% of cases, respectively. Thus, under routine teaching hospital conditions, the selection of patients with CTN for surgery cannot be based on cytological criteria alone. The FNAB in this setting should be employed exclusively to supplement the clinical and scintigraphically findings.

Adenocarcinoma, Follicular↗

[Diagnosis and therapy of Cushing syndrome].

Current diagnostic and therapeutic options in Cushing's syndrome have been retrospectively evaluated on the basis of 40 case histories of the years 1980 to 1994. After biochemical diagnosis, several radiological methods such as 131J-cholesterol-scintigraphy and, in 1 case, selective petrosal sinus blood sampling were employed. Out of 25 patients with central Cushing's syndrome 18 were cured by transsphenoidal pituitary surgery, in 1 case in combination with "Gamma-Knife" therapy. One patient was primarily treated by bilateral adrenalectomy, 5 as second intervention following unsuccessful pituitary surgery. One patient is not fully cured at present. Adrenal cortisol-producing adenomas were successfully treated by unilateral, subtotal or bilateral adrenalectomy in 9, 1 and 2 patients, respectively. Another patient with bilateral adrenal adenomas was treated medically following unilateral adrenalectomy. One patient with a cortisol-producing adrenal carcinoma died shortly after operation. One patient with an ACTH-producing pancreatic islet cell tumor died 1 year after initial remission. Adrenalectomy is the logical therapy in adrenal cortisol-producing adenomas. Improved diagnostic and surgical techniques have reduced bilateral adrenalectomy in patients with central Cushing's syndrome to rare cases in which transsphenoidal surgery (71% success rate) is the therapy of choice.

Adolescent↗

How (not) to diagnose growth hormone deficiency in adults: stimulated serum concentrations of growth hormone in healthy subjects and in patients with pituitary macroadenomas.

The secretion of growth hormone (GH) stimulated by GH-releasing hormone ([GHRH] 100 micrograms intravenously [IV]) was determined in 33 patients with nonfunctioning pituitary macroadenomas before and after transsphenoidal adenomectomy and in 28 controls. Patients who needed substitution therapy for at least one additional pituitary hormone presented with lower GH secretion than the remaining patients with pituitary tumors. However, there was a marked overlap of stimulated GH secretion between these two groups (3.2 +/- 4.3 ng/mL and 7.2 +/- 6.6 ng/mL, respectively) and between either group with the control group (7.1 +/- 5.5 ng/mL). In an independent investigation, the effect of IV GHRH (100 micrograms) on the secretion of GH in seven healthy volunteers was shown to be comparable to that seen during an insulin tolerance test ([ITT] 0.1 U/kg IV). Thus, the GHRH stimulation test, a simple and comparatively unharmful procedure, is a useful alternative to the ITT in patients with potential pituitary defects. However, the pronounced overlap of stimulated serum GH concentrations in patients with pituitary macroadenomas and those estimated in healthy subjects and in patients with nonpituitary diseases underlines the difficulty in biochemically defining acquired GH deficiency in adults. We suggest that GH therapy in adults should primarily be instituted in patients with additional defects in anterior pituitary function.

Adenoma↗

L-Arginine reduces lipid peroxidation in patients with diabetes mellitus.

A current concept for the development of diabetic long-term complications is the involvement of oxidative stress, as, e.g., lipid peroxidation, in the diabetic state. Data published recently show also oxidative damage to DNA, which might be one factor for accelerated aging and diabetic microangiopathy. In our study we tested the hypothesis that L-arginine can reduce lipid peroxidation in patients with diabetes. We performed a blind placebo controlled study with crossing over two treatment periods for 3 months. Thirty patients with diabetes mellitus were randomly assigned to treatment group A (first treatment then placebo) and B (first placebo then treatment). Treatment consisted of two daily dosages of 1 g L-arginine free base. Lipid peroxidation as reflected by malondialdehyde was evaluated in urine using a standard HPLC assay. After 3 months of treatment there was a significant reduction in malondialdehyde levels in group A (p < .0032), whereas there was no difference compared to the baseline values after three months of placebo treatment in group B (p < .97). After crossing over, there was a significant reduction in malondialdehyde levels in group B (p < .0002). Group A showed a significant increase in malondialdehyde levels (p < .0063) returning to baseline values. L-Arginine treatment was able to reduce the lipid peroxidation product malondialdehyde. This provides evidence that treatment with L-arginine may counteract lipid peroxidation and thus reduce microangiopathic long-term complications in diabetes mellitus.

Aged↗

Routine measurement of plasma calcitonin in nodular thyroid diseases.

In a prospective study, plasma concentrations of human calcitonin (hCT) were determined in 1062 consecutive patients with thyroid nodular disease. Basal plasma hCT was above the normal range (>6 pg/mL) in 55 patients and was elevated up to more than 100 pg/mL (range, 127-5459) in 3 of these 55 patients. A pentagastrin-induced rise in hCT up to more than 100 pg/mL was observed in only 1 of 38 patients with a basal concentration of hCT between 5-10 pg/mL, but was found in 10 of 31 patients with basal hCT ranging from 10-100 pg/mL. Histologically, 7 of the 14 patients with either basal or stimulated plasma concentrations of hCT above 100 pg/mL presented C cell hyperplasia, which in one case showed histological transition into a small (diameter, 3 mm) medullary thyroid carcinoma (MTC). Including this patient, MTC was found in 6 of the 12 patients. We conclude that the routine determination of hCT in all patients with thyroid nodular disease should be supplemented by pentagastrin-stimulation when the basal hCT concentration exceeds 10 pg/mL. Patients with basal and/or stimulated plasma CT concentrations of more than 100 pg/mL should be operated on because they run a substantial risk to suffer either MTC or C cell hyperplasia, a potentially precancerous condition. This will increase the chance of a timely diagnosis of MTC and provide the chance of curative surgery.

Calcitonin↗

Determination of testosterone production rates in men and women using stable isotope/dilution and mass spectrometry.

Production rates of testosterone were determined in healthy men and women during the follicular phase of their menstrual cycle using the stable isotope dilution technique and analysis by gas chromatography/mass spectrometry. In an initial series of experiments, 0.07 mg/h (men) or 0.01 mg/h (women) 1,2-d-testosterone was infused for 36 h. After an equilibration period of 12 h, blood samples were obtained at 20-min intervals throughout 24 h. In men, no diurnal rhythmicity of testosterone production was observed, whereas in women, testosterone production rates were largest from 0400-1200 h. In a second series of experiments, the infused dose of 1,2-d-testosterone was reduced to 0.015 mg/h (men) and 0.0001 mg/h (women), respectively. Blood samples were obtained at 20-min intervals during the last 12 h (0800-2000 h) of the observation period. In accordance with results obtained by others using radioactive tracers, estimated production rates were 147 +/- 31 microg/h (3.7 +/- 2.2 mg/day in men) and 1.8 +/- 0.6 microg/h (0.04 +/- 0.01 [corrected] mg/day in women). To reduce both the duration of the experiment and the number of samples to be processed, we subsequently demonstrated that similar production rates may be obtained when the equilibration period before blood sampling is reduced to 6 h and the period of blood sampling is reduced to 4 h. This protocol is suitable for clinical use in a routine setting to obtain analytically correct estimates of testosterone production in vivo.

Deuterium↗

Thromboxane A2 does not mediate angiotensin II-dependent nonischemic peripheral vasoconstriction in healthy men: a pilot study.

It has been suggested that angiotensin II-dependent hemodynamic effects are in part mediated by thromboxane A2 (TXA2). The present study investigates in 6 healthy normotensive men whether prostaglandin H2-TXA2 receptor blockade with 100 mg of linotroban (5(2-(phenylsulfonylamino)ethyl)-thienyloxy-acetic acid) p.o. influences angiotensin II-dependent peripheral regional vasoconstriction. Moreover, the regional balance of thromboxane B2 (TXB2), a stable metabolite of TXA2, across the leg vascular bed was assessed at baseline conditions as well as during exogenous infusion (0.2 microgram/min) of angiotensin II. Net transfemoral TXB2 balance was calculated from the respective arteriovenous plasma concentration differences and the corresponding regional plasma flow, the latter being determined by indocyanine-green dye, using appropriate catheterization techniques. Angiotensin II (0.2 microgram/min) induced a 66% increase in leg vascular resistance (p < 0.01) without affecting systemic hemodynamics. These regional hemodynamic effects of angiotensin II were not influenced by prostaglandin H2-TXA2 receptor blockade. Baseline TXB2 balance across the femoral vascular bed was equilibrated at slight extraction rates or around zero and remained unchanged during angiotensin II infusion. These results suggest that, in healthy man, angiotensin II-dependent, nonischemic peripheral vasoconstriction is not mediated by TXA2. Possible benefits of prostaglandin H2-TXA2 receptor blockade in pathological conditions with tissue malperfusion or ischemia are discussed.

Adult↗

[Therapeutic possibilities in metastatic pheochromocytoma].

Malignant pheochromocytomas are rare. Although 5-year survival is less than 50%, the prognosis varies. Some patients, even those with extensive metastases, have been followed up for many years. If the tumor tissue's uptake is adequate (> 5 Gy/100 mCi) the therapeutic use of 131I-meta-iodobenzylguanidin (131I-MIBG) is at present the therapy of first choice. The use of cytostatic chemotherapy should be limited to patients with rapidly progressive disease.

3-Iodobenzylguanidine↗

Effect of endothelin-1 in man--impact on basal and stimulated concentrations of luteinizing hormone, follicle-stimulating hormone, thyrotropin, growth hormone, corticotropin, and prolactin with and without pretreatment with nifedipine.

In healthy men, intravenous (IV) endothelin-1 suppresses the growth hormone (GH)-releasing hormone (GHRH)-stimulated increase in GH and prolactin (PRL) and augments corticotropin (ACTH)-releasing factor (CRF)-stimulated secretion of ACTH. Since some actions of endothelin-1 on pituitary function in vitro are antagonized by calcium channel antagonists, we have studied the effect of pretreatment with oral nifedipine (10 mg, given before infusion of endothelin-1 or vehicle) on basal and stimulated concentrations of pituitary hormones in a group of healthy men (N = 6). The augmentative effect of endothelin-1 on CRF-induced ACTH secretion (P < .05) was counteracted by pretreatment with nifedipine. Pretreatment with nifedipine further inhibited (P < .01) the GHRH-induced increase in plasma concentrations of GH (P < .05), which, in keeping with previous data, had already been reduced by IV endothelin-1 alone (P < .05). Thus, both endothelin-1 and nifedipine influence pituitary hormone secretion in healthy man. However, nifedipine does not ubiquitously counteract the effects of endothelin-1 since it enhances some of its actions on the pituitary and diminishes others. Endothelin-1 may therefore influence pituitary function by mechanisms other than activation of calcium channels alone.

Adrenocorticotropic Hormone↗