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Biomedical subjects

H Vierhapper

Publications and source records attributed to H Vierhapper.

At least 181 records · Page 10Linked to original sources
PubMed1985

Acetyl-salicylic acid impairs insulin-mediated glucose utilization and reduces insulin clearance in healthy and non-insulin-dependent diabetic man.

The effect of acetyl-salicylic acid (ASA, 3 g per day for 3 days) on glucose utilization and insulin secretion was studied in healthy volunteers and Type 2 diabetic patients using the hyperglycaemic and euglycaemic insulin clamp technique. When in healthy subjects arterial plasma glucose was acutely raised and maintained at +7 mmol/l above fasting level, the plasma insulin response was enhanced by ASA (70 +/- 7 vs. 52 +/- 7 mU/l), whereas the plasma C-peptide response was identical. Despite higher insulin concentrations, glucose utilization was not significantly altered (control, 61 +/- 7; ASA, 65 +/- 6 mumol X kg-1 X min-1) indicating impairment of tissue sensitivity to insulin by ASA. Inhibition of prostaglandin synthesis was not likely to be involved in the effect of ASA, since insulin response and glucose utilization were unchanged following treatment with indomethacin. In the euglycaemic insulin (1 mU X kg-1 X min-1) clamp studies, glucose utilization was unaltered by ASA despite higher insulin concentrations achieved during constant insulin infusion (103 +/- 4 vs. 89 +/- 4 mU/l). In Type 2 diabetic patients, fasting hyperglycaemia (10.6 +/- 1.1 mmol/l) and hepatic glucose production (15 +/- 2 mumol X kg-1 X min-1) fell upon ASA treatment (8.6 +/- 0.7 mmol/l; 13 +/- 1 mumol X kg-1 X min-1). During the hyperglycaemic clamp study, the plasma response of insulin, but not of C-peptide, was enhanced by ASA, whereas tissue sensitivity to insulin was reduced by 30 percent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Capillary gas chromatography as a tool for characterization of urinary steroid excretion in patients with congenital adrenal hyperplasia.

Urinary steroid excretion was studied by capillary gas chromatography in 23 patients with congenital adrenal hyperplasia. In 5 patients the estimated excretion rates of pregnanetriol were in or below the normal range and 7 patients presented supranormal excretion rates of tetrahydro-cortisone and/or other glucocorticoid metabolites. Deficiency of 21-hydroxylase was nevertheless demonstrated in each patient by an increased ratio of excreted precursors vs products of 21-hydroxylase, e.g. of pregnanetriol/tetrahydro-cortisone. Due to this relative deficiency of glucocorticoids the patients' steroid excretion was further characterized by a predominance of 5 alpha-hydrogenated C19O3 metabolites (11-keto-androsterone, 11-hydroxy-androsterone) over their 5 beta-hydrogenated homologues (11-keto-etiocholanolone, 11-hydroxy-etiocholanolone). An apparent preponderance in the excretion of pregnenetriol over that of pregnanetriol was found in 4 patients, but the presence of pregnenetriol was not confirmed by mass spectrometry following prepurification of the urine samples by thin-layer chromatography indicating interference of an unidentified steroid metabolite with the initial gas chromatographic analysis. The simultaneous determination of steroids serving as precursors or products of 21-hydroxylase by capillary gas chromatography helps to establish the diagnosis of 21-hydroxylase deficiency and to characterize the pattern of steroid excretion in this syndrome even in patients where the estimation of single urinary steroids may lead to erroneous conclusions.

Adolescent↗
PubMed1985

Generation of prostaglandin E2-like radioimmunoreactive material in human plasma during storage at -20 C but not at -80 C.

Concentrations of prostaglandin E2 (PGE2) as determined by radioimmunoassay following silicic-acid column chromatography in extracted samples (n = 5) of human plasma (Na2EDTA: 18 mg/5 ml blood; indomethacin: 1mg/5 ml blood) were less than 1.0 pg/ml when the samples were extracted immediately after blood withdrawal. Virtually identical concentrations of PGE2 were determined in samples stored at -80 degrees C for up to 6 months. However, when the same analytical procedures were used after prolonged storage of the plasma samples at -20 degrees C an apparent rise in the estimated plasma concentrations of PGE2 up to 5.1 +/- 1.9 pg/ml (3 months) and to 25.2 +/- 7.8 pg/ml, (6 months) was observed. Repeated freezing and rethawing of 4 plasma samples within 48 hours after blood withdrawal did not influence concentrations of PGE2 thus excluding acute destruction of residual platelets as the cause of the observed time-dependent rise in radioimmunologically determined 'PGE2'. Two plasma samples stored at -20 degrees C for 26 months were subjected to HPLC subsequent to silicic acid column chromatography. Radioimmunoassay of PGE2 performed for each eluted fraction resulted in 3 distinct peaks of "PGE2"-like activity, suggesting heterogeneity of cross-reacting compounds generated during prolonged storage at -20 degrees C. In conclusion, to determine concentrations of PGE2 in human plasma by means of radioimmunoassay the samples should either be extracted immediately after blood withdrawal or be kept at -80 degrees C.

Adult↗
PubMed1985

Contribution by the glycogen pool and adenosine 3',5'-monophosphate release to the evanescent effect of glucagon on hepatic glucose production in vitro.

To elucidate in vitro the transience of glucagon-induced hepatic glucose release, the effects of glucagon on hepatic glucose production and cAMP release were evaluated in the isolated rat liver preparation perfused by a nonrecirculating system. Glucagon was added to the infusate in stepwise increasing concentrations at 0, 60, and 100 min to give final concentrations of 2.5 X 10(-11), 10(-9), and 5 X 10(-8) M, respectively. Glucagon at 2.5 X 10(-11) M caused cAMP release [basal (mean +/- SD), 11.2 +/- 3.0 pmol/(min X 100 g BW)] to rise rapidly and plateau at 23.3 +/- 7.0 pmol/(min X 100 g BW), whereas hepatic glucose production [basal, 3.7 +/- 1.6 mumol/(min X 100 g BW)] increased only transiently to a maximum of 15.3 +/- 3.1 mumol/(min X 100 g BW) and fell thereafter. The enhanced cAMP release during the consecutive glucagon infusion was accompanied by a transient rise in hepatic glucose production during the second, but not during a third, glucagon infusion. When 3-isobutyl-1-methylxanthine, a potent phosphodiesterase inhibitor, was added to the perfusion medium (0.5 mM), the cAMP response to 2.5 X 10(-11) M glucagon was enhanced [247 +/- 124 pmol/(min X 100 g BW)] as was hepatic glucose production (+ 21%; P less than 0.05). Further augmentation of the glucagon concentration was followed by an increase in hepatic cAMP, but not glucose, release. When glucagon infusion (2.5 X 10(-11) M) was repeated with a glucagon-free period of 30 min in between, no stimulation of cAMP and consecutive glucose release was found during the second period. However, when the second glucagon dose was increased to 10(-9) M, glucose and cAMP release were again stimulated to the same extent as in experiments with no glucagon-free period in between. We conclude that the size of the glycogen pool and the cAMP concentration directly modulate hepatic glucose production and are responsible for evanescent glucagon action. This mechanism can be described by computer simulation.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Effect of insulin antibodies on insulin pharmacokinetics and glucose utilization in insulin-dependent diabetic patients.

To determine the impact of insulin-binding antibodies on total (TIRI) and free insulin (FIRI) as well as on insulin sensitivity, 10 insulin-dependent diabetic patients (IDDM) with poststimulatory C-peptide less than 100 pmol/L and an insulin binding capacity (IBC) between less than 1 and 294 micrograms/L serum were studied during and after a 1-h nonprimed, constant-rate insulin infusion (study 1: 0.057 U/kg body wt, study 2: 0.286 U/kg body wt). Euglycemia was maintained by variable glucose infusion. Control studies were performed in 5 healthy subjects. Basal TIRI (mU/L) was lowest in healthy subjects (16 +/- 1 [SE]) and elevated in diabetic patients (IBC less than 25 micrograms/L: 72 +/- 11, IBC greater than 25 micrograms/L: 1772 +/- 842), whereas serum concentrations of FIRI were considerably smaller but still two- to threefold greater (P less than 0.01) in the patients than in healthy subjects (13 +/- 1). After intravenous (i.v.) insulin administration, almost identical increments in serum TIRI were seen in healthy subjects and in diabetic patients with low IBC (less than 25 micrograms/L), whereas those with high IBC (greater than 25 micrograms/L) had a heterogeneous response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

LH-RH stimulated LH secretion in human endocrine disease.

The application of LH-RH provides means to describe the functional state of the hypothalamo-pituitary-gonadal axis and has helped to understand the regulation of gonadotropin secretion both under normal and pathological circumstances. At present, diagnostic LH-RH application appears to be most useful in patients with delayed puberty, where a biphasic response during an infusion of LH-RH excludes hypogonadotropic hypogonadism at an early clinical stage. An enhanced LH-RH induced response following exogenous intermittent LH-RH administration identifies the subgroup of hypogonadotropic patients who are suitable for subsequent LH-RH substitution therapy. In addition, subtle derangements of gonadotropin secretion have been described in a score of clinical conditions including the endocrine disorders discussed in this review. However, interesting as these observations may be theoretically, their practical value is often limited since a multitude of interfering factors, both exogenous and endogenous, results in a great variability in the obtained results, thus limiting the diagnostic value of the test in a specific patient. As of recently the clinical use of LH-RH includes its therapeutic application to replace low endogenous levels of LH-RH, whereas long-acting analogues of the natural decapeptide are employed to suppress gonadotropin secretion in an increasing field of endocrine disorders.

Adrenal Gland Diseases↗
PubMed1984

[Diagnosis and therapy of patients with simple goiter within the scope of a thyroid gland ambulatory care service].

Serum thyroxin, triiodothyronine, and basal and TRH-stimulated TSH concentrations, were determined in 285 patients with simple goitre. In addition, the efficiency of two years' therapy with a T4/T3 preparation (ratio 4:1) was investigated. Patients with goitres of larger size (stage II und III) presented with lower serum T4 and higher serum T3 concentrations than patients with smaller goitres (stage I) and controls. A decreased or elevated TSH response to TRH stimulation was more frequently found among patients with large goitres than among those with small ones. No reduction of goitre size was achieved by thyroid hormone medication in patients in whom TSH response to TRH had been decreased prior to therapy. In contrast, a reduction in goitre size was registered after two years' therapy in 84% of the patients in whom the TRH-TSH response was elevated and in 44% in whom it was normal. Small and/or diffuse goitres were more responsive to T4/T3 medication than large and/or nodular ones. These results suggest that TSH stimulation tests are of diagnostic value in patients with simple goitre and should at any rate be performed in patients with goitres of larger size before the commencement of thyroid hormone medication. The data also demonstrate that suppression of TSH secretion via administration of thyroid hormone influences thyroid growth only in a subgroup of the goitrous patients of our region.

Drug Combinations↗
PubMed1984

[Cardiovascular reflexes, vibration thresholds and electroneurography parameters of the peroneal and sural nerves in type I diabetics].

In 26 type I diabetics ranging in age from 18 to 65 years with a duration of illness of between 1 and 34 years the following investigations were performed: 1. case history and questionnaire; 2. neurological examination; 3. determination of the vibration threshold; 4. electroneurography of the peroneal nerve and the sural nerve; 5. determination of the cardiovascular reflexes; 6. medical examination and additional findings; 7. ophthalmological investigation. 21 patients showed evidence of sensorimotor polyneuropathy (SM-PNP), the average age of this group (41 years) being 10 years higher than in the group without SM-PNP (31 years). The values of HbA1c were pathological in 17 of 21 cases with SM-PNP, and 2 of 5 cases without SM-PNP. Retinopathy was found rarely in both groups. 13 patients showed evidence of autonomic neuropathy (ANP). The mean duration of illness (15.4 years) and the average age of patients (36.5 years) in this group was distinctly higher than in the group without ANP (mean duration of illness: 8.9 years, mean age: 31.9 years). 12 patients with ANP and 7 patients without ANP had abnormally high HbA1c levels. Diabetic SM-PNP was most frequently (in 19 of 21 cases) diagnosed by electroneurographical investigation of the peroneal nerve. In the diagnosis of diabetic ANP the anamnesis (8 positive findings) and the determination of the heart rate variation during deep breathing (7 positive findings) are complementary. Among the 13 patients with ANP, 12 also had SM-PNP, whereas among the 21 patients with SM-PNP only 12 showed evidence of concomitant ANP.

Adolescent↗
PubMed1984

Effect of acetylsalicylic acid and of indomethacin on diuresis in man: the role of cyclo-oxygenase inhibition.

The effect of acetylsalicylic acid (ASA, 3 g/day for 3 days) and of indomethacin (IND, 150 mg/day for 3 days) on diuresis and on the excretion of prostaglandin E2 (PGE2) was studied in six healthy, male volunteers. After overnight deprivation the subjects received an oral water load (20 ml/kg) and hourly urine volumes were replaced by an equivalent volume of water by mouth for 4 h. Pretreatment with both ASA and IND induced a comparable suppression (P less than 0.05 to less than 0.001) in the excretion of PGE2, but only IND also reduced (P less than 0.05) diuresis, free water clearance and the excretion of sodium. The excretion of creatinine was uninfluenced by both ASA and IND. These data indicate that a mechanism other than cyclo-oxygenase inhibition is involved in the effect of IND and ASA on diuresis in man.

Adult↗
PubMed1984

Induction of puberty in a patient with hypogonadotropic hypogonadism by pulsatile, subcutaneous infusions of LH-RH.

Following treatment with nocturnal, pulsatile, s.c. infusions of LH-RH (50 micrograms/night) for nine nights a twenty-year-old patient with hypogonadotropic hypogonadism presented a markedly enhanced, biphasic secretion of LH during an LH-RH infusion test (200 micrograms LH-RH i.v., t = 4 hours) indicating a hypothalamic defect and a deficiency in endogenous LH-RH production. Puberty was subsequently initiated in this patient within eight weeks of therapy with s.c. pulsatile LH-RH. These results confirm that intermittent application of LH-RH induces pituitary sensitization resulting in an enhanced response to exogenous LH-RH. This will help to select patients for prolonged therapy with intermittent s.c. LH-RH for the initiation of puberty.

Adult↗
PubMed1984

Comparative therapeutic benefit of indomethacin, hydrochlorothiazide, and acetyl-salicylic acid in a patient with nephrogenic diabetes insipidus.

To define the importance of renal prostaglandins in nephrogenic diabetes insipidus (NDI), diuresis and the urinary excretion of PGE2 and PGF2 alpha were studied in a patient with NDI before and during inhibition of endogenous prostaglandin synthesis with either indomethacin (IND) or acetyl-salicylic acid (ASA). The excretion rates of PGE2 and PGF2 alpha were in the low normal range for the patient's age group, remained unchanged during 6 h of fluid deprivation and were suppressed by IND (150 mg/day), ASA (3 g/day), and by the combination of IND and hydrochlorothiazide (HCT, 50 mg/day). However, whereas IND, HCT, and the combination of IND and HCT reduced diuresis ASA did not. Free water clearance as determined during fluid deprivation remained positive during each phase of therapy. These data fail to demonstrate a direct effect of endogenous ADH on renal prostaglandin synthesis in NDI. The ineffectiveness of ASA to reduce diuresis indicates that indomethacin affects diuresis in NDI by a mechanism other than inhibition of cyclooxygenase.

Adolescent↗
PubMed1983

[Hypogonadotropic hypogonadism and delayed puberty: differential diagnosis using the LH-RH-infusion test].

Serum concentrations of LH and FSH were determined during an intravenous infusion of LH-RH (200 micrograms, t = 4 hours) in 8 patients (age: 15 to 20 years) with delayed sexual maturation and retarded bone age. Four patients who by clinical criteria were later recognized as suffering from hypogonadotropic hypogonadism (HH) presented during the infusion of LH-RH with only a small response of LH (and, in three cases, of FSH). In 3 patients with HH a deficiency of endogenous LH-RH due to a hypothalamic defect was suggested by an enhanced secretion of LH and FSH during a second LH-RH infusion test performed after priming of the pituitary by pulsatile, subcutaneous infusions of LH-RH (50 micrograms/night for 9 consecutive nights). The fourth patient with HH, who suffered from a pituitary adenoma, failed to display this enhanced secretion of gonadotropins following pituitary priming by intermittent administration of LH-RH. As compared with the patients with HH, 4 patients in whom puberty, although delayed, later occurred spontaneously (pubertas tarda, PT), presented with a considerably more pronounced secretion of LH and FSH during the infusion of LH-RH, and priming by intermittent subcutaneous LH-RH failed to achieve further enhancement of the secretion of LH and FSH during a second infusion test in these patients. The intravenous infusion of LH-RH in combination with a protocol of pituitary priming offers a possibility of distinguishing patients with delayed puberty from those with various forms of hypogonadotropic hypogonadism.

Adolescent↗
PubMed1983

[Continuous subcutaneous insulin infusion: long-term treatment in an unselected group of insulin-dependent diabetics].

Long-term ambulatory continuous subcutaneous insulin infusion was undertaken under serial blood-glucose control in nine insulin-dependent diabetics. Before this treatment was started, haemoglobin A1 was increased (more than 13%), diabetic lipoid necrosis was present in three, proliferative diabetic retinopathy in one, treatment-resistant Candida oesophagitis in one and Addison's disease in one. During the total of 630 weeks (range 6-135 weeks) of continuous subcutaneous insulin infusion it was found that (1) the metabolic state of the patients improved significantly, the previously non-responding oesophagitis healed and one of three patients with diabetic lipoid necrosis was markedly improved; (2) the risks of insulin treatment, hypoglycaemia (especially with Addison's disease) and keto-acidosis (for technical reasons) remained; and (3) in long-standing diabetes of type I even good control of blood glucose levels (mean 113 mg/dl) could neither prevent the occurrence of proliferative diabetic retinopathy nor loss of sight.

Adult↗
PubMed1983

Insulin pharmacokinetics following continuous infusion and bolus injection of regular porcine and human insulin in healthy man.

To determine the pharmacokinetics of insulin administered by intravenous (IV) and subcutaneous (SC) pump treatment as well as by the conventional subcutaneous route, six insulin preparations of either porcine or human amino acid sequence were investigated intraindividually following IV or SC insulin infusion at two different rates (Study I) and three preparations were investigated after SC bolus injection (Study II) in healthy men. Insulin release was suppressed in Study I by IV administration of somatostatin (500 micrograms/hr) to avoid interference by endogenous insulin with the measurement of exogenous insulin. Hypoglycemia was prevented by IV administration of glucose. The data obtained demonstrated (1) greater serum concentrations of immunoreactive insulin (IRI) during continuous IV insulin infusion (141 +/- 10 (SEM) pmole/liter) than during SC insulin infusion (54 +/- 3 pmole/liter; P less than 0.0005) (0.8 U/hr); (2) return of serum IRI to baseline values following a 17-minute square wave insulin infusion (12.8 U/hr; time: 0 to 17 minutes) within 40 minutes after IV insulin infusion but not before 180 minutes after the end of SC insulin infusion; (3) peak serum IRI at 60 to 90 minutes after conventional SC insulin injection returning to baseline values at 300 minutes; and (4) identity of the pharmacokinetics of pumped human and porcine insulin within a given group as well as of the accompanying metabolic dynamics of blood glucose and nonesterified fatty acids, but heterogeneity of serum insulin after its SC bolus injection. We conclude that (1) the pharmacokinetic behavior of regular insulin depends primarily on its route of administration; (2) continuous IV infusion of an insulin dose causes significantly higher serum insulin levels than the SC administration of the identical insulin dose, and (3) hyperinsulinemia caused by a square wave insulin infusion (12.8 U/hr; time: 0 to 17 minutes) requires more than four times longer to return to baseline levels following SC administration than after IV administration of the insulin. These differences in the pharmacokinetic behavior of insulin cause a reduced bioavailability of SC administered insulin and have to be taken into account when instituting insulin treatment by various routes.

Adult↗
PubMed1983

The effect of insulin on the rise in blood pressure and plasma aldosterone after angiotensin II in normal man.

1. The effect of an intravenous infusion of insulin [2.5 units h-1 (m2 of body surface area)-1] on the rise in blood pressure and plasma aldosterone after intravenous angiotensin II (5, 10, and 20 ng min-1 kg-1) was investigated in six healthy, sodium-loaded men. 2. Serum insulin reached 96.8 +/- 18.1 mu-units/ml (control: 7.0 +/- 1.5 mu-units/ml) and serum potassium fell from 4.2 +/- 0.2 mmol/l to 3.6 +/- 0.2 mmol/l (P less than 0.005). 3. Hyperinsulinaemia increased (P less than 0.05) the secretion of aldosterone during the largest dose of angiotensin II (20 ng min-1 kg-1), but had no effect on the rise in blood pressure after angiotensin II.

Adolescent↗