Biomedical subjects

H Schmidt-Gayk

Publications and source records attributed to H Schmidt-Gayk.

At least 91 records · Page 5Linked to original sources

PubMed1991

Do limited changes in phosphate intake modulate 1,25(OH)2D3 levels in early renal failure?

A high dietary phosphate load relative to GFR is thought to explain, at least in part, diminished renal 1-alpha hydroxylase activity in early renal failure (RF). To assess the role of dietary phosphate/GFR ratio in more detail, we examined the response of 1,25(OH)2D3 concentration to a controlled isolated reduction of dietary phosphate intake for up to 10 days with no change of Ca, Na and energy intake. We studied 7 healthy controls (2 male, 5 female, median age 45 years) and 6 non-nephrotic patients with early renal failure (RF) (3 males, 3 females, median age 55 years; median Cin 60.5ml/min/1.73 m2; 41-69). During an initial 3-day period of controlled diet with usual phosphate intake no difference of UVPi (median 27.6 mmol/day, 18.9-43.8) was found between controls and RF. A diet with 15 mmol Pi/day (confirmed by duplicate meal analysis) significantly reduced median UVPi (controls: 27.7 to 11.9 mmol/d; RF 27.4 to 14.1 mmol/d) with no change of median UVCa. Median day to day variation of 1,25(OH)2D3 levels (by RIA) in controls was 15.4%. Lowering dietary phosphate intake did not significantly change median 1,25(OH)2D3 levels in controls (45.7 vs. 38.3 pg/ml) and patients with RF, respectively (23.5 vs. 19.1 pg/ml). No changes of intact iPTH values were found. The experiment had a 68% power to detect a 15% change and a 99% power to detect a 30% change at a significance level of p less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

PubMed1990

Development of a double antibody radioimmunoassay for quantitation of 1 alpha,25-dihydroxyvitamin D.

A sensitive radioimmunoassay (RIA) for 1 alpha,25-dihydroxyvitamin D [1 alpha,25(OH)2-D] with a double antibody (DAB) separation technique to separate free from bound antigen has been developed. The hormone was extracted from 1 ml serum or plasma by Extrelut columns and normal phase high performance liquid chromatography and quantitated in the DAB-RIA. The detection limit of the assay was 3.75 ng/l. The intraassay variation coefficients were 15.9% and 10.5% for samples with 1 alpha,25(OH)2D3 concentrations of 54 ng/l and 130 ng/l, respectively. The interassay variation coefficients were 18.0% and 16.7% for these two concentrations. Mean (and SD) values for 1,25(OH)2D in serum of 40 healthy subjects and 38 patients with chronic renal failure who did not receive 1,25(OH)2D3 were 62.8 ng/ml (22.2) and 12.4 ng/ml (9.8), respectively. The mean value for 7 patients with primary hyperparathyroidism was 66.5 ng/ml (35.8) before surgery. These results compared well with those of an established charcoal-based RIA. Compared to charcoal-based RIAs, the DAB-RIA is faster and requires less laborious assay procedures.

Adult↗

PubMed1990

Parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration in elderly patients.

In 50 patients of a geriatric hospital (33 women, aged 65-96 years, mean age 80 years, and 17 men, aged 68-91, mean age 78.3 years) calcium, albumin, phosphate, urea, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined. Forty patients with serum creatinine levels up to 1.4 mg/dl (124 mumols/l) and 10 patients with creatinine concentrations greater than or equal to 1.5 mg/dl (132 mumols/l) were evaluated. In patients with normal creatinine, a positive correlation was found between parathyroid hormone and age (r = 0.41; P less than 0.01). In patients with elevated creatinine, negative correlations were found in 1,25-dihydroxyvitamin D and calcium (r = -0.724; P less than 0.05), 1,25-dihydroxyvitamin D and creatinine (r = -0.79; P less than 0.01) and 1,25-dihydroxyvitamin D and phosphate (r = -0.87; P less than 0.002). The best correlation was observed in patients with elevated serum creatinine for 1,25-dihydroxyvitamin D and phosphate (r = -0.91; P less than 0.001). The results suggest that low levels of calcium and phosphate stimulate the 1-hydroxylation of 25-hydroxyvitamin D even in advanced age and that the calcium metabolism of these patients is frequently disturbed. Nineteen patients had low levels of 25-hydroxyvitamin D, indicating an insufficient supply of vitamin D or rare exposure to sunlight. In 49 of 50 patients, one ore more of the parameters of calcium metabolism were outside the normal range.

Aged↗

PubMed1990

Intact parathyroid hormone in primary hyperparathyroidism.

In 49 patients with primary hyperparathyroidism, intact parathyroid hormone (PTH) was measured with a recently developed immunoradiometric assay, and midregional PTH fragments (sequence 44-68) were measured with an established radioimmunoassay technique. In 47 normal subjects, the concentration of intact PTH ranged from 2.0 to 6.8 pmol/l, and in 49 patients with primary hyperparathyroidism it ranged from 6.4 to 80.0 pmol/l. In contrast, midregional PTH fragments were normal in seven of 49 patients with primary hyperparathyroidism. In five healthy controls and in 12 patients with surgically confirmed primary hyperparathyroidism and serum calcium levels below 3.0 mmol/l, a rapid calcium loading test was performed. In healthy controls, intact PTH was in the low normal to subnormal range within 2.5-5.0 min, and had recovered within 15 min of calcium infusion. In patients with primary hyperparathyroidism, the calcium infusion also led to a 30-50 per cent decrease in intact PTH levels within 5.0-7.5 min after injection, with a slow recovery after 10-15 min. In six of the patients with only slightly elevated basal intact PTH, a suppression to the normal range was observed. In 24 patients (16 patients with a solitary adenoma and eight patients with four-gland hyperplasia) the intact PTH levels were followed intraoperatively during parathyroidectomy, revealing a significantly different rate of decline for single adenomas compared with hyperplasia during the first 15 min after removal of the primary enlarged gland. Intact PTH values remained constantly elevated in one patient with primary hyperparathyroidism and an unsuccessful neck exploration. These results confirm that (a) the measurement of intact PTH in patients with primary hyperparathyroidism is superior to the measurement of midregional fragments; (b) PTH secretion in primary hyperparathyroidism is not totally autonomous; and (c) intraoperative monitoring of intact PTH values could be used to monitor the success of surgery.

Adenoma↗

PubMed1990

Efficacy and tolerance of cefpodoxime proxetil compared with co-amoxiclav in the treatment of exacerbations of chronic bronchitis.

This European, multicentre trial evaluated the efficacy and tolerance of cefpodoxime proxetil in comparison with co-amoxiclav (amoxycillin plus clavulanic acid) in the treatment of acute exacerbations of chronic bronchitis. The study design was double-blind and double-placebo controlled. Doses of either 200 mg bd of cefpodoxime proxetil or 500 mg/125 mg tds amoxycillin plus clavulanic acid were given orally for 9.6 +/- 1.8 days. Two hundred and fifty-one patients were enrolled in 27 centres in West Germany, France, and Italy. The overall clinical efficacy was 97.2% in the cefpodoxime proxetil group compared with 94.7% in the co-amoxiclav group. Fifty-eight adverse events, mainly gastrointestinal, occurred in 42 patients with no significant difference between the groups. A significant difference in the number of resistant pathogens on pre-treatment culture to the advantage of cefpodoxime was noted. In our experience, both drugs were of similar value in the treatment of respiratory tract infections. Thus, cefpodoxime proxetil should be an effective antibiotic for the treatment of acute exacerbations of chronic bronchitis.

Adult↗

PubMed1990

Parathyroid hormone and cirrhosis of the liver.

Fifty patients with liver cirrhosis (36 alcoholic, 1 drug-induced, 7 posthepatitic, and 6 cryptogenic) and normal renal function were investigated to determine whether PTH levels in serum, measured using the common midregion human PTH-(44-68) RIA, are elevated in such patients and whether this is related to impaired liver function rather than to the effect of secondary hyperparathyroidism. Their data were compared with those from 25 control subjects. The median PTH level of 462 +/- 18 ng/L (+/- SEM) was significantly increased (P less than 0.01) in cirrhotics compared with that of 236 +/- 13 ng/L in the control group. Significant correlations were found between PTH levels and parameters of liver function such as prothrombin time (r = -0.40; P less than 0.01), albumin as a percentage of total protein (r = -0.48; P less than 0.01), bilirubin (r = 0.35; P less than 0.05), albumin (r = -0.34; p less than 0.05), and cholesterol (r = -0.32; P less than 0.05), but not for antipyrine clearance, suggesting increasing PTH with decreasing liver function. The median calcium level (2.26 +/- 0.03 mmol/L), corrected for changes in albumin, was near the lower limit of the normal range (2.25-2.60), but corrected calcium and PTH were positively correlated (r = 0.33; P less than 0.05), indicating that the elevation is not reactive to calcium depletion. A negative correlation existed between PTH and 25-hydroxy-cholecalciferol (r = -0.49; P less than 0.05), the main circulating metabolite of vitamin D. Normal values in an immunoradiometric assay that detects the whole sequence of human PTH-(1-84) suggest that fragments rather than the intact hormone are responsible for PTH elevations in cirrhosis. The positive correlation between midregion PTH and corrected calcium is probably an artifact of the correction formula. In conclusion, midregion PTH fragments are increased in patients with liver cirrhosis. The reason for this elevation may well be the impaired liver function rather than secondary hyperparathyroidism.

Calcifediol↗

PubMed1989

Direct tubular effect on calcium retention by hydrochlorothiazide.

Previous studies with hydrochlorothiazide revealed a calcium retaining effect of this substance. The mechanism by what this is done is still matter of controverse discussion. Effects of hydrochlorothiazide on vitamin D metabolism have been reported as well as those on parathyroid function. To further clarify the calcium retaining potency of hydrochlorothiazide (HCTZ) we treated 10 healthy young volunteers for four weeks with 2 x 50 mg HCTZ. In all volunteers we observed a marked decrease in urinary calcium excretion as well as in calcium clearance. Furthermore, we found a slight rise in ionized serum calcium (6.7%) and in intact PTH, as well as a 36% drop in 1,25-(OH)2-D3-levels. These effects were reversible after discontinuation of the treatment. No change was observed in urinary cAMP, phosphate excretion, serum anorganic phosphate levels, serum calcitonin and magnesium levels. Data presented here suggest that treatment with HCTZ causes a persistent reduction in calcium excretion through direct tubular effects, inhibits hydroxylation of vitamin D, and does not affect parathyroid function.

Adult↗

PubMed1989

The hypercalcemic Walker carcinosarcoma 256 of the rat causes an increase in serum 1,25-dihydroxyvitamin D3.

We have studied vitamin D metabolism in rats with the transplantable hypercalcemic Walker carcinosarcoma 256, which is a well characterized animal model for humoral hypercalcemia of malignancy. 25-Hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) concentrations were determined in blood samples obtained from parathyroidectomized (PTX) female rats at different time intervals after intramuscular tumor cell inoculation. We observed a dramatic increase in serum 1,25(OH)2D3 (280 +/- 184 vs. 98 +/- 31 pmol/l) 6 days after tumor cell injection and 4 days after the initial rise of serum calcium, whereas 25(OH)D3 tended to decrease. In a separate control experiment we compared this to the effect of exogenous parathyroid hormone in PTX rats and found similar results. In contrast, rats exhibited no change in vitamin D metabolite blood concentration after inoculation of the normocalcemic Yoshida sarcoma, which obviously does not interfere with vitamin D metabolism. We conclude that the humoral bone-resorbing agent produced by the Walker tumor cells causes elevation of serum 1,25(OH)2D3 concentration by this fulfilling an additional criterion of PTH-like activity.

Animals↗

PubMed1989

Postoperative pentagastrin-stimulated serum calcitonin concentrations in patients with medullary thyroid carcinoma: reoperations in patients with concentrations bordering the detection limit.

The case reports on two patients with medullary thyroid carcinoma show that even postoperatively stimulated serum calcitonin (CT) concentrations near the detection limit (using a polyclonal antibody against synthetic CT) can demonstrate persistent disease. Stimulated CT concentrations can be lowered to nondetectable levels by a second and third operation if a meticulous technique is used for dissection of the lymph compartments. The patient can then be assumed to be cured. Diagnostic accuracy at very low CT concentrations can be improved by selective venous catheterization with blood sampling for CT after stimulation.

Adult↗

PubMed1989

Influence of ultraviolet irradiation on plasma vitamin D and calcitonin levels in humans.

In 13 patients with essential hypertension (EH) and in 10 normotensive controls, the influence of ultraviolet irradiation on plasma calcium, phosphorus, 25-OH-D, 1,25(OH)2D and calcitonin (CT) was studied. The basal levels of total calcium (2.47 +/- 0.02 mmol/liter) and phosphorus (1.10 +/- 0.04 mmol/liter) in patients with essential hypertension were not different from the control subjects (2.49 +/- 0.05 mmol/liter and 1.22 +/- 0.06 mmol/liter, respectively). However, patients with essential hypertension had elevated levels of 25-OH-D (68.09 +/- 7.48 vs. 26.51 +/- 3.3 mg/ml), 1,25(OH)2D (175.15 +/- 32.5 pmol/liter vs. 118.0 +/- 13.23 pmol/liter) and CT (131.7 +/- 32.36 pg/ml vs. 49.0 +/- 18.62 pg/ml) than in control subjects. In contrast to normotensive subjects, the majority of hypertensive patients showed no rise of plasma 25-OH-D and 1,25(OH)2D in response to ultraviolet irradiation. The results of this study suggest involvement of abnormal vitamin D metabolism in the pathogenesis of hypertension, at least in some patients.

Adult↗

PubMed1989

Two-site immunochemiluminometric assay of intact human parathyrin in serum with use of a tracer peptide purified by reversed-phase high-performance liquid chromatography.

For this two-site immunochemiluminometric assay of intact human parathyrin (hPTH), the luminescent tracer was synthetic hPTH(53-84), conjugated via succinimide linkage to (aminobutyl)ethyl-isoluminol hemisuccinimide (abei-h). Purification of the labeled hPTH(53-84) by reversed-phase high-performance liquid chromatography allowed isolation of the conjugate having the highest incorporation of abei-h, 1.6 mol per mole of hPTH(53-84). The solid-phase antibody directed against the N-terminal part of hPTH was immobilized by adsorption onto the polystyrene surface of the assay tube and extracted the intact hPTH and N-terminal fragments. Another antibody against synthetic hPTH(53-84), which bound to the C-terminal part of intact hPTH, was indirectly labeled at its second free binding site with the abei-h-labeled hPTH(53-84). The assay has a detection limit of 0.5 pmol/L; it is accurate, precise, and reliable; and it shows a linear response for samples containing up to 100 pmol of hPTH per liter. The normal reference interval ranged from 1.8 to 5.9 pmol/L; 56 patients with primary hyperparathyroidism had concentrations ranging from 5.9 to 113 pmol/L. The concentrations detected in patients with idiopathic hypoparathyroidism were below the normal reference interval.

Chromatography, High Pressure Liquid↗

PubMed1989

Immunoradiometric assay of carcinoembryonic antigen with use of avidin-biotin labeling.

In evaluating an enzyme-linked immunoassay of carcinoembryonic antigen (CEA) we found that the IgG fraction of polyclonal anti-CEA antibodies (DAKO) bound very well to the walls of polypropylene test tubes. We therefore developed an immunoradiometric CEA assay based on this binding of polyclonal anti-CEA antibody. We biotinylated a commercially available monoclonal antibody (Hybritech) and bound this to the CEA-anti-CEA bound to the tube wall. For detection we used 125I-labeled streptavidin. In comparison with several immunoassays for CEA this system offered several advantages such as greater linearity of the standard curve (from 0 to 74 micrograms/L), a steeper dose-response curve, and smaller coefficients of variation in the clinically useful range. This assay system may be used for other large molecules, so that only one tracer, the 125I-labeled streptavidin, has to be labeled; thus the technique seems suited for several different assays.

Antibodies, Monoclonal↗

PubMed1988

[Hormone active versus hormone inactive parathyroid gland cancer].

Problems regarding diagnosis and treatment of hormonally active and hormonally inactive parathyroid carcinomas arise from opposite sides, as is shown in two resp. cases. In functionally active tumors parathyroid origin is clear--but how to prove malignancy in early tumor stages? In inactive tumors malignancy is sound--but how to prove their parathyroid origin? Meticulous histologic examination (semithin-Layer) and cytophotometric DNA-measurement may be helpful diagnostic tools for active tumors, immunohistochemistry and analysis of parathormone fragments in plasma and tumor-cell-culture for inactive tumors. Nevertheless the surgeon's decision for radical surgery sometimes will have to be put on the intraoperative macroscopic situs--in order to provide curative treatment.

Adult↗

PubMed1988

Enhanced suppression of 1,25(OH)2D3 and intact parathyroid hormone in Graves' disease as compared to toxic nodular goiter.

1.25(OH)2D3, 25OHD3, and intact parathyroid hormone, as well as various parameters of calcium-phosphorus metabolism were measured in 38 patients with Graves' disease (GD) and in 24 patients with toxic nodular goiter (TNG). Plasma 1.25(OH)2D3 levels were lower in GD patients (82 +/- 29 pmol/liter) than in those with TNG (155 +/- 32 pmol/liter) (P less than 0.0005). The mean value of 1.25(OH)2D3 in 45 controls was intermediate between the two groups of patients (140 +/- 41) and the difference was statistically significant. GD patients before and after treatment had higher alkaline phosphatase (P less than 0.05), lower intact parathyroid hormone (PTH) (P less than 0.05), and lower 1.25(OH)2D3 levels (P less than 0.0005 in the hyperthyroid and P less than 0.01 in the euthyroid state) than TNG patients. We conclude that increased skeletal calcium resorption is due to elevated levels of T3 causing suppression of 1.25(OH)2D3 production and of PTH levels in both groups of patients albeit of different degrees. Furthermore, we postulate that the profound suppression of 1.25(OH)2D3 in GD is secondary to an immune-mediated phenomenon.

Calcitriol↗

PubMed1988

Two-site assay of intact parathyroid hormone in the investigation of primary hyperparathyroidism and other disorders of calcium metabolism compared with a midregion assay.

We compared the utility of measurements of serum intact human PTH-(1-84) and midregion human PTH-(44-68) in patients with disorders of extracellular calcium metabolism. Serum midregion PTH was determined by RIA, and serum intact PTH was measured by a sensitive and specific immunoradiometric two-site assay. The serum intact PTH concentrations in 70 patients with primary hyperparathyroidism were above the normal range in 69, and thus widely separated from the levels in 40 patients with hypercalcemia of malignancy, in whom serum intact PTH values were usually below normal. In contrast, both groups had overlapping serum midregion PTH values. In patients after renal transplantation and those with chronic renal failure, serum intact PTH levels were in the normal range twice as often as were serum midregion PTH values. The intact PTH assay was also superior in detecting venous gradients of the hormone and changes in PTH secretion caused by altered serum calcium concentrations, and serum intact PTH was remarkably low in hepatic venous effluent. We conclude that this new assay for serum intact PTH is superior to the midregion RIA in investigating parathyroid function in several different clinical conditions.

Adult↗

PubMed1988

Development of immunoradiometric assays for human thyroglobulin using monoclonal antibodies and the biotin/avidin system.

Monoclonal antibodies against human thyroglobulin were produced by the hybridoma technique. Using three non-crossreactive monoclonal antibodies, an IRMA system was developed, with a polyclonal rabbit antibody fixed on microtiter plates as first extracting antibody. The monoclonal antibodies were used as second antibody, while anti-mouse IgG-biotin from goat and [125I]streptavidin served as the indicator system. The source of the monoclonal antibodies was diluted culture medium without purification. Sensitivities of 3-4 micrograms/l were obtained with all 3 monoclonal antibodies; interassay variation was about 5%. This test system will be used for further immunological characterization of circulating thyroglobulin in different thyroid diseases.

Antibodies, Monoclonal↗

PubMed1988

Effect of long-term treatment with antiepileptic drugs on the vitamin status.

The status of vitamins A, B1, B2, B6, B12, C, D, and E as well as that of beta-carotene, biotin, and folate in the blood of over 500 epileptics was compared with that of a normal population. Male and female epileptics showed a poorer supply of vitamins B2, biotin, folate, and 25-hydroxycholecalciferol; the males, of only vitamin B6, B12, and E, and the women, of only vitamin A. Concentrations of beta-carotene and vitamin E in female epileptics were higher. The evaluation of relations between vitamin concentrations and mean daily dose, total dose of anticonvulsants, and duration of therapy suggested a possible influence of anticonvulsant medication on vitamins B1, B2, B6, C, D, E, beta-carotene, biotin, and folate. Concentrations of B vitamins as well as of folate were distinctly lower in patients under monotherapy with enzyme-inducing drugs than in those under valproate sodium. There was no relationship between bone mineral content and 25-hydroxycholecalciferol levels and between the neurographic parameters and the neurotropic vitamins of the B group, which also had no influence on concentration performance. Patients with poorer results in tests of the function of the central and the peripheral nervous system displayed a tendency towards lower vitamin-C levels. There were indications of potential links between immunological status and vitamin B6 and biotin. Males and females with a poorer supply of vitamin C, as well as males with lower riboflavin levels, showed a tendency towards macrocytic anaemia. Cerebellar disturbances were associated with lower concentrations of folate, of vitamin C or D, and possibly of biotin. The incidence of gingival hyperplasia could be linked to riboflavin, to biotin, and possibly also to vitamin C, D, or folate status.

Adult↗

PubMed1987

[Treatment of tumor hypercalcemia with clodronate. Effect on parathormone and calcitriol].

Clodronate (dichlormethylene diphosphonate) was administered to 21 patients with hypercalcemia due to malignant tumor. The drug was initially given intravenously, then orally. In 20 patients the serum calcium level had been reduced to the normal range within one week of the start of treatment (from 3.3 +/- 0.5 mmol/l to 2.4 +/- 0.3 mmol/l). With oral administration there was a renewed rise in calcium levels in some patients, which had to be treated with higher oral doses or intravenous administration. Parallel with the reduction in calcium levels there was an improvement in the originally impaired renal function. The serum level of intact parathormone(1-84) and 1.25-dihydroxy-vitamin-D3 (calcitriol) rose significantly from usually lowered initial levels. There was a non-linear inverse correlation between parathormone and calcium. No side effects were noted, even after long-term administration.

Adult↗