Studies on the mode of action of calciferol-XXXV. Comparison of the biochemical properties and ligand specificities of receptors and antibodies for 1,25-dihydroxyvitamin D3.
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Biomedical subjects
Publications and source records attributed to H Schmidt-Gayk.
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Serum levels of the peptide hormones, LH, FSH, TSH, prolactin, beta-HCG and PTH are observed to significantly modulate in patients with urogenital tumors, beta-HCG appears elevated in patients with chorioncarcinoma, teratoma and embryonal carcinoma and is shown to increase serum prolactin. TSH and prolactin are measured in pathological range in patients with renal carcinomas. Following nephrectomy serum TSH persists in high levels only in patients with advanced diseases, while PTH is more frequently suppressed in these patients. Serum LH and prolactin show a more distinct change of values in infiltrating bladder cancer, when compared to that of noninvasive bladder carcinomas. Prostate benign hyperplasia and cancer demonstrate similar ranges for peptide hormones, that will be changed by estrogen treatment in its LH, TSH and prolactin pattern. Serum levels of peptide hormones are affected by a complex system of ectopic hormone production, synthesis of peptide analogues, metabolic changes due to age and treatment.
High dose levels of calcium chloride significantly decrease serum level of parathyroid hormone (PTH) in both patients with history of idiopathic stone formation and healthy controls. Suppressibility of parathyroid glands is obtained by injection of 10 ml 10% calcium chloride without any restriction in calcium diet. Serum levels of calcium measured 14 mg/dl 10 min. after high dose calcium chloride injection and distinctly affect cAMP in urine in patients when compared to healthy controls. The elimination of electrolytes and uric acid is elevated 40 min. after calcium application in both patients and controls and returns to normal values 120 min. later. No stone formation has been observed in an eighteen mouth follow up of all subjects studied.
Peptide hormones LH, FSH, TSH, e-peptide, prolactin, HCG, PTH, calcitonin and prostaglandin F2 alpha were evaluated in 25 patients with renal adenocancer. Prolactin elevation found in 45% was unrelated to the stage of the disease, while aberrant TSH and FSH were more sensitive in indicating distant metastasis. Prostaglandin F2 alpha, measured as a stable degradation product 13,14-DHK-PGF2 alpha, was frequently elevated and normalized following tumor nephrectomy within 12 month. Serum PTH was decreased in patients with tumor dissemination suggesting resorptive hypercalcemina, whereas none of the patient had circulating HCG levels. Therefore even patients without any paraneoplastic syndromes have a frequent change of peptide hormones directly or indirectly caused by renal cancer.
Idiopathic nephrolithiasis with recurrent ca-oxalat stones are investigated for occult renal dysfunction or for disturbed clearance of PTH. After injection of PTE a significant increase of renal excretion of Na+, K+, Ca2+ and uric acid was observed normalizing within 120 min after injection. Healthy controls showed similar changes, and following PTH the cAMP generating capacity of patients with recurrent stones was in normal range. The turn over rate of PTH was 30-40 min without differences in the collectives studied.
No significant difference was found in a comparison between the values of unreduced serum folic acid of 48 epileptics treated with hydantoin and 38 controls as measured by a competitive protein-binding assay. The average folic acid value was 7.73 nmol/l in the epileptics, a little higher than the 7.18 nmol/l found in the controls. This result supports the hypothesis that the folate deficiency in epileptics is caused by blocking the conversion of folic acid to 5-methyltetrahydrofolic acid by phenytoin.
Prevalence of hypertension and "intake" of sodium chloride (as estimated from 24-hr urinary Na-excretion) were measured in a random sample (n = 800) of 20- to 40-year-old Heidelberg men. There was a high (14%) prevalence of hypertension and a high (mean = 11.32 g) NcCl intake; both showed, however, no correlation. The lack of a NaCl/blood pressure correlation in this cross-sectional study might be due to intra- and interindividual variability of both parameters and, possibly, to a "threshold" argument concerning the etiological role of sodium in hypertension.
In ten male hypophosphataemic hypercalciuric recurrent renal stone formers with absorptive hypercalciuria and ten male normophosphataemic normocalciuric control persons, fasting plasma and urine chemistry was studied throughout the day under basal conditions and following an oral phosphorus load. After overnight fasting, plasma phosphorus and TMP/GFR were lower and urinary calcium higher in patients than in controls. Both in patients and controls, plasma phosphorus rose throughout the morning hours. In the afternoon, plasma phosphorus was almost equal in patients and controls. The circadian rise of plasma phosphorus despite no increase of urinary phosphorus argues against the presence of a fixed renal tubular phosphorus leak in absorptive hypercalciuria, at least in the fasting state. Patients differed from controls not only with respect to urinary calcium, but also with respect to fasting absolute and fractional urinary excretion of sodium and chloride. Increased fractional urinary sodium was found both in normotensive and hypertensive patients. Since tubular reabsorption of phosphorus and the setting of fasting plasma phosphorus depend, among other factors, on tubular handling of sodium, the finding may be relevant for the genesis of transient fasting hypophosphataemia in absorptive hypercalciuria.
Fourteen patients (six males and eight females) have been treated with chronic hemofiltration three times weekly for three to 27 months with the post-dilution technique. All patients had previously been on regular dialysis treatment. Patients were selected for hemofiltration because of dialysis-resistent hypertension (eight), symptoms of dialysis discomfort (five), hypertriglyceridemia (five) and polyneuropathy (seven). Hypertension improved in six of eight patients, symptoms of dialysis discomfort markedly diminished in all five patients, hypertriglyceridemia did not change consistently, polyneuropathy improved in six of seven patients. Balance studies of Na, Ca and Mg revealed a positive correlation to fluid balance. Phosphate, BUN, creatinine and uric acid increased. Loss of amino acids and protein is negligible. Hormone studies showed a decrease of T3, T4 and TSH though the pituitary-thyroid axis is intact, possibly indicating a decreased TRH activity. Vitamin D remained unchanged, PTH levels increased, possibly related to a diminished excretion of phosphate and diminished intake of calcium, respectively, during hemofiltration treatment as compared to hemodialysis.
Patients with reduced renal mass (i.e., nephrectomized) and slightly decreased renal clearance (70-80%) have been treated by 4 g DNA to study uricosuria. Prompt or prolonged renal excretion of uric acid and creatinine have been observed with indirect effects on parathyroid secretion. Urinary cAMP, however, failed to correlate to the change of parathyroid function. Reversely, PTH injection significantly increases uricosuria suggesting interrelated secretion of uric acid and cAMP of the proximal tubules. In some respects this model can be used to investigate increased DNA metabolism and parathyroid function.
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The biplot technique is a very useful graphical method to display the relationships between row and column characteristics in two-way tables. This method is applicable as long as the rank-2 approximation explains a large part (e.g. 95%) of the whole variability. However, since in large tables only a rank-3 approximation will yield such a high degree of explanation, a three-dimensional biplot technique has been introduced, using a 3d-screen as a matter of presentation of clinical laboratory data. The value of such a procedure is illustrated using as a clinical example a patient population with recurrent renal stone formation due either to primary hyperparathyroidism or to idiopathic hypercalciuria.
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The effects of pulsatile and nonpulsatile flow pattern on pancreas and liver blood flow were studied in nine dogs on cardiopulmonary bypass (CPB). Furthermore, plasma levels of glucose, insulin, glucagon, growth hormone, and cholinesterase were compared in 20 patients subjected to open heart surgery with either pulsatile or nonpulsatile perfusion. Impairment of liver and pancreas function was significantly greater at the end of CPB and 48 h afterwards with nonpulsatile flow as compared with the pulsatile flow pattern. A decrease of intestinal blood flow that was demonstrated in dogs subjected to nonpulsatile perfusion could at least in part be responsible for the difference in postoperative organ function observed in patients after CPB.
To delineate the worth of chronic HF in end stage renal failure, since 1976 we have treated 9 patients with dialysis-resistant hypertension, 6 patients with dialysis intolerance, 7 patients with hypertriglyceridaemia and 7 patients with polyneuropathy. We found an improvement of polyneuropathy and volume-sodium dependent hypertension and symptoms of dialysis discomfort markedly diminished. No amelioration was detected in anaemia, hypertriglyceridaemia and volume-independent hypertension. Hyperphosphataemia was poorly controlled despite increased amounts of aluminium hydroxide. PTH values increased and renal osteopathy seemed to deteriorate.
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In a therapeutic trial 20 patients with femoral neck fractures (FNF) were treated alternatively without supplemental vitamin D, calcium and phosphate or with 15 000 I.U. vitamin D2, 500 mg Ca++ and 560 mg of phosphate daily. Within two weeks, 25-OH-D in serum increased in patients with supplementary therapy. It is concluded that in the German Federal Republic, vitamin D deficiency is frequently found in the elderly during the winter months and that vitamin D deficiency could be important for the development of FNF.
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