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Biomedical subjects

E Keck

Publications and source records attributed to E Keck.

At least 55 records · Page 3Linked to original sources

The defect of intestinal calcium transport in hyperthyroidism and its response to therapy.

Skeletal demineralization occurs in thyrotoxicosis. Fecal calcium excretion may be enhanced, and calcium balance tends to be negative. We investigated intestinal calcium transport in 12 hyperthyroid patients. Absorption was measured by segmental perfusion in the proximal jejunum at calcium concentrations commensurate with those in the fasting and postprandial states. At low luminal concentrations, under conditions where calcium is transported predominantly by active processes, the calcium absorption rate was reduced though not abolished in hyperthyroid patients (16 +/- 4 (SE) mumol/h . 30 cm segment) as compared to normal subjects (71 +/- 8 mumol/h; P less than 0.001). When perfusate calcium was raised to 5 mmol/liter there was little increment of the net absorption rate in the hyperthyroid group (45 +/- 11 mumol/h), whereas that in the normal subjects rose to 183 +/- 17 mumol/h. Likewise, the unidirectional calcium flux out of the lumen was low in hyperthyroidism (43 +/- 7 mumol/h), suggesting that low net absorption rates were not due to transmucosal calcium loss. D-Xylose permeation was similar in all study groups. Treatment of the thyroid disease led to a marked increase in calcium absorption rates from 33 +/- 10 to 124 +/- 20 mumol/h (at 2 mmol/liter P less than 0.001; n = 5) into the range of values in normal subjects (124 +/- 9 mumol/h). Circulating levels of 1,25-dihydroxyvitamin D were low in hyperthyroid patients (38 +/- 11 pg/ml) and increased during treatment to 63 +/- 11 pg/ml (P less than 0.025; n = 9), whereas 25-hydroxyvitamin D was normal and remained unchanged. We conclude that intestinal calcium transport, particularly its active component, is reversibly decreased in hyperthyroidism. The association with low plasma levels of the active vitamin D metabolite suggests that the decrease in calcium absorption may be related to calcium-regulating mechanisms as a consequence of the net calcium efflux from bone in this disease.

Adult↗

Hepatic osteodystrophy in primary biliary cirrhosis: a possible defect in Kupffer cell mediated cleavage of parathyroid hormone.

Twelve of fourteen female patients with primary biliary cirrhosis, receiving vitamin D supplementation, exhibited unequivocal signs of osteoporosis but not of osteomalacia. Vitamin D treatment reproduced normal 25-hydroxyvitamin D levels in all but two patients and the 1,25 and 24,25-dihydroxyvitamin D metabolic pathways appeared to be unimpaired. A possible mechanism for the vitamin D resistant osteoporosis has been identified following the observation that, in those patients with severe cirrhosis, the circulating concentration of intact PTH was elevated. The increase in intact hormone appears to be at the expense of the carboxyl-regional PTH produced by hepatic Kupffer cell mediated cleavage of intact PTH. As a defect in Kupffer cell function is documented in primary biliary cirrhosis we postulate that the increased intact PTH/decreased carboxyl-regional PTH concentrations arise as a result of diminished Kupffer cell mediated cleavage. The reduced generation of cleaved PTH, due to this loss of Kupffer cell activity, would thus contribute to the development of osteoporosis in primary biliary cirrhosis.

24,25-Dihydroxyvitamin D 3↗

Fate of dynamic left ventricular outflow tract obstruction after anatomic correction of transposition of the great arteries.

Fourteen patients undergoing successful anatomic correction for transposition of the great arteries had subpulmonary gradients of 20 to 120 mm Hg (mean 40) across the left ventricular outflow tract before surgery. Ten patients had an intact ventricular septum, and four had an additional ventricular septal defect. In one patient obstruction was due to ballooning of the septal leaflet of the tricuspid valve through the ventricular septal defect. In the remaining patients obstruction was due to bulging of the interventricular septum plus or minus septal hypertrophy and with or without a fibromuscular shelf. At operation the pulmonary valve was normal and the left ventricular outflow tract was of adequate dimension with no organic obstruction. No attempt at surgical widening was made. After surgery abnormalities revealed by echocardiography were immediately reversed. Routine reinvestigation 6 to 26 months after surgery in 10 patients showed no gradient across the left ventricular outflow tract and normal development of this region.

Child↗

Immunoreactive parathyroid hormone in early and advanced renal failure.

Immunoreactive parathyroid hormone (iPTH) was measured in the serum of 20 patients with early renal failure (ERF) using three assays with different specificity. Half of these patients had elevated iPTH in one or more assays, up to twice the upper limit of normal. In contrast, 36 patients with a creatinine clearance below less than 20 ml/min had an 80% elevated iPTH, up to 5 times the upper limit of normal. The patients with ERF and elevated iPTH had a lower serum calcium but no higher serum phosphate than those with normal iPTH. The differences in iPTH in early and end-stage renal failure can be explained by known differences in metabolism of different PTH forms in uremia.

Adolescent↗

[Parathormone and vitamin d3-metabolites in healthy children and children with chronic renal failure before and after kidney transplantation].

Immunoreactive parathyroid hormone (iPTH), 25(OH)D3, 24,25(OH)2D3, 1.25(OH)2D3, creatinin, phosphate and calcium were determined in 33 children suffering from chronic renal failure as well as in 7 healthy children serving as a control group. In 9 children with preterminal renal insufficiency and in 13 children who had to undergo hemodialysis iPTH and creatinin were closely related. In the hemodialysed children's group serum phosphate was significantly elevated whereas calcium did not different from the control group. Treatment with vitamin D3 showed in those children undergoing hemodialysis increased 25(OH)D3 in normal 1.25(OH)2D3 plasma levels. Nevertheless, in the children with preterminal renal insufficiency as well as the children under hemodialysis iPTH was significantly increased. Thus, it is suggested that a negative feed back regulation controls the synthesis of 1.25(OH)2D3. After kidney transplantation the serum levels of iPTH, the vitamin D3 metabolites and creatinin became normal. There was no correlation between iPTH and 25(OH)D3 or 1.25(OH)2D3, but the correlation with creatinin (P less than 0.05, r = 0.7) before and after transplantation was statistically significant. Thus, the alterations in vitamin D metabolism and the hyperparathyroidism in chronic renal osteodystrophy appear to be largely independent of each other.

Adolescent↗

Effects of calcium and calcitonin on circulating levels of glucagon and glucose in diabetes mellitus.

The effects of Ca2+ and calcitonin infusions on circulating glucagon, glucose, C-peptide, Ca2+, and calcitonin were investigated in hyper-glucagonaemic insulin-dependent diabetics. In 14 insulin-deprived diabetics and 12 healthy volunteers 2h infusions of saline (0.154 mol/1), Ca2+ (0.375 mmol/kg body weight), and calcitonin (4.5 IU/kg body weight) were performed. There were no significant changes during saline infusion. In the diabetics, Ca2+ infusions induced a rise of plasma Ca2+ up to 3.2 +/- 0.1 mmol/1 and a fall of circulating glucagon (-26.4 +/- 5.7%; p less than 0.001) and glucose (-23.3 +/- 3.6%; p less than 0.05). Plasma calcitonin rose to twice basal values (p less than 0.025). During calcitonin infusions plasma Ca2+ decreased slightly to 2.1 +/- 0.2 mmol/1; a fall was found in both glucose (-24.4 +/- 4.0%; p less than 0.05) and circulating glucagon (-22.5 +/- 4.3%; p less than 0.001). Two groups of 6 healthy volunteers were subjected to saline and Ca2+, or to Ca2+ and calcitonin infusions. Both Ca2+ and calcitonin infusions induced a fall of serum insulin (-30.1 +/- 6.6%; p less than 0.05). Calcitonin depressed circulating glucagon by -18.6 +/- 4.4% (p less than 0.025), whereas during Ca2+ infusions glucagon decreased only by -6.5 +/- 1.9% (p greater than 0.1). We conclude from our results that an increase of circulating calcitonin induced by Ca2+ infusions or by exogenous calcitonin administration appears to depress elevated circulating glucagon and glucose in insulin-dependent diabetics.

Adult↗

Protein binding assays for 25-hydroxy, 24,25-dihydroxy and 1,25-dihydroxy metabolites of vitamin D1) in human plasma.

In this study we describe protein binding assays for 25-hydroxy, 24,25-dihydroxy and 1,25-dihydroxy metabolites of vitamin D in 6 ml of plasma. The procedure involves methanol/methylene chloride extraction of plasma followed by separation and purification of mono- and dihydroxylated vitamin D metabolites on two LH 20 columns with different elution solvents. The separation of dihydroxylated vitamin D metabolites is carried out by high performance liquid chromatography (HPLC). 25-Hydroxy and 24,25-dihydroxy vitamin D are measured by competitive protein binding assays with diluted homogenate from vitamin D-deficient rat kidneys. 1,25-Dihydroxy vitamin D is measured by competitive protein binding assay with diluted cytosol from vitamin D-deficient chick intestine. The concentration of 25-hydroxy vitamin D in human plasma, as determined by this assay, was 12.2 +/- 5.9 microgram/l; of 24,25-dihydroxy vitamin D 1.5 +/- 1.0 microgram/l, and of 1,25-dihydroxy vitamin D 25.8 +/- 11.7 ng/l (means +/- S.D., n = 17, October, Düsseldorf). In April, the concentration of the vitamin D metabolites of the same subjects were: 25-hydroxy vitamin D 3.3 +/- 0.9 microgram/l; 24,25-dihydroxy vitamin D 0.17 +/- 0.04 microgram/l and 1,25-dihydroxy vitamin D 38.3 +/- 10.2 ng/l. Mean values in nonselected human plasma samples of hospitalized patients (n = 84) taken during one year were: 25-hydroxy vitamin D 5.7 +/- 2.9 microgram/l; 24,25-dihydroxy vitamin D 0.64 +/- 0.44 microgram/l; 1,25-dihydroxy vitamin D 53.3 +/- 27.6 ng/l. Mean values in pancreatectomized subjects were: 25-hydroxy vitamin D 4.2 +/- 2.6 microgram/l; 24,25-dihydroxy vitamin D 0.27 +/- 0.15 microgram/l; 1.25-dihydroxy vitamin D 19.6 +/- 11.9 ng/l (n = 10).

24,25-Dihydroxyvitamin D 3↗

[The significance of magnesium in medicine. (I) Biological function, homeostasis, ingestion and excretion (author's transl)].

Magnesium (Mg) has numerous biological functions, one of the most important being its role in the metabolism of ATP. In addition it is a significant structural element in DNA and membranes. Parathormone and metabolites of vitamin D affect Mg homeostasis. The intestinal absorption depends principally on the amount and availability of the Mg in the diet. The Mg content of the organism is effectively regulated on the other hand by adaptation of the renal excretion.

Bone and Bones↗

[The significance of magnesium in medicine. (II) Disturbances of magnesium metabolism and their treatment (author's transl)].

Magnesium (Mg) deficiency is common in diseases of the digestive tract and alcoholism, in diuretic therapy, hypocalcemia and as a congenital disturbance of absorption. The symptoms are particularly related to the heart and nervous system, but are not characteristic. Excess of Mg is observed in advanced renal failure. Compensation of the Mg deficiency partly explains the success of Mg in the treatment of cardiovascular, digestive and neuropsychiatric diseases. Parenteral feeding must contain adequate Mg. Important fields of application of Mg are the treatment of peptic ulcer and its use as a laxative.

Humans↗

Testosterone metabolism in human bone.

The conversion of [1,2,6,7-3H]testosterone to [3H]dihydrotestosterone has been assessed in ground sp¿ongiosa of normal and osteoporotic bone. The tissue was obtained from 23 patients, 18 women, 3 men and 2 children who were undergoing orthopedic surgery. The formation of dihydrotestosterone was demonstrated in all samples examined. The half maximum rate of dihydrotestosterone formation occurred at a substrate concentration of 0.3 microM a value similar to that reported for dihydrotestosterone formation in other androgen target organs. Under the standardized conditions utilized in this study the rate of dihydrotestosterone formation did not differ significantly in normal as compared to osteoporotic bone. Furthermore, the conversion of testosterone to androstenedione was also similar in osteoporotic and normal bone. Based on these studies it seems reasonable to conclude that dihydrotestosterone rather than testosterone is the active intracellular androgen in human bone since in other androgen target tissue androgen action is mediated by dihydrotestosterone if 5 alpha-reductase is present.

Adult↗

Clinical and hemodynamic results of the two-stage anatomic correction of simple transposition of the great arteries.

Between 1976-1979, 14 patients with simple transposition of the great arteries (TGA), ranging in age from 1 month to 2 1/2 years, underwent two-stage anatomic correction. Twenty patients underwent a first-stage operation, with three early deaths (15%). After the first-stage operation the peak systolic left ventricular pressure rose from 38 +/- 6 mm Hg to 79.6 +/- 11 mm Hg, with no significant change in end-diastolic pressure or ejection fraction. This was associated with a decrease in the actual pulmonary flow but no change in effective pulmonary flow. Between the first and second stages we allowed a 5-week to 9-month interval. There were four early (29%) and no late deaths. Follow-up was 5-37 months. After an initial period of cardiac failure, all patients became asymptomatic and developed normally. Rapid changes in ECG, vectocardiogram and echocardiogram toward normal were observed. Repeat cardiac catheterization was performed in nine patients, 3 weeks to 2 1/2 years after operation. Left ventricular ejection fraction was normal in all. Two who were investigated early had mild mitral regurgitation, five had minimal aortic regurgitation and one had moderate supravalvar pulmonary stenosis. The aortic and coronary anastomoses appeared to grow normally.

Blood Pressure↗

[Differential diagnosis of hypercalcaemia by measurement of renal calcium excretion during parathormone administration (author's transl)].

Rapid differential diagnosis of hypercalcaemia due to primary hyperparathyroidism or malignancy with or without bone metastases may be life saving. A parathormone infusion test (6 USP units/kg body wt X 20 min) enables a differential diagnosis within three hours by means of measurement of renal calcium excretion. In normal persons calcium excretion decreased from 147 +/- 90 to 79 +/- 54 mumol/h (x +/- s, n = 10). In primary hyperparathyroidism with hypercalcaemia the high calcium excretion remained unchanged: 716 +/- 162 mumol/h before and 804 +/- 130 mumul/h 120 minutes after the PTH infusion (n = 12). In patients with hypercalcaemia caused by bronchial carcinoma with (n = 5) and without (n = 1) bone metastases calcium excretion decreased from 552 +/- 182 to 163 +/- 114 mumol/h. As a consequence of these data this test is advisable when the indication for operation in cases with hypercalcaemia has to be reached within a few hours.

Adult↗