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Biomedical subjects

R K Rude

Publications and source records attributed to R K Rude.

At least 73 records · Page 4Linked to original sources
PubMed1985

Parenteral magnesium tolerance testing in the evaluation of magnesium deficiency.

Magnesium deficiency is a common clinical condition, frequently present even with normal serum magnesium (S-Mg) concentrations. We have studied retention of a low-dose (0.2 mEq/kg lean body weight), intravenously administered magnesium load in 6 hypomagnesemic patients and 18 normomagnesemic alcoholics as compared with 16 normal subjects. Both normomagnesemic and hypomagnesemic subjects retained significantly greater amounts of the administered magnesium than did the normal subjects. In patients who were restudied following parenteral magnesium repletion, retention of the magnesium load normalized. We conclude that increased retention of a magnesium load is a more sensitive index of magnesium deficiency than is the S-Mg concentration, and suggest that low-dose magnesium tolerance testing be used more frequently as a clinical tool in the evaluation of states of normomagnesemic magnesium deficiency.

Adult↗
PubMed1984

The effects of magnesium on calcium inhibition of parathyroid adenylate cyclase.

cAMP has been shown to mediate the response of the parathyroid gland to a number of agonists and appears to take part in the regulation of this gland by divalent cations as well. We have studied the effects of the concentrations of free magnesium (Mg+2) and ionic calcium (Ca+2) on the kinetic properties of normal porcine parathyroid adenylate cyclase. In a previous study we obtained evidence for two calcium inhibition sites in this enzyme complex. In the present study we observed that the Mg+2 concentration influences the relative contribution of these sites to the overall calcium inhibition. At a high Mg+2 concentration (10 mM), the high affinity site contributes less than 50% of the total calcium inhibitable activity, whereas at a Mg+2 concentration in the low physiological range (0.5 mM), the high affinity site accounts for all the calcium inhibitable activity. Mg+2 was found to be a potent activator of porcine parathyroid adenylate cyclase, with a Ka of Mg of 0.8-2 mM. Ionic calcium at low concentrations (0.2-5 microM) acts as a competitive inhibitor with respect to Mg+2 activation. The calcium inhibition constant was estimated to be 2-3 microM. The Km for ATPMg-2 was 0.3 mM, which is similar to that found in other studies of adenylate cyclase activity in parathyroid tissue. The effects of Ca+2 on enzymatic activity with respect to the ATPMg-2 concentration showed noncompetitive inhibition. The calcium inhibition constant with respect to its effect on Vmax (KIv) was 3 microM; the calcium inhibition constant with respect to its effect on the binding of ATPMg-2 (KIs) was 10 microM. It is concluded from these results that the concentrations of intracellular Ca+2 reported to be present in parathyroid cells could inhibit adenylate cyclase activity. The mode of calcium inhibition that involves competition with magnesium would be particularly significant at low intracellular Mg+2 concentrations, and this phenomenon may account for the parathyroid secretory defect which is a characteristic feature of the magnesium-deficient state.

Adenosine Triphosphate↗
PubMed1984

Postpartum resolution of hypocalcemia in a lactating hypoparathyroid patient.

A 24 year old woman with post-surgical hypoparathyroidism was studied during pregnancy and lactation. During pregnancy the patient required less vitamin D therapy for control of her hypoparathyroidism and, while lactating, maintained a normal serum calcium without any supplemental vitamin D. The serum parathyroid hormone concentration and plasma 1,25 (OH)2 vitamin D concentration were undetectable and low normal respectively at a time when the serum calcium concentration was normal and the patient was not on vitamin D therapy. Urinary calcium excretion was low during this period and may explain the normalization of the serum calcium. The mechanism by which the improvement in calcium metabolism occurred is unknown, but may be secondary to a direct effect of prolactin on calcium homeostasis.

Adult↗
PubMed1983

A high prevalence of hypomagnesemia and hypermagnesemia in hospitalized patients.

The prevalence of hypomagnesemia and hypermagnesemia among hospitalized patients was studied by determining magnesium levels in 621 serum samples randomly selected from those submitted to the clinical chemistry laboratory for a biochemical test panel. The reference range for serum magnesium was established in this study as 1.2 to 1.9 mEq/L from measurements of serum magnesium on 341 healthy volunteers. Hypomagnesemia (less than 1.2 mEq/L) was present in 68 patients or 11.0%, and hypermagnesemia (greater than 1.9 mEq/L) occurred in 58 patients or 9.3%. The degree of association between hypomagnesemia and hypocalcemia was assessed by measuring serum magnesium on a separate group of 61 patients with hypocalcemia (corrected calcium less than 8.6 mg/dL). Hypomagnesemia was present in 23.3% of patients hypocalcemic in the absence of renal failure; this proportion was higher significantly than the 11.0% who were hypomagnesemic in the hospitalized patient group (P less than 0.025).

Adult↗
PubMed1982

Hypercalcemia in association with a Leydig cell tumor in the rat: a model for tumor-induced hypercalcemia in man.

The etiology of tumor-induced hypercalcemia was investigated in a transplantable Leydig cell tumor of the Fischer rat. In this model, serum calcium rose from a baseline of 10.4 +/0 0.3 mg/dl to 12.5 + 0.4 mg/dl at day 10 and 16.4 +/- 1.3 mg/dl (p less than 0.001) at day 13 post transplant. Urinary calcium also increased from 1.52 +/- 0.17 mg/d to 3.52 + 0.72 mg/d (Day 12, p less than 0.01). Serum phosphate decreased from a baseline of 7.5 +/- 0.3 mg/dl to 5.5 +/- 0.6 mg/dl at day 13 (p less than 0.05). At day 13 serum immunoreactive parathyroid hormone levels fell 76% from baseline (p less than 0.01). Calcitonin increased from 59 +/- 2 pg/ml to 88 +/- 9 pg/ml (p less than 0.02). The plasma prostaglandin E metabolite, 13,14-dihydro-15-keto-PGE2 increased from 407 +/- 103 pg/ml to 647 +/-62 pg/ml (p less than 0.05) and the active Vit D compound 1,25(OH)2D increased from 94.8 +/- 5.2 pg/ml to 162.3 +/- 11.8 pg/ml (p less than 0.01). Urinary cyclic AMP did not decrease in parallel with the parathyroid hormone level and, in fact, increased from 146 +/- 3 nmol/d to 172 +/- 27 nmol/d (NS). Administration of the cyclooxygenase inhibitor indomethacin (20 mg/Kg/d) or hydrocortisone (50 mg/Kg/d) did not prevent the development of hypercalcemia. This model is similar to many patients with humoral hypercalcemia of malignancy who demonstrate suppression of parathyroid hormone with elevated urinary cyclic AMP excretion and may prove useful in the understanding of the responsible mechanisms.

Animals↗
PubMed1982

Abnormal bone and parathyroid histology in carcinoma patients with pseudohyperparathyroidism.

Postmortem bone and parathyroid gland histology in nine hypercalcemic cancer patients without bone metastases was compared to bone and parathyroid histology in ten normocalcemia patients. Parameters of parathyroid function, including serum immunoreactive parathyroid hormone, acid base status, serum phosphate, and nephrogenous cyclic AMP were measured in the hypercalcemic group and compared to normals and to patients with primary hyperparathyroidism. Bone histology in all nine hypercalcemic cancer patients showed increased osteoclastic bone resorption and increased fibrous connective tissue in the bone marrow. Parathyroid glands were of normal size in all nine patients but contained little or no fat, one criterion of parathyroid hyperplasia. In the normocalcemic cancer patients only 2/10 had minimally increased bone resorption while 7/10 had decreased or absent stromal fat in the parathyroid glands. Despite the hyperplastic appearance of the parathyroid glands, serum biochemical parameters in the hypercalcemic cancer patients indicate a state of suppressed parathyroid function suggesting that the osteoclastic bone resorption is related to a humoral substance elaborated by the tumors which is distinct from parathyroid hormone.

Adult↗
PubMed1982

Humoral hypercalcemia of malignancy: a syndrome in search of a hormone.

A women with hypercalcemia and a hypernephroma confined to the left kidney underwent nephrectomy and subsequent resolution of hypercalcemia. Serum parathyroid hormone was undetectable in peripheral blood as well as in the left renal vein at surgery. Parathyroid hormone was also undetectable in the tumor extract using three different antisera to parathyroid hormone. Measurement of plasma prostaglandin E and 13, 14-dihydro-15-keto-prostaglandin E2 revealed levels within the normal range. The serum 1,25-dihydroxyvitamin D concentration was below normal and nephrogenous cyclic adenosine monophosphate was markedly elevated. The humoral agent responsible for hypercalcemia in this patient was not identified. This case emphasizes the need to search for new hypercalcemic factors in patients with hypercalcemia of malignancy.

Adenocarcinoma↗
PubMed1982

End-organ response to adrenocorticotropin, thyrotropin, gonadotropin-releasing hormone, and glucagon in hypocalcemic magnesium deficient patients.

We have evaluated the responsiveness of hypocalcemic magnesium-deficient patients to ACTH, TRH, gonadotropin-releasing hormone, and glucagon as determined by the rise in serum cortisol, TSH, LH, and plasma cAMP concentrations, respectively. It was previously been shown that the hypocalcemia of magnesium deficiency is secondary to impaired secretion of parathyroid hormone (PTH) along with renal and skeletal resistance to the action of PTH. Since PTH secretion and action are though to be effected through the intermediary action of cAMP, and magnesium is a required cofactor for adenylate cyclase, defective generation of cAMP could account for the observed defects in PTH secretion and action. Other hormonal systems requiring the intermediary action of cAMP may be similarly affected by magnesium deficiency. The results of the present study, however, demonstrate normal responsiveness of the adrenal cortex, thyrotrophs, gonadotrophs, and liver to their respective trophic hormones in hypocalcemic magnesium-deficient patients. The reason why these responses are intact while PTH secretion and action are impaired is unknown but may be accounted for by differing magnesium requirements of the adenylate cyclase complex in these tissues.

Adrenocorticotropic Hormone↗
PubMed1982

Heterogeneity of immunoreactive calcitonin in extracts of medullary thyroid carcinoma.

Tumor extracts from 9 patients with medullary thyroid carcinoma were studied to determine if multiple forms of immunoreactive calcitonin existed within the tumors. Calcitonin was extracted from the tumors with 0.1 N formic acid and the extracts were evaluated by gel filtration on columns of Bio-Gel P-10 and radioimmunoassay of the fractions obtained. Serum calcitonin concentrations were high enough in 3 patients to allow for similar evaluation. Four immunoreactive peaks of calcitonin were found after chromatography of the tumor extracts. Three of the peaks eluted earlier than monomer human calcitonin. 6 tumor extracts contained all four immunoreactive peaks while 3 had only two. In 2 patients four immunoreactive peaks of calcitonin were found in both the serum and the tumor extracts while 1 patient had three peaks in the serum but only two peaks were detected in the tumor extract.

Adrenocorticotropic Hormone↗
PubMed1981

Bone resorption and humoral hypercalcemia of malignancy: stimulation of bone resorption in vitro by tumor extracts is inhibited by prostaglandin synthesis inhibitors.

Extracts of tumors from patients with humoral hypercalcemia of malignancy (HHM) were tested using an in vitro bone resorption assay in order to investigate the pathogenesis of the hypercalcemia. Bone resorption was assessed by comparing the percent release of previously incorporated 45Ca from paired halves of newborn mouse calvaria. Saline extracts of three out of five tumors from HHM patients caused a significant increase in 45Ca release relative to controls. Extracts of liver and non-HHM tumor did not cause significant resorption. Tumor-stimulated bone resorption was blocked by indomethacin and eicosatetraynoic acid, inhibitors of the synthesis of prostaglandins (PGs) and related metabolites of arachidonic acid, whereas resorption stimulated by parathyroid hormone (PTH), PGE2, or 1,25-(OH)2D3 was not. Furthermore, levels of immunoreactive PTH or PGE2 in tumor extracts were not sufficient to account for the degree of resorption observed. These observations indicate that PTH or PGE2 are not responsible for the bone resorption caused by extracts of tumors from these patients with HHM. Furthermore, they suggest that hypercalcemia in these patients may result from bone resorption stimulated by the local production in bone of PGs or related metabolites of arachidonic acid in response to a humoral factor elaborated by the tumor.

Adult↗
PubMed1980

Renal tubular maximum for magnesium in normal, hyperparathyroid, and hypoparathyroid man.

Magnesium infusions were carried out in normal subjects and patients with hypoparathyroidism and primary hyperparathyroidism in order to determine if a tubular maximum for magnesium (TmMg) existed in man and what influence endogenous parathyroid hormone played in renal magnesium handling. The increase in the serum ultrafiltrable magnesium concentration during the magnesium infusions resulted in an increase in urinary magnesium excretion. A TmMg of 1.4 mg/100 ml GF/1.73 m2 was found in the normal subjects under basal conditions. Similarly, TmMg values of 1.4 and 1.3 mg/100 ml GF/1.73 m2, were found in hypoparathyroid and primary hyperparathyroid subjects, respectively. Both were present under basal conditions and neither differed significantly from normal. It is concluded that a TmMg is present in man and that endogenous parathyroid hormone does not appear to play a significant physiological role in renal magnesium homeostasis.

Adult↗
PubMed1978

Parathyroid hormone secretion in magnesium deficiency.

The effect of an acute elevation of the serum magnesium concentration on the concentrations of serum immunoreactive parathyroid hormone (IPTH) were studied in hypocalcemic hypomagnesemic patients, hyperparathyroid patients, and normal individuals. Basal serum IPTH concentrations in the hypomagnesemic patients ranged from undetectable to 3 times the upper limit of normal. All hypomagnesemic patients were observed to have an immediate rise in the serum IPTH concentration after magnesium administration regardless of the basal IPTH concentration. In contrast, normal individuals and patients with primary and secondary hyperparathyroidism responded to magnesium administration with either a decrease or little change in the serum IPTH concentration. These date indicate that an acute stimulation of PTH secretion induced by magnesium is characteristic of the magnesium-deficient state. The consistency of this response suggests that impaired PTH secretion is a significant factor contributing to the hypocalcemia of magnesium deficiency.

Calcium↗
PubMed1977

Comparison of serum calcitonin levels after a 1-minute calcium injection and after pentagastrin injection in the diagnosis of medullary thyroid carcinoma.

A 1-min calcium injection was compared with a pentagastrin injection as provocative measures in stimulating calcitonin secretion in 4 patients with medullary thyroid carcinoma. In all cases the calcium injection resulted in a greater rise in serum calcitonin concentration. The patients tolerated the calcium injection well. However, two patients experienced substernal pressure and dyspnea following the pentagastrin injection. It is concluded that a 1-min calcium injection is a safe, rapid and effective procedure in the diagnosis of medullary thyroid carcinoma.

Calcitonin↗