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Biomedical subjects

F R Singer

Publications and source records attributed to F R Singer.

At least 91 records · Page 5Linked to original sources
PubMed1984

Serum thyroid hormone indexes in patients with primary hyperparathyroidism.

Serum total reverse triiodothyronine (rT3) levels are normal in patients with renal diseases with and without renal insufficiency but elevated in nonrenal nonthyroidal illnesses. To evaluate the role of secondary hyperparathyroidism of renal diseases in this difference, serum thyroid hormone levels were studied in 27 patients with primary hyperparathyroidism (PHP) and normal renal function. In PHP, total T3 levels were reduced (118 +/- 6 ng/dL, normal: 147 +/- 3 ng/dL) and correlated with PTH levels. Serum rT3 levels were also decreased (27 +/- 3 ng/dL, normal: 34 +/- 2 ng/dL). Values for serum total thyroxine (T4), T3 uptake ratio, free T4 index, and thyrotrophin were not altered. Serum rT3 levels were increased (63 +/- 13 ng/dL) in patients with hypercalcemia due to malignant neoplasms who had low T3 levels, undetectable PTH and normal renal function. Thus, PTH excess may be the factor responsible for the failure of rT3 levels to increase in PHP and secondary hyperparathyroidism.

Adult↗
PubMed1983

Preliminary trials with 24,25-dihydroxyvitamin D3 in dialysis osteomalacia.

Fifteen patients with dialysis osteomalacia were treated with 24,25-dihydroxyvitamin D3 in dosages up to 10 micrograms per day for two to 24 months. All had previously had no improvement during treatment with calcitriol but had been remarkably susceptible to hypercalcemia. When 24,25-dihydroxyvitamin D3 was given with either calcitriol or dihydrotachysterol, serum calcium levels were significantly lower than during treatment with calcitriol or dihydrotachysterol alone. Eight of nine patients who received combined therapy with 24,25-dihydroxyvitamin D3 and calcitriol for longer than two months had clinical improvement; six patients underwent repeated bone biopsy and showed evidence of improved bone mineralization. Patients who received 24,25-dihydroxyvitamin D3 alone did not improve clinically. Since 24,25-dihydroxyvitamin D3 appears to improve calcium homeostasis and bone mineralization in some patients with severe dialysis osteomalacia when administered with 1-hydroxylated vitamin D metabolites, further controlled studies are warranted.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Parathyroid gland responsiveness to acute hypocalcemia in dialysis osteomalacia.

The majority of chronic hemodialysis patients have elevated serum iPTH levels and bone disease characterized by osteitis fibrosa. However, a small group of patients develop osteomalacic bone disease associated with normal or slightly elevated iPTH values and a tendency to hypercalcemia which occurs either spontaneously or after treatment with small doses of vitamin D sterols. To examine the causes of the relatively low iPTH levels, we evaluated the change in serum iPTH levels that occurred in response to acute hypocalcemia, produced by dialysis using a low calcium dialysate, in 11 patients with osteomalacia and 8 control hemodialysis patients. Dialysis against a dialysate free of calcium for 60 to 90 min led to a fall in serum calcium to 7.5 +/- 0.2 and 7.2 +/- 0.2 mg/dl in the osteomalacic and control patients, respectively. Serum iPTH rose in controls from 1380 +/- 287 to 1960 +/- 287 pg/ml (P less than 0.01), whereas in patients with osteomalacia it rose from 360 +/- 58 to 507 +/- 104 pg/ml (P less than 0.05), a value only slightly above normal for this PTH assay. These data suggest that the relatively low basal levels of serum iPTH do not arise as a consequence of physiologic suppression of parathyroid gland function. This reduction in parathyroid function could contribute to the pathogenesis of low turnover osteomalacia.

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↗
PubMed1983

Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis.

Metabolism of [3H]25-hydroxyvitamin D3(25-OH-D3) was studied in primary cultures of pulmonary alveolar macrophages (PAM) from seven patients with sarcoidosis and two patients with idiopathic pulmonary fibrosis. Production of a [3H]1,25-dihydroxyvitamin D3 (1,25-[OH]2-D3)-like metabolite of [3H]25-OH-D3 was detected in lipid extracts of cells from five patients with sarcoidosis. Synthesis of this compound in vitro was limited to viable PAM and was greatest in cells derived from a patient with hypercalcemia and an elevated serum concentration of 1,25-dihydroxyvitamin D. The tritiated PAM metabolite coeluted with authentic 1,25-(OH)2-D3 in three different solvent systems on straight-phase high performance liquid chromatography (HPLC) and demonstrated binding to extracted receptor for 1,25-(OH)2-D3, which was identical to that of commercially available [3H]1,25-(OH)2-D3 of comparable specific activity. Incubation of PAM with high concentrations of 25-OH-D3 resulted in production of an unlabeled metabolite that co-chromatographed with the 3H-PAM metabolite on HPLC and that was bound with high affinity by both the specific receptor for 1,25-(OH)2-D3 and antiserum to 1,25-(OH)2-D3.

Calcifediol↗
PubMed1983

Evidence for a viral etiology of Paget's disease of bone.

Ultrastructural studies of the bone cells in patients with Paget's disease of bone have revealed the presence of nuclear and cytoplasmic inclusions that resemble the nucleocapsids of Paramyxoviridae virus. Immunocytologic studies of bone biopsy specimens and cultured bone cells have demonstrated positive responses with antisera against measles virus and/or respiratory syncytial virus. These observations suggest that Paget's disease may be a slow viral infection of bone. The exact nature of the putative viral agent has yet to be established.

Animals↗
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

Immunohistological demonstration of respiratory syncytial virus antigens in Paget disease of bone.

Respiratory syncytial virus antisera have been found to produce a positive immunohistologic response in osteoclasts in bone sections or in cells cultured from Paget disease lesions in 12 out of 12 patients tested. These experiments were carefully controlled by several means. Use of experimentally infected cells served as positive controls. Adsorption of antisera on human bone powder and KB cells did not remove the specific immunologic stain, but adsorption of the antisera by the virus did. Negative results were also obtained in osteoclasts of patients with primary or secondary hyperparathyroidism. In addition, negative results in specimens of Paget disease were found with antisera to measles; parainfluenza 1, 2, and 3; influenza A, B and C; rubella; and herpes simplex. These results are consistent with the hypothesis that the nuclear and cytoplasmic inclusions in the osteoclasts of Paget disease are a result of viral activity.

Antigens, Viral↗
PubMed1981

Calcitonin stimulates bone formation when administered prior to initiation of osteogenesis.

The influence of calcitonin (CT) on various stages of bone formation was investigated. A demineralized collagenous bone matrix-induced bone forming system in rats was used to temporally segregate chondrogenesis and osteogenesis. Administration of CT (15 Medical Research Council Units [MRCU]) daily) at the initiation of matrix-induced bone formation (BF) resulted in a 76% stimulation of BF as measured by 45Ca incorporation and alkaline phosphatase activity. This increase was due, in part, to a stimulation of cartilage and bone precursor cell proliferation monitored by the rate of [3H]thymidine incorporation and ornithine decarboxylase activity. Chondrogenesis on day 7 as measured by 35SO4 incorporation was increased by 52% with CT treatment. To rule out the possibility of a secondary response due to parathyroid hormone, similar studies were done in parathyroidectomized animals and CT stimulation of BF was still observed. However, when CT injections were started after cartilage formation (day 8) there was no stimulation of BF but a significant decrease in 45Ca incorporation was observed. These results indicate CT has two actions: (a) when CT is administered during the initial phases of bone formation, it increases BF due to a stimulation of proliferation of cartilage and bone precursor cells; and (b) when CT is administered after bone formation has been initiated, subsequent bone formation is suppressed.

Acid Phosphatase↗
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↗
PubMed1981

Vitamin-D-resistant osteomalacia in hemodialysis patients lacking secondary hyperparathyroidism.

We describe a sporadic, vitamin-D-resistant osteomalacic syndrome in 19 patients undergoing hemodialysis. The syndrome was found in less than 1.5% of patients from referring dialysis centers. All 19 patients had multiple fractures, severe myopathy, and many developed spontaneous hypercalcemia. Severe osteomalacia without evidence of secondary hyperparathyroidism distinguished this syndrome from other forms of renal osteodystrophy. Bone aluminum, measured in six patients, was greatly elevated. Therapy with calcitriol (1 alpha, 25-dihydroxycholecalciferol) lad to clinical improvement in seven patients with reduced pain and myopathy, decreased serum alkaline phosphatase, or both, but no improvement in bone histology. Patients who did not respond clinically to calcitriol developed marked hypercalcemia. The cause of this severe osteomalacia, which occurs despite normal or slightly elevated levels of serum calcium and phosphorus and fails to mineralize with calcitriol, is unclear.

Adult↗