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Biomedical subjects

F R Singer

Publications and source records attributed to F R Singer.

At least 109 records · Page 6Linked to original sources

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↗

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↗

Radiographic and radionuclide imaging in multiple myeloma: the role of gallium scintigraphy: concise communication.

Eighteen patients with multiple myeloma were studied using radiographs of the skeletal system, technetium phosphate bone scans, and gallium-67 scintigraphy. A total of 94 sites were used as the basis for comparison in these 18 patients. Radiographic sensitivity on a patient basis was 94%, and was 82% on a site basis. Bone scans were positive in 78% of patients and in 46% of sites. Gallium scans were positive in 56% of patients and 40% of sites. In five of the 18 patients, gallium scans showed activity in abnormal sites with a greater lesion-to-nonlesion ratio than did the bone scan. In this subgroup of patients, the disease was fulminant, and all died within 3 mo of their study. The finding of high gallium uptake in osseous sites that are normal or only slightly abnormal on bone scan has served to identify a subgroup of patients with rapidly progressive disease who may benefit from alternative treatment modalities such as radiation therapy.

Bone Neoplasms↗

Cell cultures from bone affected by Paget's disease.

Cells obtained from Paget's bone specimens were maintained in culture for up to 8 1/2 months. The cells had several characteristics of bone cells including the presence of alkaline phosphatase, acid phosphatase, or succinic dehydrogenase as demonstrated histochemically. Electron microscopy revealed nuclear inclusions similar to those found in the osterclasts of Paget's disease in 4 or 11 cultures. Immunohistology utilizing specific antisera demonstrated the presence of respiratory syncytial virus antigen(s) in 7 or 7 patients. Negative results were obtained with antisera to a variety of paramyxoviruses.

Aged↗

Salmon calcitonin therapy for Paget's disease of bone. The problem of acquired clinical resistance.

During the initial months of long-term treatment of Paget's disease of bone with salmon calcitonin, circulating alkaline phosphatase activity and urinary hydroxyproproline excretion usually decrease by about 50%. In 22 of 85 patients these parameters returned to pretreatment levels despite continuous therapy. Nineteen patients who were resistant to salmon calcitonin had salmon calcitonin antibodies in high titer. Human calcitonin has been effective in suppressing disease activity in these patients. The pathogenesis of calcitonin resistance in patients without antibodies is unknown.

Aged↗

Intestinal calcium absorption in patients with hyperthyroidism.

Intestinal 47Ca absorption was measured at 2 and 24 h after isotope ingestion in six patients with hyperthyroidism and seven normal subjects. Although 47Ca absorption was not different at 2 h, it was significantly lower (P < 0.01) after 24 h in the patients with hyperthyroidism. Factors related to the effects of thyroid hormone on intestinal function, in addition to abnormalities of vitamin D metabolism, are probably responsible for the defect.

Adult↗

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↗

Gallium scanning in Paget's disease of bone: effect of calcitonin.

Calcitonin has been used in the treatment of Paget's disease of bone, and serum alkaline phosphatase level and 24 hr urinary hydroxyproline excretion have been used to follow therapeutic response. The radionuclide bone scan has been used as a visual indicator; however, there is some uncertainty as to its value in following changes in disease activity. Four patients with both serial technetium phosphate bone scans and serial gallium studies were studied. In each case the beneficial effect of calcitonin was demonstrated more accurately with gallium than with technetium diphosphonate. Since biochemical changes in Paget's disease are believed to be mediated at the cellular level and gallium uptake depends on cellular activity, it is proposed that gallium uptake is a more appropriate measure of the activity of Paget's disease than a noncellular marker such as a technetium-containing bone scan agent.

Calcitonin↗

Effects of long-term therapy with calcitriol in patients with moderate renal failure.

Since abnormalities in divalent ion metabolism occur early in renal insufficiency, treatment of patients with moderate renal failure with calcitriol could halt and/or reverse these disturbances. The effects of long-term treatment with calcitriol (0.5 microgram/day) in three such patients were evaluated. Serum calcium level rose from 0.3 to 0.7 mg/dL. Blood parathyroid hormone levels were mildly elevated and fell to normal. Intestinal absorption of calcium increased. The patients had hypocalciuria and the urinary calcium level increased. Creatinine clearance remained stable in all patients. Iliac crest biopsy specimens obtained after double tetracycline hydrochloride labeling revealed mild osteomalacia and hyperparathyroid bone disease that healed after therapy. The data show that a small dose of calcitriol is safe and effective for the management of the derangements of divalent ion metabolism in patients with moderate renal failure.

Adult↗

Long-term culture of cells from bone affected by Paget's disease.

Cells obtained from surgical bone specimens of eight patients with Paget's disease of bone were maintained in culture for up to 8 months and seven passages. The doubling time during the period of maximal cell growth ranged from 4 to 12 days. Evidence consistent with the hypothesis that many of the cells were bone cells included the following: (a) histochemical techniques demonstrated staining of some cells for alkaline phosphatase or acid phosphatase and succinic dehydrogenase; (b) parathyroid extract stimulated increased uptake of 3H-thymidine and 3H-uridine; (c) parathyroid extract suppressed and salmon calcitonin stimulated uptake of 3H-proline; and (d) crystalline calcium deposits were found within cells and extracellularly. Ultrastructural analysis revealed that three of the eight cultures contained cells whose nuclei had inclusions which were almost identical to those found in the osteoclast nuclei of all patients with Paget's disease. The maintenance of cells derived from pagetic bone in long-term culture should aid in testing the hypothesis that Paget's disease represents a slow virus infection of bone.

Aged↗

Parathyroid hormone clearance in man.

The role of the kidney, liver, and bone and/or muscle, in the metabolic clearance of parathyroid hormone (PTH), has been examined in man. Serum was obtained from the femoral artery and the renal, hepatic, and femoral veins of nine hyperparathyroid patients undergoing selective venous catheterization. The concentration of immunoreactive parathyroid hormone (IPTH) was measured in the samples by radioimmunoassay using an antiserum predominantly specific for the aminoterminal (N-terminal) portion of the PTH molecule. Gel filtration of hyperparathyroid sera demonstrated this antiserum to measure essentially only intact PTH. The mean arteriovenous (AV) difference measured across the liver was 44%; across the kidney, 34%; and across the leg, 16%. These arteriovenous differences were all statistically significant (p less than 0.005). A significant positive correlation was found between the AV difference in IPTH across the kidney and the serum calcium concentration (r = 0.50, p less than 0.05). These studies suggest that both the liver and the kidney play major roles in the clearance of PTH in man and indicate that PTH is cleared by bone and/or muscle as well. The correlation observed between the serum calcium concentrations and the AV differences in IPTH across the kidney suggest that the rate of clearance of PTH in man may be modulated by changes in the concentration of serum calcium.

Adult↗

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↗

Osteotomy for tibia vara in Paget's disease under cover of calcitonin.

Five women with Paget's disease of the tibia were seen with pain in the knee, ankle, or both, as well as with tibial bone pain. All had tibia vara and internal torsion of the tibial shaft. Osteotomy to correct the deformities was preceded by a course of calcitonin which relieved the bone pain but did not relieve the articular pain. Relief after satisfactory correction of the tibial deformity was achieved in all patients. Calcitonin effectively minimized bleeding at the osteotomy site and complications were not encountered.

Aged↗