Biomedical subjects

B H Mitlak

Publications and source records attributed to B H Mitlak.

5 recordsLinked to original sources

PubMed1992

Intermittent administration of bovine PTH-(1-34) increases serum 1,25-dihydroxyvitamin D concentrations and spinal bone density in senile (23 month) rats.

We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p less than 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p less than 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p less than 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p less than 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p less than 0.05) over the 3 weeks of the study despite a gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1991

Pamidronate reduces PTH-mediated bone loss in a gene transfer model of hyperparathyroidism in rats.

We evaluated spinal and femoral bone mass and density utilizing dual-energy x-ray absorptiometry (DEXA) in rats in which severe hyperparathyroidism was produced by the expression of the gene for human PTH-(1-84) (hPTH). This gene was incorporated into a retroviral vector that was transfected into fibroblasts which were subsequently injected into their peritoneal cavities. Further, we examined the effect of the administration of pamidronate on bone mass and density in the presence of extremely high concentrations of hPTH. Three groups of rats were studied. Groups 1 and 2 receive the hPTH-secreting fibroblasts; group 2 subsequently received pamidronate (2.5 mg/kg IV) 18 and 27 days after receiving the fibroblasts. These animals developed levels of hPTH greater than 1.0 microgram/liter and became hypercalcemia within 20 days. These animals became lethargic and were significantly lower in weight than age-matched controls (group 3, p less than 0.05). After accounting for the animal weight there was a further significant decrease in bone mineral content and density (BMC and BMD) on day 29 attributable to hPTH-mediated bone loss. Treatment with pamidronate resulted in a higher BMC of the lumbar spine than in the untreated animals, with elevated concentrations of hPTH. The BMD was significantly higher at both the lumbar spine and femur in the pamidronate-treated animals (p less than 0.05). The CV of paired measurements of BMD was 2.7% at the spine and 1.5% of a femur, respectively. The BMC of the lumbar spine and femur was closely correlated with the ashed weight of the same bones (r = 0.92 and 0.85, respectively).

Absorptiometry, Photon↗

PubMed1991

Asymptomatic primary hyperparathyroidism.

Of 118 consecutive white patients referred for asymptomatic primary hyperparathyroidism, the diagnosis was clinically confirmed in 100, of whom 85 adults had a serum calcium less than 3.0 mM (12 mg/dl) and no skeletal, rheumatic, or significant neuropsychiatric symptoms, azotemia, or other significant illnesses. Among these 85, 68 had both asymptomatic and medically uncomplicated hyperparathyroidism, whereas 17 had historical, radiographic, or ultrasonic evidence of renal stone disease. The 20% with past or present renal calculi concentrated their urine significantly better than the 68 others (p = 0.05), but these two groups were otherwise not distinguished by the tests we performed, so all 85 patients were analyzed together. Systolic and diastolic blood pressures were normal, but premature osteopenia and/or impaired renal function were present in 29-36% of the patients. Micrometer measurements of metacarpal radiographs and 125I photon absorptiometry at the shaft of the radius revealed cortical osteopenia. Osteopenia was equally significant in the distal radius (cortical plus trabecular bone). These quantitative measurements were superior to routine bone radiography, and ROC analysis showed that 125I absorptiometry at either site was superior (p less than 0.01) to metacarpal cortex measurements for detecting premature osteopenia, which was present in more than a third of these patients. Creatinine clearances (24 h) and maximum urine concentrating capacity (overnight dehydration plus the synthetic vasopressin analog DDAVP) were each significantly reduced, despite all patients' normal BUN and serum creatinine levels. Sequential performance of a 24 h creatinine clearance and a urine concentration test revealed abnormalities in the renal function of 27 of 74 patients (36%), with a specificity of 95% and a higher sensitivity than either test alone (27-29%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Parathyroid hormone-related peptide mediates hypercalcemia in an islet cell tumor of the pancreas.

Hypercalcemia occurring in a patient with an islet cell carcinoma of the pancreas suggests the diagnosis of Multiple Endocrine Neoplasia Type I and associated hyperparathyroidism. We describe a patient with an islet cell carcinoma and hypercalcemia in whom low concentrations of PTH, the absence of skeletal metastases, hypophosphatemia, and elevated nephrogenous cAMP alternatively suggested the syndrome of humoral hypercalcemia of malignancy. The peptide PTHrP was measured in the patient's serum during the course of therapy by an immunoradiometric assay directed toward the midportion of the molecule. Hypercalcemia was treated with an investigational aminobisphosphonate. The concentration of PTHrP[56-86] increased over time and fell after the patient received chemotherapy directed toward the islet cell tumor.

Adenoma, Islet Cell↗

PubMed1991

Parathyroid function in normocalcemic renal transplant recipients: evaluation by calcium infusion.

The extent to which secondary hyperparathyroidism may involute remains poorly defined. Renal transplantation offers a clinical situation in which metabolic stimuli for hyperparathyroidism are removed. To examine whether hyperparathyroidism resolves after transplantation, we evaluated 11 renal transplant recipients who had been normocalcemic 6 or more months after transplantation using a sensitive 2-site immunoradiometric assay for intact serum PTH. Nine of the 11 had PTH concentrations within the normal range. Of these 9, 6 were found to have abnormal parathyroid function when challenged with an iv calcium infusion. The other 2 patients demonstrated significantly elevated basal PTH concentrations and elevated ionized calcium despite normal total serum calcium and albumin concentrations. In both, the PTH response to infused calcium was markedly abnormal, confirming hyperparathyroidism. The estimated renal threshold phosphate concentration was low in 4 of 9 patients with normal basal PTH concentrations and in both with elevated basal PTH. Bone mineral density, measured at the radius by single photon absorptiometry and at the spine by dual energy x-ray absorptiometry, was normal in 8 of the 9 transplant recipients who had normal basal PTH concentrations.

Adult↗