Biomedical subjects

J F Tohme

Publications and source records attributed to J F Tohme.

4 recordsLinked to original sources

PubMed1997

Tumor-induced osteomalacia: clinical and basic studies.

A patient with classic clinical and biochemical features of tumor-induced osteomalacia (hypophosphatemia, phosphaturia, and undetectable serum concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D]) was studied before and after resection of a benign extraskeletal chondroma from the plantar surface of the foot. Presurgical laboratory evaluation was notable for normal serum concentrations of calcium, intact parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), and osteocalcin, increased serum alkaline phosphate activity, and frankly elevated urinary cyclic adenosine monophosphate (cAMP) and pyridinium cross-link excretion. Quantitative histomorphometry showed severe osteomalacia and deep erosions of the cancellous surface by active osteoclasts. After resection, serum 1,25(OH)2D normalized within 24 h, while renal tubular phosphorus reabsorption and serum phosphorus did not normalized until days 2 and 3, respectively; serum Ca declined slightly, and serum intact PTH, osteocalcin, and urinary pyridinium cross-link excretion increased dramatically. Urinary cAMP excretion declined immediately after resection and then began to increase concomitant with the increase in serum intact PTH. A second bone biopsy taken 3 months after resection demonstrated complete resolution of the osteomalacia, increased mineral apposition rate (1.09 mu/day), resorption surface (9.2%), mineralizing surface (71%), and bone formation rate (0.83 mm3/mm2/day), and marked decrease in cancellous bone volume (13.1%) and trabecular connectivity compared with first biopsy. Tumor extracts did not affect phosphate transport in renal epithelial cell lines or 1 alpha-hydroxylase activity in a myelomonocytic cell line. The patient's course suggests that the normal 1,25(OH)2D and phosphorus metabolism is due to a tumor product that may be acting via stimulation of adenylate activity. Increased bone resorption prior to surgical resection suggests that the tumor may also produce an osteoclast activator. The rise in resorption surface and pyridinium cross-link excretion, increase in serum osteocalcin and bone mineralization, normalization of osteoid width, and fall in cancellous bone volume after resection are consistent with healing of osteomalacia by rapid remodeling.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed1993

Hypocalcemic emergencies.

The approach to the hypocalcemic patient is best considered with due regard to the underlying etiology and the extent to which features of hypocalcemia are present. When hypocalcemia is a medical emergency, aggressive but judicious measures must be taken immediately to correct, in part, the hypocalcemia. Parenteral therapy of hypocalcemia is advisable only under these conditions. The aim of acute management is not to return the serum calcium to normal but rather to ameliorate the acute manifestations of hypocalcemia. If the hypocalcemic state is owing to a chronic condition that will not remit, a plan for long-term management with a vitamin D preparation and calcium supplementation is implemented after the emergency therapy is provided.

Emergencies↗

PubMed1990

Suppression of parathyroid hormone secretion with oral calcium in normal subjects and patients with primary hyperparathyroidism.

Exquisite sensitivity of normal parathyroid glands to small changes in ambient calcium concentrations and impaired sensitivity in primary hyperparathyroidism have been shown in vitro. Using an assay for PTH that detects rapid changes in PTH secretion (N-terminal-specific RIA; normal range, less than 3-33 pg/mL), we determined PTH suppressibility in response to a standardized dose of oral calcium in normal subjects and patients with primary hyperparathyroidism. Nine normal subjects were given oral calcium (25 mg/kg), and blood was analyzed half-hourly for 3 h for calcium and N-terminal PTH (N-PTH). Serum calcium rose by 0.34 +/- 0.06 mg/dL (0.085 +/- 0.015 mmol/L), and N-PTH levels declined rapidly from 15.3 +/- 1.4 to 4.2 +/- 1.1 pg/mL (-73 +/- 6%; P less than 0.01). In six subjects N-PTH concentrations became undetectable. Nine patients with primary hyperparathyroidism were tested in the same manner. Serum calcium rose by 0.53 +/- 0.1 mg/dL (0.13 +/- 0.025 mmol/L), and N-PTH levels declined less, from 66 +/- 14 to 52 +/- 12 pg/mL (-21 +/- 4%; P less than 0.05). In none of the patients was the PTH reduced to less than 20 pg/mL. These results illustrate in vivo that the PTH response to oral calcium in primary hyperparathyroidism is markedly different from that in normal subjects.

Administration, Oral↗

PubMed1990

Estrogen treatment of patients with established postmenopausal osteoporosis.

We conducted a controlled study of the effects of oral estrogen therapy in postmenopausal women with established postmenopausal osteoporosis. Bone mass was measured in the lumbar vertebrae and hip using dual photon absorptiometry. Both estrogen-treated women and the control group received calcium supplements to bring total intake to approximately 1500 mg/day. For those women with an intact uterus in the estrogen wing of the study, a progestin was added to the therapy for 12-14 days each calendar month. The number of years from menopause was 14.6 +/- 0.9 in the estrogen-treated group and 13.7 +/- 1.1 in the calcium-treated group. Estrogen treatment was associated with increased vertebral bone mass by dual photon absorptiometry during the 2 years of the study (+10.6%; P less than .01). There was also an increase in bone density at the femoral neck (+5.5%; P less than .1), but the difference from the initial value was not statistically significant. The group given calcium alone lost bone at both sites, although the loss was not statistically significant at either site. The response to estrogen was greatest in those who were furthest from menopause (r = 0.38, P less than .05) and consequently among those who had the lowest bone mass (r = -0.34, P less than .05). Estrogen therapy appears to be an effective therapy for patients with established osteoporosis. Intervention is associated with a significant increase in bone mass compatible with reduced skeletal turnover and activation frequency.

Alkaline Phosphatase↗