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Biomedical subjects

M Attie

Publications and source records attributed to M Attie.

12 recordsLinked to original sources
PubMed1996

Effects of isotretinoin on bone mineralization during routine therapy with isotretinoin for acne vulgaris.

OBJECTIVE: To examine the effects of isotretinoin on bone mineralization and other markers of calcium homeostasis in individuals receiving isotretinoin for routine therapy for severe acne vulgaris. DESIGN: Cohort study. SETTING: An academic medical center. PATIENTS: Twenty individuals receiving isotretinoin for severe acne vulgaris. INTERVENTION: None. MAIN OUTCOME MEASURE: The primary outcome was the change in bone mineralization as measured by dual-energy x-ray absorptiometry of the lumbar spine and hip before and after isotretinoin therapy. Additional measurements included serum osteocalcin, calcium, 25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, and intact parathyroid hormone and urine hydroxyproline or calcium. RESULTS: No changes were noted in bone mineralization of the lumbar spine or hip. Furthermore, no alterations were noted in serum measurements of osteocalcin, calcium, 25-dihydroxyvitamin D, intact parathyroid hormone, or urine measurements of hydroxyproline or calcium. A statistically significant change was noted in 1,25-dihydroxyvitamin D when serum from before and after isotretinoin therapy was compared. CONCLUSION: The use of isotretinoin for 20 weeks for the treatment of severe acne vulgaris does not appear to have any substantial adverse effect on bone mineralization.

Acne Vulgaris↗
PubMed1991

Trabecular structure: preliminary application of MR interferometry.

A new approach to probe the structure of trabecular bone in the vertebral bodies in humans was evaluated, and preliminary data are presented. The proposed method is based on the hypothesis that the presence of two physical phases--bone and bone marrow--causes a magnetic field distribution across the imaging voxel. The resulting spread in resonance frequency produces line broadening, which is measured as the decay rate of the region of interest signal intensity that has the properties of an interferogram. The interferogram is the result of two principal chemically shifted components of bone marrow--fat and water--getting in and out of phase with one another while being attenuated by T2* processes from the magnetic field distribution within the measuring volume. The time constant for the decay (T2*) can then be obtained by means of curve-fitting techniques. T2* in healthy persons is found to increase slightly with age. However, patients with osteoporosis (low bone mineral density and/or spine compression fractures) have significantly prolonged T2* values, which are interpreted as arising from an increase in the intertrabecular space.

Adolescent↗
PubMed1989

Quantitative computed tomography reflects vertebral fracture morbidity in osteopenic patients.

We studied the relationship between spontaneous vertebral compression fractures and lumbar vertebral trabecular bone density in 69 consecutive patients with suspected osteopenia. Seven had biopsy-confirmed osteomalacia. The remaining 62 were divided into three groups: group 1--asymptomatic patients suspected of having osteopenia on plain films, but with no vertebral compression fractures (N = 24); group II--those with one to five vertebral compression fractures (N = 16); and group III--those with six or more vertebral compression fractures (N = 22). A quantitative computed tomographic (QCT) scan of the lumbar spine was performed on all patients. Patients in group I had QCT values of 94 +/- 23 mg/cm3 (mean +/- SE); those in group II had QCT values of 66 +/- 28 mg/cm3; and those in group III had values of 34 +/- 28 mg/cm3. There were significant differences among all groups (P less than .001), although there was considerable overlap of individuals among the groups. There was no significant difference between the mean QCT value of patients with one compression fracture and the value of those with between two and five compression fractures. Patients with biopsy-proven osteomalacia had higher vertebral trabecular bone density than patients with osteoporosis and compression fractures. Our study provides evidence suggesting a strong inverse relationship between QCT-measured vertebral bone density and the presence of vertebral compression fractures in a group of osteopenic patients.

Absorptiometry, Photon↗
PubMed1987

Quantitative autoradiography of parathyroid glands in rats with carbon-14-labeled amino acids.

We have utilized a quantitative autoradiographic method as a means of evaluating amino acid uptake of the rat parathyroid gland for the ultimate purpose of finding agents potentially suitable for position emission tomographic scanning of parathyroid glands. L-[1-14C]leucine and L-[guanido-14C]arginine were evaluated because of their relatively high content in the synthetic products of the parathyroid glands compared with other neck tissues, thyroid gland, and muscle. Carbon-14 leucine disappeared rapidly from plasma following intravenous injection and there was relatively selective uptake of the [14C]leucine and [14C]arginine by the parathyroid glands when compared with uptake by the thyroid gland and neck muscle. These data suggest that both agents warrant further investigation for their potential utility in positron emission tomographic scanning of the parathyroid gland.

Amino Acids↗
PubMed1985

Treatment of hypercalcemia in parathyroid cancer with WR-2721, S-2-(3-aminopropylamino)ethyl-phosphorothioic acid.

The chemoprotective and hypocalcemic agent WR-2721, S-2-(3-aminopropylamino) ethyl-phosphorothioic acid, inhibits parathyroid hormone secretion in vivo and in vitro. We report the first clinical use of WR-2721 in refractory hypercalcemia secondary to parathyroid cancer. After several days of saline diuresis the patient received WR-2721, 740 mg/m2 over 15 minutes, resulting in a fall in serum calcium from 11.76 to 9.06 mg/dL within 24 hours. Serum parathyroid hormone levels decreased from 675 to 140 microLeq/mL 2 hours after the infusion was complete. When hypercalcemia recurred the patient was retreated with differing doses and infusion rates to determine the optimal method of drug administration to provide a satisfactory hypocalcemic response without adverse effects. In this patient, WR-2721 in intravenous boluses of 150 mg/m2 was effective without adverse effects. Using high-pressure liquid chromatography with electrochemical detection, plasma pharmacokinetic studies showed that WR-2721's distribution half-life is 0.55 minutes.

Adenoma↗
PubMed1983

Hypocalcemia and inhibition of parathyroid hormone secretion after administration of WR-2721 (a radioprotective and chemoprotective agent).

We investigated the causes of the hypocalcemia associated with WR-2721, an investigational drug that protects normal tissues against the toxic effects of radiation and chemotherapy. Sixteen patients with advanced cancers had serial measurements of serum calcium and other studies of blood chemistry before and after taking the compound. In all 16 patients (18 courses) the mean serum calcium level fell from 2.33 to 1.90 mmol per liter (9.33 to 7.62 mg per deciliter, P less than 0.001) after WR-2721, and in all 8 patients from whom data were obtained, serum calcium levels remained depressed at 24 hours. In 12 patients, ionized calcium levels dropped from 0.98 to 0.80 mmol per liter (P less than 0.01). Serum magnesium values fell from 0.96 to 0.74 mmol per liter (1.91 to 1.48 mg per deciliter, P less than 0.001). There were no changes in arterial pH or serum phosphate concentrations. In nine patients urinary calcium excretion rose from 3.96 to 10.68 mumol per minute (P less than 0.01) after WR-2721. Despite hypocalcemia, parathyroid hormone levels fell in all subjects. WR-2721 also inhibited the release of parathyroid hormone from bovine parathyroid cells incubated in vitro in low (0.5 mM) concentrations of calcium. We conclude that WR-2721 inhibits the secretion of parathyroid hormone and enhances calciuria, thereby leading to hypocalcemia.

Amifostine↗
PubMed1978

Circulating parathyroid hormone activity: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism.

Three indices of circulating parathyroid hormone (PTH) activity were compared between two groups: the first a group of 23 patients from three large kindreds with autosomal dominant hypercalcemia without hypercalciuria [familial hypocalciuric hypercalcemia (FHH)] and the second a group of 64 patients with typical primary hyperparathyroidism (1HPT) manifesting comparable hypercalcemia. The group with 1HPT differed from normal with respect to plasma PTH 1HPT concentration (normal, less 0.2 ng/ml), urinary cAMP excretion per 100 ml glomerular filtrate (U cAMP/GF) (normal, 2.3 x/divided by 0.6 nmol/100 ml glomerular filtrate; mean, x/divided 1 SD), and renal tubular maximum of phosphate transport corrected for glomerular filtration rate (TMP/GFR; normal, 3.4 +/- 0.4 mg/dl; mean, +/- 1 SD). The group with 1HPT also diverged significantly from the group with FHH for all three indices: for PTH, 0.37 x/divided by .48 vs. 0.25 x/divided .46 (P less than 0.05); for UcAMP/GF, 4.3 x/divided by .53 vs. 2.6 x/divided .60 (P less than 0.0005); and for TMP/GFR, 2.0 +/- 0.6 vs. 2.6 +/- 0.7 (P less than 0.01). The between-group differences for all three indices were also significant after adjustment for their variation with serum calcium. However, only the difference in TMP/GFR remained significant after adjustment for covariance attributable to serum calcium concentration, age, and creatinine clearance. The group with FHH differed from normal for TMP/GFR but not for UcAMP/GF. However, analysis of changes in UcAMP/GF and serum calcium concentration around the time of parathyroidectomy in three patients with FHH suggested that the parathyroid glands contributed to the abnormalities of mineral homeostasis in at least one. It was concluded that higher serum concentrations of PTH do not account for the lower renal clearance of calcium and magnesium in FHH calcium concentration, the group with FHH showed indices suggesting lower circulating PTH activity than the group with 1HPT.

Calcium↗
PubMed1978

A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D.

Typical features of hereditary vitamin D-dependent (pseudovitamin D-deficient) rickets were observed beginning at ages 20 and 5 months in a brother and sister. Both had calcium malabsorption correctable with high doses of 25-hydroxyvitamin D. During periods of hypocalcemia they both manifested secondary hyperparathyroidism with hypophosphatemia and high serum concentrations of endogenously produced 1,25-dihydroxyvitamin D. In each, normalization of serum calcium concentration and resolution of osteomalacia were obtained with continuous administration of high doses of ergocalciferol or high doses of 1,25-dihydroxycholecalciferol. Chemical features of vitamin D deficiency were corrected in the presence of high circulating concentrations of 1,25-dihydroxyvitamin D2, produced endogenously, or of 1,25-dihydroxyvitamin D3, administered by mouth. Serum concentrations of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal in five first degree relatives. We conclude that in these five first degree relatives. We conclude that in these siblings, rickets and osteomalacia resulted from a hereditary decreased sensitivity to 1,25-dihydroxyvitamin D at the intestine and perhaps other vitamin D target tissues.

Absorption↗