A research paradigm for the study of personality and emotions.
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Biomedical subjects
Publications and source records attributed to S Epstein.
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To determine the relationships among bone mass, bone growth and serum glucose control in young, insulin-dependent diabetics, we performed photon absorptiometry and radiogrammetry on a clinically well-characterized group of 78 diabetics (mean age 15.2 yr, mean duration of diabetes 6.7 yr). Total and ionized calcium (TCa, ICa), magnesium (Mg), immunoreactive parathyroid hormone (iPTH) and phosphorus (P) were measured in fasting serum. Bone age was calculated from hand x-rays; and bone measurements, heights, and weights were standardized against normal groups of corresponding age, sex, and race. Mean deviation of bone mass measurement score was 1.24 SD below the normal mean (p less than .001); mean cortical area score was .22 SD and percent cortical area .25 SD below the normal means (both p less than .05). Radical width and metacarpal width for the diabetics were not less than normal. Mean percentiles for height and weight were 52.3 and 57.1 respectively, the latter significantly elevated (p less than .02). Bone mass and cortical area were inversely related to duration of disease (r = -.228, p less than .05; r = -.216, p less than .05). They were not correlated with serum parameters of mineral metabolism or of glucose control. Bone age was not significantly different from chronological age in those who had not achieved maturity (14.4 versus 14.5 yr). Mean age of menarche was 12.9 yr. When compared to normals the diabetic sample had diminished serum ICa (p less than .001), and Mg (p less than .001), though P and iPTH were not significantly different. We have demonstrated: (1) bone mass in this sample of juvenile diabetics is depressed, without evidence of impaired overall growth or delayed maturation, (2) this reduced bone mass probably results from a failure to gain the normal component of endosteal bone expected at this age, (3) this abnormality in bone growth progresses with disease but does not appear to vary with serum glucose control, and (4) in this population of diabetics there is a minimal but significant reduction in serum total and ionized calcium and serum magnesium without compensatory elevation of parathyroid hormone. The relationship of this metabolic abnormality of impaired bone growth in unknown.
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The effects of vitamin D, 2.5 mg (100,000 U)/d for 4 d, on serum calcium, serum 25-hydroxyvitamin D (25-OHD) and serum 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25(OH)2D) were compared in 24 normal adults and 12 normal children. The daily dose of vitamin D was 1,500 U/kg body wt in children weighing less than 45 kg. Vitamin D increased mean serum calcium from 9.5 +/- 0.1 to 9.8 +/- 0.1 mg/dl (P less than 0.05), increased mean serum phosphorus from 4.6 +/- 0.1 to 5.0 +/- 0.1 mg/dl (P less than 0.01), increased mean serum 25-OHD from 25 +/- 3 to 34 +/- 4 ng/ml (P less than 0.001), and increased mean serum 1 alpha, 25(OH)2D from 34 +/- 3 to 42 +/- 4 pg/ml (P less than 0.02) in children. In contrast, vitamin D increased mean serum 25-OHD from 18 +/- 2 to 39 +/- 6 ng/ml (P less than 0.001) and did not change mean serum calcium (9.4 +/- 0.1 vs. 9.5 +/- 0.1 mg/dl), mean serum phosphorus (4.0 +/- 0.1 vs. 4.1 +/- 0.1 mg/dl), or mean serum 1 alpha, 25(OH)2D (31 +/- 2 vs. 29 +/- 3 pg/ml) in adults. Mean serum 1 alpha, 25(OH)2D was significantly higher after vitamin D in children than in adults (P less than 0.02). These results provide evidence that circulating 1 alpha, 25(OH)2D is not as tightly regulated in children as it is in adults. This difference in regulation could account in part for the higher values for serum 1 alpha, 25(OH)2D observed in children.
Osteoporosis is a clinical syndrome characterized by low bone mass and fracture, primarily of vertebrae, hip, and distal forearm. Many factors play a role in the pathogenesis of the final clinical event, the fracture. In some patients an initial deficiency or rapid loss of trabecular bone may result in vertebral collapse. In others, loss of cortical bone may result in hip fracture. Fracture itself may occur not only because of low bone mass but also because of other factors intrinsic to bone, such as accumulation of microdamage, or extrinsic to bone, such as poor coordination or frequency of trauma. The many factors that play a role in the pathogenesis of the disorder may appear confusing; however, they provide several areas in which therapeutic intervention may prove to be value to the patient.
A sensitive radio-immunoassay for parathyroid hormone (PTH) using the commercially available antisera AS 211/32 and AS 211/41 has been established. The lower limit of sensitivity of the assay is 0,25 ng/ml. Seventy-nine per cent of normal subjects have PTH levels in the measurable range, with a mean of 0,49 ng/ml (SD +/- 0,26 ng/ml). Only 1 of 9 patients with proven primary hyperparathyroidism had a normal serum PTH value. The mean serum PTH value in this group was 3,0 +/- 0,26 ng/ml, which differed significantly from that in the normal group (P < 0,001). The serum PTH level of 33 patients on chronic haemodialysis was uniformly raised, while in 8 patients with hypoparathyroidism PTH levels were undetectable. Patients with malignant disease presented a mixed picture, with raised, normal or undetectable PTH levels. We investigated a possible relationship between the gut hormones, gastrin, secretin and cholecystokinin-pancreozymin (CCK-PK) and PTH secretion in human volunteers. No effect was found, although the investigations were conducted over relatively short time periods.
Studies were carried out to compare the effects of parathyroid extract (PTE) on serum and urinary calcium (Ca) and phosphorus (P), serum 25-hydroxyvitamin D (25-OHD), serum 24,25-dihydroxyvitamin D (24,25(OH)2D), serum 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)2D), and urinary cyclic AMP in two normal subjects, two patients with hypoparathyroidism (HP) and six patients with pseudohypoparathyroidism (PHP), some of whom were on suboptimal treatment with vitamin D. Two of the patients with PHP were studied while on long-term treatment with 1 alpha,25-(OH)2D3. Before PTE, serum 1 alpha, 25(OH)2D was at the lower limit of normal in one patient and was abnormally low in the other five patients. None of these individuals was on treatment with 1 alpha,25(OH)2D3. Serum 25-OHD and 24,25(OH)2D were either increased or at the upper limit of normal in the patients given vitamin D and were normal in the other patients. PTE lowered the serum P and increased the serum 1 alpha,25(OH)2D, serum and urinary Ca, urinary P, and urinary cyclic AMP in the normal subjects and patients with HP. In individual studies, changes in serum 1 alpha,25(OH)2D and serum Ca occurred in parallel before, during, and after PTE. In contrast, PTE had very little effect in the patients with PHP. Whereas there were highly significant positive correlations between serum 1 alpha,25(OH)2D in each of the normal subjects and patients with HP, there were significant correlations in only one of the patients with PHP. An increase in serum Ca in response to PTE was observed in one of the two patients with PHP who were on long-term treatment with 1 alpha,25(OH)2D3. In these individuals, PTE produced only slight increases in serum 1 alpha,25(OH)2D. Serum 25-OHD and 24,25(OH)2D were not changed by PTE in any of the subjects or patients. The results provide evidence that hypocalcemia in HP and PHP arises in part from low circulating 1 alpha,25-(OH)2D, and indicate that the lack of change in serum 1 alpha,25(OH)2D with PTE in patients with PHP is related to impaired renal adenylate cyclase and phosphaturic responses. These and previous results support the idea that diminished renal production of 1 alpha,25(OH)2D, because of a defect in the parathyroid hormone-responsive adenylate cyclase system, may be a contributing factor in the pathogenesis of the abnormal calcium metabolism in PHP.
Somatostatin-like immunoreactivity (SRIF-LI) has previously been demonstrated immunohistochemically in rat thyroid parafollicular cells. Studies were therefore performed to determine whether SRIF-LI was present in a transplantable medullary carcinoma of the thyroid (MCT) in the WAG/Rij strain of rat. SRIF-LI was found in MCT in significantly higher concentrations than in normal thyroid tissue. Thyroid and MCT SRIF-LI showed parallelism with the synthetic SRIF and RIA displacement curves and coeluted with synthetic SRIF on immunoaffinity chromatography. On gel filtration, thyroid SRIF-LI and the major peak of MCT SRIF-LI coeluted with synthetic SRIF. SRIF-LI of a larger molecular size was also present in the MCT. MCT and thyroid SRIF-LI coeluted with synthetic SRIF on high pressure liquid chromatography. MCT SRIF-LI purified by affinity chromatography was equipotent to synthetic SRIF in inhibiting dibutyryl cAMP-stimulated GH release by rat pituitary cells in monolayer culture. Serum SRIF-LI was elevated in tumor-bearing rats and showed characteristics similar to those of MCT SRIF-LI and synthetic SRIF on affinity and high pressure liquid chromatography (HPLC). Tumor-bearing rats showed diminished secretion of insulin after orally administered glucose and impaired secretion of GH in response to pentobarbital compared to normal control rats. The results indicate that SRIF-LI is produced in excessive quantities by a transplantable rat MCT and impairs the secretion of GH and insulin. The immunological, chromatographic, and biological properties of MCT SRIF-LI suggest that it is indistinguishable from synthetic SRIF.
Passive immunization with somatostatin (SRIF) antiserum suggests that gastrin, glucagon, and calcitonin secretion may be exerted either locally by contiguity of SRIF-like immunoreactivity (SRIF-LI)-containing D cells and G (gastrin) and A (glucagon) cells (paracrine) or by an endocrine effect. To determine whether a reciprocal relationship exists in man between these peptides and SRIF-LI, the effects of pentagastrin (0.5 microgram/kg BW), glucagon (1 mg), and calcium (15 mg/kg BW) on serum SRIF-LI were examined. The coexistence of SRIF-LI and calcitonin in normal thyroid parafollicular C cells and medullary carcinoma of the thyroid prompted a study of the effects of the known secretagogues of calcitonin, calcium (15 mg/kg BW), and pentagastrin (0.5 microgram/kg BW) on serum SRIF-LI. Sixteen normal subjects, two patients with metastatic medullary carcinoma of the thyroid, and one patient who had undergone thyroparathyroidectomy were evaluated. We demonstrated that whereas both pentagastrin and glucagon significantly elevated serum SRIF-LI, calcium infusion had no effect. Basal and stimulated SRIF-LI levels in the normal controls, patients with medullary carcinoma of the thyroid, and the patient with thyroparathyroidectomy were similar. These results suggest that SRIF-LI secretion is related to stimulation by peptides produced in closely juxtaposed cells, that SRIF-LI, unlike calcitonin, may not be a serum marker for medullary carcinoma of the thyroid in man, and that little, if any, serum SRIF-LI originates in the thyroid.
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Sclerosteosis is a rare autosomal recessive condition which is characterized by excessive skeletal overgrowth, distortion of the facies, cranial nerve abnormalities and raised intracranial pressure. Syndactyly and digital malformation are associated features. Radiological examination reveals thickened sclerotic bone maximally involving the skull, including the pituitary fossa. Sclerosis and hyperostosis are present throughout the skeleton. Biochemical and endocrine tests were carred out on 3 patients with sclerosteosis in an attempt to detect any dysfunction of calcium regulation of the pituitary. Results revealed no abnormality of basal parathyroid or calcitonin secretion. Histological examination revealed quantitatively increased bone resorption in comparison with normal subjects, although the pattern resembled osteosclerosis. Regulation of growth hormone, adrenocorticotrophin, gonadotrophin and thyrotrophin function were intact. We conclude that pituitary function and calcium 'homeostasis' are normal in this disorder.
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Twelve female patients undergoing intermittent hemodialysis (HD) and 5 females posttransplantation (PT) were studied. All the HD patients had menstrual disturbances and 5 had galactorrhea. The mean basal LH level was significantly elevated (p less than .05) in patients on HD compared to normal controls, but the mean LH response to luteinizing hormone releasing hormone (LRH) was not significantly different from the control group. Mean basal FSH and the FSH response to LRH was normal. In the PT pateints the LH response to LRH was significantly greater at 120 min when compared to normal females. In the HD group the serum 17B estradiol, progesterone and testosterone levels were significantly lower than in the controls but in the PT group only testosterone levels were significantly lower. These results differ from those previously found in uremic males. Elevated prolactin levels were found in the patients on hemodialysis and correlated well with the presence of galactorrhea. These was no correlation between the elevated prolactin levels and amenorrhea in the patients on hemodialysis but one PT patient with amenorrhea had elevated prolactin levels.