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Biomedical subjects

H Heath

Publications and source records attributed to H Heath.

At least 181 records · Page 10Linked to original sources

Pheochromocytoma associated with hypercalcemia and ectopic secretion of calcitonin.

A 17-year-old woman manifested fever, abdominal pain, headache, and hypertension caused by a solitary, benign pheochromocytoma. She also had hypercalcemia and elevated plasma immunoreactive calcitonin levels. After removal of the pheochromocytoma, calcium and calcitonin levels returned to normal. Studies of peripheral and tumor venous blood showed no excess or ectopic parathyroid hormone secretion, but the tumor contained and secreted calcitonin. Sporadic pheochromocytoma may secrete calcitonin and cause hypercalcemia by non-parathyroid hormone-mediated mechanisms. The potential is clearly present for confusion with multiple endocrine neoplasia, type 2 (medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism).

Adolescent↗

Comparison of the effects of pentagastrin and meal-stimulated gastrin on plasma calcitonin in normal man.

We compared the effects of exogenous pentagastrin and meal-stimulated gastrin on plasma immunoreactive calcitonin (iCT) in various studies of 13 normal adult men. Bolus intravenous injection of pentagastrin (0.5 microgram/kg) produced increases of iCT in 8 of 9 men. There was a linearly increasing response of iCT concentrations to increasing doses of pentagastrin (0.0625, 0.125, 0.25, and 0.5 microgram/kg) and to achieved serum immunoreactive pentagastrin concentrations (r = 0.72, P less than 0.01). To determine the effects of endogenous gastrin upon peripheral iCT concentrations, we measured serum immunoreactive gastrin (iG) and plasma iCT in four men at frequent intervals for 240 min after ingestion of low- (100 mg) and high- (400 mg) calcium meals. Serum iG increased in all subjects, with a peak at approximately 30 min. However, plasma iCT levels were unchanged from basal throughout the study. The increase of pentagastrin (0.3 pmol/ml) which caused a barely detectable increase of iCT was five- to tenfold greater than the mean maximal increases of gastrin after low- and high-calcium meals (0.04 and 0.06 pmol/ml, respectively). These results suggest that increases of plasma iCT concentrations after administration of pentagastrin in man reflect pharmacologic phenomena and that postprandial gastrin secretion may be insufficient to affect peripheral iCT concentrations.

Adult↗

Evaluation of the mutagenic potential of mycotoxins using Salmonella typhimurium and Saccharomyces cerevisiae.

The mutagenic effects of fiteen mycotoxins on Salmonella typhimurium strains TA1535, TA1537 and TA1538 and Saccharomyces cerevisiae strain D-3 were tested. Only aflatoxin B1 and sterigmatocystin were mutagenic. Both were active against S. typhimurium strain TA1538 and S. cerevisiae strain D-3; however, both required activation by the hepatic S-9 enzyme preparation. A positive correlation between the other mycotoxins reported to be carcinogenic and the two in vitro test systems employed was not demonstrated in our hands.

Aflatoxins↗

Reduced-volume radioimmunoassays for parathyrin and calcitonin in serum, for use in pediatric and small-animal studies.

Radioimmunoassays for circulating parathyrin and calcitonin used in most laboratories require 0.6--0.7 ml of serum or plasma, or more, for assay of one hormone. Such volumes are often difficult to obtain safely or repeatedly from pediatric patients or in small-animal studies. We modified our existing procedures to markedly decrease sample and reagent requirements. All reagent volumes were proportionately reduced to one-fourth the usual (from 500 microliter final incubation volume to 125 microliter), and serum or plasma volumes from 200, 100, and 50 microliter to 50, 25, and 10 microliter. We used smaller (10.3 X 50 mm) tubes and slightly modified the separation with charcoal. Results, validated by studies in rats, showed the sensitivity to match that of the usual assays; inter- and intra-assay variance was less than 20%. Simultaneous regular- and reduced-volume assays of parathyrin in sera from 19 children gave almost identical results (r = 0.9987). Both hormones can be assayed in less than 400 microliter of serum.

Adolescent↗

Plasma calcitonin in normal man. Differences between men and women.

We measured plasma calcitonin concentrations in healthy volunteers (20 men, ages 23-45 yr, mean, 30 yr; 25 women, ages 21-46 yr, mean, 30 yr) with a radioimmunoassay capable of detecting 5 pg of calcitonin/500 mul incubation volume, or 25 pg/ml of unextracted plasma. All subjects had 4-h calcium infusion (15 mg Ca/kg), and 24 subjects had intravenous pentagastrin injection (0.5 mug/kg) on separate days. Men had higher basal plasma immunoreactive calcitonin concentrations than women (P < 0.001): mean, 49 pg/ml (range, <25-73) and 31 pg/ml (range, <25-51), respectively. 18 of the 20 men (90%) responded to induced hypercalcemia with increases in plasma immunoreactive calcitonin; only 14 of the 25 women (56%) responded. In men, the mean increase of plasma immunoreactive calcitonin+/-SE was 58+/-9 pg/ml, but for women was only 25+/-6 pg/ml. 8 of 10 men (80%) responded to pentagastrin with an increase of plasma immunoreactive calcitonin >30 pg/ml, compared with such a response in only 1 of 14 women (7%). These differences of plasma immunoreactive calcitonin responses between the sexes were statistically significant (calcium infusion, P < 0.02; pentagastrin, P < 0.001). The physiologic importance of these observations is unknown, but we speculate that a lifelong, relative deficiency of calcitonin in some women could play a role in age- and sex-related bone loss, particularly during the estrogen-deficient postmenopausal years.

Adult↗

The development of retinopathy in sucrose-fed and streptozotocin-diabetic rats.

Normal and streptozotocin-diabetic rats have been maintained for 6--11 months on completely balanced, reconstituted diets in which the sole source of carbohydrate was either 68% corn starch or 68% sucrose. The retinal vascular system was isolated by trypsin digestion and examined histologically for the presence of tortuosity and irregularity of capillary diameter, increased PAS-positive deposits, microaneurysms, loss of pericytes, endothelial proliferation, acellularity and strand formation. None of these pathological changes occurred in normal rats fed a starch-rich diet, but all developed to a similar extent in the sucrose-fed normal rats and the starch-fed diabetic group. The changes were more severe in sucrose-fed diabetic rats after 6 months. In all groups the retinopathy progressed with time. The possibility that a factor common to both the ingestion of a sucrose-rich diet and streptozotocin diabetes in rats has been considered since, histologically, the retinopathy observed was identical both with respect to severity and rate of development in normoglycaemia, sucrose-fed and hyperglycaemia, starch-fed diabetic rats.

Animals↗

The sorbitol pathway: effect of streptozotocin induced diabetes and the feeding of a sucrose-rich diet on glucose, sorbitol and fructose in the retina, blood and liver of rats.

The sorbitol, fructose and glucose content of the retina, blood and liver from normal and streptozotocin diabetic rats fed either a starch- or sucrose-rich diet for 15 days has been determined. The sorbitol and fructose level in the retina was much higher than that in either the liver or blood and was significantly increased in diabetes on either diet. Such increases in the sorbitol concentration did not occur in either the liver or the blood during diabetes, and the possibility that the sorbitol pathway can play an important metabolic role in the diabetic retina has been discussed. The feeding of a sucrose- as opposed to a starch-rich diet did not significantly alter the concentrations of glucose, sorbitol or fructose in the normal rat retina but caused a marked elevation in the diabetic state.

Animals↗

Preoperative diagnosis of occult parathyroid hyperplasia by calcium infusion in patients with multiple endocrine neoplasia, type 2a.

Hereditary multiple endocrine neoplasia, type 2 (MEN 2) comprises medullary thyroid carcinoma (MTC) and bilateral pheochromocytoma; the syndrome includes two major variants, MEN 2a (normal appearance, parathyroid disease common) and MEN 2b (mucosal neuromas, Marfanoid habitus, parathyroid disease rate). Patients with MEN 2a may be normocalcemic, with normal basal serum immunoreactive parathyroid hormone (iPTH) levels, yet have parathyroid hyperplasia discovered during thyroid surgery. In an attempt to predict the presence of this occult parathyroid hyperplasia, we performed calcium infusion (15 mg Ca++/kg/4 hours) in six patients with MEN 2a, seven patients with MEN 2b, and eight normal subjects. iPTH was measured in samples taken at one hour intervals during the infusion with a sensitive radioimmunoassay (antiserum GP 1M [Arnaud]). The iPTH values (expressed as per cent of the basal value) in the normal, MEN 2a, and MEN 2b groups at the fourth hour were 38.0 +/- 3.8% (mean +/- SE), 79.2 +/- 7.2%, and 47.8 +/- 5.2%. These iPTH values for patients with MEN 2a were significantly different from normal (P less than 0.001) and from those of the patients with MEN 2b (P less than 0.001). All MEN 2a patients had parathyroid hyperplasia at cervical exploration; parathyroid histology in the MEN 2b patients was normal. Failure of iPTH suppressibility in the MEN 2a patients was not due either to the plasma calcitonin or to achieved serum calcium concentrations. The normal iPTH suppressibility in MEN 2b is consistent with the concept that the parathyroid disease in MEN 2a is genetically determined, and not secondary to MTC and high plasma calcitonin concentration. Calcium infusion combined with the measurement of serum iPTH levels may detect occult parathyroid hyperplasia in patients with MEN 2a, normocalcemia, and normal basal iPTH values. The identification and follow-up of similar patients should establish the natural history of this unusual parathyroid disease.

Adolescent↗

Glucose, glucose-6-phosphate, lactate and pyruvate content of the retina, blood and liver of streptozotocin-diabetic rats fed sucrose- or starch-rich diets.

The feeding of starch- or sucrose-rich diets to normal rats for 20 days resulted in a significant increase in lactate level and L/P ratio in the retina in the sucrose-fed animals. There was no correlation between the glucose and lactate content of the blood and retina and it was concluded that the increased lactate content of the retina was derived from the fructose moiety of the sucrose. Liver hypertrophy occurred in both normal and diabetic animals fed the sucrose diet. When streptozotocin-diabetic rats were maintained for 20 days on the same diets significant increases in the lactic acid content of the blood and liver occurred, but the high level of lactate in the retina of the sucrose-fed normal rats was not further elevated. The feeding of sucrose to diabetic rats resulted in better metabolic control of both blood glucose and lactate as compared with the maintenance of these animals on a starch diet.

Animals↗