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Biomedical subjects

M H Wheeler

Publications and source records attributed to M H Wheeler.

At least 73 records · Page 4Linked to original sources

Secretion of intact PTH by dispersed human hyperparathyroid cells.

The rate of secretion of intact PTH by cells dispersed from adenomatous and hyperplastic human parathyroid tissue was measured using a two-site immunochemiluminometric assay specific for the intact peptide. Secretion rates were monitored following incubation in high and low-calcium media. The mean rate of secretion from hyperplastic cells was significantly greater (P less than 0.05) at low calcium and significantly more suppressible at high calcium (P less than 0.01) compared with adenomatous cells. These studies have demonstrated: (1) the calcium-dependent secretion of intact PTH, (2) that intact hormone release contributes to the non-suppressible component of secretion, and (3) differences in the secretory characteristics of adenomatous and hyperplastic parathyroid cells.

Adenoma↗

The effect of preoperative Lugol's iodine on thyroid blood flow in patients with Graves' hyperthyroidism.

A study was conducted to investigate the effect of Lugol's iodine on the superior thyroid artery (STA) blood flow with use of a Duplex ultrasound scanner for 12 patients with Graves' disease. All patients were treated with antithyroid drugs until they were euthyroid and then, with randomization, the patients received either Lugol's iodine, 0.3 ml thrice daily, or placebo for 9 days in a double-blind fashion. Antithyroid drugs were continued throughout the study. Reduction in the diameter, time-averaged velocity (TAV), and volume flow (VF) of the STAs was demonstrated in all patients in the treatment group, whereas there were no consistent trends in the placebo group. The changes in TAV and VF were significantly different between the placebo and treatment groups (p less than 0.01 for TAV and p less than 0.005 for VF). These changes were more marked in patients with high initial VF and minimal in patients with low initial VF. On the basis of these results, we recommend that patients with high thyroid blood flow before thyroidectomy should receive Lugol's iodine preoperatively.

Adult↗

Studies in patients with hyperparathyroidism using a new two-site immunochemiluminometric assay for circulating intact (1-84) parathyroid hormone.

A recently developed chemiluminescent immunoassay for 1-84 intact parathyroid hormone (PTH) demonstrated increased specificity by virtue of two-site antibody binding and increased sensitivity by use of a chemiluminescent technique. Basal PTH levels were measured in three groups of subjects: (1) normal (n = 82), (2) hyperparathyroidism (n = 31), and (3) patients with hypercalcemia of malignancy (n = 16). There was good discrimination between normal (1.2 to 9.4 pmol/L) and hyperparathyroid subjects (9.2 to 53.4 pmol/L). In persons with hypercalcemia of malignancy all PTH levels were within the normal range (0.8 to 5.2 pmol/L) or suppressed. PTH release was stimulated by the intramuscular injection of 100 IU salmon calcitonin in 6 normal controls, 10 patients with primary hyperparathyroidism due to adenoma, and 5 with four-gland hyperplasia. There was no significant rise in PTH concentration and out of the normal range in the control subjects, but the adenoma patients demonstrated a mean rise of 24.4%, 26%, and 33%, and hyperplasia patients, a mean rise of 37%, 47%, and 37% over basal levels at 120, 180, and 240 minutes. The mean absolute rise in PTH concentration was 13.4 +/- 7.7 pmol/gm of parathyroid tissue in the adenomas and 27.2 +/- 9.5 pmol/gm of parathyroid tissue in the hyperplastic glands; this difference was significant (p less than 0.05). Serial blood samples from a central vein were taken at surgery for hyperparathyroidism, and the rate of decay of the intact hormone was studied in 9 patients after removal of the parathyroid tissue. This decay was rapid with a half-life of 300 seconds. We conclude that this new specific and sensitive intact PTH assay will provide a valuable means of investigating dynamic aspects of parathyroid physiology.

Adult↗

Thyroid follow-up.

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Follow-Up Studies↗

The association of neurofibromatosis, pheochromocytoma, and somatostatin-rich duodenal carcinoid tumor.

The association of neurofibromatosis and pheochromocytoma is well recognized; more recently, attention has been drawn to links between neurofibromatosis, pheochromocytoma, and ampullary somatostatin-rich carcinoid. Because of this association, the duodenum was explored during a recent laparotomy for resection of bilateral pheochromocytoma in a patient with von Recklinghausen's disease. A clinically unsuspected ampullary tumor was discovered; this proved to be in part a ganglioneuroma and in part a somatostatin-rich carcinoid. This paper presents full details of this carefully investigated and documented case and reviews the recent advances in this field. These studies lead us to conclude that: the clinical association of neurofibromatosis, pheochromocytoma, and D cell carcinoids ("somatostatinomas") of the ampullary region is confirmed; this association may be more common than has been previously thought, and the duodenum should be carefully examined in any patient with neurofibromatosis who undergoes laparotomy for pheochromocytoma.

Adrenal Gland Neoplasms↗

Melanin biosynthesis and the metabolism of flaviolin and 2-hydroxyjuglone in Wangiella dermatitidis.

Melanin biosynthesis in the human pathogen Wangiella dermatitidis was inhibited by tricyclazole, causing pentaketide melanin metabolites to accumulate in the cultures. One of these metabolites, scytalone, was racemic and thus different than the (+)-enantiomer from Verticillium dahliae. An albino mutant of W. dermatitidis metabolized scytalone to a pigment ultrastructurally identical to wild-type melanin. Cell-free homogenates of the wild type carried out typical reductive and dehydrative reactions with known melanin intermediates and the reductive reactions were inhibited by tricyclazole. Other reductive and dehydrative reactions that utilize flaviolin and 2-hydroxyjuglone were studied anaerobically with homogenates from both the wild type and the albino mutant. The homogenates converted flaviolin to 5-hydroxyscytalone and products identical to those obtained from 2-hydroxyjuglone. The albino, in culture, carried out the same reactions with 2-hydroxyjuglone but metabolized flaviolin to a number of unknown colored products apparently through oxidative reactions. Similarities between the melanin pathway and the flaviolin and 2-hydroxyjuglone branch pathways are discussed and tricyclazole is shown to inhibit reductive reactions with naphthols in the three pathways.

Melanins↗

Bile exclusion from the duodenum. Its effect on gastric and pancreatic function in the dog.

The effect of diverting bile from the duodenum in four dogs with cholecystojejunostomy was studied using a double-marker perfusion technique. After the diversion procedure, a liquid meal increased acid secretion from 0.8 mmol H+/min to 1.48 mmol H+/min (P less than 0.05, paired t test); there was an associated rise in serum levels of gastrin 120 min after feeding (P less than 0.001, paired t test). Pancreatic secretion of trypsin decreased from 3.91 IU/min to 2.66 IU/min after bile diversion (P less than 0.01, paired t test), and the level of CCK was significantly lower 60 min after feeding (P less than 0.05, paired t test). There was no significant change in the rate of gastric emptying after bile diversion, but the pH of duodenal contents was lower in the later stages of digestion. These changes may explain the reported increase of peptic ulcer after diverting bile from the duodenum, and the procedure should not be considered unless the consequences of acid hypersecretion and pancreatic inhibition have been anticipated.

Amylases↗

Pentaketide metabolites of melanin synthesis in the dematiaceous fungus Wangiella dermatitidis.

Melanin synthesis in the dematiaceous, polymorphic hyphomycete Wangiella dermatitidis, a human pathogen, was investigated by biochemical and physiological techniques. Mutants with a decrease or loss in melanin synthesis were induced and isolated. Melanin precursors were obtained from the mutants, purified, and then identified by comparison with authentic compounds from Verticillium dahliae . Isolation of scytalone , vermelone , flaviolin , and 1,8- dihydroxynaphthalene from the mutants of Wangiella dermatitidis, and cross-feeding of the mutants with those of Verticillium dahliae indicated that melanin synthesis in this organism took place by the pentaketide pathway. Melanin that formed in cell walls of an albino mutant treated with scytalone was identified in appearance to that in cell walls of the wild-type strain. This also suggested that pentaketide synthesis of melanin occurred in the fungus.

Melanins↗

Bile diversion from the duodenum: its effect on gastric and pancreatic function.

The effect of diverting bile from the duodenum in four dogs by cholecysto-jejunostomy was studied using a double-marker perfusion technique. During digestion of a liquid meal, acid secretion increased from 0.8 mmol H+/min to 1.48 mmol H+/min (p less than 0.05, paired t test); there was an associated rise in serum levels of gastrin 120 minutes after feeding (p less than 0.001, paired t test). Pancreatic secretion of trypsin decreased from 3.91 IU/min to 2.66 IU/min after bile diversion (p less than 0.01, paired t test) and the level of CCK was significantly lower 60 mins after feeding (p less than 0.05, paired t test). There was no significant change in the rate at which the liquid meal emptied from the stomach after bile diversion but the pH of duodenal contents was lower during the later stages of digestion. These changes may explain the reported increase of peptic ulcer after diverting bile from the duodenum and the procedure should not be considered unless the consequences of acid hypersecretion and pancreatic inhibition have been anticipated.

Animals↗