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Biomedical subjects

T H Hsu

Publications and source records attributed to T H Hsu.

At least 19 recordsLinked to original sources

Comparisons of different animal skins with human skin in drug percutaneous penetration studies.

The in vitro penetration of theophylline, sodium diclofenac and benzoic acid through artificial cellulose membrane and eight animal skins was investigated. The intact animal skins including stratum corneum (SC) and viable epidermis were taken from frog, snake with or without scales, nude mice, Sprague-Dawley rat, porcine and human prepuce and thigh skin. The results indicated that the penetration was fastest through cellulose membrane and frog skin and slowest through human prepuce and thigh skin. The snake skin with scales slowed down the penetration rate more significantly than the scaled skin. Benzoic acid was the fastest penetrant through all animal skins. The permeable behaviors of sodium diclofenac through SC and intact skin of snake, porcine and human were compared. In porcine, sodium diclofenac penetrated through SC at a rate 33 times higher than through intact skin, but in snake and human skin, the rate through SC was only 2.2 and 1.6 times higher than through intact ones. This implies that both viable epidermis and SC were the major rate limiting barriers in drug penetration. DSC thermograms and IR spectra showed that the SC of snake, porcine and human thigh were very similar in structure and components. The study suggests that snake skin, porcine skin and human prepuce skin could replace the human skin in in vitro drug penetration experiments.

Animals

The effects of L-dopa on in vitro and in vivo calcitonin release from medullary thyroid carcinoma.

The in vivo and in vitro effects of the dopamine precursor L-dopa on basal and stimulated calcitonin release from medullary thyroid carcinoma have been studied. In six studies of five patients, including 7- to 8-h control and test periods, oral L-dopa depressed basal calcitonin secretion by an average of 35%; the peak effects occurred within 30 min of drug administration and lasted for as long as 4 h. In seven of eight patients with medullary thyroid carcinoma (three infused with calcium and five with pentagastrin), L-dopa inhibited to varying degrees peak levels of stimulated calcitonin release and total calcitonin secretion; basal calcitonin levels, where directly tested, also again generally fell after L-dopa by an average of 50%. In a short term organ culture system using medullary thyroid carcinoma tissues, calcitonin secretion into the medium was linear with time for 2 h and could be stimulated by dibutyryl cAMP and pentagastrin. L-Dopa, in concentrations from 0.5--3.0 mM, inhibited basal calcitonin secretion (ranging from 25--55%). Addition of the L-dopa decarboxylase inhibitor, alpha-methyldopa, abolished the inhibitory effects of L-dopa. Another L-dopa decarboxylase inhibitor, carbidopa, stimulated calcitonin secretion in vitro; this effect may be independent of the L-dopa decarboxylase-inhibiting properties of this drug since alpha-methyldopa alone did not stimulate calcitonin secretion. It is concluded that the amine precursor L-dopa inhibits calcitonin release in patients with medullary thyroid carcinoma; the in vitro studies suggest that a portion of this effect may involve direct metabolism of L-dopa to dopamine in the tumor tissue itself. The importance of considering the uptake of amine precursors and the subsequent metabolism of these compounds as a modulating site for peptide hormone release from peripheral endocrine tissues is stressed.

Calcitonin

Hypoglycemic coma with ketoacidosis in nondiabetic alcoholics.

Five nondiabetic, chronically alcoholic patients presented in a comatose state during a two month prospective study and were found to be ketoacidotic. All of the patients were men, 28 to 59 years old. The usual history was one of chronic heavy, daily alcohol consumption until one to three days before presentation, when persistent anorexia, abdominal distress, nausea and vomiting commenced, with abstention from food thereafter. The patients were found to be in hypoglycemic coma, with diaphoresis, tachypnea and tachycardia, and immediately awoke when intravenous infusion of glucose was started. Serum glucose ranged between 19 and 27 mg per dl, the average arterial pH was 7.19 and the mean anion gap was 25 mEq per liter. Reaction with Acetest tablets was positive for ketones in both serum and urine in three of the patients. Serum beta-hydroxybutyrate was elevated in the four patients in whom it was measured. Lactic acidosis was not present. All patients were managed with prolonged intravenous infusions of glucose and saline solutions, and within 12 to 18 hours they were feeling well and findings on serum chemistry studies were normal. Follow-up after three months showed no repeated difficulties. The combination of alcoholic ketoacidosis and hypoglycemic coma in nondiabetic persons has not been described in the literature as a clinical entity; it may, however, represent a common but unrecognized syndrome. Therefore, because of its potentially serious consequences and because treatment is simple and effective, this entity must be thought of in alcoholic patients with altered mental status.

Acidosis

A study of age-dependent changes in thyroid function tests in adults.

Total serum thyroxine (T4), triiodothyronine (T3), T3 resin uptake (T3U), thyrotrophin (TSH), and reverse T3 (rT3) were measured in 209 healthy adults 20--89 yr old. Mean T4 values for men were stable throughout life, but in females under age 60, T4 values were significantly higher than in older women. Values for T3U in males were significantly higher than in females throughout all decades, although females had a significant increase in T3U after age 60. TSH values increased significantly in females over age 60. Throughout all decades, males had stable TSH levels that were slightly higher than the female results before age 60 and lower thereafter. Mean serum T3 declined similarly for both sexes with increasing age, although not to the extent previously reported. Men had significantly higher mean rT3 values over all decades than females, although female rT3 levels decreased after age 50 whereas males maintained stable values. The physiologic reasons for these findings may be due to sex-related changes in binding proteins and alterations in metabolic clearance rates, production, and degradation of these hormones with increasing age.

Adult

Thyrotoxicosis in a patient with secondary hypothyroidism.

We have described a patient with panhypopituitarism who developed thyrotoxicosis. There is a widespread belief that pituitary thyrotropin (TSH) is not a pathogenetic factor in most patients with thyrotoxicosis. Due to technical reasons, however, it has been difficult to entirely exclude the role(s) of TSH in the development of thyrotoxicosis. In this report hyperthyroidism appeared in a patient with TSH deficiency proved by the lack of response to TRH administration. This is the first known case in which TRH stimulation demonstrated total abscence of TSH before the onset of thyrotoxicosis. We cannot exclude the possibility that factors of adenohypophyseal origin play some role in the pathogenesis of thyrotoxicosis, but TSH per se does not play a role in the development of Graves' thyrotoxicosis.

Humans

Sudden onset of unilateral third nerve paresis in a patient with Cushing syndrome.

Extraocular muscle pareses in patients with Cushing syndrome are virtually always associated with a greatly enlarged pituitary tumor and with advancement on oculomotor nerves. The present report concerns a patient with a rapidly progressive adrenocorticotropic hormone (ACTH)-dependent hyperadrenocorticism and sudden onset of an unilateral third nerve paresis. The patient had no demonstrable pituitary tumor. After a total adrenalectomy and correction of hyperadrenocortisolism, his third nerve paresis subsided. Ocular paresis may occur in a patient with Cushing syndrome even in the absence of mechanical involvement of ocular nerves by a pituitary tumor.

17-Hydroxycorticosteroids

Breast carcinoma, thyroid carcinoma, and T3 thyrotoxicosis in a male cretin.

A male patient with clinical and radiographic evidence of cretinism was found to have T3 thyrotoxicosis. The cause was thought to be a well-differentiated follicular carcinoma of the thyroid. Although the disease was not documented, the patient probably had long-standing hypothyroidism. Untreated primary thyroid failure accompanied by high serum thyroid stimulating hormone (TSH) may be carcinogenic to the thyroid. The association of thyroid abnormalities and male breast carcinoma is discussed.

Adenocarcinoma

Differential ovarian and adrenal vein catheterization.

Twenty-two hirsute women underwent percutaneous adrenal and ovarian vein catheterization to differentiate and localize excessive hormonal output. All studies were done under fluoroscopic control; catheter placement was verified by venography, and blood samples were withdrawn for hormonal analysis. The right ovarian vein was successfully sampled in 42 per cent of attempts; the left ovarian vein, in 75 per cent; the right adrenal vein, in 56 per cent; and the left adrenal vein, in 100 per cent. Bilateral catheterization did not prove clinically useful. First, anatomic variations in venous size and drainage made catheterization and bilateral sampling difficult. Second, adrenal secretion is both episodic and parallel, necessitating both simultaneous catheterization and serial sampling for adequate diagnosis. The stress of the procedure may provoke increased adrenal output. Third, since ovarian secretion is not parallel, and since increased hormone output has been documented in that ovary containing developing follicles or a corpus luteum, distinguishing ovarian dysfunction proved difficult. Finally, for a time-consuming procedure, patient discomfort cannot be disregarded. This technique has not proved to be a reliable means of determining the site of androgen hypersecretion and thus cannot be recommended in the routine evaluation of female hirsutism.

17-Ketosteroids

Potentiation of the ACTH response to metyrapone by L-dopa in the monkey.

The intravenous injection of L-Dopa (15 mg/kg) to monkeys (Macaca mulatta) failed to alter plasma concentrations of ACTH and of 11-deoxy-cortisol. When cortisol synthesis was blocked with iv metyrapone, potentiation of ACTH secretion by L-Dopa became apparent. Simultaneous injection of L-Dopa and metyrapone resulted in a marked increase in plasma ACTH from 93 +/- 18 pg/ml to 432 +/- 80 pg/ml, whereas plasma 11-deoxycortisol increased from 1.5 +/- 0.2 mug/100 ml to 14.6 +/- 1.0 mug/100 ml 90 min after treatment. Throughout the experiment the rise in ACTH and in 11-deoxycortisol following coadministration of L-Dopa and metyrapone was significantly (P less than 0.01) higher than that produced by metyrapone administration alone. The results suggest that acute administration of L-Dopa in monkeys enhances the response of ACTH to metyrapone. L-Dopa (or one of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of hypothalamic corticotropin regulatory factor(s) and thereby enhance the release of ACTH.

Adrenocorticotropic Hormone

Juvenile diabetes mellitus after forty years.

Seventy-three patients with juvenile diabetes mellitus for a mean duration of 42.9 years were retrospectively studied on a multidisciplinary basis. Only three of this group of patients were socially disabled as a result of their long-standing illness. Of all the complications, insulin-induced hypoglycemia was most common. Although diabetic retinopathy was clinically evident in about 75 per cent of patients, only 50 per cent of these seventy-three patients had a significant visual impairment. Nephropathy was apparent in 59 per cent of patients, and neuropathy was demonstrable in half of them. Significant peripheral vascular system impairment was present in 40 per cent and major cardiac complication in 20 percent.

Achievement