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Biomedical subjects

V S Fang

Publications and source records attributed to V S Fang.

At least 127 records · Page 7Linked to original sources

The effects of fluoxymesterone administration on testicular function.

Long term daily administration of fluoxymesterone (9alpha-fluoro-17alpha-methyl-11beta, 17beta-dihydroxyandrost-4-en-3-one) was associated with a modest suppression of sperm production and a profound suppression of testosterone levels in the absence of significant effects on plasma gonadotropin levels. Nine normal male volunteers took either 10, 20, or 30 mg of fluoxymesterone daily for twelve weeks. Plasma samples were obtained for testosterone, estrogen, LH and FSH levels at biweekly intervals before, during and for up to 12 weeks after fluoxymesterone treatment. Samples were obtained for dehydroepiandrosterone sulfate, testosterone binding globulin and free testosterone assays at representative times before, during and after treatment. Although lower sperm counts were observed at several points during both the treatment and follow up periods, significant consistent suppression of spermatogenesis could not be demonstrated. Reduced plasma testosterone levels were seen within 24 h after beginning fluoxymesterone, and further reductions were noted throughout the treatment period. Changes in plasma estrogen levels did not correlate with fluoxymesterone administration. Neither plasma LH nor plasma FSH levels were significantly altered by fluoxymesterone. A short term study utilizing a single dose of fluoxymesterone yielded similar findings. It is proposed that fluoxymesterone has a local effect on the Leydig cell which is not mediated by gonadotropins.

Adult↗

Follow-up study of male and female offspring of DES-exposed mothers.

This follow-up study presents the effects of DES on the genital tract of male and female offspring of mothers who were part of a double-blind, placebo-controlled investigation during 1951 and 1952 aimed at determining the effect of DES on pregnancy. Epididymal cysts, hypotrophic testes, and capsular induration were the more common genital lesions found in 25% of 163 DES-exposed males as compared to 6% in 168 control males. Semen analysis data on 39 subjects of the DES-exposed group and 25 subjects of the control group showed that 26% of the DES-exposed group produced an ejaculate volume under 1.5 ml; no such cases were observed in the control group. The average values for sperm density ant total motile spermatozoa per ejaculate, although in the normal range, were more than two times lower in the DES-exposed group as compared to the controls. A quality score of greater than 10 ("severely pathologic semen") was found in 28% of the DES-exposed group as compared to 0 in the control group. An association of pathologic semen quality with physical abnormalities was found only in the DES-exposed group. Two cases of azoospermia, one without genital abnormalities on physical examination and one with bilateral hypotrophic testes were observed so far in the DES-exposed group. Eighteen percent of 229 DES-exposed female patients had irregular menstrual cycles (oligomenorrhea) as compared to 10% of 136 controls. The history of pregnancy revealed a lower incidence of pregnancy in the DES-exposed group (18%) than in the control group (33%). Circumferential ridges of the vagina and cervix were seen in 40% of 229 DES-exposed females but in none of 136 controls. Colposcopic findings in the vagina revealed adenosis in 66.8% of the DES-exposed females and in 3.6% of the control group. Dysplastic lesions were more prevalent in the vagina and cervix of the DES-exposed subjects. No cases of cancer were observed in either the male or female offspring.

Cell Count↗

Radioimmunoassay for MM and BB isoenzymes of creatine kinase substantiated by clinical application.

We have developed a radioimmunoassay technique that is highly specific for measuring the MM isoenzyme of creatine kinase. The specificity of the radioimmunoassay for the BB isoenzyme was poor. In patients with treated Duchenne-type muscular dystrophy or untreated hypothyroidism, the MM isoenzyme, but not the BB isoenzyme value, was consistently above above normal. In the radioimmunoassay for the BB isoenzyme the antisera might cross react with other materials and the inactivated isoenzyme, but not with MM or MB isoenzymes.

Antibody Specificity↗

The effect of neuroleptics on serum prolactin in schizophrenic patients.

Serum prolactin levels were studied before and during long-term administration of phenothiazines on a twice daily schedule to 27 newly admitted schizophrenic patients. An increase in serum prolactin is believed to be a reflection of inhibition of dopamine receptors in the hypothalamopituitary axis. By 72 hours after the initiation of treatment, all 27 patients had persistently elevated serum prolactin levels averaging 3.2-fold and 3.8-fold in men and women, respectively. There was a lag between clinical response and dopamine blockade, as indicated by serum prolactin levels in most patients. Serum prolactin levels remained elevated during the one- to three-month period subjects were studied, suggesting there was no tolerance to this effect of phenothiazines. Serum prolactin levels tended to be higher with thioridazine than on equivalent doses of chlorpromazine or trifluoperazine hydrochloride. There was some evidence that the magnitude of the serum prolactin elevation correlated with clinical response. After cessation of phenothiazines, serum prolactin levels rapidly reverted to normal within 48 to 96 hours.

Acute Disease↗

Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess.

It has been previously suggested that inherited thyroxine-binding globulin (TBG) abnormalities in man may be due to mutations at a single X-chromosome-linked locus controlling TBG synthesis. However, abnormalities in TBG degradation have not been excluded. The availability of purified human TBG and its successful labeling with radioiodide allowed us to examine such possibility. Human TBG was purified by affinity chromatography, labeled under sterile conditions with 131I or 125I,, and mixed with [125I]thyroxine (T4) or [131I]T4, respectively, before their intravenous injection. Blood and urine samples were collected over a 10-day period, and the turnover parameters were calculated. In eight normal volunteers mean values +/-SD for TBG and T4 respectively, were as follows: Half time (t1/2) 5.3 +/- 0.4 and 7.0 +/- 0.6 days; distribution space (DS) 7.2 +/- 1.0 and 10.8 +/- 1.2 liters; and total daily degradation (D) 0.211 +/- 0.053 and 0.088 +/- 0.011 mumol/day. In all subjects, t1/2 of TBG was shorter than that of T4; and the DS was smaller. 2.4 mol of TBG was degraded for each mole of T4. In five of six subjects from four families, comprising hemizygous and heterozygous carriers of TBG absence, decrease, and excess, the t1/2 and DS for TBG were within the normal range. The D of TBG was proportional to the serum concentration of the protein. Changes in the T4 kinetics in these patients were compatible with euthyroidism and with the known alterations in the extrathyroidal T4 pool associated with the changes in serum TBG concentration. A striking decrease in the t1/2 of TBG was found only in a patient with acquired diminution in TBG concentration and in patients with thyrotoxicosis or other conditions apparently unrelated to thyroid dysfunction. TBG t1/2 was 2.5 days in a patient with multiple myeloma and 3.6 days in two patients with thyrotoxicosis. Decreased TBG t1/2 was also observed in three of six patients with nonthyroidal pathology and was associated with an increase in TBG D disproportionate to their level of serum TBG. These studies indicate that changes in TBG concentration in patients with X-chromosome-linked TBG abnormalities are due to alterations in its rate of synthesis. In other conditions, abnormalities of TBG degradation and/or rate of synthesis may be found.

Adult↗

Studies on the antitesticular action of DL-6-(N-2-pipecolinomethyl)-5-hydroxy-indane (PMHI) in the rat.

Both prepubertal and adult rats were treated with a single oral dose of either 60 mg or 120 mg of dl-6-(N-pipecolinomethyl)-5-hydroxy indane maleate (PMHI) per kg of body weight. Their testicular weights were drastically reduced compared with those of the controls. A follow-up, beginning on the third day post-treatment and continuing for a period of 50 days, showed that the body weight growth of PMHI-treated rats was not retarded. The hormonal profile indicated that, except for FSH which showed a transitory elevation in PMHI-treated immature rats, the serum levels of LH, estrogen, and testosterone were indistinguishable from those of the controls. Testicular histology revealed that the spermatogenic process in PMHI-treated rats recovered at a dose-related rate. EM sections of testes of adult rats indicated that cytoplasmic vacuolation appeared in the Sertoli cells 5 h post-treatment. The consequent cascade of arrested spermiogenesis included abnormal acrosomal condensation of spermatids and sloughing of polynucleated spermatids. Some spermatocytes also seemed to be affected, but spermatogonia and Leydig cells remained intact. These results indicate the PMHI acts primarily on Sertoli cells and causes arrest in the spermiogenetic stage of the spermatids. At a higher and toxic dose of PMHI, however, the earlier germinal elements might also be affected, due to the extensive damage to the supporting Sertoli cells.

Age Factors↗

Episodic 24-hour cortisol secretory patterns in patients awaiting elective cardiac surgery.

The 24-hour pattern of plasma cortisol concentration in four patients on the day before major elective surgery was compared with that of five similarly hospitalized control subjects to study the effect of the expectation of surgery on the secretion pattern. Using an indwelling venous catheter, which extended outside the patient's room, to collect blood samples every 20 minutes for 24 hours, it was found that cortisol was secreted episodically in both control subjects and presurgical patients. The nychthermal patterns of plasma cortisol concentration in the two groups were indistinguishable for most of the day despite the occurrence of intermittent events which appeared to cause anxiety in the presurgical patients. However, between 9 PM and 11 PM, while each presurgical patient was being preoperatively prepared (body shaving, wash, and enema), a major pulse of cortisol secretion occurred, raising the plasma cortisol concentration to between 6.9-10.5 standard deviations above that of the control subject mean for that time of day. We conclude that 1) expectation of a major surgical procedure for several weeks does not result in chronic activation of the pituitary-adrenocortical axis, 2) many discrete anxiety-provoking events do not evoke cortisol secretory episodes, 3) most episodes of cortisol secretion are part of an endogenous cyclical pattern with a circadian distribution and are not a direct result of environmental stimuli, and 4) preoperative preparation evokes a major cortisol secretory response in patients awaiting surgery. Whether that release of cortisol is a response to the physical manipulations or the psychological implications of that stimulus is presently unknown.

Adult↗

Restoration of plasma testosterone levels in uremic men with clomiphene citrate.

Five men with chronic renal failure and symptoms suggestive to androgen deficiency were treated with clomiphene citrate (Clomid) at a dose of 100 mg/day for a period of 5 to 12 months. The treatment resulted uniformly in increased libido, sexual potency, and a general sense of well-being. Circulating testosterone rose from mean basal value of 223 +/- 164 to 879 +/- 171 ng/dl (SD), representing a mean increment of 290%. Mean serum lutenizing hormone (LH) and follicle-stimulating hormone (FSH) values before treatment were 76 +/- 40 and 143 +/- 85 ng/ml (SD). During treatment, both LH and FSH increased dramatically to 518 +/- 302 and 787 +/- 291 ng/ml (SD), respectively. Both serum gonadotropin values are expressed as ng/ml of LER 907. The effect of clomiphene on spermatogenesis in these subjects was inconclusive as either improvement or deterioration occured. In these five patients, serum prolactin was not related in any way to testicular function as its values were consistently in the normal range throughout the entire study period. Serum total estrogen, however, was elevated in all; the significance of this high circulating estrogen in relation to gonadal dysfunction in uremia is not clear at the present time. However, we found that normalization of circulating androgen was beneficial to our patients and that long-term clomiphene treatment achieved this goal by increasing pituitary gonadotropin secretion and secondarily stimulating testicular hormonogenesis.

Clomiphene↗

Induction of lactogenic receptors. II. Studies on the liver of hypophysectomized male rats and on rats bearing a growth hormone secreting tumor.

The role of growth hormone (GH), as well as prolactin and ACTH, in the induction of the PRL receptor was investigated both in hypophysectomized male rat livers and in the livers of male rats bearing a GH secreting tumor. After 7 days of s.c. injections, specific binding (% SB) of PRL in controls and rats treated with oPRL, hGH, ACTH, hCG, estradiol (E2), or testosterone (T) was approximately 1%. Treatment with oPRL plus ACTH increased SB to 4%; adding E2 to this combination produced a further increase to 8%, whereas the addition of T decreased hepatic binding to 1%. Combination of hGH with ACTH was most effective, giving a SB of 33%, which is similar to that observed in the liver of rats bearing a GH secreting tumor (36%). These studies suggest that GH acts synergistically with PRL and/or ACTH to increase lactogenic binding sites in the male rat liver and that sex steroids have a modulating effect on this action.

Adrenocorticotropic Hormone↗

Effect of apomorphine plus 5-hydroxytryptophan on plasma prolactin levels in male rats.

The relative potency of dopaminergic inhibition and serotonergic stimulation of prolactin secretion in male rats was compared. 5-Hydroxytryptophan (5-HTP), 100 mg/kg, i.p., the precursor of serotonin, produced a 6-11 fold increase in plasma prolactin. Apomorphine, a dopamine agonist, at doses of 1-10 mg/kg, i.p., had no significant effect on plasma prolactin. However, when apomorphine was given with or before 5-HTP, it nearly completely blocked the increase in prolactin produced by 5-htp. these results indicate that inhibition of prolactin secretion by dopaminergic stimulation can overcome the prolactin releasing effect of serotonin. The results are consistent with the hypothesis that prolactin secretion is ordinarily under a weak serotonergic stimulation and a profound dopaminergic inhibition. It is also possible that apomorphine affects plasma prolactin levels by increasing prolactin clearance.

5-Hydroxytryptophan↗