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Biomedical subjects

N S Jiang

Publications and source records attributed to N S Jiang.

At least 19 recordsLinked to original sources

Biochemical evaluation of adrenal dysfunction: the laboratory perspective.

In this study, we reviewed the diagnostic efficiency of laboratory tests that are performed for assessment of patients with Cushing's syndrome or adrenal insufficiency. Baseline laboratory data from patients subsequently diagnosed with adrenal dysfunction were analyzed for tests performed between 1987 and 1989 at our institution. Results were analyzed for 36 patients diagnosed with pituitary-dependent Cushing's syndrome, 15 with ectopic Cushing's syndrome, 12 with adrenal-dependent Cushing's syndrome, 20 with primary adrenal insufficiency, and 7 with secondary adrenal insufficiency. Tests reviewed were plasma cortisol, plasma corticotropin, urinary free cortisol, urinary 17-ketosteroids, urinary ketogenic steroids, low-dose and high-dose dexamethasone suppression, and metyrapone stimulation. Our findings suggest that a substantial proportion of diagnoses could be based on the results of three tests--plasma corticotropin, plasma cortisol, and urinary free cortisol. We present a nomogram that combines the results of plasma corticotropin and plasma cortisol testing to enhance the diagnostic efficiency of these tests.

Adolescent

Effect of megestrol acetate on the human pituitary-adrenal axis.

A few previous reports have suggested that megestrol acetate, a synthetic progestational agent frequently used as an antineoplastic drug, suppresses serum cortisol concentrations in humans. To explore this concept further, we prospectively performed several measurements of the pituitary-adrenal axis in patients receiving megestrol acetate (160 or 800 mg/day). The data from these evaluations demonstrate that megestrol acetate reversibly decreases serum cortisol concentrations in humans and that this effect seems to originate from a suppression of the pituitary-adrenal axis. Additional studies should be conducted to determine the implications of the low levels of serum cortisol.

Humans

Recent developments in the diagnosis and treatment of pheochromocytoma.

The investigation and management of pheochromocytoma have been of special interest at the Mayo Clinic since 1926, when Dr. C. H. Mayo successfully removed an adrenal tumor. Recent clinical developments include the detection of asymptomatic paroxysms of hypertension by 24-hour ambulatory monitoring, detailed characterization of catecholamine cardiomyopathy by echocardiography, and further experience with Carney's triad and other polyglandular and multiple neoplasia syndromes associated with pheochromocytoma. Refinement in interpretation of catecholamine measurements and the development of radionuclide scanning with m-[131I]iodobenzylguanidine, computed tomography, and magnetic resonance imaging have greatly enhanced our diagnostic acumen. Developments in antihypertensive drug therapy and chemotherapy have improved our management of cathecholamine hypersecretion and tumor growth, respectively, in inoperable patients and in the preparation of patients for anesthesia and surgical treatment. Flow cytometry to detect abnormal DNA histograms may prove particularly useful in predicting the malignant nature of the tumors.

Adrenal Gland Neoplasms

Ovine corticotropin releasing hormone stimulation test: normal value study.

We determined the pituitary-adrenal response to 1 microgram/kg of ovine corticotropin releasing hormone (oCRH) administered as an intravenous bolus injection in 50 normal subjects. Brief facial flushing was noted in 44% of the subjects; no other side effects were reported. Plasma corticotropin levels increased from a median of 30.2 pg/ml at baseline to a median peak level of 77.8 pg/ml after administration of oCRH; the peak response occurred at the 30- to 45-minute or the 45- to 60-minute time point. Plasma cortisol levels increased from a median of 10.8 micrograms/dl at baseline to a median peak level of 22.0 micrograms/dl after administration of oCRH; the peak response occurred at the 45- to 60-minute time point. Plasma beta-endorphin levels increased from a median of 9.5 pg/ml at baseline to a median peak level of 23.0 pg/ml after administration of oCRH; the peak response occurred at the 15- to 30-minute or the 30- to 45-minute time point. The responsiveness to oCRH was unaffected by age, sex, or body mass index of the subjects.

Adrenocorticotropic Hormone

Estrogen and progesterone receptors in meningiomas: comparison of nuclear binding, dextran-coated charcoal, and immunoperoxidase staining assays.

We studied the status of estrogen (ER) and progesterone (PR) receptors in meningiomas removed from 52 patients, comparing dextran-coated charcoal (DCC), nuclear binding (NB), and immunoperoxidase (IP) assays. Each of the assays was performed independently by investigators well-experienced with these assays. The NB assay is a new assay that measures functional steroid receptors--that is, the activation of the receptor and its binding to the nucleus. The assay is very sensitive and requires a relatively small amount of tissue as compared with the DCC assay. In agreement with data from other studies. PR were detected in most meningiomas by all 3 methods: in 69% of the cases by NB, in 76% by DCC, and in 89% by IP. ER were detected in only a few cases: in 33% by NB, in 2% by DCC, and in none by the IP assay. The agreement for PR sites was 62% for all 3 assays; it was 66% between the NB and DCC assays, 67% between the NB and IP assays, and 86% between the DCC and IP assays. Of 26 cases that were positive by the DCC assay, 6 (23%) were negative by NB. The overall agreement for all three ER assays was 65%. The data suggest that the majority of meningiomas contain high-affinity receptors for progesterone, that estrogen receptors are present in only a few meningiomas, and that some of these estrogen and progesterone receptors appear to be functional.

Adolescent

The effects of synthetic alpha-subunit peptides on thyroid-stimulating immunoglobulin activity.

Synthetic peptides, representing specific portions of the alpha-subunit of the human glycoprotein hormones, can inhibit both the binding of labeled TSH to thyroid membranes and adenylate cyclase stimulation by TSH in vitro. The same synthetic peptides (alpha 26-46 and alpha 31-45) significantly (P less than 0.05) inhibited the adenylate cyclase-stimulating activity of thyroid-stimulating immunoglobulins (TSI) from 10 patients with hyperthyroid Graves' disease. Peptide alpha 26-46 was the most potent, resulting in 79.1 +/- 8.8% (+/- SE) inhibition at 133 micrograms/mL, while peptide alpha 31-45 inhibited TSI activity by 36.3 +/- 5.2%. Peptides alpha 61-75 and alpha 81-92, that had only minimal ability to inhibit TSH-mediated cAMP generation, did not significantly inhibit TSI activity. The inhibitory action of alpha 26-46 was dose dependent, and a significant negative correlation was found between the maximum TSI activity of the serum sample and the inhibition achieved by the synthetic peptide, suggesting that differences in TSI affinity and/or titer may account for the variable inhibitory activity of the peptides. These results suggest that TSI interact with the TSH receptor at the site that recognizes the portion of the TSH alpha-subunit represented by the synthetic peptide alpha 26-46 and, thus, support the concept that the TSH-binding site of the TSH receptor is the site of antigen binding between TSI and the thyroid cell.

Cyclic AMP

Comparative effectiveness of dextrothyroxine and levothyroxine in correcting hypothyroidism and lowering blood lipid levels in hypothyroid patients.

Data reported here establish that treatment regimens of 4 mg dextrothyroxine and 0.15 mg levothyroxine in hypothyroid subjects produce similar degrees of lowering of serum TSH, cholesterol, triglycerides, and phospholipid levels and equal stimulation of metabolic rate. The Murphy-Pattee total T4 determination applied to blood samples drawn 24 h after the last dose of dextrothyroxine can be used to assess adequacy of treatment. Correction of hypothyroidism requires high serum levels of dextrothyroxine than of levothyroxine. Serum T3 levels increase in patients treated with dextrothyroxine. In the treatment of hypothyroidism, the cholesterol-lowering and metabolic rate-stimulating effects of dextrothyroxine do not appear to be dissociated. Further studies are needed to determine whether such an effect can be demonstrated in euthyroid hypercholesterolemic subjects with doses established herein as equivalent in terms of the stimulating effect on metabolic rate.

Basal Metabolism

Human corticotropin (ACTH) radioimmunoassay with synthetic 1--24 ACTH.

A corticotropin antiserum was obtained from rabbits immunized with synthetic 1--24 corticotropin conjugated with bovine serum albumin. The antiserum did not cross react with synthetic alpha-melanotropin or with synthetic beta-endorphin and had a cross reactivity of 0.23% with human beta-lipotropin. We developed a radioimmunoassay with the antiserum obtained, in which we used polyethylene glycol in conjunction with a second precipitating antibody for fast (15-min) separation of antibody-bound and free corticotropin. The assay had a sensitivity of 16 ng/L and was validated on patients with various pituitary and adrenal diseases. From 103 normal subjects, the median value for corticotropin in specimens collected during the morning was 34 ng/L of plasma; the upper 95% confidence limit of the normal range was 98 ng/L.

Adrenal Gland Diseases

Analysis for urinary catecholamines by liquid chromatography with amperometric detection: methodology and clinical interpretation of results.

A method is presented for the quantitative analysis of urinary unconjugated norepinephrine, epinephrine, and dopamine as discrete entities. The procedure requires initial purification of the specimen on aluminum oxide and a boric acid-gel. We used "high-performance" reversed-phase paired-ion chromatography, with a flow-through amperometric cell as the detector. The CV was 6% for determination of norepinephrine, 11% for epinephrine, and 6% for dopamine monitored at physiologic concentrations of these compounds in urine. In a population study, urine specimens from 117 normal pediatric and adult subjects, 85 hypertensive patients, and 22 patients with surgically proved pheochromocytoma were analyzed. The specificity of the method for detection of pheochromocytoma was 100%, with a sensitivity of 97%.

Adolescent

Thyrotropin receptors in normal and pathological human thyroid tissues.

The properties of TSH receptors in normal and pathological human thyroid tissues were studied. Highly purified bovine TSH after lactoperoxidase iodination retained full biological activity, as assessed by radioreceptor assay. Binding of bovine [125I]TSH to 1000 x g pellets of human thyroid homogenate was specific with respect to hormone and tissue. Total binding amounted to 50-60% of total radioactivity using 10 mg (wet weight) normal thyroid tissue. Nonspecific binding was only 6% of total radioactivity. Normal thyroid tissue contained two orders of binding sites, which were shown to be independent of each other by Hill plot analysis. The high affinity sites [equilibrium dissociation constant (Kd), 0.015-0.16 x 10-9 M] were present in concentrations of 1.05-9.30 pmol/mg protein and concentrations of low affinity sites (Kd, 1.2-2.4 x 10-9 M) were 35.9-213 pmol/mg. In all pathological thyroid tissue studied, two orders of binding sites were found with dissociation constants similar to those of normal tissues, but the number of binding sites was markedly reduced. Both orders of binding sites in solitary "cold" adenomas and only the low affinity sites in thyroid tissue from patients with Graves' disease were significantly reduced in number (P less than 0.01). There was a questionable decrease in high affinity sites in the Graves' tissue (P = 0.05). We have found the definite presence but a decreased number of binding sites in both orders of receptors in papillary and follicular carcinomas. There were few or no binding sites in medullary carcinoma.

Adenocarcinoma

Abnormalities of endogenous glucagon and insulin in unstable diabetes.

The responses of glucagon, growth hormone, and insulin secretion to the oral administration of glucose and to the intravenous infusion of saline, arginine, and insulin were measured in seven patients who had stable diabetes, eight who had unstable diabetes, and seven healthy volunteers. Hyperglycemia suppressed secretion of glucagon in normal subjects but not in diabetics. The oral glucose and arginine infusion tests demonstrated partial preservation of insulin-secretory ability in stable diabetics and its virxual absence in unstable diabetics. Glucagon responses to arginine infusion were similar in all three groups. In response to hypoglycemia induced by insulin infusion, the concentrations of plasma glucagon increased in normal subjects and, to a lesser extent, in stable diabetics but increased in only two of the unstable diabetics. The impairment in glucagon response during hypoglycemia in diabetics correlated positively with the degree of diabetic instability and insulin deficiency during glucose and arginine testing. The severity of the insulin deficiency also correlated with the degree of diabetic instability. These findings support the hypothesis that inherent abnormalities of insulin and glucagon secretion may account for many of the clinical characteristics of unstable and stable diabetic patients.

Adult

Radioimmunoassay of human homologous prolactin in serum with commercially available reagents.

A clincally useful and reproducible radioimmunoassay for human homologous prolactin, established with commercially available reagents, was studied and validated. We present detailed conditions for iodination and purification of labeled prolactin and the optimal conditions for the assay. By the method, we found values (microgram/liter) as follows for serum prolactin: normal men. 8.9 +/- 5.2 (mean +/- SD); normal women, 11.8 +/- 5.5; normal women taking contraceptive pills, 9.2 +/- 5.0; pregnant women in the third trimester, 188 +/- 69.5; patients with various diseases other than of the hypothalamic-pituitary axis, 9.3 +/- 6.3; in some patients with amenorrhea and galactorrhea of diverse origin, 78.2 +/- 87.4; and in some patients with surgically proven pituitary tumor, 1414 +/- 1980. Results under provocative testing are also presented for a patient with normal hypothalamic-pituitary function.

Chlorpromazine

Determination of free thyroxine in serum by radioimmunoassay.

We describe a sensitive and specific radioimmunoassay for free thyroxine, directly determined in the diffusate obtained from equilibrium dialysis of serum. The intra- and interassay precisions were 7.5 +/- 0.27 and 9.1 +/- 0.58 ng/liter (mean +/- SD), respectively. The free thyroxine concentrations of normal persons and patients with thyroid disease were as follows: normal, 7.6 +/- 1.7; euthyroid patients receiving phenytoin, 6.9 +/- 1.4; hypothyroidism, 2.9 +/- 1.3; and hyperthyroidism, 32.3 +/- 12.3 ng/liter (mean +/- SD).

Cross Reactions

Further study on the two-column plasma catecholamine assay.

The two-column procedure for plasma catecholamine determination was adopted as a routine diagnostic test. It was found that the recovery of catecholamine added to properly preserved plasma was 65%. The most efficient recovery occurred when the water content of alumina used was above 23%. Both interassay and intra-assay precision were +/- 10% (coefficient of variation). The catecholamine was stable, in properly preserved plasma, for at least 18 days at -20 degrees C.

Aluminum

Insulinoma: clinical and diagnostic features of 60 consecutive cases.

Insulinoma is a rare tumor, occurring more often in women and in the older age range. Eighty percent of patients have a single benign tumor, usually less than or equal to 2 cm in diameter, located with about equal frequency in body, head, or tail of the pancreas and amenable to surgical cure. About 10% have multiple tumors; in this group there is a high incidence of multiple endocrine neoplasia type I syndrome. The remaining 10% of patients have metastatic malignant insulinoma. Symptoms are intermittent, recur at irregular intervals in the food-deprived state over a median of 1 1/2 years, and arise from varying degrees of neuroglycopenia. Symptoms often lead to misdiagnosis as a neurologic or psychiatric disorder. Transient neurologic deficits and EEG abnormalities can be observed during hypoglycemia. Diagnosis requires repeated demonstration of hypoglycemia (glucose less than or equal to 40 mg/dl) during spontaneous or provoked symptoms, relief with ingestion of carbohydrates, simultaneous hyperinsulinemia (serum insulin greater than 6 muU/ml), and absence of insulin antibodies. A useful diagnostic adjunct is the intravenous tolbutamide test, for which new diagnostic criteria are presented.

Adenoma, Islet Cell