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Biomedical subjects

S A Wells

Publications and source records attributed to S A Wells.

At least 163 records · Page 9Linked to original sources

Anaplastic variants of medullary thyroid carcinoma: a light-microscopic and immunohistochemical study.

Three unusual cases of anaplastic medullary thyroid crcinoma, two having small cell characteristics and one having the features of an anaplastic giant-cell carcinoma, were encountered during a review of 110 cases of familial and sporadic medullary carcinoma. Immunoperoxidase demonstration of calcitonin within tumor cells in these three cases enabled differentiation of the two small cell variants from lymphoma or other small cell carcinomas, and differentiation of the anaplastic giant-cell variant from other giant cell carcinomas of the thyroid. Although the existence of small cell carcinomas of the thyroid gland has been questioned, this study shows that small cell carcinomas of the thyroid gland do exist and that at least some are variants of medullary carcinoma. Whereas previous immunohistochemical studies have been successfully employed in defining the spectrum of C-cell proliferative disorders and in understanding the evolution of medullary thyroid carcinoma, this study demonstrates the value of these techniques in diagnostic pathology. Immunoperoxidase staining can be successfully used in differentiating unusual variants of medullary carcinoma from other thyroid tumors.

Adult↗

VMA excretion in patients with pheochromocytoma.

Studies in 20 patients, and a reanalysis of previously published data demonstrate that there is a significant linear relationship between the rate of urinary excretion of 3-methoxy-4-hydroxymandelic acid and the size of a pheochromocytoma. This relationship is most significantly demonstrated in a small group of patients with bilateral adrenal disease as part of the MEN II syndrome. Since not all pheochromocytomas are accurately localized preoperatively and significant numbers can be bilateral or extra-adrenal, this predictive index of tumor size has useful surgical implications. An obvious discrepancy between a prediction of size and operative findings should alert the surgeon to a more thorough search of the opposite adrenal and, indeed, all extra-adrenal paraganglionic sites for other secreting tumor tissue.

Adrenal Gland Neoplasms↗

The value of serial plasma levels of carcinoembryonic antigen and gross cyst disease fluid protein in patients with breast carcinoma and osseous metastases.

Serial plasma levels of the glucoprotein tumor markers carcinoembryonic antigen (CEA) and gross cyst disease fluid protein (GCDFP) were evaluated in 83 patients undergoing treatment for predominant osseous metastases from breast carcinoma. Abnormal plasma levels of CEA (greater than 10 ng/ml) and/or GCDFP (greater than 150 ng/ml) were observed in 53 (63.8%) subjects. Fifty-six courses of hormonal and chemical therapy were evaluated. Clinical response to therapy correlated positively with alterations in serial plasma levels of CEA and/or GCDFP. Increasing plasma levels of tumor markers were associated with clinical disease progression whereas decreasing plasma levels were associated with and generally preceded clinical disease remission. Of patients with metastatic carcinoma of the breast, responses to therapy are most difficult to evaluate in those with bone metastases. Serial determinations of plasma levels of CEA and/or GCDFP provide an objective indication of disease progression and regression and appear to be useful with skeletal x-rays and bone scans in evaluating patients with carcinoma of the breast.

Apolipoproteins↗

Long-term evaluation of patients with primary parathyroid hyperplasia managed by total parathyroidectomy and heterotopic autotransplantation.

Since 1973, we have performed total parathyroidectomy and forearm parathyroid autotransplantation in 36 patients with generalized (four gland) primary parathyroid hyperplasia. Twenty (56%) patients had nonfamilial parathyroid hyperplasia (NFPH) and 16 (44%) patients had familial parathyroid hyperplasia (FPH). Twenty-one patients (Group A) were undergoing operation for the first time and 15 (Group B) were having either second, third or fourth re-explorations for persistent hyperparathyroidism. All patients in Group A and nine patients in Group B had parathyroid resection and immediate autotransplantation as a single procedure. Six Group B patients had hyperfunctioning parathyroid tissue resected, cryopreserved, and subsequently grafted when it was evident that they had been rendered aparathyroid. A sustained differential elevation (13.7 fold +/- 2.7) of parathyroid hormone was detected in the antecubital vein of the grafted compared to the nongrafted arm in 35 (97%) patients. Two (5.6%) of the 36 patients (both with FPH; one Group A and one Group B) required permanent oral calcium and vitamin D replacement therapy and one (3%) patient (NFPH: Group A) had persistent hypercalcemia postoperatively, presumably due to a supernumerary gland. The remaining 33 (92%) patients became normocalcemia after surgery and 23 (70%) of them remained so. Ten (30%) of the 33 patients developed recurrent graft dependent hyperparathyroidism. Eight patients were from the group with FPH (8/14, 57%) and two were from the group with NFPH (2/19, 11%)(FPH vs. NFPH, p < 0.005). Because of symptoms of hypercalcemia or a serum calcium concentration exceeding 11 mg/dl, partial graft resection was performed in five patients and four became normocalcemic. Patients with generalized primary parathyroid hyperplasia may be difficult to cure, especially if the disease is familial. The technique of total parathyroidectomy and heterotopic autotransplantation of fresh or cryopreserved parathyroid tissue offers distinct advantages over alternative techniques.

Humans↗

Preservation of androgen secretion during estrogen suppression with aminoglutethimide in the treatment of metastatic breast carcinoma.

We evaluated the comparative effects of aminoglutethimide (AG) on androgen and estrogen levels estrone ([E1], estradiol [E2], plasma dehydroepiandrosterone-sulfate [DHEA-S], testosterone [T], dihydrotestosterone [DHT], delta 4-androstenedione [delta 4-A]), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin in postmenopausal patients with breast cancer randomly allocated to either AG treatment or bilateral surgical adrenalectomy as a control group. In response to either treatment, the plasma levels of E1 fell 62-75% (P less than 0.001) and urine E1 85.7-88.7% (P less than 0.001) in all study days over a 12-wk period. Similarly, the concentrations of E2 in plasma and urine fell 40-72% without statistically significant differences between the two treatment modalities. The relatively weak androgen, DHEA-S, was reduced by 92% (877.3 +/- 184.6 to 71.8 +/- 14.5 ng/ml) at 12 wk in women treated with AG, but suppressed nearly 99% (1,151 +/- 262 to 5.8 +/- 3.3 ng/ml) in adrenalectomized women. At all time points after treatment, the DHEA-S levels were significantly higher in patients receiving AG. Plasma concentrations of the potent androgens, T and DHT, were also relatively preserved during AG treatment. T levels were never significantly reduced by AG, and DHT concentrations were decreased only at the 4th wk to a maximum of 20%. delta 4-A levels fell 56% in response to this drug only on the 12th wk of therapy (basal, 0.79 +/- 0.09 ng/ml; 12 wk, 0.35 +/- 0.07 ng/ml). In marked contrast, all androgens fell significantly at each time period in response to surgical adrenalectomy, with an 81% maximum suppression of T, 73% of DHT, and 97% of delta 4-A. In response to estrogen suppression, plasma levels of FSH, LH, and prolactin did not change significantly throughout the treatment period in either therapy group. To examine possible contributions of the postmenopausal ovary to hormone levels during therapy, data from surgically castrate and spontaneously menopausal women were evaluated separately. No significant differences between the two groups were observed for E1, E2, T, DHT, DHEA-S, delta 4-A, LH, FSH, and prolactin. We conclude that equivalent and highly significant estrogen suppression occurs with either AG or surgical adrenalectomy although androgen secretion is preserved during AG treatment but not after surgical adrenalectomy. The combined effects of estrogen deprivation associated with androgen preservation might be significant in the therapeutic action of AG in hormone-responsive neoplasms.

Adrenalectomy↗

Resistance of the ovary to blockade of aromatization with aminoglutethimide.

Aminoglutethimide (AG) is a potent inhibitor of aromatization in placental microsomes and in peripheral tissues in postmenopausal women. Aromatase inhibitors have been used to block estrogen production and induce breast tumor regression in rodents. To inhibit ovarian estrogen production, we administered various doses of AG and its highly potent D-stereoisomer to premenopausal women with breast carcinoma. However, at no dose level did AG consistently lower estrone and estradiol concentrations in plasma below those observed in normal menstruating women. Uniform increments in LH and FSH were also not observed. Only during the luteal phase were the levels of estradiol (but not estrone) significantly suppressed. These observations are best explained by the possibility that aromatase enzymes in the ovary, as opposed to those in the placenta and in peripheral tissues, are partially resistant to the effects of AG.

Adult↗

Evaluation of baboon antiserum to carcinoembryonic antigen.

The common baboon (Papio), immunized with carcinoembryonic antigen (CEA), was found to form specific-site antibodies for CEA. The baboon antiserum does not recognize colon carcinoma antigen-III, but does demonstrate similar ionic strength effects to those previously described for goat antisera to the CEA-specific site(s). Baboon specific-site antibody for CEA can be used for radioimmunoassay of CEA in plasma and gives similar results to the commercial (Roche) goat anti-CEA.

Animals↗

Effects of calcium and cyclic nucleotides on rat calcitonin and parathyroid hormone secretion.

Recently we developed a system for studying concurrent secretion of calcitonin (CT)and parathyroid hormone(PTH)in vitro from single rat thyroparathyroid gland complexes. In the present study, mechanisms involved in secretion of CT and PTH were explored by altering the medium [Ca ] and by using the Ca antagonist, verapamil. We also re-examined the idea that cyclic nucleotides may help regulate secretion of these hormones and attempted to determine if effects of cyclic nucleotides might be altered by changes in medium [Ca]. Thyroparathyroid glands from 8-day-old rats were incubated in serum-free medium for 8h, and CT and PTH levels in the medium were measured by radioimmunoassays. We show for the first time that: (1) although low [Ca] is well known to promote PTH release, some extracellular Ca is needed for PTH secretion to occur at a maximal rate; (2) inhibition of Ca entry into cells with verapamil mimics the effects of low medium Ca on both CT and PTH release; and (3) cyclic nucleotides may exert their effects on secretion of CT and PTH at least in part via effects on Ca entry into cells.

Animals↗

Adrenal-cortical function in patients with medullary carcinoma of the thyroid and pheochromocytoma.

Medullary carcinoma of the thyroid (MCT) is reported to synthesize ACTH. This ACTH is believed to be responsible for the development of Cushing's syndrome in some patients with MCT. To determine the frequency of occurrence of adrenal cortical overactivity in patients with MCT, we measured plasma cortisol concentration and the urinary excretion of 17-hydroxycorticosteroids, 17-ketosteroids and urinary free cortisol in 22 patients with MCT and 7 patients with MCT plus pheochromocytomas. The patients with MCT and MCT plus pheochromocytoma had similar adrenal cortical function to age and sex matched normal subjects. We conclude that adrenal cortical function is usually normal in patients with MCT.

17-Hydroxycorticosteroids↗