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Biomedical subjects

S A Wells

Publications and source records attributed to S A Wells.

At least 145 records · Page 8Linked to original sources
PubMed1982

Review: Medullary carcinoma of the thyroid: radiographic features of a unique tumor.

Medullary carcinoma of the thyroid is a unique neoplasm characterized by consistent production of a hormonal marker, calcitonin, calcification of both primary and metastatic foci, and association with other endocrine neoplasms. It accounts for 3.5%--10% of all thyroid malignancies. First described by Hazard et al. [1] in 1959, this neoplasm has become the focus of increasing clinical and experimental investigation. It occurs both sporadically and in families. When familial, it is seen as a component of the multiple endocrine neoplasia type II (MEN-II) syndromes. Interest in medullary carcinoma of the thyroid far exceeds that warranted by its infrequent occurrence. Over 200 articles dealing with this tumor have appeared in the medical literature in the last 10 years. This may be attributed to the number of distinctive properties of the tumor: the familial occurrence when associated with endocrinopathies, the propensity to produce amyloid, and the great synthetic capability for the biogenic amines calcitonin, serotonin, histaminase, and prostaglandins. Of greatest importance is the value of calcitonin radioimmunoassay for detecting patients with the tumor even though it may be evident clinically. Fifty-three patients with surgically and biochemically proven medullary carcinoma were evaluated and followed at Duke University Medical Center from 1968 to 1981. Ten patients with sporadic tumor, 37 with MEN type IIa, and six with MEN type IIb prompted this review. They will be used to illustrate the varied and sometimes characteristic radiographic manifestations of medullary carcinoma of the thyroid. This tumor has a spectrum of radiographic features in multiple organs that, when familial, facilitate its recognition and treatment.

Adolescent↗
PubMed1982

Osteomalacia after parathyroidectomy in patients with uremia.

Five patients on maintenance dialysis had symptoms of osteomalacia, proven by biopsy, after parathyroidectomy. In all five patients clinical and radiographic manifestations of secondary hyperparathyroidism were present before surgery, and in two patients preoperative biopsy of bone confirmed the existence of osteitis fibrosa. Like previously described patients with osteomalacia all five had multiple fractures and normal or high serum calcium concentrations that rose to abnormally high values on treatment with vitamin D or dihydrotachysterol. Quantitative histomorphometry of biopsy after parathyroidectomy showed no residual parathyroid hormone effect and nearly complete cessation of mineralization. Four patients had forearm autografts of parathyroid tissue that appeared to be functioning at very low rates according to paired venous sampling, and all five patients had relatively low circulating concentrations of parathyroid hormone. This and earlier experiences reported by others suggest that secondary hyperparathyroidism may have an important facilitative role in the mineralization of bone in uremic patients.

Adult↗
PubMed1982

Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma.

Hormone-dependent breast carcinomas respond to deprivation of biologically active estrogens with objectively quantifiable tumor regression. Aminoglutethimide, a known inhibitor of steroid synthesis, is also a potent blocker of the aromatase enzyme and, thus, of estrogen production. We developed an effective regimen to inhibit estrogen production in postmenopausal women using aminoglutethimide and replacement glucocorticoid. One hundred forty-seven women initially received aminoglutethimide and replacement glucocorticoid as treatment of metastatic breast carcinoma. One hundred twenty-nine women are currently evaluable for assessment of clinical and hormonal responses. Thirty-seven percent of unselected women and 49% of estrogen receptor-positive patients experienced objective tumor regression. Responses occurred predominantly in soft tissue (47%) and bone (35%) and lasted 30 +/- 9.1 months for complete and 14 +/- 1.5 months for partial regressions. Plasma and urinary estrogen levels fell equally in responder versus nonresponder groups whereas androgen levels declined less in patients with progressive disease.

Aminoglutethimide↗
PubMed1982

Carcinoembryonic antigen in nonhuman primates.

Blood levels of carcinoembryonic antigen (CEA) have been measured in several nonhuman primate species. Only gorillas and chimpanzees were found to have significant elevations of CEA-like activity in their blood compared to the normal values of less than 2.5 ng/ml in humans. The average CEA level in 134 chimpanzees was 25.2 ng/ml (range, 4.2--95 ng/ml) and in 13 gorillas it was 32 ng/ml (range, 12.4--61.9 ng/ml). These levels were not related to sex. Blood levels repeatedly taken over a 1 1/2-year period remained relatively stable in both species. Analysis of parallelism of immunologic reactivity showed chimpanzee CEA to be similar to but not identical with human CEA. The molecular size of chimpanzee CEA was also similar to that of human CEA.

Animals↗
PubMed1982

Biochemical correlates of morphologic differentiation in human breast cancer.

In 115 breast carcinoma tissues, histologica grade and cell cytosol concentrations of estrogen receptor (ER) and progesterone receptor (PR) and two breast cyst fluid proteins (gross cystic disease fluid protein [GCDFP-15] and nonreceptor progesterone-binding protein [PBP]) were deterMined. Higher levels (expressed as femtomoles per milligram of protein) of ER (128 +/- 28 versus 11 +/- 1, P less than 0.001) and PR (82 +/- 16 versus 3 +/- 1, P less than 0.001) were found in grade 1 (well-differentiated) carcinomas as compared with grade 3 (poorly differentiated) carcinomas. Similarly, higher concentrations (expressed as nanograms per milligram of cytosol protein) of GCDFP-15 (2110 +/- 840 versus 210 +/- 40, p less than 0.001) and PBP (4920 +/- 1200 versus 370 +/- 60, P less than 0.001) were found in grade 1 as compared with grade 3 carcinomas. Tumor cytosols that contained low levels of both cyst proteins (less than 225 ng/mg GCDFP-15 and less than 750 ng/mg PBP) had a high incidence of grade 3 (35 of 46, 78%) or grade 2 (15 of 46, 33%) histologic findings and had a high incidence of receptor-negative specimens (27 of 52, 52%). Based on these cutoff levels, grade 2 lesions were subdivided into a "high" cyst protein group, which had ER and PR levels similar to grade 1 tumors (93.1 +/- 26.7 for ER and 84.7 +/- 32.4 for PR, P greater than 0.3), and a "low" group, which had receptor values similar to grade 3 carcinomas (14.1 +/- 5.3 for ER and 9.1 +/- 5.2 for PR, P less than 0.3). Although the mean cytosol content of carcinoembryonic antigen (CEA) was significantly higher in malignant tissues (125 +/- 27 ng/mg cytosol protein) than in benign tissues (4.8 +/- 1 ng/mg cytosol protein), the CEA content was not significantly different between grades 1 and 3 tumors.

Apolipoproteins↗
PubMed1981

A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer.

We randomized 96 postmenopausal women with metastatic breast carcinoma to receive surgical adrenalectomy or medical therapy with an adrenal inhibitor, aminoglutethimide (AG), plus replacement hydrocortisone. Before randomization, women were stratified according to disease-free interval, site of dominant disease, and estrogen-receptor status. Of 40 evaluable women treated with AG and hydrocortisone, 53 per cent had objective responses, as compared with 45 per cent of 29 women undergoing surgical adrenalectomy (P value not significant). Responses lasted a mean of 17.2 months in the medical group and greater than 17.1 months in the surgical group (not significant). Estrogen levels fell similarly in response to either treatment, whereas AG and hydrocortisone preserved androgen production. A null hypothesis tested the single question asked by this study: "Is surgical adrenalectomy superior to treatment with AG and hydrocortisone?" Rejection at significance levels of P = 0.01 and P = 0.07 for differences of 20 per cent and 10 per cent, respectively, suggested that medical therapy with AG and hydrocortisone may be logically chosen in place of surgical adrenalectomy.

Adrenalectomy↗
PubMed1981

Clinical and radiographic correlations in breast cancer patients with osseous metastases.

Serial metastatic bone series on 12 patients with skeletal metastases from carcinoma of breast were studied. Changes in the clinical and radiographic parameters of the patients were correlated. Patients were all treated on a research protocol evaluating "medical adrenalectomy" with aminoglutethimide or surgical adrenalectomy. Seventeen clinical changes were noted in twelve patients. Sixteen of these observations demonstrated positive clinical correlations with concurrent skeletal radiographs. A lytic bone pattern correlated clinically with progressive tumor growth. A blastic bone pattern was present when objective clinical data indicated disease remission.

Adrenalectomy↗
PubMed1981

Histologic study of the ocular lesions in multiple endocrine neoplasia syndrome type IIb.

We studied the clinical and histopathologic findings in the eyes of two patients with multiple endocrine neoplasia type IIb. A prominent clinical feature of this condition is enlarged nonmyelinated corneal nerves composed of bundles of axons associated with Schwann cells. Prominent corneal nerves within an otherwise normal corneal stroma are an important clinical feature of multiple endocrine neoplasia type IIb. Because of this, ophthalmologists are in a position to make an early diagnosis and hence to recommend diagnostic procedures and treatment for the associated potentially fatal medullary carcinoma of the thyroid and pheochromocytomas.

Adolescent↗
PubMed1981

Adenylate cyclase activity in human parathyroid tissues: reduced sensitivity to suppression by calcium in parathyroid adenomas as compared with normal glands form normocalcemic subjects or noninvolved glands from hyperparathyroid subjects.

To examine whether alterations in parathyroid adenylate cyclase might be associated with glandular hyperfunction, we compared enzyme activity in membranes from 7 normal glands with activity from 18 abnormal and 5 noninvolved glands from patients with primary hyperparathyroidism. Compared with the normal glands, the specific enzyme activity after full stimulation with guanyl-5'yl imidodiphosphate was significantly decreased in both hyperplastic and noninvolved glands from the hyperparathyroid subjects. While the enzyme activity of all tissues could be suppressed by calcium, a twofold higher calcium concentration was required for comparable suppression of the enzyme from adenomas as compared with normal or noninvolved glands. Alterations in the adenylate cyclase complex of hyperplastic parathyroid glands may explain, in part, the elevated "set point" for calcium homeostasis in primary hyperparathyroidism.

Adenoma↗
PubMed1981

Management of hereditary medullary thyroid carcinoma.

In this paper we have briefly outlined our views on the management of hereditary MTC. We have stressed the fact that although many patients with the usual form of disease have an indolent clinical course there exists a population of patients who may be at risk for widely disseminated virulent tumour. Also, some patients can have marked invasion of adjacent tissues in the cervical region from localized tumour. Hence it seems rational to attempt removal of the primary tumour prior to the development of regional or distant metastases. The role of the combined calcium-pentagastrin provocative test to identify patients with preclinical disease has been outlined. The only definitive treatment for the disease is total thyroidectomy with resection of adjacent cervical nodes. Many patients who are treated at a time when the disease has become clinically detectable will have residual tumour or recurrence as indicated by abnormal calcitonin levels in the blood. Since most of these patients seem to take an indolent clinical course, it is suggested that they should not be treated with radiation therapy and/or chemotherapy, even though residual MTC is known to be present. Even in patients with advanced stages of MTC, the use of chemotherapy and radiation therapy has not been encouraging. However, some aspects of the management of patients with aggressive disease are discussed. Finally, the lack of features to predict which patients may have a poor prognosis is outlined and some new approaches to defining such parameters are discussed.

Antineoplastic Agents↗
PubMed1981

Medullary carcinoma of the thyroid in the multiple endocrine neoplasia IIA syndrome.

Clinical, biochemical, and morphologic parameters in 72 patients with familial medullary thyroid carcinoma (MTC) associated with multiple endocrine neoplasia IIA (MEN IIA) were reviewed. Sixty-nine patients had undergone total thyroid resection. In 27 patients (Group I) the thyroid tumors were smaller than 0.7 cm in diameter; five of these patients had C-cell hyperplasia alone. In 19 patients (Group II) tumors ranged from 0.7 to 1.5 cm, and in 26 patients (Group III) they were larger than 1.5 cm. The mean ages at surgery were 19.6 years (Group I), 33.7 years (Group II), and 32.2 years (Group III). Regional lymph node metastases occurred less often in patients of Group I, 4/20 (20%) and Group II, 4/13 (30%) than in those of Group III, 14/17 (82%) [p = 0.0001]. Elevated postoperative plasma calcitonin levels, indicative of residual MTC, were observed less frequently in patients in Group I, 6/27 (22%) and Group II, 6/15 (50%) than in Group III, 11/15 (73%) [p = 0.005]. All of the patients in Group I and Group II are alive (mean follow-up of 3.5 years and 6.0 years following surgery), whereas 6/26 (23%) Group III patients have died of metastatic MTC, three within 2 years of initial diagnosis. Histologic features varied with tumor diameter. All tumors from patients in Group III contained amyloid, while the majority of those from patients in Group I had an infiltrative configuration and 9/22 tumors lacked amyloid. Among neoplasms from patients in Group III, mitotic figures correlated with distant metastases or death from tumor. Only 1/16 patients who died from MTC had a distinctive tumor morphology, namely a prominent component of small cell anaplastic carcinoma. Early detection of minimal MTC in MEN IIA family members offers the best chance of curing patients with this potentially fatal lesion.

Adolescent↗
PubMed1981

Stimulation of in vitro release of calcitonin from rat and human C-cells by cimetidine.

Previous reports have suggested that the H2-receptor blocker, cimetidine, can inhibit parathyroid hormone (PTH) release. The present studies were designed in an attempt to see whether cimetidine affects secretion of calcitonin (CT) as well. Entire thyroparathyroid glands from 8-day-old baby rats or small pieces of a human medullary thyroid carcinoma were incubated at 37 C for up to 8 h in chemically defined culture medium gassed with 95% 02-5% CO2. With rat thyroparathyroids, both CT and PTH released into medium were measured using RIAs that detect that rat hormones. CT secreted from human C-cells was measured using an RIA for human CT. The results were: (A) As we had found previously, cimetidine at doses of 3 x 10(-3) M and 9 x 10(-3) M inhibited PTH release from rat thyroparathyroids by as much as 50-60% (p less than 0.05 - less than 0.001). In these same experiments, cimetidine produced increases of approximately 1- to 5-fold in the CT levels found in the medium (p less than 0.05 - less than 0.001). (B) Fragments of human medullary thyroid carcinoma incubated for 3 h in the presence of 10(-5) M cimetidine released considerably more CT than tissue incubated in control medium (48 +/- 9.3 vs 21 +/- 3.6 ng CT/microgram tissue protein, p less than 0.05). Our results show that cimetidine in vitro not only can inhibit secretion of PTH but also apparently can promote the release of CT from both rat and human C-cells. Whether this effect is mediated by H2 receptors and whether it is of any physiological significance awaits clarification.

Animals↗
PubMed1980

Comparison of sex steroid receptor analyses and carcinoembryonic antigen with clinical response to hormone therapy.

This study corroborates previous reports which suggested the efficacy of estrogen receptor (ER) analysis in predicting responses of patients with metastatic mammary carcinoma to hormonal therapeutic manipulation. The predictive value of multiconcentration titration and sucrose density gradient analyses of ERs and progesterone receptors (PRs) are compared. The predictive value of ER analyses can be improved by the discrimination of 8S versus 4S binding species or by the use of PR analysis in combination with ER analysis. The tumor-associated antigen, carcinoembryonic antigen (CEA), is evolving as an important quantitative aid in evaluating the clinical responses to patients receiving hormonal therapy.

Adrenalectomy↗
PubMed1980

Analysis of amniotic fluid, maternal plasma, and cord blood for a human breast gross cystic disease fluid protein.

Amniotic fluid was analyzed for the presence of the 15,000 monomer molecular size glycoprotein found in human breast gross cystic disease fluid (GCDFP-15). From 24 weeks' gestation a log-linear increase in levels of GCDFP-15 was noted. The levels of GCDFP-15 doubled every 16 to 28 days, and the highest value recorded was 7,200 ng/ml. At delivery, levels of GCDFP-15 in cord blood plasma were in a background range (mean, 8 ng/ml). Maternal plasma levels of GCDFP-15 were one to tenfold higher in the third trimester of pregnancy when compared to those in nonpregnant women. Since saliva is known to contain high concentrations of GCDFP-15 (10 to 70 micrograms/ml), it is proposed that the levels in amniotic fluid originate from saliva and tracheobronchial secretions.

Amniotic Fluid↗
PubMed1980

Influence of estrogen receptor status on response of metastatic breast cancer to aminoglutethimide therapy.

Aminoglutethimide (AG) is an effective chemical ablative form of therapy for metastatic breast cancer in postmenopausal women. Estrogen receptor (ER) status in breast cancer is useful in predicting the response to the hormonal treatments. Of 134 postmenopausal metastatic breast cancer patients treated with AG, ER analysis was done in 63 patients, 52 of whom are now evaluable. ER biopsy was performed prior to Ag therapy in 61 patients, but the results were not known to the investigators. ER value greater than or equal to 10 fmol/mg cytosol protein was considered ER positive (ER+), 4-9.9 fmol/mg borderline, and less than 4 fmol/mg ER negative (ER-). In 38 ER+ patients, objective response rate was 50% (three complete response, 16 partial response) and eight stabilization. Median duration of objective response was 15 months. Forty-three percent of the patients with borderline estrogen receptor level responded objectively (three partial response) with the median duration of response eleven months. Fourteen percent of ER- patients responded objectively (one complete response). Hence the estrogen receptor level predicts response in ER+ and ER borderline patients treated with AG.

Aminoglutethimide↗