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Biomedical subjects

G S Leight

Publications and source records attributed to G S Leight.

At least 37 records · Page 2Linked to original sources
PubMed1990

Function in athymic nude mice of parathyroid heterografts from patients with primary hyperparathyroidism and secondary hyperparathyroidism.

Heterotransplantation of adenomatous parathyroid glandular tissue from humans with primary hyperparathyroidism into athymic nude mice creates a unique animal model of this disease. The mice manifest high concentrations of both midregion/C-terminal human parathyroid hormone and biologically active intact human parathyroid hormone relative to either mice with no implants or mice that received normal human parathyroid tissue. Secretion of these substances is maintained in most mice for at least 9 to 13 months after implantation. In addition, animals that have experienced implantation exhibit other characteristics associated with human primary hyperparathyroidism including relative hypercalcemia and increased renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity. We also measured these parameters in a group of nude mice that received transplantation of a similar mass of hyperplastic parathyroid tissue that was obtained from patients with uremic secondary hyperparathyroidism. Although we hypothesized that the level of human parathyroid hormone secretion from these implants would fall over time in response to the normal host environment, hormone levels remained as high as those in recipients of adenomatous heterografts, even after 9 to 13 months. Moreover, similar biologic effect of the excess parathyroid hormone (i.e., relative hypercalcemia, hyperphosphatasemia, and increased 1,25-dihydroxyvitamin D biosynthesis) were detected. These animal models should prove extremely useful in supplementing our understanding of hyperparathyroid disorder in man.

Adenoma↗
PubMed1989

Cystosarcoma phyllodes. Effective therapy with cisplatin and etoposide chemotherapy.

Cystosarcoma phyllodes is an unusual breast neoplasm that rarely metastasizes. Most series report chemotherapy, radiation, and hormonal therapy to be ineffective. Three patients were treated with cisplatin and etoposide combination chemotherapy with effective palliation in two patients. Radiation therapy was effective in controlling symptomatic metastasis in all three patients. Hormonal therapy was ineffective in two patients despite the presence of positive hormone receptors. Chemotherapy and radiotherapy may be more effective in the treatment of this tumor than has been reported, although there is no apparent role for hormonal therapy. Functional hormone receptors are probably not present.

Adult↗
PubMed1989

Immunocytochemical analysis of estrogen receptors as a predictor of prognosis in breast cancer patients: comparison with quantitative biochemical methods.

Biochemical quantitation of estrogen receptors has been used to predict prognosis in breast cancer. Immunocytochemical analysis of estrogen receptors correlates with biochemical analysis but has very few follow-up studies in the literature to validate it as a prognostic indicator. 257 patients were followed for up to 10 years (median, 6.2 years) after primary surgical treatment. Estrogen receptor analysis using both biochemical and immunocytochemical techniques was performed on their tumor specimens. Patients with positive estrogen receptor values had longer survival than patients with negative values. This was demonstrated by both methods in the first 5 years of follow-up but only by immunochemistry after 5 years. The relationship between estrogen receptor status and disease-free interval was less strong than with survival. This study demonstrates that immunocytochemical estrogen receptor analysis was of prognostic significance.

Biomarkers, Tumor↗
PubMed1989

Cell dissociation techniques in human breast cancer--variations in tumor cell viability and DNA ploidy.

Approximately 70% of breast cancers contain cell populations with hyperdiploid (greater than G0/G1) DNA content; however, cells cultured from breast cancers have only diploid DNA contents and karyotypes. Mechanically dissociated cells rarely, if ever, grow in culture, while enzymatically dissociated cells do grow in most cases. To determine if cell dissociation techniques used to prepare cells for culture and other laboratory procedures select for cells with specific features, and if tumor cells are killed in the process, breast cancer cells obtained by mechanical dissociation and by enzymatic dissociation were examined for DNA content and cell viability (measured by dye exclusion). Mechanical dissociation yielded more dead cells and cells with hyperdiploid (greater than G0/G1) DNA than did enzymatic dissociation. Hyperdiploid cells were also found in the dye-excluding population with each dissociation technique, suggesting that the hyperdiploid cells were not always dead. We conclude that, in vivo, tumors contain cellular subpopulations with low viability and hyperdiploid (greater than G0/G1) DNA patterns. The extent to which these subpopulations are present in a sample depends on the dissociation technique employed. That only diploid cells are found in cultures of primary breast cancers may be because enzymatic dissociation, used to prepare cells for culture, yields predominantly diploid cells. These observations also have important implications for interpreting measurements made on dispersed cells, e.g., viability, DNA content, and other cytochemical markers.

Breast Neoplasms↗
PubMed1989

MR evaluation of adrenal masses at 1.5 T.

We retrospectively studied the value of MR imaging at 1.5 T to distinguish between nonadenomatous (n = 17) and adenomatous (n = 15) adrenal masses on the basis of (1) signal-intensity ratios on T1- and T2-weighted spin-echo images, (2) T2 relaxation times, and (3) T2 relaxation-time ratios. Univariate and then multivariate logistic regression were applied to these quantitative parameters to determine which of these best discriminated nonadenomas from adenomas, and whether or not more than one of these parameters improved the prediction. The adrenal mass/liver signal-intensity ratio on T2-weighted spin-echo images could not be used to differentiate nonadenomas from adenomas. Adrenal mass/fat signal-intensity ratios on T2-weighted spin-echo images, adrenal/liver T2 relaxation-time ratios, and adrenal mass T2 relaxation times were best for distinguishing nonadenomas from adenomas. By using a T2 value of greater than 61 msec, the true-positive ratio/false-positive ratio of differentiating nonadenomas from adenomas was 100%/20%; at greater than 82 msec, it was 64%/0.06%. The adrenal mass/fat signal-intensity ratios on T2-weighted spin-echo images and the adrenal/liver T2 relaxation-time ratios showed similar inherent discriminatory capacity. Overlap remains despite the use of these parameters. On the basis of this preliminary information, we conclude that MR has merit for the characterization of adrenal masses at 1.5 T. T2 relaxation time of the adrenal mass shows the greatest promise for discriminating nonadenomas from adenomas.

Adenoma↗
PubMed1989

Circadian rhythms for calcium, inorganic phosphorus, and parathyroid hormone in primary hyperparathyroidism: functional and practical considerations.

We obtained serial serum and urine samples from 14 patients with primary hyperparathyroidism both before and 3 to 9 months after excision of their parathyroid adenomas to (1) determine whether the circadian rhythms for calcium, phosphorus, and parathyroid hormone (PTH) previously described in normal human beings are disturbed in this disorder; (2) gauge the effect of surgical treatment on the patterns observed before intervention; and (3) ascertain whether time(s) of blood sampling can be defined for optimal biochemical detection of the disease. Significant rhythms for serum phosphorus, ionized calcium, PTH, urine phosphorus, and urine calcium were observed in many but not all patients before and after surgery. Nonetheless, collective analysis revealed the following: (1) diurnal patterns for serum ionized calcium, phosphorus, urine calcium, and urine phosphorus in patients with primary hyperparathyroidism both before and after surgery, whereas a rhythm for serum PTH was uniquely observed after surgical treatment; and (2) no significant correlation between preoperative serum ionized calcium and PTH but restoration of the expected reciprocal relationship between these variables after surgery. Although variability in individual expression of the rhythm for PTH precludes precise definition of a sampling "window" when hormone levels are likely to be highest, collection of data at points throughout the day helped establish the diagnosis of primary hyperparathyroidism in several patients with borderline serum biochemistries.

Adenoma↗
PubMed1988

Benign retroperitoneal schwannoma.

A case of benign retroperitoneal Schwannoma is presented, with special attention to clarification of often confused pathologic nomenclature. The radiologic diagnosis and the literature on this rare tumor are reviewed.

Adult↗
PubMed1987

Inflammatory breast carcinoma. Effective multimodal approach.

Twenty-two patients with inflammatory breast carcinoma received preoperative chemotherapy consisting of weekly administration of cyclophosphamide, doxorubicin hydrochloride, fluorouracil, and vincristine sulfate for six weeks. Postoperative therapy consisted of 22 weeks of biweekly administration of these drugs. Regional radiotherapeutic consolidation followed chemotherapy. Nineteen patients completed therapy. Twelve of these patients remain disease free (median, 15 months; range, four to 32 months). Median disease-free survival for all 22 patients is 13 months or more (range, zero to 32 months). Median overall survival is 18 months or more (range, one to 33 months). This regimen compares favorably with prolonged adjuvant and maintenance chemotherapy for inflammatory breast carcinoma.

Adult↗
PubMed1987

Estrogen receptor determination by monoclonal antibody in fine needle aspiration breast cancer cytologies: a marker of hormone response.

A monoclonal antibody (H222) prepared against purified estrogen receptor has been demonstrated to be highly specific and sensitive in an immunohistochemical assay for the detection and quantification of estrogen receptor in human breast carcinoma biopsy specimens. To evaluate the clinical applicability of this assay in cytologic specimens, response to therapy in 12 patients with recurrent breast cancer was correlated with H222 antibody localization in specimens obtained by fine needle aspiration biopsy. All 7 patients with positive H222 responded to hormone therapy (1 complete and 3 partial remissions and 3 stable disease), while 1 of 5 patients with negative H222 responded (1 stable disease). This experience suggests a role for immunohistochemical estrogen receptor determinations in prediction of response to hormonal therapy in patients whose tumor is accessible only to aspiration biopsy. Special care in the handling and interpretation of specimens is essential to optimal application of this method.

Adult↗
PubMed1987

Benign adrenal lesions mimicking malignancy on MR imaging: report of two cases.

Two cases of nonmalignant adrenal masses with prolonged T2 relaxation time and increased adrenal/liver signal ratios are reported. These two cases, one a functioning adenoma with small areas of hemorrhage and the other tuberculosis, emphasize that increased signal intensity in an adrenal mass on T2-weighted images is not always due to malignancy or a pheochromocytoma. While the signal characteristics of an adrenal mass are useful in distinguishing malignancy or pheochromocytoma from benign adenomas, other studies (such as computed tomography for the detection of hemorrhage), clinical evaluation, and percutaneous biopsy remain useful in the investigation of an adrenal mass.

Adenocarcinoma↗
PubMed1987

What is the clinical significance of bone loss in primary hyperparathyroidism?

To help determine the clinical significance of the bone loss associated with primary hyperparathyroidism, we studied the prevalence of vertebral fractures in a group of patients with this disorder. From a registry of parathyroidectomies, 206 cases were reviewed, and lateral chest roentgenograms were studied for the presence of fractures. All roentgenograms were interpreted by two of the investigators who were "blinded" to diagnoses. Comparisons of readings were made that assured interrater agreement. A group of patients who underwent cholecystectomy served as controls. Studied in a logistic regression analysis model, controlling for the effects of age, sex, and race, primary hyperparathyroidism was found to be significantly associated with vertebral fractures. Subgroup analyses performed on the patients with hyperparathyroidism failed to identify specific biochemical or clinical markers associated with fractures. Our results suggest that the bone loss of primary hyperparathyroidism is clinically significant, leading not only to decreased bone densities but also to an increased prevalence of fractures.

Adult↗
PubMed1986

Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity.

In an evaluation of 213 patients from 15 kindreds with familial medullary thyroid carcinoma (MTC), we detected 41 subjects from two kindreds (L and O) who had MTC but no extra-thyroidal manifestations (hyperparathyroidism, phaeochromocytomas or mucosal neuromas) of multiple endocrine neoplasia (MEN) type IIa or IIb. In screening 178 members of the L and O kindreds, we found no evidence that any of them had died from MTC. To assess whether the malignancy was relatively indolent in these families, 20 selected subjects from the two kindreds were compared with 33 MEN IIa subjects. Both groups had clinically occult disease which was diagnosed biochemically by documenting elevated plasma calcitonin (CT) levels following stimulation with intravenous calcium and pentagastrin. There were no differences in the peak stimulated plasma CT levels at the time of diagnosis (1055 +/- 236 pg/ml versus 1096 +/- 191 pg/ml) or the incidence of regional lymph node metastases (0/20 versus 1/33) in the two groups. The mean age at diagnosis, however, was significantly higher in patients of the L and O kindreds than in patients with MEN IIa (43.1 +/- 3.4 years versus 21.1 +/- 2.2 years; P less than 0.001) indicating that in the two kindreds the MTC either developed at a later age or grew more slowly. This study demonstrates that MTC may occur in a familial pattern distinct from its presentation as MEN IIa or MEN IIb. In this setting it appears to be the least aggressive form of MTC yet described.

Adolescent↗
PubMed1986

Fluoxymesterone stimulation of tumor marker secretion in patients with breast carcinoma.

The gross cystic disease fluid protein of 15,000 MW (GCDFP-15) has been demonstrated to be a circulating glycoprotein tumor marker for breast carcinoma in approximately 40% of patients with advanced disease. A recent retrospective analysis of plasma GCDFP-15 levels in patients with advanced breast cancer suggested that androgen therapy could cause significant increases in plasma levels in the absence of disease progression. In order to evaluate the frequency, time course, and intensity of the androgen effect on GCDFP-15 production, a prospective study was initiated. Twenty-nine patients with stage IV breast carcinoma were treated with fluoxymesterone (20 or 30 mg/d). Plasma levels of GCDFP-15 and carcinoembryonic antigen (CEA) were measured by radioimmunoassay before and at various times during therapy. By day 6 of therapy, plasma GCDFP-15 had increased significantly (p = 0.03) from a mean basal level of 58 +/- 12 ng/ml to 160 +/- 60 ng/ml. By contrast, the mean CEA levels in the same patients increased only from 36 +/- 14 ng/ml. The distribution of percent increases in plasma GCDFP-15 was not uniform, but patients with high (greater than 82 ng/ml) basal levels had marked (greater than or equal to 75%) increases in 6/6 (100%) cases, whereas patients with low (less than 30 ng/ml) basal levels had similar increases in only 2/15 (13%) cases. Urinary excretion of GCDFP-15 usually paralleled the increases in plasma levels of the glycoprotein during the first six days of therapy. A linear correlation between percent change in plasma and percent change in urinary GCDFP-15 was demonstrated. A permanent cell line of human breast carcinoma, T47-D, was stimulated to secrete GCDFP-15 in vitro by androgen, but not by estrogen. From these data, we conclude that androgens can specifically stimulate secretion of GCDFP-15 by breast carcinoma tissue in most patients with elevated plasma levels of GCDFP-15, and in some patients with normal levels. The stimulation occurs within days and is not associated with clinical signs of tumor growth.

Apolipoproteins↗
PubMed1986

Intraluminal thrombus and bowel obstruction in acute leukemia due to bleeding Meckel's diverticulum.

Gastrointestinal bleeding from Meckel's diverticulum resulted in small bowel obstruction by thrombus in two patients with acute myelogenous leukemia during bone marrow aplasia and recovery from induction chemotherapy. Although gastrointestinal symptoms and complications are common in acute leukemia, these two cases are unique and describe a new syndrome that requires prompt recognition and surgical intervention. The complication of localized bowel obstruction by intraluminal thrombus is heretofore unreported.

Adult↗
PubMed1986

Stimulation of insulin secretion by a rapid intravenous calcium infusion in patients with beta-cell neoplasms of the pancreas.

The effects of calcium on fasting plasma insulin and glucose levels were compared in 16 normal subjects and 11 patients with beta-cell neoplasms of the pancreas. Calcium was administered iv either as a rapid calcium infusion (RCI; 2 mg/kg in 1 min) or as a long calcium infusion (LCI; 12 mg/kg in 3 h). In normal subjects, the RCI produced a rise in mean plasma insulin from 11 +/- 1 (+/- SEM) microU/ml basally to a peak of 18 +/- 2 microU/ml (P less than 0.001). No consistent pattern of change in insulin levels occurred during the LCI, and plasma glucose levels did not change significantly with either test. In the patients with beta-cell neoplasms, the RCI resulted in a rapid increase in mean plasma insulin from 36 +/- 6 microU/ml to a peak level of 312 +/- 67 microU/ml (P less than 0.002). With the LCI, a more gradual rise in insulin from 35 +/- 11 to 92 +/- 36 microU/ml occurred (P less than 0.002). The mean increase in insulin in the patients with beta-cell neoplasms was significantly greater for the RCI than for the LCI (P less than 0.01). Pronounced increments in plasma insulin occurred in all 11 patients after the RCI, but in only 3 of 8 patients during the LCI. Plasma glucose levels declined significantly from 69 +/- 7 to 56 +/- 8 mg/dl during the RCI (P less than 0.05) and from 69 +/- 8 to 49 +/- 7 mg/dl during the LCI (P less than 0.005). Symptomatic hypoglycemia developed in 3 patients during the LCI but did not occur after the RCI. These data indicate that calcium is a more effective insulin secretagogue in patients with beta-cell neoplasms when administered as an RCI than as an LCI, and suggest that the RCI may be a useful test for the diagnosis of insulin-secreting tumors.

Adenoma, Islet Cell↗
PubMed1986

MRI with surface coils for parathyroid tumors: preliminary investigation.

The ability of MRI to detect parathyroid gland enlargement was assessed using 1.5-T systems and surface coil reception. Nine patients with primary hyperparathyroidism were studied before surgical neck exploration. Five-millimeter-thick axial images were obtained from the thyroid cartilage to the sternal notch. Both T1 and T2 contrast-weighted spin-echo sequences were performed in most cases. MRI correctly identified six out of seven parathyroid adenomas. In the false-negative case, T2 contrast-weighted sequences were not performed for technical reasons. In the one case of surgically proven parathyroid hyperplasia, a lesion identified by MRI as a parathyroid adenoma coincided at surgery with the largest of three hyperplastic parathyroid glands. A single case demonstrated a potential pitfall in the search for ectopic parathyroid glands: A large colloid cyst in the posterior portion of the thyroid gland showed signal characteristics indistinguishable from a parathyroid adenoma. The enlarged parathyroid glands were best visualized on T2 contrast-weighted sequences, with the lesions demonstrating greater signal than surrounding tissues.

Adenoma↗
PubMed1986

Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors.

A monoclonal antibody to human estrogen receptor protein (H222 Sp gamma), amplified via immunoperoxidase techniques, was used in the analysis of estrogen receptor in 452 breast carcinomas, 100 endometrial carcinomas, and 15 melanomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining (HSCORE). Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis. In all cases H222 Sp gamma localized in the nucleus of target cells. A semiquantitative correlation existed between HSCORE and biochemical assays for breast and endometrial tissues. The sensitivities and specificities for HSCORE as compared to the biochemical assays ranged from 80 to 95% and from 74 to 94%, respectively. HSCORE correlated with tumor grade for breast and endometrial carcinoma. Immunohistochemical evaluation showed no specific staining in melanomas. The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied.

Antibodies, Monoclonal↗