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Biomedical subjects

G S Leight

Publications and source records attributed to G S Leight.

At least 19 recordsLinked to original sources
PubMed1995

Hyperparathyroidism in high-risk surgical patients: evaluation with double-phase technetium-99m sestamibi imaging.

PURPOSE: To evaluate the accuracy of technetium-99m sestamibi as a single agent in the detection and localization of hyperfunctioning parathyroid tissue in patients who underwent prior neck exploration or who otherwise are high surgical risks. MATERIALS AND METHODS: Thirty-nine patients with hyperparathyroidism underwent 40 double-phase Tc-99m sestamibi studies. Histopathologic correlation was obtained for all studies. RESULTS: Thirty patients had solitary adenomas, and nine had hyperplastic glands. One developed recurrent hypercalcemia after five-gland resection and underwent repeat imaging and operation. Double-phase sestamibi imaging prospectively enabled localization of 46 (77%) of 60 abnormal glands. Twenty-eight (93%) of 30 adenomas were correctly localized, whereas 18 (60%) of 30 hyperplastic glands were localized. The overall specificity of the study was 98% with one false-positive study. Gland weight and vascularity were statistically significant predictors of uptake of sestamibi. CONCLUSION: Double-phase Tc-99m sestamibi imaging is a promising technique for localization of parathyroid adenomas in high-risk surgical patients. Localization of multiple hyperplastic glands remains a challenge.

Adenoma↗
PubMed1993

Preoperative endocrine tumor localization utilizing a cost-effective approach.

Endocrine tumors commonly produce characteristic clinical signs, and laboratory tests lead to accurate diagnosis in a high percentage of cases. The successful management of these tumors usually requires complete surgical resection. A large number of preoperative localization procedures to facilitate the operative management of these tumors have been developed. This report reviews the recent contributions to this literature, with a particular emphasis on cost-effective use of these procedures.

Adenoma↗
PubMed1992

Non-autonomy of parathyroid hormone secretion in acute primary hyperparathyroidism.

A patient with acute primary hyperparathyroidism treated with mithramycin preoperatively, underwent neck exploration and two enlarged parathyroid glands were excised: one huge adenoma (6g) and another smaller gland. Mithramycin was administered preoperatively to lower life-threatening hypercalcaemia, and parathyroid slices from the huge adenoma removed at surgery were submitted in vitro to various calcium concentrations in the media to determine the influence of calcium on parathyroid adenoma secretory pattern in acute primary hyperparathyroidism. Mithramycin induced a significant decline in calcium levels and significant elevations of calciotrophic hormones (intact PTH, mid-region specific PTH, calcitonin and calcitriol). Significant suppression in PTH output in vitro was achieved by increasing calcium levels in the media. These results exclude autonomous PTH secretion (non-calcium dependent) as a possible aetiology of acute primary hyperparathyroidism. We suggest that a sudden increase in the set-point of the diseased parathyroid cells in the presence of a huge cell mass accounts, in large part, for both the marked hypercalcaemia and elevated PTH levels in this patient.

Acute Disease↗
PubMed1991

Parathyroid hormone secretion and target organ response in experimental acute pancreatitis.

To determine changes in parathyroid hormone secretion and target organ response caused by acute pancreatitis before the development of systemic toxic conditions, experimental acute pancreatitis was induced in rats with a choline-deficient, ethionine-supplemented diet. After 7 days, the rats were weighed and bled, and one kidney was assayed for 25-hydroxyvitamin D1 hydroxylase activity. Several manifestations of pancreatitis were observed in rats given the diet: weight loss (from 29.6 to 26.3 g vs that for control rats, from 29 to 52.8 g) and lower dietary intake (15.5 vs 47 g per rat per 7 days). Serum amylase levels fell from 1794 to 350 U/L in rats given the choline-deficient, ethionine-supplemented diet compared with levels of 1800 to 2100 U/L in control rats. The pancreases of rats given the choline-deficient, ethionine-supplemented diet showed degeneration, necrosis, and hemorrhaging. Serum levels of calcium, phosphorus, chloride, and parathyroid hormone did not change significantly throughout the experiment. Renal 25-hydroxyvitamin D1 hydroxylase activity was higher than in control rats (8.9 +/- 0.8 vs 7.6 +/- 0.6 fmol/mg of kidney per minute). Acute pancreatitis in this experimental animal model does not alter serum levels of calcium and parathyroid hormone or reduce target organ responsiveness to the hormone.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1991

The role of circulating N-terminal parathyroid hormone fragments in the early postparathyroid adenomectomy period.

Calcium metabolism and hormonal control after parathyroid adenomectomy are poorly understood. During the first postoperative hours, biologically active intact parathyroid hormone (PTH) (hPTH 1-84) levels are subnormal and, in spite of down-regulation of PTH peripheral receptors (caused by hypercalcemia before surgery), total and ionized calcium concentrations are maintained in the normal range. Serum samples from 20 patients with primary hyperparathyroidism were collected in the immediate preoperative period and 4 and 48 hours after excision of one parathyroid adenoma. Total and ionized calcium, intact (iPTH), midregion (mrPTH) specific PTH (hPTH 53-68), and N-terminal PTH (N-PTH) serum concentrations were determined. Levels of N-PTH were obtained with a radioimmunoassay by a modified reverse immunoextraction procedure that measures N-PTH fragments after exclusion of the interfering iPTH. No significant correlation was found between ionized and total calcium, mrPTH, and iPTH. However, total and ionized calcium levels correlated well with N-PTH (r = 0.9999, p = 0.0054, and r = 0.9993, and p = 0.0226, respectively). The data suggest that the relatively moderate decrease in calcium levels, in spite of marked decrease in circulating iPTH during the first postoperative hours, may be attributable to the minimal decrease of the bioactive N-PTH epitope concentrations. We would hypothesize that hPTH (1-34) fragments may play a significant role in regulating serum calcium levels in the early postoperative period.

Adenoma↗
PubMed1991

The role of resection in the management of melanoma metastatic to the adrenal gland.

Melanoma metastatic to the adrenal gland diagnosed before death was exceedingly rare before the development of computed tomographic (CT) scanning. The records of 28 patients with melanoma metastatic to the adrenal gland seen since 1975 were reviewed. Eighteen patients were men and 10 were women. Twenty-three patients had unilateral disease. Four patients were diagnosed only at autopsy, leaving 24 for analysis of treatment and survival. Twenty-one patients had received specific active immunotherapy, four had received chemotherapy (dacarbazine, lomustin, bleomycin, and vincristine), and three had received both before the diagnosis of their adrenal disease. Adrenal metastases were diagnosed by CT scanning in 14 patients with symptoms, 10 (91%) of whom had pain. Ten patients were diagnosed by CT before entry into a chemotherapy protocol. Of eight patients who underwent resection of all known disease, five underwent unilateral adrenalectomy, two underwent unilateral adrenalectomy and bowel resection, and one underwent bilateral adrenalectomy. Two patients underwent partial resection of large unilateral tumors. Fourteen patients with adrenal metastases and disease elsewhere were initiated or continued with chemotherapy or were treated symptomatically. Mean survival in the group that underwent resection for cure was 59 months (3 to 112 months), whereas survival in the group with unresectable tumors was 15 months (1.5 to 132 months). Four of eight patients who underwent resection for cure lived more than 5 years after detection of adrenal metastasis, whereas in only one of 14 patients with unresectable tumors was the same true. Patients with metastatic melanoma localized to one or both adrenal glands may benefit from early detection and surgical intervention.

Adrenal Gland Neoplasms↗
PubMed1991

Iodine 131-labeled metaiodobenzylguanidine scintigraphy and biochemical analyses in suspected pheochromocytoma.

Detection of abnormal catecholamine levels and localization of tumor mass are important factors in the diagnosis and treatment of pheochromocytoma. Iodine 131-labeled metaiodobenzylguanidine scintigraphy was performed in 64 patients with suspected pheochromocytoma if their urinary catecholamine levels were borderline or elevated, or if the clinical suspicion for pheochromocytoma was high in spite of normal urinary catecholamine determinations. The 131I-metaiodobenzylguanidine scans were evaluated for abnormal localization of tracer. Twenty-four-hour urine collections were analyzed for vanillylmandelic acid, homovanillic acid, dopamine, epinephrine, and norepinephrine. Thirty of the 64 patients had pheochromocytomas. The 131I-metaiodobenzylguanidine scan had a sensitivity and a specificity of 88%. The 24-hour urine vanillylmandelic acid and norepinephrine measurements had the best sensitivity (97%), while the vanillylmandelic acid and homovanillic acid measurements had the best specificity (91%). In patients in whom the vanillylmandelic acid measurement and the 131I-metaiodobenzylguanidine scan were normal, no pheochromocytomas were found. In patients in whom the vanillylmandelic acid measurement and 131I-metaiodobenzylguanidine scan were abnormal, a pheochromocytoma was always present. The 131I-metaiodobenzylguanidine scan often documents the presence or absence of a pheochromocytoma and provides localization of the tumor in the preoperative evaluation of these patients.

3-Iodobenzylguanidine↗
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↗