Search PubMed⌕ Search

Biomedical subjects

G S Leight

Publications and source records attributed to G S Leight.

At least 19 recordsLinked to original sources
PubMed1996

Uremic leontiasis ossea: "bighead" disease in humans? Radiologic, clinical, and pathologic features.

PURPOSE: To describe the clinical, radiologic, and pathologic findings in patients with uremic leontiasis ossea (ULO). MATERIALS AND METHODS: Five patients with renal osteodystrophy developed marked hyperostosis of the facial and cranial bones. Radiologic studies included plain radiography of the skull (n = 5), computed tomography with three-dimensional reconstruction (n = 4), magnetic resonance imaging (n = 3), and fluorine-18 sodium fluoride positron emission tomography (PET) (n = 1). Specimens from bone biopsies (three patients) were examined. RESULTS: Skull and facial alterations were remarkably similar. Numerous nodules of varying attenuation and signal intensity in the widened diploic space suggested brown tumors in different stages of evolution. Biochemical data and PET findings enabled confirmation of markedly increased bone turnover. Bone specimens demonstrated severe osteitis fibrosa. After parathyroidectomy, facial changes in all patients stabilized or improved mildly. CONCLUSION: A similar entity in animals, "bighead" disease, which results from nutritional and uremic secondary hyperparathyroidism, may provide a useful animal model for ULO in humans. Mild forms of this entity may be more common than the scarcity of previous reports suggests.

Adult↗
PubMed1996

The complementary roles of fast spin-echo MR imaging and double-phase 99m Tc-sestamibi scintigraphy for localization of hyperfunctioning parathyroid glands.

OBJECTIVE: Our purpose was to evaluate and compare prospectively fast spin-echo MR imaging and double-phase technetium-99m-sestamibi scintigraphy for preoperative localization of hyperfunctioning parathyroid glands in high-risk surgical patients. SUBJECTS AND METHODS: Twenty-five patients, including 17 with a history of neck surgery, underwent preoperative MR imaging and technetium-99m-sestamibi scintigraphy. Initial interpretation of each study was made independently by two radiologists and then done in combination. At surgery, the location, weight, and dimensions, as well as detailed histopathologic evaluations, of all excised glands were recorded. RESULTS: All but two patients became normocalcemic after surgery. MR and sestamibi imaging revealed 31 of 37 (84%) and 29 of 37 (79%) of all abnormal glands, respectively. Sensitivities of MR and sestamibi imaging were higher for adenomas (17 of 18 [94%] and 16 of 18 [89%], respectively) than for hyperplastic glands (14 of 19 [74%] and 13 of 19 [68%], respectively). The specificity of sestamibi imaging (94%) exceeded that of MR imaging (75%). All ectopic glands (n = 8) were correctly localized by both techniques. Glands with atypical MR imaging characteristics (isointense or hyperintense to normal thyroid on T1-weighted spin-echo and fast spin-echo images) were more likely to have increased fat, chronic hemorrhage, or sclerosis and fibrosis (p < .05). When MR imaging and sestamibi studies were interpreted together, their sensitivities for adenomas and for hyperplastic glands were 94% (17 of 18) and 84% (16 of 19), respectively. Overall sensitivity of MR imaging and sestamibi studies interpreted together was 89%; overall specificity was 95%. CONCLUSION: The greater specificity and anatomic coverage of sestamibi scintigraphy coupled with the greater anatomic detail provided by MR imaging and its improved sensitivity over sestamibi imaging in specific patients may justify using both techniques in high-risk surgical patients who have hyperparathyroidism, particularly patients undergoing repeat surgery.

Adenoma↗
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↗
PubMed1994

Surgical treatment of primary hyperaldosteronism.

OBJECTIVE: A retrospective review of patients with primary hyperaldosteronism treated at the Duke University Medical Center was performed. SUMMARY BACKGROUND DATA: The management of patients with primary hyperaldosteronism has changed dramatically in the past 20 years. The outcome of surgical treatment was examined to optimize the management of these patients. METHODS: All patients who were evaluated for primary hyperaldosteronism before operation and who had adrenal surgery at Duke University Medical Center from 1970 to 1993 were included in the study. RESULTS: A ratio of plasma aldosterone concentration to plasma renin activity greater than 250 was predictive of hyperaldosteronism in 94% of patients. This ratio also predicted the size of the adenoma. Surgical treatment cured hypokalemia in 90% of the patients. Hypertension was cured or greatly improved, with an average decrease of 50.4 mmHg and 25.2 mmHg for systolic and diastolic pressures, respectively. Patients who had hypertension for less than 5 years achieved a satisfactory blood pressure response more often (13 of 14 patients) than did patients who had hypertension for 5 or more years (15 of 20 patients). CONCLUSIONS: Preoperative evaluation of patients with primary hyperaldosteronism using current modes allows a posterior approach to be used in most patients. Adrenalectomy cures hypokalemia and hypertension; however, patients with a history of hypertension for less than 5 years may be more likely to be cured by adrenal resection.

Adenoma↗
PubMed1993

CT in the diagnosis of primary aldosteronism: sensitivity in 29 patients.

OBJECTIVE: The most common cause of primary aldosteronism is a small aldosterone-secreting adrenal adenoma. With improvements in CT technology, smaller adrenal lesions can now be detected. We reviewed our experience with 29 patients with primary aldosteronism to assess the sensitivity of CT in detecting aldosterone-secreting adenomas. MATERIALS AND METHODS: The records of all patients with biochemically proved Conn's syndrome who were referred for adrenal CT between 1982 and 1991 were reviewed. The CT examinations of each of these 29 patients were reviewed for evidence of hyperplasia or an adenoma. The interpretations were correlated with subsequent adrenal venous sampling (20 patients) or surgery (17 patients). RESULTS: Fourteen of 17 aldosteronomas were detected on CT scans (sensitivity, 82%). Adrenal tumors were not seen on CT scans in any of the 12 patients with hyperplasia, although the glands appeared diffusely enlarged in only seven of these patients. In no case was an adrenal tumor seen on CT scans that was not found at surgery (positive predictive value, 100%). CONCLUSION: If CT scans of patients with Conn's syndrome show a focal mass, ipsilateral adrenalectomy can be performed with the expectation of cure. If no mass is found, adrenal venous sampling can be used to detect an adenoma not shown on CT.

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↗