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Biomedical subjects

S E Carty

Publications and source records attributed to S E Carty.

At least 19 recordsLinked to original sources
PubMed1999

Human telomerase reverse transcriptase (hTERT) gene expression in FNA samples from thyroid neoplasms.

BACKGROUND: Although fine-needle aspiration (FNA) is the most sensitive method for the detection of thyroid carcinoma, it cannot provide a definitive diagnosis of malignancy in 60% of the patients operated on for suspicious lesions. Recently, human telomerase reverse transcriptase (hTERT) has been found to be a diagnostic marker of malignancy. We therefore sought to determine whether hTERT gene expression could serve as an adjunct to FNA in the differential diagnosis of thyroid nodules. METHODS: Twenty-four FNA samples from thyroid nodules that were suspected of malignancy were collected. RNA was extracted, and hTERT gene expression was examined by RT-PCR. Cytologic and histologic examinations were also performed. RESULTS: Two of three follicular, three of three Hürthle cell, and eight of eight papillary thyroid carcinomas had corresponding FNA samples that were positive for hTERT. One of two Hürthle cell adenomas was hTERT positive. FNA samples from three follicular adenomas and five hyperplastic nodules were negative for hTERT. Positive and negative predictive values were 93% and 90%, respectively. CONCLUSIONS: The detection of hTERT gene expression in thyroid FNA samples holds promise as a diagnostic marker in the distinction of benign from malignant thyroid lesions. Its application could alter the surgical management of these patients.

Adenocarcinoma, Follicular↗
PubMed1998

Prognostic markers in pheochromocytoma.

Clinical and histopathological features do not reliably distinguish between benign and malignant pheochromocytomas. Additional markers that might be useful prognostic indicators in the pathological assessment of these tumors are sought. Immunohistochemical expression of MIB-1, Bcl-2, cathepsin B, cathepsin D, basic fibroblast growth factor (bFGF), c-met, and type IV collagenase were studied on formalin-fixed tissue from 33 nonconsecutive cases of pheochromocytoma, selected on the basis of reliable long-term follow-up, to determine associations with malignancy. The study group included 33 patients, 19 men and 14 women, with a mean age of 45 years, including five cases of neurofibromatosis (NF), three familial, and one MEN IIb. Mean follow-up was 63.2 months. Ten patients were determined to have malignant pheochromocytomas by the presence of metastatic disease. Features found to be associated with malignancy included MIB-1 labeling index (5% vs 1%) (P = .0009), male gender (90% vs 43%) (P = .008), extra-adrenal location (40% vs 9%) (P = .03), tumor weight (481 g vs 124 g) (P = .05), and young age (38 years vs 49 years) (P = .05). None of the five cases with NF were malignant (P = .04). S-100 positivity showed a significant (P = .02) but nonlinear association with benign tumors. Absent S-100 correlated with greater tumor weight. Malignancy was not associated with right versus left side or bilaterality, although bilateral tumors were smaller. C-met, bFGF, cathepsin B, cathepsin D, and collagenase were strongly expressed in most tumors and were not predictive of outcome, nor was bcl-2, which was variably expressed. Using multiple logistic regression with malignancy as the dependent variable, MIB-1 continued to show a significant association with malignancy (P = .005) independent of any association with sex, age, or extra-adrenal location. Using a cutoff value of MIB-1 labeling of greater than 3% yielded a specificity of 100% and a sensitivity of 50% in predicting malignancy.

Adrenal Gland Neoplasms↗
PubMed1998

The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1.

BACKGROUND: Some experts maintain that (1) > 90% of patients with multiple endocrine neoplasia type 1 (MEN1) are first seen with hyperparathyroidism (HPTH) so that routine screening for other features is unnecessary and (2) MEN1 has > or = 94% penetrance by age 50 years. METHODS: We constructed a regional registry of patients with or at risk for MEN1 and examined phenotypic profiles in 34 patients. MEN1 was defined as (1) endocrinopathy of 2 of the 3 principal related tissues (parathyroid, gastrointestinal endocrine, pituitary) or (2) 1 such feature plus a first-degree relative with MEN1. RESULTS: The initial feature of MEN1 was HPTH in 50%, pituitary tumor in 18%, and gastrointestinal endocrine tumor in 32% of patients, with overall incidences of 82%, 65%, and 74%, respectively. HPTH developed by age 50 years in 73% of patients and by age 70 years in 83%. Penetrance of MEN1 at age 50 years was 82%. Associated features included renal (1) and rectal (1) cancer, malignant thymic carcinoid (1), and malignant pheochromocytoma (1). CONCLUSIONS: Expression of MEN1 can vary considerably from established patterns. In our geographic region HPTH does not routinely precede other features of MEN1 and cannot be used to distinguish affected patients among those at risk. MEN1 can be inapparent until late in life and may be significantly underdiagnosed.

Adolescent↗
PubMed1998

Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma: validation of utility as a clinical marker.

OBJECTIVE: To determine if the serum level of interleukin-6 (IL-6) was elevated in patients with hepatic malignancies or correlated with radiologic tumor burden. SUMMARY BACKGROUND DATA: High serum levels of IL-6 signify an adverse prognosis in many patients with cancer. IL-6 is a growth factor for bile duct epithelium. METHODS: Using bioactive and enzyme-linked immunosorbent assays, serum level of IL-6 was measured in 35 healthy adults and in 60 patients presenting for definitive management of cholangiocarcinoma (CC) (15 patients), hepatocellular carcinoma (HCC) (14), metastatic colorectal cancer (MCRC) (26), and benign biliary disease (BBD) (5). Patients with clinical conditions known to raise the serum level of IL-6 were excluded. Tumor burden was calculated from concurrent computed tomography scans. IL-6 levels were measured 2 weeks after resection in 3 CC patients. Secretion of IL-6 was examined in 3 human CC cell lines. RESULTS: An elevated level of bioactive IL-6 was detected in every patient with CC and in 13 of 14 patients with HCC, 14 of 26 patients with MCRC, 2 of 5 patients with BBD, and 3 of 35 healthy adults. Median and mean levels of bioactive IL-6 were higher in CC than in other neoplasms (p < 0.026) and for all tumor groups differed from healthy adults (p < or = 0.026). IL-6 level was elevated more often in primary than in secondary liver neoplasms (p = 0.02), distinguished patients with CC or MCRC from BBD (p = 0.014 and 0.031, respectively), correlated with tumor burden in CC (p < 0.001), and dropped sharply after CC resection. CC line SG231 secreted bioactive IL-6. CONCLUSIONS: In selected patients, a high serum level of IL-6 marks patients with CC and correlates with tumor burden both before and after resection. IL-6 levels are elevated in patients with other liver neoplasms and may distinguish patients with hepatic malignancies from those with benign disease.

Adult↗
PubMed1997

Thyroid carcinoma found at parathyroidectomy: association with primary, secondary, and tertiary hyperparathyroidism.

BACKGROUND: Frequent reports of an association between primary hyperparathyroidism (HPT) and well differentiated thyroid carcinoma, compared with the few reports of associated secondary HPT and thyroid carcinoma, may have implications for different etiologic relationships between the conditions. METHODS: A retrospective review was performed of patients who underwent surgery for HPT between 1975 and 1996 in a single institution. The prevalence of well differentiated thyroid carcinoma diagnosed at the time of parathyroidectomy (PTX) was compared for patients with primary, secondary, or tertiary HPT. RESULTS: There were 845 operations for HPT in 824 patients. Twenty-two patients were found to have thyroid carcinoma at the time of PTX. Thyroid carcinoma was found in 2.6% of the patients with primary and 3.2% of the patients with either secondary or tertiary HPT (P = 0.550). Twenty-one of the patients had papillary carcinoma and 1 had a follicular carcinoma. Eighteen of the carcinomas were < 1 cm in size. A prior history of head and neck irradiation was associated with the diagnosis of thyroid carcinoma at the time of PTX (P < 0.001). Neither renal failure, organ transplantation, female gender, lymphocytic infiltration, nor follicular adenoma of the adjacent thyroid were significant in the association between HPT and thyroid carcinoma. CONCLUSIONS: These data suggest that the association between thyroid carcinoma and HPT is coincidental and possibly related to the closer surveillance of the thyroid gland due to PTX and often concomitant removal of thyroid tissue. Patients with HPT and a history of head and neck irradiation are at increased risk of thyroid carcinoma.

Adolescent↗
PubMed1997

Retroperitoneal bronchogenic cyst masquerading clinically and radiologically as a phaeochromocytoma.

Bronchogenic cysts are relatively rare congenital anomalies that represent malformations of the embryonic foregut and are morphologically expressed as maldevelopments of the respiratory system. Anatomically, they can be positioned at any location along the central axis of the respiratory system, but are more commonly discovered in the thorax. Infradiaphragmatic bronchogenic cysts are rare and retroperitoneal ones distinctly unusual. We report a retroperitoneal bronchogenic cyst clinically masquerading as a phaeochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1997

Concise parathyroidectomy: the impact of preoperative SPECT 99mTc sestamibi scanning and intraoperative quick parathormone assay.

BACKGROUND: Results of initial operation for sporadic primary hyperparathyroidism are generally excellent, yet today there is pressure to improve outcome and resource utilization. METHODS: We designed a prospective longitudinal cohort study comparing two approaches to concise parathyroidectomy. Strategy A was defined as the palpation method for selective unilateral exploration. Strategy B was defined as the routine use of both preoperative 99mTc sestamibi single photon emission computed tomography (SPECT) imaging and intraoperative quick parathormone assay. With either strategy the study period was 19 months and patients explored unilaterally were candidates for same-day discharge. We compared surgical outcome for 128 consecutive consenting patients each with 6 months or more of follow-up (mean 12 +/- 7.6 months). RESULTS: Demographic, biochemical and pathologic findings did not differ between groups. SPECT imaging precisely localized hyperfunctioning parathyroid tissue. Compared with Strategy A (n = 61), the 67 patients treated by use of Strategy B experienced a higher rate of unilateral exploration (41.0% versus 62.7%, p < 0.00001) and a shorter length of stay (1.07 versus 1.90 days, p < 0.00001) and tended to have shorter operative times, fewer operative failures, and less morbidity. Total perioperative costs did not differ between groups. CONCLUSIONS: Routine use of intraoperative quick parathormone measurement and preoperative 99mTc sestamibi SPECT is as safe, effective, and cost-effective as conventional approaches to parathyroidectomy. Use of this strategy is associated with significant reductions in extent of surgery and length of hospital stay.

Adult↗
PubMed1997

Parathyroid hyperplasia, thymic carcinoid and pituitary adenoma detected with technetium-99m-MIBI in MEN type I.

We report a case of a 57-yr-old woman with history of multiple endocrine neoplasia type I (MEN I). A 99mTc-sestamibi scan demonstrated a hyperplastic parathyroid gland, a large anterior mediastinal mass and a pituitary adenoma during a study done to evaluate recurrent hyperparathyroidism. The importance of this case is that much of the nonparathyroid pathology in patients with MEN I syndrome may be detected with this one study.

Carcinoid Tumor↗
PubMed1996

Parathyroid adenomas: accurate detection and localization with Tc-99m sestamibi SPECT.

PURPOSE: To evaluate the ability to detect and localize parathyroid adenomas with technetium-99m sestamibi single photon emission computed tomography (SPECT). MATERIALS AND METHODS: Forty-seven adult patients underwent Tc-99m sestamibi SPECT. Early (15-30 minutes after injection) and delayed (2-4 hours after injection) images were acquired. Thirty-three patients were examined for initial parathyroid surgery; the remaining 14, for repeat surgery because of persistent or recurrent hyperparathyroidism. SPECT reprojection images viewed in a rotating cine-display mode were read independently by two nuclear medicine physicians who were blinded to the results of other localization studies. Thirty-seven patients underwent subsequent neck exploration. SPECT findings were compared with surgical and histopathologic findings. RESULTS: In the 37 patients who underwent surgery, parathyroid adenomas were confirmed in 34 (92%) and hyperplasia in three (8%). In 31 patients, adenomas were correctly detected and localized with early SPECT images (sensitivity, 91%). In contrast, the sensitivity of delayed SPECT images was 74% (25 of 34 patients) for detection and 32% (11 of 34 patients) for localization. Early SPECT images were significantly better for localization (P < .001) and detection (P = .03). CONCLUSION: For Tc-99m sestamibi parathyroid imaging, early SPECT images were the most accurate in the detection and localization of parathyroid adenomas.

Adenoma↗
PubMed1993

Success of unilateral neck exploration for sporadic primary hyperparathyroidism.

BACKGROUND: Unilateral neck exploration for primary hyperparathyroidism (PHPTH) is controversial because of concern about missed multiglandular disease. METHODS: In patients with sporadic PHPTH our approach has been arbitrarily to surgically explore the right neck first unless preoperative or intraoperative evidence suggests left-sided parathyroid pathologic condition. When an adenoma is identified and a normal ipsilateral gland is confirmed on histologic examination, the contralateral side is not explored. A 15-year series of 371 patients with sporadic PHPTH was reviewed retrospectively to determine the efficacy of this strategy. RESULTS: At operation unilateral exploration was possible in 125 patients (34%). Of these 122 had a single adenoma and two patients had parathyroid carcinoma. One patient with unrecognized hyperplasia required subsequent subtotal parathyroidectomy. There were no major complications. Bilateral surgical exploration was required in 246 patients including 18 with hyperplasia, 4 with double adenomas, and 4 with parathyroid cancer. Bilateral surgical exploration failed in 18 patients (14 persistent and 4 recurrent PHPTH) and was complicated by one recurrent nerve palsy and two cases of permanent hypocalcemia. Operative time was significantly shorter in the unilaterally explored group. CONCLUSIONS: When possible, unilateral exploration for PHPTH is safe and effective, avoids obliterative scarring of the contralateral neck, and may reduce morbidity and operative time.

Adenoma↗
PubMed1992

Prospective study of aggressive resection of metastatic pancreatic endocrine tumors.

BACKGROUND: Because metastatic pancreatic endocrine tumors (MPET) have a poor prognosis, 17 patients with potentially resectable MPET were prospectively studied to define the efficacy of aggressive resection. METHODS: Patients underwent resection when the full extent of MPET was deemed operable after imaging studies were obtained. Two patients underwent three reoperations for recurrent tumor. RESULTS: MPET were completely excised in 16 of 20 cases by major resections of liver, viscera, and nodes, with no operative mortality. Survival was 87% at 2 years and 79% at 5 years with mean follow-up of 3.2 years. Median imaging disease-free interval was 1.8 years, and four of 17 patients remain biochemically cured. After aggressive resection patients with MPET limited in extent had higher survival than patients with extensive MPET (p < 0.019). In a nonrandomized cohort of 25 patients with inoperable tumor, survival was 60% at 2 years and 28% at 5 years. CONCLUSIONS: In select patients MPET can be resected safely with a favorable outcome; most patients will experience recurrence, but some may be cured. Resection of extensive MPET does not appear to improve survival. Resection of limited MPET should be considered as life-extending and potentially curative therapy.

Adult↗
PubMed1991

Decreased IL-6 secretion by fibroblasts following repeated doses of TNF alpha or IL-1 alpha: post-transcriptional gene regulation.

Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) are pluripotent cytokines mediating the host response to sepsis, injury, and cancer. Animals can be protected from the lethal effects of TNF alpha by repeated administration of sublethal doses, but the mechanism of this effect is not known. Human foreskin fibroblasts (FS4 cells), which rapidly elaborate interleukin-6 (IL-6) when stimulated with TNF alpha or IL-1 alpha, were grown in culture as confluent monolayers and their secretion of IL-6 was quantitated using the murine B9-hybridoma bioassay against an external reference of human recombinant IL-6 (Genetics Institute). When FS4 cells were incubated with human recombinant TNF alpha (50 ng/ml; Cetus) or recombinant IL-1 alpha (30 pg/ml; Genzyme) a rapid increase in IL-6 production was measured over control, rising to IL-6 levels of 71.7 +/- 5.9 units/ml with TNF alpha and 54.0 +/- 1.2 units/ml with IL-1 alpha after 7.5 hr incubation. FS4 cells which were exposed to cytokine, rinsed, and then reexposed to cytokine 24 hr later produced significantly less IL-6 [38.1 +/- 2.8 units/ml with second exposure to TNF alpha (P less than 0.05), and 18.3 +/- 1.9 units/ml with second exposure to IL-1 alpha (P less than 0.01)]. Successive daily exposure to TNF alpha or IL-1 alpha caused a further stepwise diminution of IL-6 secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Tolerance↗
PubMed1985

Amine transport into chromaffin ghosts. Kinetic measurements of net uptake of biologically and pharmacologically relevant amines using an on-line amperometric technique.

The kinetic parameters for net transport of dopamine, epinephrine, norepinephrine, 5-hydroxytryptamine, S alpha-methyldopamine, R alpha-methyldopamine, and 1R,2S alpha-methylnorepinephrine into highly purified bovine chromaffin ghosts were determined using an on-line amperometric technique. Chromaffin ghosts devoid of endogenous amines were formed from lysis of chromaffin granules under hypotonic conditions, extensive washing of the scattered membranes, followed by resuspension in iso-osmotic media and overnight dialysis. When chromaffin ghosts formed so as to generate and maintain a large delta pH were suspended in 185 mM KCl, 10 mM Hepes at pH 7.0, 37 degrees C, the addition of MgATP resulted in rapid acidification of the intravesicular space, which was maintained at pH 6.0 (+/- 0.1) for over 30 min. Kinetic net amine transport was subsequently measured with a glassy carbon electrode. The initial rates of uptake were found to follow Michaelis-Menten kinetics. Computer based statistical analysis of the data using distribution-free procedures yielded Km (and V) values as follows: in microM (nmol X mg protein-1 X min-1) dopamine, 16.2 (14.0); R-norepinephrine, 32.5 (12.9); R-epinephrine, 35.1 (15.2); 5-hydroxytryptamine, 4.7 (5.1); S alpha-methyldopamine, 17.7 (11.2); R alpha-methyldopamine, 44.2 (9.9); 1R,2S alpha-methylnorepinephrine, 76.5 (12.5). The physiologic and pharmacologic implications of these kinetic parameters are discussed.

Adrenal Medulla↗