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N A Patwardhan

Publications and source records attributed to N A Patwardhan.

18 recordsLinked to original sources
PubMed2001

Expression of eukaryotic translation initiation factors 4E and 2alpha correlates with the progression of thyroid carcinoma.

Cell growth and proliferation depend on protein synthesis that is regulated, in part, by two eukaryotic translation initiation factors, eIF-4E and eIF-2alpha. These factors are transiently increased as normal cells respond to growth factors and are constitutively elevated in transformed cells. In cultured cells, eIF-4E facilitates cell cycle progression by increasing the expression of cell cycle promoting proteins including cyclin D1. Our previous study revealed elevated cyclin D1 expression in histologically more aggressive thyroid carcinomas as compared to conventional papillary carcinoma. We hypothesized that the increased cyclin D1 expression might correlate with increased eIF-4E expression. We, therefore studied the expression of eIF-4E by immunohistochemistry in 25 cases of conventional papillary carcinoma (CPC) and 28 cases of aggressive thyroid carcinomas (ATC), the latter included 11 tall cell/columnar cell variant of papillary carcinoma, 5 insular carcinomas, and 12 anaplastic carcinomas. We also analyzed the expression of eIF-2a in the same samples as this factor is usually regulated similarly to eIF-4E in cell culture models. Of the 25 CPC, 13 were eIF-4E positive (11 weakly and 2 strongly), and 19 were eIF-2a positive (14 weakly and 5 strongly). Conversely, of the 28 ATC, 25 were eIF-4E positive (4 weakly and 21 strongly), and 23 were eIF-2alpha positive (4 weakly and 19 strongly). There was a significantly increased expression of both eIF-4E (p < 0.001) and eIF-2alpha (p < 0.001) in ATC compared to CPC, suggesting that these translation initiation factors may play a role in the progression of thyroid cancer.

Antibody Specificity↗
PubMed2000

The role of cell cycle regulatory protein, cyclin D1, in the progression of thyroid cancer.

Cell cycle progression is facilitated by cyclin-dependent kinases that are activated by cyclins including cyclin D1 and inactivated by cyclin-dependent kinase inhibitors (CDKIs) such as p27. Our previous studies have demonstrated decreased p27 expression in both papillary and more aggressive carcinomas of the thyroid compared to thyroid adenoma and almost similar level of cyclin D1 expression between thyroid adenoma and papillary carcinoma. These results indicate that CDKIs may have an important role in the carcinogenesis of the thyroid and that they probably have a limited role in malignant progression of the thyroid cancer. The role of cyclin D1 in malignant progression of thyroid carcinoma has yet to be established. We studied the expression of cyclin D1 by immunohistochemistry in 34 cases of conventional papillary carcinoma (CPC), 10 cases of minimally invasive follicular carcinoma (MIFC), and 32 cases of more aggressive thyroid carcinoma (ATC), which included 11 tall cell variants, one columnar cell variant of papillary carcinoma, seven insular carcinomas, and 13 anaplastic carcinomas. Cyclin D1 staining was classified by staining score as 0, negative; 1+, less than 25%; 2+, 25 to 50%; and 3+, more than 50% tumor cells staining positive. Kruskal-Wallis one-way ANOVA and Wilcoxon Rank Sum/Mann-Whitney U Test was used to assess the difference in the expression of cyclin D1 between the study groups. Twenty-eight out of the 34 CPCs were cyclin D1 positive, 24 (70%) were 1+, 3 (9%) were 2+, and one (3%) were 3+ positive. Seven of 10 MIFCs were cyclin D1 positive, five (71%) were 1+, and the remaining two (29%) were 2+ positive. On the other hand, 28 of 32 ATCs showed cyclin D1 immunostaining. Of these, three (9%) were 1+, five (13%) were 2+, and 20 (63%) were 3+ positive. This study demonstrates a significant overexpression of cyclin D1 in ATC compared CPC (P < .001) and MIFC (P < .005), suggesting that the cyclin D1 expression may play a role in tumor progression and may have prognostic significance in thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed1998

CD57 (Leu-7) expression is helpful in diagnosis of the follicular variant of papillary thyroid carcinoma.

CD57 (HNK-1) is a oligosaccharide antigen that is expressed by cells of several lineages. It is present on multipotential neuroepithelial cells during embryogenesis, and tumours of epithelial, neuroectodermal and nerve sheath origin also express CD57. Its role in the diagnosis of thyroid tumours is controversial. We have studied CD57 expression by immunohistochemistry to determine its utility in the classification of thyroid follicular lesions. Study material included 114 normal thyroid sections, 77 benign thyroid lesions (29 colloid nodules, 22 follicular adenomas, 20 cases of Hashimoto's thyroiditis and 6 of Grave's disease) and 83 thyroid carcinomas, including 31 follicular variants of papillary carcinoma. We observed CD57 positivity in 95% of thyroid carcinomas, 27% of follicular adenomas and 10% of colloid nodules. It was not expressed in the normal thyroid. CD57 expression in thyroid carcinomas was significantly different from that in normal and benign thyroid lesions (P < 0.0001). The follicular variant of papillary thyroid carcinoma also showed significantly higher CD57 expression than colloid nodules (P < 0.0009) or follicular adenomas (P < 0.0009). No significant difference was seen between colloid nodules and follicular adenomas. We conclude that CD57 immunohistochemistry is valuable in the classification of thyroid follicular lesions into benign and malignant groups and is also helpful in the diagnosis of the follicular variant of papillary thyroid carcinoma.

Adenoma↗
PubMed1996

Bilateral cervical plexus block for thyroidectomy and parathyroidectomy in healthy and high risk patients.

We evaluated the benefits of bilateral deep cervical plexus block regional anesthesia in healthy and high risk patients undergoing thyroid and parathyroid surgery and assessed its effects on respiratory function. Twenty-one patients undergoing thyroid and parathyroid operations were studied. Bilateral superficial and deep plexus blocks were performed in all patients except one (who received only superficial plexus block because of a slightly prolonged prothrombin time) with 0.375-0.5% bupivacaine with 1:200,000 epinephrine. Intraoperatively, supplemental intravenous sedatives/narcotics were titrated to achieve patient comfort and cooperation. To allay anxiety, patients were allowed to listen to music via headphones intraoperatively. Forced vital capacity was measured before block, 10 minutes after the block and in the recovery room in half the patients. Eighteen patients tolerated the procedure well with supplemental sedation. Two patients required supplemental inhalation anesthesia via mask and one required tracheal intubation because of coughing prior to surgery. Three high risk patients tolerated the procedure well requiring only intraarterial line monitoring. Postoperatively, 11 patients had minimal incisional pain, 13 patients had mild pain on swallowing and 2 patients complained of nausea. There were no significant differences in the baseline forced vital capacity vs. forced vital capacity measured after the block and in the recovery room. This study indicates that regional anesthesia is an appropriate alternative to general anesthesia in selected patients undergoing thyroid and parathyroid surgery and did not compromise respiratory function.

Adult↗
PubMed1994

Changing clinical practice. Prospective study of the impact of continuing medical education and quality assurance programs on use of prophylaxis for venous thromboembolism.

OBJECTIVE: To determine the effect of continuing medical education (CME) with and without a quality assurance component (CME+QA) on physician practices in the prevention of venous thromboembolism. METHODS: A communitywide study was performed in 15 short-stay hospitals in central Massachusetts. The study population included 3158 patients in acute-care hospitals with multiple risk factors for venous thromboembolism. Study hospitals were randomly assigned to one of two educational strategies or to a control group that received no intervention. RESULTS: The proportion of patients at high risk for venous thromboembolism who received effective methods of prophylaxis increased significantly from 29% in 1986 to 52% in 1989 (P < .001). This increase was seen in all study groups: control hospitals, 40% to 51% (P < .001); CME hospitals, 21% to 49% (P < .0001); and CME+QA hospitals, 27% to 55% (P < .0001). The increase in prophylaxis use from 1986 to 1989 was significantly greater among patients cared for in hospitals whose physicians participated in a formal CME program (an increase of 28%) than in control hospitals (an increase of 11%) (P < .001). There was no significant difference in the use of prophylaxis in hospitals whose physicians received CME+QA interventions compared with hospitals whose physicians received CME interventions alone (identical increases of 28%). CONCLUSION: A formal CME program significantly increased the frequency with which physicians prescribed prophylaxis for venous thromboembolism. We believe the key factor in our CME interventions that motivated clinicians to change their practices was the provision of hospital-specific data demonstrating a compelling need for improvement. Despite the substantial investment by hospitals in QA, traditional QA intervention appeared to provide no additional benefit. Even after extensive CME/QA interventions, prophylaxis for venous thromboembolism remained underutilized, suggesting the need to develop new approaches to changing clinical practice.

Aged↗
PubMed1994

Tumor necrosis factor-alpha decreases thyrotropin-induced 5'-deiodinase activity in FRTL-5 thyroid cells.

Tumor necrosis factor-alpha (TNF-alpha) exerts various effects on many cell types. Acute administration of TNF-alpha to rats decrease hepatic 5'-deiodinase activity (5'D-I) and TNF-alpha has been implicated in the pathogenesis of the low triiodothyronine syndrome in non-thyroidal illness in humans. The thyroid, liver and kidney are rich in 5'D-I. Unlike hepatic and renal 5'D-I, thyroid 5'D-I is regulated by thyrotropin. We have investigated the effects of TNF-alpha on 5'D-I in FRTL-5 cells, a cultured rat thyroid follicular cell line. Tumor necrosis factor-alpha did not significantly affect basal 5'D-I but thyrotropin markedly increased 5'D-I (p < 0.001). This TSH-induced increase in 5'D-I was attenuated by TNF-alpha in a dose-dependent manner (p < 0.001). Enzyme kinetic analysis demonstrated that thyrotropin increased 5'D-I by increasing Vmax (p < 0.01) without significantly affecting Km. Likewise, TNF-alpha decreased the thyrotropin-induced 5'D-I by decreasing Vmax (p < 0.05) but not Km. The effect of TNF-alpha on thyrotropin-induced 5'D-I in FRTL-5 cells is probably mediated through post-thyrotropin-induced generation of cyclic adenosine monophosphate (cAMP) because TNF-alpha inhibited both dibutyryl cAMP (p < 0.001) and forskolin (p < 0.001)-induced increases in 5'D-I without affecting cAMP generation stimulated by thyrotropin. In conclusion, we have demonstrated that TNF-alpha inhibits thyrotropin-induced 5'D-I activity in FRTL-5 cells by pathways distal to the generation of cAMP and that TNF-alpha may play a role in the modulation of the production of triiodothyronine by the thyroid gland. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Surgery still has a role in Graves' hyperthyroidism.

BACKGROUND: A recent survey of American thyroidologists defining their management of a 43-year-old woman with hyperthyroid Graves' disease and a thyroid weighing 40 to 50 grams revealed that 69% recommended iodine 131 therapy, 30% prolonged antithyroid drug therapy, and only 1% operation. If the patient was younger or had a larger thyroid, 4% to 7% of the respondents recommended operation. METHODS: In our clinic we often recommend operation for young adult patients with large goiters who have had recurrent hyperthyroidism after antithyroid drug (ATD) therapy, have allergic reactions to ATD, are not compliant, are ATD failures, or refuse 131I therapy. Thus operation for Graves' disease is recommended more frequently in our clinic than this survey indicates. From 1980 to 1992, 81 patients with Graves' disease (15 men and 66 women; mean age, 30 years) underwent a subtotal thyroidectomy. Patients had been pretreated with antithyroid drugs and saturated solution of potassium iodide, and thyroid conditions were normal at the time of operation. All patients underwent subtotal thyroidectomy by one surgeon and 3 to 5 grams of thyroid were left on each side. RESULTS: There was no permanent recurrent nerve damage or hypoparathyroidism. Hyperthyroidism recurred in one patient (1.2%). Hypothyroidism developed in 59% of our patients, 77% within 1 year after operation, which was easily managed with replacement doses of levothyroxine. Ophthalmopathy had not developed or progressed in any patient, as has recently been suggested to occur after 131I therapy of Graves' disease. CONCLUSIONS: Because our patients are almost always hospitalized for no more than 24 to 36 hours, have had no complications except for hypothyroidism, have had their disease abruptly terminated, did not have ophthalmopathy, required far fewer physician visits and laboratory tests compared with patients treated with ATD or 131I, surgery remains a reasonable approach to the management of Graves' disease.

Adolescent↗
PubMed1991

Physician practices in the prevention of venous thromboembolism.

OBJECTIVE: To determine the rate of use of prophylaxis for venous thromboembolism in high-risk hospital patients. DESIGN: A retrospective medical record review. SETTING: A community-wide study in 16 short-stay hospitals in central Massachusetts. PATIENTS: A total of 2017 patients with multiple risk factors for venous thromboembolism. MEASUREMENTS AND MAIN RESULTS: On the basis of age, length of hospitalization, and the presence of at least one additional major risk factor, 17% of 151,349 discharges (25,410 patients) were identified as being at high risk for venous thromboembolism. Eight percent of these discharges were randomly selected for medical record review. Prophylaxis for venous thromboembolism was received by 32% of these high-risk patients. Prophylaxis use among the 16 study hospitals varied widely, ranging from 9% to 56%, and was higher in teaching hospitals than in nonteaching hospitals (44% compared with 19%; P less than 0.001). One or more of the following methods of prophylaxis was used: low-dose heparin (78%), intermittent calf compression (13%), warfarin (12%), and inferior vena caval filter (3%). Use of prophylaxis increased with the number of risk factors identified (P less than 0.001). CONCLUSION: Prophylaxis for venous thromboemobolism is underused, particularly in nonteaching hospitals.

Adult↗
PubMed1991

Effect of tumor necrosis factor on growth and function in FRTL5 cells.

Tumor necrosis factor (TNF) is a cytokine produced by inflammatory macrophages and monocytes. FRTL5 cells are a continuous line of functional, nontransformed rat thyroid cells that depend on thyroid-stimulating hormone (TSH) for sustained growth. The following experiments characterize the effects of TNF on growth and differentiated functions in FRTL5 cells. Cells were incubated with different concentrations of TNF (1 to 100 ng/ml), alone or with TSH. FRTL5 cell proliferation was assessed by 3H-thymidine incorporation assays. Differentiated functions were studied by measuring radioactive iodine uptake (RAI) and triiodothyronine (T3) production. TNF inhibited FRTL5 cell growth both in basal conditions and after cells had been exposed to TSH. TNF caused small inhibition of both basal RAI uptake and T3 release but greatly decreased TSH-stimulated RAI uptake and T3 secretion. In summary, TNF appears to affect both growth and differentiated functions in the FRTL5 cell line. Although it is difficult to extrapolate these in vitro results to the human disease state, we postulate that TNF production in septic states may contribute to the pathogenesis of the low T3 syndrome; moreover, locally produced TNF may modulate thyroid function in autoimmune thyroid diseases.

Animals↗
PubMed1991

A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study.

A community-wide study was conducted in 16 short-stay hospitals in metropolitan Worcester, Mass, to examine the incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism in patients hospitalized between July 1, 1985, and December 31, 1986. The average annual incidence of deep vein thrombosis alone was 48 per 100,000, while the incidence of pulmonary embolism with or without deep vein thrombosis was 23 per 100,000. The incidence rates of deep vein thrombosis and pulmonary embolism increased exponentially with age. The in-hospital case-fatality rate of venous thromboembolism was 12%. Among patients discharged from the hospital, the long-term case-fatality rates were 19%, 25%, and 30% at 1, 2, and 3 years after hospital discharge. Extrapolation of the data from this population-based study suggests that there are approximately 170,000 new cases of clinically recognized venous thromboembolism in patients treated in short-stay hospitals in the United States each year, and 99,000 hospitalizations for recurrent disease. Because of the silent nature of this disease and the low rate of autopsy in the United States, the total incidence, prevalence, and mortality rates of venous thromboembolism remain elusive.

Adolescent↗
PubMed1990

Thyroidectomy for amiodarone-induced thyrotoxicosis.

Amiodarone hydrochloride, an iodine-rich drug used in the treatment of tachyarrhythmias, is responsible for the development of thyrotoxicosis in approximately 10% of patients who reside in areas of moderate iodine deficiency. Treatment of amiodarone-induced thyrotoxicosis is difficult since the drug has a prolonged half-life, cardiac decompensation due to underlying heart disease occurs often, and discontinuation of amiodarone therapy may not be possible. We report a patient with severe thyrotoxicosis who received amiodarone for 34 months. Prolonged treatment with methimazole, potassium perchlorate, iopanoic acid, and dexamethasone was unsuccessful in controlling the hyperthyroid state. A near-total thyroidectomy resulted in rapid amelioration of thyrotoxicosis. Since surgery results in rapid control of thyrotoxicosis and permits continued therapy with amiodarone, we suggest that near-total thyroidectomy warrants consideration as definitive treatment for resistant amiodarone-induced thyrotoxicosis.

Amiodarone↗
PubMed1988

Graves' disease: changes in TSH receptor and anti-microsomal antibodies after thyroidectomy.

It has been suggested that intrathyroidal plasma cells are the major site of TSH receptor antibody synthesis in Graves' disease (GD). To investigate this hypothesis, serial serum levels of TSH receptor antibodies, as determined by a recently developed immunoprecipitation assay (IPA), were measured in 13 patients with GD before and after subtotal thyroidectomy (Tx). Pretreatment TSH receptor antibody levels (86.4 +/- 26.8 pM/ml; mean +/- s.d.) decreased significantly due to antithyroid drug therapy to 60.3 +/- 21.5 pM/ml (P less than 0.05) just before Tx. However, 4 h after Tx, there was a significant increase (84.9 +/- 35.5 pM/ml; P less than 0.05) due to leakage of antibodies from the manipulated thyroid gland. After Tx, no major decrease in autoantibody levels occurred; TSH receptor antibodies were still detectable 1 to 7 months after Tx (88.7 +/- 44.6 pM/ml). Neither an acute change nor an overall reduction in anti-microsomal (M) antibody titres was observed after Tx. Our conclusions are that serum TSH antibody levels exhibited a drug-induced decrease before Tx and an immediate, but transient, post-operative increase. The post-operative increase was caused by leakage of preformed TSH receptor antibodies from the manipulated thyroid gland. Several months after Tx, TSH receptor and anti-M antibodies were present in the same serum concentrations as before treatment. The present data does not support the hypothesis that plasma cells in the thyroid gland are the major site of autoantibody synthesis in GD at the time of Tx.

Adolescent↗
PubMed1986

Chronic acalculous gallbladder disease: multiimaging evaluation with clinical-pathologic correlation.

Despite the recent advances in hepatobiliary imaging, the diagnosis of chronic acalculous gallbladder disease remains difficult. A retrospective study was undertaken to assess the value of a multiimaging approach in detecting chronic acalculous gallbladder disease and in predicting which patients would obtain symptomatic relief after cholecystectomy. Of 199 patients with chronic cholecystitis, 26 (13%) had no gallstones. Of these 26, only 17 (65%) had symptoms related to chronic cholecystitis; in the remainder, the histologic diagnosis was made incidentally. After cholecystectomy, 13 (76%) of the 17 symptomatic patients obtained long-term symptomatic relief, while in four, the symptoms recurred. Among patients with histologic changes of chronic cholecystitis, biliary scintigraphy was the most sensitive technique (sensitivity, 89%). The sensitivity of sonography and oral cholecystography was 61.5% and 66%, respectively. However, for identifying symptomatic patients who may obtain long-term symptomatic relief after cholecystectomy, the accuracy of sonography, oral cholecystography, and biliary scintigraphy was 82%, 86%, and 38%, respectively. When two tests were in agreement the accuracy was 88%. For chronic acalculous cholecystitis, more than one study must be performed in order to make the correct diagnosis and to predict good results from cholecystectomy.

Adult↗
PubMed1982

Suspected deep vein thrombosis. Management by impedance plethysmography.

Controversy exists as to whether patients suspected of having deep vein thrombosis (DVT) can be studied safely without venography, with its attendant expense, inconvenience, and potential risk. We used impedance plethysmography (IPG) in 1,464 consecutive patients suspected of having DVT, with 96% of these patients with normal IPGs, there were no fatal pulmonary emboli (PE). The incidence of nonfatal PE was 1%. In 284 outpatients suspected of having DVT, but discharged without treatment because of normal IPGs, only one patient returned with subsequent symptoms of DVT (0.4%). Noninvasive testing with IPG is a safe and highly cost-effective alternative to venography for routine management of patients suspected of DVT.

Adolescent↗
PubMed1977

Impedance plethysmography: correlation with contrast venography.

Impedance plethysmography is a noninvasive, indirect test for deep venous occlusion in the lower limbs. The results of ascending contrast venography impedance plethysmography have been compared in 315 limbs. Impedance plethysmography was positive in 77 of 79 limbs with acute deep vein thrombosis proximal to the calf. It was positive in 6 of 27 limbs with clot isolated in the calf. Only 7 false-positive plethysmograms were found in 161 normal contrast venograms. The clinical implications of these data are discussed.

False Positive Reactions↗
PubMedDate not supplied

Noninvasive detection of axillary and subclavian venous thrombosis by impedance plethysmography.

Venous occlusion impedance plethysmography (IPG) is an objective noninvasive test which is widely employed for the detection of deep venous thrombosis (DVT) in the lower extremities. The IPG technique is easily adapted to the evaluation of upper extremity venous thrombosis, as demonstrated in 46 patients with symptoms of axillary and subclavian venous thrombosis (88 limbs) and 26 normal volunteers (52 limbs). Venograms were obtained in 18 patients (22 limbs) and correlated in all cases with the previous IPG interpretation. The test procedure and interpretation criteria for the noninvasive detection of upper extremity deep venous thrombosis are similar to those previously developed for the lower extremities, but with more emphasis on comparison with the contralateral limb. Vascular laboratories performing IPG for lower extremity DVT should be able to employ this test for the detection of upper extremity venous thrombosis as well.

Adolescent↗