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Biomedical subjects

W M Linehan

Publications and source records attributed to W M Linehan.

At least 199 records · Page 11Linked to original sources
PubMed1991

A report of familial carotid body tumors and multiple extra-adrenal pheochromocytomas.

A case of familial carotid body tumors and multiple extra-adrenal pheochromocytomas is reported. The carotid body tumors, resected previously, were bilateral and associated with 4 intra-abdominal extra-adrenal pheochromocytomas. Magnetic resonance imaging was far superior to computerized tomography and 131iodine-metaiodobenzylguanidine in visualizing the intra-abdominal lesions, and may soon become the imaging technique of choice in the evaluation of patients with suspected pheochromocytoma.

3-Iodobenzylguanidine↗
PubMed1991

von Hippel-Lindau disease: inadequacy of angiography for identification of renal cancers.

Selective renal angiograms were retrospectively evaluated for the identification of renal cell cancers in patients with von Hippel-Lindau disease (VHL). Seven patients underwent angiography and surgery because of solid or complex renal masses identified at cross-sectional imaging. Nine kidneys underwent detailed examination by the surgeon and by a pathologist. There were 31 renal cancers. Angiography had enabled identification of only five cancers (16%), and six others (19%) had been suspected. Cancers detected angiographically were larger than those not detected (P less than .05). Solid tumors tended to appear less hypervascular than expected and occasionally had the angiographic appearance of atypical cysts. There were no false-positive angiograms. Angiography revealed only one cancer not previously suspected and changed the surgeon's approach for only one kidney (11%). The sensitivity and specificity of angiography were 35% and 100%, respectively. In these patients, selective renal angiography is not helpful for the detection or exclusion of cancer in a kidney. It does not have a limited role for vascular mapping prior to partial nephrectomy or tumor enucleation.

Adult↗
PubMed1991

Central nervous system involvement in Von Hippel-Lindau disease.

Fifty individuals with Von Hippel-Lindau disease (VHL) were studied with gadolinium-enhanced magnetic resonance imaging (MRI) to determine the frequency and distribution of CNS lesions. The associated clinical features were also reviewed. Thirty-six (72%) of the 50 had 1 or more CNS tumors. The most frequently affected sites in the CNS excluding the retina were the cerebellum (52%), spinal cord (44%), and brainstem (18%). New regional predilections for the craniocervical junction and conus medullaris were demonstrated by this study. Forty-one percent of all VHL patients with CNS tumors were neurologically asymptomatic: cerebellar tumors (50%), spinal cord tumors (50%), and brainstem tumors (44%) were often without clinical signs or symptoms. Multiple lesions were common. The mean age of all VHL patients (34.5 years) was similar to the mean age of all CNS VHL patients (34.4 years), suggesting a lack of age association. CNS lesions commonly occurred in the 2nd decade of life. All patients at risk for VHL should be evaluated using gadolinium-enhanced MRI after 10 years of age, although ophthalmic examination should be initiated within the 1st 2 years of life. Enhanced MRI is particularly useful in the detection of CNS tumors in patients with the VHL gene.

Adolescent↗
PubMed1991

Inhibitory effects of gossypol on adrenal function.

Gossypol, an antifertility agent, has inhibitory actions on many membrane-associated enzymes, suggesting that this agent might have a generalized effect on cell membranes. This hypothesis was examined in the present study using membranes and dispersed cells prepared from human and rat adrenal glands. Four parameters were determined: microviscosity as measured by fluorescence polarization of human adrenal microsomal- and mitochondrial-enriched membranes, adrenal steroidogenic enzymes; and cAMP and cortisol responses to ACTH. It was found that gossypol increased the polarization constants of microsomes and mitochondria in a dose-dependent manner. Of the three adrenal enzymes tested, both 3 beta-hydroxysteroid dehydrogenase delta 5-delta 4 isomerase and 11-hydroxylase were inhibited by gossypol, but not 21-hydroxylase. Using intact human adrenocortical cells, high doses of gossypol also inhibited the ACTH-stimulated cAMP and cortisol levels. The in vivo corticosterone response to ACTH in rats subjected to chronic gossypol treatment was also found to be reduced. These findings suggest that gossypol has multiple effects on adrenal function. Its effects on membrane microviscosity, adrenal steroidogenesis, cAMP and corticosterone responses to ACTH stimulation probably occur through a generalized membrane effect.

Adrenal Glands↗
PubMed1991

Use of suramin in treatment of prostatic carcinoma refractory to conventional hormonal manipulation.

Suramin and related compounds, in view of their growth factor and enzyme binding properties, represent in many respects a novel approach to the treatment of cancer. Although in this preliminary analysis of suramin use in the treatment of metastatic prostate cancer, the objective response rate does not appear impressive, much work still needs to be done to optimize suramin's administration to patients and to elucidate its various postulated mechanisms of action. The development of related compounds with more specific enzyme and growth factor antagonist properties is under way.

Adrenal Cortex↗
PubMed1990

Unexplained excess risk of bladder cancer in men.

In nearly all populations studied, the risk of bladder cancer is two to four times as great in men as in women. We estimated what the gender-specific incidence rates would be in the absence of exposure to known carcinogenic factors. The data used were obtained from interviews with 2,806 white individuals with bladder cancer and 5,258 white controls in the National Bladder Cancer Study and from incidence data for 1978 from the National Cancer Institute Surveillance, Epidemiology, and End Results Program. The total age-adjusted incidence of bladder cancer was 27.5 cases per 100,000 person-years for men and 7.0 for women, yielding a ratio of 3.9. Even in the absence of exposure to cigarettes, occupational hazards, or urinary tract infection, the gender-related risk persisted; the incidence of bladder cancer was 11.0 in men and 4.1 in women, yielding a ratio of 2.7. Possible explanations for the excessive risk in men include environmental and dietary exposures not yet identified and innate sexual characteristics such as anatomic differences, urination habits, or hormonal factors.

Adult↗
PubMed1990

Collecting duct carcinoma of the kidney.

Collecting duct carcinoma is an unusual variant of renal cell carcinoma, whose appearance and behavior are not well established. We identified six cases of collecting duct carcinoma in our files. The clinical, pathologic, and immunohistochemical characteristics of these tumors are reported. The most common symptom was gross hematuria (four cases). Two patients had cervical adenopathy due to metastatic tumor. Four rapidly developed systemic metastases and died within 4 to 24 months. The primary renal tumors were located predominantly in the renal medulla and pelvis and had a partially cystic white-gray appearance. Histologic examination showed prominent tubulopapillary structures, nests of clear cells, and infiltrating tubules in a dense desmoplastic stroma. Atypical hyperplastic changes were found in some of the adjacent collecting ducts. Mucicarminophilic material was present in glandular elements in all six cases. Immunohistochemical studies revealed positivity with antibodies to epithelial membrane antigen, keratins, peanut agglutinin, vimentin, Leu M1 and lysozyme. The location of this tumor in the medulla, its distinctive histologic appearance, mucin positivity, expression of high molecular weight cytokeratins, and peanut agglutinin suggest that this is a distinct clinicopathologic entity which has an aggressive clinical course.

Adult↗
PubMed1990

Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells.

A total of 63 patients with metastatic renal cell carcinoma with the primary kidney tumor in place was accepted as candidates for immunotherapy at the Surgery Branch of the National Cancer Institute. Of the 63 patients 54 underwent nephrectomy and 9 were treated with the primary kidney tumor in place. Many of the patients underwent associated procedures, such as regional lymphadenectomy (11), venacavotomy with extraction of tumor thrombus (9), hepatic resection (2), pulmonary wedge resection (2), cholecystectomy (2), splenectomy (2), distal pancreatectomy (1), omentectomy (1) and contralateral adrenalectomy (1). Of the 54 patients 20 were not able to enter therapy because of tumor-related (17) or other medical (3) reasons that developed between the operation and therapy, while 34 were able to receive immunotherapy postoperatively. The 20 patients who were treated with either high dose interleukin-2 or interleukin-2 plus lymphokine activated killer cells soon postoperatively (mean 2.1 months) were able to tolerate roughly the same amount of interleukin-2 as the 74 who had undergone nephrectomy before referral to our institute and who were treated for a mean of 22 months after nephrectomy. Further studies, including a prospective, randomized trial, will be required to define the role of nephrectomy in patients with advanced renal cell carcinoma before treatment with interleukin-2 based immunotherapies.

Carcinoma, Renal Cell↗
PubMed1990

Epidermal growth factor receptor gene analysis in renal cell carcinoma.

The epidermal growth factor receptor binds the mitogens epidermal growth factor and transforming growth factor-alpha. Increased expression of the epidermal growth factor receptor has been noted in many types of tumors and is associated with gene amplification in several including epidermoid carcinoma, lung carcinoma, breast carcinoma and glioblastoma. We have recently observed increased expression of the epidermal growth factor receptor messenger RNA in neoplastic tissue relative to normal kidney tissue from patients with renal cell carcinoma. To determine if epidermal growth factor receptor gene amplification was present in renal cell carcinoma, DNA was extracted from renal cell carcinoma cell lines and from normal kidney and renal cell carcinoma tissues derived from radical nephrectomy specimens from thirty patients. DNA was analyzed by Southern blot hybridization. There was no epidermal growth factor receptor gene amplification detected in the renal cell carcinoma samples studied, indicating the increased epidermal growth factor gene expression observed in renal cell carcinoma does not occur through gene amplification. Unlike other tumors with enhanced epidermal growth factor receptor gene expression, amplification of this gene does not appear to be a common feature of renal cell carcinoma.

Adenocarcinoma↗
PubMed1990

Surgical management of pheochromocytoma with the use of metyrosine.

Despite recommended preoperative preparation with alpha-adrenergic blockers, severe hemodynamic instability may occur during operations to resect pheochromocytoma. We combined the alpha-blocker phenoxybenzamine with the tyrosine hydroxylase inhibitor metyrosine in an attempt to better manage the hypertension of patients with pheochromocytoma undergoing surgical resection. This report reviews the cases of 25 consecutive patients undergoing surgery for known intra-abdominal pheochromocytoma. Each patient had elevated serum or urine levels of catecholamines or their metabolites. Nineteen patients were prepared before operation with phenoxybenzamine and metyrosine and six patients were given phenoxybenzamine alone. There were no significant differences in maximum, minimum, or mean blood pressure before or after tumor resection between patients who received metyrosine and those who did not. However careful review suggested that those who received metyrosine had more severe disease as judged by biochemical criteria. Study of selected patients matched for age and severity of disease suggested that the intraoperative blood pressure management of patients prepared with phenoxybenzamine and metyrosine was facilitated. In addition metyrosine-prepared patients lost less blood and required less volume replacement during surgery than did non-metyrosine-prepared patients. There were no apparent differences in postoperative fluid requirements. Although the study is not a prospective randomized trial, a retrospective review of patients managed with the combination of phenoxybenzamine and metyrosine suggests that surgery to resect pheochromocytoma can be better performed with both drugs than with phenoxybenzamine alone. The combination regimen appears to result in better blood pressure control, less blood loss, and the need for less intraoperative fluid replacement than does the traditional method of single-agent alpha-adrenergic blockade.

Adrenal Gland Neoplasms↗
PubMed1990

von Hippel-Lindau disease: radiologic screening for visceral manifestations.

The visceral manifestations of von Hippel-Lindau (VHL) disease can cause significant morbidity and mortality. The authors prospectively screened 37 persons from a single kindred. Twenty-five subjects underwent abdominal ultrasound (US), contrast material-enhanced abdominal computed tomography (CT), and nonenhanced abdominal magnetic resonance (MR) imaging. Eight subjects younger than 16 years of age underwent abdominal US and MR imaging only. Scrotal US was employed in 25 male patients. Eleven subjects had renal cysts or tumors. Contrast-enhanced CT depicted renal abnormalities in 10 of these subjects, US in seven, and MR imaging in nine. Among 12 subjects with pancreatic cysts or tumors, CT showed pancreatic abnormalities in all 12, US in nine, and MR imaging in nine. Three subjects (mean age, 34.5 years) had renal tumors, and three had pancreatic masses. Scrotal US revealed epididymal cystadenomas in seven subjects; two of these tumors were surgically verified. A combination of contrast-enhanced CT and scrotal US in male patients appears to be the best way to screen for visceral manifestations of VHL disease.

Adolescent↗
PubMed1990

Papillary cystadenoma of the epididymis. A report of three cases with lectin histochemistry.

Papillary cystadenoma of the epididymis is an uncommon benign tumor associated with von Hippel-Lindau disease. Since metastatic renal cell carcinoma may be histologically similar to papillary cystadenoma, and both are associated with von Hippel-Lindau disease, differentiation between these two entities may be difficult. We performed lectin histochemistry studies on three papillary cystadenomas and compared the results with the staining observed in epididymal ducts, epididymal efferent ductules, and three renal cell carcinomas. Common positive staining was observed following incubation with soybean agglutinin in epididymal ducts and two of the three papillary cystadenomas, while the three renal cell carcinomas did not stain. When epididymal tumors histologically consistent with papillary cystadenoma fail to react with soybean agglutinin, thorough clinical evaluation for an occult renal cell carcinoma should be performed.

Adult↗
PubMed1989

Expression of transforming growth factor alpha in normal human adult kidney and enhanced expression of transforming growth factors alpha and beta 1 in renal cell carcinoma.

Normal kidney and renal cell carcinoma tissues from ten patients were studied for mRNA and DNA for both transforming growth factors alpha and beta 1. Northern and Southern hybridizations were conducted on samples extracted from the solid tumor and surrounding normal tissues and two tumor-derived cell lines. Low levels of constitutive expression of TGF-alpha mRNA were detected in all normal kidney tissues; six of the ten patients, however, demonstrated an increased (2- to 8-fold) expression of TGF-alpha in the tumor versus normal kidney as determined by densitometry of RNA blots. All ten patients had elevated mRNA levels for TGF-beta 1 in the tumor (2.5-to 22-fold increase) relative to normal kidney. Two tumor-derived cell lines also expressed TGF-alpha and TGF-beta 1 mRNA. Southern blot hybridization of the DNA extracted from the normal tumor pairs revealed no gene amplification or gross rearrangement for either the TGF-alpha or TGF-beta 1 genes. These results demonstrate the expected constitutive expression of TGF-beta 1 by normal kidney; however, the constitutive expression of TGF-alpha by Northern blot analysis in normal adult human kidney is previously unreported. Enhanced expression of TGF-alpha and TGF-beta 1 mRNA in solid tumor may be related to the development of renal cell carcinoma.

Autoradiography↗
PubMed1989

The detection of renal carcinoma extension into the renal vein and inferior vena cava: a prospective comparison of venacavography and magnetic resonance imaging.

Accurate preoperative evaluation of the inferior vena cava and renal vein in patients with renal cell carcinoma is mandatory to plan a successful surgical approach. The presence of venous extension may alter transfusion and anesthetic requirements, as well as require the addition of a vascular surgeon to the operative team. Venacavography traditionally has been considered the most reliable method to identify tumor thrombus, although magnetic resonance imaging has been proposed as a possible noninvasive alternative. We compared prospectively the accuracy of these 2 methods in 44 consecutive patients with renal cell carcinoma who subsequently underwent nephrectomy. Of the 44 patients 11 (25%) had tumor extension into the inferior vena cava and 17 (39%) had involvement of the renal vein at operation. Venacavography and magnetic resonance imaging correctly identified 9 of the 11 patients (82%) with inferior vena caval thrombus. When the results of both tests were combined, all 11 cases of vena caval extension were identified. Venacavography was slightly more sensitive (71%) in identifying the presence of renal vein thrombus than magnetic resonance imaging (65%) but these differences were not statistically significant. Magnetic resonance imaging better localized the thrombus within the renal vein. We conclude that venacavography and magnetic resonance imaging offer equal diagnostic accuracy in the identification of venous extension of renal cell carcinoma. The combination of both tests results in higher diagnostic yield than either test alone. Neither test by itself is reliable in the presence of a large, bulky adenopathic lesion that compresses the inferior vena cava.

Adult↗
PubMed1989

Clinically occult Leydig cell tumor presenting with gynecomastia.

An occult Leydig cell tumor is described in a patient who presented with gynecomastia. Diagnosis was established by means of testicular ultrasonography and selective testicular venous sampling. The pathophysiology and management of this rare disease entity are discussed.

Adult↗
PubMed1989

Epidermal growth factor receptor gene expression in normal human kidney and renal cell carcinoma.

The epidermal growth factor receptor (EGFr) is a transmembrane glycoprotein detected on many cells and tissues including neoplastic and normal kidney. EGFr binds the mitogenic polypeptide hormone epidermal growth factor (EGF) as well as EGF-related transforming growth factor-alpha (TGF-alpha). Increases in EGFr gene expression and protein production have been implicated in the development of the malignant phenotype for certain cancers. To determine if alterations in EGFr gene expression are present in human renal cell carcinoma, paired samples of normal and neoplastic renal tissue from ten patients with advanced renal cell carcinoma were analyzed for EGFr mRNA content by Northern blot hybridization. The EGFr gene was constitutively expressed in 90% of normal kidney samples. In seven out of nine evaluable patients, tumors expressed 1.7 to 8.4 times more EGFr mRNA than corresponding normal tissue. Two patients showed no elevation of tumor EGFr mRNA and one patient had no identifiable EGFr transcripts in either neoplastic or normal kidney. Expression of EGFr mRNA was also detected in three tumor-derived and two established renal cell carcinoma cell lines. EGFr transcripts were not found in tumor infiltrating lymphocytes (TIL). These findings suggest that overexpression of EGFr mRNA may be associated with malignant transformation in renal cell carcinomas.

Blotting, Northern↗