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Evan S Siegelman

Publications and source records attributed to Evan S Siegelman.

At least 19 recordsLinked to original sources
PubMed2007

Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia.

BACKGROUND: Patients with homozygous familial hypercholesterolemia have markedly elevated cholesterol levels, which respond poorly to drug therapy, and a very high risk of premature cardiovascular disease. Inhibition of the microsomal triglyceride transfer protein may be effective in reducing cholesterol levels in these patients. METHODS: We conducted a dose-escalation study to examine the safety, tolerability, and effects on lipid levels of BMS-201038, an inhibitor of the microsomal triglyceride transfer protein, in six patients with homozygous familial hypercholesterolemia. All lipid-lowering therapies were suspended 4 weeks before treatment. The patients received BMS-201038 at four different doses (0.03, 0.1, 0.3, and 1.0 mg per kilogram of body weight per day), each for 4 weeks, and returned for a final visit after a 4-week drug washout period. Analysis of lipid levels, safety laboratory analyses, and magnetic resonance imaging of the liver for fat content were performed throughout the study. RESULTS: All patients tolerated titration to the highest dose, 1.0 mg per kilogram per day. Treatment at this dose decreased low-density lipoprotein (LDL) cholesterol levels by 50.9% and apolipoprotein B levels by 55.6% from baseline (P<0.001 for both comparisons). Kinetic studies showed a marked reduction in the production of apolipoprotein B. The most serious adverse events were elevation of liver aminotransferase levels and accumulation of hepatic fat, which at the highest dose ranged from less than 10% to more than 40%. CONCLUSIONS: Inhibition of the microsomal triglyceride transfer protein by BMS-201038 resulted in the reduction of LDL cholesterol levels in patients with homozygous familial hypercholesterolemia, owing to reduced production of apolipoprotein B. However, the therapy was associated with elevated liver aminotransferase levels and hepatic fat accumulation.

Adolescent↗
PubMed2006

Incidence of benign pathologic findings at partial nephrectomy for solitary renal mass presumed to be renal cell carcinoma on preoperative imaging.

OBJECTIVES: To determine the incidence of benign pathologic findings at partial nephrectomy for a solitary renal lesion when preoperative imaging is reviewed by an experienced team of academic genitourinary radiologists. METHODS: From 1996 to 2004, 143 patients underwent resection of a solitary renal lesion for presumed renal cell carcinoma amenable to partial nephrectomy. Our experienced team of genitourinary radiologists interpreted all preoperative imaging scans. Of the 143 patients, 44 underwent partial nephrectomy for a solitary lesion less than 2 cm, 85 for a lesion 2 to 4 cm, and 14 for a lesion greater than 4 cm. RESULTS: Of the 143 solitary masses resected, 23 revealed benign pathologic findings (16.1%). Ten lesions (43.5%) were angiomyolipomas (AMLs), eight (34.8%) were oncocytomas, three (13.0%) were benign Bosniak-type cysts, and one each was a low-grade spindle cell lesion most consistent with mesoblastic nephroma, and a metanephric adenoma. CONCLUSIONS: A significant fraction of small solitary renal masses presumed to be renal cell carcinoma had benign pathologic findings on resection, despite thorough expert radiologic review. Management should favor parenchyma-sparing approaches, because resection serves not only a therapeutic but also a diagnostic function. Patients should be counseled accordingly when faced with the diagnosis of renal mass.

Adenoma↗
PubMed2005

Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of Radiology Imaging Network 6651-Gynecologic Oncology Group 183.

PURPOSE: To compare magnetic resonance imaging (MRI) and computed tomography (CT) with each other and to International Federation of Gynecology and Obstetrics (FIGO) clinical staging in the pretreatment evaluation of early invasive cervical cancer, using surgicopathologic findings as the reference standard. PATIENTS AND METHODS: This prospective multicenter clinical study was conducted by the American College of Radiology Imaging Network and the Gynecologic Oncology Group from March 2000 to November 2002; 25 United States health centers enrolled 208 consecutive patients with biopsy-confirmed cervical cancer of FIGO stage > or = IB who were scheduled for surgery based on clinical assessment. Patients underwent FIGO clinical staging, helical CT, and MRI. Surgicopathologic findings constituted the reference standard for statistical analysis. RESULTS: Complete data were available for 172 patients; surgicopathologic findings were consistent with FIGO stages IA to IIA in 76% and stage > or = IIB in 21%. For the detection of advanced stage (> or = IIB), sensitivity was poor for FIGO clinical staging (29%), CT (42%), and MRI (53%); specificity was 99% for FIGO clinical staging, 82% for CT, and 74% for MRI; and negative predictive value was 84% for FIGO clinical staging, 84% for CT, and 85% for MRI. MRI (area under the receiver operating characteristic curve [AUC], 0.88) was significantly better than CT (AUC, 0.73) for detecting cervical tumors (P = .014). For 85% of patients, FIGO clinical staging forms were submitted after MRI and/or CT was performed. CONCLUSION: CT and MRI performed similarly; both had lower staging accuracy than in prior single-institution studies. Accuracy of FIGO clinical staging was higher than previously reported. The temporal data suggest that FIGO clinical staging was influenced by CT and MRI findings.

Adenocarcinoma↗
PubMed2005

Efficacy and safety of MR imaging with liver-specific contrast agent: U.S. multicenter phase III study.

PURPOSE: To assess prospectively the efficacy and safety of postcontrast magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) compared with that of precontrast MR imaging in patients who are known to have or are suspected of having liver lesions and who are scheduled for hepatic surgery. MATERIALS AND METHODS: Investigational review board approval and written informed consent were obtained. HIPAA went into effect after data collection. A total of 172 patients were enrolled. After precontrast MR imaging, 169 patients (94 men, 75 women; mean age, 61 years; age range, 19-84 years) received an intravenous bolus of 25 micromol/kg Gd-EOB-DTPA and underwent dynamic gradient-recalled-echo and delayed MR imaging 20 minutes after injection. Arterial and portal phase computed tomography (CT) were performed within 6 weeks of MR imaging. The standard of reference was surgery with intraoperative ultrasonography (US) and biopsy and/or pathologic evaluation of resected liver segments and/or 3-month follow-up of nonresected segments if intraoperative US was not available. Three blinded reviewers and unblinded site investigators identified liver lesions on segment maps. The Wilcoxon signed rank test was used to compare differences in per-patient sensitivity of precontrast and postcontrast MR images. Adverse events were recorded, and patient monitoring and laboratory assay were performed at time of injection and up to 24 hours after contrast material administration. RESULTS: At MR imaging, 316 lesions were identified in 131 patients. In 77% (P = .012), 72% (P = .15), and 71% (P = .027) of patients for readers 1, 2, and 3, respectively, more lesions were seen at precontrast and postcontrast MR imaging combined than at precontrast MR imaging alone. Sensitivity values for blinded readings were significantly greater at postcontrast MR imaging than at precontrast MR imaging for two of three blinded readers. For all blinded readers, combined precontrast and postcontrast MR images showed no difference in sensitivity compared with helical CT scans. The use of MR imaging, however, yielded fewer patients with at least one false-positive lesion (37%, 31%, and 34% of patients for readers 1, 2, and 3, respectively) than did helical CT (45%, 36%, and 43% of patients for readers 1, 2, and 3, respectively). CONCLUSION: Compared with precontrast MR imaging, postcontrast MR imaging with Gd-EOB-DTPA demonstrated improved sensitivity for lesion detection in the majority of blinded readers, with no substantial adverse events.

Adult↗
PubMed2005

Extrathoracic solitary fibrous tumor of the pelvic peritoneum with central malignant degeneration on CT and MRI.

We describe a 61-year-old man who presented with an extrathoracic solitary fibrous tumor (SFT) of the pelvic peritoneum with central malignant degeneration as seen on computed tomography (CT), magnetic resonance imaging (MRI), and histopathology. When a central focus of heterogeneity and variable contrast enhancement are identified within a fibrous tumor of the pelvis on CT or MRI, malignant degeneration of an extrathoracic SFT, although rare, should be considered as a diagnostic possibility.

Humans↗
PubMed2004

MR imaging of the bladder.

MR imaging is a useful modality for evaluating diseases of the bladder. MR imaging can detect and stage bladder cancer by determining the presence and depth of muscle invasion. Direct multiplanar imaging and superb soft-tissue contrast make MR imaging an ideal modality for evaluating less common neoplastic diseases of the bladder, such as urachal carcinoma, and tumors that develop within bladder diverticula. Dynamic breath-held fast T2-weighted imaging can evaluate for cystocele and other components of pelvic floor relaxation.

Humans↗
PubMed2003

Gadolinium susceptibility artifact causing false positive stenosis isolated to the proximal common carotid artery in 3D dynamic contrast medium enhanced MR angiography of the thorax--a brief review of causes and prevention.

Due to the close proximity of arteries and veins in the superior mediastinum and upper extremities, T2* shortening effects of the gadolinium within the central veins may cause artifactual vascular stenosis (susceptibility artifact) on arterial-phase MR angiographic images of the major branches of the aortic arch. We report a case of artifactual stenosis isolated to the origin of the left common carotid artery on arterial-phase MR angiography, secondary to susceptibility artifact from non-diluted gadolinium in the adjacent brachiocephalic vein. The cause of the artifact, its identification and prevention is reviewed.

Adult↗
PubMed2003

Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival?

There is growing interest in more widespread application of isolated islet transplantation for the treatment of type 1 diabetes; however, the sequelae of long-term islet residence within the liver are unknown. We report herein a consequence of intraportal islet transplantation, specifically the development of periportal hepatic steatosis apparently induced by the local secretion of insulin within the liver.

Follow-Up Studies↗
PubMed2002

Cirrhosis: MR imaging features.

The intent of this article is to provide a comprehensive review of MR imaging findings of cirrhosis and discusses clinical implications. Areas of focus include: (1) Morphologic changes of the liver in advanced cirrhosis and in early cirrhosis, (2) the frequency and imaging spectrum of intra- and extrahepatic changes in cirrhosis such as regenerative nodules, nodular liver surface, hepatic iron deposition, fibrosis, dilation of right inferior phrenic artery, gastrointestinal wall thickening, and portal hypertension, (3) serial MR findings of clinically progressive cirrhosis, (4) newly described MR sign of cirrhosis (an expanded gallbladder fossa sign), and (5) complications after liver transplantation. Understanding these MR features related to cirrhosis is helpful in clinical MR practice.

Humans↗
PubMed2002

MR imaging of iron depositional disease.

This article discusses the physiology of iron metabolism in humans. The pathophysiology and MR imaging findings of disorders that result in iron deposition in the liver are described. Emphasis is placed on genetic, clinical, and imaging findings of hemochromatosis. Radiologists should familiarize themselves with the patterns of iron deposition on MR images in order to suggest a potential etiology, which may not be known at the time of imaging.

Hemochromatosis↗
PubMed2002

MR imaging of the gallbladder.

T2-weighted imaging and MRCP, which have high sensitivity to edema and fluid, are paramount in the evaluation of certain gallbladder diseases, such as cholelithiasis, cholecystitis, adenomyomatosis, and cystic duct abnormalities. Dynamic gadolinium-enhanced MR imaging has the potential to differentiate among the many nonspecific-appearing lesions involving the gallbladder. MR imaging may not yet replace ultrasound as the workhorse of acute gallbladder imaging. Currently, MRCP is an ideal complementary study to inconclusive sonographic studies and can help plan surgical intervention in the setting of acute cholecystitis. Further investigation of hepatobiliary contrast agents, however, may reveal that MR imaging may be considered as first-line imaging in the acute setting.

Adenomyoma↗
PubMed2002

Multimodality diagnosis of liver tumors: feature analysis with CT, liver-specific and contrast-enhanced MR, and a computer model.

RATIONALE AND OBJECTIVES: The purpose of this study was to measure and to clarify the diagnostic contributions of image-based features in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. MATERIALS AND METHODS: Six experienced abdominal radiologists each read images from 146 cases (including a contrast material-enhanced computed tomographic [CT] scan and contrast-enhanced and unenhanced magnetic resonance [MR] images) following a checklist-questionnaire requiring them to rate quantitatively each of as many as 131 image features and then reported on each of the two differentiations. The diagnostic value of each feature was assessed, and linear discriminant analysis was used to develop statistical prediction rules (SPRs) for merging feature data into computerized "second opinions." For the two differentiations, accuracy (area under the receiver operating characteristic curve [Az]) was then determined for the radiologists' readings by themselves and for each of three SPRs. RESULTS: Thirty-seven candidate features had diagnostic value for each of the two differentiations (a slightly different feature set for each). Radiologists' performance at both differentiations was excellent (Az = 0.929 [benign vs malignant] and 0.926 [hepatocyte-containing vs non-hepatocyte-containing]). Performance of the SPR that operated on the features from all modalities together was better than that of radiologists (Az = 0.936 [benign vs malignant] and 0.951 [hepatocyte-containing vs non-hepatocyte-containing]), but this difference was of marginal statistical significance (P = .11). Contrast-enhanced MR imaging and contrast-enhanced CT each made significant adjunctive contributions to accuracy compared with unenhanced MR imaging alone. CONCLUSION: Many CT- and MR imaging-based features have diagnostic value in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. Radiologists could also benefit from the fully informed SPR's "second opinions."

Adult↗
PubMed2002

Magnetic resonance imaging techniques.

In this article we describe state-of-the art techniques for magnetic resonance imaging of the liver. T1-weighted, T2-weighted, and heavily T2-weighted pulse sequences are discussed. Gadolinium-enhanced hepatic parenchymal imaging and magnetic resonance angiography are also described. A comprehensive MR imaging examination of the liver affords evaluation of focal and diffuse hepatic parenchymal disease, biliary disease, and vascular pathology.

Contrast Media↗
PubMed2002

Liver lesions: manganese-enhanced MR and dual-phase helical CT for preoperative detection and characterization comparison with receiver operating characteristic analysis.

PURPOSE: The purpose of this study was to compare, by means of receiver operating characteristic (ROC) analysis, dual-phase helical computed tomography (CT) and manganese-enhanced magnetic resonance (MR) imaging in the detection and characterization of hepatic lesions in patients prior to surgery. MATERIALS AND METHODS: Twenty-five patients known to have or suspected of having hepatic lesions who were eligible for surgery underwent dual-phase (ie, arterial and portal phase) helical CT and phased-array MR imaging (ie, unenhanced fast spin-echo T2-weighted imaging and gradient-echo T1-weighted imaging performed before and after administration of mangafodipir trisodium). All images were reviewed independently by three off-site blinded reviewers who separately reviewed the CT scans and MR images. The standard of reference was findings at surgery, intraoperative ultrasonography (US), and histopathologic examination. ROC curves were established to analyze the results for each reader and modality. RESULTS: Ninety-four lesions (77 malignant and 17 benign) were revealed at surgery, intraoperative US, and/or histopathologic examination. The overall rate of lesion detection for the three readers at CT was 81.9% +/- 7.8, 90.4% +/- 5.9, and 76.6% +/- 8.6. At MR imaging, the detection rates were 72.3% +/- 9.0, 71.3% +/- 9.1, and 69.1% +/- 9.3 (P =.001 for the difference between MR and CT). The average rate of false-positive diagnoses in patients was 14.1% at CT and 6.4% at MR imaging (P =.06 for the difference between MR and CT). The mean areas under the alternative-free-response ROC curves were 0.74 for MR and 0.72 for CT (P =.751, not significant). CONCLUSION: In detection and characterization of liver lesions, manganese-enhanced MR imaging and dual-phase helical CT were not statistically different.

Adult↗