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1.
Radiol Cardiothorac Imaging ; 4(6): e220155, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36601454

ABSTRACT

Limited aortic intimal tear is an uncommon lesion of the dissection spectrum. The lesion has several imaging features that are not well known, including asymmetric aortic contour abnormalities, filling defects, and various morphologic patterns, such as linear, L-shaped, T-shaped, and stellate configurations. Hemorrhage of the aortic wall may also be present in patients with this rare entity. This imaging essay reviews the CT imaging findings and clinical characteristics of patients with limited intimal tears. Keywords: Aorta, CT © RSNA, 2022.

2.
Radiographics ; 41(2): 425-446, 2021.
Article in English | MEDLINE | ID: mdl-33646901

ABSTRACT

Acute aortic dissection is the prototype of acute aortic syndromes (AASs), which include intramural hematoma, limited intimal tear, penetrating atherosclerotic ulcer, traumatic or iatrogenic aortic dissection, and leaking or ruptured aortic aneurysm. The manifestation is usually sudden and catastrophic with acutely severe tearing chest or back pain. However, clinical symptoms do not allow distinction between AAS types and other acute pathologic conditions. Diagnostic imaging is essential to rapidly confirm and accurately diagnose the type, magnitude, and complications of AASs. CT fast acquisition of volumetric datasets has become instrumental in diagnosis, surveillance, and intervention planning. Most critical findings affecting initial intervention and prognosis are obtained at CT, including involvement of the ascending aorta, primary intimal tear location, rupture, malperfusion, size and patency of the false lumen, complexity and extent of the dissection, maximum caliber of the aorta, and progression or postintervention complications. Involvement of the ascending aorta-Stanford type A-has the most rapid lethal complications and requires surgical intervention to affect its morbidity and mortality. Lesions not involving the ascending aorta-Stanford type B-have a lesser rate of complications in the acute phase. During the acute to longitudinal progression, various specific and nonspecific imaging findings are encountered, including pleural and pericardial effusions, fluid collections, progression including aortic enlargement, and postoperative changes that can be discerned at CT. A systematic analysis algorithm is proposed for CT of the entire aorta throughout the continuum of AASs into the chronic and posttreated disease state, which synthesizes and communicates salient findings to all care providers. Online supplemental material is available for this article. ©RSNA, 2021.


Subject(s)
Aortic Dissection , Acute Disease , Aortic Dissection/diagnostic imaging , Aorta , Diagnostic Imaging , Hematoma/diagnostic imaging , Humans , Syndrome
3.
Semin Ultrasound CT MR ; 38(6): 584-593, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29179898

ABSTRACT

Intrathoracic paragangliomas are uncommon and only represent 1%-2% of paragangliomas. They are most commonly found in mediastinal compartments (aortopulmonary window or posterior mediastinum). Computed tomography, magnetic resonance, and specific nuclear medicine radiotracers are routinely used to characterize these lesions and help exclude other more common conditions. Selective angiography is currently used for preoperative embolization and mapping of the vascular supply before surgical resection, rather than for diagnostic purposes alone.


Subject(s)
Paraganglioma/diagnosis , Thoracic Neoplasms/diagnosis , Adult , Female , Humans , Male , Middle Aged , Positron-Emission Tomography
4.
J Thorac Imaging ; 31(6): 380-390, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27768631

ABSTRACT

PURPOSE: Coronary-pulmonary arterial fistulas (CPAFs) are rare coronary artery anomalies that have been described only in limited case reports. This study aims to evaluate the clinical presentation and imaging findings of CPAFs collected from 6 participating medical centers along with CPAFs reported in the literature, to discern any general trends present in CPAFs. MATERIALS AND METHODS: A total of 25 cases of CPAF diagnosed by coronary computed tomography angiography were collected across 6 participating institutions. In addition, utilizing a PubMed literature search, 78 additional CPAF cases were obtained. The imaging findings and relevant clinical history were reviewed. RESULTS: Of the 103 CPAF patients, 60 (63% of patients with sex known) were male, with ages ranging from newborn to 88 years (mean=46.1 y). The most common symptoms reported were chest pain (n=40, 39%) and dyspnea (n=26, 25%), with a murmur as the most common physical examination finding (n=38, 37%). The most common coronary artery of origin for a CPAF was the left main/left anterior descending (n=87, 84%), followed by the right coronary artery (n=39, 38%). The fistula most commonly terminated in the main pulmonary artery (n=92, 89%). Multiple CPAFs were present in 46 cases (45%). Coronary artery aneurysms were identified in 20 cases (19%). Pediatric CPAF cases were usually associated with pulmonary atresia with ventricular septal defect. CONCLUSIONS: CPAFs are seen in a variety of clinical settings, from infants with advanced congenital heart disease to elderly patients who have undergone revascularization surgery. Although coronary artery fistulas have previously been described as rarely involving multiple coronary arteries, with the right coronary artery being most often involved, our series demonstrates that multiple fistulas are commonly present, with the most common pattern being between the left main/left anterior descending and the main pulmonary trunk.


Subject(s)
Arterio-Arterial Fistula/diagnostic imaging , Coronary Vessel Anomalies/diagnostic imaging , Pulmonary Artery/abnormalities , Pulmonary Artery/diagnostic imaging , Computed Tomography Angiography , Coronary Angiography , Coronary Vessels/diagnostic imaging , Humans
5.
Radiographics ; 36(4): 963-83, 2016.
Article in English | MEDLINE | ID: mdl-27399236

ABSTRACT

Myriad infectious organisms can infect the endocardium, myocardium, and pericardium, including bacteria, fungi, parasites, and viruses. Significant cardiac infections are rare in the general population but are associated with high morbidity and mortality as well as increased risk in certain populations, such as the elderly, those undergoing cardiac instrumentation, and intravenous drug abusers. Diagnostic imaging of cardiac infections plays an important role despite its variable sensitivity and specificity, which are due in part to the nonspecific manifestations of the central inflammatory process of infection and the time of onset with respect to the time of imaging. The primary imaging modality remains echocardiography. However, cardiac computed tomography and magnetic resonance (MR) imaging have emerged as the modalities of choice wherever available, especially for diagnosis of complex infectious complications including abscesses, infected prosthetic material, central lines and instruments, and the cryptic manifestations of viral and parasitic diseases. MR imaging can provide functional, morphologic, and prognostic value in a single examination by allowing characterization of inflammatory changes from the acute to chronic stages, including edema and the patterns and extent of delayed gadolinium enhancement. We review the heterogeneous and diverse group of cardiac infections based on their site of primary cardiac involvement with emphasis on their cross-sectional imaging manifestations. Online supplemental material is available for this article. (©)RSNA, 2016.


Subject(s)
Heart Diseases/diagnostic imaging , Heart Diseases/physiopathology , Infections/diagnostic imaging , Infections/physiopathology , Diagnosis, Differential , Diagnostic Imaging , Heart Diseases/microbiology , Humans , Infections/microbiology
6.
Radiographics ; 36(2): 335-54, 2016.
Article in English | MEDLINE | ID: mdl-26963450

ABSTRACT

Hypertrophic cardiomyopathy (HCM) is a heterogeneous group of diseases related to sarcomere gene mutations exhibiting heterogeneous phenotypes with an autosomal dominant mendelian pattern of inheritance. The disorder is characterized by diverse phenotypic expressions and variable natural progression, which may range from dyspnea and/or syncope to sudden cardiac death. It is found across all racial groups and is associated with left ventricular hypertrophy in the absence of another systemic or cardiac disease. The management of HCM is based on a thorough understanding of the underlying morphology, pathophysiology, and clinical course. Imaging findings of HCM mirror the variable expressivity and penetrance heterogeneity, with the added advantage of diagnosis even in cases where a specific mutation may not yet be found. The diagnostic information obtained from imaging varies depending on the specific stage of HCM-phenotype manifestation, including the prehypertrophic, hypertrophic, and later stages of adverse remodeling into the burned-out phase of overt heart failure. However, subtle or obvious, these imaging findings become critical components in diagnosis, management, and follow-up of HCM patients. Although diagnosis of HCM traditionally relies on clinical assessment and transthoracic echocardiography, recent studies have demonstrated increased utility of multidetector computed tomography (CT) and particularly cardiac magnetic resonance (MR) imaging in diagnosis, phenotype differentiation, therapeutic planning, and prognostication. In this article, we provide an overview of the genetics, pathophysiology, and clinical manifestations of HCM, with the spectrum of imaging findings at MR imaging and CT and their contribution in diagnosis, risk stratification, and therapy.


Subject(s)
Cardiomyopathy, Hypertrophic, Familial/diagnostic imaging , Magnetic Resonance Imaging, Cine , Multidetector Computed Tomography , Cardiomyopathies/diagnosis , Cardiomyopathy, Hypertrophic, Familial/genetics , Cardiomyopathy, Hypertrophic, Familial/physiopathology , Cardiomyopathy, Hypertrophic, Familial/therapy , Diagnosis, Differential , Disease Management , Disease Progression , Genes, Dominant , Genetic Association Studies , Genetic Testing , Heart Failure/etiology , Heart Septum/diagnostic imaging , Heart Septum/pathology , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Humans , Hypertension, Pulmonary/etiology , Muscle Proteins/genetics , Penetrance , Sarcomeres/ultrastructure , Ventricular Outflow Obstruction/diagnostic imaging , Ventricular Outflow Obstruction/etiology
7.
Radiographics ; 33(1): 3-19, 2013.
Article in English | MEDLINE | ID: mdl-23322824

ABSTRACT

Multidetector computed tomography (CT) is the modality of choice for the evaluation of facial trauma because it helps accurately identify and characterize fractures and associated complications, thereby aiding timely clinical management and surgical planning. In particular, CT clearly depicts clinically relevant fractures in the eight osseous struts or buttresses that function as an underlying scaffold for facial structures. Information about the involvement of specific facial buttresses in a complex fracture is helpful for determining the type of fracture present and for identifying associated soft-tissue injuries that may require urgent care or surgery. Various kinds of complications can be expected to occur in Le Fort fractures, which affect the full thickness of the pterygoid plates, with resultant dissociation of part or all of the maxilla from the skull base; naso-orbitoethmoid complex fractures, which involve the medial orbital wall, nasal bone, ethmoid sinuses, and, often, the attachment site of the medial canthal tendon; zygomaticomaxillary complex fractures, which disrupt all four zygomatic sutures and may lead to enophthalmos due to increased orbital volume because of angulation of the lateral orbital wall; orbital "blowout" fractures, which may result in extraocular muscle herniation or entrapment and injuries to the globe or the infraorbital nerve; and fractures of the alveolar process, which are treated as open fractures because of their extension through the gingiva to the oral cavity and their resultant vulnerability to infection. Similarly, extension of a frontal sinus fracture through the posterior sinus wall creates a portal to the anterior cranial fossa and may lead to cerebrospinal fluid leakage, intracranial hemorrhage, or intracranial infection.


Subject(s)
Facial Bones/diagnostic imaging , Facial Bones/injuries , Facial Injuries/diagnostic imaging , Skull Fractures/diagnostic imaging , Tomography, X-Ray Computed , Diagnosis, Differential , Humans
8.
Semin Ultrasound CT MR ; 33(6): 473-84, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23168059

ABSTRACT

This review focuses on the embryology and normal imaging anatomy of the pulmonary circulation, with emphasis on the major arterial and venous vasculature. The pulmonary circulation and parenchyma have a complex intertwined embryologic origin. Understanding the embryologic basis of normal pulmonary vasculature aids recognition of anomalies and visceral situs in the chest. Adaptive changes to congenital anomalies of the pulmonary arterial vasculature are used to contrast from normal and review associated temporal adaptive vascular and parenchymal changes.


Subject(s)
Bronchial Arteries/anatomy & histology , Microvessels/anatomy & histology , Pulmonary Artery/anatomy & histology , Pulmonary Circulation , Pulmonary Veins/anatomy & histology , Bronchial Arteries/diagnostic imaging , Bronchial Arteries/embryology , Humans , Microvessels/diagnostic imaging , Microvessels/embryology , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/embryology , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/embryology , Reference Values , Tomography, X-Ray Computed/methods
9.
Semin Ultrasound CT MR ; 33(6): 485-99, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23168060

ABSTRACT

Developmental lung anomalies are classified into 3 main categories: bronchopulmonary (lung bud) anomalies, vascular anomalies, and combined lung and vascular anomalies. These anomalies are uncommon, and patients are at times asymptomatic; hence, identifying a developmental lung anomaly in the adult can be a challenge. Pulmonary vascular anomalies include interruption or absence of the main pulmonary artery, anomalous origin of the left pulmonary artery from the right pulmonary artery, anomalous pulmonary venous drainage (partial or complete), and pulmonary arteriovenous malformations. Systemic vascular anomalies comprise persistent left superior vena cava, anomalies of azygos and hemiazygos systems, and anomalies of the thoracic aorta and its major branches. In this article, we present embryology, classification, epidemiology, clinical presentation, and imaging features of anomalous pulmonary venous connections, with special emphasis on multidetector computed tomography and magnetic resonance imaging. These state-of-art imaging techniques have facilitated accurate and prompt diagnosis of these anomalies.


Subject(s)
Lung/abnormalities , Pulmonary Artery/abnormalities , Pulmonary Veins/abnormalities , Vascular Malformations/diagnosis , Bronchi/abnormalities , Bronchi/pathology , Bronchography/methods , Humans , Lung/diagnostic imaging , Lung/pathology , Magnetic Resonance Angiography/methods , Multidetector Computed Tomography/methods , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/pathology , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/pathology
11.
Semin Ultrasound CT MR ; 33(3): 169-90, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22624964

ABSTRACT

This review focuses on the embryology and anatomy of the aorta with some imaging examples. Dividing the aorta by segments of unique function and embryogenesis facilitates organizing the group of potential anomalies encountered. A basic understanding of the embryologic development of the aorta and its major branches helps in understanding and recognizing typical and atypical anatomic findings. Diagnostic imaging of the aorta and its major branches can be accomplished by invasive and noninvasive methods, based on the clinical scenario and the age of the patient. In this review, computed tomography and magnetic resonance imaging examples are emphasized.


Subject(s)
Aorta/anatomy & histology , Aorta/embryology , Diagnostic Imaging/methods , Models, Anatomic , Humans
12.
J Magn Reson Imaging ; 35(6): 1445-52, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22246813

ABSTRACT

PURPOSE: To systematically evaluate and compare the performance of water-saturated and nonwater-saturated T1-weighted 3.0 T magnetic resonance imaging (MRI) in the application of visceral adipose tissue (VAT) quantification. MATERIALS AND METHODS: Forty-five patients underwent abdomen MRI using two different sequences at 3.0 T: 1) a traditional T1-weighted gradient echo sequence, and 2) the same sequence with water presaturation to enhance fat and nonfat contrast. VAT amounts from both water-saturated and nonwater-saturated images were quantified with a manual thresholding technique and an automated segmentation method to study quantification variability and consistency of the two imaging techniques. RESULTS: Nonwater-saturated MRI had significantly larger coefficient of variation than water-saturated MRI in the imaging reproducibility study based on 112 slices from seven subjects (11.4% vs. 2.5%, P < 0.0001). VAT volumes measured from the nonwater-saturation MRI sequence had significantly higher variability than those from water-saturation images even when using a manual quantification method based on images from 38 subjects (1.76% vs. 1.08%, P < 0.001). In addition, the VAT volume amounts from nonwater-saturation images and water-saturated images quantified with the automatic and manual quantification methods were statistically consistent. CONCLUSION: Water-saturated MRI sequences at 3.0 T for VAT quantification improve reproducibility and decrease variability compared with nonwater saturated sequences, especially with the use of automatic quantification methods.


Subject(s)
Algorithms , Body Water , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Intra-Abdominal Fat/pathology , Magnetic Resonance Imaging/methods , Subtraction Technique , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
13.
J Magn Reson Imaging ; 34(6): 1452-7, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21964770

ABSTRACT

PURPOSE: To quantitatively estimate the impact of partial volume effects on visceral adipose tissue (VAT) quantification using typical resolution magnetic resonance imaging (MRI). MATERIALS AND METHODS: Nine normal or overweight subjects were scanned at central abdomen levels with a water-saturated, balanced steady-state free precession (b-SSFP) sequence. The water-saturation effectiveness was evaluated with region-of-interest analysis on fat, muscle, bowel, and noise areas. The number of full-volume (FV) and partial-volume (PV) fat pixels was estimated based on a gray-level histogram model of water-saturated images. Both FV and PV fat amounts were quantified. RESULTS: High-quality, fat-only images were generated with the b-SSFP imaging method. Fat SNR was 77.7 ± 25.6 and water-saturation was effective, with the average fat-to-water signal intensity ratio = 20.7 ± 3.8. The average ratio of partial- to full-volume fat amounts was 104.0%. The ratio was higher with lower body mass index (BMI) and PV fat amount only increased slightly when BMI increased. CONCLUSION: PV fat contributes a significant amount of fat to fat measurements on typical spatial resolution MRI on normal and overweight subjects. The relative PV fat contribution is markedly higher in slimmer patients. Inclusion of this portion of the adipose tissue will increase overall accuracy and decrease variability of VAT quantification using MRI.


Subject(s)
Adipose Tissue/anatomy & histology , Magnetic Resonance Imaging , Adult , Female , Humans , Male , Organ Size , Viscera , Water
14.
J Magn Reson Imaging ; 34(4): 852-60, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21769972

ABSTRACT

PURPOSE: To introduce and describe the feasibility of a novel method for abdominal fat segmentation on both water-saturated and non-water-saturated MR images with improved absolute fat tissue quantification. MATERIALS AND METHODS: A general fat distribution model which fits both water-saturated (WS) and non-water-saturated (NWS) MR images based on image gray-level histogram is first proposed. Next, a novel fuzzy c-means clustering step followed by a simple thresholding is proposed to achieve automated and accurate abdominal quantification taking into consideration the partial-volume effects (PVE) in abdominal MR images. Eleven subjects were scanned at central abdomen levels with both WS and NWS MRI techniques. Synthesized "noisy" NWS (nNWS) images were also generated to study the impact of reduced SNR on fat quantification using the novel approach. The visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) amounts of the WS MR images were quantified with a traditional intensity thresholding method as a reference to evaluate the performance of the novel method on WS, NWS, and nNWS MR images. RESULTS: The novel approach resulted in consistent SAT and VAT amounts for WS, NWS, and nNWS images. Automatic segmentation and incorporation of spatial information during segmentation improved speed and accuracy. These results were in good agreement with those from the WS images quantified with a traditional intensity thresholding method and accounted for PVE contributions. CONCLUSION: The proposed method using a novel fuzzy c-means clustering method followed by thresholding can achieve consistent quantitative results on both WS and NWS abdominal MR images while accounting for PVE contributing inaccuracies.


Subject(s)
Abdominal Fat/anatomy & histology , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Magnetic Resonance Imaging/methods , Adipose Tissue/anatomy & histology , Adipose Tissue/metabolism , Analysis of Variance , Body Composition , Feasibility Studies , Fuzzy Logic , Humans , Obesity/diagnosis , Reproducibility of Results , Sampling Studies , Water
16.
Acad Med ; 82(7): 625-32, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17595557

ABSTRACT

PURPOSE: For decades, the U.S. clinical research enterprise and its workforce have faced diminishing numbers and significant challenges. This study, conducted by the Institute of Medicine's Clinical Research Roundtable (CRR), sought to learn about the perceptions by medical and nursing school deans of these challenges or the efforts and strategies needed to address them. METHOD: The authors mailed structured questionnaires about clinical research and workforce issues to medical and nursing school deans in the continental United States in the fall of 2003, and on October 16 and 17, 2003, the CRR held a two-day workshop with deans and their representatives to discuss the survey findings and to propose solutions. RESULTS: Survey participation was 55 (45%) for medical school deans and 37 (46%) for nursing school deans. Various efforts exist at individual schools for recruitment, training, and retention of clinical researchers. Most of the responding medical (53; 96.7%) and nursing (28; 75.4%) school deans reported that demand for clinical researchers exceeded or sharply exceeded supply, and about half of these institutions had a formal mentor program for their students. The percentage of graduates with methodological training in clinical research varied widely, with a mode of 10% and 100% for medical and nursing schools, respectively. Most medical school deans (47; 85.5%) rated their basic research enterprises good to excellent, whereas only a third (19; 34.6%) rated their clinical research programs similarly. Likewise, nursing school deans rated their basic research programs more favorably (23; 62.2%) than they rated their clinical research enterprises (17; 46.0%). However, prioritization of changes needed to address the challenges facing clinical research and its workforce were similar for medical and nursing school deans. CONCLUSIONS: Clinical research is underdeveloped and underrepresented within the clinical research enterprise. There is a need to develop and execute uniform strategies to grow and expand the clinical research workforce. Workshop participants, including 14 deans or their representatives as panelists and CRR members, proposed solutions and strategies.


Subject(s)
Biomedical Research/organization & administration , Biomedical Research/standards , Faculty, Medical , Faculty, Nursing , Leadership , Schools, Medical , Schools, Nursing , United States
17.
Genes Chromosomes Cancer ; 45(7): 702-16, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16615098

ABSTRACT

Studies on the genetic basis of prostate cancer (PCa) have lead to mixed results with the only consensus being that PCa is a complex disease. Our goal was to gain insight into potential events involved in the acquisition of the androgen-refractory phenotype in PCa cells regardless of DNA-change dependence. To this end, we examined two LNCaP PCa cell line models of progression-one developed in vivo and one developed in vitro-using molecular cytogenetic and microarray gene expression analyses and extended this investigation of specific events into PCa tumors. The chromosomal changes observed in both in vivo and in vitro androgen-independent cell lines are similar to those seen in PCa during tumor progression. Correspondingly, gene expression analysis showed significant heterogeneity in the genes expressed among androgen-independent cells, but with some common gene expression changes that correlated with the acquired androgen-independent phenotype. Thus, growth conditions under which the cells progress appeared to impact the mechanisms used for progression, albeit within tumor-type-specific pathways. Our findings suggest that a dynamic and adaptable combination of epigenetic and DNA-change-dependent events can be used by PCa cells for the acquisition of the androgen-independent phenotype. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.


Subject(s)
Androgens/metabolism , Epigenesis, Genetic , Prostatic Neoplasms/genetics , Animals , Cell Line, Tumor , Chromosome Banding , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization, Fluorescence , Loss of Heterozygosity , Male , Mice , Oligonucleotide Array Sequence Analysis , Phenotype , Prostatic Neoplasms/metabolism , Spectral Karyotyping
18.
Acad Med ; 81(2): 107-12, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16436570

ABSTRACT

The development of a robust national clinical research enterprise is needed to improve health care, but faces formidable challenges. To define the impediments and formulate solutions, the Institute of Medicine's Clinical Research Roundtable convened leaders from medical specialty and clinical research societies in 2003. Participants considered how to influence clinical research funding priorities, promote mechanisms to train physicians and other health care professionals to conduct clinical research, and how to encourage health care providers to follow evidence-based medical practice. Consensus emerged on multiple issues, including intersociety collaboration, the need for a core clinical research curriculum for training the new cadre of clinical researchers, joint advocacy for increased funding of clinical research and for the education of policymakers and the public on the benefits of clinical research. Specific recommendations were made on mechanisms for recruitment, training, and retention of clinical research trainees and mentors. Steps were outlined (1) to overcome career disincentives and develop appropriate reward systems for mentors and trainees, (2) to encourage use of web-based and continuing-medical-education-based mechanisms to bring practitioners up to date on issues in and results of clinical research, and (3) to create incentives for individuals, clinics, and hospitals to practice evidence-based medicine (EBM). Collectively, the response and proposed strategies can serve as a roadmap to improve clinical research funding and training, evidence-based medical practice, and health care quality.


Subject(s)
Biomedical Research/education , Evidence-Based Medicine/education , Leadership , Medicine/organization & administration , Research Support as Topic/organization & administration , Societies, Medical/organization & administration , Specialization , Cooperative Behavior , Curriculum , Humans , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Policy Making , Research , United States
19.
J Androl ; 25(6): 944-53, 2004.
Article in English | MEDLINE | ID: mdl-15477368

ABSTRACT

We sought preclinical data on the cellular and molecular effects of dutasteride in androgen-responsive, human prostate cancer (PCa) cells to better understand the mechanisms of action of 5 alpha-reductase inhibition in these cells. We used the human prostate cancer cell line LNCaP, which exhibits most features of PCa cells including androgen responsiveness. Our findings show that dutasteride kills PCa cells in vitro; it dramatically reduced viability and proliferation and disrupted genes and cellular pathways involved in metabolic, cell cycle, and apoptotic responses besides those expected in androgen-signaling pathways. Microchip gene array expression analysis revealed activation of genes in the FasL/tumor necrosis factor alpha (TNF-alpha) apoptotic and cell-survival pathways, correlating with the growth and survival effects in the LNCaP cells. Real-time polymerase chain reaction confirmed expression level changes seen by microarray analysis of candidate genes such as PLA2G2A, CDK8, CASP7, MDK, and NKX3.1. Collectively, our findings delineate the cellular and molecular effects of dutasteride in androgen-responsive PCa cells in vitro and may lead to its better therapeutic and chemopreventive use in PCa.


Subject(s)
Azasteroids/pharmacology , Cholestenone 5 alpha-Reductase/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Gene Expression , Prostatic Neoplasms/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cell Survival/genetics , Dutasteride , Humans , Male , Oligonucleotide Array Sequence Analysis , Prostatic Neoplasms/pathology , Prostatic Neoplasms/physiopathology , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics
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