Jones S.,Howard Hughes Medical Institute |
Wang T.-L.,Johns Hopkins Medical Institutes |
Shih I.-M.,Johns Hopkins Medical Institutes |
Mao T.-L.,National Taiwan University |
And 9 more authors.
Science | Year: 2010
Ovarian clear cell carcinoma (OCCC) is an aggressive human cancer that is generally resistant to therapy. To explore the genetic origin of OCCC, we determined the exomic sequences of eight tumors after immunoaffinity purification of cancer cells. Through comparative analyses of normal cells from the same patients, we identified four genes that were mutated in at least two tumors. PIK3CA, which encodes a subunit of phosphatidylinositol-3 kinase, and KRAS, which encodes a well-known oncoprotein, had previously been implicated in OCCC. The other two mutated genes were previously unknown to be involved in OCCC: PPP2R1A encodes a regulatory subunit of serine/threonine phosphatase 2, and ARID1A encodes adenine-thymine (AT)-rich interactive domain - containing protein 1A, which participates in chromatin remodeling. The nature and pattern of the mutations suggest that PPP2R1A functions as an oncogene and ARID1A as a tumor-suppressor gene. In a total of 42 OCCCs, 7% had mutations in PPP2R1A and 57% had mutations in ARID1A. These results suggest that aberrant chromatin remodeling contributes to the pathogenesis of OCCC.
Harthun N.L.,Johns Hopkins Medical Institutes |
Lau C.L.,University of Virginia
Journal of Vascular Surgery | Year: 2011
Objectives: Serial computed tomography (CT) scanning is routinely used to follow up endovascular exclusion of abdominal aortic aneurysms (AAAs). Nonvascular diseases can be identified, and these exams include images of the lung bases, which can provide information that leads to the diagnosis of pulmonary neoplasms. This study was conducted to determine the rate and type of pulmonary-based oncologic diseases identified by serial CT scanning of patients with endovascular repair of AAAs. Methods: A retrospective review of 138 consecutive patients receiving endovascular AAA exclusion during an 8-year period was performed. Length of follow-up and number of CT scans performed was recorded. CT characteristics of the lesion (size, character, and suspicion of malignancy), type of biopsy procedure performed, and final pathologic diagnosis were collected. Oncologic treatments and survival length were also evaluated. Results: Pulmonary lesions were found in 25 patients (18%), of whom 5 (4%) died during follow-up, and 13 (9%) had stable, subcentimeter lesions and continue to have surveillance from vascular specialists only. Seven patients (5%) with pulmonary lesions were referred for evaluation by thoracic surgeons. Six patients (4%) underwent biopsy of the lesion and were diagnosed with cancer. One patient refused a biopsy and is being monitored with serial CT scans. Four lung cancers (1 small cell and 3 non-small cell), one primary pulmonary carcinoid tumor, and one B-cell lymphoma were discovered. No changes were noted in the lesions in the patient receiving CT surveillance. More than half of the cancers were diagnosed in stage I, with a mean lesion diameter of 11 mm at biopsy. Of 25 patients with pulmonary nodules, 24 were men. The patients diagnosed with cancer are all still alive, with a mean survival length of 2.5 years (range, 0.5-6 years) after oncologic treatment. Conclusions: Serial CT scans may reveal a high rate of pulmonary malignancies in a population with AAAs. Attention to the incidental finding of pulmonary nodules on CT scans and arrangement of appropriate follow-up by the vascular surgeon is important for patients undergoing surveillance after endovascular AAA repair. These results indicate that aggressive management of these lesions (early thoracic surgery consultation and biopsy) is appropriate in this high-risk population and may offer early diagnosis and improved long-term survival. © 2011 Society for Vascular Surgery.
Harthun N.L.,Johns Hopkins Medical Institutes |
Gahtan V.,Syracuse University
American Journal of Surgery | Year: 2011
Vascular surgery has undergone a minimally invasive revolution in the past 15 years. The subspecialty emerged with many changes to its training paradigms that have made this field more attractive to both medical student and general surgery resident candidates. Commitment to diagnosis and treatment of arterial, venous, and lymphatic systems disorders remains the cornerstone of this profession, but an entirely new generation of endovascular treatments has been added to the staple of open surgical procedures used to treat these diseases. A wide variety of practice options are available, ranging from high-stress, technologically demanding complex arterial repairs to low-risk, outpatient, venous insufficiency treatment and all combinations in-between. Many online resources are available to allow an interested candidate to stay current with all the exciting changes in the field. This information is maintained by strong national organizations of vascular surgeons. Copyright © 2011 Published by Elsevier Inc.
Kadin M.E.,Boston University |
Pavlov I.Y.,University of Utah |
Delgado J.C.,University of Utah |
Vonderheid E.C.,Johns Hopkins Medical Institutes
Journal of Investigative Dermatology | Year: 2012
Histopathology alone cannot predict the outcome of patients with CD30+ primary cutaneous lymphoproliferative disorders (CD30CLPD) and early mycosis fungoides (MF). To test the hypothesis that serum cytokines/cytokine receptors provide prognostic information in these disorders, we measured soluble CD30 (sCD30), sCD25, and selected cytokines in cell cultures and sera of 116 patients with CD30CLPD and 96 patients with early MF followed up to 20 years. Significant positive correlation was found between sCD30 levels and sCD25, CD40L, IL-6, and IL-8, suggesting that CD30+ neoplastic cells secrete these cytokines, but not Th2 cytokines. In vitro studies confirmed that sCD30, sCD25, IL-6, and IL-8 are secreted by CD30CLPD-derived cell lines. CD30CLPD patients with above normal sCD30 and sCD25 levels had worse overall and disease-related survivals, but only sCD30 retained significance in Cox models that included advanced age. High sCD30 also identified patients with worse survival in early MF. Increased IL-6 and IL-8 levels correlated with poor disease-related survival in CD30CLPD patients. We conclude that (1) neoplastic cells of some CD30CLPD patients do not resemble Th2 cells, and that (2) high serum sCD30, sCD25, IL-6, and perhaps IL-8 levels may provide prognostic information useful for patient management. © 2012 The Society for Investigative Dermatology.
Wang X.,U.S. National Institutes of Health |
Wang X.,Johns Hopkins Medical Institutes |
Cutting G.R.,U.S. National Institutes of Health |
Cutting G.R.,Johns Hopkins Medical Institutes
Advances in Oto-Rhino-Laryngology | Year: 2011
Chronic rhinosinusitis (CRS) is a persistent inflammatory condition involving the nasal and paranasal mucosa. It is the most prevalent chronic condition in the United States. Sinonasal inflammation is also a common clinical presentation in a variety of systemic conditions. The etiology of CRS is complicated as a variety of extrinsic and intrinsic factors are frequently involved. Extrinsic factors include microbial infections that trigger abnormal immune responses. Intrinsic factors may predispose an individual to infection or exaggerated inflammatory responses. Several systemic conditions such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD), asthma, immunohyperresponsiveness, and immunodeficiencies illustrate the role of genetic abnormalities in the development of CRS. Both common and rare genetic variants have been found in an association with CRS. A role for genetic factors is also supported by the demonstration of CRS clustering in families. Although the majority of CRS cases are considered to be idiopathic, the pathological evidence suggests that the chronic condition could be an overlapped presentation of multiple underlying mechanisms. Systemic conditions may have an impact on the incidence, severity, prognosis, or treatment of patients with CRS. Evaluation for underlying conditions may help the otolaryngologist manage the symptoms of CRS and optimize therapy. Copyright © 2011 S. Karger AG, Basel.
Brown J.C.,Wilmer Eye Institute |
Goldstein J.E.,Johns Hopkins Medical Institutes |
Chan T.L.,Johns Hopkins Medical Institutes |
Massof R.,Johns Hopkins Medical Institutes |
Ramulu P.,Wilmer Eye Institute
Ophthalmology | Year: 2014
Purpose To characterize functional complaints of new low-vision rehabilitation patients. Design Prospective observational study. Participants The Low Vision Rehabilitation Outcomes Study recruited 819 patients between 2008 and 2011 from 28 clinical centers in the United States. Methods New patients referred for low-vision rehabilitation were asked, "What are your chief complaints about your vision?" before their appointment. Full patient statements were transcribed as free text. Two methods assessed whether statements indicated difficulty in each of 13 functional categories: (1) assessment by 2 masked clinicians reading the statement, and (2) a computerized search of the text for specific words or word fragments. Logistic regression models were used to predict the influence of age, gender, and visual acuity on the likelihood of reporting a complaint in each functional category. Main Outcome Measures Prevalence and risk factors for patient concerns within various functional categories. Results Reading was the most common functional complaint (66.4% of patients). Other functional difficulties expressed by at least 10% of patients included driving (27.8%), using visual assistive equipment (17.5%), mobility (16.3%), performing in-home activities (15.1%), lighting and glare (11.7%), and facial recognition and social interactions (10.3%). Good agreement was noted between the masked clinician graders and the computerized algorithm for categorization of functional complaints (median κ of 0.84 across the 13 categories). Multivariate logistic regression models demonstrated that the likelihood of reading difficulties increased mildly with age (odds ratio, 1.4 per 10-year increment in age; 95% confidence interval, 1.3-1.6), but did not differ with visual acuity (P = 0.09). Additionally, men were more likely to report driving difficulties and difficulties related to lighting, whereas women were more likely to report difficulty with either in-home activities or facial recognition or social interaction (P<0.05 for all). Mobility concerns, defined as walking difficulty and out-of-home activities, showed no relationship to gender, age, or visual acuity. Conclusions Reading was the most commonly reported difficulty, regardless of the patient's diagnosis. Neither visual acuity nor gender were predictive of reading concerns, although, age showed a small effect. Addressing reading rehabilitation should be a cornerstone of low-vision therapy. © 2014 by the American Academy of Ophthalmology.
Cheng A.,Johns Hopkins Medical Institutes |
Tereshchenko L.G.,Johns Hopkins Medical Institutes
Journal of Electrocardiology | Year: 2011
Cardiac pacing has played a significant role in mitigating morbidity and mortality associated with bradyarrhythmias. Throughout the years, advances made in battery reliability, lead performance, and device portability have rapidly expanded the use of cardiac pacemakers in many different disease states. Despite the benefits, there has been growing awareness of the potential deleterious effects of long-term artificial electrical stimulation including the development of ventricular dyssynchrony and atrial fibrillation. Given their association with an increased risk for heart failure and possibly death, several advances aimed at minimizing them have been made in recent years including changes in atrioventricular pacing algorithms, novel pacing mode modifications, and better identification of hemodynamically optimal pacing sites. This article reviews the advances made and the future direction of innovations in cardiac pacing. Copyright © 2011 Published by Elsevier Inc. All rights reserved.
Beaulieu R.J.,Johns Hopkins Medical Institutes |
Arnaoutakis K.D.,Johns Hopkins Medical Institutes |
Abularrage C.J.,Johns Hopkins Hospital |
Efron D.T.,Johns Hopkins Hospital |
And 2 more authors.
Journal of Vascular Surgery | Year: 2014
Introduction Acute mesenteric ischemia (AMI) is a commonly fatal result of inadequate bowel perfusion that requires immediate evaluation by both vascular and general surgeons. Treatment often involves vascular repair as well as bowel resection and the possible need for parenteral nutrition. Little data exist regarding the rates of bowel resection following endovascular vs open repair of AMI. Methods Using the National Inpatient Sample database, admissions from 2005 through 2009 were identified according to International Classification of Diseases, Ninth Revision codes correlating to both AMI (557.0) and subsequent vascular intervention (39.26, 38.16, 38.06, 39.9, 99.10). Patients with a diagnosis of AMI but no intervention or nonemergent admission status were excluded. Patient level data regarding age, gender, and comorbidities were also examined. Outcome measures included mortality, length of stay, the need for bowel resection (45.6, 45.71-9, 45.8), or infusion of total parenteral nutrition (TPN; 99.10) during the same hospitalization. Statistical analysis was conducted by χ2 tests and Wilcoxon rank-sum comparisons. Results Of 23,744 patients presenting with AMI, 4665 underwent interventional treatment from 2005 through 2009. Of these patients, 57.1% were female, and the mean age was 70.5 years. A total of 679 patients underwent vascular intervention; 514 (75.7%) underwent open surgery and 165 (24.3%) underwent endovascular treatment overall during the study period. The proportion of patients undergoing endovascular repair increased from 11.9% of patients in 2005 to 30.0% in 2009. Severity of comorbidities, as measured by the Charlson index, did not differ significantly between the treatment groups. Mortality was significantly more commonly associated with open revascularization compared with endovascular intervention (39.3% vs 24.9%; P =.01). Length of stay was also significantly longer in the patient group undergoing open revascularization (12.9 vs 17.1 days; P =.006). During the study time period, 14.4% of patients undergoing endovascular procedures required bowel resection compared with 33.4% for open revascularization (P <.001). Endovascular repair was also less commonly associated with requirement for TPN support (13.7% vs 24.4%; P =.025). Conclusions Endovascular intervention for AMI had increased significantly in the modern era. Among AMI patients undergoing revascularization, endovascular treatment was associated with decreased mortality and shorter length of stay. Furthermore, endovascular intervention was associated with lower rates of bowel resection and need for TPN. Further research is warranted to determine if increased use of endovascular repair could improve overall and gastrointestinal outcomes among patients requiring vascular repair for AMI. Copyright © 2014 by the Society for Vascular Surgery.
Marvel C.L.,Johns Hopkins Medical Institutes |
Desmond J.E.,Johns Hopkins Medical Institutes
Cortex | Year: 2010
Contributions of cerebro-cerebellar function to executive verbal working memory were examined using event-related functional magnetic resonance imaging (fMRI) while 16 subjects completed two versions of the Sternberg task. In both versions subjects were presented with two or six target letters during the encoding phase, which were held in memory during the maintenance phase. A single probe letter was presented during the retrieval phase. In the " match condition" , subjects decided whether the probe matched the target letters. In the " executive condition" , subjects created a new probe by counting two alphabetical letters forward (e.g., f → h) and decided whether the new probe matched the target letters. Neural activity during the match and executive conditions was compared during each phase of the task. There were four main findings. First, cerebro-cerebellar activity increased as a function of executive load. Second, the dorsal cerebellar dentate co-activated with the supplementary motor area (SMA) during encoding. This likely represented the formation of an articulatory (motor) trajectory. Third, the ventral cerebellar dentate co-activated with anterior prefrontal regions Brodmann Area (BA) 9/46 and the pre-SMA during retrieval. This likely represented the manipulation of information and formation of a response. A functional dissociation between the dorsal " motor" dentate and " cognitive" ventral dentate agrees with neuroanatomical tract tracing studies that have demonstrated separate neural pathways involving each region of the dentate: the dorsal dentate projects to frontal motor areas (including the SMA), and the ventral dentate projects to frontal cognitive areas (including BA 9/46 and the pre-SMA). Finally, activity during the maintenance phase in BA 9, anterior insula, pre-SMA and ventral dentate predicted subsequent accuracy of response to the probe during the retrieval phase. This finding underscored the significant contribution of the pre-SMA/ventral dentate pathway - observed several seconds prior to any motor response to the probe - to executive verbal working memory. © 2009 Elsevier Srl.
Krebsbach A.,Johns Hopkins Medical Institutes |
Alhumaid F.,Johns Hopkins Medical Institutes |
Henrikson C.A.,Johns Hopkins Medical Institutes |
Calkins H.,Johns Hopkins Medical Institutes |
And 2 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2011
Premature Failure of a Riata Defibrillator Lead. A 63-year-old woman with a St. Jude Medical Riata 1570 right ventricular lead complained of intermittent hiccups 2 months after implant. Interrogation revealed elevated pacing threshold and diaphragmatic stimulation. Pacing and shock lead impedances remained stable. No inappropriate sensing was noted. Fluoroscopic examination of the lead revealed a thin radio-opaque wire seen between the 2 defibrillator coils away from the main body of the lead. After extraction, a tear in the insulation of the lead was noted allowing the inner wire to protrude. This case illustrates a novel mechanism of insulation failure without inappropriate sensing or impedance change. © 2011 Wiley Periodicals, Inc.