Medicine and Health Sciences Commons^™

Mice Deficient In Involucrin, Envoplakin, And Periplakin Have A Defective Epidermal Barrier., Lisa M Sevilla, Rachida Nachat, Karen R Groot, John F Klement, Jouni Uitto, Philippe Djian, Arto Määttä, Fiona M Watt

Department of Dermatology and Cutaneous Biology Faculty Papers

The cornified envelope is assembled from transglutaminase cross-linked proteins and lipids in the outermost epidermal layers and is essential for skin barrier function. Involucrin, envoplakin, and periplakin form the protein scaffold on which the envelope assembles. To examine their combined function, we generated mice deficient in all three genes. The triple knockouts have delayed embryonic barrier formation and postnatal hyperkeratosis (abnormal accumulation of cornified cells) resulting from impaired desquamation. Cornified envelopes form but are ultrastructurally abnormal, with reduced lipid content and decreased mechanical integrity. Expression of proteases is reduced and the protease inhibitor, serpina1b, is highly upregulated, resulting in defective …

Short-Wavelength Light Sensitivity Of Circadian, Pupillary, And Visual Awareness In Humans Lacking An Outer Retina, Farhan H. Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo Iii, Charles A. Czeisler, Russell G. Foster, Merrick J. Moseley, Steven W. Lockley

Department of Neurology Faculty Papers

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found …

How To Prevent Perioperative Myocardial Injury: The Conundrum Continues, Jian-Zhong Sun, David Maguire

Department of Anesthesiology Faculty Papers

BACKGROUND: Perioperative myocardial injury (PMI) remains a major cause of perioperative morbidity and mortality but clinical strategies to prevent PMI are still uncertain.

METHODS AND RESULTS: We comprehensively searched PubMed for major research articles concerning clinical strategies to prevent PMI. The key findings are as follows: (1) the American College of Cardiology/American Heart Association guideline update for perioperative cardiovascular evaluation for noncardiac surgery is very useful to stratify cardiac risk preoperatively; (2) cardiac troponin has emerged as a biomarker to diagnose postoperative PMI and to predict clinical outcomes; (3) coronary revascularization before noncardiac surgery probably would provide cardiac protection in …

Targeted Therapies In The Management Of Metastatic Bladder Cancer., Matteo Fassan, Edouard J. Trabulsi, Leonard G Gomella, Raffaele Baffa

Department of Urology Faculty Papers

The management of metastatic urothelial carcinoma (UC) of the bladder is a common and complex clinical challenge. Despite the fact that UC is one of the most frequent tumors in the population, long term survival for metastatic disease remains low, and chemotherapy is curative for only a small minority of patients. UC is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment. The problems of clinical practice in the field of metastatic bladder cancer have begun to stimulate translational research. Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of …

Renal Cell Carcinoma Metastatic To The Duodenum: Treatment By Classic Pancreaticoduodenectomy And Review Of The Literature, Robert Adamo, Patrick J. Greaney Jr., Agnieszka Witkiewicz, Eugene P. Kennedy, Charles J. Yeo

Department of Surgery Faculty Papers

Renal cell cancer (RCC) most commonly metastasizes to the lungs, bones, liver, renal fossa, and brain, although metastases can occur elsewhere. RCC metastatic to the duodenum is especially rare, with only a small number of cases reported in the literature. Herein, we describe a case of an 86-year-old woman with a history of RCC treated by radical nephrectomy 13 years previously. The patient presented with duodenal obstruction and anemia from a solitary duodenal mass invading into the pancreas and was treated via classic pancreaticoduodenectomy. Preoperative imaging and intra-operative assessment showed no evidence of other disease. Pathology confirmed metastatic RCC without …

Special Article: Physical Activity, Physical Fitness, And Cardiovascular Risk Factors In Childhood, Samuel S. Gidding

Department of Pediatrics Faculty Papers

In adults, physical activity and exercise training are associated with reduced cardiovascular morbidity and mortality, a reduced likelihood of developing adverse cardiovascular risk factors, and improved insulin sensitivity. In childhood, participation in appropriate physical activity may prevent the development of cardiovascular risk factors in the future and complement treatment of existing cardiovascular risk factors, including hypertension, dyslipidemia, and overweight. Exercise in children can also significantly improve insulin sensitivity independent of weight loss. These e fects are mediated in overweight children by increases in lean body mass relative to fat mass and associated improvements in inflammatory mediators, endothelial function, and the …

Aoa Symposium. Orthopaedists Partnering With Other Physicians To Provide Musculoskeletal Care., Alan Hilibrand, Kurt P Spindler, Scott D Boden

Rothman Institute Faculty Papers

No abstract provided.

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model., Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J Yasha Kresh, John W.C. Entwistle, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …

Robot-Assisted Prostate Brachytherapy, Yan Yu, Tarun Podder, Y D. Zhang, W S. Ng, V Misic, J Sherman, L Fu, D Fuller, D J. Rubens, J D. Strang, R A. Brasacchio, E M. Messing

Department of Radiation Oncology Faculty Papers

Abstract: In contemporary brachytherapy procedures, needle placement at the desired target is challenging due to a variety of reasons. A robot-assisted brachytherapy system can potentially improve needle placement and seed delivery, resulting in enhanced therapeutic delivery. In this paper we present a 16 DOF (degrees-of-freedom) robotic system (9DOF positioning module and 7DOF surgery module) developed and fabricated for prostate brachytherapy. Strategies to reduce needle deflection and target movement were incorporated after extensive experimental validation. Provisions for needle motion and force feedback were included into the system for improving robot control and seed delivery. Preliminary experimental results reveal that the prototype …

Developing "Human Functioning And Rehabilitation Research" From The Comprehensive Perspective., Gerold Stucki, Jan Dietrich Reinhardt, Gunnar Grimby, John Melvin

Department of Rehabilitation Medicine Faculty Papers

With the International Classification of Functioning, Disability and Health (ICF) the World Health Organization (WHO) has prepared the ground for a comprehensive understanding of Human Functioning and Rehabilitation Research, integrating the biomedical perspective on impairment with the social model of disability. This poses a number of old and new challenges regarding the enhancement of adequate research capacity. Here we will summarize approaches to address these challenges with respect to 3 areas: the organization of Human Functioning and Rehabilitation Research into distinct scientific fields, the development of suitable academic training programmes and the building of university centres and collaboration networks.

An Update On The Diagnosis And Treatment Of Early Lyme Disease: "Focusing On The Bull's Eye, You May Miss The Mark", Amber Stonehouse, James S. Studdiford, C. Amber Henry

Department of Family & Community Medicine Faculty Papers

To confidently diagnose and treat Lyme disease, the clinician must first understand the natural history of this disease, especially its protean early manifestations. Emergency physicians, primary care physicians, and other providers need to be vigilant in terms of the timely recognition of erythema migrans (EM), the unique marker of early localized stage 1 disease. The classic EM, originally described as a slowly expanding bull's eye lesion, is now recognized to be present in only the minority of cases (9%); the dominant morphologic lesion of EM is now recognized to be the diffusely homogenous red plaque or patch, which occurs in …

Paraumbilical Collateral Veins On Mri As Possible Protection Against Portal Venous Thrombosis In Candidates For Liver Transplantation, Sachit Verma, Donald G. Mitchell, Yulia Lakhman, Diane Bergin, Ronald J. Dolin, Cataldo Doria, Laurence Parker

Department of Radiology Faculty Papers

Background: We retrospectively evaluate the potential protective influence of patent paraumblical vein (PUV) collaterals against portal vein (PV) thrombosis and reduced PV diameter in candidates for orthotopic liver transplant (OLT)

Methods: Dynamic 3D contrast-enhanced MRI at 1.5T was obtained in 309 patients with cirrhosis without evidence of malignancy. All MR studies were reviewed by one reader for PUV collaterals, PV thrombosis and PV diameter. Statistical analysis was performed by Fisher exact tests; 50 selected studies were reviewed independently by two additional readers to determine interobserver agreement via intraclass correlation coefficient (ICC).

Results: Patent PUV was noted in …

Rhabdomyolysis After Laparoscopic Nephrectomy., Deborah T. Glassman, William G. Merriam, Edouard J. Trabulsi, Dolores Byrne, Leonard Gomella

Department of Urology Faculty Papers

BACKGROUND AND OBJECTIVES: Laparoscopic renal surgery has become a widely applied technique in recent years. The development of postoperative rhabdomyolysis is a known but rare complication of laparoscopic renal surgery. Herein, 4 cases of rhabdomyolysis and a review of the literature are presented with respect to pathogenesis, treatment, and prevention of this dire complication. METHODS: A retrospective review of over 600 laparoscopic renal operations over the past 8 years was performed. All cases of postoperative rhabdomyolysis were identified. A Medline search was performed to find articles related to the development of postoperative rhabdomyolysis. Cases of rhabdomyolysis developing after laparoscopic renal …

Teaching Case: Occipital Neuralgia In A Young Patient - Expert Commentary, Avi Ashkenazi

Department of Neurology Faculty Papers

Expert commentary on Carayannopoulos, AG. Teaching case: Occipital neuralgia in a young patient, 47(9):1367-1368, October 2007.

Regional Variability In Use Of A Novel Assessment Of Thoracolumbar Spine Fractures: United States Versus International Surgeons., John Ratliff, Neel Anand, Alexander R Vaccaro, Moe R Lim, Joon Y Lee, Paul Arnold, James Harrop, Raja Rampersaud, Christopher M Bono, Ralf H Gahr

Department of Neurosurgery Faculty Papers

BACKGROUND: Considerable variability exists in clinical approaches to thoracolumbar fractures. Controversy in evaluation and nomenclature contribute to this confusion, with significant differences found between physicians, between different specialties, and in different geographic regions. A new classification system for thoracolumbar injuries, the Thoracolumbar Injury Severity Score (TLISS), was recently described by Vaccaro. No assessment of regional differences has been described. We report regional variability in use of the TLISS system between United States and non-US surgeons.

METHODS: Twenty-eight spine surgeons (8 neurosurgeons and 20 orthopedic surgeons) reviewed 56 clinical thoracolumbar injury case histories, which included pertinent imaging studies. Cases were classified …

Regional Variability In Use Of A Novel Assessment Of Thoracolumbar Spine Fractures: United States Versus International Surgeons, John Ratliff, Neel Anand, Alexander R. Vaccaro, Moe R. Lim, Joon Y. Lee, Paul Arnold, James S. Harrop, Raja Rampersaud, Christopher M. Bono, Ralf H. Gahr, Trauma Study Group Spine

Department of Orthopaedic Surgery Faculty Papers

Background: Considerable variability exists in clinical approaches to thoracolumbar fractures. Controversy in evaluation and nomenclature contribute to this confusion, with significant differences found between physicians, between different specialties, and in different geographic regions. A new classification system for thoracolumbar injuries, the Thoracolumbar Injury Severity Score (TLISS), was recently described by Vaccaro. No assessment of regional differences has been described. We report regional variability in use of the TLISS system between United States and non-US surgeons.

Methods: Twenty-eight spine surgeons (8 neurosurgeons and 20 orthopedic surgeons) reviewed 56 clinical thoracolumbar injury case histories, which included pertinent imaging studies. Cases were classified …

Turf Wars In Radiology: What Must Academic Radiology Do?, Vijay M. Rao, David C. Levin

Department of Radiology Faculty Papers

In a previous article in this series, we called upon private practice radiology groups to better support radiology research financially, but also pointed out that academic radiology must make some changes as well. In this article, we discuss those changes in detail. They include revising the structure of the radiology residency, changing the timing of the American Board of Radiology oral examinations, requiring that all residents receive research training, and emphasizing the value of clinical and translational research. The Society of Chairmen of Academic Radiology Departments (SCARD) needs to assume a leadership role in implementing these changes.

Teaching Case: Headache Stigmata, Michael Marmura, Seymour Solomon

Department of Neurology Faculty Papers

A 38-year-old man with past medical history of hypertension and obesity presented to our clinic for evaluation of severe headaches and multiple episodes of discoloration of the forehead on the same side as the headache.

Does ‘Excessive’ Anticoagulation Predispose To Periprosthetic Infection?, Javad Parvizi, Elie Ghanem, Ashish Joshi, Peter F. Sharkey, William J. Hozack, Richard H. Rothman

Department of Orthopaedic Surgery Faculty Papers

Background
Although persistent drainage and hematoma formation are recognized risk factors for the development of periprosthetic infection, it is not known if excess anticoagulation is a predisposing factor.

Methods
We conducted a 2 to 1 case-control study with 78 cases who underwent revision for septic failure. The controls underwent the same index procedure but did not develop consequent infection. Patient comorbidities, medications, intraoperative, and postoperative factors were compared.

Results
Postoperative wound complications including development of hematoma and wound drainage were significant risk factors for periprosthetic infection. A mean international normalized ratio of greater than 1.5 was found to be more …

Phosphorylation-Induced Conformational Switching Of Cpi-17 Produces A Potent Myosin Phosphatase Inhibitor, Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-Ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Phosphorylation of endogenous inhibitor proteins specific for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. Phosphorylation of Thr38 in the inhibitor protein CPI-17 transduces G-protein-mediated signaling into a > 1000-fold increase of inhibitory potency toward myosin phosphatase. We show here the solution NMR structure of phospho-T38-CPI-17 with r. m. s. d. of 0.36 ± 0.06 Å for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes the PP1 inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side-chains, which is not formed …

Baseline Hbv Dna Level Is The Most Important Factor Associated With Virologic Breakthrough In Chronic Hepatitis B Treated With Lamivudine., Hee Bok Chae, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Aim: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT).

Methods: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups.

Results: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline …

Barriers To Recovery And Recommendations For Change: The Pennsylvania Consensus Conference On Psychiatry's Role., Joseph A. Rogers, Michael J. Vergare, Richard C. Baron, Mark S. Salzer

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE: Recovery has emerged over the past decade as a dominant theme in public mental health care.

METHODS: The 2006 Pennsylvania Consensus Conference brought together 24 community psychiatrists to explore the barriers they experienced in promoting recovery and their recommendations for change.

RESULTS: Twelve barriers were identified and classified into one of three categories: psychiatry knowledge, roles, and training; the need to transform public mental health systems and services; and environmental barriers to opportunity. Participants made 22 recommendations to address these barriers through changes in policies, programs, and psychiatric knowledge and practice.

CONCLUSIONS: The recommendations identify areas for change that …

Platelet Hyperreactivity: Predictive And Intrinsic Properties., Paul F. Bray

Cardeza Foundation for Hematologic Research

Platelet thrombi are central to the development of most vascular ischemic events. There is marked interindividual variation in platelet responsiveness, with some subjects displaying platelet hyperreactivity. An increasing number of reports indicate that there are laboratory measures of platelet function that predict clinical thrombotic events. Some, but not all, measures of platelet function are reproducible. Platelet hyperreactivity can be assessed with multiple stimuli in multiple assays and is more likely to be present in women and in subjects who have elevated fibrinogen levels.

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model, Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J. Yasha Kresh, John W.C. Entwhistle Iii, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Relationships Between Scores On The Jefferson Scale Of Physician Empathy, Patient Perceptions Of Physician Empathy, And Humanistic Approaches To Patient Care: A Validity Study., Karen M. Glaser, Fred W. Markham, Herbert M. Adler, Patrick R. Mcmanus, Mohammadreza Hojat

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Empathy is the backbone of a positive physician-patient relationship. Physician empathy and the patient's awareness of the physician's empathic concern can lead to a more positive clinical outcome.

MATERIAL/METHODS: The Jefferson Scale of Physician Empathy (JSPE) was completed by 36 physicians in the Family Medicine residency program at Thomas Jefferson University Hospital, and 90 patients evaluated these physicians by completing the Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE), and a survey about physicians' humanistic approaches to patient care.

RESULTS: A statistically significant correlation was found between scores of the JSPE and JSPPPE (r=0.48, p

CONCLUSIONS: These findings …

Allergic Contact Dermatitis From Tea Tree Oil

Department of Family & Community Medicine Faculty Papers

The sudden appearance of a pruritic confluent erythematous rash on the anterior neck and upper back prompted a 30-year-old woman to seek medical attention. She had recently started applying 5% tea tree oil to the area to treat chronic, recurrent tinea versicolor. An herbal specialist had recommended this therapy.

Resected Serous Cystic Neoplasms Of The Pancreas: Locally Aggressive Behavior As A Predictor Of Malignant Disease? A Review Of 158 Patients With Recommendations For Treatment., Charles Galanis, Amir Zamani, John L. Cameron, Kurtis A. Campbell, Keith D. Lillemoe, David Caparrelli, David Chang, Ralph H. Hruban, Charles Yeo

Department of Surgery Faculty Papers

Background: Serous cystic neoplasms of the pancreas are regarded as a benign entity with rare malignant potential. Surgical resection is generally considered curative. Objective: To perform the largest single institution review of patients who underwent surgical resection for serous cystic neoplasms of the pancreas in the hopes of guiding future management. Methods: Between June 1988 and January 2005, 158 patients with serous cystic neoplasms of the pancreas underwent surgical resection. A retrospective analysis was performed. Univariate and multivariate models were used to determine factors influencing perioperative morbidity and mortality. Major complications were defined as pancreatic fistula or anastomotic leak, postoperative …

Gangliocytic Paraganglioma: Case Report And Review Of The Literature, Agnes Witkiewicz, Avi Galler, Charles Yeo

Department of Surgery Faculty Papers

Gangliocytic paraganglioma is a rare tumor, which occurs nearly exclusively in the second portion of the duodenum. Generally, this tumor has a benign clinical course, although rarely, it may recur or metastasize to regional lymph nodes. Only one case with distant metastasis has been reported. We present a case of duodenal gangliocytic paraganglioma treated first by local resection followed by pylorus-preserving pancreaticoduodenectomy. Examination of the first specimen revealed focal nuclear pleomorphism and mitotic activity, in addition to the presence of three characteristic histologic components: epithelioid, ganglion, and spindle cell. In the subsequent pancreaticoduodenectomy specimen, there was no residual tumor identified …

Meeting Report: The Role Of Environmental Lighting And Circadian Disruption In Cancer And Other Diseases, Richard G. Stevens, David E. Blask, George C. Brainard, Johnni Hansen, Steven W. Lockley, Ignacio Provencio, Mark S. Rea, Leslie Reinlib

Department of Neurology Faculty Papers

Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have …