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Vital Signs, Fall 2008, Boonshoft School Of Medicine

Vital Signs

A fifty-five page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, a research spotlight, and more.

Molecular Ablation Of Transforming Growth Factor Beta Signaling Pathways By Tyrosine Kinase Inhibition: The Coming Of A Promising New Era In The Treatment Of Tissue Fibrosis., Joel Rosenbloom, Sergio A. Jimenez

Department of Medicine Faculty Papers

No abstract provided.

Digest Of The Philadelphia College Of Osteopathic Medicine (Fall 2008), Philadelphia College Of Osteopathic Medicine

Digest

The Fall 2008 issue of the Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Opening Remarks
• PCOM Updates and Kudos
• Development News
• Global Warming’s Health Crisis
• Weather Disasters
• Emerging Infectious Diseases
• What Can Be Done?
• Water-Borne Diseases
• Heat Related Illnesses
• Heat Intensifies Air Pollution
• What Can Health Professionals Do?
• Extreme Climate Events and Mental Health Disorders
• Common Goals
• Medical Marriages
• Starting Out
• Practicing Together
• Military Match
• A Family Tradition
• Research: Fruit of the Vine May Combat Prostrate Cancer
• Class Notes
• In Memoriam
• My Turn Essay
• PCOM Events

Characterization Of Kaposi's Sarcoma-Associated Herpesvirus Orf11 As A Possible Dutpase, Christina N. Ramirez

Seton Hall University Dissertations and Theses (ETDs)

A dUTPase is a crucial enzyme that hydrolyzes dUTP to dUMP. This reaction prevents the mutagenic or lethal misincorporation of uracil into DNA. For that reason, the enzyme is required for efficient DNA replication. Previous studies have shown that has ORFl l dUTPase-like motifs and thus may be a dUTPase. Generally, gammaherpesviruses contain six characteristic dUTPase motifs. In particular ORFl 1 and contains motifs 1, 2, 4, 6. While the characteristic motifs of gamroaberpesviruses include motifs 1, 2, 3, 4, 5, and 6, the number of dUTPase-like motifs in ORFl 1 's protein sequence is substantial. Thus, ORFl 1 may …

Predictive Model Of Blood Transfusion During Cabg Surgery In Pakistan, Sana Shoukat, Saqib A Gowani, Farhad Khimani, Faraz A Khan, Mohammad Zaman, Hasanat Sharif

Section of Cardiothoracic Surgery

OBJECTIVE: To determine predictors of need for transfusion of blood and blood products and create a clinical predictive model to reduce indiscriminate use of blood products during surgery.

METHOD: We conducted a retrospective chart review of 485 patients who underwent coronary artery bypass surgery from January 2004 to December 2004 at a Tertiary Care Hospital in Karachi, Pakistan. Independent predictors associated with transfusion were identified and a clinical prediction model developed.

RESULTS: The transfusion rate was 37.1%. A predictive model was created based on the presence of pulmonary disease, diabetes mellitus, low ejection fraction and recent/ongoing myocardial infarction.

CONCLUSION: The …

Associations Between Performance On The Rey-Osterrieth Complex Figure And Regional Brain Volumes In Children With And Without Velocardiofacial Syndrome, Kevin M. Antshel, Jena Peebles, Nuria Abdulsabur, Anne Marie Higgins, Nancy Roizen, Robert J. Shprintzen, Wanda Fremont, Robert Natasi, Wendy R. Kates

Communication Disorders Faculty Publications

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race, and gender-ratio comparable sample of 59 control participants were included in the project. Participants received an MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white …

Pegylated Interferon 2a And 2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Hiv Infected Patients., Ravinder Dhillon, Simona Rossi, Steven K Herrine

Department of Medicine Faculty Papers

Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA …

Infant Mortality In Delaware: The Need To Improve Maternal Health And Reduce Premature Births., David A. Paul. Md

Department of Pediatrics Faculty Papers

Delaware's high infant mortality rate continues to be driven by an increasing number of premature births. Premature birth is a complex problem with both social and medical roots. Based on the CDC road map, programs aimed at improving preconception health of women of childbearing age are blossoming in Delaware. In addition, Delaware's infant mortality rate can only be reduced if we are able to diminish disparities in health care delivery, and improve the social factors influencing infant mortality. These factors include diminishing family support, low high school graduation rate, poor housing, and a lack of health insurance.

Role Of Nono-Histone Interaction In Tnfα-Suppressed Prolyl-4-Hydroxylase Α1, Cheng Zhang, Ming-Xiang Zhang, Ying H Shen, Jared K Burks, Xiao-Nan Li, Scott A Lemaire, Koichi Yoshimura, Hiroki Aoki, Masunori Matsuzaki, Feng-Shuang An, David A Engler, Risë K Matsunami, Joseph S Coselli, Yun Zhang, Xing Li Wang

Faculty, Staff and Student Publications

Inflammation is a key process in cardiovascular diseases. The extracellular matrix (ECM) of the vasculature is a major target of inflammatory cytokines, and TNFalpha regulates ECM metabolism by affecting collagen production. In this study, we have examined the pathways mediating TNFalpha-induced suppression of prolyl-4 hydroxylase alpha1 (P4Halpha1), the rate-limiting isoform of P4H responsible for procollagen hydroxylation, maturation, and organization. Using human aortic smooth muscle cells, we found that TNFalpha activated the MKK4-JNK1 pathway, which induced histone (H) 4 lysine 12 acetylation within the TNFalpha response element in the P4Halpha1 promoter. The acetylated-H4 then recruited a transcription factor, NonO, which, in …

Structures And Functions Of The Normal And Injured Human Olfactory Epithelium, Jonathan P Schuermann, Jianwen Jiang, Jorge Cuellar, Oscar Llorca, Liping Wang, Luis E Gimenez, Suping Jin, Alexander B Taylor, Borries Demeler, Kevin A Morano, P John Hart, Jose M Valpuesta, Eileen M Lafer, Rui Sousa

Faculty, Staff and Student Publications

Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of …

Manipulations Of Macrophage Activation Through Targeted Delivery Of Interferon Regulatory Factor Genes Mediated By Recombinant Adenovirus-Conjugated Zymosan, Mengmeng Zhang

All Theses

According to the different phenotypes and distinct patterns of gene expression, macrophages can be subdivided into two types: M1 and M2. The M1 macrophages, which are activated through the classical pathway, have a proinflammatory characteristic, providing an in-front defense line against different kinds of pathogens as well as malignant cells. On the other hand, the M2 macrophages are immunosuppressive and instead can promote tumor growth and dissemination. The solid tumor tissues are often infiltrated with a large number of macrophages, the so-called tumor-associated macrophages (TAMs). TAMs, which are polarized into M2 phenotype under the tumor microenvironment, promote tumor progression by …

Multi-Scale Modeling Of Angiotensin Ii Induced Neuronal Regulatory Mechanisms In The Brain, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Poster Presentation.

Perceptions About The Cause Of Schizophrenia And The Subsequent Help Seeking Behavior In A Pakistani Population - Results Of A Cross-Sectional Survey, Syed Nabeel Zafar, Reema Syed, Sarah Tehseen, Saqib A. Gowani, Sana Waqar, Amina Zubair, Wajeeha Yousaf, Akbar J. Zubairi, Haider Naqvi

Department of Psychiatry

Background: There is a cultural variability around the perception of what causes the syndrome of schizophrenia. Generally Patients with schizophrenia are considered dangerous. They are isolated and treatment is delayed. Studies have shown favorable prognosis with good family and social support, early diagnosis and management. Duration of untreated psychosis is a bad prognostic indicator. We aimed to determine the perceptions regarding the etiology of schizophrenia and the subsequent help seeking behavior. Methods: This cross-sectional study was carried out on a sample of 404 people at the out Patient departments of Aga Khan University Hospital Karachi. Data was collected via a …

Drug-Prescribing Patterns During Pregnancy In The Tertiary Care Hospitals Of Pakistan: A Cross Sectional Study., Dileep K Rohra, Nirmal Das, Syed I Azam, Nazir A Solangi, Zahida Memon, Abdul M Shaikh, Nusrat H Khan

Department of Biological & Biomedical Sciences

Background: The rationale for use of drugs during pregnancy requires a careful assessment as in addition to the mother, the health and life of her unborn child is also at stake. Information on the use of drugs during pregnancy is not available in Pakistan. The aim of this study was to evaluate the patterns of drug prescriptions to pregnant women in tertiary care hospitals of Pakistan. Methods: This was a cross-sectional study conducted at five tertiary care hospitals of Pakistan. Copies of outPatient medicinal prescriptions given to pregnant Patients attending the antenatal clinics were collected. The drugs were classified according …

Increased Clusterin Expression In Fuchs’ Endothelial Dystrophy, Ula V. Jurkunas, Maya Bitar, Ian Rawe, Deshea L. Harris, Kathryn Colby, Nancy C. Joyce

Ophthalmology

Purpose: To compare the relative expression of peroxiredoxin (Prx) proteins in normal human corneal endothelium with endothelium in corneas affected by Fuchs’ endothelial dystrophy (FED) and between normal human endothelium and epithelial/stromal tissue.

Methods: Human corneal endothelial cell-Descemet’s membrane (HCEC-DM) complexes from normal and FED corneal buttons were dissected from the epithelium/stroma. For proteomic analysis, HCEC-DM protein extracts were separated by using two-dimensional gel electrophoresis. Relative differences in protein spot density was analyzed. Proteins of interest, including Prx isoforms, were identified by MALDI-TOF (matrix-assisted desorption ionization-time of flight) mass spectrometry. Western blot analysis compared the relative expression of Prx isoforms …

A Pooled Analysis Of Two Placebo-Controlled Trials Of Desvenlafaxine In Major Depressive Disorder., Daniel Z Lieberman, Stuart A Montgomery, Karen A Tourian, Claudine Brisard, Gregory Rosas, Krishna Padmanabhan, Jean-Michel Germain, Bruno Pitrosky

Psychiatry and Behavioral Sciences Faculty Publications

The efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) were evaluated in two similarly designed, phase 3, randomized, double-blind, placebo-controlled, venlafaxine-extended-release-referenced, flexible-dose studies of outpatients with a primary diagnosis of major depressive disorder. Owing to a high placebo response, the individual studies were underpowered. Therefore, a post-hoc pooled analysis was performed (desvenlafaxine and placebo data were pooled; venlafaxine extended release data were not, owing to different flexible-dose regimens in the two studies). The primary outcome measure was the change from baseline on the 17-item Hamilton Rating Scale for Depression; the Clinical Global Impressions-Improvement item score was a secondary …

Time Trends In The Incidence Of Cancer Cervix In Karachi South, 1995-2002, Yasmin Bhurgri, Shahid Pervez, Naila Kayani, Muneeza Afif, Imran Tahir, Kauser Nazir, Ahmed Usman, Naveen Faridi, Hadi Bhurgri, Jawaid Malik, Imtiaz Bashir, Asif Bhurgri, Rashida Ahmed, Sheema H Hasan, Mohammad Khurshid, S. M. H. Zaidi

Department of Pathology and Laboratory Medicine

Introduction:The objective of the study was to determine the trends of cancer cervix in Karachi South during an eight (1995-2002) year period. Methododology: Cancer cervix cases recorded at Karachi Cancer Registry during 1st January 1995 to 31st December 2002 were analyzed. Trends were studied by analyzing the age standardized incidence rates (ASR)s in 2 time periods, 1995-97 and 1998-2002.

Results:

Cancer cervix ranked sixth in the 1995-97 period the age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.81 and 3.22. It reached the fifth ranking in the 1998-2002 period with an ASR and …

Medical Students: Abuse Of Psychoactive Substances And Sexuality Aspects, Kepler Alencar Mendes Carvalho, Maria José Carvalho Sant'anna, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

University students aged 17 to 24 years of age are prone to many risk factors.

OBJECTIVES: Identify risk factors related to exploring sexuality and characteristics of consumption of psychoactive substances in students attending medical school.

METHODS: 465 Medical students from Santa Casa of São Paulo Faculty of Medical Sciences (FCMSCSP) were prospectively and transversely evaluated during 2005. An anonymous, semi-structured, self-filling questionnaire was used. The average age of the students was 21.5 years, 43% females. 76.2% preferred alcohol, and 11.1% tobacco consumption; chloroethane (lança-perfume) consumption occurred in 22.6% and 15.3% consumption of other types of illicit drugs, with marijuana as …

Medical Supervision Of Young Female Athletes Training In Complex Coordinational Sports, Irina Schevchenko, Viktor V. Abramov, Paul T Gibson, Hatim A. Omar

Pediatrics Faculty Publications

This article proposes simple medical criteria that can be used by trainers and others for effective medical supervision of young female athletes.

METHODS: The cross-sectional, age-stratified study compared girls 10-17 years of age involved in intensive training in gymnastic floor exercises, trampoline, or badminton. Each sport and/or control group was represented by 40-45 girls. Data included medical history, morphometric variables and observation of biological development.

RESULTS: Gymnasts started training earliest (approximately 5-years-old) and trained most intensely (18-20 h/wk), followed by trampolinists and then badmintonists. Height, weight, body mass index, and % body fat were reduced in athletes, with gymnasts showing …

The Temporal Relationship Between The Coronavirus Disease 2019 (Covid-19) Pandemic And Preterm Birth, Harold E Bedell, Mahalakshmi Ramamurthy, Saumil S Patel, Shobana Subramaniam, Lan-Phuong Vu-Yu, Jianliang Tong

Faculty, Staff and Student Publications

Despite rapid to-and-fro motion of the retinal image that results from their incessant involuntary eye movements, persons with infantile nystagmus (IN) rarely report the perception of motion smear. We performed two experiments to determine if the reduction of perceived motion smear in persons with IN is associated with an increase in the speed of the temporal impulse response. In Experiment 1, increment thresholds were determined for pairs of successively presented flashes of a long horizontal line, presented on a 65-cd/m2 background field. The stimulus-onset asynchrony (SOA) between the first and second flash varied from 5.9 to 234 ms. In experiment …

Water-Soluble Fullerene (C60) Derivatives As Nonviral Gene-Delivery Vectors, Balaji Sitharaman, Tatiana Y Zakharian, Anita Saraf, Preeti Misra, Jared Ashcroft, Su Pan, Quynh P Pham, Antonios G Mikos, Lon J Wilson, David A Engler

Faculty, Staff and Student Publications

A new class of water-soluble C60 transfecting agents has been prepared using Hirsch-Bingel chemistry and assessed for their ability to act as gene-delivery vectors in vitro. In an effort to elucidate the relationship between the hydrophobicity of the fullerene core, the hydrophilicity of the water-solubilizing groups, and the overall charge state of the C60 vectors in gene delivery and expression, several different C60 derivatives were synthesized to yield either positively charged, negatively charged, or neutral chemical functionalities under physiological conditions. These fullerene derivatives were then tested for their ability to transfect cells grown in culture with DNA carrying the green …

Synaptotagmin-2 Controls Regulated Exocytosis But Not Other Secretory Responses Of Mast Cells*, Qun-Fang Wan, Alejandro Vila, Zhen-Yu Zhou, Ruth Heidelberger

Faculty, Staff and Student Publications

To better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of 7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time …

Brain Death: Concepts And Knowledge Amongst Health Professionals In Province Of Sindh, Pakistan, Mughis Sheerani, Mian Zainul Sajadeen Urfy, Bhojo A Khealani, Junaid Patel, Qamarunnisa, Suresh Rath

Section of Neurology

OBJECTIVE: Last few decades have seen improved resuscitative measures and use of life saving machines like ventilators. Due to these dramatic interventions, end of life decisions, including brain death and organ transplantation, have become more complex and a major problem in our clinical practice. This study was done to find the opinion and awareness of physicians regarding issues surrounding brain death in this region.

METHODS: A total of 259 questionnaires were analyzed that encompassed physicians at different level of training and students in the final year of their training, from five major tertiary care centres, located at Karachi and Hyderabad …

In Vivo Murine Melanoma Tumor Responses To Nanosecond Pulsed Electric Field Treatment, Xinhua Chen

Theses and Dissertations in Biomedical Sciences

High intensity nanosecond pulsed electric fields (nsPEF) were applied to melanoma tumors to observe functional and structural biological changes and to investigate the possible molecular mechanisms responsible. An animal model was set up by injecting B16F10 mouse melanoma cells into SKH-1 mice. A treatment (Tx) of 100 pulses: 300 nanosecond duration; 40 kV/cm field strength; at 0.5 Hz rate were delivered to melanoma tumors in 120 mice. The nsPEF Txcaused tumor self-destruction with sharply decreased cell volumes and shrunken nuclei. The apoptotic biochemical tests confirmed nsPEF Tx induced apoptosis in a time-dependent manner. Examination of gross vessel and micro-vessel density …

Nanosecond Pulsed Electric Fields Induce A Mitochondria-Independent Apoptosis In B16f10 Melanoma Cells In Vitro, Wentia Elissa Ford

Theses and Dissertations in Biomedical Sciences

Nanosecond pulsed electric fields (nsPEFs) are ultra-short pulses that induce direct electric field and biological effects that initiate apoptosis. Here the application of ten 300ns pulses ranging in electric fields from 12kV/cm-60kV/cm was administered to determine the effects on B16F10 melanoma cells evaluated by in vitro studies. Initial application of nsPEFs demonstrated apoptosis induction in an electric field- and pulse number-dependent manner measured by caspase activation that correlated with decrease in cell viability 24hr post pulse. In addition caspase activity was shown to be independent of calcium mobilization though ions may play a part in other aspects of apoptosis. The …

Study To Prospectively Evaluate Reamed Intramedually Nails In Patients With Tibial Fractures (S.P.R.I.N.T.): Study Rationale And Design, Franklin D. Shuler Md, Phd

Orthopaedics

Background: Surgeons agree on the benefits of operative treatment of tibial fractures – the most common of long bone fractures – with an intramedullary rod or nail. Rates of re-operation remain high – between 23% and 60% in prior trials – and the two alternative nailing approaches, reamed or non-reamed, each have a compelling biological rationale and strong proponents, resulting in ongoing controversy regarding which is better.

Methods/Design: The objective of this trial was to assess the impact of reamed versus non-reamed intramedullary nailing on rates of re-operation in patients with open and closed fractures of the tibial shaft. The …

Role Played By Serum, A Biological Cue, In The Adherence Of Enterococcus Faecalis To Extracellular Matrix Proteins, Collagen, Fibrinogen, And Fibronectin, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: Most previous studies have found that Enterococcus faecalis isolates do not show significant adherence to fibronectin and fibrinogen.

METHODS: The influence of various conditions on E. faecalis adherence to extracellular matrix (ECM) proteins was evaluated using a radiolabeled-cell adherence assay.

RESULTS: Among the conditions studied, growth in 40% horse serum (a biological cue with potential clinical relevance) elicited adherence of all 46 E. faecalis strains tested to fibronectin and fibrinogen but not to elastin; adherence levels were independent of strain source, and adherence was eliminated by treating cells with trypsin. As previously reported, serum also elicited adherence to collagen. …

Blood Utilization In Children Managed Non-Operatively For Blunt Solid Organ Injury., Scott J. Keckler, Kuojen Tsao, Susan W. Sharp, G W. Holcomb Iii, Daniel J. Ostlie, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Blood product utilization is an important issue in health care, given the frequent shortages in hospitals and the societal burden required to maintain the supply. Therefore, we retrospectively audited our blunt spleen/liver trauma experience to determine the percentage of cross-matched blood that was transfused to see whether more stringent typing criteria should be applied.

METHODS: A retrospective analysis of a recent 7-year experience with nonoperative management in patients with blunt spleen or liver injury was performed. Demographics, packed red blood cells prepared by cross-match, and transfusions were measured. Unmatched, O-type blood given in the trauma bay was excluded. Patients …

Fluorescence Tomography Characterization For Sub-Surface Imaging With Protoporphyrin Ix, Dax Kepshire, Scott C. Davis, Hamid Dehghani, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

Optical imaging of fluorescent objects embedded in a tissue simulating medium was characterized using non-contact based approaches to fluorescence remittance imaging (FRI) and sub-surface fluorescence diffuse optical tomography (FDOT). Using Protoporphyrin IX as a fluorescent agent, experiments were performed on tissue phantoms comprised of typical in-vivo tumor to normal tissue contrast ratios, ranging from 3.5:1 up to 10:1. It was found that tomographic imaging was able to recover interior inclusions with high contrast relative to the background; however, simple planar fluorescence imaging provided a superior contrast to noise ratio. Overall, FRI performed optimally when the object was located on or …

Nerve Growth Factor Regulation Of Cyclin D1 In Pc12 Cells Through A P21ras Extracellular Signal-Regulated Kinase Pathway Requires Cooperative Interactions Between Sp1 And Nuclear Factor-Kappab., Francesco Marampon, Mathew C Casimiro, Maofu Fu, Michael J Powell, Vladimir M Popov, Jaime Lindsay, Bianca M Zani, Carmela Ciccarelli, Genichi Watanabe, Richard J Lee, Richard G Pestell

Department of Cancer Biology Faculty Papers

The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21(RAS) pathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF …