Digital Commons Network^™

Multicenter Randomized Phase Ii Study Of Weekly Or Twice-Weekly Bortezomib Plus Rituximab In Patients With Relapsed Or Refractory Follicular Or Marginal-Zone B-Cell Lymphoma, Sven De Vos, André Goy, Shaker R. Dakhil, Mansoor Saleh, Peter Mclaughlin, Robert Belt, Christopher R. Flowers, Mark Knapp, Lowell Hart, Dipti Patel-Donnelly

Haematology and Oncology, East Africa

Purpose: To determine overall response rate (ORR), time to progression (TTP), and duration of response (DOR) with twice-weekly/weekly bortezomib plus rituximab, and evaluate safety/tolerability, in patients with relapsed or refractory CD20+ follicular lymphoma (FL) or marginal-zone lymphoma.

Patients and Methods: Patients were randomly assigned (minimization method) to bortezomib 1.3 mg/m2 twice weekly (days 1, 4, 8, and 11; 21-day cycle, five cycles; arm A) or bortezomib 1.6 mg/m2 weekly (days 1, 8, 15, and 22; 35-day cycle, three cycles; arm B) plus rituximab 375 mg/m2 weekly for 4 weeks (both arms). Response/progression was determined by International Workshop Response Criteria using …

Advances In Progenitor Cell Therapy Using Scaffolding Constructs For Central Nervous System Injury, Peter A Walker, Kevin R Aroom, Fernando Jimenez, Shinil K Shah, Matthew T Harting, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and …

In Reply To Dr. Hurkmans Et Al., Ying Xiao, Phd, Lech S. Papiez, Phd, James M. Galvin, Dsc

Department of Radiation Oncology Faculty Papers

No abstract provided.

Effects Of Functional Appliances On Pharyngeal Airway Dimensions: A Cone Beam Computed Tomography Study, Melissa K. Lee

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Functional appliances are intended to correct by incremental advancement of the mandible for correction of skeletal Class 11 relationships. Similar in design to functional appliances, mandibular advancing devices (MAD) are used for obstructive sleep apnea (OSA) patients as they increase the size of the airway by drawing the tongue and soft palate forwards, and thus maintain its patency during sleep. It has been shown that significant increases in airway dimensions and decreases in airway resistance were gained in OSA patients while evaluated with a MAD in place. This retrospective study evaluated volumetric, cross-sectional area and linear changes in the …

The Elucidation Of Metabolic Pathways And Their Improvements Using Stable Optimization Of Large-Scale Kinetic Models Of Cellular Systems, Evgeni V. Nikolaev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Metabolic engineering of cellular systems to maximize reaction fluxes or metabolite concentrations still presents a significant challenge by encountering unpredictable instabilities that can be caused by simultaneous or consecutive enhancements of many reaction steps. It can therefore be important to select carefully small subsets of key enzymes for their subsequent stable modification compatible with cell physiology. To address this important problem, we introduce a general mixed integer non-linear problem (MINLP) formulation to compute automatically which enzyme levels should be modulated and which enzyme regulatory structures should be altered to achieve the given optimization goal using non-linear kinetic models of relevant …

Evidence Base For The Use Of Selected Complementary And Alternative Therapies By Patients With Diabetes: Preface, Ruth Lindquist, Byron Hoogwerf

University Faculty Publications and Creative Works

No abstract provided.

A Comparative Study Of The Genotype Mtbdrplus® Assay Against A Standard Culture Method For Diagnosis And Drug Susceptibility Testing Of Tuberculosis, Peris W. Thamaini

Master of Medicine in Clinical Pathology

Background: Nearly one-third of the global population, i.e. two billion people, is infected with Mycobacterium tuberculosis and is at risk of developing the disease. More than eight million people develop active tuberculosis (TB) every year, with about two million dying from the disease annually. Diagnosis of tuberculosis inKenya remains dependent on smear microscopy. New methods of TB diagnosis are needed which have better accuracy and are still cost effective. Molecular methods of TB diagnosis have come under investigation in a lot of studies recently. However, they have their own limitations including the inability to differentiate between active organisms and dead …

Mechanisms Of Primary Axonal Damage In A Viral Model Of Multiple Sclerosis., Jayasri Das Sarma, Lawrence C. Kenyon, Susan T. Hingley, Kenneth S. Shindler

Department of Neurology Faculty Papers

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Recent studies have demonstrated that significant axonal injury also occurs in MS patients and correlates with neurological dysfunction, but it is not known whether this neuronal damage is a primary disease process, or occurs only secondary to demyelination. In the current studies, neurotropic strains of mouse hepatitis virus (MHV) that induce meningitis, encephalitis, and demyelination in the CNS, an animal model of MS, were used to evaluate mechanisms of axonal injury. The pathogenic properties of genetically engineered isogenic spike protein recombinant demyelinating and nondemyelinating strains of MHV were compared. …

Expression Of An Alternate Splice Form Of Bmi-1 In Multiple Myeloma, Adam Austin, Kristine Veys, Debbie Wong, James Tung

Undergraduate Research Opportunities Program (UROP)

The concept of “tumor stem cells” has garnered much attention in the last few years. Tumor stem cells are believed to exist among a heterogeneous group of cells that constitute a tumor. These tumor stem cells often express genes that are important for stem cell function, cell division, and maintenance of pluripotent state in stem cells. Stem cell or stem cell maintenance genes such as SALL 4 and Bmi-1 are often seen in these cancer cells and contribute to self-renewing divisions and cancer cell survival. In particular, high expression of Bmi-1 (B lymphoma mouse Moloney leukemia virus insertion region), a …

Pdest Fg12-Cmv Dsred Vector, Jarod Wolffis, Sheri L. Holmen

Undergraduate Research Opportunities Program (UROP)

Melanoma is the most rapidly increasing malignancy among young people in the United States. If detected early, the disease is easily treated; however, once the disease has metastasized it is largely refractory to conventional therapies and is associated with a high mortality rate. The development of human cancer from a pre-malignant primary tumor to a metastatic lesion that develops at secondary sites is thought to be a multi-step process, requiring many genetic and epigenetic events that provide a growth advantage to cells. It is still unclear which of the many genetic changes in human cancers are required for metastasis. Therefore, …

A Generalized Beta Model For The Age Distribution Of Cancers: Application To Pancreatic And Kidney Cancer., Tengiz Mdzinarishvili, Michael X. Gleason, Leo Kinarsky, Simon Sherman

Journal Articles: Eppley Institute

The relationships between cancer incidence rates and the age of patients at cancer diagnosis are a quantitative basis for modeling age distributions of cancer. The obtained model parameters are needed to build rigorous statistical and biological models of cancer development. In this work, a new mathematical model, called the Generalized Beta (GB) model is proposed. Confidence intervals for parameters of this model are derived from a regression analysis. The GB model was used to approximate the incidence rates of the first primary, microscopically confirmed cases of pancreatic cancer (PC) and kidney cancer (KC) that served as a test bed for …

Inaugural Target Discovery World Congress 2009: Interactive Cardiovascular And Thoracic Surgery, Michael Holinstat, Ph.D.

Department of Medicine Faculty Papers

Dr. Michael Holinstat advocated a preferred therapeutic approach to treatment of platelet clot formation: to target signaling components downstream of receptor activation.

Use Of Magnetic Resonance Spectroscopy (Mrs) To Improve Magnetic Resonance Imaging (Mri) In The Diagnosis Of Intracranial Pathology, Done At Aga Khan University, Joyce Sande

Master of Medicine in Imaging and Diagnostic Radiology

Introduction: Magnetic Resonance Spectroscopy (MRS)is a potentially useful adjunct to Magnetic Resonance Imaging (MRI) in thecharacterization of focal brain lesions. This study was aimed at showing that by the additional use of MRS (MRI, MRS), the characterization of a focal brain lesion into neoplastic, or non- neoplastic (infective, or degenerative) can be improved, as compared to the use of MRI alone. Study question: Does the additional use of MRS improve MRI differentiation of neoplastic from non- neoplastic (infective or degenerative) focal brain lesions? Methods: The design was prospective, analytical and comparative. 80 consecutive patients were enrolled. Conventional MRI of the …

Flagellum-Mediated Biofilm Defense Mechanisms Of Pseudomonas Aeruginosa Against Host-Derived Lactoferrin, Jeff G. Leid, Mathias Kerr, Candice Selgado, Chelsa Johnson, Gabriel Moreno, Alyssa Smith, Mark E. Shirtliff, Georg A. O'Toole, Emily K. Cope

Dartmouth Scholarship

Chronic infection with the gram-negative organism Pseudomonas aeruginosa is a leading cause of morbidity and mortality in human patients, despite high doses of antibiotics used to treat the various diseases this organism causes. These infections are chronic because P. aeruginosa readily forms biofilms, which are inherently resistant to antibiotics as well as the host's immune system. Our laboratory has been investigating specific mutations in P. aeruginosa that regulate biofilm bacterial susceptibility to the host. To continue our investigation of the role of genetics in bacterial biofilm host resistance, we examined P. aeruginosa biofilms that lack the flgK gene. This mutant …

Expression Of Cpi-17 In Smooth Muscle During Embryonic Development And In Neointimal Lesion Formation., Jee In Kim, Garbo D Young, Li Jin, Avril V Somlyo, Masumi Eto

Department of Molecular Physiology and Biophysics Faculty Papers

Ca(2+) sensitivity of smooth muscle (SM) contraction is determined by CPI-17, an inhibitor protein for myosin light chain phosphatase (MLCP). CPI-17 is highly expressed in mature SM cells, but the expression level varies under pathological conditions. Here, we determined the expression of CPI-17 in embryonic SM tissues and arterial neointimal lesions using immunohistochemistry. As seen in adult animals, the predominant expression of CPI-17 was detected at SM tissues on mouse embryonic sections, whereas MLCP was ubiquitously expressed. Compared with SM alpha-actin, CPI-17 expression doubled in arterial SM from embryonic day E10 to E14. Like SM alpha-actin and other SM marker …

Tuberculous And Cryptococcal Meningitis In A Setting With High Tb And Low Hiv Prevalence, Afrasyab Khan, Bushra Jamil, Rahmat Ali, Sana Sultan

Section of Pulmonary & Critical Care

OBJECTIVE: To compare the differences in presentation and outcome of patients with tuberculous meningitis (TBM) and cryptococcal meningitis (CCM).

STUDY DESIGN: Case series.

PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from December 1995 to December 2005.

METHODOLOGY: Patients with a confirmed diagnosis of TBM or CCM were included in this study. The signs and symptoms, laboratory findings and other variables of patients were entered and analyzed by Statistical Package for Social Sciences (SPSS) Software version 14.

RESULTS: We compared 16 patients of TBM with 11 of CCM. None of the patients with TBM were Human Immunodeficiency …

Solar Water Disinfection In Household Settings:Hype Or Hope?, Zulfiqar Ahmed Bhutta

Woman and Child Health

No abstract provided.

Modern Approaches To Pediatric Brain Injury Therapy, Peter A Walker, Matthew T Harting, James E Baumgartner, Stephen Fletcher, Nathan Strobel, Charles S Cox

Faculty, Staff and Student Publications

Each year, pediatric traumatic brain injury (TBI) accounts for 435,000 emergency department visits, 37,000 hospital admissions, and approximately 2,500 deaths in the United States. TBI results in immediate injury from direct mechanical force and shear. Secondary injury results from the release of biochemical or inflammatory factors that alter the loco-regional milieu in the acute, subacute, and delayed intervals after a mechanical insult. Preliminary preclinical and clinical research is underway to evaluate the benefit from progenitor cell therapeutics, hypertonic saline infusion, and controlled hypothermia. However, all phase III clinical trials investigating pharmacologic monotherapy for TBI have shown no benefit. A recent …

Associations Of The Plasticity Region Ofh. Pyloriin Patients With Gastroduodenal Diseases, Javed Yakoob, Z Abbas, Shagufta Naz, Shahab Abid, Wasim Jafri

Section of Gastroenterology

No abstract provided.

Effect Of California Mission Fig Consumption On Levels Of C-Reactive Protein And Antioxidant Levels, Rasha Abdrabou

Loma Linda University Electronic Theses, Dissertations & Projects

Polyphenols exert anti-inflammatory and antioxidant effects. We investigated the effect of consumption of polyphenol-rich figs on high sensitivity C-reactive protein (CRP) and antioxidant levels in hyperlipidemic subjects. The purpose of this study was to examine the effect of fig consumption on C-reactive protein and antioxidant levels. Analyses were carried out on collected data from September to December of 2008. Using a crossover design, one hundred and two participants were recruited and randomized into an intervention phase (eating figs) and a control phase (not eating figs) for 5 weeks. Blood samples were drawn from each group at the 4th and 5th …

Posttraumatic Spiritual Growth: A Phenomenological Study Of Cancer Survivors, Ryan Myles Denney

Dissertations

A small but growing body of research has sought to investigate the specific role of religion and spirituality in posttraumatic growth. Recently investigations have begun to focus on spiritual growth following trauma, specifically that of cancer patients and survivors. The purpose of this qualitative study was to investigate how having cancer effects the spiritual growth of cancer survivors across a multidimensional conceptualization of spirituality (Hill 2005; Tsang & McCullough, 2003). The researcher investigated the lived experience of thirteen cancer survivors with posttraumatic spiritual growth using a phenomenological method of data analysis. Participants reported experiencing spiritual growth across the following domains …

Cardioprotective Effect Of Adiponectin Is Partially Mediated By Its Ampk-Independent Antinitrative Action., Yajing Wang, Ling Tao, Yuexing Yuan, Wayne Bond Lau, Rong Li, Bernard L. Lopez, Theodore A. Christopher, Rong Tian, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) exerts its metabolic regulation largely through AMP-dependent protein kinase (AMPK). However, the role of AMPK in APN's antiapoptotic effect in ischemic-reperfused (I/R) adult cardiomyocytes remains incompletely understood. The present study was designed to determine the involvement of AMPK in the antiapoptotic signaling of APN. Cardiomyocytes from adult male mice overexpressing a dominant-negative alpha(2)-subunit of AMPK (AMPK-DN) or wild-type (WT) littermates were subjected to simulated I/R (SI/R) and pretreated with 2 microg/ml globular domain of APN (gAPN) or vehicle. SI/R-induced cardiomyocyte apoptosis was modestly increased in AMPK-DN cardiomyocytes (P < 0.05). Treatment with gAPN significantly reduced SI/R-induced apoptosis in WT cardiomyocytes as well as in AMPK-DN cardiomyocytes, indicating that the antiapoptotic effect of gAPN is partially AMPK independent. Furthermore, gAPN-induced endothelial nitric oxide synthase (eNOS) phosphorylation was significantly reduced in AMPK-DN cardiomyocytes, suggesting that the APN-eNOS signaling axis is impaired in AMPK-DN cardiomyocytes. Additional experiments demonstrated that treatment of AMPK-DN cardiomyocytes with gAPN reduced SI/R-induced NADPH oxidase overexpression, decreased superoxide generation, and blocked peroxynitrite formation to the same extent as that observed in WT cardiomyocytes. Collectively, our present study demonstrated that although the metabolic and eNOS activation effect of APN is largely mediated by AMPK, the superoxide-suppressing effect of APN is not mediated by AMPK, and this AMPK-independent antioxidant property of APN increased nitric oxide bioavailability and exerted significant antiapoptotic effect.

H. Pylori Infection In Children: Population-Based Age-Specific Prevalence And Risk Factors In A Developing Country, Wasim Jafri, Javed Yakoob, Shahab Abid, S Siddiqui, Nasim Jafri, Safia Awan, Shaikh Qamaruddin Nizami

Section of Gastroenterology

No abstract provided.

Functional State Following The Fontan Procedure., Ismee A. Williams, Lynn A. Sleeper, Steven D. Colan, Minmin Lu, Elizabeth A. Stephenson, Jane W. Newburger, Welton M. Gersony, Meryl S. Cohen, James F. Cnota, Andrew M. Atz, Richard V. Williams, Renee Margossian, Andrew J. Powell, Mario P. Stylianou, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall function.

METHODS AND RESULTS: We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by …

Persistent Lithium-Induced Neurotoxicity: Direct Effect Of Lithium And/Or Hypernatremia?, Ioana-Mihaela Popescu, James A. Bourgeois

Jefferson Journal of Psychiatry

Abstract Lithium has been used in the treatment of bipolar affective disorder (BAD) for more than 50 years. Features of lithium toxicity include drowsiness, slurred speech, ataxia, psychomotor slowing, polyneuropathy, impaired memory, seizures, coma and death. Lithium neurotoxicity is usually reversible on cessation of its administration, and irreversible toxicity is uncommon. However, persistent neurological sequelae may follow lithium intoxication. There may be a contribution to neurotoxicity from the SIADH associated with lithium toxicity in addition to the direct effects of lithium itself. We describe a case of lithium toxicity with persistent delirium in a patient with a brief period of …

Tactile Hallucinations: Presenting Symptom Of Schizophrenia, Virgen M. Quinones

Jefferson Journal of Psychiatry

Although previous reports about tactile hallucinations of sexual content suggesting Schizophrenia are known2, this disorder has been characterized mostly by hallucinations of visual/auditory content. At Schizophrenia presentation these two types of hallucinations are the prominent features. This report describes a patient who had no previous psychiatric symptoms and for whom tactile hallucinations were the presenting symptom of Schizophrenia.

Esophageal Squamous Cell Carcinoma Risk Factors In A Kenyan Population: A Case Control Study, Stanley M. Machoki

Master of Medicine in General Surgery

Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy inKenya with a dismal outcome with a majority of patients presenting late. The factors that are operative in the etiology of this disease and its geographic distribution withinKenya have not been characterized thus far. Objectives: The objective of this study was to determine the association of ESCC with Khat chewing, which is prevalent in parts ofKenya, and other commonly implicated risk factors (i.e. smoking, alcohol, diet, socioeconomic status, caustic ingestion and first degree family history of ESCC). We also determined the geographic (provincial) origin, age/sex and ethnicity of cases visiting …

R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

We investigated the molecular bases of spondyloepiphyseal dysplasia (SED) associated with the R992C (p.R1192C) substitution in collagen II. At the protein level, we analyzed the structure and integrity of mutant molecules, and at the cellular level, we specifically studied the effects of the presence of the R992C collagen II on the biological processes taking place in host cells. Our studies demonstrated that mutant collagen II molecules were characterized by altered electrophoretic mobility, relatively low thermostability, the presence of atypical disulfide bonds, and slow rates of secretion into the extracellular space. Analyses of cellular responses to the presence of the mutant …

The Effect Of Endothelin-1 On The Expression Of Cdk Inhibitors P21 & P27 In Bovine Corneal Endothelial Cells, Lakshmi Reddy Bollu

Masters Theses & Specialist Projects

Mammalian corneal endothelial cells are considered to be non-proliferative due to the arrest of cells at the G1 phase of the cell cycle. The purpose of this study was to determine whether the down regulation of cyclin dependant kinase inhibitors (p21cip1 and p27kip1) levels by Endothelin-1 (ET-1), would overcome the G1 phase arrest and promote cell cycle progression and proliferation in cultured BCECs (Bovine corneal endothelial cells). BCECs were isolated from bovine corneas and cultured in DMEM supplemented with 10% serum. 5-Bromo 2-deoxy Uridine (BrdU) incorporation was determined in serum starved cultures in 24-well plates as a measure of cell …

Central Role Of Tau Protein In Alzheimer»S Disease And Related Tauopathies, Khalid Iqbal, Omar Chohan, Inge Grundke-Iqbal

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.