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Digest Of The Philadelphia College Of Osteopathic Medicine (Summer 2002), Philadelphia College Of Osteopathic Medicine

Digest

The Summer 2002 Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Opening Remarks
• PCOM Updates
• It's a Family Practice Affair
• Helping People Age Successfully
• Why Don't Patients Comply?
• Class Notes
• In Memoriam
• My Turn
• Andrew Taylor Still Legacy Society
• PCOM Events

Update - May 2002, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- The Compleat Physician
-- Informed Consent Documentation for Total Artificial Hearth Technology
-- Ralph J. and Carolyn Thompson Endowment established in 2001

Extended Preservation Of Non-Heart-Beating Donor Livers With Normothermic Machine Perfusion., Shawn D. St Peter, C J. Imber, I Lopez, D Hughes, P J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Non-heart-beating donor (NHBD) livers represent an important organ pool, but are seldom utilized clinically and require rapid retrieval and implantation. Experimental work with oxygenated perfusion during preservation has shown promising results by recovering function in these livers. This study compared sanguinous perfusion with cold storage for extended preservation of the NHBD liver in a porcine model.

METHODS: Porcine livers were subjected to 60 min of in vivo total warm ischaemia before flushing, after which they were preserved by one of two methods: group 1 (n = 4), University of Wisconsin (UW) solution by standard cold storage for 24 h; …

Hepatic Steatosis And Its Relationship To Transplantation., Charles J. Imber, Shawn D. St Peter, Ashok Handa, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Fatty infiltration of the liver is common in the brain-dead donor population and has a strong correlation with primary nonfunction after cold preservation, a condition that is catastrophic to liver transplant recipients. This literature review examines factors associated with the development, diagnosis, quantification, and clinical management of this difficult condition.

Vital Signs, Spring 2002, Boonshoft School Of Medicine

Vital Signs

A twenty-eight page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes feature articles, an alumni profile, class notes, and more.

Cd8+-T-Cell Immunity Against Toxoplasma Gondii Can Be Induced But Not Maintained In Mice Lacking Conventional Cd4+ T Cells, Lori Casciotti, Kenneth H. Ely, Martha E. Williams, Imtiaz A. Khan

Dartmouth Scholarship

T-cell immunity is critical for survival of hosts infected with Toxoplasma gondii. Among the cells in the T-cell population, CD8⁺ T cells are considered the major effector cells against this parasite. It is believed that CD4⁺ T cells may be crucial for induction of the CD8⁺-T-cell response against T. gondii. In the present study, CD4^−/− mice were used to evaluate the role of conventional CD4⁺ T cells in the immune response against T. gondii infection. CD4^−/− mice infected with T. gondii exhibited lower gamma interferon (IFN-γ) messages in the majority of their …

2001 Cancer Care Annual Report, Children's Mercy Hospital

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Hospital, Kansas City MO, a pediatric medical center, with a focus on Wilms' Tumor.

Appropriate Use Of Clopidogrel, Cyrus R Kumana, Bernard Man-Yung Cheung, Ij Lauder

Journal of the Hong Kong College of Cardiology

Clopidogrel (Plavix®) is an orally administered pro-drug, whose pharmacology and therapeutic role has been extensively reviewed in recent publications.1-5 In essence, it results in selective and irreversible antagonism of ADP-induced platelet aggregation. Such aggregation normally results in the surface expression of platelet glycoprotein (GP) IIb/IIIa receptors, which facilitate fibrinogen binding as well as consequential further platelet aggregation – the final common pathway of vascular occlusion. Specific cytochrome P450 enzymes are thought to generate the responsible active metabolite (believed to persist transiently). However, dosage adjustment is not recommended in hepatic impairment (unless severe) and drug-drug interactions and co-administration with meals are …

Primaquine-Induced Hemolytic Anemia: Formation And Mechanism Of Action Of The Hemotoxic Metabolite 6-Methoxy-8-Hudroxylamoniquinoline (Maq-Noh), Laura Jane Campbell-Bolchoz

MUSC Theses and Dissertations

Primaquine is an important antimalarial drug that is often dose-limited in therapy by the onset of hemolytic anemia. It is well accepted that this toxicity is due to the action of its metabolites and not the parent compound. However, the toxic species have not been identified and little is known about the mechanism underlying primaquine-induced red cell injury. Previous studies to identify the hemotoxic metabolites have focused on the redox active phenolic derivatives of primaquine and have shown that a number of these compounds are capable of decreasing red cell GSH levels and oxidizing oxyhemoglobin to methemoglobin. However, these derivatives …

Beta-Galactosidase As A Marker Of Ischemic Injury And A Mechanism For Viability Assessment In Porcine Liver Transplantation., Shawn D. St Peter, Charles J. Imber, Inigo Lopez De Cenarruzabeitia, James Mcguire, Tim James, Richard Taylor, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Glycohydrolases are a group of enzymes contained predominantly within lysosomes, which are released during Kupffer cell activation or death. One of these, beta-galactosidase, has been proposed as a marker of ischemia-reperfusion injury in the liver because Kupffer cell activation represents a primary event in the injurious reperfusion cascade. In this study, we compared B-galactosidase with more traditional indicators of liver injury and function in a porcine model of liver preservation. Porcine livers were allocated into two groups: group C (n = 5), preserved in University of Wisconsin solution by standard cold storage for 24 hours, and group W (n = …

Placental Peroxisome Proliferator-Activated Receptor Gamma And Leptin Receptor In Human Pregnancy, Gwyneth H. Gladstones

Theses : Honours

Leptin is a 16kDa peptide hormone that has recently been implicated in human reproductive processes. Like other hormones, leptin exerts its influence through its receptor. Of the three major isoforms of the receptor (OB-Ra, OB-Rb, and 0B-Re), OB-Ra (the dominant short form) has been implicated in transport processes within rat and human placentas, suggesting a role for it in implantation and pregnancy maintenance. The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that are a subfamily of nuclear hormone receptors. PPARs form heterodimers with another nuclear hormone receptor, RXRα, before binding to PPAR response elements (PPREs). Recently PPARϒ/RXRα heterodimers have …

Differential Synthesis Of Beta-Tubulin Isotypes In Gerbil Nasal Epithelia, Karen Woo, Heather Jensen Smith, Richard F. Ludueña, Richard Hallworth

Journal Articles: Eppley Institute

Compartmentalization of beta-tubulin isotypes within cells according to function was examined in gerbil olfactory and respiratory epithelia by using specific antibodies to four beta-tubulin isotypes (beta(I), beta(II), beta(III), and beta(IV)). Isotype synthesis was cell-type-specific, but the localization of the isotypes was not compartmentalized. All four isotypes were found in the cilia, dendrites, somata, and axons of olfactory neurons. Only two isotypes (beta(I) and beta(IV)) were present in the cilia of nasal respiratory epithelial cells. The beta(IV) isotype, thought to be an essential component of cilia, was present in olfactory neurons and respiratory epithelial cells, which are ciliated, but was not …

Spatio-Temporal Variation In Activation Intervals During Ventricular Fibrillation, Sachin Anil Moghe

University of Kentucky Doctoral Dissertations

Spatio-temporal variation in activation rates during ventricular fibrillation (VF)provides insight into mechanisms of sustained re-entry during VF. This study had three objectives related to spatio-temporal dynamics in activation rates during VF.

The first objective was to quantify spatio-temporal variability in activation rates,that is, in dominant frequencies, computed from epicardial electrograms recorded during VF in swine. Results showed that temporally and spatially, dominant frequencies variedas much as 20% of the mean dominant frequency, and the mean dominant frequencies increased during first 30 sec of VF. These results suggest that activation rates are nonstationary during VF.

The second objective of the study …

Effect Of Zinc On The Treatment Of Plasmodium Falciparum Malaria In Children: A Randomized Controlled Trial, F. Sempertegui, B. Estrella, F.R. Toapanta, D.S. Torres, D.E. Calahorrano, K. Yeboah-Antwi, E. Addo-Yobo, P. Arthur, S. Newton, Zul Premji, M. Hubert, C.S. Makwaya, F. Ssengooba, J. Konde-Lule, E. Mukisa, D.H. Hamer, W. Macleod, C. Duggan, W. Fawzi, J. Simon, V. Mwanakasale, M. Mulenga, T. Sukwa, J. Tshiula

Pathology, East Africa

Background: Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria.

Objective: The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken.

Design: Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and ≥ 2000 asexual forms of Plasmodium falciparum/μL in a thick blood smear received chloroquine and were randomly assigned to …

Staphylococcus Aureus Agr And Sara Functions Are Required For Invasive Infection But Not Inflammatory Responses In The Lung, Geoffrey Heyer, Shahryar Saba, Robert Adamo, William Rush, Grace Soong, Ambrose Cheung, Alice Prince

Dartmouth Scholarship

Staphylococcus aureus strains lacking agr- and sarA-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast, agr and especially sarA mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs.

Acute Lung Injury/Acute Respiratory Distress Syndrome, Fazal Hameed Khan

Department of Anaesthesia

Reports of pulmonary physiopathological insults following severe trauma resulting in respiratory failure are not new in medical literature^1,2. In 1967 Ashbaugh and colleagues described a syndrome of acute respiratory distress following a variety of precipitating conditions³. Severe hypoxemia, diffuse pulmonary infiltrates, poor lung compliance and absence of left heart failure characterize this condition. Ashbaugh et al⁴ subsequently named it as adult respiratory distress syndrome to differentiate it from infant respiratory distress syndrome. It was proposed at that time that both conditions manifest similar physiopathological changes. It was also referred to as “traumatic wet lung”, “congestive …

Regulation Of Type-Ii Collagen Gene Expression During Human Chondrocyte De-Differentiation And Recovery Of Chondrocyte-Specific Phenotype In Culture Involves Sry-Type High-Mobility-Group Box (Sox) Transcription Factors, David G. Stokes, Gang Liu, Rita Dharmavaram, David Hawkins, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

During ex vivo growth as monolayer cultures, chondrocytes proliferate and undergo a process of de-differentiation. This process involves a change in morphology and a change from expression of chondrocyte-specific genes to that of genes that are normally expressed in fibroblasts. Transfer of the monolayer chondrocyte culture to three-dimensional culture systems induces the cells to re-acquire a chondrocyte-specific phenotype and produce a cartilaginous-like tissue in vitro. We investigated mechanisms involved in the control of the de-differentiation and re-differentiation process in vitro. De-differentiated chondrocytes re-acquired their chondrocyte-specific phenotype when cultured on poly-(2-hydroxyethyl methacrylate) (polyHEMA) as assayed by morphology, reverse transcriptase PCR of …

Evaluation Of Cholera Vaccines Formulated With Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant In Mice, Jia-Yan Wu, William F. Wade, Ronald K. Taylor

Dartmouth Scholarship

Cholera is an acute diarrheal disease that is caused by the gram-negative bacterium Vibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. Recent studies on the molecular nature of the virulence components that contribute to V. cholerae pathogenesis have provided insights into possible approaches for the development of a defined subunit cholera vaccine. Genetic analysis has demonstrated that the toxin-coregulated pilus (TCP) is the major factor that contributes to colonization of the human intestine by V. cholerae. In …

Immune Response Genes Modulate Serologic Responses To Vibrio Cholerae Tcpa Pilin Peptides, Michael D. Meeks, Terri K. Wade, Ronald K. Taylor, William F. Wade

Dartmouth Scholarship

Cholera is an enteric disease caused by Vibrio cholerae. Toxin-coregulated pilus (TCP), a type 4 pilus expressed by V. cholerae, is a cholera virulence factor that is required for host colonization. The TCP polymer is composed of subunits of TcpA pilin. Antibodies directed against TcpA are protective in animal models of cholera. While natural or recombinant forms of TcpA are difficult to purify to homogeneity, it is anticipated that synthesized TcpA peptides might serve as immunogens in a subunit vaccine. We wanted to assess the potential for effects of the immune response (Ir) gene that could complicate a peptide-based …

Anti-Class Ii Monoclonal Antibody-Targeted Vibrio Cholerae Tcpa Pilin: Modulation Of Serologic Response, Epitope Specificity, And Isotype, Jia-Yan Wu, Ronald K. Taylor, William F. Wade

Dartmouth Scholarship

Toxin-coregulated pilus (TCP) is a colonization factor required for cholera infection. It is not a strong immunogen when delivered in the context of whole cells, yet pilus subunits or TcpA derivative synthetic peptides induce protective responses. We examined the efficacy of immunizing mice with TCP conjugated to anti-class II monoclonal antibodies (MAb) with or without the addition of cholera toxin (CT) or anti-CD40 MAb to determine if the serologic response to TcpA could be manipulated. Anti-class II MAb-targeted TCP influenced the anti-TCP peptide serologic response with respect to titer and isotype. Responses to TcpA peptide 4 were induced with class …

Evaluation Of A Tetracycline-Inducible Promoter In Staphylococcus Aureus In Vitro And In Vivo And Its Application In Demonstrating The Role Of Sigb In Microcolony Formation, B. T. Bateman, N. P. Donegan, T. M. Jarry, M. Palma

Dartmouth Scholarship

An inducible promoter system provides a powerful tool for studying the genetic basis for virulence. A variety of inducible systems have been used in other organisms, including pXyl-xylR-inducible promoter, the pSpac-lacI system, and the arabinose-inducible P_BAD promoter, but each of these systems has limitations in its application to Staphylococcus aureus. In this study, we demonstrated the efficacy of a tetracycline-inducible promoter system in inducing gene expression in S. aureus in vitro and inside epithelial cells as well as in an animal model of infection. Using the xyl/tetO promoter::gfp_uvr fusion carried on a shuttle …

Sensitivity Of Bovine Blastocyst Gene Expression Patterns To Culture Environments Assessed By Differential Display Rt-Pcr., D R Natale, P A De Sousa, M E Westhusin, A J Watson

Obstetrics & Gynaecology Publications

The use of culture media to support the development of preimplantation embryos to the blastocyst stage is often associated with detrimental effects on normal development. These effects have been uncovered largely by investigating the phenotypic abnormalities displayed by fetuses and newborns derived from cultured preimplantation embryos. Research to understand the impact of culture on the embryonic developmental programme has focused on embryo metabolism, gene expression and genomic imprinting. We have used differential display RT-PCR to examine culture influences on global transcript pools in bovine embryos. Others have examined culture influences on candidate "marker genes" in cultured murine, ovine and bovine …

Asymmetrical Response Of P38 Kinase Activation To Volume Changes In Primary Rat Astrocytes, Dazhong Xu, Ling Wang, James E. Olson, Luo Lu

Emergency Medicine Faculty Publications

Activation of p38 kinase by osmotic stress has been documented in many cells; however, no report has distinguished the effects of cell volume on p38 activity from the effects of the altered osmotic condition per se. Here we report asymmetrical activation of astrocyte p38 mitogen-activated protein (MAP) kinase in response to volume increases and volume decreases. We separate effects of cell volume changes from the effects of osmotic exposure on p38 activation. Exposure to 400, 500, or 600 mOsm phosphate-buffered saline (PBS) caused cell shrinkage and an osmolality-dependent increase in p38 activity to 175%, 409%, or 518%, respectively, compared with …

Medical Education Digest, Vol. 3 No. 4 (September 15, 2001), Nova Southeastern University

Medical Education Digest

No abstract provided.

Therapeutic Electromagnetic Field Effects On Angiogenesis And Tumor Growth, C. Douglas Williams, Marko S. Markov, W. Elaine Hardman, Ivan L. Cameron

Biochemistry and Microbiology

Background: A new approach to cancer therapy based on the application of therapeutic electromagnetic fields (TEMF) has been developed by EMF Therapeutics, Inc., Chattanooga, TN, USA. This study was designed to assess the effect of TEMF on tumor vascularization and growth of murine 16/C mammmary adenocarcinoma cells in C3H/HeJ mice.

Materials and Methods: Implanted tumors were allowed to grow for seven days until the tumor volume reached 100 mm3 before treatment was started. Mice (20 per control, 10 per EMF exposed group) received treatment (10 minutes per day with 0, 10 mT, 15 mT or 20 mT) with a 120 …

Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that tumor necrosis factor-α (TNF-α) can augment the antitumor effects of radiation, inhibiting tumor progression to a greater extent than either modality alone. However, nonspecific toxicities associated with TNF-α have limited its use as an adjuvant. This limitation is potentially resolved with the encapsulation of TNF-α in sterically stabilized, PEGylated liposomes (STEALTH®). Thus, the overall hypothesis of the research was that the combination of radiation with STEALTH® liposome encapsulated TNF-α (SL-TNF-α) will have greater efficacy and fewer dose-limiting side effects in the LS174T human colorectal tumor xenograft model compared to the combination of free TNF-α and …

Protection Against Traumatic Brain Injury, Stephen William Scheff

Sanders-Brown Center on Aging Faculty Patents

The present invention relates to therapeutic uses of cyclosporin A to reduce adverse effects of neural injury.

Cyclooxygenase-2 And Prostaglandin E(2)(Pge(2)) Receptor Messenger Rnas Are Affected By Bovine Oocyte Maturation Time And Cumulus-Oocyte Complex Quality, And Pge(2) Induces Moderate Expansion Of The Bovine Cumulus In Vitro., M D Calder, A N Caveney, M E Westhusin, A J Watson

Obstetrics & Gynaecology Publications

Expression of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) receptor 2 (EP2) are necessary for rodent cumulus expansion in vivo. Prostaglandin E(2) receptor 3 (EP3) has been detected in bovine preovulatory follicles and corpora lutea. The current experiments examined the effect of PGE(2) on bovine cumulus expansion in vitro and expression of COX-2, EP1, EP2, EP3, and EP4 mRNAs in bovine cumulus-oocyte complexes (COCs) at 0, 6, 12, 18, and 24 h time points during maturation in vitro. Concentrations of PGE(2) above 50 ng/ml resulted in moderate cumulus expansion of bovine COCs, but expansion did not occur in the absence of …

Oncolog, Volume 46, Number 07/08, July/August 2001, Mariann Crapanzano, Noelle Heinze, Wendeline Jongenberger Mba

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Chemoprevention Researchers Look for Ways to Halt the Process of Carcinogenesis
• House Call: HPV and Cancer: What Every Woman--and Man--Should Know
• Chemoprevention Trial Targets Former Smokers
• DiaLog: Serving International Clients, by Wendeline Jongenberger, MBA, Director, International Programs
• Protocols: Chemoprevention Clinical Trials

Estrogen Regulation Of The Pregnant Baboon Placental 11Β-Hydroxysteroid Dehydrogenase (11Β-Hsd)-Catalyzed Metabolism Of Cortisol And Cortisone And Its Effect On The Development Of The Fetal Hypothalamic-Pituitary-Adrenal Axis, William Adair Davies

Theses and Dissertations in Biomedical Sciences

Pepe and Albrecht previously demonstrated that the estrogen-regulated change in transuteroplacental metabolism of cortisol (F) and cortisone (E) from preferential reduction (E to F) at midgestation to oxidation (F to E) near term results in a decline of bioactive cortisol crossing the placenta and reaching the fetus culminating in activation of the hypothalamic-pituitary adrenal axis of the baboon and the ontogenesis of rate-limiting steroidogenic enzymes culminating in de novo F secretion. Protein kinase A (PK-A) activity in the baboon fetal adrenal gland cytosolic fraction was increased 2-fold both at term [day 165 of gestation (term = 184 days)] and following …