Medicine and Health Sciences Commons^™

Heterogeneous Immunological Landscapes And Medieval Plague : An Invitation To A New Dialogue Between Historians And Immunologists., Fabian Crespo, Matthew B. Lawrenz

Fabian Crespo

Efforts to understand the differential mortality caused by plague must account for many factors, including human immune responses. In this essay we are particularly interested in those people who were exposed to the Yersinia pestis pathogen during the Black Death, but who had differing fates—survival or death—that could depend on which individuals (once infected) were able to mount an appropriate immune response as a result of biological, environmental, and social factors. The proposed model suggests that historians of the medieval world could make a significant contribution to the study of human health, and especially the role of human immunology in …

Involvement Of Reactive Oxygen Species In A Feed-Forward Mechanism Of Na/K-Atpase Mediated Signaling, Yanling Yan, Anna P. Shapiro, Steven Haller, Vinal Katragadda, Lijun Liu, Jiang Tian, Venkatesha Basrur, Deepak Malhotra, Zi-Jian Xie, Nader G. Abraham, Joseph I. Shapiro Md, Jiang Liu

Yanling Yan

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial ²²Na⁺ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, …

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Yanling Yan

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed …

Left Ventricular Noncompaction Syndrome: A Rare Congenital Cardiomyopathy, Ashwini V. Mallad, Mbbs, Waseem Ahmed, Md, Madhulika Urella, Md, Dr. Mehiar El-Hamdani, Md, Facc, Fscai

Mehiar El Hamdani, MD

Isolated left ventricular noncompaction cardiomyopathy (LVNC) is a rare congenital condition occurring due to arrest of myocardial compaction in the first trimester, resulting in a thin layer of compacted epicardium and thick hypertrabeculated myocardium containing deep recesses. This article presents a 44-year-old female with progressive dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and pleuritic chest pain. Examination revealed elevated jugular venous distention, lower extremity edema, and bibasilar crackles on lung auscultation, while the electrocardiogram (EKG) exhibited left bundle branch block. Two-dimensional echocardiography (2D-Echo) showed a dilated left ventricle (LV) with ejection fraction (EF) of 25% and severe diffuse hypokinesia. Cardiac magnetic resonance …

Gradenigo Syndrome: A Rare Complication Of Otitis Media, Paul Brent Ferguson, Md

Paul Ferguson

Gradenigo syndrome is a very rare complication of otitis media that if left unrecognized and subsequently untreated will result in severe neurologic sequelae. Gradenigo Syndrome clinically represented by the triad of otitis media, ipsilateral, abducens nerve palsy and dysasthesia within the V1 and V2 divisions of the trigeminal nerve branches. We describe a 4 year-old patient who presented with headache, facial pain, diplopia and a recent history of upper respiratory tract symptomatology. Examination revealed an abducens palsy with subsequent magnetic resonance imaging demonstrating inflammation in the left petrous apex and along the tracts of the 6th, 7th, and 8th cranial …

Involvement Of Reactive Oxygen Species In A Feed-Forward Mechanism Of Na/K-Atpase Mediated Signaling, Yanling Yan, Anna P. Shapiro, Steven Haller, Vinal Katragadda, Lijun Liu, Jiang Tian, Venkatesha Basrur, Deepak Malhotra, Zi-Jian Xie, Nader G. Abraham, Joseph I. Shapiro Md, Jiang Liu

Zijian Xie

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial ²²Na⁺ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, …

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Franklin D. Shuler

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K2 (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation of …

Verification Of Out-Of-Control Situations Detected By "Average Of Normal" Approach., Jiakai Liu, Chin Hon Tan, Tze Ping Loh, Tony Badrick

Tony Badrick

OBJECTIVES: "Average of normal" (AoN) or "moving average" is increasingly used as an adjunct quality control tool in laboratory practice. Little guidance exists on how to verify if an out-of-control situation in the AoN chart is due to a shift in analytical performance, or underlying patient characteristics. DESIGN AND METHODS: Through simulation based on clinical data, we examined 1) the location of the last apparently stable period in the AoN control chart after an analytical shift, and 2) an approach to verify if the observed shift is related to an analytical shift by repeat testing of archived patient samples from …

Malnutrition In The Older Australian Rural Rehabilitation Community : Indentification, Patient Outcomes And The Role Of Informal Caregivers, Skye Marshall

Skye Marshall

Enhancing the effectiveness of nutritional care to improve the overall health of older adults will be key in reducing hospital and aged care facility demand, a priority target of current health service research and policy. Engaging informal caregivers as part of the nutrition care team presents an opportunity for improving the nutrition status of older Australians in rehabilitation and the community. This thesis provides evidence to improve malnutrition screening, assessment, diagnosis and resource allocation in rehabilitation facilities. It also makes recommendations to improve nutrition intervention in practice, and for how intervention studies should be designed in this setting. The thesis …

Process Evaluation Of A Patient-Centred, Patientdirected, Group-Based Education Program For The Management Of Type 2 Diabetes Mellitus, Kate Odgers-Jewell, Elisabeth Isenring, Rae Thomas, Dianne P Reidlinger

Rae Thomas

Aim: The present study developed and evaluated a patient-centred, patient-directed, group-based education program for the management of type 2 diabetes mellitus. Methods: Two frameworks, the Medical Research Council (MRC) framework for developing and evaluating complex interventions and the RE-AIM framework were followed. Data to develop the intervention were sourced from scoping of the literature and formative evaluation. Program evaluation comprised analysis of primary recruitment of participants through general practitioners, baseline and end-point measures of anthropometry, four validated questionnaires, contemporaneous facilitator notes and telephone interviews with participants. Results: A total of 16 participants enrolled in the intervention. Post-intervention results were obtained …

Process Evaluation Of A Patient-Centred, Patientdirected, Group-Based Education Program For The Management Of Type 2 Diabetes Mellitus, Kate Odgers-Jewell, Elisabeth Isenring, Rae Thomas, Dianne P Reidlinger

Liz Isenring

Aim: The present study developed and evaluated a patient-centred, patient-directed, group-based education program for the management of type 2 diabetes mellitus. Methods: Two frameworks, the Medical Research Council (MRC) framework for developing and evaluating complex interventions and the RE-AIM framework were followed. Data to develop the intervention were sourced from scoping of the literature and formative evaluation. Program evaluation comprised analysis of primary recruitment of participants through general practitioners, baseline and end-point measures of anthropometry, four validated questionnaires, contemporaneous facilitator notes and telephone interviews with participants. Results: A total of 16 participants enrolled in the intervention. Post-intervention results were obtained …

Redefining Myeloid Subsets In Murine Spleen, Ying-Ying Hey, Jonathan K H Tan, Helen C O'Neill

Helen O'Neill

Spleen is known to contain multiple dendritic and myeloid cell subsets, distinguishable on the basis of phenotype, function and anatomical location. As a result of recent intensive flow cytometric analyses, splenic dendritic cell (DC) subsets are now better characterized than other myeloid subsets. In order to identify and fully characterize a novel splenic subset termed "L-DC" in relation to other myeloid cells, it was necessary to investigate myeloid subsets in more detail. In terms of cell surface phenotype, L-DC were initially characterized as a CD11b(hi)CD11c(lo)MHCII(-)Ly6C(-)Ly6G(-) subset in murine spleen. Their expression of CD43, lack of MHCII, and a low level …

Primary Care Clinicians Use Of Genomics And Pharmacogenomic Testing, Heather Bittner-Fagan Md, Mph, Brian Stello Md, Christopher V. Chambers Md, Geoffrey Mills Md, Phd, Beth Careyva Md, Melanie B. Johnson Mpa, Dierdre B. Axell-House Ba, Michael P. Rosenthal Md

Beth A. Careyva, M.D.

No abstract provided.

Chimpanzee Research: An Examination Of Its Contribution To Biomedical Knowledge And Efficacy In Combating Human Diseases, Jarrod Bailey, Jonathan Balcombe, Theodora Capaldo

Jonathan Balcombe, PhD

Research on captive chimpanzees incurs considerable animal welfare, ethical and financial costs. Advocates of such research claim these costs are outweighed by substantial advancements in biomedical knowledge, and that the genetic similarity of chimpanzees to humans enables the former to make critical contributions to preventing, diagnosing and combating human diseases. To assess these claims, we examined the disciplines investigated in 749 studies of captive chimpanzees published from 1995-2004 inclusive, and subjected 95 randomly selected papers to a detailed citation analysis:

49.5% (47/95) of papers had not been cited at the time of this study; 38.5% (34/95) were cited by 116 …

An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey

Jarrod Bailey, PhD

Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jarrod Bailey, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, PhD

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s …

Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, PhD

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98–99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis C virus …

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

Animal tests yield misleading results.

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, PhD

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

Due to limited human exposure data, risk classification and the consequent regulation of exposure to potential carcinogens has conventionally relied mainly upon animal tests. However, several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. To investigate the reasons for this, we surveyed 160 chemicals possessing animal but not human exposure data within the US Environmental Protection Agency chemicals database, but which had received human carcinogenicity assessments by 1 January 2004. We discovered the use of a wide variety of species, with rodents predominating, and of a wide variety of routes of administration, and that there were …

The Residency Cpc As A Means Of Faculty Development, Kathleen E. Kane Md, Kevin R. Weaver Do, Gavin C. Barr Jr. Md, Amy B. Smith Phd, Andrew C. Miller Do, Charles C. Worrilow Md, Terrence E. Goyke Do, Dawn M. Yenser, Bryan G. Kane Md

Charles Worrilow, MD.

No abstract provided.

Advancing Drug Delivery Systems For The Treatment Of Multiple Sclerosis, I. Tabansky, M. D. Messina, C. Bangeranye, J. Goldstein, K. M. Blitz-Shabbir, S. Machado, V. Jeganathan, P. Wright, S. Najjar, J. N. Stern

Joel N.H. Stern

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the …

The Residency Cpc As A Means Of Faculty Development, Kathleen E. Kane Md, Kevin R. Weaver Do, Gavin C. Barr Jr. Md, Amy B. Smith Phd, Andrew C. Miller Do, Charles C. Worrilow Md, Terrence E. Goyke Do, Dawn M. Yenser, Bryan G. Kane Md

Kevin Weaver, D.O., FACOEP

No abstract provided.

Cardiopulmonary Resuscitation Prescription Program: A Prospective Randomized Pilot Study, Marna R. Greenberg Do, Mph, Facep, Gavin Barr Md, Valerie Rupp Rn, Bsn, Nainesh C. Patel Md, Kevin R. Weaver Do, Kimberly Hamilton Ba, James F. Reed Iii, Phd

Kevin Weaver, D.O., FACOEP

No abstract provided.

Effect Of Standard Treatment Guidelines With Or Without Prescription Audit On Prescribing For Acute Respiratory Tract Infection (Ari) And Diarrhoea In Some Thana Health Complexes (Thcs) Of Bangladesh, M. O. Faruk Khan, A.K. Azad Chowdhury, M. A. Matin, K. Begum, M. A. Galib

M. O. Faruk Khan

Inappropriate prescribing for ARI and diarrhoea is a serious health problem in many developing countries including Bangladesh. A baseline retrospective prescribing survey for ARI and diarrhoea have been conducted in randomly selected 60 thana health complexes (THCs) of Dhaka division of Bangladesh. In the 38 of 60 THCs, the prescribers did not comply with the standard treatment guidelines (STG) for ARI. They are marked as 'unsatisfactory performers'. In these THCs unnecessary antibiotics were prescribed in more than 50% of the encounters. The study further revealed that in 26 THCs, comprising 41.6% of the 38 THCs, the situation was even worse …