Digital Commons Network^™

The Earliest Dipodomyine Heteromyid In North America And The Phylogenetic Relationships Of Geomorph Rodent, Steven J Norris

Faculty, Staff and Student Publications

The proteome of the spirochete bacterium Borrelia burgdorferi, the tick-borne agent of Lyme disease, has been characterized by two different approaches using mass spectrometry, providing a launching point for future studies on the dramatic changes in protein expression that occur during transmission of the bacterium between ticks and mammals.

Construction Of Improved Temperature-Sensitive And Mobilizable Vectors And Their Use For Constructing Mutations In The Adhesin-Encoding Acm Gene Of Poorly Transformable Clinical Enterococcus Faecium Strains, Sreedhar R Nallapareddy, Kavindra V Singh, Barbara E Murray

Faculty, Staff and Student Publications

Inactivation by allelic exchange in clinical isolates of the emerging nosocomial pathogen Enterococcus faecium has been hindered by lack of efficient tools, and, in this study, transformation of clinical isolates was found to be particularly problematic. For this reason, a vector for allelic replacement (pTEX5500ts) was constructed that includes (i) the pWV01-based gram-positive repAts replication region, which is known to confer a high degree of temperature intolerance, (ii) Escherichia coli oriR from pUC18, (iii) two extended multiple-cloning sites located upstream and downstream of one of the marker genes for efficient cloning of flanking regions for double-crossover mutagenesis, (iv) transcriptional terminator …

Embryonic Stem Cell-Derived Hematopoietic Stem Cells, Yuan Wang, Frank Yates, Olaia Naveiras, Patricia Ernst, George Q. Daley

Dartmouth Scholarship

Despite two decades of studies documenting the in vitro blood-forming potential of murine embryonic stem cells (ESCs), achieving stable long-term blood engraftment of ESC-derived hematopoietic stem cells in irradiated mice has proven difficult. We have exploited the Cdx-Hox pathway, a genetic program important for blood development, to enhance the differentiation of ESCs along the hematopoietic lineage. Using an embryonic stem cell line engineered with tetracycline-inducible Cdx4 , we demonstrate that ectopic Cdx4 expression promotes hematopoietic mesoderm specification, increases hematopoietic progenitor formation, and, together with HoxB4, enhances multilineage hematopoietic engraftment of lethally irradiated adult mice. Clonal analysis of retroviral integration sites …

Visibility, Visual Awareness, And Visual Masking Of Simple Unattended Targets Are Confined To Areas In The Occipital Cortex Beyond Human V1/V2, Peter U. Tse, Susanna Martinez-Conde, Alexander A. Schlegel, Stephen L. Macknik

Dartmouth Scholarship

In visual masking, visible targets are rendered invisible by modifying the context in which they are presented, but not by modifying the targets themselves. Here, we localize the neuronal correlates of visual awareness in the human brain by using visual masking illusions. We compare monoptic visual masking activation, which we find within all retinotopic visual areas, with dichoptic masking activation, which we find only in those retinotopic areas downstream of V2. Because monoptic and dichoptic masking are equivalent in magnitude perceptually, the present results establish a lower bound for maintenance of visual awareness of simple unattended targets. Moreover, we find …

Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander

Dartmouth Scholarship

The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican …

Principal Component Analysis For Predicting Transcription-Factor Binding Motifs From Array-Derived Data, Yunlong Liu, Matthew P Vincenti, Hiroki Yokota

Dartmouth Scholarship

The responses to interleukin 1 (IL-1) in human chondrocytes constitute a complex regulatory mechanism, where multiple transcription factors interact combinatorially to transcription-factor binding motifs (TFBMs). In order to select a critical set of TFBMs from genomic DNA information and an array-derived data, an efficient algorithm to solve a combinatorial optimization problem is required. Although computational approaches based on evolutionary algorithms are commonly employed, an analytical algorithm would be useful to predict TFBMs at nearly no computational cost and evaluate varying modelling conditions. Singular value decomposition (SVD) is a powerful method to derive primary components of a given matrix. Applying SVD …

Barnacles, Old Age Marks, Or Just Plain Seborrheic Keratoses., Lawrence Charles Parish, Joseph A. Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

Growing older may mean more wrinkles and creaking joints, but why does it also entail an accumulation of barnacles. These brown, somewhat friable, often warty lesions are more common on senior citizens but are not necessarily limited to the chronologically challenged. Seborrheic keratoses (SKs) can be easily recognized (fig 1), but the itching and the occasional scratch-induced dermatitis make them more than a cosmetic nuisance. (fig 2)

SKs can go by a variety of names, ranging from basal cell papillomas, senile warts, and senile keratoses to seborrheic verrucae and verrucous senilis. The various terms provide no more information on their …

Evaluation Of Stature Development During Childhood And Adolescence In Individuals With Familial Hypophosphatemic Rickets, Mauro M. S. Borghi, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

This review was conducted to study the diagnosis, treatment, and growth progression in infants and adolescents with familial hypophosphatemic rickets. The bibliographic search was carried out utilizing the electronic databases MEDLINE, OVID, and LILACS and by direct research within the last 15 years using the keywords rickets, familial hypophosphatemia, vitamin D deficiency, stature growth, childhood, and adolescence. Article selection was done by comparing the evaluation of the growth in patients with familial hypophosphatemic rickets, including the variables that might affect them, for possible future therapeutic proposals. It is concluded that the most significant fact in the treatment of familial hypophosphatemic …

Near-Infrared Characterization Of Breast Tumors In Vivo Using Spectrally-Constrained Reconstruction, Subhadra Srinivasan, Brian W. Pogue, Ben Brooksby, Shudong Jiang, Hamid Dehghani, Christine Kogel, Wendy A. Wells, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six …

Taxol-Stabilized Microtubules Can Position The Cytokinetic Furrow In Mammalian Cells, Katie Shannon, Julie C. Canman, C. Ben Moree, Jennifer S. Tirnauer, Edward D. Salmon

Biological Sciences Faculty Research & Creative Works

How microtubules act to position the plane of cell division during cytokinesis is a topic of much debate. Recently, we showed that a subpopulation of stable microtubules extends past chromosomes and interacts with the cell cortex at the site of furrowing, suggesting that these stabilized microtubules may stimulate contractility. To test the hypothesis that stable microtubules can position furrows, we used taxol to rapidly suppress microtubule dynamics during various stages of mitosis in PtK1 cells. Cells with stabilized prometaphase or metaphase microtubule arrays were able to initiate furrowing when induced into anaphase by inhibition of the spindle checkpoint. In these …

The Chemical Species Of Aluminum Influences Its Paracellular Flux Across And Uptake Into Caco-2 Cells, A Model Of Gastrointestinal Absorption, Yuzhao Zhou, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) can cause neurotoxicity, a low-turnover osteomalacia, and microcytic anemia. To test the null hypothesis that the chemical form (species) of Al does not influence its mechanism or rate of absorption from the gastrointestinal tract, Al flux across and uptake into Caco-2 cells was investigated. Caco-2 cells were grown on porous membranes mounted in vertical diffusion chambers or in 35-mm-diameter plastic cell culture dishes. When 8 mM ²⁷Al was introduced as the ion, citrate, maltolate, fluoride, or hydroxide, the apical to basolateral apparent permeability (P_app) of Al correlated highly with the P_app of lucifer yellow …

Cpg Oligodeoxynucleotides Stimulate Cord Blood Mononuclear Cells To Produce Immunoglobulins., Cheri D Landers, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

CpG oligodeoxynucleotides (ODNs) stimulate adult B cells leading to cellular proliferation and immunoglobulin production. It is unknown if CpG-ODNs similarly stimulate neonatal human B cells. Neonates have immature immune responses and are poorly responsive to thymus independent antigens such as polysaccharides. We determined umbilical cord cells' response to CpG-ODNs. Adult and umbilical cord B cells produced similar amounts of IgM (adult 1371 +/- 352 vs. cord 1873 +/- 1084 ng/ml) in response to CpG-ODN stimulation. Although CpG-ODN was able to stimulate adult IgG and IgA production, cord cells produced less IgG (153 +/- 58 vs. 10 +/- 2.5 ng/ml) and …

C-Jun N-Terminal Kinase (Jnk) Is Required For Survival And Proliferation Of B-Lymphoma Cells, Murali Gururajan, Roger Chui, Anbu K. Karuppannan, Jiyuan Ke, C. Darrell Jennings, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Several primary murine and human B lymphomas and cell lines were found to constitutively express high levels of the activated form of c-jun N-terminal kinase (JNK), a member of the mitogen-activated protein (MAP) kinase family. Proliferation of murine B lymphomas CH31, CH12.Lx, BKS-2, and WEHI-231 and the human B lymphomas BJAB, RAMOS, RAJI, OCI-Ly7, and OCI-Ly10 was strongly inhibited by SP600125, an anthrapyrazolone inhibitor of JNK, in a dose-dependent manner. The lymphoma cells underwent apoptosis and arrested at the G2/M phase of cell cycle. Furthermore, JNK-specific small interfering RNA (siRNA) inhibited the growth of both murine and human B lymphomas. …

Basal Endothelial Nitric Oxide Release Is Preserved In Overweight And Obese Adults, Christopher A Desouza, Gary P. Van Guilder, Jared J Greiner, Derek T Smith, Greta L Hoetzer, Brian L Stauffer

Health and Nutritional Sciences Faculty Publications

OBJECTIVE: Impaired basal nitric oxide release is associated with a number of cardiovascular disorders including hypertension, arterial spasm, and myocardial infarction. We determined whether basal endothelial nitric oxide release is reduced in otherwise healthy overweight and obese adult humans.
RESEARCH METHODS AND PROCEDURES: Seventy sedentary adults were studied: 32 normal weight (BMI/m(2)), 24 overweight (BMI > or = 25 < 30 kg/m(2)), and 14 obese (BMI > or = 30 kg/m(2)). Forearm blood flow (FBF) responses to intra-arterial infusions of N(g)-monomethyl-L-arginine (5 mg/min), a nitric oxide synthase inhibitor, were used as an index of basal nitric oxide release.
RESULTS: N(g)-monomethyl-L-arginine elicited significant reductions in FBF in the normal weight …

Tcpf Is A Soluble Colonization Factor And Protective Antigen Secreted By El Tor And Classical O1 And O139 Vibrio Cholerae Serogroups, Thomas J. Kirn, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae causes diarrhea by colonizing the human small bowel and intoxicating epithelial cells. Colonization is a required step in pathogenesis, and strains defective for colonization are significantly attenuated. The best-characterized V. cholerae colonization factor is the toxin-coregulated pilus (TCP). It has been demonstrated that TCP is required for V. cholerae colonization in both humans and mice. TCP enhances bacterial interactions that allow microcolony formation and thereby promotes survival in the intestine. We have recently discovered that the TCP biogenesis apparatus also serves as a secretion system, mediating the terminal step in the extracellular secretion pathway of TcpF. TcpF was …

Donepezil Effects On Mood In Patients With Schizophrenia And Schizoaffective Disorder, S Craig Risch, Michael D. Horner, Susan R. Mcgurk, Simmy Palecko, John S. Markowitz, Ziad Nahas, C. Lindsay Devane

Dartmouth Scholarship

Donepezil, 5 mg/d for 6 wk then 10 mg/d for 6 wk, and placebo daily for 12 wk in a double-blind cross-over paradigm, was added to the therapeutic regimen of 13 patients with schizophrenia or schizoaffective disorders, clinically stable on atypical antipsychotic medications. Patients had varying degrees of depressive symptoms, ranging from no depression to clinically significant depression. There was no worsening or induction of depression in individual patients or the group as a whole. In addition there was a statistically significant antidepressant effect in the group as a whole during the donepezil condition and a clinically significant antidepressant effect …

The Human Paf Complex Coordinates Transcription With Events Downstream Of Rna Synthesis., Bing Zhu, Subhrangsu S. Mandal, Anh-Dung Pham, Yong Zheng, Hediye Erdjument-Bromage, Surinder K. Batra, Paul Tempst, Danny Reinberg

Journal Articles: Biochemistry & Molecular Biology

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specific subunit, hSki8. RNAi against hSki8 or hCtr9 reduces the cellular levels of other hPAF subunits and of mono- and trimethylated H3-Lys 4 and dimethylated H3-Lys 79. The hSki8 subunit is also a component of the human SKI (hSKI) complex. Yeast SKI complex is cytoplasmic and together with Exosome mediates …

Erythroid Cell-Specific Α-Globin Gene Regulation By The Cp2 Transcription Factor Family, Ho C. Kang, Jui Hyung Chae, Yeon H. Lee, Mi-Ae Park, June Ho Shin, Sung-Hyun Kim, Sang-Kyu Ye, Yoon Shin Cho, Steven Fiering, Chul Geun Kim

Dartmouth Scholarship

We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of alpha-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of …

A Human T-Cell Lymphotropic Virus Type 1 Enhancer Of Myc Transforming Potential Stabilizes Myc-Tip60 Transcriptional Interactions, Soumya Awasthi, Anima Sharma, Kasuen Wong, Junyu Zhang, Elizabeth F. Matlock, Lowery Rogers, Pamela Motloch, Shigeki Takemoto, Hirokuni Taguchi, Michael D. Cole

Dartmouth Scholarship

The human T-cell lymphotropic virus type 1 (HTLV-1) infects and transforms CD4+ lymphocytes and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive lymphoproliferative disease that is often fatal. Here, we demonstrate that the HTLV-1 pX splice-variant p30II markedly enhances the transforming potential of Myc and transcriptionally activates the human cyclin D2 promoter, dependent upon its conserved Myc-responsive E-box enhancer elements, which are associated with increased S-phase entry and multinucleation. Enhancement of c-Myc transforming activity by HTLV-1 p30II is dependent upon the transcriptional coactivators, transforming transcriptional activator protein/p434 and TIP60, and it requires TIP60 histone acetyltransferase (HAT) activity and correlates with the …

Gonadal Steroids Differentially Modulate Neurotoxicity Of Hiv And Cocaine: Testosterone And Ici 182,780 Sensitive Mechanism, Sherie L. Kendall, Caroline F. Anderson, Avindra Nath, Jadwiga Turchan-Cholewo, Cantey L. Land, Charles F. Mactutus, Rosemarie M. Booze

Behavioral Science Faculty Publications

BACKGROUND: HIV Associated Dementia (HAD) is a common complication of human immunodeficiency virus (HIV) infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein) have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, …

A Critical Role For Kalirin In Ngf Signaling Through Trka, Kausik Chakrabarti, Rong Lin, Noraisha I. Schiller, Yanping Wang, David Koubi, Ying-Xin Fan, Brian B. Rudkin, Gibbes R. Johnson, Martin R. Schiller

Life Sciences Faculty Research

Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low …

Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony

Paediatrics Publications

Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis …

Effect Of Non-Metabolized Sweeteners On Health Parameters In Humans, Matthew Alan Leonhardt

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The demand for functional foods is on the rise. These are food products that, besides providing energy and nutrients for life, provide additional health benefits. Xylitol, a five-carbon sugar alcohol, is a possible functional food, as well as a sugar replacement. The cost of xylitol has led manufacturers to add inulin, a nondigestible oligosaccharide, as an extender. Both xylitol and inulin have been suggested to provide added health benefits beyond being a reduced calorie replacement for sugar. We tested their impact on several human health parameters (fecal weight, fecal pH, fecal % moisture, blood lipids, blood glucose, and fecal micro …

Osler And The Infected Letter, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The spread of infectious agents through the mail has concerned public health officials for 5 centuries. The dissemination of anthrax spores in the US mail in 2001 was a recent example. In 1901, two medical journals reported outbreaks of smallpox presumably introduced by letters contaminated with variola viruses. The stability and infectivity of the smallpox virus are reviewed from both a historical (anecdotal) perspective and modern virologic studies. Bubonic plague was the contagious disease that led to quarantines as early as the 14th century in port cities in southern Europe. Later, smallpox, cholera, typhus, and yellow fever were recognized as …

Cart: An Hrs/Actinin-4/Berp/Myosin V Protein Complex Required For Efficient Receptor Recycling, Qing Yan, Wei Sun, Pekka Kujala, Yasmin Lotfi, Thomas A Vida, Andrew J Bean

Faculty, Staff and Student Publications

Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The …

Quadratic Regression Analysis For Gene Discovery And Pattern Recognition For Non-Cyclic Short Time-Course Microarray Experiments, Hua Liu, Sergey Tarima, Aaron S. Borders, Thomas V. Getchell, Marilyn L. Getchell, Arnold J. Stromberg

Statistics Faculty Publications

BACKGROUND: Cluster analyses are used to analyze microarray time-course data for gene discovery and pattern recognition. However, in general, these methods do not take advantage of the fact that time is a continuous variable, and existing clustering methods often group biologically unrelated genes together.

RESULTS: We propose a quadratic regression method for identification of differentially expressed genes and classification of genes based on their temporal expression profiles for non-cyclic short time-course microarray data. This method treats time as a continuous variable, therefore preserves actual time information. We applied this method to a microarray time-course study of gene expression at short …

Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin

Department of Medical Oncology Faculty Papers

When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate …

Microsomal Prostaglandin E Synthase-1: The Inducible Synthase For Prostaglandin E2, Annaleise V. Sampey, Seetha Monrad, Leslie J. Crofford

Internal Medicine Faculty Publications

Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme that catalyzes the conversion of prostaglandin (PG)H2 to PGE2. Proinflammatory stimuli markedly increase levels of mPGES-1 expression both in vivo and in vitro. mPGES-1 knockout studies and animal models of inflammatory arthritis also provide a strong basis for the contribution of mPGES-1 in the increased local production of PGE2 observed in inflammatory arthritis. The focus of this article is to review some recent advances in our understanding of mechanisms specific to the regulation of inducible mPGES-1 in inflammatory arthritis.

Identification And Expansion Of Pancreatic Stem/Progenitor Cells., You-Qing Zhang, Marcie Kritzik, Nora Sarvetnick

Journal Articles: Regenerative Medicine

Pancreatic islet transplantation represents an attractive approach for the treatment of diabetes. However, the limited availability of donor islets has largely hampered this approach. In this respect, the use of alternative sources of islets such as the ex vivo expansion and differentiation of functional endocrine cells for treating diabetes has become the major focus of diabetes research. Adult pancreatic stem cells /progenitor cells have yet to be recognized because limited markers exist for their identification. While the pancreas has the capacity to regenerate under certain circumstances, questions where adult pancreatic stem/progenitor cells are localized, how they are regulated, and even …

Bench-To-Bedside Review: Rhabdomyolysis -- An Overview For Clinicians., Ana L Huerta-Alardín, Joseph Varon, Paul E Marik

Jefferson Hospital Staff Papers and Presentations

Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration.