Internal Medicine Commons^™

Spinal Cord Protection: Lessons Learned From Endovascular Repair, Jennifer N Dulin, Meredith L Moore, Kevin W Gates, Joanna H Queen, Raymond J Grill

Faculty, Staff and Student Publications

There is a high incidence of infertility in males following traumatic spinal cord injury (SCI). Quality of semen is frequently poor in these patients, but the pathophysiological mechanism(s) causing this are not known. Blood-testis barrier (BTB) integrity following SCI has not previously been examined. The objective of this study was to characterize the effects of spinal contusion injury on the BTB in the rat. 63 adult, male Sprague Dawley rats received SCI (n = 28), laminectomy only (n = 7) or served as uninjured, age-matched controls (n = 28). Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), BTB permeability to the …

Chondrosarcoma Of The Mobile Spine And Sacrum, Ryan M Stuckey, Rex A W Marco

Faculty, Staff and Student Publications

Chondrosarcoma is a rare malignant tumor of bone. This family of tumors can be primary malignant tumors or a secondary malignant transformation of an underlying benign cartilage tumor. Pain is often the initial presenting complaint when chondrosarcoma involves the spine. In the mobile spine, chondrosarcoma commonly presents within the vertebral body and shows a predilection for the thoracic spine. Due to the resistance of chondrosarcoma to both radiation and chemotherapy, treatment is focused on surgery. With en bloc excision of chondrosarcoma of the mobile spine and sacrum patients can have local recurrence rates as low as 20%.

The Hypoxia-Adenosine Link During Myocardial Ischemia—Reperfusion Injury, Diana Panesso, Maria C Montealegre, Sandra Rincón, Maria F Mojica, Louis B Rice, Kavindra V Singh, Barbara E Murray, Cesar A Arias

Faculty, Staff and Student Publications

BACKGROUND: Plasmids containing hylEfm (pHylEfm) were previously shown to increase gastrointestinal colonization and lethality of Enterococcus faecium in experimental peritonitis. The hylEfm gene, predicting a glycosyl hydrolase, has been considered as a virulence determinant of hospital-associated E. faecium, although its direct contribution to virulence has not been investigated. Here, we constructed mutants of the hylEfm-region and we evaluated their effect on virulence using a murine peritonitis model.

RESULTS: Five mutants of the hylEfm-region of pHylEfmTX16 from the sequenced endocarditis strain (TX16 [DO]) were obtained using an adaptation of the PheS* system and were evaluated in a commensal strain TX1330RF to …

Case Of “Slow” Stroke From Carotid Artery Occlusion Treated By Delayed But Cautious Endovascular Intervention, Kachi Illoh, Emilio Supsupin, Hashem M Shaltoni, Edwin D Cacayorin

Faculty, Staff and Student Publications

In a challenging case of carotid occlusion with slowly evolving stroke, we used brain imaging to facilitate endovascular revascularization resulting in the relief of the patient's symptoms. Patients with carotid occlusion and continued neurological worsening or fluctuations present enormous treatment challenges. These patients may present "slow" strokes with subacute infarcts that present significant challenges and risks during attempts at revascularization of the occluded artery. We present such a case in which we used multimodal imaging techniques, including MR-perfusion, to facilitate endovascular revascularization. Our approach of delayed but cautious intra-arterial thrombolytic therapy, guided by brain imaging, and followed by stent placement …

Acceptability Of Behavioral Treatments For Insomnia, Daniel Bluestein, Amanda C. Healey, Carolyn M. Rutledge

Ellmer School of Nursing Faculty Publications

Background: Behavioral treatments for insomnia are safe and efficacious but may not be embraced by patients in primary care. Understanding factors associated with acceptability can enhance successful use of these modalities. The objective of this study was to identify demographic and clinical/psychosocial correlates of behavioral insomnia treatment acceptability.

Methods: This nonexperimental, inventory-based, cross-sectional study enrolled patients from a hospital-sponsored primary care clinic and 2 urban academic family practices. Participants (n = 236) were 18 years of age or older who had clinically significant insomnia (Insomnia Severity Index score >= 8) and were recruited consecutively at these sites. A study coordinator …

Association Of Retinoic Acid Receptor Genes With Meningomyelocele, Phong X Tran, Kit Sing Au, Alanna C Morrison, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Hope Northrup

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM.

METHODS: We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our …

Immunopathology Of Postprimary Tuberculosis: Increased T-Regulatory Cells And Dec-205-Positive Foamy Macrophages In Cavitary Lesions, Kerry J Welsh, Semyon A Risin, Jeffrey K Actor, Robert L Hunter

Faculty, Staff and Student Publications

Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, lipid pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in lipid pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker …

Probing The Mechanical Properties Of Tnf-A Stimulated Endothelial Cell With Atomic Force Microscopy, Sei-Young Lee, Ana-Maria Zaske, Tommaso Novellino, Delia Danila, Mauro Ferrari, Jodie Conyers, Paolo Decuzzi

Faculty, Staff and Student Publications

TNF-α (tumor necrosis factor-α) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-α is elevated (> 1 pg/mL) in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-α could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1) mechanical properties, employing atomic force microscopy; 2) cytoskeletal organization, through fluorescence microscopy; and 3) membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation …

Alterations In Content And Localization Of Defensins In Rat Ileum And Jejunum Following Ischemia-Reperfusion Specific Peptides, In Specific Places, For Specific Jobs?, Rosemary A Kozar, Rachel J Santora, Brian J Poindexter, Stephen M Milner, Roger J Bick

Faculty, Staff and Student Publications

Objective: To determine alterations in quantities and distributions of natural antimicrobials following ischemia-reperfusion injury. We hypothesized that these compounds would be upregulated in areas of small intestine where changes in permeability and cellular disruption were likely and where protective mechanisms would be initiated. Methods: Rats with ischemia-reperfusion underwent superior mesenteric artery clamping and reperfusion. Shams were subjected to laparotomy but no clamping. Ileum and jejunum were harvested and sectioned, and subjected to fluorescence deconvolution microscopy for determinations of content and localization of rat beta defensins, 1, 2, 3; rat neutrophil protein-1; and cathelicidin LL-37. Modeling was performed to determine cellular …

Complete Genome Sequence Of Treponema Paraluiscuniculi, Strain Cuniculi A: The Loss Of Infectivity To Humans Is Associated With Genome Decay, David Smajs, Marie Zobaníková, Michal Strouhal, Darina Cejková, Shannon Dugan-Rocha, Petra Pospíšilová, Steven J Norris, Tom Albert, Xiang Qin, Kym Hallsworth-Pepin, Christian Buhay, Donna M Muzny, Lei Chen, Richard A Gibbs, George M Weinstock

Faculty, Staff and Student Publications

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In …

Re: Sleep And The Family Doctor: Time To Lead, D. Bluestein, A. C. Healey, C. M. Rutledge

Ellmer School of Nursing Faculty Publications

No abstract provided.

Enterococcus Faecalis Rnjb Is Required For Pilin Gene Expression And Biofilm Formation, Peng Gao, Kenneth L Pinkston, Sreedhar R Nallapareddy, Ambro Van Hoof, Barbara E Murray, Barrett R Harvey

Faculty, Staff and Student Publications

Pili in Gram-positive bacteria play a major role in the colonization of host tissue and in the development of biofilms. They are promising candidates for vaccines or drug targets since they are highly immunogenic and share common structural and functional features among various Gram-positive pathogens. Numerous publications have helped build a detailed understanding of pilus surface assembly, yet regulation of pilin gene expression has not been well defined. Utilizing a monoclonal antibody developed against the Enterococcus faecalis major pilus protein EbpC, we identified mutants from a transposon (Tn) insertion library which lack surface-exposed Ebp pili. In addition to insertions in …

Peripheral Arterial Disease In Hiv Positive And Negative Subjects At The Aga Khan University Hospital, Nairobi, Farida Kaittany

Master of Medicine in Internal Medicine

Aim: To determine the prevalence of peripheral arterial disease (PAD) amongst HIV positive patients and HIV negative subjects and associated risk factors at Aga Khan Hospital Nairobi Design: Cross-sectional descriptive study Patients and Setting: A group of 125 HIV positive and 120 HIV negative subjects aged between 40 – 70 years were included in the study. HIV negative subjects were sampled from HIV positive patients attending the HIV outpatient clinic while HIV negative subjects were sampled from blood donor unit at theAga KhanUniversityHospital. Methodology: Two separate convenient samples were selected for the study. The first sample was a group of …

A Randomised Comparative Trial Of Seven Versus Fourteen Day Triple Therapy For Helicobacter Pylori Eradication At The Aga Khan University Hospital, Nairobi, Ahmed Sokwala

Master of Medicine in Internal Medicine

Background: Helicobacter is associated with a number of important upper gastrointestinal conditions including chronic gastritis, peptic ulcer disease, and gastric malignancy. Proton pump inhibitor -based triple therapies are considered the standard regimens for Helicobacter pylori eradication, but the optimal duration of these regimens is still controversial. Local studies are required to evaluate the H. pylori eradication rates in a country for adequate eradication to prevent H. pylori infection and complications Objectives: The main objective of this study was to compare 7 day and 14 day regimens and determine the optimum duration of triple therapy for H. pylori eradication. Methods: A …

Histamine Reduces Flash Sensitivity Of On Ganglion Cells In The Primate Retina, Nikolay P Akimov, David W Marshak, Laura J Frishman, Randolph D Glickman, Rafail G Yusupov

Faculty, Staff and Student Publications

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded …

A Direct Role For Secretory Phospholipase A2 And Lyso-Phosphatidylcholine In The Mediation Of Lipopolysaccharide-Induced Gastric Injury, Elizabeth J Dial, Duy M Tran, Jimmy J Romero, Mayssa Zayat, Lenard M Lichtenberger

Faculty, Staff and Student Publications

Endotoxemia from sepsis can injure the gastrointestinal tract through mechanisms that have not been fully elucidated. We have shown that LPS induces an increase in gastric permeability in parallel with the luminal appearance of secretory phospholipase A2 (sPLA2) and its product, lysophosphatidylcholine (lyso-PC). We proposed that sPLA2 acted on the gastric hydrophobic barrier, composed primarily of phosphatidylcholine (PC), to degrade it and produce lyso-PC, an agent that is damaging to the mucosa. In the present study, we have tested whether lyso-PC and/or sPLA2 have direct damaging effects on the hydrophobic barriers of synthetic and mucosal surfaces. Rats were administered LPS …

Progressive Regression Of Left Ventricular Hypertrophy Two Years After Bariatric Surgery, Mohamed F Algahim, Thomas R Lux, Joshua G Leichman, Anthony F Boyer, Charles C Miller, Susan T Laing, Erik B Wilson, Terry Scarborough, Sherman Yu, Brad Snyder, Carol Wolin-Riklin, Ursula G Kyle, Heinrich Taegtmeyer

Faculty, Staff and Student Publications

BACKGROUND: Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass.

METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic …

Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment For Cellular Physiology, Michael J Byrne, M Neal Waxham, Yoshihisa Kubota

Faculty, Staff and Student Publications

In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into …

Thoracic Aortic Disease In Tuberous Sclerosis Complex: Molecular Pathogenesis And Potential Therapies In Tsc2+/- Mice, Jiumei Cao, Limin Gong, Dong-Chuan Guo, Ulrike Mietzsch, Shao-Qing Kuang, Callie S Kwartler, Hazim Safi, Anthony Estrera, Michael J Gambello, Dianna M Milewicz

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is a genetic disorder with pleiotropic manifestations caused by heterozygous mutations in either TSC1 or TSC2. One of the less investigated complications of TSC is the formation of aneurysms of the descending aorta, which are characterized on pathologic examination by smooth muscle cell (SMC) proliferation in the aortic media. SMCs were explanted from Tsc2(+/-) mice to investigate the pathogenesis of aortic aneurysms caused by TSC2 mutations. Tsc2(+/-) SMCs demonstrated increased phosphorylation of mammalian target of rapamycin (mTOR), S6 and p70S6K and increased proliferation rates compared with wild-type (WT) SMCs. Tsc2(+/-) SMCs also had reduced expression of …

Perfusion In Rat Brain At 7 T With Arterial Spin Labeling Using Fair-Truefisp And Quipss, Emilio Esparza-Coss, Jarek Wosik, Ponnada A Narayana

Faculty, Staff and Student Publications

Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling is reported. A flow-sensitive alternating recovery sequence, coupled with a balanced gradient fast imaging with steady-state precession readout section was used to minimize ghosting and geometric distortions, while achieving high signal-to-noise ratio. The quantitative imaging of perfusion using a single subtraction method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the …