Cleveland, OH, United States
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Pundik S.,Case Western Reserve University | Xu K.,Cleveland Veterans Affairs Medical Center | Sundararajan S.,Case Western Reserve University | Sundararajan S.,University Hospitals Case Medical Center
Neurology | Year: 2012

Energy production for the maintenance of brain function fails rapidly with the onset of ischemia and is reinstituted with timely reperfusion. The key bioenergetic organelle, the mitochondrion, is strongly affected by a cascade of events occurring with ischemia and reperfusion. Enhanced production of reactive oxygen species, disruption of calcium homeostasis, and an inflammatory response are induced by reperfusion and have a profound effect on cellular bioenergetics in reversible stroke. The impact of perturbed bioenergetics on cellular homeostasis/function during and after ischemia are discussed. Because mitochondrial function can be compromised by derangements at more than one of the susceptible sites on this organelle, we propose that a combination therapy is needed for the restoration and maintenance of cellular bioenergetics after reperfusion. © 2012 American Academy of Neurology.


Otter J.A.,Imperial College London | Donskey C.,Cleveland Veterans Affairs Medical Center | Yezli S.,Global Center for Mass Gatherings Medicine | Douthwaite S.,King's College London | And 2 more authors.
Journal of Hospital Infection | Year: 2016

Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings. © 2015 The Healthcare Infection Society.


Weintraub D.,University of Pennsylvania | Weintraub D.,Mental Illness and Parkinsons Disease Research | Chen P.,Cleveland Veterans Affairs Medical Center | Chen P.,Case Western Reserve University | And 3 more authors.
Archives of Neurology | Year: 2011

Background: Antipsychotic (AP) use is common in Parkinson disease (PD), but APs can worsen parkinsonism, evidence for efficacy is limited, and use in patients with dementia increases mortality. Objective: To examine the frequency and characteristics, including changes over time, of AP use in a large cohort of patients with PD. Design: Using Veterans Affairs data from fiscal year (FY) 2008, rates and predictors of AP prescribing were determined for patients with PD and psychosis stratified by dementia status (N=2597) and a comparison group of patients with dementia and psychosis without PD (N=6907). Fiscal year 2008 and FY2002 data were compared to examine changes in AP prescribing over time. Setting: Department of Veterans Affairs outpatient facilities. Participants: Outpatients with PD and psychosis and outpatients without PD with dementia and psychosis, all receiving care at Veterans Affairs facilities in FY2002 and FY2008. Main Outcome Measure: Antipsychotic prescribing, including overall, class, and specific medications. Results: In FY2008, 50% of patients with PD having a diagnosis of psychosis were prescribed an AP. Among treated patients, the atypical AP quetiapine was most frequently prescribed (66%), but approximately 30% received high-potency APs. Clozapine was rarely prescribed (<2%). In multivariate models, diagnoses of PD and dementia were associated with AP use. Comparing FY2008 with FY2002, AP use in PD was unchanged, with decreases in risperidone and olanzapine use offset by an increase in quetiapine prescribing and the introduction of aripiprazole. Conclusions: Half of the patients with PD and psychosis receive APs, not uncommonly high-potency agents associated with worsening parkinsonism, and frequency of use has been unchanged since the "black box" warning for AP use in patients with dementia was issued. Recent trends are a shift to quetiapine use and the common use of aripiprazole. As psychosis and dementia are frequently comorbid in PD, safety risks associated with AP use in this population need to be assessed. ©2011 American Medical Association. All rights reserved.


Stiefel U.,Research Service | Stiefel U.,Cleveland Veterans Affairs Medical Center | Cadnum J.L.,Research Service | Eckstein B.C.,Research Service | And 4 more authors.
Infection Control and Hospital Epidemiology | Year: 2011

In a study of 40 methicillin-resistant Staphylococcus aureus (MRSA) carriers, hand contamination was equally likely after contact with commonly examined skin sites and commonly touched environmental surfaces in patient rooms (40% vs 45%). These findings suggest that contaminated surfaces may be an important source of MRSA transmission. © 2011 by the Society for Healthcare Epidemiology of America. All rights reserved.


Guerrero D.M.,Case Western Reserve University | Becker J.C.,Cleveland Veterans Affairs Medical Center | Eckstein E.C.,Cleveland Veterans Affairs Medical Center | Kundrapu S.,Case Western Reserve University | And 5 more authors.
Journal of Hospital Infection | Year: 2013

Asymptomatic carriage of Clostridium difficile is common in hospitals, but the risk for transmission by carriers is unclear. In this point prevalence culture survey of asymptomatic hospitalized patients, 18 of 149 (12%) were carriers of toxigenic C. difficile. By comparison with C. difficile infection (CDI) patients, the prevalence of skin and/or environmental contamination was significantly lower in asymptomatic carriers (3/18, 17% versus 5/6, 83%; P=0.007), but carriers outnumbered CDI patients in the hospital by a factor of 3 to 1. These data suggest that asymptomatic carriers have the potential to contribute to C. difficile transmission in hospitals. © 2013.


Dumford III D.,University Hospitals of Cleveland | Suwantarat N.,University Hospitals of Cleveland | Bhasker V.,University Hospitals of Cleveland | Kundrapu S.,Case Western Reserve University | And 6 more authors.
Infection Control and Hospital Epidemiology | Year: 2013

Design. We conducted an investigation after identifying a cluster of 4 serious infections following transrectal ultrasound-guided biopsy of the prostate (TRUBP) during a 2-month period. Setting. Veterans Affairs medical center. Patients. Patients with urinary tract infection (UTI) after TRUBP and time-matched controls with no evidence of infection. Methods. The incidence of UTI within 30 days after TRUBP was calculated from 2002 through 2010. We evaluated the correlation between infection with fluoroquinolone-resistant gram-negative bacilli (GNB) and fluoroquinolone resistance in outpatient Escherichia coli urinary isolates and performed a case-control study to determine risk factors for infection with fluoroquinolone-resistant GNB. Processes for TRUBP prophylaxis, procedures, and equipment sterilization were reviewed. Results. An outbreak of UTI due to fluoroquinolone-resistant E. coli after TRUBP began 2 years before the cluster was identified and was correlated with increasing fluoroquinolone resistance in outpatient E. coli. No deficiencies were identified in equipment processing or biopsy procedures. Fluoroquinolone-resistant E. coli UTI after TRUBP was independently associated with prior infection with fluoroquinolone- resistant GNB (adjusted odds ratio, 20.8; P=.005). A prediction rule including prior UTI, hospitalization in the past year, and previous infection with fluoroquinolone-resistant GNB identified only 17 (49%) of 35 cases. Conclusions. The outbreak of fluoroquinolone-resistant E. coli infections after TRUBP closely paralleled rising rates of fluoroquinolone resistance among outpatient E. coli isolates. The delayed detection of the outbreak and the absence of sensitive predictors of infection suggest that active surveillance for infection after TRUBP is necessary in the context of increasing fluoroquinolone resistance in the United States. © 2013 by The Society for Healthcare Epidemiology of America. All rights reserved.


Berger D.S.,Cleveland Clinic | Berger D.S.,Montefiore Medical Center | Moyer M.,Cleveland Veterans Affairs Medical Center | Kliment G.M.,Cleveland Clinic | And 3 more authors.
PLoS ONE | Year: 2011

Background: CUG-BP and ETR-3-like factor (CELF) proteins regulate tissue- and developmental stage-specific alternative splicing in striated muscle. We previously demonstrated that heart muscle-specific expression of a nuclear dominant negative CELF protein in transgenic mice (MHC-CELFΔ) effectively disrupts endogenous CELF activity in the heart in vivo, resulting in impaired cardiac function. In this study, transgenic mice that express the dominant negative protein under a skeletal muscle-specific promoter (Myo-CELFΔ) were generated to investigate the role of CELF-mediated alternative splicing programs in normal skeletal muscle. Methodology/Principal Findings: Myo-CELFΔ mice exhibit modest changes in CELF-mediated alternative splicing in skeletal muscle, accompanied by a reduction of endomysial and perimysial spaces, an increase in fiber size variability, and an increase in slow twitch muscle fibers. Weight gain and mean body weight, total number of muscle fibers, and overall muscle strength were not affected. Conclusions/Significance: Although these findings demonstrate that CELF activity contributes to the normal alternative splicing of a subset of muscle transcripts in vivo, the mildness of the effects in Myo-CELFΔ muscles compared to those in MHC-CELFΔ hearts suggests CELF activity may be less determinative for alternative splicing in skeletal muscle than in heart muscle. Nonetheless, even these small changes in CELF-mediated splicing regulation were sufficient to alter muscle organization and muscle fiber properties affected in myotonic dystrophy. This lends further evidence to the hypothesis that dysregulation of CELF-mediated alternative splicing programs may be responsible for the disruption of these properties during muscle pathogenesis. © 2011 Berger et al.


Sethi A.K.,Cleveland Veterans Affairs Medical Center | Al-Nassir W.N.,Cleveland Veterans Affairs Medical Center | Nerandzic M.M.,Case Western Reserve University | Bobulsky G.S.,Case Western Reserve University | And 2 more authors.
Infection Control and Hospital Epidemiology | Year: 2010

background. Current guidelines for control of Clostridium difficile infection (CDI) suggest that contact precautions be discontinued after diarrhea resolves. However, limited information is available regarding the frequency of skin contamination and environmental shedding of C. difficile during and after treatment. design. We conducted a 9-month prospective, observational study involving 52 patients receiving therapy for CDI. Stool samples, skin (chest and abdomen) samples, and samples from environmental sites were cultured for C. difficile before, during, and after treatment. Polymerase chain reaction ribotyping was performed to determine the relatedness of stool, skin, and environmental isolates. results. Fifty-two patients with CDI were studied. C. difficile was suppressed to undetectable levels in stool samples from most patients during treatment; however, 1-4 weeks after treatment, 56% of patients who had samples tested were asymptomatic carriers of C. difficile. The frequencies of skin contamination and environmental shedding remained high at the time of resolution of diarrhea (60% and 37%, respectively), were lower at the end of treatment (32% and 14%, respectively), and again increased 1-4 weeks after treatment (58% and 50%, respectively). Skin and environmental contamination after treatment was associated with use of antibiotics for non-CDI indications. Ninety-four percent of skin isolates and 82% of environmental isolates were genetically identical to concurrent stool isolates. conclusions. Skin contamination and environmental shedding of C. difficile often persist at the time of resolution of diarrhea, and recurrent shedding is common 1-4 weeks after therapy. These results provide support for the recommendation that contact precautions be continued until hospital discharge if rates of CDI remain high despite implementation of standard infection-control measures. © 2009 by The Society for Healthcare Epidemiology of America.


Suwantarat N.,University Hospitals of Cleveland | Dumford III D.M.,University Hospitals of Cleveland | Ponce-Terashima R.,University Hospitals of Cleveland | Kundrapu S.,University Hospitals of Cleveland | And 4 more authors.
Infection Control and Hospital Epidemiology | Year: 2013

For patients undergoing transrectal ultrasound-guided biopsy of the prostate (TRUBP), use of rectal screening culture results to guide antimicrobial prophylaxis was effective for prevention of fluoroquinolone-resistant Escherichia coli infections. In practice, elimination of infections after TRUBP required the rectal screening protocol and addition of gentamicin for patients missing prior screening. © 2013 by The Society for Healthcare Epidemiology of America. All rights reserved.


Kil W.J.,Cleveland Veterans Affairs Medical Center | Kulasekere C.,Cleveland Veterans Affairs Medical Center | Derrwaldt R.,Cleveland Veterans Affairs Medical Center | Bugno J.,Cleveland Veterans Affairs Medical Center | Hatch C.,Cleveland Veterans Affairs Medical Center
Oncotarget | Year: 2016

Purpose: To assess changes in oral cavity (OC) shapes and radiation doses to tongue with different tongue positions during intensity-modulated radiation therapy (IMRT) in patients with head and neck squamous cell carcinoma (HNSCC) but who refused or did not tolerate an intraoral device (IOD), such as bite block, tongue blade, or mouthpiece. Results: Tongue volume outside of OC was 7.1 ± 3.8 cm3 (5.4 ± 2.6% of entire OC and 7.8 ± 3.1% of oral tongue) in IMRT-S. Dmean of OC was 34.9 ± 8.0 Gy and 31.4 ± 8.7 Gy with IMRT-N and IMRT-S, respectively (p < 0.001). OC volume receiving ≥ 36 Gy (V36) was 40.6 ± 16.9% with IMRT-N and 33.0 ± 17.0% with IMRT-S (p < 0.001). Dmean of tongue was 38.1 ± 7.9 Gy and 32.8 ± 8.8 Gy in IMRT-N and IMRT-S, respectively (p < 0.001). V15, V30, and V45 of tongue were significantly lower in IMRT-S (85.3 ± 15.0%, 50.6 ± 16.2%, 24.3 ± 16.0%, respectively) than IMRT-N (94.4 ± 10.6%, 64.7 ± 16.2%, 34.0 ± 18.6%, respectively) (all p < 0.001). Positional offsets of tongue during the course of IMRT-S was -0.1 ± 0.2 cm, 0.01 ± 0.1 cm, and -0.1 ± 0.2 cm (vertical, longitudinal, and lateral, respectively). Methods: 13 patients with HNSCC underwent CT-simulations both with a neutral tongue position and a stick-out tongue for IMRT planning (IMRT-N and IMRT-S, respectively). Planning objectives were to deliver 70 Gy, 63 Gy, and 56 Gy in 35 fractions to 95% of PTVs. Radiation Therapy Oncology Group (RTOG) recommended dose constraints were applied. Data are presented as mean ± standard deviation and compared using the student t-test. Conclusions: IMRT-S for patients with HNSCC who refused or could not tolerate an IOD has significant decreased radiation dose to the tongue than IMRT-N, which may potentially reduce RT related toxicity in tongue in selected patients.

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