Bhatia N.S.,Illinois Neurological Institute |
Sampath R.,Ibis Biosciences |
Ranken R.,Ibis Biosciences |
Rounds M.A.,Ibis Biosciences |
And 3 more authors.
Journal of Clinical Microbiology | Year: 2012
We describe the utility of PCR and electrospray ionization with mass spectrometry (PCR/ESI-MS) of culture-negative cerebrospinal fluid (CSF) in order to identify Gram-positive cocci noted on a Gram stain of CSF from a previously healthy 26-year-old man with community-acquired pneumonia (CAP) and multiple brain abscesses. CSF samples were obtained 2 weeks apart, first by lumbar puncture and 2 weeks later from an external ventricular drain that was inserted into the right ventricle. Both CSF cultures were negative. A Gram stain of bronchoalveolar lavage (BAL) fluid was notable for many Gram-positive cocci (GPC), but cultures of BAL fluid and subcarinal lymph node biopsy tissue were negative. PCR/ESI-MS detected Streptococcus intermedius, a common cause of brain abscesses, in both CSF samples as well as in the fixed tissue from the biopsy. This unique case confirms S. intermedius pulmonary infection as the source of metastatic CNS infection and reveals the potential of PCR/ESI-MS to detect a streptococcal pathogen not captured by conventional cultures. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Learmonth Y.C.,University of Illinois at Urbana - Champaign |
Motl R.W.,University of Illinois at Urbana - Champaign |
Sandroff B.M.,University of Illinois at Urbana - Champaign |
Pula J.H.,Illinois College |
And 2 more authors.
BMC Neurology | Year: 2013
Background: The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research. This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes.Methods: 96 persons with MS provided demographic/clinical information, completed the PDDS and other PROs including the Multiple Sclerosis Walking Scale-12 (MSWS-12), and underwent a neurological examination for generating FS and EDSS scores. Participants completed assessments of cognition, ambulation including the 6-minute walk (6 MW), and wore an accelerometer during waking hours over seven days.Results: There was a strong correlation between EDSS and PDDS scores (ρ = .783). PDDS and EDSS scores were strongly correlated with Pyramidal (ρ = .578 & ρ = .647, respectively) and Cerebellar (ρ = .501 & ρ = .528, respectively) FS scores as well as 6 MW distance (ρ = .704 & ρ = .805, respectively), MSWS-12 scores (ρ = .801 & ρ = .729, respectively), and accelerometer steps/day (ρ = -.740 & ρ = -.717, respectively).Conclusion: This study provides novel evidence supporting the PDDS as valid PRO of disability in MS. © 2013 Learmonth et al.; licensee BioMed Central Ltd.
Crockett C.D.,University of Iowa |
Ruggieri A.,Hospital for Sick Children |
Gujrati M.,Illinois College |
Zallek C.M.,Illinois Neurological Institute |
And 3 more authors.
Muscle and Nerve | Year: 2014
Introduction: X-linked myopathy with excessive autophagy (XMEA) is characterized by autophagic vacuoles with sarcolemmal features. Mutations in VMA21 result in insufficient lysosome acidification, causing progressive proximal weakness with onset before age 20 years and loss of ambulation by middle age. Methods: We describe a patient with onset of slowly progressive proximal weakness of the lower limbs after age 50, who maintains ambulation with the assistance of a cane at age 71. Results: Muscle biopsy at age 66 showed complex muscle fiber splitting, internalized capillaries, and vacuolar changes characteristic of autophagic vacuolar myopathy. Vacuoles stained positive for sarcolemmal proteins, LAMP2, and complement C5b-9. Ultrastructural evaluation further revealed basal lamina reduplication and extensive autophagosome extrusion. Sanger sequencing identified a known pathologic splice site mutation in VMA21 (c.164-7T>G). Conclusions: This case expands the clinical phenotype of XMEA and suggests VMA21 sequencing be considered in evaluating men with LAMP2-positive autophagic vacuolar myopathy. © 2014 Wiley Periodicals, Inc.
Velpula K.K.,Illinois Neurological Institute |
Bhasin A.,Illinois Neurological Institute |
Asuthkar S.,Illinois Neurological Institute |
Tsung A.J.,Illinois Neurological Institute |
Tsung A.J.,Illinois College
Cancer Research | Year: 2013
Glioblastoma multiforme is the most aggressive primary brain tumor in adults. Overexpression of the EGF receptor (EGFR) is recognized as a widespread oncogenic signature in glioblastoma multiforme, but the complexity of its contributions is not fully understood, nor the most effective ways to leverage anti-EGFR therapy in this setting. Hypoxia is known to drive the aggressive character of glioblastoma multiforme by promoting aerobic glycolysis rather than pyruvate oxidation carried out in mitochondria (OXPHOS), a phenomenon termed the Warburg effect, which is a general feature of oncogenesis. In this study, we report that hypoxia drives expression of the pyruvate dehydrogenase kinase (PDK1) and EGFR along with the hypoxiainducing factor (HIF)-1a in human glioblastoma multiforme cells. PDK1 is a HIF-1-regulated gene and our findings indicated that hypoxia-induced PDK1 expression may promote EGFR activation, initiating a feedforward loop that can sustain malignant progression. RNAi-mediated attenuation of PDK1 and EGFR lowered PDK1-EGFR activation and decreased HIF-1a expression, shifting the Warburg phenotype to OXPHOS and inhibiting glioblastoma multiforme growth and proliferation. In clinical specimens of glioblastoma multiforme, we found that immunohistochemical expression of PDK1, EGFR, and HIF-1a were elevated in glioblastoma multiforme specimens when compared with normal brain tissues. Collectively, our studies establish PDK1 as a key driver and candidate therapeutic target in glioblastoma multiforme. © 2013 American Association for Cancer Research.
Velpula K.K.,Illinois College |
Dasari V.R.,Illinois College |
Asuthkar S.,Illinois College |
Gorantla B.,Illinois College |
Tsung A.J.,Illinois Neurological Institute
Translational Oncology | Year: 2012
Receptor tyrosine kinases (RTK) and their ligands control critical biologic processes, such as cell proliferation, migration, and differentiation. Aberrant expression of these receptor kinases in tumor cells alters multiple downstream signaling cascades that ultimately drive the malignant phenotype by enhancing tumor cell proliferation, invasion, metastasis, and angiogenesis. As observed in human glioblastoma (hGBM) and other cancers, this dysregulation of RTK networks correlates with poor patient survival. Epidermal growth factor receptor (EGFR) and c-Met, two well-known receptor kinases, are coexpressed in multiple cancers including hGBM, corroborating that their downstreamsignaling pathways enhance a malignant phenotype. The integration of c-Met and EGFR signaling in cancer cells indicates that treatment regimens designed to target both receptor pathways simultaneously could prove effective, though resistance to tyrosine kinase inhibitors continues to be a substantial obstacle. In the present study, we analyzed the antitumor efficacy of EGFR inhibitors erlotinib and gefitinib and c-Met inhibitor PHA-665752, along with their respective small hairpin RNAs (shRNAs) alone or in combination with human umbilical cord blood stem cells (hUCBSCs), in glioma cell lines and in animal xenograft models.We also measured the effect of dual inhibition of EGFR/c-Met pathways on invasion and wound healing. Combination treatments of hUCBSC with tyrosine kinase inhibitors significantly inhibited invasion and wound healing in U251 and 5310 cell lines, thereby indicating the role of hUCBSC in inhibition of RTK-driven cell behavior. Further, the EGFR and c-Met localization in glioma cells and hGBM clinical specimens indicated that a possible cross talk exists between EGFR and c-Met signaling pathway. © 2012 Neoplasia Press, Inc.
Chelluboina B.,Illinois College |
Klopfenstein J.D.,Illinois College |
Klopfenstein J.D.,Illinois Neurological Institute |
Pinson D.M.,Illinois College |
And 4 more authors.
Stroke | Year: 2015
Background and Purpose - Matrix metalloproteinases (MMPs) have a central role in compromising the integrity of the blood-brain barrier (BBB). The role of MMP-12 in brain damage after ischemic stroke remains unknown. The main objective of the current study is to investigate the effect of MMP-12 suppression at an early time point before reperfusion on the BBB damage in rats. Methods - Sprague-Dawley rats were subjected to middle cerebral artery occlusion and reperfusion. MMP-12 shRNA-expressing plasmids formulated as nanoparticles were administered at a dose of 1 mg/kg body weight. The involvement of MMP-12 on BBB damage was assessed by performing various techniques, including Evans blue dye extravasation, 2,3,5-triphenyltetrazolium chloride staining, immunoblot, gelatin zymography, and immunofluorescence analysis. Results - MMP-12 is upregulated ≈31-, 47-, and 66-fold in rats subjected 1-, 2-, or 4-hour ischemia, respectively, followed by 1-day reperfusion. MMP-12 suppression protected the BBB integrity by inhibiting the degradation of tight-junction proteins. Either intravenous or intra-arterial delivery of MMP-12 shRNA-expressing plasmid significantly reduced the percent Evans blue dye extravasation and infarct size. Furthermore, MMP-12 suppression reduced the endogenous levels of other proteases, such as tissue-type plasminogen activator and MMP-9, which are also known to be the key players involved in BBB damage. Conclusions - These results demonstrate the adverse role of MMP-12 in acute brain damage that occurs after ischemic stroke and, thereby, suggesting that MMP-12 suppression could be a promising therapeutic target for cerebral ischemia. © 2015 American Heart Association, Inc.
Neils D.M.,Illinois Neurological Institute |
Wang H.,Illinois College |
Lin J.,Illinois Neurological Institute
Surgical Neurology International | Year: 2013
Background: Endoscopic third ventriculostomy (ETV) is an effective surgical option for the treatment of shunt malfunction. The role of postoperative cerebrospinal fluid (CSF) diversion is not clearly understood at this time. We compare the effects of shunt-removal/ligation, shunt externalization or external ventricular drain placement, and no treatment to the indwelling shunt at the time of ETV. Methods: We retrospectively reviewed the records of 20 consecutive patients treated at our institution for shunt malfunction with ETV. Patient data were retrospectively evaluated for the effect that the fate of the shunt plays on ETV success rates. Results: In our series of 20 patients we had an overall success rate of 70% with using ETV for shunt malfunction. Patients who had their shunts ligated at the time of surgery had a success rate of 88%, in comparison to those whom the shunt was left untouched who had a success rate of 60%, or patients who had a perioperative external ventricular drain placed the success rate was 50%. Conclusions: This series of ETV for shunt malfunction performed at a single center by a single surgeon shows a success rate similar to the published literature range of 67 to 80 percent success whether the shunt is ligated or left undisturbed. It is not necessary to ligate the in situ shunt at the time of ETV; however, there may be a trend toward an improved success rate with shunt ligation. Further studies with a greater numbers of patients are warranted. Copyright © 2013 Neils MD.
Beck A.R.,Illinois State University |
Thompson J.R.,Illinois State University |
Kosuwan K.,Srinakharinwirot University |
Prochnow J.M.,Illinois Neurological Institute
Journal of Speech, Language, and Hearing Research | Year: 2010
Purpose: Study 1 developed the Assessment of Attitudes Toward Augmentative and Alternative Communication-2 (AATAAC-2) to assess adolescents' attitudes toward peers who use AAC. Study 2 used the AATAAC-2 to examine influences of familiarity with people with disabilities; type of AAC device; and various combinations of gender of rater, AAC user, and communication partner on adolescents' attitudes. Method: In Study 1, 194 adolescents viewed videotapes depicting adolescents using AAC, then completed AATAAC-2. Study 2 utilized 8 videotapes depicting 4 different gender combinations of AAC user and communication partner as experimental stimuli. Each gender combination was filmed twice: once with a static touch screen device, and once with a dynamic touch screen device. One-hundred thirty-six adolescents were randomly assigned to view 1 of the 8 videos. Participants then completed AATAAC-2. Results: Study 1 demonstrated that AATAAC-2 has adequate psychometric properties. Raters' responses in Study 2 indicated no main effect of device type; girls were more positive than boys; and familiarity with peers with disabilities was associated with more positive attitudes. No 2-way interactions were significant; 3-way interaction of level of familiarity, gender, and type of device used was significant. Conclusions: Familiarity and gender contribute to adolescents' attitudes; type of AAC device combined with these factors to influence attitudes © American Speech-Language-Hearing Association.
Ji R.,Beijing Tiantan Hospital |
Wang D.,Illinois Neurological Institute |
Shen H.,University of North Carolina at Chapel Hill |
Pan Y.,Beijing Tiantan Hospital |
And 4 more authors.
Stroke | Year: 2013
BACKGROUND AND PURPOSE - Medical complications are common among patients with stroke. However, little is known about the potential interrelationship among them. In the present study, we aimed to investigate the association between common in-hospital medical complications after acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH). METHODS - We analyzed patients enrolled in the China National Stroke Registry from 2007 to 2008. The occurrence of 11 common stroke-associated medical complications during acute hospitalization was prospectively registered. Multivariable analysis using generalized estimation equation was performed to assess association between medical complications in AIS and ICH cohort, respectively. RESULTS - A total of 14 702 patients with AIS and 5221 patients with ICH were enrolled. The median age was 65 years (interquartile range, 55-74 years), and 38.1% were female. The median length of hospital stay was 14 days (interquartile range, 10-20 days) for AIS and 18 days (interquartile range, 11-26 days) for ICH. Pneumonia was the most common medical complication after AIS (11.4%) and ICH (16.8%). In the AIS cohort, after adjusting for potential confounders, pneumonia was significantly associated with development of gastrointestinal bleeding (adjusted odds ratio [OR], 8.35; 95% confidence interval [CI], 6.27-11.1; P<0.001), decubitus ulcer (adjusted OR, 5.31; 95% CI, 3.39-8.31; P<0.001), deep vein thrombosis (adjusted OR, 4.27; 95% CI, 2.41-7.59; P<0.001), epileptic seizure (adjusted OR, 3.96; 95% CI, 2.67-5.88; P<0.001), urinary tract infection (adjusted OR, 3.34; 95% CI, 2.73-4.10; P<0.001), atrial fibrillation/flutter (adjusted OR, 3.17; 95% CI, 2.58-3.90; P<0.001), and recurrent stroke (adjusted OR, 2.65; 95% CI, 2.07-3.40; P<0.001). Similar significant association between pneumonia and development of several nonpneumonia medical complications was verified in ICH cohort as well. CONCLUSIONS - Pneumonia is closely associated with the development of several nonpneumonia medical complications after AIS and ICH. © 2013 American Heart Association, Inc.
Parker S.,Illinois Neurological Institute |
Ali Y.,Illinois Neurological Institute
Current Cardiology Reports | Year: 2015
When intravenous (IV) tissue-type plasminogen activator (t-PA) was originally approved by the Food and Drug Administration (FDA) for acute ischemic stroke (AIS) in 1996, there was a lengthy list of contraindications. In the 19 years since the approval of t-PA for AIS, it has been used off label and in patients with those contraindications. In February 2015, the list of contraindications for IV t-PA in AIS was revised and several of the previous contraindications were removed. As only 4 % of patients with ischemic stroke receive treatment with IV t-PA, these changes increase the number of patients eligible for treatment. Anytime there is a significant change in the indications and treatment paradigm with a medication, there can be some resistance to the adaptation of the change into physician’s treating habits. We seek to review what the changes to t-PA contraindications are, how they came about, as well as the literature on the previously off-label and currently off-label use of IV t-PA for patients with AIS. © 2015, Springer Science+Business Media New York.