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Lyden P.,Cedars Sinai Medical Center | Lyden P.,University of California at San Diego | Ernstrom K.,University of California at San Diego | Cruz-Flores S.,St Louis University Medical Center | And 7 more authors.
Neurocritical Care | Year: 2012

Background: Therapeutic hypothermia is a promising neuroprotective therapy with multiple mechanisms of action. We demonstrated the feasibility of thrombolysis combined with endovascular hypothermia, but not all patients achieved effective cooling. We sought to identify the factors that determined effective cooling. Methods: In 26 patients who underwent endovascular hypothermia, we computed four measures of effective cooling: time to reach target; Area-Under-the-Curve (AUC) 34 ratio; AUC-34; and AUC-35. By multivariate regression, we examined the effects of age, weight, starting temperature, body mass index, body surface area (BSA), gender, shivering, and total meperidine dose on the four outcome measures. Results: In univariate analyses, all four outcome measures were significantly influenced by BSA (p < 0.01 in all univariate analyses). Time to reach target temperature was quicker in older patients (p < 0.01). Shivering and meperidine dose were highly intercorrelated (r = 0.6, p < 0.01) and both marginally influenced all four outcome measures. In multivariate analysis, AUC ratio and time to reach target temperature were significantly influenced by BSA (p < 0.01) and meperidine (p < 0.05); AUC-34 was influenced only by BSA (p < 0.01). The AUC-35 was influenced by BSA (p < 0.01), shivering, and total meperidine dose (p < 0.05). Conclusions: The most important determinant of effective cooling during endovascular hypothermia is BSA; larger patients are more difficult to cool and maintain in therapeutic range. Older patients cool more quickly. Shivering was well controlled by the combination of meperidine, buspirone, and surface counter-warming and only minimally influenced cooling effectiveness. Future trials of therapeutic hypothermia may include added measures to cool larger patients more effectively. © Springer Science+Business Media, LLC 2012.

Balucani C.,SUNY Downstate Medical Center | Balucani C.,University of Perugia | Grotta J.C.,UTHealth Medical School
Neurology | Year: 2012

There is a great need for new treatments for acute ischemic stroke that will achieve greater rates of arterial recanalization and increase the population of patients who may benefit. Of several approaches under investigation, intra-arterial therapy (IAT) is the farthest along in clinical development, but experience has shown that the increased rates of recanalization achieved are not always translated to improved patient outcomes. Proper patient selection, allied to efficient strategies aiming at faster recanalization and reperfusion, may result in better clinical outcomes and more rational use of therapeutic resources. While high-tech multimodal imaging has the great promise of identifying hypoperfused but still viable brain tissue, a number of clues suggest that relatively low-tech approaches similar to those that were used to demonstrate the efficacy of systemic thrombolysis, and which have emphasized the key role of time and clinical factors such as age, glucose, stroke severity, and infarct on noncontrast CT scan, deserve greater study as an efficient way to optimize IAT. Eventually it will be a combination of predictors that will enable us to most precisely identify the best patients for IAT and any other new revascularization therapies. Copyright © 2012 by AAN Enterprises, Inc.

Barbosa I.G.,Federal University of Minas Gerais | Machado-Vieira R.,University of Sao Paulo | Machado-Vieira R.,U.S. National Institutes of Health | Soares J.C.,UTHealth Medical School | Teixeira A.L.,Federal University of Minas Gerais
NeuroImmunoModulation | Year: 2014

Bipolar disorder (BD) is a psychiatric condition associated with elevated frequency of clinical comorbidities and cognitive impairment. The neurobiology of BD is not completely understood. Recent evidence has implicated immune dysfunction in its physiopathology. Here, we review several data supporting the presence of immunological dysfunction in BD: (i) increased frequency of autoimmune diseases; (ii) distinct immune cell profile; (iii) release of/altered cytokines by stimulated mononuclear cells; (iv) elevated levels of circulating immune markers, and (v) inflammatory changes in the central nervous system. We also discuss the interplay between immunological dysfunction and neuroprogression in BD. © 2014 S. Karger AG, Basel.

Northrup T.F.,University of Texas Health Science Center at Houston | Khan A.M.,UTHealth Medical School | Jacob P.,University of California at San Francisco | Benowitz N.L.,University of California at San Francisco | And 4 more authors.
Tobacco Control | Year: 2015

Background Tobacco has regained the status of the world's number two killer behind heart/vascular disease. Thirdhand smoke (THS) residue and particles from secondhand smoke (SHS) are suspected health hazards (eg, DNA damage) that are likely to contribute to morbidity and mortality, especially in vulnerable children. THS is easily transported and deposited indoors, where it persists and exposes individuals for months, creating potential health consequences in seemingly nicotine-free environments, particularly for vulnerable patients. We collected THS data to estimate infant exposure in the neonatal ICU (NICU) after visits from household smokers. Infant exposure to nicotine, potentially from THS, was assessed via assays of infant urine. Methods Participants were mothers who smoked and had an infant in the NICU (N=5). Participants provided surface nicotine samples from their fingers, infants' crib/incubator and hospital-provided furniture. Infant urine was analysed for cotinine, cotinine's major metabolite: trans-30-hydroxycotinine (3HC) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the nicotine-derived and tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Results Incubators/cribs and other furniture had detectable surface nicotine. Detectable levels of cotinine, 3HC and NNAL were found in the infants' urine. Discussion THS appears to be ubiquitous, even in closely guarded healthcare settings. Future research will address potential health consequences and THSreduction policies. Ultimately, hospital policies and interventions to reduce THS transport and exposure may prove necessary, especially for immunocompromised children. © 2015 by the BMJ Publishing Group Ltd.

Zhao Z.,UTHealth Medical School | Miki T.,UTHealth Medical School | van Oort-Jansen A.,UTHealth Medical School | Matsumoto T.,UTHealth Medical School | And 2 more authors.
Physiological Genomics | Year: 2011

There is currently much interest in clinical applications of therapeutic hypothermia. Hypothermia can be a consequence of hypometabolism. We have recently established a procedure for the induction of a reversible deep hypometabolic state in mice using 5'-adenosine monophosphate (5'- AMP) in conjunction with moderate ambient temperature. The current study aims at investigating the impact of this technology at the gene expression level in a major metabolic organ, the liver. Our findings reveal that expression levels of the majority of genes in liver are not significantly altered by deep hypometabolism. However, among those affected by hypometabolism, more genes are differentially upregulated than downregulated both in a deep hypometabolic state and in the early arousal state. These altered gene expression levels during 5'-AMP induced hypometabolism are largely restored to normal levels within 2 days of the treatment. Our data also suggest that temporal control of circadian genes is largely stalled during deep hypometabolism. © 2011 the American Physiological Society.

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