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Hawwa N.,Medicine Institute | Schreiber Jr. M.J.,Glickman Urological and Kidney Institute | Tang W.H.W.,Cleveland Clinic
Current Heart Failure Reports | Year: 2013

Chronic kidney disease (CKD) significantly increases cardiovascular morbidity and mortality. CKD remains an under-represented population in cardiovascular clinical trials, and cardiovascular disease is an under-treated entity in CKD. Traditional cardiovascular risk factors in conjunction with uremia-related complications often progress to myocardial dysfunction. Such uremic cardiomyopathy leads to over-activation of neurohormonal pathways with detrimental effects. Management of the reno-cardiac syndrome (RCS) requires the targeting of these multiple facets. In this article we discuss the relevant pathophysiology of RCS, and present the clinical data related to its management. © 2012 Springer Science+Business Media New York. Source

Nagarajan V.,Medicine Institute | Cauthen C.A.,Cleveland Clinic | Starling R.C.,Cleveland Clinic | Tang W.H.W.,Cleveland Clinic
Congestive Heart Failure | Year: 2013

Obese patients have been noted to have better prognosis in many conditions including heart failure. We hypothesize that this favorable prognosis for obesity may not be seen in patients with morbid obesity and advanced heart failure. A total of 501 consecutive patients with advanced heart failure referred for heart transplant evaluation to the Cleveland Clinic were studied. Patients were categorized into 3 groups based on their body mass index score as nonobese (≤30 kg/m2), obese (30.1-40 kg/m2), and morbidly obese (≥40 kg/m2). There were fewer cardiovascular risk factors in the morbidly obese group. Unadjusted event-free survival rates were 48.4%, 57.4%, and 28.6% in the nonobese, obese, and morbidly obese groups, respectively (P=.02). In univariate analysis, both the nonobese group (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09-1.91; P=.01) and the morbidly obese group (HR, 2.46; 95% CI, 1.40-4.30; P=.002) had significantly higher risk of all-cause mortality/transplantation compared with the obese group. This difference persisted in multivariate analysis after adjustment for confounding factors. Our study re-emphasizes the presence of an obesity paradox even in patients with very advanced heart failure. This favorable prognosis, however, may not be relevant in patients with morbidly obesity. Cardiovascular risk factors may not contribute to this phenomenon. © 2013 Wiley Periodicals, Inc. Source

Kurada S.,Medicine Institute | Alkhouri N.,Cleveland Clinic | Fiocchi C.,Digestive Disease Institute | Fiocchi C.,Cleveland Clinic Lerner Research Institute | And 3 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2015

Background There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease. Aim Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD. Methods A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed. Results Mean breath pentane, ethane, propane, 1-octene, 3-methylhexane, 1-decene and NO levels were elevated (P < 0.05 to P < 10-7) and mean breath 1-nonene, (E)-2-nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)-2-nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin-1β showed an inverse relation with clinical disease activity. Conclusions Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well-designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD. © 2014 John Wiley & Sons Ltd. Source

Dutta R.,Cleveland Clinic | Chang A.,Cleveland Clinic | Doud M.K.,Cleveland Clinic | Kidd G.J.,Cleveland Clinic | And 6 more authors.
Annals of Neurology | Year: 2011

Objective: Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system. Although the clinical impact of gray matter pathology in MS brains is unknown, 30 to 40% of MS patients demonstrate memory impairment. The molecular basis of this memory dysfunction has not yet been investigated in MS patients. Methods: To investigate possible mechanisms of memory impairment in MS patients, we compared morphological and molecular changes in myelinated and demyelinated hippocampi from postmortem MS brains. Results: Demyelinated hippocampi had minimal neuronal loss but significant decreases in synaptic density. Neuronal proteins essential for axonal transport, synaptic plasticity, glutamate neurotransmission, glutamate homeostasis, and memory/learning were significantly decreased in demyelinated hippocampi, but not in demyelinated motor cortices from MS brains. Interpretation: Collectively, these data support hippocampal demyelination as a cause of synaptic alterations in MS patients and establish that the neuronal genes regulated by myelination reflect specific functions of neuronal subpopulations. Copyright © 2010 American Neurological Association. Source

Husseinzadeh H.D.,Medicine Institute | Garcia J.A.,Cleveland Clinic
Current Clinical Pharmacology | Year: 2011

Inhibitors of the mammalian target of rapamycin (mTOR) have entered the landscape of treatment for advanced RCC. Their development has been based on their unique biology and their potential to simultaneously inhibit both tumor cell proliferation and angiogenesis. Despite the solid biologic rationale for their development, existing clinical data is somewhat mixed. Although Temsirolimus is capable of improving overall survival it does so only in a minority of selected mRCC patients and its effects on tumor burden reduction and PFS are minimal. Similarly the activity and clinical utility of Everolimus in the refractory setting is questionable. First, because it is unknown if mTOR becomes the major driver or cancer growth after developing progressive disease on a VEGF inhibitor and secondly because existing sequential VEGF data in same setting appears to be the same if not a bit more robust to that reported with Everolimus. Combination of mTOR and VEGF inhibitors has been disappointing due to the excessive toxicities encountered in early trials without a noticeable difference in efficacy. Efforts are now placed in a series of novel compounds capable of inhibiting both mTOR and the upstream signaling pathway of PI3K/AKT. © 2011 Bentham Science Publishers. Source

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