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1.
PLoS One ; 9(4): e91437, 2014.
Article in English | MEDLINE | ID: mdl-24743685

ABSTRACT

OBJECTIVES: A recent genome wide association study (GWAS) by LeMaire et al. found that two single nucleotide polymorphisms (SNPs), rs2118181 and rs10519177 in the FBN-1 gene (encoding Fibrillin-1), were associated with thoracic aortic dissection (TAD), non-dissecting thoracic aortic aneurysm (TAA), and thoracic aortic aneurysm or dissection (TAAD); the largest effect was observed for the association of rs2118181 with TAD. We investigated whether rs2118181 and rs10519177 were associated with TAD, TAA, and TAAD in the Yale study. METHODS: The genotypes of rs2118181 and rs10519177 were determined for participants in the Yale study: 637 TAAD cases (140 TAD, 497 TAA) and 275 controls from the United States, Hungary, and Greece. The association of the genotypes with TAD, TAA and TAAD were assessed using logistic regression models adjusted for sex, age, study center and hypertension. RESULTS AND CONCLUSIONS: In the Yale study, rs2118181 was associated with TAD: compared with non-carriers, carriers of the risk allele had an unadjusted odds ratio for TAD of 1.80 (95% CI 1.15-2.80) and they had odds ratio for TAD of 1.87 (95% CI 1.09-3.20) after adjusting for sex, age, study center and hypertension. We did not find significant differences in aortic size, a potential confounder for TAD, between rs2118181 risk variant carriers and non-carriers: mean aortic size was 5.56 (95% CI: 5.37-5.73) for risk variant carriers (CC+CT) and was 5.48 (95% CI: 5.36-5.61) for noncarriers (TT) (p = 0.56). rs2118181 was not associated with TAA or TAAD. rs10519177 was not associated with TAD, TAA, or TAAD in the Yale study. Thus, the Yale study provided further support for the association of the FBN-1 rs2118181SNP with TAD.


Subject(s)
Aortic Aneurysm, Thoracic/genetics , Aortic Dissection/genetics , Genetic Predisposition to Disease/genetics , Microfilament Proteins/genetics , Polymorphism, Single Nucleotide , Female , Fibrillin-1 , Fibrillins , Gene Frequency , Humans , Male , Middle Aged
2.
J Neurointerv Surg ; 4(2): 130-3, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21990455

ABSTRACT

BACKGROUND: The neuroprotective effects of cooling the spinal cord in a sheep model by a self-contained intrathecal catheter was reported recently by the authors. The present study was designed to determine if cooling catheters in the lateral ventricles of the brain can effectively cool the CSF and thereby reduce brain temperature while maintaining systemic normothermia. METHODS: The cooling catheter is a self-contained system that circulates a cold fluid and cools the CSF that circulates in the brain. The CSF in turn cools the surrounding brain by conduction. Burr holes were made in the skull and the catheter was placed into the lateral ventricles using the standard method for placement of ventriculostomy catheters. To monitor the cooling effect, four temperature probes were placed in the brain (left and right hemispheres of the brain in anterior and posterior locations to the ventricles). RESULTS: Five experiments were successfully completed. The mean brain temperature for all sheep decreased to 34.5°C (mean) during the 3 h cooling period (9.7% reduction from baseline brain temperature of 38.2°C). Cooling fluid was circulated through the catheter at a rate of 50 ml/min. The lowest achieved brain temperature during cooling was 26.7°C. When cooling was stopped, the brain temperature readings equilibrated with the core temperature promptly. Post mortem examination of the brains showed no morphologic changes under gross or histologic examinations. CONCLUSION: Localized cooling of the brain to moderate hypothermic levels while maintaining relative systemic normothermia was demonstrated in an animal model with intraventricular cooling catheters.


Subject(s)
Brain Injuries/therapy , Catheterization/methods , Hypothermia, Induced/methods , Ventriculostomy/methods , Animals , Brain Injuries/physiopathology , Catheters , Hypothermia, Induced/instrumentation , Lateral Ventricles/physiopathology , Models, Animal , Sheep , Ventriculostomy/instrumentation
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