Biomedical subjects

Janice Carrozzella

Publications and source records attributed to Janice Carrozzella.

6 recordsLinked to original sources

PubMed2005

Revascularization end points in stroke interventional trials: recanalization versus reperfusion in IMS-I.

BACKGROUND AND PURPOSE: The acute stroke literature lacks a standard convention regarding the critical end point of revascularization. Two distinct parameters may be clinically important: (1) recanalization of the primary arterial occlusive lesion (AOL) and (2) global reperfusion of the distal vascular bed. We sought to determine their relationship in the Interventional Management of Stroke (IMS) Phase I trial of combined intravenous (IV) and intraarterial (IA) recombinant tissue plasminogen activator. METHODS: Sixty-one angiograms were reanalyzed using recanalization and reperfusion scores. The AOL Score was defined as: 0=no recanalization of the primary occlusion, I=incomplete or partial recanalization of the primary occlusion with no distal flow, II=incomplete or partial recanalization of the primary occlusion with distal flow, or III=complete recanalization of the primary occlusion with distal flow. The Thrombolysis in Myocardial Infarction (TIMI) Score was defined as: 0=no perfusion, 1=perfusion past the initial occlusion but no distal branch filling, 2=perfusion and incomplete or slow distal branch filling, or 3=full perfusion with filling of all distal branches. We compared the 2 scores with one another and with good clinical outcome (modified Rankin Score zero to 2). RESULTS: AOL and TIMI scores showed modest agreement (kappa, 0.30; confidence interval, 0.16 to 0.44). Good clinical outcome was seen in 49% of patients with AOL II/III scores (P=0.055) and 54% with TIMI 2/3 scores (P=0.019). The 2 methods did not significantly differ in predicting outcome (P=0.13). CONCLUSIONS: AOL recanalization and TIMI reperfusion scores comparably predict clinical outcome in this treatment paradigm. Other modalities may show different relationships between these 2 revascularization end points. Future studies should distinguish between these parameters semantically and methodologically.

Acute Disease↗

PubMed2005

Bilirubin production and oxidation in CSF of patients with cerebral vasospasm after subarachnoid hemorrhage.

Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) remains a significant cause of mortality and morbidity; however, the etiology is, as yet, unknown, despite intensive research efforts. Research in this laboratory indicates that bilirubin and oxidative stress may be responsible by leading to formation of bilirubin oxidation products (BOXes), so we investigated changes in bilirubin concentration and oxidative stress in vitro, and in cerebral spinal fluid (CSF) from SAH patients. Non-SAH CSF, a source of heme oxygenase I (HO-1), and blood were incubated, and in vitro bilirubin production measured. Cerebrospinal fluid from SAH patients was collected, categorized using stimulation of vascular smooth muscle metabolism in vitro, and information obtained regarding occurrence of vasospasm in the patients. Cerebral spinal fluid was analyzed for hemoglobin, total protein and bilirubin, BOXes, malonyldialdehyde and peroxidized lipids (indicators of an oxidizing environment), and HO-1 concentration. The formation of bilirubin in vitro requires that CSF is present, as well as whole, non-anti-coagulated blood. Bilirubin, BOXes, HO-1, and peroxidized lipid content were significantly higher in CSF from SAH patients with vasospasm, compared with nonvasospasm SAH CSF, and correlated with occurrence of vasospasm. We conclude that vasospasm may be more likely in patients with elevated BOXes. The conditions necessary for the formation of BOXes are indeed present in CSF from SAH patients with vasospasm, but not CSF from SAH patients without vasospasm.

Adult↗

PubMed2004

Apolipoprotein E isoprotein-specific interactions with tissue plasminogen activator.

Apolipoprotein E (Apo E) is an important genetic risk factor for multiple neurological, vascular and cardiovascular diseases. Previously, we reported Apo E isoprotein-specific modulation of tissue plasminogen activator (tPA) using an in vitro blood-clotting assay. Here, we studied the conformational changes of Apo E2, E3 and E4 in the presence of tPA and vice versa using circular dichroism (CD) and dual polarization interferometry (DPI). We report isoprotein and state-specific intermolecular interactions between the Apo E isoforms and tPA. Apo E2 interaction with immobilized tPA leads to significant conformational changes which are not observed with Apo E3 or E4. Additionally, tPA induces changes in helicity of lipidated Apo E2 whereas no detectable changes were observed in Apo E3 or E4. The Tukey's test for interaction indicated a significant (P < 0.001) interaction between tPA and Apo E2 in the lipidated environment. These results may be important regarding the mechanism by which Apo E has isoprotein-specific effects on many biological processes and diseases involving blood clotting, proteolysis and perfusion.

Apolipoproteins E↗

PubMed2002

Isoforms of apolipoprotein E can modulate tPA-induced clot lysis in vitro.

Apo E, and its respective isoforms, have been linked to outcome and survival in cerebral vascular and cardiovascular diseases. The effectiveness of intravenous tPA in patients with acute ischemic stroke appears to be enhanced in patients who have an Apo E2 phenotype. The ability of Apo E isoproteins (endogenous Apo E isoproteins or exogenous Apo E isoproteins) to modulate tPA-induced clot lysis in vitro was assessed using an in vitro clot assay system. Blood samples were obtained from 18-volunteers with three Apo E genotypes: E2, E3 and E4. tPA-induced clot lysis (0-4 microgram/ml tPA), was assessed in the presence or absence of supplemental Apo E2, E3 or E4 (9.8 microgram/ml). tPA-induced clot lysis was significantly (P equal or less than 0.0001) enhanced by supplementation with Apo E2 (EC50 0.20 0.06 microgram/ml) as compared to tPA alone (0.72 0.19). Apo E4 supplementation caused a significant (P < or = 0.05) inhibition of clot lysis (0.98 0.23), but there was no significant change caused by Apo E3. The genotype of the volunteer did not significantly affect the ability of the supplemental Apo E from modulating tPA-induced clot lysis. We conclude that the administration of Apo E isoproteins can modulate clot lysis in vitro. Our results suggest that the Apo E isoprotein may have an impact on clot dissolution and the effectiveness of thrombolytic therapy.

Apolipoprotein E2↗

PubMed2002

Emergency stroke management: a new era.

This article discusses the recent advances and the current state of treatment of acute stroke. It outlines key components to ensure stroke victims receive emergent treatment in a coordinated and comprehensive healthcare delivery system.

Algorithms↗

PubMed2002

Subarachnoid hemorrhage: a preventable disease with a heritable component.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) caused by ruptured intracranial aneurysm affects approximately 16 000 Americans annually, and almost 40% of affected patients die within 30 days despite the best current therapy. Prevention of SAH is therefore of paramount importance. We present a preliminary analysis of risk factors for SAH from our population-based, case-control study. METHODS: Cases were prospectively collected and matched 2:1 by age, race, and gender to controls using random digit dialing. Personal risk factor history, family history, neuroimaging data, and genetic samples were obtained. Univariate and bivariate analyses were performed and population-attributable risks estimated. Multivariable analysis was performed using conditional logistic regression. RESULTS: Between June 1997 and February 2000, 107 cases and 197 controls were enrolled. In bivariate analyses, a large proportion of population-attributable risk for SAH could be explained by modifiable risk factors: smoking, hypertension, and heavy alcohol use. In multivariable analysis, current cigarette smoking, history of hypertension, frequent alcohol use, lower body mass index, and a family history of a relative with SAH or intracranial aneurysm were found to be significant, independent risk factors for SAH. CONCLUSION: Our data confirm previous reports that SAH clusters within some families independent of environmental risk factors, suggesting that SAH has a significant genetic component. Yet, even among families at increased risk of SAH, smoking cessation, treatment of hypertension, and reduced alcohol intake may substantially decrease SAH risk. The independent associations with heavy alcohol use and low body mass index with SAH may be confounded by smoking and require further study.

Alcoholism↗