$388 Thursday, November 10, 2005 Poster Abstracts

80% (wt/wt) magnetite). Given the high redrculat ion times of t-PA- loaded magnetic spheres in the human circulation, these results are promising and support the concept of magnetically guided, non- invasive, targeted t-PA delivery.

1128 Magnetically guided targeted drug delivery across the blood brain barrier: a mathematical feasibility gtudy

Chen, H 1.~, Kanfinski, MD 2~, Caviness, TL 1,~, Guy, SG ~, Rosengart, A J 1.. 1Departments of Neurology and Surgery" (Neurosurgery), The University of Chicago and Pritzker School of Medicine, Chicago, USA; 2Chemical Engineering Division, Argonne National Laboratory, Argonne, USA; 3Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, USA; 14Collaborative Investigators for Applied Nanotechnology in Medicine * Co-Principal Investigators

We propose a magnetically guided delivery system utilizing designer, biocompatible, and non-toxic superparamagnetic nanoparticles for drug delivery across the blood brain barrier. Different from traditional magnetic drug targeting system, the new approach exploits the use of tfigh gradient magnetic separation (HGMS) within the brain paren- chyma. A small biocompatible, ferromagnetic mesh is implanted into at brain targeting site. An externally applied magnetic field (homo- geneous or gradient) magnetizes the implanted mesh inducing local magnetic distortions and creating relatively high magnetic gradients. Such magnetic gradients can redirect freely circulating medicated magnetic spheres leading to focal concentration of the entrapped drug(s) selectively at the target site. We now present the first feasibility evaluation of such a delivery system and investigated the collection efficiency (CE) of magnetic nanoparricles from capillary flow by studying 1) an implanted ferromagnetic micro-wire mesh (distant to capillaries) plus external magnetic field gradients (homogenous and gradient), and 2) extracranial maguets only, no mesh. The results show that the presence of a ferromagnetic mesh improves CE of nanoparticles into the parenchyma. At the presence of one piece of micro-wire, 25?,'8 and 40?,'8 CE is achieved at 0.5 and 1.0 mm/s local flow velocities, respectively. Envisioning multiple implanted mesh wires the proposed system shows promise for future magnetic drug targeting across the blood brain barrier.

1129 The prevalence of ealdftcation in lntracranial Arteries and its risk factors

Xiang Yan Chen, MD l#, Ka Sing Wong, MD 2, Wynuie W.M. Lain, MD 3, Ho Keung Ng, MD ~. 1Department ofAnawmical & Cellular Pathology, the Chinese University of Hong Kong, Shatin, Hong Kong SAR; 2Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Shatin, Hong Kong SAR; 3Department of Diagnostic Radiology & Organ Imaging, the Chinese University of Hong Kong, Shatin, Hong Kong SAR

Purpose: To investigate the prevalence and location of calcification in intracranial arteries and its risk factors. Methods: All patients referred to PWH for brain CT screening in Dec 2004 were recruited. All patients received a questionnaire regarding their medical history and serum chemistry values. CT examina- tions were done with a 16- slice MDCT (multi-detector-row computed tomography). Results: Four hundred and ninety cases, (mean age, 62.92 years old), were included. There were three hundred and forty cases (69.4%) had intracranial artery caldficarion. The highest prevalence of intracranial artery caldficarion was seen in ICA (60%), followed by in vertebral artery (20%), in MCA (5%) and basilar artery (15%). The cases with calcification were significantly older than those without calcification (p < 0.001). A significantly higher prevalence of calcification were seen among the cases with versus without hypertension (p < 0.001),

diabetes (p < 0.001), renal failure (p < 0.05), atrial fibrillation (iJ < 0.05), smoking (p < 0.05), hyperlipidemia (iJ < 0.001), ischemic heart disease (p < 0.05) and ischemic stroke (p < 0.001). The mean value of serum phosphate, serum urea and CRP level was also significantly lfigher in the cases with intracranial artery calcification (p < 0.05, respectively). Stepwise nmltiple logistic regression (shown in table 3) showed age (RR -- 2.795 per 10 years), a history of ischemic stroke (RR -- 3.915), and white blood cells count (RR -- 1.107) to be independently associated with intracranial artery calcification. Contusions: Vascular calcification occurs frequently in the intracranial arteries. Besides age, lfistory of ischemic stroke and WBC may be also risk factors of intracranial artery calcification.

1130 Atorvastatin protects against Cerebral Infarction via Inhibiting N A D P H Oxidase-Derived Superoxide in Isehemie Stroke

Hong, H Lz, Zeng, JS z, Guan, y y 3 Chen, AF 1. 1Departments of Pharmacology and Neurology and Neuroseienee Program, Michigan State University, East Lansing, USA; 2Department of Neurology, Sun Yat-Sen University, Guangzhou, China; 3Department of Pharmacology, Sun Yat-Sen University, Guangzhou, China

Background: Statins have recently been shown to exert neuronal protection in ischemic stroke. Reactive oxygen species, specifically superoxide formed during the early phase of reperfusion, augment neuronal injury. N A D P H oxidase is a key enzyme for superoxide production. The present study tested the hypothesis that atorvastarin protects against cerebral infarction via inhibition of N A D P H oxidase- derived superoxide in transient focal ischemia. Methods: Transient focal ischemia was created in halothane- anesthetized adult male Sprague-Dawley rats (1250-300 g) by middle cerebral artery occlusion (MCAO). Atorvastarin (Lipitor TM, 10 mg/kg) was administrated subcutaneously 3 times before MCAO. Infarct volume was measured by triphenyltetrazolium chloride staining. N A D P H oxidase enzymatic activity and superoxide levels were quart- rifled in both the ischemic core and penmnbral regions by hidgenin (15 #M)-enhanced chemiluminescence. The expression of NADPH oxidase membrane subunit gp91 ph°~' and membrane-translocated subunit p47 pl~°~ and small GTPase Roe-1 were determined by Western blot analyses. Results: N A D P H oxidase activity and superoxide levels increased following reperfusion and peaked within 2 hours of reperfusion in the penumbra, but not in the ischemic core in MCAO rats. Ator- vastatin pretreatment prevented this increases, blunted the expression of membrane subunit gp91 pl,°~ and prevented the translocation of cytoplasmic subunit p47 pl~°~ to the membrane in the penmnbra 2 hours after reperfusion. Consequently, cerebral infarct volume was signifi- cantly reduced in atorvastatin-treated compared to non-treated MCAO rats 24 hours after reperfusion. Conclusion: These results indicate that atorvastatin protects against cerebral infarction via inhibition of N A D P H oxidase-derived super- oxide in transient focal ischenfia.

1131 Itdiibition of Brain GTP Cydohydrolase I and Telrahydrobiopterin Attenuates Cerebral Infarction via Reducing iNOS and Peroxynitrite in Ischemic Stroke

Zheng, JS 1, Hong, H 1, Majid, A ~, Kaufinan, DI ~, Chen, AF t. :Departments of Pharmacology and Neurology and Neuroscience Program, 3fiehigan State University, East Lansing, USA

Background: Inducible nitric oxide synthase (iNOS)-derived peroxyni- trite (ONOO-) during ischemia/reperfusion contributes to ischemic brain injury. However, iNOS regulation in ischemic stroke remains unknown. Tetrahydrobiopterin (BH4) is an essential cofactor for NOS activity. The present study tested the hypothesis that inhibition of endogenous BH4 rate-limiting etazyme GTP cyclohydrolase I

Poster Abstracts Thursday, November 10, 2005 $389

(GTPCH I) and thus BH 4 synthesis, reduces cerebral infarction via inhibiting iNOS and ONTO- in transient focal ischemia. Methods: Focal ischemJa (12 hrs) was created in adult male Sprague- Dawley rats (250 300 g) by middle cerebral artery occlusion (MCAO). Rats were treated 12 hrs prior to MCAO with vehicle or diamino- 6-hydroxypyrimJdine (DAHP, 0.5g/kg, i.p.), a selective GTPCH I inhibitor. Brains were harvested 24 hrs following reperfusion for assays of infarct volume, blood brain barrier (BBB) permeability, GTPCH I activity, BH4 levels, GTPCH I and NOS m R N A and protein expression, and superoxide (02) and O N t O levels. Results: Endogenous GTPCH I activity, BH4 levels and iNOS acti- vity, Oa and O N t O levels were all augmented following ischerraa/ reperfusion. DAHP treatment significantly reduced GTPCH I activity, resulting in decreased BH 4 levels, iNOS activity and ONTO- levels. Consequently, DAHP treatment significantly reduced the infarct size compared to the non-treated group (22.3 ± 5.6 vs. 38.3 ± 7.4"/0, n -- 6, P < 0.05). Similarly, BBB permeability was significantly reduced following DAHP pretreatment compared to either the control group (4.11 -c 0.22 vs.7.78 ± 0.44/~g/g tissue, n -- 5, P < 0.05). Conclusion: These results demonstrate that blockade of endogenous brain BH4 synthesis attenuates cerebral infarction via inhibiting iNOS and O N t O , which may provide a mechanistic basis of novel the- rapeutic strategies for ischemic stroke.

1132 Pereutaneous Endoscopic Gastrostomy hi Stroke patients: complications and outcome

Cho, S l, Choi, E 2, Yang, H a, Son, 13. 1SungAe General Hospital SeouL Korea; 2Hanaro Medical Foundation Seozd, Korea; 3 Wonlcwang University Hospital Korea

Pro'pose: The aim of this study was to investigate the safety, outcome, and long-term complications of percataneous endoscopic gastrostomy (PEG) placements in patients with stroke. Methods: A PEG was placed in 60 patients with stroke between 1 June 2002 and 31 December 2004 using the pull techrfique. A retrospective study of complications and outcome was performed, with a follow-up period ranging from 1 to 31 months. Results: The PEG was successfully placed in all 60 clffldren (140 male, 20 female; median age 65 y, range 38 y ~-' 89 y). There were no procedure-related deaths and no 30-day mortality. There were no immediate procedure-related complications. Late complications included wound infection (17%), aspiration pneumorfia (10%), wound bleeding (7"/0), accidental PEG renloval (17°,5), paralytic ileus (15°,5), overgrowth of granulation tissue (15"/o), PEG occlusion (13"/o), PEG leakage (3?,'o), buried bumper syndrome (13%), and gastrointest- inal bleeding (12%). In 6 patients (10%), PEG could be subsequently removed due to improvement in swallowing. Six patients (110%) had their PEG removed due to the re-establishinent o f oral feeding, with median time of use 6 months. Sixteen patients (127°,5) died during the period of study (median time-to-death 7.3 months, range 1.3 13.2 months). Thirty eight patients (163%) still have their PEGs at present (median time of use 18.2 months, range 1.4 ~ 31.8 months). All complications arose within the f r s t 2 months after PEG insertion. Conclusions: PEG provides an effective alternative method of enteral feeding, but its impact on outcome remains uncertain. Late complica- tions occurred in one third of the patients. Removal of the gastros- tomy tube and resumption of oral feeding was possible in 10% of the patients. However, long-term complications and morbidity occur in a significant proportion of patients.

1133 Aortic Arch Disease - Does oral anticoagulation work?

Chowdary G¥'S 1, Jaishree Naryanan T 1, Murthy JMK 1, Guruprasad H 1. 2Department of Neurology, The Institute of Neurological Sciences, CARE Hospital Narnpally, Hyderabad, India

Background: Severe atherosclerotic aortic arch disease is an important risk factor for stroke in the elderly. The place of anticoagulants, antiplatelet agents, and statins in secondary prevention is unclear. Methods: Consecutive patients with CAD and stroke or transient ischemic attack (TIA) were prospectively studied and only patients in whom aorto-entbolisnl was the stroke mechatffsm were included. All patients had trans-esophageal echocardiography (TEE) to grade the severity of the aortic, arch disease and only grade IV or V were considered. The patients were anticoagnlated with either warfarin or nicoumalone with target international normalization ratio (INR) of 2.0 2.5. Patients also received clopidogrel 75 mg per day and atorvastatin 10 mg per day. Follow-up TEE was performed at 6 months. Results: A total of 25 patients were recruited so far and at the time of the analysis 17 patients had follow-up TEE. TIAs were the presenting feature in 5 and 11 had non-disabling stroke. The mean age was 55 years and males accounted for 76°,5. Of the 17 patients in 12 (69%) repeat TEE showed regression of the aortic arch disease from grade IV-V to grade III or less and could be taken off the anticoagnlation. The remairfing 5 did not show any regression of the aortic arch disease. There were no major hemorrhagic complication or recurrence of coronary or cerebral vascular events. Conclusion: Even though tiffs is a lffghly select group of patients and the nmnbers were small, tiffs study suggests that the combination of dopidogrel, anticoagulant, and statins may cause regression of aortic arch atheromatous plaques.

1134 Long-term survival among Medicare beneficiaries with hltraeranial Hemorrhage

Lee, W ~, Christensen, Nl 2, Joshi, A ~, Wang, Q~, Pashos, C 2. 1Abt Associates 1no., HERQuLES, Bethesda, MD, USA; 2Novo Nordisk A/S, Bagsvaerd, Demnar]c; SNovo Nordis]c Inc., Princeton, N J, USA

Background: Nearly three-quarters o f stroke patients in the Ulffted States (US) are elderly Medicare beneficiaries. This study provides the first estimate of long-term survival among U.S. Medicare bene- ficiaries diagnosed with Subarachnoid Hemorrhage (SAH), Intracer- ebral Hemorrhage (rCH), and other or unspecified Intracrmffal Henlorrhage (rH). Methods: A retrospective study was conducted using comprehensive medical claims data from a 5% national random sanrple of Medicare beneficiaries. Those newly diagnosed with SAH (ICD-9-CM code: 430.xx), ICH (431.x~x) or other intracranial hemorrhage (432.xx) were followed longitudinally from their incident event in 1997 to 2001. Rates of mortality and stroke recurrence were assessed. Results: 3,248 patients were identified with SAH (in - 389, 11.9"/0), ICH (in - 2061, 63.4"/0), or IH (in - 798, 24.5"/0). Cohorts differed significantly as to age and race/ethnicity distribution. Patients in the age group 75-84 years comprised 35.7, 44.4% and 44.1% of the SAH, ICH and IH cohorts, respectively and African-Americans comprised a greater proportion regardless of type of hemorrhage. Approximately half of all patients had congestive heart failure and diabetes at time of stroke onset and over 90% had a diagnosis of hypertension. Mortality was 33.2%, 25.5?,'o and 167,'o during the irfitial hospitalization, and 41.97,'o, 48.9%, and 56.5?,'o at one year for SAH, ICH and IH, respectively. Survival through four years post-event was 5.9"/0, 6.4"/0 and 6.5"/0. Stroke recurrence rates within one year were 5.1"/o, 3.9% and 5.4%. Conclusion: SAH, ICH and intracratffal hemorrhage (IH) exact a heavy mortality toll among U.S. Medicare beneficiaries. These results reinforce the absence and need for optimal treatment alternatives.

1135 Long-term mortality, morbidity and health care interventions following hltraeerebral Hemorrhage: a 9-year cohort study