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BACKGROUND@#High on-treatment platelet reactivity (HTPR) has been suggested as a risk factor for patients with ischemic vascular disease. We explored a predictive model of platelet reactivity to clopidogrel and the relationship with clinical outcomes.@*METHODS@#A total of 441 patients were included. Platelet reactivity was measured by light transmittance aggregometry after receiving dual antiplatelet therapy. HTPR was defined by the consensus cutoff of maximal platelet aggregation >46% by light transmittance aggregometry. CYP2C19 loss-of-function polymorphisms were identified by DNA microarray analysis. The data were compared by binary logistic regression to find the risk factors. The primary endpoint was major adverse clinical events (MACEs), and patients were followed for a median time of 29 months. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the patients with HTPR and non-HTPR.@*RESULTS@#The rate of HTPR was 17.2%. Logistic regression identified the following predictors of HTPR: age, therapy regimen, body mass index, diabetes history, CYP2C192, or CYP2C193 variant. The area under the curve of receiver operating characteristic for the HTPR predictive model was 0.793 (95% confidence interval: 0.738-0.848). Kaplan-Meier analysis showed that patients with HTPR had a higher incidence of MACE than those with non-HTPR (21.1% vs. 9.9%; χ = 7.572, P = 0.010).@*CONCLUSIONS@#Our results suggest that advanced age, higher body mass index, treatment with regular dual antiplatelet therapy, diabetes, and CYP2C192 or CYP2C193 carriers are significantly associated with HTPR to clopidogrel. The predictive model of HTPR has useful discrimination and good calibration and may predict long-term MACE.

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Background:@#High on-treatment platelet reactivity (HTPR) has been suggested as a risk factor for patients with ischemic vascular disease. We explored a predictive model of platelet reactivity to clopidogrel and the relationship with clinical outcomes.@*Methods:@#A total of 441 patients were included. Platelet reactivity was measured by light transmittance aggregometry after receiving dual antiplatelet therapy. HTPR was defined by the consensus cutoff of maximal platelet aggregation >46% by light transmittance aggregometry. CYP2C19 loss-of-function polymorphisms were identified by DNA microarray analysis. The data were compared by binary logistic regression to find the risk factors. The primary endpoint was major adverse clinical events (MACEs), and patients were followed for a median time of 29 months. Survival curves were constructed with Kaplan-Meier estimates and compared by logrank tests between the patients with HTPR and non-HTPR.@*Results:@#The rate of HTPR was 17.2%. Logistic regression identified the following predictors of HTPR: age, therapy regimen, body mass index, diabetes history, CYP2C19*2, or CYP2C19*3 variant. The area under the curve of receiver operating characteristic for the HTPR predictive model was 0.793 (95% confidence interval: 0.738–0.848). Kaplan-Meier analysis showed that patients with HTPR had a higher incidence of MACE than those with non-HTPR (21.1% vs. 9.9%; χ2 = 7.572, P = 0.010).@*Conclusions:@#Our results suggest that advanced age, higher body mass index, treatment with regular dual antiplatelet therapy, diabetes, and CYP2C19*2 or CYP2C19*3 carriers are significantly associated with HTPR to clopidogrel. The predictive model of HTPR has useful discrimination and good calibration and may predict long-term MACE.

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<p><b>BACKGROUND</b>Cerebral arteriovenous malformation (cAVM) is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cytokines to make a better understanding of the potential aberrant signaling in the pathogenesis of cAVM and found useful proteins in predicting the risk of cerebral hemorrhage.</p><p><b>METHODS</b>Immunohistochemical analysis was conducted on specimens from twenty patients with cAVM diagnosed via magnetic resonance imaging and digital subtraction angiography and twenty primary epilepsy controls using antibodies against vascular endothelial growth factor receptor-2 (VEGFR-2), matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule (VCAM-1), and endothelial nitric oxide synthase (eNOS). Western blotting and real-time fluorescent quantitative polymerase chain reaction (PCR) were performed to determine protein and mRNA expression levels. Student's t-test was used for statistical analysis.</p><p><b>RESULTS</b>VEGFR-2, MMP-9, VCAM-1, and eNOS expression levels increased in patients with cAVM compared with those in normal cerebral vascular tissue, as determined by immunohistochemical analysis. In addition, Western blotting and real-time PCR showed that the protein and mRNA expression levels of VEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the control group, all the differences mentioned were statistically significant (P < 0.05).</p><p><b>CONCLUSIONS</b>VEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients with cAVM and might play important roles in angiogenesis, vascular remodeling, and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be potential excellent group proteins in predicting the risk of cerebral hemorrhage at arteriovenous malformation.</p>

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Objective To study the clinical characteristics and digital subtract angiography (DSA) manifestations of the hemorrhagic moyamoya disease in adults. Methods A retrospective study was conducted to analyze the clinical data and DSA imaging of 68 adult patients who had been diagnosed with intracerebral hemorrhage on CT and with moyamoya on DSA. Results They were 23 males and 45 females with an average of 37.8 years. Their DSA manifestations included bilateral lesions on the anterior cerebral circulation in 57 cases, 19 of whom had combined lesions on the posterior cerebral circulation; unilateral lesion on the anterior cerebral circulation in 9 cases, 6 of whom had combined lesions on the posterior cerebral circulation; simple lesions on the posterior cerebral circulation in 2 cases;simple lesions on the anterior cerebral circulation in 41 cases.Intracranial aneurysm was complicated in 11 cases, 7 of whom underwent aneurysm embolization or clipping of the aneurysm neck. Cerebral infarction was complicated in 13 cases. Repeated hemorrhage for twice or more occurred in 17 cases.Ventricle hemorrhage occurred in 59 cases, parenchymal hemorrhage in 7 cases, and subarachnoid hemorrhage in 2 cases. Craniotomy was performed in 6 cases of massive intracranial bleeding.Conclusions Adult patients with hemorrhagic moyamoya disease, particular middle-aged women,usually have a major manifestation of intraventricular hemorrhage. Surgical interventions for combined aneurysms and symptoms can achieve a good therapeutic effect, but it is difficult to prevent re-hemorrhage.DSA is the primary method to determine specific characteristics of moyamoya lesions and consequently to choose a proper treatment.

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Objective To investigate the efficacy of transvenous embolization in the management of cavernous dural arteriovenous fistulas. Methods Nine patients with cavernous dural arteriovenous fistulas diagnosed by digital subtraction angiography (DSA) were treated by transvenous embolization. Results Eight of the 9 patients were cured and 1 patient showed symptomatic improvement after the operations. No deterioration or death occurred in these cases. Follow-up of the patients for 2 to 96 months found no cases of relapse or exacerbation. Conclusion Transvenous embolization is effective and safe in the management of cerebral dural arteriovenous fistulas.

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Objective To analyze the therapeutic effects of microvaseular decompression on primary trigeminal neuralgia. Methods The general clinical data,culprit vessels and therapeutic effects of the surgical interventions were analyzed in 181 patients(aged from 24 to 79 years with a mean of54.9 years,including 78 male and 103 female patients)with established diagnosis of primary trigeminal neuralgia admitted from January,2000 to Deceber,2007. Results Blood type O was present in 43.65%of the 181 patients with trigeminal neuralgia,which had an increasing tendency compared to the national norm(33.8%).The morbidity ratio between the right and left side was 1.8:l in these patients.Forty-five patients(24.86%)were identified to have more than 2 culprit vessels.The culprit vessels included the superior cerebellar artery(96 cases),posterior inferior cerebellar artery(7 cases),anterior inferior cerebellar artery(25 cases),arteries communicated with veins(25 cases),internal auditory artery (13 cases),basilar artery(15 cases),vertical artery(9 cases),exclusive veins(15 cases,mainly vena pelrosa and bridging vein)and unknown vessels(9 cases).of the 181 cases,171(94.48%)were cured within one month,9(4.97%)showed relieved symptoms but required drug therapy,and 1 was in vegetative state(0.55%). Conclusions Patients with blood type O may have greater chance of developing primary trigeminal neuralgia.Microvascular decompression is an ideal treatment for primary trigeminal neuralgia,and clear identification of the culprit vessels can be crucial for decreasing the postoperative recurrence.

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Objective To study the relationships between hypertensive intracerebral hemorrhage (HICH) and family history of hypertensive disease, gender, age and disease course in Guangzhou. Methods The clinical profiles of 425 (269 male and 156 female) patients with HICH admitted to Nanfang Hospital, Guangzhou from 2000 to 2004 were collected. The relationships between disease incidences in different family histories of hypertensive disease, genders, ages, courses of disease and blood pressure were analyzed. Results In all 425 cases with HICH, the ratio of male to female of people with family history of hypertensive disease was significantly higher than that without in male.There were no obvious differences between with and without family history in female. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in the male than in the female in young group. In middle-aged group and elder group, there were no significant differences in SBP and DBP between the male and the female. The distributions of SBP and DBP were all acute stage＞ subacute stage＞ convalescence stage. Conclusions Hypertensive disease should be supplied with different strategies of prevention and cure in accordance with different ages, genders and courses of disease, which can decrease the incidence of hypertensive intracerebral hemorrhage maximally.

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Objective To investigate the variation of electrocardiogram (ECG) in the course of aneurysmal subarachnoid hemorrhage (SAH) for predicting the prognosis. Methods The in-hospital data of 108 cases with aneurysmal SAH who had underwent ECG re-examination were retrospectivelyanalyzed to find out the relationship between characters of ECG and prognosis. Results Of the 108 cases, aneurysm clamping by eraniotomy was performed in 41 and endovascular intervention in 67; a total of 89 cases (82.4%) presented abnormal ECG primitively, 62 patients had 2 kinds of ECG changes at least; 71 patients presented abnormal ST-T, 13 cases with abnormal cardiac rhythm, 14 cases with delayed Q-T intermediate stage, 37 cases with abnormal T wave, 9 cases with abnormal Q wave, and 7 cases with other changes; 99 cases recovered in ECG re-examination, 5 cases partly recovered and 4 cases aggravated. GOS score was 4-5 in 98 cases, 3 in 7 cases, and 1-2 in 3 cases. Conclusion Though the type of ECG variation has no significant correlation with SAIl prognosis, ECG monitoring during the course of SAH is of important value for predicting the prognosis.

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<p><b>OBJECTIVE</b>To assess the value of (1)H-magnetic resonance spectroscopy ((1)H-MRS) in evaluating cerebral vasospasm resulting from subarachnoid hemorrhage (SAH).</p><p><b>METHODS</b>Six dogs were subjected to autologous non-heparinized blood injection via cisternal puncture twice at one-day interval to establish models of SAH, and another 6 received injections with normal saline in an identical manner. (1)H-MRS scan was performed on the 3rd, 7th and 14th days after the injections to measure the changes of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho). After the (1)H-MRS scan, all the dogs underwent brain digital subtraction angiography (DSA) for determining the basilar artery diameter.</p><p><b>RESULTS</b>DSA results on day 3 presented development of obvious vasospasm of the basilar artery, which was most evident on day 7 and recovered obviously on day 14. (1)H-MRS results demonstrated obvious changes of NAA, Cho and Cr on days 3 and 7 in SAH model group, and NAA declined to the lowest level on day 3 followed by gradual ascending till reaching the normal level on day 14. Cho decreased slightly on day 3, then increased and reached the peak level on day 7 and then decreased. Cr rose steadily from day 3 to 14, but since day 7, the rise slowed down obviously and Cr maintain a level not significantly different from that on day 14 (P>0.05). The functional results of (1)H-MRS were consistent with the DSA results.</p><p><b>CONCLUSION</b>(1)H-MRS can be used to monitor the development of cerebral vasospasm resulting from SAH as a good evaluation method for functional imaging.</p>

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<p><b>OBJECTIVE</b>To explore the expression of transforming growth factor beta1 (TGFbeta1) and its type I receptors activin-like kinase 1 (ALK1) and ALK5 mRNA in the development of brain arteriovenous malformation (BAVM).</p><p><b>METHODS</b>The mRNA expressions of TGFbeta1, ALK1and ALK5 were detected with semiquantitative RT-PCR in patients with BAVM.</p><p><b>RESULTS</b>The expressions of TGFbeta1 and ALK5 mRNA increased significantly in BAVM, and their relative expression quantity were 0.777-/+0.047 and 0.585-/+0.074, respectively. However, ALK1 mRNA expression declined significantlies with a relative expression of 0.173-/+0.044 in comparison with the control group (0.720-/+0.098, P<0.01).</p><p><b>CONCLUSION</b>The balance of TGFbeta1 and its type I receptors ALK1 and ALK5 mRNA expressions may play important role in the development of BAVM.</p>

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<p><b>OBJECTIVE</b>To study the mechanism of Ca(2+) on the apoptosis induced by hyperthermia in neonate rat hippocampal neurons to provide the applicative evidence of dantrolene for preventing brain injuries.</p><p><b>METHODS</b>Dantrolene, Ca(2+) specific blocking agent, was used in the hyperthermia-induced apoptosis of primary hippocampal neurons in vitro to observe its effect on the apoptosis, fluorescent intensity, and dynamic change of Ca(2+) by flowcytometry and laser confocal microscopy.</p><p><b>RESULTS</b>The rate of apoptosis was decreased significantly after hyperthermia treatment by dantrolene sodium. The intracellular Ca(2+) fluorescent intensity in 42 degrees C treatment group (107.35 +/- 6.0) was significantly lower than that in control group (159.12 +/- 33.8). The concentration of Ca(2+) began to decrease 20 approximately 25 s after adding dantrolene sodium, and reached the lowest level about 50 s later, and then kept lower than the basal level.</p><p><b>CONCLUSION</b>Dantrolene sodium has an important protective effect on hippocampal neurons apoptosis induced by hyperthermia and may have some applicative value of preventing heat-induced brain injury.</p>

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<p><b>OBJECTIVE</b>To study the early change of serum nitric oxide (NO) after acute heat exposure with trauma and the effect of NO on mean arterial pressure (MAP), thus to provide theoretical basis for studying the mechanism of NO effect in acute stress.</p><p><b>METHODS</b>The rabbit model of acute heat exposure combined with trauma was established. The animals were divided into four groups, including control, trauma, hyperthermia and hyperthermia combined with trauma. The levels of NO were measured at different time points: 0 h, 1 h, 2 h and MAP was monitored throughout the whole experiment.</p><p><b>RESULTS</b>The concentration of NO declined at first and then increased at 1 h or so after acute heat exposure and trauma. The levels of NO in hyperthermia with trauma group at 1 h, 2 h were (42.75 +/- 8.24), (59.54 +/- 9.05) micro mol/L respectively (P < 0.05), while those in control group were (56.63 +/- 3.79) and (55.22 +/- 7.15) micro mol/L, the difference at 1h between two groups was significant (P < 0.05). Under the circumstance of hyperthermia and trauma, the level of MAP declined to the lowest point at 60 - 70 min and then showed a transient rise, after that, the level declined rapidly.</p><p><b>CONCLUSIONS</b>At the early stage of acute heat exposure and trauma, the concentration of serum NO declined at first and then increased, and had certain relationship with the change of MAP.</p>

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