ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background—CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an inherited condition that causes repeated small-scale strokes in adults. CADASIL is caused only by mutations in the humanNOTCH3gene that increase or decrease the number of cysteines within the epidermal growth factor (EGF) repeats of the NOTCH3 protein.Drosophilalethal-Abruptex is a similar condition because it is also caused only by mutations that increase or decrease the number of cysteines within the EGF repeat portion of the Notch protein.Summary of Comment—Drosophilalethal-Abruptex and human CADASIL are precisely analogous at the molecular level, and both are genetically dominant. These precise similarities, together with the fact that the structure and function of Notch has been highly conserved throughout the animal kingdom, provide an animal model for the molecular and genetic aspects of human CADASIL. It also provides support for Spinner’s proposal that CADASIL results from dominant inhibition of the Notch pathway.Conclusions—Because the phenotypes of Notch mutations are cell-autonomous, the symptoms of CADASIL indicate that adult vascular smooth muscle cells require the continuing function of theNOTCH3pathway in the adult. For this reason, further analysis of theNOTCH3pathway may provide more general insights into the biology of vascular smooth muscle cells. In the case of CADASIL, the powerful genetic tools available inDrosophilashould help to facilitate future research.

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background—Recombinant tissue plasminogen activator (rTPA) is an established treatment for acute ischemic stroke. The rate and type of protocol violations in rTPA use and their effect on patient outcomes in this setting are not well understood.Objective—The objective of this study was to examine associations between protocol violations and outcomes in community-based rTPA use.Methods—We reviewed medical records of stroke patients treated with rTPA in 10 acute-care hospitals in Indianapolis from July 1996 to February 1998 and assessed complications and outcome. Retrospective National Institute of Health Stroke Scale (on admission and discharge), Canadian Neurological Scale, and length of hospital stay were calculated. Appropriate use of rTPA was determined by the National Institute of Neurological Disorders and Stroke (NINDS) protocol.Results—Fifty patients (mean age, 66 years; 76% white; 56% men) were treated by general neurologists (70%), stroke neurologists (24%), or emergency physicians (6%). Mean times to hospital arrival, brain CT, and start of rTPA infusion were 44, 86, and 141 minutes, respectively. In-hospital mortality rate was 10% (4 intracerebral hemorrhage [ICH], 1 cardiogenic shock). Complications were more frequent among patients with protocol violations (n=8) compared with those without all hemorrhages (75% versus 10%,P<0.001), symptomatic ICH (38% versus 5%,P<0.02), and ICH attributable to rTPA, occurring within 36 hours (38% versus 2.4%,P<0.01), respectively.Conclusions—NINDS protocol violations are relatively common and are associated with symptomatic cerebral and systemic hemorrhages. When the NINDS protocol is strictly followed, hemorrhage rates in community-based rTPA use are similar to those in the NINDS trial.

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background and Purpose—Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations inNotch3. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells. To study cerebrovascular function in CADASIL, we performed measurements on cerebral hemodynamics by using transcranial Doppler sonography.Methods—Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO2reactivity, and the resistance index were measured by bilateral transcranial Doppler sonography in 29 CADASIL individuals (mean age, 49.0±2.4 years) and an equal number of age- and sex-matched control subjects.Results—Compared with control subjects, CO2reactivity was reduced in CADASIL (33.4±2.7% versus 45.3±3.0%;P<0.01). This difference remained significant when only nondisabled CADASIL individuals (Rankin=0, n=21) were included in the analysis (P<0.05). CO2reactivity was significantly lower in disabled than in nondisabled CADASIL individuals (24.5±2.7% versus 36.8±3.4%;P<0.05). MCA MFV was reduced in CADASIL (45.6±2.2 cm/s versus 54.2±2.4 cm/s;P<0.05) and correlated negatively with age both in affected individuals (r=−0.314;P<0.05) and control subjects (r=−0.339;P<0.05). Resistance index was not significantly altered (59.0±1.0% versus 57.7±1.2%;P=0.42).Conclusions—In CADASIL, there is a reduction of both CO2reactivity and basal MCA MFV. The reduced CO2reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO2reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background and Purpose—To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]).Methods—We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti–factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index ≥90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration.Results—The proportion of patients with Barthel Index ≥90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed.Conclusions—Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background and Purpose—Recent evidence suggests that physiological changes in the concentration of endogenous estrogens may influence stroke outcome. The purpose of this study was to determine a menstrual cycle–related profile of blood flow through the carotid arteries and its correlation with estrogen concentration.Methods—The flow velocity and cross-sectional area of the common carotid artery, internal carotid artery (ICA), and external carotid artery (ECA) were measured with duplex Doppler sonography throughout the menstrual cycle in 14 healthy women. Concentration of plasma 17&bgr;-estradiol, progesterone, hematocrit, hemoglobin, and blood pressure were also determined.Results—In the follicular phase, the concentration of estrogen increased to reach a peak on day 14, whereas concentration of progesterone remained low. The mean and end-diastolic velocities in the ICA increased on average by 15% of their base values, along with increasing concentrations of estrogen (r=0.59 and 0.65, respectively). The profile of flow velocity changes in this artery corresponded to the profile of estrogen concentration. In contrast to the ICA, flow velocities in the ECA decreased from their base value, reaching their minimum in the luteal phase. The mean flow velocity in the common carotid artery increased on day 14 by just 2% of its base value. The lumen of the carotid arteries was stable throughout the cycle. Hematocrit, hemoglobin, and systolic blood pressure also remained unchanged.Conclusions—Increased concentration of endogenous estrogen correlates with substantial augmentation of flow in the internal carotid artery. This promotion of flow is caused mainly by decreased cerebrovascular resistance with consequent “stealing” of blood from the ECA.

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background and Purpose—The excess risk of stroke seen in the black population has not been explained by differences in age, sex, and social class, although differences in the frequency of cerebrovascular risk factors may be partly responsible. Data on risk factor profiles for the UK black stroke population are sparse. Previous studies have contrasted the association of cerebrovascular risk factors between hemorrhagic and ischemic stroke and between etiologic subtypes of infarct. The relationship of cerebrovascular risk factors to clinical classifications of stroke, however, has been little examined. The aim of this study was to establish the frequency of cerebrovascular risk factors in patients with first-ever strokes in the South London, UK, population and to examine the relationship of these risk factors to both ethnicity and Bamford stroke subtype.Methods—The study included 1254 first-ever stroke patients registered in the South London Community Stroke Register between 1995 and 1998; 995 patients (79.3%) were white, 203 (16.2%) were black, 52 (4.1%) were of other ethnic origin, and 4 (0.3%) were of unknown ethnic origin.Results—In multivariate analysis, increasing age (P<0.001) and previous cerebrovascular disease (P=0.007) were independently associated with infarct rather than hemorrhage. Atrial fibrillation was associated with all nonlacunar (P=0.02), total anterior circulation (P=0.007), and partial anterior circulation infarcts (P=0.02) compared with the lacunar group. All other risk factors were similar between infarct subtypes. Risk factors for hemorrhage subtypes were similar in multivariate analysis; increasing age was the only factor associated with primary intracerebral hemorrhage over subarachnoid hemorrhage (P<0.001). The black stroke population suffered significantly less atrial fibrillation (P=0.001) and engaged in less alcohol excess (P<0.001) and were less likely to have ever smoked (P<0.001). Hypertension (P<0.001) and diabetes mellitus (P<0.001) were more prevalent in the black population.Conclusions—Physiological cerebrovascular risk factors for the UK black population are similar to those of the US black population, but behavioral risk factors differ. Risk factors differ between ethnic groups in the United Kingdom, and future measures for secondary prevention should take this into consideration. Bamford clinical subtypes bear little association with cerebrovascular risk factors. Other classification systems, such as those that classify stroke by etiology, may be more useful in explaining the excess risk of stroke and the scope for its prevention.

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background and Purpose—Polyamines are mainly restricted to the intracellular space. During focal cerebral ischemia, polyamines are released from the intracellular compartment. Experimental studies have implicated a marked elevation in brain tissue and blood. The aim of our study was to investigate whether the elevation of polyamines in the blood of patients with focal cerebral ischemia correlates with the clinical outcome and the infarct volume.Methods—Polyamines were measured in 16 patients with focal cerebral ischemia and in 8 healthy control subjects. Blood samples for polyamine measurement were taken at admission and at fixed time points for the next 28 days. Polyamines were analyzed in red blood cells by a high-pressure liquid chromatography system. Clinical findings were recorded with the NIH Stroke Scale score. Volume of infarction was analyzed from cranial CT at admission and on days 4 to 6 after ischemia.Results—A significant increase of the spermidine level in the peripheral blood could be observed in all patients with focal cerebral ischemia as compared with control subjects (P<0.01), starting with the admission. Spermidine values correlated positively with the clinical outcome at several time points in the first 48 hours (r=0.90 to 0.40;P<0.01) and with the infarct volume in cranial CT on days 4 to 6 (r=0.91;P<0.01).Conclusions—As hypothesized from experimental data, polyamine levels in blood increase in patients after focal cerebral ischemia. The results indicate that the peripheral spermidine level is closely associated with the clinical outcome as well as with the infarction volume. Therefore, polyamines may be used as a novel predictor for the prognosis of patients with focal cerebral ischemia.

ISSN:0039-2499    

出版商:OVID    

年代:2001

数据来源: OVID