Ischemic cerebral edema (ICE) is a recognized cause of secondary neurological deterioration after large hemispheric stroke, but little is known about the scope of its impact. To study edema in less ...severe stroke, our group has developed several markers of cerebral edema using brain magnetic resonance imaging (MRI). These tools, which are based on categorical and volumetric measurements in serial diffusion-weighted imaging (DWI), are applicable to a wide variety of stroke volumes. Further, these metrics provide distinct volumetric measurements attributable to ICE, infarct growth, and hemorrhagic transformation. We previously reported that ICE independently predicted neurological outcome after adjustment for known risk factors. We found that an ICE volume of 11 mL or greater was associated with worse neurological outcome.
...we also share the view that the most straightforward way of accounting for disease severity in any analysis is to measure it objectively. ...analyses not included in the manuscript based on ...iterative restriction by survival time up to 5 days from admission do not result in a significant association, regardless of the interval length. ...we do not propose that our study has definitively demonstrated a role for confounding by indication; only that its presence is supported by our observations.
OBJECTIVETo examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a ...Mendelian randomization approach.
METHODSWe undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.
RESULTSA 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio OR 1.49, 95% confidence interval CI 1.32−1.68, p = 1.1 × 10). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96−1.30, p = 0.14; p for heterogeneity = 2.6 × 10) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84−1.33, p = 0.64; p for heterogeneity = 8.6 × 10) when compared with that for CHD.
CONCLUSIONSIn contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
The Knockout Mouse Project Austin, Christopher P; Battey, James F; Bradley, Allan ...
Nature genetics,
09/2004, Letnik:
36, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for ...biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.
Objective: Genetic variants varepsilon2/varepsilon4 within the APOE gene are established risk factors for lobar intracerebral hemorrhage (ICH). Published preliminary data suggest a potential role for ...APOE varepsilon4 in risk of nonlobar ICH. We therefore investigated the role of APOE in recurrent nonlobar ICH, and sought to clarify whether effects of APOE on circulating lipids mediate this association. Methods: Three hundred sixty-three survivors of nonlobar ICH were followed prospectively for ICH recurrence, with APOE genotype determined at enrollment. All participants had clinical, demographic, and laboratory data captured at time of index ICH and during follow-up. Using a multivariate model, we performed association and interaction analyses of the relationships among APOE genotype, lipid levels, and recurrent nonlobar ICH. Results: We observed 29 nonlobar ICH recurrences among 363 survivors. APOE varepsilon4 was associated with recurrent nonlobar ICH (hazard ratio = 1.31; 95% confidence interval = 1.02-2.69; p = 0.038) after adjustment for age/sex/ethnicity and cardiovascular risk factors. Increasing low-density lipoprotein (LDL) levels were associated with decreased risk of recurrent nonlobar ICH (p = 0.027), as were decreasing HDL levels (p = 0.046). LDL levels modified the association of APOE varepsilon4 with recurrent nonlobar ICH (mediation p < 0.05). No associations were identified between APOE varepsilon2 and recurrent nonlobar ICH. Conclusion: APOE varepsilon4 is associated with recurrent ICH in nonlobar brain regions, providing further evidence for its causal role in ICH unrelated to cerebral amyloid angiopathy. LDL levels modulated this effect, suggesting that circulating lipid levels may mediate a portion of the role of APOE varepsilon4 in nonlobar ICH.
Lateral view of MRI reconstruction of the brain surface of a California sea lion. The reconstruction placed in a parasagittal section through surrounding head structures. See Montie et al., on page ...1523, in this issue.
Although percutaneous transluminal coronary angioplasty (PTCA) is frequently performed in patients with multivessel coronary artery disease, its value as compared with coronary-artery bypass grafting ...(CABG) has not been established. In contrast, bypass surgery has been the standard form of revascularization for patients with multivessel coronary disease. Trials comparing surgery with medical therapy have consistently shown greater improvement in angina after surgery, although improved survival has been documented only in certain subgroups of patients with multivessel disease
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