Results of this systematic literature review suggest that the overall incidence of CMs in children born of WWE is approximately threefold that of healthy women. The risk is elevated for all AED monotherapy and further elevated for AED polytherapy compared to women without epilepsy. The risk was significantly higher for children exposed to valproate monotherapy and to polytherapy of 2 or more drugs when the polytherapy combination included phenobarital, phenytoin, or valproate. Further research is needed to delineate the specific risk for each individual AED and to determine underlying mechanisms including genetic risk factors.
Background: Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer’s disease (AD) by geographic region and country. Methods: A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. Results: Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5–51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4–10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9–66.7), e4/4 prevalence: 14.1% (95% CI: 12.2–16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. Conclusions: APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.
A structured review of published papers was done to assess the efficacy and safety of fasciectomy and fasciotomy in European patients with Dupuytren's contracture. The outcomes varied across 48 studies. For fasciectomy, outcomes and results were as follows: the proportions of patients with a 100% correction in contracture angle ranged from 61 to 97%, the mean improvement in contracture angle ranged from 58 to 79%, and cases judged excellent/good ranged from 63 to 90%. Fasciotomy had similar outcomes, with a mean improvement in contracture angle ranging from 46 to 88%. Immediate failures upon recovery were reported for both procedures. The average recurrence rates were 39% after a fasciectomy and 62% after a fasciotomy at a median time of about 4 years. Overall, about 20% of fasciectomy and fasciotomy patients experienced an adverse event. In summary, postoperative outcomes were successful, but surgical complications were common and recurrence of a contracture was likely within a few years.
Background: The Ε4 allele of apolipoprotein E (APOE) is associated with Alzheimer’s disease (AD). However, attributable risk due to APOE4 varies by region and by race/ethnicity. Methods: A literature review and meta-analysis were conducted to estimate the prevalence of APOE4 by geographic area among AD patients. Results: Although estimates varied significantly by study design and case definition, AD patients recruited in Asian and southern European/Mediterranean communities seemed to have significantly lower E4 carrier status estimates (37 and 43%) than those recruited in North America (58%) or northern Europe (64%; all: p < 0.05). Conclusions: APOE4 genotype frequency varies among AD patients in regional patterns similar to that of the general population. Study level differences may also contribute to the heterogeneity of published estimates of APOE4 in AD cases.
The monocyte chemotactic protein-1 (MCP-1) receptor (MCP-1R) is expressed on monocytes, a subpopulation of memory T lymphocytes, and basophils. Two alternatively spliced forms of MCP-1R, CCR2A and CCR2B, exist and differ only in their carboxyl-terminal tails. To determine whether CCR2A and CCR2B receptors function similarly, Jurkat T cells were stably transfected with plasmids encoding the human CCR2A or CCR2B gene. Nanomolar concentrations of MCP-1 induced chemotaxis in the CCR2B transfectants that express high, intermediate, and low levels of MCP-1R. Peak chemotactic activity was shifted to the right as receptor number decreased. Five-fold more MCP-1 was required to initiate chemotaxis of the CCR2A low transfectant, but the peak of chemotaxis was similar for the CCR2A and CCR2B transfectants expressing similar numbers of receptors. MCP-1-induced chemotaxis was sensitive to pertussis toxin, implying that both CCR2A and CCR2B are Giα protein coupled. MCP-1 induced a transient Ca2+ flux in the CCR2B transfectant that was partially sensitive to pertussis toxin. In contrast, MCP-1 did not induce Ca2+ flux in the CCR2A transfectant. Since MCP-1 can stimulate chemotaxis of the CCR2A transfectant without inducing Ca2+ mobilization, Ca2+ flux may not be required for MCP-1-induced chemotaxis in the Jurkat transfectants. These results indicate that functional differences exist between the CCR2A and CCR2B transfectants that can be attributed solely to differences in the carboxyl-terminal tail.
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