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Sharon K Krueger Lisbeth K Siddens Sarah R Martin Zhen Yu Clifford B Pereira Erwin T Cabacungan Ronald N Hines Kristin G Ardlie Judy L Raucy David E Williams 《Drug metabolism and disposition》2004,32(12):1337-1340
A polymorphism for the phase I drug-metabolizing enzyme, flavin-containing monooxygenase isoform 2 (FMO2), encoding either truncated inactive protein, FMO2X472 (FMO2.2A), or full-length active enzyme, FMO2Q472 (FMO2.1), is known and exhibits significant interethnic differences in allelic frequency. FMO2 is the major or sole FMO isoform expressed in the lung of most mammals, including nonhuman primates. To date, FMO2.1 has been found only in African-American and Hispanic populations, rendering individuals with this allele subject to drug metabolism that is potentially different from that of the general population. Approximately 26% of African-Americans (n = 180) possess the FMO2*1 allele. In preliminary studies, we initially estimated that 5% of Hispanics (n = 40) have the FMO2*1 allele, but access to large cohorts of individuals of defined national origin has allowed us to determine the occurrence among Mexican-American and Puerto Rican-American groups. We used allele-specific genotyping to detect FMO2*1 from 632 Hispanic individuals, including 280 individuals of Mexican origin and 327 individuals of Puerto Rican origin. Statistical analysis indicated that results from Mexican (five sample sources) and Puerto Rican (three sample sources) samples were consistent with the hypothesis of homogeneity within each group from different sources. Data were subsequently pooled across sources to test for evidence of a difference in occurrence of FMO2*1 between ethnic groups. There was strong evidence (p = 0.0066) that FMO2*1 is more common among Puerto Ricans (7%) than among individuals of Mexican descent (2%). The overall occurrence of FMO2*1 among Hispanics of all origins is estimated to be between 2 and 7%. 相似文献
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Patient‐ and family‐centred care in the intensive care unit: a challenge in the daily practice of healthcare professionals
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76.
Rebecca Erwin Wells MD MPH Catherine E. Kerr PhD Jennifer Wolkin PhD Michelle Dossett MD PhD Roger B. Davis ScD Jacquelyn Walsh BS Robert B. Wall MDiv MSN Jian Kong MD MPH Ted Kaptchuk Daniel Press MD Russell S. Phillips MD Gloria Yeh MD MPH 《Journal of the American Geriatrics Society》2013,61(4):642-645
77.
Erwin L. Roggen 《Toxicology in vitro》2013,27(3):1122-1126
The contribution of the Sens-it-iv project to the reduction and replacement of animal experimentation is 3-fold. The funding of basic research has expanded the existing scientific knowledge thereby strengthening the understanding of the cellular and molecular mechanisms driving skin and respiratory sensitization. Examples are given on how a better understanding was used to improve existing test concepts. This knowledge was also applied to develop novel test systems. While some of test systems did not reach sufficient maturity for being considered for pre-validation others did and entered into the Sens-it-iv toolbox.In the process, developments outside the Sens-it-iv orbit were carefully followed and assessed in order to avoid duplication and to assure synergy between the ongoing activities (e.g. Cosmetics Europe Task Force for Sensitization).Tests from the Sens-it-iv toolbox were submitted to the European Reference Laboratory for Alternative Methods (EuRL-ECVAM) to initiate the rigid procedures for regulatory acceptance by national and international authorities. In spite of not being validated yet, selected tests were already applied in a weight-of-evidence approach in the context of REACH. Furthermore, several chemical, pharmaceutical, cosmetic and consumer product companies are currently assessing selected tests and testing strategies for their value as tools for screening and hazard identification using in house compounds and mixtures.The main points of concern related to transfer to and implementation by industry were cost, through-put and applicability domain, rather than regulatory acceptance. These issues are currently addressed in applied research projects which are financially supported by individual companies, or consortia of companies, representing the various industry sectors. 相似文献
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Kaemmerer H Bauer U Pensl U Oechslin E Gravenhorst V Franke A Hager A Balling G Hauser M Eicken A Hess J 《The American journal of cardiology》2008,101(4):521-525
The aim of the study was to assess the quantity and nature of emergencies affecting adults with congenital cardiac disease (CCD) and evaluate infrastructural requirements for adequate management. There is an increasing number of adults with CCD requiring specialized complex care. This multicenter study evaluated all emergency admissions to 1 of 5 centers for adults with CCD within 1 year. Within 1 year, there were 1,033 admissions of adults with CCD, and 201 (160 patients; age 16 to 71 years) were emergencies. Underlying cardiac anomalies were univentricular heart (22%), complete transposition (14%), tetralogy of Fallot (21%), and others (43%). Seventy percent of patients had undergone previous cardiac surgery. The main reason for acute admission was cardiovascular (arrhythmia, heart failure, syncope, aortic dissection, and endocarditis). Diagnostic procedures most often assigned were echocardiography (n = 223), chest x-ray (n = 95), Holter electrocardiography (n = 85), cardiac catheterization/electrophysiologic study (n = 39), and others (n = 143). Forty-six patients underwent surgery (cardiovascular n = 41, general n = 5) or electrophysiologic treatment (n = 41). One hundred twenty-six of 201 emergencies (63%) required cooperation with another specialized department: surgery (n = 46), internal medicine (n = 42), neurology (n = 12), ophthalmology (n = 6), otorhinolaryngology (n = 5), gynecology (n = 5), psychiatry (n = 4), radiology (n = 3), dermatology (n = 2), and orthopedics (n = 2). In conclusion, physicians and consultants attending adult patients with CCD need a high degree of specialized experience concerning the cardiac anomaly to manage emergencies properly. Furthermore, a wide range of noncardiac diagnostic and therapeutic procedures must be available. Data support the demand for a multidisciplinary approach in specialized centers for adequate care of adults with CCD. 相似文献
80.
Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation 总被引:13,自引:0,他引:13
Geuken E Visser D Kuipers F Blokzijl H Leuvenink HG de Jong KP Peeters PM Jansen PL Slooff MJ Gouw AS Porte RJ 《Journal of hepatology》2004,41(6):1017-1025
BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily posttransplantation for determination of bile composition. Hepatic expression of bile transporters was studied before and after transplantation. Histopathological criteria as well as biliary concentrations of alkaline phosphatase (ALP) and gamma-glutamyltransferase (gamma-GT) were used to quantify bile duct injury. RESULTS: Early after transplantation, bile salt secretion increased more rapidly than phospholipid secretion, resulting in high biliary bile salt/phospholipid ratio (BA/PL). In parallel with this, mRNA levels of the bile salt transporters NTCP and BSEP increased significantly after transplantation, whereas phospholipid translocator MDR3 mRNA levels remained unchanged. Bile duct injury correlated significantly with bile salt secretion and was associated with a high biliary BA/PL ratio. CONCLUSIONS: Bile salt secretion after human liver transplantation recovers more rapidly than phospholipid secretion. This results in cytotoxic bile formation and correlates with bile duct injury. These findings suggest that endogenous bile salts have a role in the pathogenesis of bile duct injury after liver transplantation. 相似文献