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51.
Scott S Auerbach Joshua G Dekeyser Matthew A Stoner Curtis J Omiecinski 《Drug metabolism and disposition》2007,35(3):428-439
The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode structurally diverse proteins. One form of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are predicted to reshape the ligand-binding pocket. The current studies show a marked, ligand-independent, CAR2-mediated transactivation of reporters containing optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand binding domain was critical for achieving these effects. CAR2 interaction with SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher constitutive activity. Alternatively, mutating Ser233 to an aspartate residue drastically reduced the transactivation capacity of CAR2. The respective abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter element correlated with their ability to interact with RxRalpha and to recruit SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In addition, CAR2 displays novel dose responses to clotrimazole and androstanol compared with the reference form of the receptor while at the same time retaining the ability to bind CITCO. This result supports a hypothesis whereby the four-amino-acid insertion in CAR2 structurally modifies its ligand binding pocket, suggesting that CAR2 is regulated by a set of ligands distinct from those governing the activity of reference CAR. 相似文献
52.
FDA’S Perspectives on Cardiovascular Devices 总被引:1,自引:0,他引:1
Eric A. Chen Sonna M. Patel-Raman Kathryn O’Callaghan Matthew G. Hillebrenner 《Journal of cardiovascular translational research》2009,2(2):143-146
The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a
review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices
and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the
health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug
& Cosmetic Act, §903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 ). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization
therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA’s review of extensive preclinical
bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer
to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device
performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different
marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular
device in a U.S. clinical trial. 相似文献
53.
Anna Krygowska-Wajs William P. Cheshire Zbigniew K. Wszolek Alicja Hubalewska-Dydejczyk Barbara Jasinska-Myga Matthew J. Farrer Marek Moskala Anna Sowa-Staszczak 《Parkinsonism & related disorders》2009,15(9):692-696
ObjectiveTo assess for the presence of gastric dysmotility in familial and sporadic Parkinson disease (PD).Methods10 subjects with familial Parkinson disease (fPD), 35 subjects with sporadic Parkinson disease (sPD), and 15 controls, all from academic tertiary care movement disorders centers, were studied. fPD was defined as the presence of at least 2 affected individuals within 2–3 consecutive generations in a family. Molecular genetic analysis has not revealed, thus far, any known genomic abnormality in these families. Gastric emptying was assessed by dynamic abdominal scintigraphy over 92 min following ingestion of a solid meal containing 99mTc-labeled colloid of 40 MBq activity. The main outcome measures were gastric emptying half-time and radiotracer activity over the gastric area at 46 and at 92 min.ResultsGastric emptying time was delayed in 60% of subjects with PD. In comparison to mean t1/2 of 38 ± 7 min in controls, mean t1/2 was 58 ± 25 min in fPD (p = 0.02) and 46 ± 25 min in sPD (p = 0.10). Both fPD and sPD groups included subjects with delayed gastric emptying at an early stage of disease.ConclusionsPatients with fPD showed significantly delayed gastric emptying in comparison to normal age-matched individuals. Further studies of gastrointestinal dysfunction in PD, particularly fPD, are warranted. 相似文献
54.
Chad G. Ball Andrew W. Kirkpatrick Matthew Smith Robert H. Mulloy Leonard Tse Ian B. Anderson 《European journal of trauma and emergency surgery》2007,33(5):550-552
Abstract We report a case of SMV injury in a critically ill patient. The patient was a 19-year-old woman involved in a motor vehicle
collision. Her injuries included grade II splenic and renal lacerations, devascularized and lacerated right and transverse
colon, a transected transverse mesocolon, a massive shear injury of her abdominal wall, and two partial SMV transections.
At initial damage control laparotomy, the SMV was ligated, the devascularized bowel resected and a temporary abdominal closure
applied. At re-operation, a mesocaval shunt using saphenous vein was employed. The shunt failed and the patient required a
saphenous vein jump graft. Although visceral vascular injuries are rare, ligation of the SMV in a damage control situation
is acceptable. This case study is the first to discuss appropriate treatment when interruption to a patient's collateral visceral
venous drainage limits the surgeon’s ability to ligate. In these situations, bypass shunts may be successful. 相似文献
55.
56.
Reframing climate change as a public health issue: an exploratory study of public reactions 总被引:1,自引:0,他引:1
Edward W Maibach Matthew Nisbet Paula Baldwin Karen Akerlof Guoqing Diao 《BMC public health》2010,10(1):299
Background
Climate change is taking a toll on human health, and some leaders in the public health community have urged their colleagues to give voice to its health implications. Previous research has shown that Americans are only dimly aware of the health implications of climate change, yet the literature on issue framing suggests that providing a novel frame - such as human health - may be potentially useful in enhancing public engagement. We conducted an exploratory study in the United States of people's reactions to a public health-framed short essay on climate change. 相似文献57.
58.
Margaret MacDonald Matthew Law John Kaldor Jim Hales Gregory J. Dore 《The International journal on drug policy》2003,14(5-6):353
Objective: To examine the effectiveness of needle and syringe programmes (NSPs) in preventing HIV transmission among injecting drug users (IDUs).Methods: An ecological study design was used to determine change in HIV prevalence among injecting drug users between cities with and without NSPs. Several data sources, such as electronic journal databases, surveillance reports, websites, and index review of relevant journals, were used to identify studies of HIV seroprevalence among IDUs, and presence of NSPs. The rate of change in HIV prevalence was estimated by regression analysis.Results: There were 778 years of data from 99 cities globally included in the analysis. HIV prevalence decreased by 18.6% per annum in cities that introduce NSPs, and increased by 8.1% in cities that had never introduced NSPs (mean difference −24.7% [95% CI: −43.8, 0.5%], P=0.06). The mean difference was –33% when comparison was weighted to one over the variance of the regression estimator (29% decrease in cities with NSPs and 5% increase in cities without NSPs, P<0.001). When analysis was restricted to cities with first HIV seroprevalence less than 10%, the average annual change in seroprevalence was 18% lower in cities with NSPs (P=0.03).Conclusions: Despite the inherent limitations within an ecological study design, the study provides additional evidence that NSPs reduce transmission of HIV infection. The rapid spread of HIV among IDU populations and increasing rates of injecting in many countries calls for scaling up of NSPs as well as other harm reduction strategies. 相似文献
59.
Michael D. Lara M.D. Matthew T. Baker M.D. Christopher J. Larson PA-C R.D. Michelle A. Mathiason M.S. Pamela J. Lambert R.N. Shanu N. Kothari M.D. 《Surgery for obesity and related diseases》2005,1(1):597-21
BACKGROUND: There is no consensus regarding the optimal rate of follow-up in the post-bariatric surgery patient population. METHODS: The records of all patients who underwent laparoscopic Roux-en-Y gastric bypass from 2001 to 2003 were reviewed. Using patient zip codes, travel distances were calculated between the patients' places of residence and our clinic. Patients were then assigned to 1 of 3 cohorts according to the following distances: (1) < 50 miles, (2) 50 to 100 miles, and (3) > 100 miles. Patient compliance with follow-up appointments at 3 weeks, 3 months, 6 months, 9 months, and 12 months was analyzed. Linear trends were identified using the Mantel-Haenszel test. Age and sex were analyzed as possible predictors of compliance using the chi(2) test. P values < .05 were considered statistically significant. RESULTS: The study group comprised 150 patients (127 females and 23 males). The 3 cohorts contained 115, 21, and 14 patients, respectively. All patients in each cohort were compliant with the 3-week follow-up appointment. Although there were differences in compliance between cohorts at each of the remaining appointments, only the 9-month (70.3% vs 61.9% vs 35.7%) visit showed statistical significance (P = .035). The 6-month visit trended toward significance (85.2% vs 76.2% vs 64.3%; P = .088). Males were more likely to be compliant with the 12-month follow-up (P = .040). When controlling for sex, travel distance was also a predictor of compliance at this follow-up visit (P = .024). Age was not predictive of compliance (P = .827). CONCLUSION: Based on our findings, we conclude that travel distance from the clinic does not significantly affect compliance at the initial follow-up, 3-month, and 12-month appointments. However, distance does tend to affect compliance at the 6-month appointment and significantly affects compliance at the 9-month appointment. Males are more likely to be compliant at the 12 month follow-up visit. We must continue to strive for 100% follow-up in our post-bariatric surgery patients. 相似文献
60.
Alok Bhargava Matthew Jukes Damaris Ngorosho Charles Khilma Donald A P Bundy 《American journal of human biology》2005,17(3):280-292
This paper models the proximate determinants of school attendance and scores on cognitive and educational achievement tests and on school examinations of over 600 schoolchildren from the Control group of a randomized trial in Tanzania, where children in the Intervention group heavily infected with hookworm and schistosomiasis received treatment. The modeling approach used a random effects framework and incorporated the inter-relationships between school attendance and performance on various tests, controlling for children's health status, socioeconomic variables, grade level, and the educational infrastructure. The empirical results showed the importance of variables such as children's height and hemoglobin concentration for the scores, especially on educational achievement tests that are easy to implement in developing countries. Also, teacher experience and work assignments were significant predictors of the scores on educational achievement tests, and there was some evidence of multiplicative effects of children's heights and work assignments on the test scores. Lastly, some comparisons were made for changes in test scores of treated children in the Intervention group with the untreated children in the Control group. 相似文献