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21.
We have identified a novel RPGR gene mutation in a large Dutch family with X-linked retinitis pigmentosa (RP3). In affected members, a G-->T transversion was found at position +1 of the 5' splice site of intron 5 of the RPGR (retinitis pigmentosa GTPase regulator) gene. Analysis of this mutation at the RNA level showed cryptic splicing upstream of the mutation in exon 5 leading to a frameshift and downstream termination codon. Identification of the causative mutation in this family has facilitated the detection of females at risk of having an affected son. 相似文献
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Resistance to diet-induced obesity is associated with increased proopiomelanocortin mRNA and decreased neuropeptide Y mRNA in the hypothalamus 总被引:11,自引:0,他引:11
Mechanisms mediating genetic susceptibility to diet-induced obesity have not been completely elucidated. Elevated hypothalamic neuropeptide Y (NPY) and decreased hypothalamic proopiomelanocortin (POMC) are thought to promote the development and maintenance of obesity. To assess the potential role of hypothalamic neuropeptide gene expression in diet-induced obesity, the present study examined effects of a high-fat diet on hypothalamic NPY and POMC mRNA in three strains of mice that differ in susceptibility to develop diet-induced obesity. C57BL/6J, CBA, and A/J mice were fed either normal rodent chow or a high-fat diet for 14 weeks after which hypothalamic gene expression was measured. On the high-fat diet, C57BL/6J mice gained the most weight, whereas A/J mice gained the least weight. On the high-fat diet, NPY mRNA significantly decreased as body weight increased in CBA and A/J mice, but not in C57BL/6J mice. In addition, POMC mRNA significantly increased as body weight increased in A/J mice, but not in CBA and C57BL/6J mice. Since decreased NPY mRNA and increased POMC mRNA would presumably attenuate weight gain, these results suggest that a high-fat diet produces compensatory changes in hypothalamic gene expression in mice resistant to diet-induced obesity but not in mice susceptible to diet-induced obesity. 相似文献
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The anomaly, the chronic patient and the play of medical power 总被引:8,自引:7,他引:1
Abstract In the middle of the twentieth century, the anomaly, the person whose body suffered the effects of an accident and who elicited a compassionate response designed to protect the anomaly from the effects of the accident, disappeared. The 'disabled,' the 'handicapped,' and the 'chronic patient' replaced the anomaly in medical discourse. This change is reflected in specific, technical aspects of medicine - medicine's understanding and treatment of two anomalous bodies and in general medical ideology and the organization of medical care. The change extended the medical gaze to the most intimate aspects of life and to the fine seams of society where the anomaly used to wander. We must understand this change as part of the paradoxical play of medical power. Medical power became more totalizing, integrative and rapidly responsive just as it became more unobtrusive, humane and liberating. 相似文献
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The epidemiology of Parkinson's disease. A case-control study of young-onset and old-onset patients 总被引:6,自引:0,他引:6
M Stern E Dulaney S B Gruber L Golbe M Bergen H Hurtig S Gollomp P Stolley 《Archives of neurology》1991,48(9):903-907
While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests that certain external factors, ie, environmental agents, may act as neurotoxins, initiating the chain of oxidative reactions that ultimately destroy neurons in the substantia nigra. Young-onset PD might result from greater exposure to a putative neurotoxin. This hypothesis has rekindled interest in the epidemiology of PD. We therefore conducted a detailed analysis of various environmental exposures and early life experiences in 80 patients with old-onset PD (at an age older than 60 years), 69 young-onset patients (younger than 40 years), and 149 age- and sex-matched control subjects. Contrary to previous reports, we were unable to implicate well water or exposure to herbicides, pesticides, or industrial toxins as significant PD risk factors. A residential history of rural living was reported by more patient cases than control subjects and was marginally significant. On the other hand, at least one episode of head trauma "severe enough to cause vertigo, dizziness, blurred or double vision, seizures or convulsions, transient memory loss, personality changes, or paralysis" occurred significantly more often prior to disease onset in patients with both young-onset and old-onset PD than in control subjects (odds ratio = 2.7). When adjusted for head trauma and rural living, smoking was inversely associated with PD, as has been previously reported (odds ratio = 0.5). There were no significant differences in early life experiences or environmental exposures between young-onset and old-onset patients. We suggest that the risk of developing PD is influenced by a variety of factors.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Daniel C Malone Jacob Abarca Philip D Hansten Amy J Grizzle Edward P Armstrong Robin C Van Bergen Babette S Duncan-Edgar Steven L Solomon Richard B Lipton 《Journal of the American Pharmacists Association》2004,44(2):142-151
OBJECTIVE: To develop a list of clinically important drug-drug interactions (DDIs) likely to be encountered in community and ambulatory pharmacy settings and detected by a computerized pharmacy system. DESIGN: Cross-sectional, one-time evaluation. SETTING: United States in fall 2001. PARTICIPANTS: An expert panel comprising two physicians, two clinical pharmacists, and an expert on DDIs. INTERVENTIONS: Systematic review of drug interaction compendia and published literature, ratings (on a 1 to 10 scale) of various clinical aspects of DDIs (e.g., clinical importance, quality and quantity of evidence, causal relationship, risk of morbidity and mortality), and a modified Delphi consensus-building process. MAIN OUTCOME MEASURE: Panelists' opinions about clinical importance of DDIs. RESULTS: The expert panel considered 56 DDIs. Of these, 28 had a mean clinical importance score of 8.0 or more. The ratings for clinical importance ranged from 3.2 to 9.6, with a mean +/- SD of 7.5 +/- 1.5 across the combinations examined. The mean score for the quality of literature suggesting the interaction exists ranged from 1.0 to 9.6, with a mean +/- SD of 5.8 +/- 2.5. In terms of substantiation of the interactions evaluated, the mean +/- SD rating was 6.3 +/- 2.2, with a range from 1.4 to 9.2. Through the modified Delphi process, the panel determined that 25 interactions were clinically important. CONCLUSION: Using an expert panel and a standard evaluation tool, 25 clinically important drug interactions that are likely to occur in the community and ambulatory pharmacy settings were identified. Pharmacists should take steps to prevent patients from receiving these interacting medications, and computer software vendors should focus interaction alerts on these and similarly important DDIs. 相似文献
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Evaluating surgical competency with the American Board of Surgery In-Training Examination, skill testing, and intraoperative assessment 总被引:6,自引:0,他引:6
BACKGROUND: Evaluation of surgical competency should include assessment of knowledge, technical skill, and judgment. The purpose of this study was to determine the relationship between the American Board of Surgery In-Training Examination (ABSITE), skill testing, and intraoperative assessment. METHODS: Postgraduate year 2 (PGY-2) and postgraduate year 3 (PGY-3) surgery residents (n = 33) were tested by means of (1) the ABSITE, (2) skill testing on a laparoscopic video-trainer, and (3) intra-operative global assessments during laparoscopic cholecystectomy. The Pearson correlation was used to determine the correlation between the ABSITE, skill testing, and intraoperative assessments. For the comparison of PGY-2 and PGY-3 resident performance, Wilcoxon rank sum tests were used. RESULTS: The ABSITE scores did not correlate with skill testing or intraoperative assessments (not significant). Skill testing correlated with the intraoperative composite score and with 4 of 8 operative performance criteria (P<.05). The ABSITE scores and skill testing were not different for PGY-2 and PGY-3 residents (not significant). Intraoperative assessments were better in 5 of 8 criteria and the composite score for PGY-3 versus PGY-2 residents (P<.05), which demonstrated construct validity. CONCLUSIONS: The ABSITE measures knowledge but does not correlate with technical skill or operative performance. Residency programs should use multiple assessment instruments to evaluate competency. There may be a role for both skill testing and intraoperative assessment in the evaluation of surgical competency. 相似文献
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