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51.
Genetic testing for hereditary nonpolyposis colorectal cancer 总被引:1,自引:0,他引:1
Hoedema R Monroe T Bos C Palmer S Kim D Marvin M Luchtefeld M 《The American surgeon》2003,69(5):387-91; discussion 391-2
Approximately 80 per cent of patients with colorectal cancer have sporadic disease whereas the remaining 20 per cent seem to have a genetic component. Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common autosomal dominant hereditary syndrome predisposing to colorectal cancer. Various methods have been described to screen for HNPCC and to directly test for mismatch repair gene mutations. This study evaluates the initial results of 1) microsatellite instability (MSI) and immunohistochemistry (IHC) staining of tumors and 2) genetic sequencing for mismatch repair gene mutations in patients suspected to have HNPCC. Appropriate patients for HNPCC testing were identified through a high-risk colorectal cancer clinic. Of those patients screened only those who met Amsterdam criteria (AC) for HNPCC or were young age onset (YAO) (<40 years of age) were eligible for testing. The tumors underwent testing for MSI and had IHC performed in those patients with available tumor specimens. MSI was performed on the five markers approved by the NIH consensus conference. MSI-High (MSI-H) was defined as two or more markers being unstable. IHC was done with commercially available stains for MLH1 and MSH2. All patients had sequencing of the MLH1 and MSH2 genes performed to search for mutations by a commercial laboratory. Genetic counseling was provided and written informed consent was obtained. Fourteen patients were part of kindreds that met the AC. An additional 10 patients were <40 years of age at diagnosis of colorectal cancer but lacked any family history. Testing for MSI and IHC was performed on those available tissue blocks. Of the AC patients five had MSH2 mutations and two had MLH1 variants. Of the five with MSH2 mutations three of four had MSI-H tumors and all four had loss of expression of MSH2 on IHC. Of the MLH1 variants only one had MSI-H tumor and lacked expression of MLH-1 on IHC. Of those patients with no mutation identified three of six had MSI-H tumors. For those patients YAO no genetic mutations were identified. Two of the seven had MSI-H tumors. Genetic testing for HNPCC even in those patients fulfilling the rigid AC yielded mutations in only five of 14 patients with variants of unknown significance being found in an additional two patients. Only one MSH2 variant of unknown significance was identified in the 10 YAO patients, which would suggest that screening in this group of patients with MSI and/or IHC would be appropriate. 相似文献
52.
Julian Brunner Cindy L. Cain Elizabeth M. Yano Alison B. Hamilton 《Women's health issues》2019,29(1):64-71
Background
The Veterans Health Administration (VHA) faces challenges in providing comprehensive, gender-sensitive care for women. National policies have led to important advancements, but local leadership also plays a vital role in implementing changes and operationalizing national priorities. In this article, we explore the notions of ideal women veterans' health care articulated by women's health leaders at local VHA facilities and regional networks, with the goal of identifying elements that could inform practice and policy.Methods
We conducted semistructured interviews with 86 local and regional women's health leaders at 12 VHA medical centers across four regions. At the conclusion of interviews about women's primary care, participants were asked to imagine “ideal care” for women veterans. Interviews were transcribed and coded using a hybrid inductive/deductive approach.Results
In describing ideal care, participants commonly touched on whether women veterans should have separate primary care services from men; the need for childcare, expanded reproductive health services, resources, and staffing; geographic accessibility; the value of input from women veterans; the physical appearance of facilities; fostering active interest in women's health across providers and staff; and the relative priority of women's health at the VHA.Conclusions
Policy and practice changes to care for women veterans must be mindful of key stakeholders' vision for that care. Specific features of that vision include clinic construction that anticipates a growing patient population, providing childcare and expanded reproductive health services, ensuring adequate support staff, expanding mechanisms to incorporate women veterans' input, and fostering a culture oriented towards women's health at the organizational level. 相似文献53.
AbstractObjectives: To achieve a better understanding of medication non-adherence determinants in older people with dementia from caregivers’ perspectives and possible management solutions to improve medication adherence.Method: Semi-structured telephone interviews were conducted with 20 caregivers of older people with dementia living in the community. Data was analyzed using an inductive thematic analysis based on Braun and Clarke’s method.Findings: Four themes emerged: dementia symptoms influence medication adherence, medication increases caregiver burden, lack of self-efficacy, medication aids and technology to enhance medication adherence. Caregivers’ lack of knowledge reduces their self-efficacy in managing medications and increases their burden of care. The majority of caregivers used technology and welcomed its use to assist them with their role.Conclusion: Caregivers require knowledge and support such as a multifaceted technology based intervention to assist with medication adherence. 相似文献
54.
55.
Cuiqing Fan Chuntao Zhao Feng Zhang Meenu Kesarwani Zhaowei Tu Xiongwei Cai Ashley Kuenzi Davis Lingli Xu Cindy L. Hochstetler Xiaoyi Chen Fukun Guo Gang Huang Mohammad Azam Weidong Tian Q. Richard Lu Yi Zheng 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(1)
56.
57.
Spence JP Liang T Eriksson CJ Taylor RE Wall TL Ehlers CL Carr LG 《Alcoholism, clinical and experimental research》2003,27(9):1389-1394
BACKGROUND: Cytosolic aldehyde dehydrogenase, or ALDH1A1, functions in ethanol detoxification, metabolism of neurotransmitters, and synthesis of retinoic acid. Because the promoter region of a gene can influence gene expression, the ALDH1A1 promoter regions were studied to identify polymorphism, to assess their functional significance, and to determine whether they were associated with a risk for developing alcoholism. METHODS: Sequence analysis was performed in the promoter region by using Asian, Caucasian, and African American subjects. The resulting polymorphisms were assessed for frequency in Asian, Caucasian, Jewish, and African American populations and tested for associations with alcohol dependence in Asian and African American populations of alcoholics and controls. The functional significance of each polymorphism was determined through in vitro expression analysis by using HeLa and HepG2 cells. RESULTS: Two polymorphisms, a 17 base pair (bp) deletion (-416/-432) and a 3 bp insertion (-524), were discovered in the ALDH1A1 promoter region: ALDH1A1*2 and ALDH1A1*3, respectively. ALDH1A1*2 was observed at frequencies of 0.035, 0.023, 0.023, and 0.012 in the Asian, Caucasian, Jewish, and African American populations, respectively. ALDH1A1*3 was observed only in the African American population, at a frequency of 0.029. By using HeLa and HepG2 cells for in vitro expression, the activity of the luciferase reporter gene was significantly decreased after transient transfection of ALDH1A1*3-luciferase compared with the wild-type construct ALDH1A1*1-luciferase. In an African American population, a trend for higher frequencies of the ALDH1A1*2 and ALDH1A1*3 alleles was observed in a population of alcoholics (p = 0.03 and f = 0.12, respectively) compared with the control population. CONCLUSIONS: ALDH1A1*2 and ALDH1A1*3 may influence ALDH1A1 gene expression. Both ALDH1A1*2 and ALDH1A1*3 produce a trend in an African American population that may be indicative of an association with alcoholism; however, more samples are required to validate this observation. The underlying mechanisms contributing to these trends are still unknown. 相似文献
58.
Pioglitazone administration decreases cardiovascular disease risk factors in insulin-resistant smokers 总被引:1,自引:0,他引:1
Abbasi F Farin HM Lamendola C McGraw L McLaughlin T Reaven GM 《Metabolism: clinical and experimental》2008,57(8):1108-1114
Insulin sensitivity varies in cigarette smokers, and there is evidence that cardiovascular disease (CVD) risk is greatest in those smokers who are also insulin resistant. To extend these observations, we sought to (1) compare CVD risk factors in smokers who do not plan to stop smoking, divided into insulin-resistant (IR) and insulin-sensitive (IS) subgroups, and (2) evaluate the ability of drug-induced changes in insulin sensitivity to decrease CVD risk. Thirty-six cigarette smokers were divided into IR (n = 19) and IS (n = 17) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test (the higher the SSPG, the more insulin resistant the individual). In addition, baseline measurements were made of fasting lipid and lipoprotein concentrations; inflammatory markers; and daylong glucose, insulin, and free fatty acid responses to test meals. All subjects were treated with pioglitazone for 12 weeks, after which all baseline measurements were repeated. Baseline triglyceride and high-density lipoprotein cholesterol concentrations were significantly different in IR as compared with IS smokers (P < .05) both before and after adjustment for differences in sex and body mass index. After pioglitazone treatment, SSPG concentration significantly fell in the IR smokers (P < .001), associated with a significant improvement in the atherogenic lipoprotein profile seen at baseline (P ≤ .03) and a decrease in soluble intercellular adhesion molecule 1 and C-reactive protein concentrations (P = .01 and .02, respectively), whereas the IS smokers only had a significant increase in high-density lipoprotein cholesterol (P = .004) and a decrease in soluble intercellular adhesion molecule 1 (P = .02) and CRP (P = .07) levels. In conclusion, cigarette smokers have profound differences in CVD risk factors related to their degree of insulin sensitivity. It is suggested that, in addition to smoking cessation efforts, attention should be given to identifying the subgroup of smokers most at risk for CVD, but unwilling or unable to stop smoking, and to initiating appropriate therapeutic interventions to decrease CVD in this high-risk group. 相似文献
59.
Mehta RH Harjai KJ Cox DA Stone GW Brodie BR Boura J Grines L O'Neill W Grines CL;Primary Angioplasty in Myocardial Infarction investigators 《The American journal of cardiology》2005,96(7):901-906
Little is known about the influence of stenting versus balloon angioplasty on long-term outcomes (particularly mortality) after primary percutaneous coronary intervention (PCI). We evaluated 2,087 patients with ST-elevation myocardial infarction enrolled in various Primary Angioplasty in Myocardial Infarction (PAMI) trials in the United States, who underwent primary PCI. The main outcome was all-cause mortality at 5 years, obtained through the National Death Index. Of the 2,087 patients, stenting was performed in 692 (33%). The absolute difference in the hospital (2.2% vs 3.3%), 1-year (3.3% vs 5.2%), and 5-year (10% vs 13%) mortality rates favored patients receiving a stent versus conventional balloon therapy, with the difference increasing with time. A multivariate Cox model identified stent use (vs balloon alone) as an independent correlate of lower 5-year mortality (hazard ratio 0.60, 95% confidence interval 0.42 to 0.85). The absolute reduction in mortality was greatest in the highest risk group. In conclusion, compared with balloon angioplasty, stenting during primary PCI not only resulted in better angiographic and short-term outcomes, but also in a sustained beneficial effect on mortality at 5 years. These data support the routine use of coronary stenting in most patients undergoing primary PCI, when feasible. 相似文献
60.