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Kisiel J.B.,Mayo Medical School | Yab T.C.,Mayo Medical School | Nazer Hussain F.T.,Mayo Medical School | Taylor W.R.,Mayo Medical School | And 7 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2013

Background Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD-CRN) are suboptimal. Aim To test the feasibility of using stool assay of exfoliated DNA markers to detect IBD-CRN. Methods This investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD-CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD-CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method. Results IBD-CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD-CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade. Conclusion These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease. © 2013 Blackwell Publishing Ltd. Source

Arabia G.,Rochester College | Arabia G.,University of Catanzaro | Grossardt B.R.,Biomedical Statistics and Informatics | Bower J.H.,Rochester College | And 4 more authors.
Neurology | Year: 2010

OBJECTIVE: It has been suggested that people who develop Parkinson disease (PD) may have a characteristic premorbid personality. We tested this hypothesis using a large historical cohort study with long follow-up. METHODS: We conducted a historical cohort study in the region including the 120-mile radius centered in Rochester, MN. We recruited 7,216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 through 1965 and we considered 5 MMPI scales to measure sensation seeking, hypomania, positive emotionality, social introversion, and constraint. A total of 6,822 subjects (94.5% of the baseline sample) were followed over 4 decades either actively (via interview and examination) or passively (via medical records). RESULTS: During follow-up, 227 subjects developed parkinsonism (156 developed PD). The 3 MMPI scales that we selected to measure the extroverted personality construct (sensation seeking, hypomania, and positive emotionality) did not show the expected pattern of higher scores associated with reduced risk of PD. Similarly, the 2 MMPI scales that we selected to measure the introverted personality construct (social introversion and constraint) did not show the expected pattern of higher scores associated with increased risk of PD. However, higher scores for constraint were associated with an increased risk of all types of parkinsonism pooled together (hazard ratio 1.39; 95% CI 1.06-1.84; p = 0.02). CONCLUSIONS: We suggest that personality traits related to introversion and extroversion do not predict the risk of PD. © 2010 by AAN Enterprises, Inc. Source

Larsen B.T.,Mayo Medical School | Edwards W.D.,Mayo Medical School | Jensen M.H.,Divisions of Cardiovascular Diseases | Johnson C.H.,Divisions of Cardiovascular Diseases | And 3 more authors.
American Journal of Surgical Pathology | Year: 2013

Hypothenar hammer syndrome (HHS) is characterized by digital ischemia after repetitive traumatic injury to the ulnar artery. Some hypothesize that susceptible patients have an intrinsic vasculopathy such as fibromuscular dysplasia (FMD). To investigate this hypothesis, we reviewed our institutional experience with this syndrome over 25 years. Clinical records were reviewed from all patients who underwent surgical treatment for HHS (1987 to 2011), and histologic features of excised ulnar arteries were characterized. A total of 67 patients (mean age 45 y; range, 21 to 75 y; 65 men) were treated for unilateral or bilateral disease. Common symptoms included digital pain (96% of cases), cold intolerance (79%), cyanosis (70%), numbness (54%), tingling (51%), and ulceration (40%). Angiography showed ulnar artery occlusion (89%), irregularity (56%), tortuosity (46%), and digital emboli (89%). Common pathologic features (from 75 specimens) included: luminal thrombosis (87%); intimal thickening (60%) and fibrosis (57%); internal elastic membrane disruption (95%); medial fibrosis (96%), hypertrophy (43%), neovascularization (49%), dilatation (29%), and disruption (25%); and adventitial neovascularization (53%). Specific features of dysplasia were present in 10 cases (15%), including smooth muscle disorganization and additional smooth muscle bundles outside the external elastic membrane, but typical FMD was not identified. Histologic features in HHS most often represent secondary changes consistent with repetitive trauma. Dysplastic features can be found in occasional cases, but FMD does not appear to contribute to HHS in most patients. Angiography should be interpreted with caution in superficial locations, as a string-of-beads appearance may simply reflect a posttraumatic corkscrew deformity of the ulnar artery.Copyright © 2013 by Lippincott Williams &Wilkins. Source

Roberts R.O.,Divisions of Epidemiology | Cha R.H.,Biomedical Statistics and Informatics | Mielke M.M.,Divisions of Epidemiology | Geda Y.E.,Divisions of Epidemiology | And 3 more authors.
Neurology | Year: 2015

Objective: To determine risk and protective factors for mild cognitive impairment (MCI) among persons 85 years and older. Methods: Participants in the population-based prospective Mayo Clinic Study of Aging were comprehensively evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed by self-reported questionnaire; vascular and comorbid conditions were abstracted from participants' medical records. Results: Of 256 participants who were cognitively normal at enrollment (median age 87.3 years, 62% women), 121 developed MCI at a median 4.1 years of follow-up. Predictors of MCI were APOE ε4 allele (hazard ratio [HR] 1.89; p 0.008), current depressive symptoms (HR 1.78; p 0.02), midlife onset of hypertension (HR 2.43; p 0.005), increasing number of vascular diseases (HR 1.13; p 0.02), and chronic conditions from the Charlson Comorbidity Index (HR 1.08; p 0.006). Models were adjusted for sex and education, with age as the time variable. The risk of MCI was reduced for participants who reported engagement in artistic (HR 0.27; p 0.03), craft (HR 0.55; p 0.02), and social (HR 0.45; p 0.005) activities in both midlife and late life, and in the use of a computer in late life (HR 0.47; p 0.008). Conclusions: Chronic disease burden increases risk of MCI, whereas certain lifestyle factors reduce risk in persons 85 years and older. This implies that preventive strategies for MCI may need to begin in midlife and should persist throughout late life. © 2015 American Academy of Neurology. Source

Onkendi E.O.,Mayo Medical School | Naik N.D.,Mayo Medical School | Rosedahl J.K.,Biomedical Statistics and Informatics | Harmsen S.W.,Biomedical Statistics and Informatics | And 4 more authors.
Journal of Gastrointestinal Surgery | Year: 2014

Background: Data comparing operative and endoscopic resection of adenomas of the ampulla of Vater are limited. Our aims were to evaluate and compare the long-term results and outcomes of endoscopic and operative resections of benign tumors of the ampulla of Vater as well as to determine which features of benign periampullary neoplasms would predict recurrence or failure of endoscopic therapy and therefore need for operative treatment. Methods: Retrospective review of all patients treated for adenomas of ampulla of Vater at our institution from 1994 to 2009. Results: Over a 15-year span, 180 patients (mean age 59 years) were treated for benign adenomas of the ampulla of Vater with a mean follow-up of 4.4 years. Obstructive jaundice was more common in the operative resection group (p = 0.006). The adenomas were tubular in 83 patients (44 %), tubulovillous in 77 (45 %) and villous in 20 (11 %). Endoscopic resection alone was performed in 130 patients (78 %). Operative resection was performed in 50 patients (28 %), with pancreatoduodenectomy in 40, transduodenal local resection in 9, and pancreas-sparing total duodenectomy in 1. Nine patients who underwent endoscopic resection initially were endoscopic treatment failures. Fifty-eight percent of endoscopically treated patients required one endoscopic resection, while 58 (42 %) required two or more endoscopic resections (range 2–8). Patients who underwent operative resection had larger tumors with a mean size of 3.7 ± 2.8 versus 1.8 ± 1.5 cm in those treated by endoscopic resection (p < 0.001) or intraductal extension (p = 0.02). Intraductal extension and ulceration had no effect on recurrence if completely resected endoscopically (p = 0.41 and p = 0.98, respectively). Postoperative complications occurred in 58 % of patients, and post-endoscopic complications in 29 % (p < 0.001). Endoscopic resection was associated with a greater than fivefold risk of recurrence than operative resection (p = 0.006); 4 % of recurrences had invasive carcinomas. When comparing patients who underwent local resections only (endoscopic and operative), there was no difference in the recurrence rate between endoscopic resection and operative transduodenal resection (32 versus 33 %; p = 0.49). The need for two or more endoscopic resections for complete tumor removal was associated with 13-fold greater risk of recurrence (p < 0.001). Conclusion: There is no significant difference between endoscopic and local operative resections of benign adenomas of ampulla of Vater; recurrences are more common when two or more endoscopic resections are required for complete tumor removal. Appropriate adenomas for endoscopic resection included tumors <3.6 cm that do not extend far enough intraductally (on EUS) to preclude an endoscopic snare ampullectomy. © 2014, The Society for Surgery of the Alimentary Tract. Source

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