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Article ; Online: Moving beyond diet and colorectal cancer.

Pusatcioglu, Cenk K / Braunschweig, Carol

Journal of the American Dietetic Association

2011 Volume 111, Issue 10, Page(s) 1476–1478

MeSH term(s)	Body Height ; Body Mass Index ; Body Weight ; Colonic Neoplasms/epidemiology ; Diet ; Female ; Fruit ; Humans ; Male ; Nutrition Surveys ; Obesity/epidemiology ; Rectal Neoplasms/epidemiology ; Vegetables
Language	English
Publishing date	2011-09-28
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	390806-9
ISSN	1878-3570 ; 0002-8223
ISSN (online)	1878-3570
ISSN	0002-8223
DOI	10.1016/j.jada.2011.07.015
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Article ; Online: Clinical Presentation of Acute Gastroenteritis in Children With Functional Abdominal Pain Disorders.

Saps, Miguel / Mintjens, Stijn / Pusatcioglu, Cenk K / Cohen, Daniel M / Sternberg, Petra

Journal of pediatric gastroenterology and nutrition

2017 Volume 65, Issue 2, Page(s) 165–167

Abstract: Visceral hypersensitivity and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with visceral hypersensitivity would report more pain if their gut is acutely inflamed. The ... ...

Abstract	Visceral hypersensitivity and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with visceral hypersensitivity would report more pain if their gut is acutely inflamed. The aim of the study was to compare clinical symptoms and somatization of children with and without FAPDs at time of an episode of acute gastroenteritis. Seventy children with acute gastroenteritis and their parents completed the Rome III Diagnostic Questionnaire for Pediatric Functional GI Disorders and the Children's Somatization Inventory. Twenty-one percent of children were diagnosed with an FAPD. Children with FAPDs showed significantly more nongastrointestinal somatic symptoms than children without FAPDs. There were no significant differences in abdominal pain, nausea, vomiting, or school absenteeism between both groups at time of consultation.
MeSH term(s)	Abdominal Pain/diagnosis ; Abdominal Pain/etiology ; Abdominal Pain/psychology ; Acute Disease ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Gastroenteritis/complications ; Gastroenteritis/diagnosis ; Gastroenteritis/psychology ; Humans ; Irritable Bowel Syndrome/complications ; Irritable Bowel Syndrome/psychology ; Male ; Prospective Studies ; Severity of Illness Index ; Somatoform Disorders/complications ; Somatoform Disorders/diagnosis ; Somatoform Disorders/psychology
Language	English
Publishing date	2017-07-20
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000001466
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Article ; Online: Clinical presentation of acute gastroenteritis in children with functional gastrointestinal disorders.

Saps, Miguel / Mintjens, Stijn / Pusatcioglu, Cenk K / Cohen, Daniel M / Sternberg, Petra

Journal of pediatric gastroenterology and nutrition

2016

Abstract: Visceral hypersensitivity (VH) and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with VH would report more pain if their gut is acutely inflamed. Aims- Compare clinical ... ...

Abstract	Visceral hypersensitivity (VH) and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with VH would report more pain if their gut is acutely inflamed. Aims- Compare clinical symptoms and somatization of children with and without FAPDs at time of an episode of acute gastroenteritis (AGE). Seventy children with AGE and their parents completed the Rome III Diagnostic Questionnaire for Pediatric Functional GI Disorders and the Children's Somatization Inventory. Twenty-one percent of children were diagnosed with a FAPD. Children with FAPDs showed significantly more non-gastrointestinal somatic symptoms than children without FAPDs. There were no significant differences in abdominal pain, nausea, vomiting, or school absenteeism between both groups at time of consultation.
Language	English
Publishing date	2016-11-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000001466
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Article ; Online: A comprehensive review of randomized placebo-controlled pharmacological clinical trials in children with functional abdominal pain disorders.

Saps, Miguel / Biring, Harman S / Pusatcioglu, Cenk K / Mintjens, Stijn / Rzeznikiewiz, Damian

Journal of pediatric gastroenterology and nutrition

2015 Volume 60, Issue 5, Page(s) 645–653

Abstract: Objectives: Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are the most common cause of consultation to pediatric gastroenterology; however, no medications have been approved to treat this group of disorders in children. The ...

Abstract	Objectives: Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are the most common cause of consultation to pediatric gastroenterology; however, no medications have been approved to treat this group of disorders in children. The Food and Drug Administration have published recommendations for clinical trials on AP-FGIDs in adults but not in children. The lack of methodological guidelines and accepted primary endpoints for clinical trials in children hampers the progress of the field, making the approval of new medications difficult. A necessary first step to determine the feasibility of clinical trials in children and provide recommendations on the best design for future trials is to review the methods, ability to recruit, attrition rate, and results of previous clinical trials. We designed a comprehensive review of pharmacological clinical trials in AP-FGIDs in children focused on study design. Methods: Study eligibility was randomized controlled trials (RCTs) evaluating the efficacy of pharmacological interventions compared with that of placebo in children and adolescents with AP-FGIDs. Results: There is no evidence to support the use of most commonly used drugs in children. Only 7 pharmacological RCTs on AP-FGIDs in children were found. Most studies were single center based and had a small sample size. The methods and outcomes were heterogeneous. Primary endpoints varied widely among studies. Many of the RCTs did not show a consistently significant benefit of the drug over placebo in some or all of the outcomes. We found a considerable risk of bias in most studies. None of the studies have considered minimal clinically important differences in their selection of primary endpoints. Conclusions: Few randomized clinical trials have been conducted. Most studies have methodological limitations and small sample size. There is an urgent need for well-designed randomized clinical trials using age-appropriate validated outcome measures.
MeSH term(s)	Abdominal Pain/drug therapy ; Abdominal Pain/etiology ; Adolescent ; Child ; Gastrointestinal Diseases/complications ; Humans ; Placebos/therapeutic use ; Randomized Controlled Trials as Topic ; Research Design
Chemical Substances	Placebos
Language	English
Publishing date	2015-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000000718
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Construct validity of the pediatric Rome III criteria.

Saps, Miguel / Nichols-Vinueza, Diana X / Mintjens, Stijn / Pusatcioglu, Cenk K / Velasco-Benítez, Carlos A

Journal of pediatric gastroenterology and nutrition

2014 Volume 59, Issue 5, Page(s) 577–581

Abstract: Objectives: Functional gastrointestinal disorders (FGIDs) are common. The diagnosis of FGIDs is based on the Rome criteria, a symptom-based diagnostic classification established by expert consensus. There is little evidence of validity for the pediatric ...

Abstract	Objectives: Functional gastrointestinal disorders (FGIDs) are common. The diagnosis of FGIDs is based on the Rome criteria, a symptom-based diagnostic classification established by expert consensus. There is little evidence of validity for the pediatric Rome III criteria. The construct validity of the criteria, an overarching term that incorporates other forms of validity, has never been assessed. We assessed the construct validity of the Rome III criteria. Methods: Children from 2 schools in Colombia completed the Questionnaire on Pediatric Gastrointestinal Symptoms at baseline and weekly questionnaires of somatic symptoms and disability for 8 weeks (presence and intensity of gastrointestinal symptoms, nongastrointestinal symptoms, impact on daily activities). A total of 255 children completed at least 6 weekly surveys (2041 surveys). Results: At baseline, 27.8% children were diagnosed as having an FGID. Prevalence of nausea (Δ 7.8%, 95% confidence interval [CI] 4.46-11.14), constipation (Δ 4.39%, 95% CI 1.79-6.99), diarrhea (Δ 6.69%, 95% CI 3.25-10.13), headache (Δ 7.4%, 95% CI 3.51-11.09), chest pain (Δ 9.04%, 95% CI 5.20-12.88), and limb pain (Δ 4.07%, 95% CI 1.76-6.37) and intensity of nausea (Δ 0.23, 95% CI 0.127-0.333), diarrhea (Δ 0.30, 95% CI 0.211-0.389), abdominal pain (Δ 0.18, 95% CI 0.069-0.291), headache (Δ 0.17, 95% CI 0.091-0.249), and limb pain (Δ 0.30, 95% CI 0.084-0.516) were higher in children with FGIDs (P < 0.001). Children with FGIDs had greater interference with daily activities (P < 0.001). Conclusions: Children with a Rome III diagnosis had significantly more gastrointestinal and nongastrointestinal complaints, and greater intensity of symptoms and disability than children without an FGID diagnosis. The study suggests that the Rome III pediatric criteria have adequate construct validity.
MeSH term(s)	Activities of Daily Living ; Child ; Colombia/epidemiology ; Constipation/diagnosis ; Constipation/etiology ; Diagnosis, Differential ; Diarrhea/diagnosis ; Diarrhea/etiology ; Female ; Gastrointestinal Diseases/complications ; Gastrointestinal Diseases/diagnosis ; Gastrointestinal Diseases/epidemiology ; Health Surveys ; Humans ; Male ; Nausea/diagnosis ; Nausea/etiology ; Pain/diagnosis ; Pain/etiology ; Prevalence ; Severity of Illness Index ; Surveys and Questionnaires ; Symptom Assessment
Language	English
Publishing date	2014-11
Publishing country	United States
Document type	Journal Article ; Validation Studies
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000000482
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Systemic and tumor level iron regulation in men with colorectal cancer: a case control study

Pusatcioglu, Cenk K / Nemeth, Elizabeta / Fantuzzi, Giamila / Llor, Xavier / Freels, Sally / Tussing-Humphreys, Lisa / Cabay, Robert J / Linzmeier, Rose / Ng, Damond / Clark, Julia / Braunschweig, Carol

Nutrition & metabolism. 2014 Dec., v. 11, no. 1

2014

Abstract: BACKGROUND: Increased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations ... ...

Abstract	BACKGROUND: Increased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations are decreased during low iron status and increased during inflammation. The role of hepcidin and the factors influencing its regulation in CRC remains largely unknown. This study explored systemic and tumor level iron regulation in men with CRC. METHODS: The participants were 20 CRC cases and 20 healthy control subjects. Colonic tissue (adenocarcinoma [cases] healthy mucosa [controls]) was subjected to quantitative PCR (hepcidin, iron transporters and IL-6) and Perls’ iron staining. Serum was analyzed using ELISA for hepcidin, iron status (sTfR) and inflammatory markers (CRP, IL-6, TNF-α). Anthropometrics, dietary iron intake and medical history were obtained. RESULTS: Cases and controls were similar in demographics, medication use and dietary iron intake. Systemically, cases compared to controls had lower iron status (sTfR: 21.6 vs 11.8 nmol/L, p < 0.05) and higher marker of inflammation (CRP: 8.3 vs 3.4 μg/mL, p < 0.05). Serum hepcidin was mildly decreased in cases compared to controls; however, it was within the normal range for both groups. Within colonic tissue, 30% of cases (6/20) presented iron accumulation compared to 5% of controls (1/20) (χ² = 5.0; p < 0.05) and higher marker of inflammation (IL-6: 9.4-fold higher compared to controls, p < 0.05). Presence of adenocarcinoma iron accumulation was associated with higher serum hepcidin (iron accumulation group 80.8 vs iron absence group 22.0 ng/mL, p < 0.05). CONCLUSIONS: While CRC subjects had serum hepcidin concentrations in the normal range, it was higher given their degree of iron restriction. Inappropriately elevated serum hepcidin may reduce duodenal iron absorption and further increase colonic adenocarcinoma iron exposure. Future clinical studies need to assess the appropriateness of dietary iron intake or iron supplementation in patients with CRC.
Keywords	adenocarcinoma ; blood serum ; case-control studies ; clinical trials ; colorectal neoplasms ; demographic statistics ; drug therapy ; enterocytes ; enzyme-linked immunosorbent assay ; hepcidin ; inflammation ; interleukin-6 ; iron absorption ; liver ; medical history ; men ; patients ; quantitative polymerase chain reaction ; risk ; transporters ; tumor necrosis factor-alpha
Language	English
Dates of publication	2014-12
Size	p. 595.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	2160376-5
ISSN	1743-7075
ISSN	1743-7075
DOI	10.1186/1743-7075-11-21
Database	NAL-Catalogue (AGRICOLA)

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Article: Systemic and tumor level iron regulation in men with colorectal cancer: a case control study.

Nutrition & metabolism

2014 Volume 11, Page(s) 21

Abstract: Background: Increased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations ... ...

Abstract	Background: Increased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations are decreased during low iron status and increased during inflammation. The role of hepcidin and the factors influencing its regulation in CRC remains largely unknown. This study explored systemic and tumor level iron regulation in men with CRC. Methods: The participants were 20 CRC cases and 20 healthy control subjects. Colonic tissue (adenocarcinoma [cases] healthy mucosa [controls]) was subjected to quantitative PCR (hepcidin, iron transporters and IL-6) and Perls' iron staining. Serum was analyzed using ELISA for hepcidin, iron status (sTfR) and inflammatory markers (CRP, IL-6, TNF-α). Anthropometrics, dietary iron intake and medical history were obtained. Results: Cases and controls were similar in demographics, medication use and dietary iron intake. Systemically, cases compared to controls had lower iron status (sTfR: 21.6 vs 11.8 nmol/L, p < 0.05) and higher marker of inflammation (CRP: 8.3 vs 3.4 μg/mL, p < 0.05). Serum hepcidin was mildly decreased in cases compared to controls; however, it was within the normal range for both groups. Within colonic tissue, 30% of cases (6/20) presented iron accumulation compared to 5% of controls (1/20) (χ(2) = 5.0; p < 0.05) and higher marker of inflammation (IL-6: 9.4-fold higher compared to controls, p < 0.05). Presence of adenocarcinoma iron accumulation was associated with higher serum hepcidin (iron accumulation group 80.8 vs iron absence group 22.0 ng/mL, p < 0.05). Conclusions: While CRC subjects had serum hepcidin concentrations in the normal range, it was higher given their degree of iron restriction. Inappropriately elevated serum hepcidin may reduce duodenal iron absorption and further increase colonic adenocarcinoma iron exposure. Future clinical studies need to assess the appropriateness of dietary iron intake or iron supplementation in patients with CRC.
Language	English
Publishing date	2014-05-13
Publishing country	England
Document type	Journal Article
ISSN	1743-7075
ISSN	1743-7075
DOI	10.1186/1743-7075-11-21
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Article ; Online: Excess of proximal microsatellite-stable colorectal cancer in African Americans from a multiethnic study.

Xicola, Rosa M / Gagnon, Molly / Clark, Julia R / Carroll, Timothy / Gao, Weihua / Fernandez, Christian / Mijic, Dragana / Rawson, James B / Janoski, Ashley / Pusatcioglu, Cenk K / Rajaram, Priyanka / Gluskin, Adam B / Regan, Maureen / Chaudhry, Vivek / Abcarian, Herand / Blumetti, Jennifer / Cintron, Jose / Melson, Joshua / Xie, Hui /

Guzman, Grace / Emmadi, Rajyasree / Alagiozian-Angelova, Victoria / Kupfer, Sonia S / Braunschweig, Carol / Ellis, Nathan A / Llor, Xavier

Clinical cancer research : an official journal of the American Association for Cancer Research

2014 Volume 20, Issue 18, Page(s) 4962–4970

Abstract: Purpose: African Americans (AA) have the highest incidence of colorectal cancer compared with other U.S. populations and more proximal colorectal cancers. The objective is to elucidate the basis of these cancer disparities.: Experimental design: Of ... ...

Abstract	Purpose: African Americans (AA) have the highest incidence of colorectal cancer compared with other U.S. populations and more proximal colorectal cancers. The objective is to elucidate the basis of these cancer disparities. Experimental design: Of note, 566 AA and 328 non-Hispanic White (NHW) colorectal cancers were ascertained in five Chicago hospitals. Clinical and exposure data were collected. Microsatellite instability (MSI) and BRAF (V600E) and KRAS mutations were tested. Statistical significance of categorical variables was tested by the Fisher exact test or logistic regression and age by the Mann-Whitney U test. Results: Over a 10-year period, the median age at diagnosis significantly decreased for both AAs (68-61; P < 0.01) and NHWs (64.5- 62; P = 0.04); more AA patients were diagnosed before age 50 than NHWs (22% vs. 15%; P = 0.01). AAs had more proximal colorectal cancer than NHWs (49.5% vs. 33.7%; P < 0.01), but overall frequencies of MSI, BRAF and KRAS mutations were not different nor were they different by location in the colon. Proximal colorectal cancers often presented with lymphocytic infiltrate (P < 0.01) and were diagnosed at older ages (P = 0.02). Smoking, drinking, and obesity were less common in this group, but results were not statistically significant. Conclusions: Patients with colorectal cancer have gotten progressively younger. The excess of colorectal cancer in AAs predominantly consists of more proximal, microsatellite stable tumors, commonly presenting lymphocytic infiltrate and less often associated with toxic exposures or a higher BMI. Younger AAs had more distal colorectal cancers than older ones. These data suggest two different mechanisms driving younger age and proximal location of colorectal cancers in AAs.
MeSH term(s)	African Americans/genetics ; Age Distribution ; Age of Onset ; Aged ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Humans ; Microsatellite Instability ; Middle Aged ; Mutation ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins/genetics
Chemical Substances	KRAS protein, human ; Proto-Oncogene Proteins ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2014-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-14-0353
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