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Irritable Bowel Syndrome: HELP
Articles by Walter Morales
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, W. Morales wrote the following 8 articles about Irritable Bowel Syndrome.
 
+ Citations + Abstracts
1 Article Second-Generation Biomarker Testing for Irritable Bowel Syndrome Using Plasma Anti-CdtB and Anti-Vinculin Levels. 2019

Morales, Walter / Rezaie, Ali / Barlow, Gillian / Pimentel, Mark. ·Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 240E, Los Angeles, CA, 90048, USA. · Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 240E, Los Angeles, CA, 90048, USA. pimentelm@cshs.org. ·Dig Dis Sci · Pubmed #31152332.

ABSTRACT: BACKGROUND: ELISA testing for anti-CdtB and anti-vinculin can discriminate patients with irritable bowel syndrome with diarrhea (IBS-D) from those with inflammatory bowel disease (IBD). However, recent findings suggest the antigens can suffer from epitope instability. AIM: This study aimed to assess effects of incorporating epitope stabilization on test characteristics for distinguishing IBS-D from IBD subjects. METHODS: Plasma samples from IBS-D subjects from a large-scale clinical trial and subjects with endoscopically active IBD without concurrent immunomodulator therapy were used. After epitope stabilization, CdtB and vinculin were used in ELISA testing. Optical density readings were compared between IBS-D and IBD subjects. RESULTS: Samples from 100 IBS-D and 31 IBD (22 UC and 9 CD) subjects were tested. IBS-D subjects had higher anti-CdtB titers (P = 0.0001) and higher anti-vinculin titers (P = 0.004) than IBD subjects. The specificities of anti-CdtB and anti-vinculin to differentiate IBS-D from IBD were 93.5% and 90.9%, respectively, with sensitivities of 43.0% and 52.2%, respectively. The positive likelihood ratios of identifying IBS-D with anti-CdtB and anti-vinculin were 6.7 and 5.7, respectively. Assuming a pretest probability of 57% for diagnosis of IBS-D in patients with abdominal pain and change in bowel habits, testing positive for both antibodies resulted in a posttest probability of > 98%. CONCLUSIONS: Performing epitope stabilization for CdtB and vinculin enhances the test characteristics of ELISAs for anti-CdtB and anti-vinculin in discriminating IBS-D from IBD. Measurement of anti-CdtB and anti-vinculin with this second-generation methodology may further advance our understanding of the role of immunity in functional bowel diseases.

2 Article Assessment of Anti-vinculin and Anti-cytolethal Distending Toxin B Antibodies in Subtypes of Irritable Bowel Syndrome. 2017

Rezaie, Ali / Park, Sung Chul / Morales, Walter / Marsh, Emily / Lembo, Anthony / Kim, Jae Hak / Weitsman, Stacy / Chua, Kathleen S / Barlow, Gillian M / Pimentel, Mark. ·GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA. ali.rezaie@cshs.org. · GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians Bldg, #E226, Los Angeles, CA, 90048, USA. · Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea. · Beth Israel Deaconess Medical Center, Boston, MA, USA. · Department of Internal Medicine, Dongguk University Ilsan Hospital, The Graduate School of Dongguk University, Goyang, South Korea. ·Dig Dis Sci · Pubmed #28451914.

ABSTRACT: BACKGROUND: Antibodies to cytolethal distending toxin B (CdtB) and vinculin are novel biomarkers that rule-in and differentiate irritable bowel syndrome with diarrhea (IBS-D) from other causes of diarrhea and healthy controls. AIM: To determine whether these antibodies can also diagnose and differentiate other IBS subtypes. METHODS: Subjects with IBS-D based on Rome III criteria (n = 2375) were recruited from a large-scale multicenter clinical trial (TARGET 3). Healthy subjects without gastrointestinal (GI) diseases or symptoms (n = 43) and subjects with mixed IBS (IBS-M) (n = 25) or IBS with constipation (IBS-C) (n = 30) were recruited from two major medical centers. Plasma levels of anti-CdtB and anti-vinculin antibodies in all subjects were determined by enzyme-linked immunosorbent assay. Optical densities of ≥1.68 and ≥2.80 were considered positive for anti-vinculin and anti-CdtB, respectively. Plasma levels of anti-CdtB and anti-vinculin antibodies were highest in IBS-D and lowest in IBS-C and healthy controls (P < 0.001). Levels in IBS-C subjects were not statistically different from controls (P > 0.1). Positivity for anti-CdtB or anti-vinculin resulted in a statistically significant negative gradient from IBS-D (58.1%) to IBS-M (44.0%), IBS-C (26.7%), and controls (16.3%) (P < 0.001). CONCLUSIONS: Anti-CdtB and anti-vinculin titers and positivity rates differ in IBS subtypes, with higher antibody levels and positivity rates in IBS-D and IBS-M, and lower levels in IBS-C subjects that are similar to those in healthy controls. These antibodies appear useful in the diagnosis of IBS-M and IBS-D, but not IBS-C. Furthermore, these findings suggest that IBS-C is pathophysiologically distinct from subtypes with diarrheal components (i.e., IBS-M and IBS-D).

3 Article Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects. 2015

Pimentel, Mark / Morales, Walter / Rezaie, Ali / Marsh, Emily / Lembo, Anthony / Mirocha, James / Leffler, Daniel A / Marsh, Zachary / Weitsman, Stacy / Chua, Kathleen S / Barlow, Gillian M / Bortey, Enoch / Forbes, William / Yu, Allen / Chang, Christopher. ·GI Motility Program, Cedars-Sinai Medical Center, Los Angeles, California, United States of America. · Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America. · Department of Biostatistics, Cedars-Sinai Medical Center, Los Angeles, California, United States of America. · Salix Pharmaceuticals, Inc., Raleigh, North Carolina, United States of America. ·PLoS One · Pubmed #25970536.

ABSTRACT: Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding "organic" conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density≥2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD≥1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.

4 Article Effect of repeated Campylobacter jejuni infection on gut flora and mucosal defense in a rat model of post infectious functional and microbial bowel changes. 2013

Sung, J / Morales, W / Kim, G / Pokkunuri, V / Weitsman, S / Rooks, E / Marsh, Z / Barlow, G M / Chang, C / Pimentel, M. ·GI Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. ·Neurogastroenterol Motil · Pubmed #23521493.

ABSTRACT: BACKGROUND: Campylobacter jejuni infection is a leading cause of gastroenteritis and post infectious irritable bowel syndrome (PI-IBS). Unanswered questions include the role of cytokines, effects on gut flora, and why IBS is not more prevalent in countries with higher gastroenteritis rates. Therefore, we determined the effects of early and repeat C. jejuni infections on post infectious phenotypes, gut flora, and cytokine levels in a rat model of functional bowel and microbial changes. METHODS: Sprague-Dawley rats were gavaged with 10(8)  cfu C. jejuni as juveniles and again as adults (J+/A+), as adults only (J-/A+), or vehicle (controls). Stool consistency during acute colonization, post infectious stool wet weight, total bacteria and Methanobrevibacter smithii levels in bowel segments, and ileal cytokines were evaluated. KEY RESULTS: C. jejuni colonization was longer for first exposures as juveniles (43.4 ± 1.7 days) vs. adults (30.4 ± 3.5 days) (P < 0.01) and shortest for second exposures (10.5 ± 1.7 days, P < 0.05). Small intestinal bacterial overgrowth (SIBO) was more prevalent in J+/A+ (47%) than J-/A+ rats (26%) (P = 0.019), but J-/A+ rats had greater stool consistency alterations (P < 0.01). Ileal β-defensin 2, TLR-4, IL-8, and β-defensin 6 levels were increased in J-/A+ rats and further increased in J+/A+ rats; TNF-α was highest and IL6 lowest in J-/A+ rats. Total bacteria increased, and M. smithii decreased, with successive infections. CONCLUSIONS & INFERENCES: We conclude that C. jejuni infection results in long-term alterations in small bowel flora, including methanogens. Mucosal defense mediators appear related to the number of infections, but not to SIBO development or the development of functional bowel phenotypes.

5 Article Methanobrevibacter smithii is the predominant methanogen in patients with constipation-predominant IBS and methane on breath. 2012

Kim, Gene / Deepinder, Fnu / Morales, Walter / Hwang, Laura / Weitsman, Stacy / Chang, Christopher / Gunsalus, Robert / Pimentel, Mark. ·GI Motility Program, Division of Gastroenterology, Cedars Sinai Medical Center, 8730, Alden Dr, Suite 225 E, Los Angeles, CA 90048, USA. ·Dig Dis Sci · Pubmed #22573345.

ABSTRACT: PURPOSE: Among irritable bowel syndrome (IBS) patients, breath methane producers overwhelmingly have constipation predominance (C-IBS). Although the most common methanogen in humans is Methanobrevibacter smithii, incidence and type of methanogenic bacteria in C-IBS patients are unknown. METHODS: By use of a questionnaire and lactulose breath testing, subjects with Rome II C-IBS and methane (>3 ppm) were selected (n = 9). The control group included subjects with IBS who had no breath methane (n = 10). Presence of bacterial DNA was assessed in a stool sample of each subject by quantitative-PCR using universal 16S rDNA primer. M. smithii was quantified by use of a specific rpoB gene primer. RESULTS: M. smithii was detected in both methane and non-methane subjects. However, counts and relative proportion of M. smithii were significantly higher for methane-positive than for methane-negative subjects (1.8 × 10(7) ± 3.0 × 10(7) vs 3.2 × 10(5) ± 7.6 × 10(5) copies/g wet stool, P < 0.001; and 7.1 ± 6.3 % vs 0.24 ± 0.47 %, P = 0.02 respectively). The minimum threshold of M. smithii resulting in positive lactulose breath testing for methane was 4.2 × 10(5) copies/g wet stool or 1.2 % of total stool bacteria. Finally, area-under-curve for breath methane correlated significantly with both absolute quantity and percentage of M. smithii in stool (R = 0.76; P < 0.001 and R = 0.77; P < 0.001 respectively). CONCLUSIONS: M. smithii is the predominant methanogen in C-IBS patients with methane on breath testing. The number and proportion of M. smithii in stool correlate well with amount of breath methane.

6 Article Effects of rifaximin treatment and retreatment in nonconstipated IBS subjects. 2011

Pimentel, Mark / Morales, Walter / Chua, Kathleen / Barlow, Gillian / Weitsman, Stacy / Kim, Gene / Amichai, Meridythe M / Pokkunuri, Venkata / Rook, Emily / Mathur, Ruchi / Marsh, Zachary. ·GI Motility Program, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 225E, Los Angeles, CA 90048, USA. pimentelm@cshs.org ·Dig Dis Sci · Pubmed #21559740.

ABSTRACT: METHODS: Charts of patients who were seen at a tertiary care medical center between 2007 and 2011 were reviewed. After exclusion criteria were applied, subjects who had received rifaximin and were seen for retreatment were fully reviewed. During review, demographic information, duration of response, and success of treatment and retreatment were evaluated. RESULTS: A total of 522 charts were reviewed. Of these 522 charts, 71 subjects were nonconstipated IBS subjects who had received at least one retreatment. Of these, 48 had a second, 22 had a third, 7 had a fourth, and 4 had a fifth treatment. More than 75% of subjects who initially responded to rifaximin also responded to any further retreatment, with no significant reduction in benefit for successive retreatments. Furthermore, there was no change in the duration of benefit (median time between treatments) for successive retreatments. CONCLUSIONS: Retreatment with rifaximin for subjects with nonconstipated IBS in a real-world clinical practice was successful up to five times without decrease in duration or effect.

7 Article Acute and chronic histological changes of the small bowel secondary to C. jejuni infection in a rat model for post-infectious IBS. 2011

Morales, Walter / Pimentel, Mark / Hwang, Laura / Kunkel, David / Pokkunuri, Venkata / Basseri, Benjamin / Low, Kimberly / Wang, Hanlin / Conklin, Jeffrey L / Chang, Christopher. ·GI Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite, 2 East, Los Angeles, CA 90048, USA. ·Dig Dis Sci · Pubmed #21409374.

ABSTRACT: BACKGROUND: Campylobacter jejuni has been implicated in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS) in humans, effects which may be because of cytolethal distending toxin (CDT). In this study, we characterized both acute and chronic-phase histological changes of the small bowel in rats exposed to wild-type C. jejuni 81-176, or a strain that does not produce CDT, by using a validated rat model of PI-IBS. METHODS: Sprague-Dawley rats were given 1.0 × 10(8) CFU of either wild-type C. jejuni 81-176 (C+, PI/C+) or the CDT-negative strain (CDT-), or vehicle alone (Control). Acute-phase rats (C+, CDT-) were euthanized on days 2, 4, 8, 16, and 32. Chronic-phase rats (PI/C+, Control) were euthanized 3 months after clearing the initial infection. Segments of duodenum, jejunum, and ileum were resected and the contents plated for C. jejuni culture, and tissue sections were stained for histology. RESULTS: We observed preferential infection of the ileum and jejunum by Campylobacter jejuni. Compared with controls, epithelial cell basal membrane ballooning, villous tip disruption, and reduced villous-to-crypt ratios were observed for both C+ and CDT- rats. Villous widening, the only result significantly different in C+ vs. CDT- rats, was greatest at day 4 (134.1 ± 21.12 μm vs. 109.9 ± 10.6 μm for CDT-, P < 0.01). Little or no cellular inflammatory changes were seen during acute C. jejuni infection. Three months after clearing the initial infection, no histological changes remained. CONCLUSION: Significant histological changes, with the absence of inflammatory cells, are seen in the duodenum, jejunum, and ileum of rats during acute infection with C. jejuni. These changes occurred irrespective of the presence or absence of the CDT toxin.

8 Article ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS. 2010

Jee, Sam-Ryong / Morales, Walter / Low, Kimberly / Chang, Christopher / Zhu, Amy / Pokkunuri, Venkata / Chatterjee, Soumya / Soffer, Edy / Conklin, Jeffrey L / Pimentel, Mark. ·GI Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center, 8730 Alden Drive, Los Angeles, CA 90048, USA. ·World J Gastroenterol · Pubmed #20677340.

ABSTRACT: AIM: To investigate the interstitial cells of Cajal (ICC) number using a new rat model. METHODS: Sprague-Dawley rats were assigned to two groups. The first group received gavage with Campylobacter jejuni (C. jejuni) 81-176. The second group was gavaged with placebo. Three months after clearance of Campylobacter from the stool, precise segments of duodenum, jejunum, and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags. Deep muscular plexus ICC (DMP-ICC) were quantified by two blinded readers assessing the tissue in a random, coded order. The number of ICC per villus was compared among controls, Campylobacter recovered rats without small intestinal bacterial overgrowth (SIBO), and Campylobacter recovered rats with SIBO. RESULTS: Three months after recovery, 27% of rats gavaged with C. jejuni had SIBO. The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum. Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO. If ileal density of DMP-ICC was < 0.12 ICC/villus, 54% of rats had SIBO compared to 9% among ileal sections with > 0.12 (P < 0.05). If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel, 88% of these had SIBO compared to 6% in those who did not (P < 0.001). CONCLUSION: In this post-infectious rat model, the development of SIBO appears to be associated with a reduction in DMP-ICC. Further study of this rat model might help understand the pathophysiology of post-infectious irritable bowel syndrome.