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  • 1
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    Validating biomarkers of treatable mechanisms in irritable bowel syndrome
    Wiley ; 2014
    In:  Neurogastroenterology & Motility Vol. 26, No. 12 ( 2014-12), p. 1677-1685
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    In: Neurogastroenterology & Motility, Wiley, Vol. 26, No. 12 ( 2014-12), p. 1677-1685
    Abstract: A valid biomarker is ‘an indicator of normal biologic or pathogenic processes, or pharmacological responses to a therapeutic intervention’. There is no validated biomarker for irritable bowel syndrome ( IBS ). The aim of the study was to assess ability of three quantitative traits to identify treatable processes to discriminate between IBS ‐diarrhea ( IBS ‐D) patients, IBS ‐constipation ( IBS ‐C) patients and healthy volunteers ( HV ). Methods In 30 HV , 30 IBS ‐C patients and 64 IBS ‐D patients, we characterized bowel symptoms and quantitated pathophysiological mechanisms: bile acid ( BA ) synthesis (serum C4 and FGF 19), fecal BA and fat, colonic transit ( CT ), and intestinal permeability ( IP ). We used multiple logistic regression and receiver‐operating characteristic ( ROC AUC ) to appraise three factors (fecal BA , CT , and IP ) individually and in combination to identify discriminant targets for treatment in IBS . Key Results There were significant associations between the three subgroups and symptoms reflecting bowel function and the quantitative traits. There were significant associations between fecal BA and CT at 48 h ( r  = 0.43; p   〈  0.001) and between fecal BA and IP ( r  = 0.23; p  = 0.015). Individually, fecal BA and CT 48 (but not IP ) were significant independent predictors for distinguishing HV from IBS . In combination, they discriminated HV from IBS ‐D patients ( ROC AUC 0.70), HV from IBS ‐C patients ( ROC AUC 0.73), and IBS ‐C patients from IBS ‐D patients ( ROC AUC 0.86). Colonic transit and fecal BA excretion together discriminate between healthy volunteers and IBS ‐C patients or IBS ‐D patients, or between the IBS subgroups with 75–90% specificity at 60% sensitivity. Conclusions & Inferences Colonic transit and fecal BA individually and together constitute useful biomarkers to identify treatable mechanisms in IBS and to differentiate subgroups of IBS .
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2014.26.issue-12
    DOI: 10.1111/nmo.12421
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 2
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    Effect of neostigmine on gastroduodenal motility in patients with suspected gastrointestinal motility disorders
    Wiley ; 2015
    In:  Neurogastroenterology & Motility Vol. 27, No. 12 ( 2015-12), p. 1736-1746
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    In: Neurogastroenterology & Motility, Wiley, Vol. 27, No. 12 ( 2015-12), p. 1736-1746
    Abstract: Acetylcholinesterase inhibitors ( ACI s), e.g., neostigmine, are known to increase upper and lower gastrointestinal ( GI ) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity. Methods In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy. Key Results The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity ( p 〈 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction. Conclusions & Inferences Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer‐acting ACI s for treating antroduodenal dysmotility warrant further study.
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2015.27.issue-12
    DOI: 10.1111/nmo.12669
    Language: English
    Publisher: Wiley
    Publication Date: 2015
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  • 3
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    Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome
    Wiley ; 2015
    In:  Neurogastroenterology & Motility Vol. 27, No. 1 ( 2015-01), p. 92-98
    Details
    In: Neurogastroenterology & Motility, Wiley, Vol. 27, No. 1 ( 2015-01), p. 92-98
    Abstract: Gastrointestinal symptoms are common in the postural orthostatic tachycardia syndrome ( POTS ). However, few studies have evaluated gastrointestinal transit in POTS . Our primary objectives were to evaluate gastrointestinal emptying and the relationship with autonomic dysfunctions in POTS . Methods We reviewed the complete medical records of all patients aged 18 years and older with POTS diagnosed by a standardized autonomic reflex screen who also had a scintigraphic assessment of gastrointestinal transit at Mayo Clinic Rochester between 1998 and 2012. Associations between specific gastric emptying and autonomic (i.e., cardiovagal, adrenergic, and sudomotor) disturbances were evaluated. Key Results Among 163 patients (140 women, mean [± SEM ] age 30 [±1] years), 55 (34%) had normal, 30 (18%) had delayed, and 78 (48%) had rapid gastric emptying. Fifty‐eight patients (36%) had clinical features of physical deconditioning, which was associated ( p  = 0.02) with rapid gastric emptying. Associations with delayed gastric emptying included vomiting, which was more common ( p   〈  0.003), and anxiety or depression, which was less common ( p  = 0.02). The tilt‐associated increase in heart rate and reduction in systolic BP at 1 min was associated ( p   〈  0.05), being greater in patients with delayed gastric emptying. Conclusions & Inferences Two‐thirds of patients with POTS and GI symptoms had abnormal, most frequently rapid gastric emptying. Except for more severe adrenergic impairment in patients with delayed gastric emptying, the pattern of autonomic dysfunction did not discriminate among gastric emptying groups. Further studies are necessary to ascertain whether extravascular volume depletion and/or deconditioning contribute to POTS in patients with gastrointestinal symptoms.
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2014.27.issue-1
    DOI: 10.1111/nmo.12480
    Language: English
    Publisher: Wiley
    Publication Date: 2015
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  • 4
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    Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women
    Wiley ; 2006
    In:  Neurogastroenterology & Motility Vol. 18, No. 10 ( 2006-10), p. 911-918
    Details
    In: Neurogastroenterology & Motility, Wiley, Vol. 18, No. 10 ( 2006-10), p. 911-918
    Abstract: Abstract  Females are disproportionately affected by constipation, which is often aggravated during pregnancy. Bowel function also changes during the luteal phase of the menstrual cycle. The aim was to compare the effects of acute administration of female sex steroids on gastric emptying, small bowel transit and colonic transit in healthy postmenopausal subjects. A second aim was to determine whether withdrawal of the hormones was associated with a change in transit. Forty‐nine postmenopausal females were randomized to receive for 7 days 400 mg day −1 micronized progesterone, 0.2 mg day −1 oestradiol, combination of the two, or placebo. Treatment groups were balanced on age. Participants underwent whole gut transit measurement by scintigraphy using a 99m‐labeled technetium‐egg meal and 111‐labeled indium‐charcoal via a delayed‐release capsule. Transit measurement was repeated after withdrawal of the study medications. The primary endpoints were ascending colon (AC) emptying half‐life time ( t 1/2 ) and colonic geometric centre (GC) at 24 h. Secondary analysis variables were GC at 4 and 48 h, gastric emptying t 1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t 1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo. Oestradiol and progesterone resulted in looser stool consistency. Withdrawal of the hormone supplement was not associated with significant alteration in transit. Micronized progesterone does not retard colonic transit in postmenopausal females.
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2006.18.issue-10
    DOI: 10.1111/j.1365-2982.2006.00808.x
    Language: English
    Publisher: Wiley
    Publication Date: 2006
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  • 5
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    Contractile response to colonic distention is influenced by oscillation frequency
    Wiley ; 2005
    In:  Neurogastroenterology & Motility Vol. 17, No. 1 ( 2005-02), p. 64-75
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    In: Neurogastroenterology & Motility, Wiley, Vol. 17, No. 1 ( 2005-02), p. 64-75
    Abstract: Abstract  Static colonic mechanical properties are characterized by stepwise balloon distention. It is unclear whether the state of contractile activation affects frequency‐dependent differences in biomechanical properties. Our aim was to investigate the frequency‐dependence of colonic mechanical properties by sinusoidal oscillation. A descending colonic balloon was sinusoidally oscillated by 25 mL at 5, 10 and 20 cpm in randomized order for 20 min at each frequency in six healthy subjects before and after neostigmine. Volume oscillation was between 75–100 mL before, and 25–50 mL after neostigmine. Pressure waveforms were most variable shortly after commencing oscillation, reflecting an initial contractile response to distention. Elastance (i.e. pressure response to imposed volume) and hysteresivity were estimated; hysteresivity represents the proportion of energy added to the system during inflation, which cannot be recovered during deflation. Colonic elastance was frequency dependent, being highest and most variable at 10 cpm. In contrast, hysteresivity was not significantly different across frequencies. Neostigmine increased mean colonic elastance at all frequencies, and hysteresivity only at 5 cpm. Thus, colonic mechanical properties, particularly elastance are frequency‐dependent. The frequency‐dependence of colonic mechanical properties is worthy of future study because it may provide insights into reflex responses in health and disease.
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2005.17.issue-1
    DOI: 10.1111/j.1365-2982.2004.00601.x
    Language: English
    Publisher: Wiley
    Publication Date: 2005
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  • 6
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    Reproducibility of gastric emptying assessed with scintigraphy in patients with upper GI symptoms
    Wiley ; 2018
    In:  Neurogastroenterology & Motility Vol. 30, No. 10 ( 2018-10)
    Details
    In: Neurogastroenterology & Motility, Wiley, Vol. 30, No. 10 ( 2018-10)
    Abstract: The reproducibility of gastric emptying ( GE ) measured with scintigraphy in patients is poorly understood. Our aims were to assess the intra and inter‐individual reproducibility of these parameters in patients with upper gastrointestinal symptoms. Methods Sixty patients (21 diabetics, 39 non‐diabetics) with upper gastrointestinal symptoms underwent scintigraphic‐assessment of GE of a solid meal (296 kcal, 30% fat) over 4 hours on two occasions at an average interval of 15 days. The concordance correlation coefficient ( CCC ), intra and inter‐individual coefficients of variation ( COV ) of GE endpoints were analyzed. Results The GE t 1/2 was 134 ± 8 minutes (mean ±  SEM ) for the first and 128 ± 6 minutes for the second study. The mean (95% CI ) CCC between the two studies was 0.79 (0.67, 0.87) for GE at 1 hour, 0.83 (0.75, 0.9) for GE at 2 hours, 0.54 (0.34, 0.7) for GE at 4 hours, and 0.79 (0.68, 0.86) for GE t 1/2 . However, in 18 of 60 patients (30%), the characterization of GE as normal, delayed, or rapid differed between the first and second studies. For gastric empting t 1/2 , the inter‐individual coefficients of variation was 40%; the intra‐individual COV was 20%, comparable in diabetics and non‐diabetics, and greater in patients with rapid (28%) than delayed (18%) or normal GE (12%). Conclusions & Inferences Among patients with upper gastrointestinal symptoms, GE measured with scintigraphy is relatively reproducible. In 30% of cases, the interpretation was different between the two assessments. Hence, a diagnosis of gastroparesis based on a single study may occasionally be inaccurate.
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2018.30.issue-10
    DOI: 10.1111/nmo.13365
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 7
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    A novel technique for bedside anorectal manometry in humans
    Wiley ; 2015
    In:  Neurogastroenterology & Motility Vol. 27, No. 10 ( 2015-10), p. 1504-1508
    Details
    In: Neurogastroenterology & Motility, Wiley, Vol. 27, No. 10 ( 2015-10), p. 1504-1508
    Abstract: Currently, anorectal manometry ( ARM ), which is used to diagnose defecatory disorders and identify anal weakness in fecal incontinence ( FI ) is generally conducted in specialized laboratories. Our aims were to compare anorectal functions measured with high‐resolution manometry ( HRM ) and a novel portable manometry device. Methods Anal pressures at rest, during squeeze, and simulated evacuation, and rectal sensation were evaluated with portable and HRM in 20 healthy women, 19 women with constipation, and 11 with FI . The relationship between anal pressures measured with portable and HRM was assessed by the concordance correlation coefficient ( CCC ), Bland Altman test, and paired t ‐tests. Key Results Anal pressures at rest ( CCC 0.45; 95% CI : 0.29, 0.58) and during squeeze ( CCC 0.60; 95% CI : 0.46, 0.72) measured with portable and HRM were correlated and inversely associated with the risk of FI . During simulated evacuation, the CCC for rectal pressure (0.62; 95% CI : 0.43, 0.76) was greater than that for anal pressure ( CCC 0.22; 95% CI : 0.04, 0.39) and the rectoanal gradient ( CCC 0.22; 95% CI : 0.02, 0.41). Rectal sensory thresholds for first sensation, the desire to defecate, and urgency measured by portable and HRM were also significantly correlated between techniques. For several parameters, differences between portable and HRM were statistically significant and the Bland Altman test was positive. Conclusions & Inferences Anorectal pressures and rectal sensation can be conveniently measured by portable manometry and are significantly correlated with high‐resolution manometry.
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2015.27.issue-10
    DOI: 10.1111/nmo.12636
    Language: English
    Publisher: Wiley
    Publication Date: 2015
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  • 8
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    Gastric motor disturbances in patients with idiopathic rapid gastric emptying : Mechanisms of rapid gastric emptying
    Wiley ; 2011
    In:  Neurogastroenterology & Motility Vol. 23, No. 7 ( 2011-07), p. 617-e252
    Details
    In: Neurogastroenterology & Motility, Wiley, Vol. 23, No. 7 ( 2011-07), p. 617-e252
    Type of Medium: Online Resource
    ISSN: 1350-1925
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2011.23.issue-7
    DOI: 10.1111/j.1365-2982.2011.01710.x
    Language: English
    Publisher: Wiley
    Publication Date: 2011
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  • 9
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    Effects of hemin on heme oxygenase‐1, gastric emptying, and symptoms in diabetic gastroparesis
    Wiley ; 2016
    In:  Neurogastroenterology & Motility Vol. 28, No. 11 ( 2016-11), p. 1731-1740
    Details
    In: Neurogastroenterology & Motility, Wiley, Vol. 28, No. 11 ( 2016-11), p. 1731-1740
    Abstract: Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase ( HO 1) leads to loss of interstitial cells of Cajal and delayed gastric emptying ( GE ) in non‐obese diabetic mice. Our hypothesis was that hemin upregulation of HO 1 would restore normal GE in humans with gastroparesis. Aims To compare effects of hemin and placebo infusions on HO 1 activity and protein, GE , autonomic function, and gastrointestinal symptoms in diabetic gastroparesis. Methods In a single‐center, double‐blind, placebo‐controlled, randomized clinical trial, we compared intravenous hemin, prepared in albumin, or albumin alone (placebo) in 20 patients, aged 41 ± 5 ( SEM ) years with diabetic gastroparesis. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 additional weeks. Assessments included blood tests for HO 1 protein and enzyme activity levels, GE with 13 C‐spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks. Key Results Nine of 11 patients randomized to hemin completed all study procedures. Compared to placebo, hemin increased HO 1 protein on days 3 ( p = 0.0002) and 7 ( p = 0.008) and HO 1 activity on day 3 ( p = 0.0003) but not after. Gastric emptying, autonomic functions, and symptoms did not differ significantly in the hemin group relative to placebo. Conclusions & Inferences Hemin failed to sustain increased HO 1 levels beyond a week and did not improve GE or symptoms in diabetic gastroparesis. Further studies are necessary to ascertain whether more frequent hemin infusions or other drugs would have a more sustained effect on HO 1 and improve GE .
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2016.28.issue-11
    DOI: 10.1111/nmo.12874
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 10
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    Semi-automated vectorial analysis of anorectal motion by magnetic resonance defecography in healthy subjects and fecal incontinence : Semi-automated anorectal motion analysis
    Wiley ; 2012
    In:  Neurogastroenterology & Motility Vol. 24, No. 10 ( 2012-10), p. e467-e475
    Details
    In: Neurogastroenterology & Motility, Wiley, Vol. 24, No. 10 ( 2012-10), p. e467-e475
    Type of Medium: Online Resource
    ISSN: 1350-1925
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2012.24.issue-10
    DOI: 10.1111/j.1365-2982.2012.01962.x
    Language: English
    Publisher: Wiley
    Publication Date: 2012
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