| 1. |
- Bednarska, Olga, et al.
(författare)
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Neurotransmittor Concentration in Pregenual ACC in Stool Consistency Patient Subgroups With IBS
- 2014
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Konferensbidrag (refereegranskat)abstract
- IntroductionThe Anterior Cingulate Cortex (ACC) is a key region of the central autonomic brain network. Irritable Bowel Syndrome (IBS) is characterized abdominal pain and bowel habit disturbances. Autonomic dysregulation has been reported in IBS as well as altered ACC activation in pregenual ACC during visceral stimulation 1 2. Glutamate is the major excitatory and Gamma-aminobutyric acid (GABA) the major inhibitory neurotransmitter in the brain.Aim & MethodsWe aimed to measure neurotransmitter concentration in the pregenual ACC, in stool consistency subgroups with IBS by using quantitative neurotransmitter Magnetic Resonance Spectroscopy (qMRS)Seven patients with IBS-mixed (6 women) and five patients with IBS -diarrhea (4 women) according to Rome 3 were included. Mean age was 34.2 years (SD 5.3) with no significant difference between subgroups. Patients completed symptom severity score (IBS-SSS). Quantitative MRS was measured in a 3T MRI scanner. A water-suppressed MEGA-PRESS sequence (TR 2.0 s, TE 68 ms) was used with the editing pulses placed at 1.90 ppm (‘ON-dynamics’) and at 7.46 ppm (‘OFF-dynamics’) with a voxel (3x3x3 cm3) placed in the pACC. Each MEGA-PRESS measurement resulted in a sequence of 40 OFF- and ON-dynamics, where each was computed by 8 phase cycles. Directly after each water-suppressed MEGA-PRESS measurement, a shorter 2-dynamic unsuppressed water MEGA-PRESS measurement was performed within the same voxel, which was used to obtain the concentrations in physically well-defined units of [mM]. The GABA concentrations were computed by averaging the difference spectra obtained by subtracting each OFF-dynamic from subsequent ON-dynamic and using LCModel (Version 6.3) for the final quantification. The Glutamate concentrations were obtained by only averaging the OFF-dynamics, which were not affected by the editing pulses. Additionally, all dynamics were phase and frequency corrected prior to the averaging. For group comparison unpaired T-tests were used.ResultsPatients had moderate to severe symptoms with IBS-SSS of 367 (SD 79.7). There was no significant difference between IBS subgroups in terms of IBS-SSS. Mean pACC GABA concentration was 1.66 (SD 0.17) mM in IBS-M and 1.65 (SD 0.27) mM in IBS-D. There was no significant difference between groups (p=0.9). Mean pACC Glutamate concentration was 4.54 (0.35) mM in IBS-M and 5.13 (SD 0.64) mM in IBS-D. There was no significant difference between groups, although a trend with p=0.06 was observed.ConclusionFurther qMRS data have to be collected in IBS patients as well as healthy controls to evaluate if IBS subgroups demonstrate alterations in pACC glutamate and GABA concentrations
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| 5. |
- Larsson, M., et al.
(författare)
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Brain Response to Expectation and Delivery of Rectal Distensions Before and After Hypnotherapy and Education Intervention in Irritable Bowel Syndrome (IBS) : an fMRI Study
- 2011
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Konferensbidrag (refereegranskat)abstract
- Aim & MethodsWe aimed to determine the effect of standardized hypnosis treatment (HYP) on symptom outcomes and brain activity compared to an education intervention (EDU). Twenty-seven women with IBS were evaluated before and after treatment with hypnotherapy (n=17) or educational intervention (n=10). Behavioural treatment outcomes were determined by Severity Scoring System (IBS-SSS). A decrease of 50 points in SSS score was considered clinically significant treatment response. Blood oxygenated level dependent (BOLD) signal were acquired by using a 1.5 T magnetic resonance scanner during expectation and delivery of large rectal distension (45 mmHg). Group comparisons of treatment effects were performed within the general linear model in SPM8. Region of interest analyses were performed with significance threshold of p<0.05, family-wise error corrected.ResultsThere were no group differences in baseline SSS scores. Clinically significant change in SSS was observed in HYP (82%, n=14) and EDU (60%, n=6). Mean improvement in SSS was 108 (range -277 to 29) in HYP and 62 (range -250 to 79) in EDU (ns). During cued expectation of rectal distension, HYP was associated with significantly decreased activation in the left dorsal and ventral anterior insula, left mid insula, left ventrolateral prefrontal cortex (vlPFC) and left dorsolateral prefrontal cortex (dlPFC). Respectively, the EDU group showed less BOLD activity in the left ventral anterior insula after treatment. No significant treatment effect on brain response to the 45 mmHg distension was observed.ConclusionWhile both treatments improve IBS symptoms, the standardized hypnosis treatment has a more widespread central effect compared to education. The brain effects are seen during the expectation of rectal discomfort, but not during the experience of aversive rectal distensions. These findings are consistent with a HYP-induced reduction in pain expectation, rather than pain perception
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| 6. |
- Larsson, Mats, et al.
(författare)
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Brain Responses to Visceral Stimuli Reflect Visceral Sensitivity Thresholds in Patients With Irritable Bowel Syndrome
- 2012
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Ingår i: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 142:3, s. 463-472
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS:Only a fraction of patients with irritable bowel syndrome (IBS) have increased perceptual sensitivity to rectal distension, indicating differences in processing and/or modulation of visceral afferent signals. We investigated the brain mechanisms of these perceptual differences.METHODS:We analyzed data from 44 women with IBS and 20 female healthy subjects (controls). IBS symptom severity was determined by a severity scoring system. Anxiety and depression symptoms were assessed using the hospital anxiety and depression score. Blood oxygen level-dependent signals were measured by functional magnetic resonance imaging during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data were compared among 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls. Results were reported significant if peak P-values were ≤.05, with family-wise error correction in regions of interest.RESULTS:The subgroups of patients with IBS were similar in age, symptom duration, psychological symptoms, and IBS symptom severity. Although brain responses to distension were similar between normosensitive patients and controls, hypersensitive patients with IBS had greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in right hippocampus than controls.CONCLUSIONS:Despite similarities in symptoms, hyper- and normosensitive patients with IBS differ in cerebral responses to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input.
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| 7. |
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| 8. |
- Lowén, Mats, et al.
(författare)
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Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome
- 2013
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 37:12, s. 1184-1197
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Tidskriftsartikel (refereegranskat)abstract
- Background Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. Aim To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Methods Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45mmHg) and low-intensity (15mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. Results Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P=0.006, and cluster size 101, P=0.005 respectively). Moreover HYP responders demonstrated a prepost treatment BOLD attenuation in posterior insula (cluster sizes 59, P=0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P=0.05). Prepost differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. Conclusions The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. Clinical trial number: NCT01815164.
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| 10. |
- Walter, Susanna A, et al.
(författare)
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Prospective Diary Evaluation of Unexplained Abdominal Pain and Bowel Dysfunction : A Population-Based Colonoscopy Study
- 2011
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Ingår i: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 56:5, s. 1444-1451
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Diagnostic criteria for irritable bowel syndrome (IBS) have not been validated by prospective symptom diary. We investigated the bowel patterns in community subjects with and without non-organic abdominal pain, and compared the symptoms with subjects fulfilling the Rome II criteria (IBS). METHODS: From the Swedish population register, a random sample completed an abdominal symptom questionnaire. Responders were subsequently invited for a clinical evaluation and offered a colonoscopy regardless of whether they had abdominal symptoms or not. A total of 268 subjects underwent colonoscopy, clinical evaluation by gastroenterologist, laboratory investigations, and completed the Rome questionnaire and prospective gastrointestinal (GI) symptom diaries for 1 week. Twenty-three subjects of 268 were excluded due to organic GI disease. RESULTS: Subjects recorded 2,194 bowel movements and 370 abdominal pain episodes on 1,504 days. Subjects with pain in the diary (n = 81) had higher stool frequency (P = 0.01), more urgency (P = 0.0002), feelings of incomplete evacuation (P = 0.0002), nausea (P = 0.0009), and abdominal bloating (P = 0.0005) than subjects without pain (n = 151). Twenty-eight subjects (12%) fulfilled the Rome II criteria for IBS. Together, they had 96 pain episodes but only 4% were improved by defecation; 29% of the pain episodes started or worsened after a meal. Subjects with IBS and other subjects with non-organic abdominal pain (n = 64) exhibited no differences in terms of the proportions of pain episodes improved by defecation, bloating, stool frequency, consistency, or defecatory symptoms. CONCLUSIONS: Current criteria for IBS that rely on recall of the relationship between abdominal pain and bowel disturbance may overcall this association when measured prospectively.
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| 11. |
- Walter, Susanna, et al.
(författare)
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Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 25:9, s. 741-E576
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Tidskriftsartikel (refereegranskat)abstract
- Background Abdominal pain is common in the community, but only a subset meet diagnostic criteria for irritable bowel syndrome (IBS). Although anxiety and depression have been linked to IBS, the role of mood disturbances in the remainder with symptoms remains unclear. We aimed to study the associations between abdominal pain, anxiety, depression, and quality of life in the general population who were free of organic colonic disease by colonoscopy. Methods Two hundred and seventy-two randomly selected subjects from the general population, mean age 54 years (27-71), were clinically evaluated, had a colonoscopy and laboratory investigations to exclude organic gastrointestinal (GI) disease. All subjects completed GI symptom diaries for 1 week, the Rome II modular questionnaire, the Hospital Anxiety and Depression Scale, and Short Form 36. Key Results Twenty-two subjects were excluded due to organic disease; 1532 daily symptom records were available for analysis in the remainder. Thirty-four percent (n = 83) recorded at least one episode of abdominal pain on the diary. Twelve percent fulfilled Rome II criteria for IBS. Both anxiety and depression scores were higher in subjects who reported abdominal pain vs those who did not (P andlt; 0.0005 and P andlt; 0.0005). Anxiety and depression scores independently from IBS diagnosis (Rome II) predicted pain reporting and also correlated positively with pain burden. Quality of life scores were generally lower in subjects with abdominal pain. Conclusions andamp; Inferences Anxiety and depression are linked to functional abdominal pain, not only in subjects with IBS but also in otherwise healthy people with milder, subtle GI symptoms.
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| 12. |
- Walter, Susanna, et al.
(författare)
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Anorectal function in patients with collagenous colitis in active and clinically quiescent phase, in comparison with healthy controls
- 2010
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Ingår i: Neurogastroenterology and Motility. - : Blackwell Publishing Ltd. - 1350-1925 .- 1365-2982. ; 22:5, s. 534-
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Tidskriftsartikel (refereegranskat)abstract
- Background Collagenous colitis (CC) is characterized by chronic watery diarrhea, a macroscopically normal colonic mucosa but typical microscopic inflammation. Chronic mucosal inflammation of the colon and rectum has earlier been associated with altered visceral sensitivity, but anorectal function has never been reported in cases of CC. Methods Fifteen patients with CC in active phase recorded their symptoms. The severity of inflammation was determined in mucosal biopsies. Anorectal function was assessed and compared with that of 15 healthy volunteers of corresponding age and matched for gender. After 6 weeks of budesonide treatment when the patients were in clinical remission anorectal function was re-assessed. Key Results All patients had inflammation also in rectum. Patients in active phase had, during rectal balloon distension a higher rectal sensory threshold for the feeling of first sensation, compared with controls (P = 0.02). There were no differences in rectal sensory threshold for the feeling of urgency or maximum distension, between patients with CC in active phase and healthy controls. Rectal volume at first sensation was significantly greater in patients than in controls (P = 0.02), but there were no differences at urgency or maximum distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and all went into clinical remission. No differences in anorectal function were measured when patients had active disease, compared with clinical remission. Conclusions andamp; Inferences Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC.
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| 13. |
- Walter, Susanna, et al.
(författare)
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Assessment of normal bowel habits in the general adult population: the Popcol study
- 2010
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Ingår i: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. - : Taylor andamp; Francis. - 0036-5521 .- 1502-7708. ; 45:5, s. 556-566
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Defining normal stool habit is important when evaluating diarrhoea or constipation, but common confounders such as irritable bowel syndrome (IBS) or the intake of medications with gastrointestinal side effects have not been considered in earlier population based studies defining what is normal. We hypothesized that the exclusion of subjects with common confounders would help to better understand what are "normal bowel habits". We aimed to prospectively study bowel habits in a carefully studied random sample of the general population. Material and methods. Two hundred and sixty-eight randomly selected subjects between 18 and 70 years completed symptom diaries for one week and were clinically evaluated by a gastroenterologist. They also had a colonoscopy and laboratory investigations to exclude organic disease. Results. One hundred and twenty-four subjects had no organic gastrointestinal abnormality, IBS, or relevant medication; 98% of them had between three stools per day and three per week. Seventy-seven percent of all stools were normal, 12% hard, and 10% loose in consistency. Urgency was reported by 36%; straining by 47% and incomplete defecation by 46%. After the exclusion of subjects with organic abnormalities, women had significantly more symptoms than men in terms of abdominal pain, bloating, constipation, urgency, and feeling of incomplete evacuation but these gender differences disappeared after excluding subjects with IBS. Conclusions. This study confirms that normal stool frequency is between three per week and three per day. We could not demonstrate any gender or age differences in terms of stool frequency, defecatory symptoms or abdominal bloating. Some degree of urgency, straining, and incomplete evacuation should be considered normal.
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| 14. |
- Walter, Susanna, et al.
(författare)
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Association between bowel symptoms, symptom severity, and quality of life in Swedish patients with fecal incontinence
- 2011
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Health Care. - 0036-5521 .- 1502-7708. ; 46:1, s. 6-12
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The association between abdominal symptoms, disease severity of fecal incontinence (FI), and quality of life (QoL) is not yet clear. We hypothesized that it would become clearer by prospective diary data. We also aimed to compare QoL of FI patients with ulcerative colitis (UC) patients in relapse and remission. Material and methods. Sixty-five consecutive female patients with FI recorded bowel symptoms prospectively on diary cards. QoL was evaluated with the disease specific short health scale questionnaire (SHS). Patients with UC in remission and relapse were used as a reference group regarding SHS. Results. FI patients had median 3.5 leakage episodes/week. In all, 48% of bowel movements were associated with urgency. Urgency was correlated to decreased QoL according to SHS domains: symptoms (Rho = 0.54, p = 0.0002), function (Rho = 0.48, p = 0.0008), and disease related worry (Rho = 0.32, p = 0.027). Abdominal pain and bloating, reported by nearly half of patients, correlated to deceased QoL but not to number of leakages. QoL of patients with FI compared to UC in active phase (n = 35) was similar. FI patients had decreased QoL compared to UC in remission (n = 94) in all dimensions of SHS: symptoms (p < 0.0001), function (p < 0.0001), disease related worry (p < 0.0001), and general well being (p = 0.03). Conclusion. Urgency and irritable bowel syndrome (IBS)-like symptoms were associated with decreased QoL in FI. Therefore, IBS should be considered as an important confounding factor in FI QoL studies. QoL in patients with FI was considerably decreased, in a similar extent as in patients with UC in relapse.
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| 16. |
- Walter, Susanna, et al.
(författare)
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Su2113 High-Intense Rectal Urgency and Its Representation in the Brain
- 2013
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Konferensbidrag (refereegranskat)abstract
- Background: Several brain imaging studies have demonstrated that visceral distensions activate the insular cortex but there is limited knowledge about which subregions of the insula underpin the feeling of rectal urgency. An isobaric rectal balloon distension can be subdivided into the inflation phase when pressure is rising (rise) and a stable phase, when the pressure is constant. The rise phase is characterized by a more distinct sensation of urgency (Akervall et al., 1988). We aimed to study the BOLD response during the rise phase of a standardized rectal distension in subregions of the insula, in healthy controls.Method:Twenty right-handed female healthy volunteers (mean age 32.2 yrs, range 21-54) were included. Rectal pressure sensory thresholds were determined before functional Magnetic Resonance Imaging (fMRI) while the subjects were placed in the MR scanner. Blood Oxygen Level Dependent (BOLD) signals were measured during the rise periods (6.6-7.2 sec) of 20 rectal distensions (45mmHg). Regions of interest (ROIs) included 10 insula subregions: Left (L) and right (R) anterior ventral, anterior dorsal, posterior ventral, posterior dorsal and mid insula. Results were reported as significant if peak p-value were, 0.05 with familywise error (FWE) correction in the ROIs.Results: The mean values for rectal sensory thresholds for first sensation, first sensation of urgency and maximum tolerable distension were 16 mmHg (SD 3.9), 28mmHg (SD 6.2) and 55 mmHg (SD 12.3), respectively. Complete fMRI data were available from 18 subjects. The rise period of the rectal distension generated significant BOLD activation in the right hemisphere in the anterior dorsal, anterior ventral, mid and posterior ventral parts of the insula. On the left side BOLD activity was generated in mid, posterior ventral and posterior dorsal parts of the insula but not in the anterior insula. Akervall S et al, 1988, Manovolumetry: A new method for investigation of anorectal function. Gut 29:614-623.
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| 18. |
- Zhang, Xuehong, et al.
(författare)
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Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status : a pooled analysis of 18 prospective cohort studies
- 2012
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Ingår i: American Journal of Clinical Nutrition. - : OXFORD UNIV PRESS. - 0002-9165 .- 1938-3207. ; 95:3, s. 713-725
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. Objective: We investigated these associations in a pooled analysis of 18 cohort studies. Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. Results: alpha-Carotene, beta-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER-) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): alpha-carotene (0.87; 95% CI: 0.78, 0.97), beta-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): a-carotene (1.04; 95% CI: 0.99, 1.09), beta-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for beta-cryptoxanthin were not significant, inverse trends were observed for ER- and ER+ breast cancer (P-trend <= 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. Conclusions: Intakes of alpha-carotene, beta-carotene, and lutein/zeaxanthin were inversely associated with risk of ER-, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources. Am J Clin Nutr 2012;95:713-25.
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| 19. |
- Zhang, Xuehong, et al.
(författare)
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Risk of Colon Cancer and Coffee, Tea, and Sugar-Sweetened Soft Drink Intake : Pooled Analysis of Prospective Cohort Studies
- 2010
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Ingår i: Journal of the National Cancer Institute. - : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 102:11, s. 771-783
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Tidskriftsartikel (refereegranskat)abstract
- The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved. We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731 441 participants followed for up to 6-20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided. Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, P-trend = .68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, P-trend = .01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, P-trend = .91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P > .20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P > .05). Drinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study.
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