Colonic sensory and motor function in irritable bowel syndrome and diverticular disease

Chapter 1 is a general introduction. Chapter 2: left-colonic motility patterns were studied in fully ambulant non-constipated IBS patients compared to healthy controls. (HAPCs) were identified. In IBS the descending colon had a decreased overall frequency of phasic contractions and motility index as compared to the sigmoid colon, whereas healthy controls did not show regional differences. In IBS the number of high amplitude propagated contractions (HAPCs) was increased and propagated more distally than did HAPCs in controls. Clustered HAPCs were more frequently observed in IBS and these were found to be related to bowel movements. Chapter 3: evaluates the effect of the 5-HT3-antagonist alosetron on left colonic motility and stool characteristics in non-constipated IBS patients and controls. Using a double-blind, randomized, crossover design and an ambulant manometry technique, motility was studied on day 7 of treatment. Alosetron increased contractile frequency in the sigmoid colon and the amplitude of contractions in the descending colon, increased the number of HAPCs in IBS and prolonged the distance of HAPC propagation. Paradoxically, stool frequency was decreased and stools became firmer during alosetron treatment. In Chapter 4 abdominal pain and HAPCs, here called high-amplitude propagated pressure waves (HAPPWs), were recorded in IBS and controls. The aim of this study was to quantify the association between pain episodes and HAPPWs, assessed by a modification of the symptom association probability (SAP). Four of the 7 IBS patients had SAP scores > 95%, meaning the association between HAPPWs and pain occurred by chance was less than 5%. A correlation was found between duration of pain and number of HAPPWs related. An association between HAPPWs and pain, recorded under physiological conditions, can be demonstrated and quantified in IBS patients. Chapter 5 evaluates colorectal periprandial tone and phasic motility in patients with asymptomatic (ADD) and symptomatic uncomplicated diverticular disease (SUDD) and controls. Rectal tone was not different between groups. In the sigmoid a trend towards a decreased volume was found in SUDD as compared to ADD. Phasic motility was increased in ADD as compared to controls and SUDD. A negative correlation between sigmoid barostat volume and phasic motility was found in SUDD only. Differences in tonic and phasic motility in the sigmoid colon indicate that not only symptoms but also motility might be a discriminating factor in SUDD and ADD. In Chapter 6 perception and compliance of the colorectal wall in ADD, SUDD and healthy controls was studied, using a dual barostat device and stepwise intermittent isobaric distensions. SUDD showed increased perception scores in the rectum as compared to controls and ADD. Increased perception in SUDD was also found in the sigmoid colon as compared to controls. No differences in perception score was found between ADD and controls. In the rectum and sigmoid compliance was comparable for all three groups. It is concluded that hyperperception can be found in SUDD but not in ADD which can not be explained by a change in wall compliance

Two major QTLs on chr. 2BL and 3BS influence grain yield in durum wheat across a broad range of water regimes

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Evolution of Costs of Inflammatory Bowel Disease over Two Years of Follow-Up

BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Colonic sensory and motor function in irritable bowel syndrome and diverticular disease

Chapter 1 is a general introduction. Chapter 2: left-colonic motility patterns were studied in fully ambulant non-constipated IBS patients compared to healthy controls. (HAPCs) were identified. In IBS the descending colon had a decreased overall frequency of phasic contractions and motility index as compared to the sigmoid colon, whereas healthy controls did not show regional differences. In IBS the number of high amplitude propagated contractions (HAPCs) was increased and propagated more distally than did HAPCs in controls. Clustered HAPCs were more frequently observed in IBS and these were found to be related to bowel movements. Chapter 3: evaluates the effect of the 5-HT3-antagonist alosetron on left colonic motility and stool characteristics in non-constipated IBS patients and controls. Using a double-blind, randomized, crossover design and an ambulant manometry technique, motility was studied on day 7 of treatment. Alosetron increased contractile frequency in the sigmoid colon and the amplitude of contractions in the descending colon, increased the number of HAPCs in IBS and prolonged the distance of HAPC propagation. Paradoxically, stool frequency was decreased and stools became firmer during alosetron treatment. In Chapter 4 abdominal pain and HAPCs, here called high-amplitude propagated pressure waves (HAPPWs), were recorded in IBS and controls. The aim of this study was to quantify the association between pain episodes and HAPPWs, assessed by a modification of the symptom association probability (SAP). Four of the 7 IBS patients had SAP scores > 95%, meaning the association between HAPPWs and pain occurred by chance was less than 5%. A correlation was found between duration of pain and number of HAPPWs related. An association between HAPPWs and pain, recorded under physiological conditions, can be demonstrated and quantified in IBS patients. Chapter 5 evaluates colorectal periprandial tone and phasic motility in patients with asymptomatic (ADD) and symptomatic uncomplicated diverticular disease (SUDD) and controls. Rectal tone was not different between groups. In the sigmoid a trend towards a decreased volume was found in SUDD as compared to ADD. Phasic motility was increased in ADD as compared to controls and SUDD. A negative correlation between sigmoid barostat volume and phasic motility was found in SUDD only. Differences in tonic and phasic motility in the sigmoid colon indicate that not only symptoms but also motility might be a discriminating factor in SUDD and ADD. In Chapter 6 perception and compliance of the colorectal wall in ADD, SUDD and healthy controls was studied, using a dual barostat device and stepwise intermittent isobaric distensions. SUDD showed increased perception scores in the rectum as compared to controls and ADD. Increased perception in SUDD was also found in the sigmoid colon as compared to controls. No differences in perception score was found between ADD and controls. In the rectum and sigmoid compliance was comparable for all three groups. It is concluded that hyperperception can be found in SUDD but not in ADD which can not be explained by a change in wall compliance

Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease

Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR(+)CD38(+) EM CD4(+) T cells, T regulatory-like cells, PD1(+) EM CD8(+) T cells, neutrophils, CD27(+) TCR gamma delta cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4(+) T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4(+) T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD

High power microwaves - measures and countermeasures

The technological development within the area of High Power Microwaves (HPM) has made it possible to produce more and more powerful microwave sources for large operational installations, but at the same time made it possible to generate relatively strong fields with compact systems that can be contained in a briefcase or the like. Therefore, the potential threat from HPM has increased significantly. Unprotected electronic components can be damaged at distances up to tens of kilometers, and possible disturbances with fatal consequences are considered realistic in operational scenarios, including critical elements of civilian infrastructure, where the possibility of sabotage and terrorism is a serious concern. In particular, IT-systems exposed to HPM are at great risk, and unprotected systems located inside buildings, shelters etc. can be disturbed or damaged by HPM from rather compact and simple devices. Potential attacks with current and generally available radio frequency weapon technology must be taken into account in any scenario where malfunction of electronic systems could have fatal consequences. On the other hand, radio frequency weapons belong to the more general class of non-lethal weapons that can be used to eliminate hostile capabilities with a minimum of casualties and collateral damages. This paper addresses a range of relevant issues related to the use of HPM as a terror weapon as well as a weapon against terrorism

Sex-Related Differences in Patients With Inflammatory Bowel Disease: Results of 2 Prospective Cohort Studies

Cellular mechanisms in basic and clinical gastroenterology and hepatolog