L. Van Oudenhove

The impact of major depressive disorder on the short- and long-term outcome of Crohn's disease treatment with infliximab

Background:  Major depressive disorder is the most common psychiatric diagnosis in Crohns disease. In other chronic diseases, evidence suggests that depression influences the course of the disease. Strong evidence of such a mediating role of major depressive disorder in Crohns disease has never been found.

Peripheral and central mechanisms of visceral sensitization in man

Abstract  Visceral hypersensitivity (perception of gastrointestinal sensory events at a lower‐than‐normal threshold) is considered to be an important pathophysiological mechanism in the development of functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome, non‐cardiac chest pain and functional dyspepsia. These disorders are associated with significant health care and socioeconomic costs due to factors such as repeated visits to consultants, hospitalizations and work absenteeism. Despite the presence of extensive evidence linking visceral hypersensitivity and FGIDs, the mechanism(s) underlying visceral hypersensitivity has not been fully elucidated. Suggested hypotheses include sensitization of afferent neurones, both at the level of the enteric and the (afferent) autonomic nervous system (peripheral sensitization), sensitization of spinal cord dorsal horn neurones (central sensitization) and psychosocial factors/psychiatric comorbidity influencing the processing of afferent signals at the level of the brain. Importantly, these hypotheses may be complementary rather than mutually exclusive. However, the degree to which each of these mechanisms contributes to the overall perception of visceral pain, and therefore the generation of symptoms, still remains unclear. This article discusses the mechanisms that may underlie visceral hypersensitivity, with reference to FGIDs. Understanding these mechanisms is essential in order to improve the diagnosis and treatment of patients with these disorders.

Immune dysfunction in patients with functional gastrointestinal disorders

Abstract  There is increasing evidence for involvement of the immune system in functional gastrointestinal disorder (FGID), including onset after acute gastrointestinal infections, genotypes resulting in altered cytokine expression and abnormal presence of immune cells. Our aim was to assess cellular and humoral immune responses in (i) FGIDs, compared to healthy subjects and (ii) acute vs unspecified onset FGIDs. Lymphocytic [interleukin (IL)‐5, IL‐10, IL‐13 and interferon γ (IFN‐γ)] and monocytic [IL‐10, IL‐12, tumour necrosis factor (TNF)‐α] cytokine production was characterized at baseline and after stimulation with phytohemagglutinine and anti‐CD28 or lipopolysaccharide (LPS) in controls (n = 32), irritable bowel syndrome (IBS) (n = 30), functional dyspepsia (FD) (n = 23) and non‐cardiac chest pain (NCCP) (n = 15). Serum IL‐6 and IL‐10 concentrations were compared, and the immunophenotype was assessed using fluorescent‐activated cell sorter. Findings were compared for acute vs unspecified onset FGID. Compared to controls, stimulated lymphocyte expression of IL‐5 and IL‐13 was enhanced in IBS, FD and NCCP (all P < 0.05). Conversely, the stimulated monocytic IL‐12 and lymphocytic IL‐10 expression were reduced in IBS and FD, while IFN‐γ expression was also reduced in FD patients. Except for an increase in the numbers of CD3+CD45RA+CD45RO+ cells, no distinct cellular profile was detected. Patients with a presumed acute onset of their symptoms had higher serum IL‐10 levels and more CD3+CD45RA+CD45RO+ cells, while TNF‐α levels following stimulation with LPS were higher in FD patients reporting an acute onset. A shift towards a Th2 cytokine profile is present in FGID, while the cellular immunophenotype remains largely unchanged. Further research is indicated and could provide new therapeutic strategies for these disorders.

Influence of buspirone on gastric sensorimotor function in man

Background  Previous studies have suggested involvement of 5HT1 receptors in the control of gastric tone.

Intragastric pressure during food intake: a physiological and minimally invasive method to assess gastric accommodation

Background  The stomach relaxes upon food intake and thereby provides a reservoir while keeping the intragastric pressure (IGP) low. We set out to determine whether we could use IGP as a measurement for stomach accommodation during food intake.

Influence of abuse history on gastric sensorimotor function in functional dyspepsia

Abstract  Patients with functional gastrointestinal disorders have elevated rates of sexual or physical abuse, which may be associated with altered rectal sensorimotor function in irritable bowel syndrome. The aim was to study the association between abuse history and gastric sensorimotor function in functional dyspepsia (FD). We studied gastric sensorimotor function with barostat (sensitivity, compliance and accommodation) and gastric emptying test in 233 consecutive FD patients from a tertiary care centre (162 women, mean age 41.6 ± 0.9). Patients filled out self‐report questionnaires on history of sexual and physical abuse during childhood or adulthood. Eighty‐four patients (out of 198, 42.4%) reported an overall history of abuse [sexual and physical in respectively 30.0% (60/200) and 20.3% (42/207)]. FD patients reporting general as well as severe childhood sexual abuse have significantly lower discomfort thresholds during gastric distension [respectively 10.5 ± 0.4 vs 7.5 ± 1.0 mmHg above minimal distending pressure (MDP), P = 0.014 and 10.5 ± 0.4 vs 6.6 ± 1.2 mmHg above MDP, P = 0.007]. The corresponding intra‐balloon volume was also significantly lower (respectively 579 ± 21 vs 422 ± 59 mL, P = 0.013 and 579 ± 19 vs 423 ± 79 mL, P = 0.033). Gastric accommodation was significantly more pronounced in patients reporting rape during adulthood (91 ± 12 vs 130 ± 40 mL, P = 0.016). Abuse history was not associated with differences in gastric emptying. A history of abuse is associated with alterations in gastric sensorimotor function in FD. Particularly sexual abuse, rather than physical abuse, may influence gastric sensitivity and motor function.

Cortical deactivations during gastric fundus distension in health: visceral pain-specific response or attenuation of ‘default mode’ brain function? A H215O-PET study

Abstract  Gastric distension activates a cerebral network including brainstem, thalamus, insula, perigenual anterior cingulate, cerebellum, ventrolateral prefrontal cortex and potentially somatosensory regions. Cortical deactivations during gastric distension have hardly been reported. To describe brain areas of decreased activity during gastric fundus distension compared to baseline, using data from our previously published study (Gastroenterology, 128, 2005 and 564). H215O‐brain positron emission tomography was performed in 11 healthy volunteers during five conditions (random order): (C1) no distension (baseline); isobaric distension to individual thresholds for (C2) first, (C3) marked, (C4) unpleasant sensation and (C5) sham distension. Subtraction analyses were performed (in SPM2) to determine deactivated areas during distension compared to baseline, with a threshold of Puncorrected_voxel_level < 0.001 and Pcorrected_cluster_level < 0.05. Baseline–maximal distension (C1–C4) yielded significant deactivations in: (i) bilateral occipital, lateral parietal and temporal cortex as well as medial parietal lobe (posterior cingulate and precuneus) and medial temporal lobe (hippocampus and amygdala), (ii) right dorsolateral and dorso‐ and ventromedial PFC, (iii) left subgenual ACC and bilateral caudate head. Intragastric pressure and epigastric sensation score correlated negatively with brain activity in similar regions. The right hippocampus/amygdala deactivation was specific to sham. Gastric fundus distension in health is associated with extensive cortical deactivations, besides the activations described before. Whether this represents task‐independent suspension of ‘default mode’ activity (as described in various cognitive tasks) or an visceral pain/interoception‐specific process remains to be elucidated.

Associations between gastric sensorimotor function, depression, somatization, and symptom‐based subgroups in functional gastroduodenal disorders: are all symptoms equal?

Background  Previous work indicated that psychosocial factors (depression and somatization) are more strongly associated with symptom severity and weight loss in functional dyspepsia (FD) than gastric sensorimotor function. However, there is conflicting evidence regarding the association of these etiopathogenetic factors with Rome III symptom‐based subgroups in FD [epigastric pain syndrome (EPS), postprandial distress syndrome (PDS)]. We aimed to test whether gastric sensitivity and emptying, depression, and somatization are differentially associated with empirically derived functional gastroduodenal disorders (FGD) symptom factors in one comprehensive model.

Factors associated with co-morbid irritable bowel syndrome and chronic fatigue-like symptoms in functional dyspepsia

Background  It is unclear which factors explain the high co‐morbidity between functional dyspepsia (FD) and other functional somatic syndromes. The aim of this study is to investigate the association between gastric sensorimotor function, psychosocial factors and ‘somatization’ on the one hand, and co‐morbid irritable bowel syndrome (IBS) and chronic fatigue (CF)‐like symptoms on the other, in FD.

Bile Acids Aspiration Reduces Survival in Lung Transplant Recipients with BOS Despite Azithromycin

Azithromycin (AZM) improved bronchiolitis obliterans syndrome (BOS) and reduced aspiration in lung transplant (LTx) recipients. We hypothesize that AZM could improve graft and overall survival more efficiently in LTx patients with BOS who have bile acid (BA) aspiration by protecting against the aspiration‐induced progression of BOS. The goal was to compare FEV1 (% baseline), BOS progression and overall survival in LTx recipients treated with AZM for BOS, both with versus without BA aspiration. Therefore, LTx recipients treated with AZM for BOS were recruited and broncho‐alveolar lavage (BAL) samples were analyzed for the presence of BA and neutrophilia before the start of AZM treatment. Short‐term effect of AZM on FEV1 and BAL neutrophilia was assessed, progression of BOS and survival were followed‐up for 3 years and results were compared between patients with/without BA aspiration. 19/37 LTx patients had BA in BAL. BA aspiration predisposed to a significantly worse outcome, in terms of decline in FEV1, progression of BOS ≥ 1 and survival. AZM does not seem to protect against the long‐term allograft dysfunction caused by gastroesophageal reflux (GER) and aspiration and an additional treatment targeting aspiration may be indicated in those LTx patients.