[Functional gastrointestinal disorders].
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Biomedical subjects
Publications and source records attributed to T Liebregts.
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Functional gastrointestinal disorders such as functional (or non-ulcer) dyspepsia are characterized by a broad spectrum of symptoms referred to the upper abdomen without a detectable cause utilizing routine diagnostic measures. It is now believed that disordered gut function (including abnormalities like disturbances of motility such as postprandial fundic relaxation, gastric emptying and disturbed visceral sensory function) play a key role for the manifestation of these disorders. The underlying pathophysiology is not yet fully understood. However, the available data suggest that a number of factors may contribute to the manifestation of symptoms. These factors include environmental factors such as acute infections as trigger event, psychological stressors that may precede acute exacerbations and a genetic predisposition. Considering the large number of mechanisms, a treatment targeting a single mechanism is unlikely to be effective in all patients. Indeed, chemically defined treatments usually gain a 10-15% superiority over placebo. In recent years placebo-controlled studies have demonstrated superiority of a commercial multicomponent herbal preparation, STW 5, with the trade name Iberogast, for the treatment of patients with functional dyspepsia and irritable bowel syndrome. This phytopharmacon is a combination of nine plant extracts each with a number of different active constituents. Pharmacological studies have shown different effects of the single plant extracts on the (molecular) mechanisms which are discussed as underlying the manifestation of symptoms. Various well-controlled clinical trials have independently confirmed clinical efficacy and safety. The clinically efficacy of this multicomponent herbal preparation questions the current trend of highly targeted drug molecules that usually target one single receptor population while it has not been shown that a single receptor group plays a pivotal role for the control of symptoms. Herbal medicines are obtained from various plants and contain complex extracts with a large number of different active substances. While there are only limited head-to-head comparisons with conventional chemically defined medications, the combination of extracts with various gastrointestinal active ingredients appears to be advantageous for a heterogeneous condition such as functional dyspepsia.
Dyspepsia comprises a broad spectrum of predominantly upper abdominal symptoms, such as pain, indigestion, nausea, early satiety and bloating. While these symptoms are highly prevalent, in less than 50% of patients presenting with dyspepsia, structural lesions or biochemical abnormalities are found that explain the symptoms when routine clinical tests are used. In patients without structural lesions the diagnosis of functional dyspepsia is justified. Exclusion of life-threatening disorders as the cause of symptoms and reassurance of the patient as well as proper explanation of the diagnosis and its underlying disease mechanisms (i.e. symptoms are due to a sensitive gut) is crucial and can be considered as an essential element of treatment. Since there is a remarkable comorbidity of anxiety and depression, psychosomatic interventions might be necessary in selected patients. Based on controlled clinical trials few drugs, such as proton pump inhibitors, prokinetics, tricyclic antidepressants, simethicone and selected herbal preparations have been found to be effective for treatment of functional dyspepsia. Effects of H. pylori eradication, even though strongly advocated, are most likely due to undiagnosed peptic ulcer disease in a very small group of patients. While there is currently no therapy that cures functional dyspepsia, the therapeutic target is to control symptoms.
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AIM: To validate the gastrointestinal symptom score as an outcome measure for functional dyspepsia. METHODS: In focus groups, 10 dyspepsia-specific items including nausea, sickness, vomiting, bloating, abdominal cramps, early satiety, acidic eructation/heartburn, loss of appetite, retrosternal discomfort, epigastric pain/upper abdominal pain were identified. Ninety-five patients with functional dyspepsia and 56 healthy controls were recruited and responsiveness evaluated by analysing gastrointestinal symptom score data from 357 patients from previous placebo-controlled trials. Gastrointestinal symptom score response data were correlated with the patient's global assessments of efficacy. Convergent validity was assessed by correlating the gastrointestinal symptom score with the results obtained by the Nepean Dyspepsia Index. RESULTS: Sensitivity: In patients and healthy controls gastrointestinal symptom score yielded consistently different scores (all P < 0.0001). TEST-RETEST RELIABILITY: Gastrointestinal symptom score determined at the two time points were significantly correlated (r-values ranging from 0.842 to 0.901). CONVERGENCE VALIDITY: Gastrointestinal symptom score of both rating groups were significantly correlated with the symptom-specific component of the Nepean Dyspepsia Index (r-vales ranging from 0.666 to 0.764, P < 0.01). RESPONSIVENESS: Responses of gastrointestinal symptom score during treatment were different for patients with a global self assessment as responders compared with non-responders (all P < 0.0055). CONCLUSION: The gastrointestinal symptom score is a valid and reliable instrument to assess symptom intensities in patients with functional dyspepsia.
Patients with irritable bowel syndrome (IBS) are highly prevalent among subjects seeking medical attention at the general practitioner or specialist level. While IBS lacks any disease associated excess mortality, this disorders is relevant to the affected subjects due to the considerable burden with regard to the symptoms and an impaired quality of life. Furthermore, this disease has a substantial impact on society due to the economical consequences. In recent years substantial progress has been achieved regarding our pathophysiological understanding. However, as usual, there has been a substantial delay between the discovery of disease mechanisms and its translation into improved patient care. For diagnosing IBS standardized criteria have been established (i. e. Rome II- or the DGVS-criteria). Regarding treatment, life style advice such as avoidance of specific nutrients that precipitate or aggravate or the "little psychotherapy" (addressing patients concerns and anxiety regarding the symptoms) are considered essential. However, the overall response rate is disappointing. Evidence-based pharmacological interventions include herbal preparations, spasmolytics, low dose tricyclic antidepressants and 5-HT-3-receptor antagonists and 5-HT-4-receptor agonists. At present no cure for patients with IBS exists. Thus, all currently available treatments target palliation of symptoms. This, however, may change in the future.
OBJECTIVE: Visceral hyperalgesia (VH) plays a key role for the manifestation of functional gastrointestinal (GI) disorders. In a subgroup of patients, the initial manifestation is preceded by GI inflammation. Recent studies have demonstrated an improvement of inflammation and symptoms during treatment with Escherichia coli Nissle 1917 (EcN). AIM: We aimed to characterize the effects of EcN on visceral sensitivity in a rat model of post-inflammatory VH. METHODS: Male Lewis rats underwent colorectal instillation of trinitrobenzenesulphonic acid (TNBS) plus an equal amount of ethanol (test group) or physiological saline solution (control group). After 28, 35 and 42 days, standardized colorectal distensions were performed and the visceromotor reflex (VMR) of abdominal wall muscles was quantified by electromyographic recording. From day 28 onwards, EcN was administered in drinking water. RESULTS: After TNBS, a significant increase of VMR was observed compared with saline controls over all study days. Administration of EcN reduced the TNBS-induced hyperalgesia [EcN: 863+/-125 microV vs placebo: 1258+/-157 microV (P<0.05)] at day 35, while there were no significant alterations at any other study day. CONCLUSION: The EcN administration caused a significant reduction of VH. Whether EcN might play a role in the treatment of post-infectious functional bowel disorders remains to be investigated in further studies.
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Acute gastrointestinal infections with transient mucosal inflammation frequently precede the onset of functional GI disorders with altered visceral sensory function. We hypothesized that an acute inflammation of the mucosa is linked to long-lasting alterations of afferent visceral pathways. Utilizing abdominal wall electromyography, we tested the visceromotor response to tonic rectal distension (60 mm Hg/3 min) in fasted, conscious, male Lewis rats (n = 40) with a barostat device before and 2, 4, 15, and 17 weeks after rectal instillation of saline or trinitrobenzenesulfonic acid plus ethanol. Tissue samples from paired controls were obtained to assess histologic tissue alterations. Inflammatory changes were present up to 2 weeks after acid/ethanol instillation but not after saline instillation. Compared to baseline measurements, the visceromotor response to colorectal distension increased significantly and reached a maximum 17 weeks (P < 0.001) after induction of colitis, while it decreased in control experiments (P < 0.05). In conclusion, these data suggest that an acute inflammation has long-term effects on somatosensory functioning.
Gastro-oesophageal reflux disease (GERD) is a highly prevalent disorder in all Western countries. Interestingly, prevalence rates appear to be increasing in these countries, with a remarkable increase of GERD-related lethal and nonlethal complications. However, these complications are rare on a global scale. This review aims to summarize the current concepts of genetic, lifestyle and environmental factors that need to be considered whilst caring for patients with these disorders. GERD is defined by the augmented exposure of oesophageal mucosa to acidic content, and is associated with specific symptoms or mucosal lesions. A number of factors may contribute to the manifestation of GERD. Although recent studies emphasize the role of genetic factors, there are many other risk factors that play a pivotal role in the development of GERD and GERD complications. Some nutritional factors are believed to aggravate acidic reflux either by delaying gastric emptying or diminishing the pressure of the lower oesophageal sphincters. Patients are often advised to sleep with their heads elevated, but this advice is not easy to follow and has not been proven effective with regard to long-term outcome. Other lifestyle modifications include changes to the patient's diet, which are important but not frequently sufficient. Thus, medication is usually necessary for symptom control. Proton pump inhibitors are now mainstream treatment for the reduction of acid secretion in patients with severe manifestations and 4-week healing rates are approaching 90%.
Most patients with functional bowel disorders complain of daytime symptoms while they remain asymptomatic at night. As symptoms are associated with heightened visceral sensitivity, we hypothesized that circadian fluctuations of the visceral sensory function occur. At four different timepoints (06.00, 12.00, 18.00 and 24.00 h), colorectal distensions (CRD) were performed in fasting conscious male Lewis rats using a balloon catheter and a barostat device. The abdominal wall contractions (behavioural pain response) were assessed during colorectal distension by abdominal wall electromyography (EMG). Plasma levels for endogenous cortisol were determined simultaneously at these timepoints. EMG responses to CRD were significantly (P < 0.05) higher at midnight and in the early morning. Plasma cortisol levels peaked in the evening. In night-active Lewis rats, the behavioural pain response to noxious visceral stimulation is augmented at night and fluctuations of visceral sensitivity are accompanied by circadian changes of plasma concentrations of endogenous cortisol. We conclude that there are marked circadian fluctuations in visceral sensory functions. Thresholds are low during time periods of normal behavioural activity. These findings suggest that fluctuation of the sensory functions may be linked to the circadian variability of symptoms in patients with functional GI disorders.