[Irritable bowel syndrome--role of motility inhibitors].
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Antidiarrheals↗
Biomedical subjects
G Holtmann
Publications and source records attributed to G Holtmann.
[Therapy of functional dyspepsia (irritable stomach syndrome].
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Analgesics, Non-Narcotic↗
H. pylori and functional dyspepsia: increased serum antibodies as an independent risk factor?
The relationship between H. pylori and functional dyspepsia is controversial. Hypothesizing that subjects with a more intense immune response to H. pylori (and hence higher antibody titers) would be at greater risk of dyspepsia, we aimed to identify risk factors for the development of dyspeptic symptoms. In all, 491 healthy blood donors with no history of peptic ulceration and 74 consecutive patients with a confirmed diagnosis of functional dyspepsia were studied. Symptoms and potential risk factors [nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, and smoking] were measured by a validated questionnaire. H. pylori status was determined by IgG antibodies using a validated ELISA test with a cutoff titer for a positive serology of 10 units/ml. Logistic regression analysis assessed the association between risk factors and dyspepsia. Among blood donors, 21% (95% CI 17.6-24.8) reported dyspepsia (pain localized to the upper abdomen); 7.7% (95% CI 5.5-10.4) had frequent dyspepsia (>6 times in the prior year). The age-adjusted prevalence of H. pylori was not significantly different in blood donors with (39.5%, 95% CI 24.0-56.6) and without frequent dyspepsia (34.2%, 95% CI 29.8-38.36), but was significantly greater in patients with functional dyspepsia (68.8%, 95% CI 57.3-77.9). In the combined study population of blood donors and patients with functional dyspepsia, logistic regression adjusting for age identified the following independent risk factors for frequent dyspepsia: high serum antibody levels against H. pylori (OR for IgG titer >50 units/ml vs H. pylori titers 11-50 units/ml 4.6, 95% CI 2.7-7.8) and consumption of standard NSAIDs (OR 2.4,95% CI 1.3-4.5). In contrast, alcohol (OR 0.6, 95% CI 0.3-1.0), smoking (OR 1.5, 95% CI 1.0-2.3) or positive H. pylori serology with titers < or = 50 units/ml (OR 1.6, 95% CI 0.8-2.9) were not associated with frequent dyspepsia. In conclusion, in a subgroup of H. pylori-infected subjects who have high antibody titers, H. pylori appears to be associated with functional dyspepsia.
Adolescent↗
Diurnal variation of abdominal motor responses to colorectal distension and plasma cortisol levels in rats.
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.
Abdomen↗
[Guidelines of the German Society of Digestive and Metabolic Diseases for treatment of dyspepsia].
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Adult↗
The management of irritable bowel syndrome: a European, primary and secondary care collaboration.
OBJECTIVE: To develop recommendations for the diagnosis and management of irritable bowel syndrome for European doctors delivering primary care. These recommendations can be adapted by local medical groups according to their language, custom and health-care systems. METHODS: Twenty-one general practitioners and gastroenterologists from Europe attended a workshop planned by a steering committee. After a state-of-the-art symposium, four working groups considered the following aspects of irritable bowel syndrome management: what to tell the patient, diagnosis, non-medical treatment and psychosocial management. Current and future drug management was reviewed by the steering committee. The resulting recommendations were considered at two plenary sessions during the meeting, and by circulation of the material during development of the manuscript. RESULTS: The process permitted a unique dialogue between general practitioners and gastroenterologists, in which it was necessary to reconcile the specialists' emphasis on thoroughness with the practical, epidemiological and economic realities of primary care. Despite this dichotomy, consensus was achieved. CONCLUSIONS: European general practitioners and gastroenterologists have produced recommendations that emphasize education of the patient, a positive symptom-based diagnosis, diet and lifestyle advice, psychological support and a critical analysis of current specific psychological and pharmacological treatments.
Colonic Diseases, Functional↗
Epithelial cell-derived components induce transforming growth factor-alpha mRNA expression and epithelial cell proliferation in vitro.
BACKGROUND: Epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha protect the gastrointestinal mucosa against injury. In response to mucosal injury TGF-alpha, but not EGF, is locally increasingly expressed in the mucosa of the rat colon and stomach 4-8 h after injury. The aim of our present study was to characterize the possible signal for the induction of TGF-alpha expression. METHODS: Monolayers of the non-transformed intestinal epithelial cell (IEC)-6 and IEC-18 lines were harvested, homogenized and shock-frozen at -80 degrees C for 1 h. Cell cultures of intact IEC-6 or IEC-18 cells were exposed to these cell homogenates and modulation of epithelial cell migration and proliferation was evaluated using standardized procedures as described previously. TGF-alpha mRNA expression in the exposed epithelial cell monolayers was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and normalized to the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RESULTS: The proliferation of IEC-6 and IEC-18 epithelial cell monolayers was significantly inhibited if epithelial cell homogenates of 2000 cells/ml or more, and significantly induced if homogenates of less than 2000 cells/ml, were applied to the medium of the monolayers in vitro. In proliferating epithelial cells, a significant two-fold increase in TGF-alpha mRNA expression was obtained at 48 h and 72 h after application of the cell homogenates. The homogenate-induced epithelial cell proliferation was completely abolished after preincubation of the epithelial cell homogenates with neutralizing monoclonal anti-TGF-alpha antibodies. No effect on epithelial cell migration was noticed after application of epithelial-cell homogenates to the cell cultures. CONCLUSIONS: Epithelial cell-derived components induce TGF-alpha mRNA expression and TGF-alpha-dependent cell proliferation of intact epithelial cells. We hypothesize that epithelial cell interaction bears one of the possible signals for the increased TGF-alpha mRNA expression after mucosal injury.
Animals↗
Epidemiological trends of functional gastrointestinal disorders.
Functional gastrointestinal disorders are highly prevalent in the population and in primary and secondary care centers. Most likely they have been highly prevalent for centuries but in the past the lack of appropriate diagnostic measures did not enable the precise exclusion of structural causes of symptoms. In recent decades the prevalence rates of Helicobacter pylori has clearly decreased. As a result the incidence of H. pylori-related structural diseases in the upper gut decreased. Thus the relative proportion of functional gastrointestinal disorders has increased and may result in the overall impression that the prevalence of functional gastrointestinal disorders has increased. Thus, the available data do not provide evidence that the prevalence of these disorders has changed in recent decades.
Colonic Diseases, Functional↗
MR colonography without colonic cleansing: a new strategy to improve patient acceptance.
OBJECTIVE: MR colonography permits accurate detection of colonic polyps larger than 8 mm. Patient acceptance remains limited because of the need for bowel cleansing. The aim of this study was to develop and assess a strategy obviating colonic cleansing by performing MR colonography in conjunction with fecal tagging based on the oral administration of barium. SUBJECTS AND METHODS: Six healthy volunteers and six patients with suspected colorectal tumors, undergoing conventional colonoscopy within 1 week of MR imaging, were included in this study. For fecal tagging, 200 mL of a barium-containing contrast agent was ingested with each of four principal meals preceding the examination. For MR colonography, the colon was filled with a barium and water mixture while gadobenate dimeglumine (0.2 mmol/kg) was injected IV. RESULTS: The combination of fecal tagging and colonic filling with barium resulted in a homogeneously low signal throughout the colonic lumen in all 12 subjects. IV injection of gadolinium caused avid enhancement of the colonic wall. Similarly, lesions arising from the colonic wall enhanced avidly. In the six evaluated patients, MR colonography correctly identified two colonic carcinomas in two patients and one polyp in each of another two patients. CONCLUSION: Fecal tagging obviates bowel cleansing and should, therefore, enhance patient acceptance for MR colonoscopy. Barium used as the tagging agent is promising because it is inexpensive, commercially available, and characterized by an excellent safety profile.
Adult↗
Reflux disease: the disorder of the third millennium.
Gastro-oesophageal reflux disease (GORD) affects a large group of patients and has a negative impact on quality of life. In addition, this disorder is associated with considerable long-term morbidity and mortality. In Western countries, between 10% and 30% of the population is affected by GORD. Symptoms of GORD include retrosternal burning and regurgitation, which are highly predictive of acid exposure to the oesophageal mucosa. However, erosions or ulcers in the oesophageal mucosa occur in fewer than 30% of patients with this disorder as assessed by current endoscopic techniques. Treatment of symptoms in this patient population is nonetheless of paramount importance. Current data indicate that the prevalence of GORD is increasing in the population as a whole. Although the exact reasons for this increase are unknown, changes in diet and lifestyle may play some role. Furthermore, a decreasing prevalence of Helicobacter pylori infection in the population, which is thought to exert some protection against GORD, may also be involved. Along with the increasing prevalence of GORD is an increase in GORD-related complications, including Barrett's oesophagus and oesophageal adenocarcinoma. Given the delay in onset of these GORD-associated complications, these findings are particularly alarming. As these trends continue, current techniques for the treatment of GORD will need to be refined and reevaluated in terms of quality-of-life issues, health care utilization, and cost-efficacy. Treatment of GORD in the future will require effective techniques to control symptoms, maintain remission, and prevent complications in the affected patient.
Adenocarcinoma↗
[Lumbar radical nephrectomy. A retrospective analysis of 186 cases].
186 cases of nephrectomy for renal cell cancer are studied retrospectively. The overall 5-year survival rate was 77.2%. According to the 4th edition of the "TNM" classification system of UICC the survival rates of patients with T2-(n = 97), T3a (n = 58) and T3b-tumors (n = 25) were 80.9%, 79.3% and 65.6%, respectively. No patient with a stage T4 tumor (n = 6) survived longer than 20 months. The 5-year survival rate of patients with N1-lymph node metastases was 83.3% (n = 8); without lymph node metastases 78.3% (n = 152), respectively. There was no survival longer than 20 months in case of N2-lymph node metastases (n = 13). According to the grading survival rates of 95.4% (G1, n = 46), 71.2% (G2, n = 130) and 71.4% (G3, n = 8) resulted.
Adult↗
Panel discussion - unresolved issues
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Journal Article↗
Gastrointestinal symptoms and subjects cluster into distinct upper and lower groupings in the community: a four nations study.
OBJECTIVE: It is unknown whether distinct functional GI (GI) symptom groupings occur in the general population and whether these are similar across different cultures. Although symptom-based diagnostic criteria have been developed for upper and lower GI syndromes (the Rome criteria), the classification is controversial. We aimed to identify whether independent symptom-based subgroups exist in four countries consistent with the Rome criteria. METHODS: Random samples of the community were mailed a validated questionnaire based on the Bowel Disease Questionnaire in Rochester, MN (n = 2,220), in Sydney, Australia (n = 1,135), and in Essen, Germany (n = 500). A different validated questionnaire was mailed to a random sample in Osthammar, Sweden (n = 1,517). Only the common questions (n = 22) were used in the current analysis, and these were essentially identical in wording. The underlying structure of the item responses was examined using factor analysis. Initial factors were extracted using principal components analysis and then rotated using Varimax. Clustering of symptoms among individuals was examined though cluster analysis, using the factors as the basis for clustering. RESULTS: Response rates varied from 64% to 80%; responders and nonresponders were similar sociodemographically. All four studies yielded similar factor structures. All countries reported symptom groupings consistent with the irritable bowel syndrome (IBS), dyspepsia and/or gastroesophageal reflux, and constipation; all except Sweden also had a diarrhea group. The cluster analysis yielded slightly more disparate results but a healthy group was present in all populations. All four populations had an IBS and/or bowel dysfunction cluster identified; a gastroesophageal reflux cluster was also present in all countries. CONCLUSIONS: The similarity of factor and cluster structures found in these four nations suggest that patterns of GI symptoms and groupings of individuals are similar across these Western cultures. These results are consistent with the current international Rome classification for separate upper and lower functional GI disorders.
Adult↗
Differences in gastric mechanosensory function after repeated ramp distensions in non-consulters with dyspepsia and healthy controls.
BACKGROUND: Abnormal visceral mechano-sensory function has been reported in 50% of non-ulcer (functional) dyspepsia patients. However, only a minority of subjects with functional dyspepsia ever seek medical attention. Whether factors promoting health care seeking behaviour explain visceral hypersensitivity is unknown. Decreased rectal thresholds following sigmoid mechanical stimulation have been observed in irritable bowel but this mechanism has not been evaluated in functional dyspepsia. AIMS: To compare visceral mechanosensory function in healthy asymptomatic subjects and non-consulters with chronic unexplained dyspepsia. METHODS: Forty two volunteers were recruited: 10 had a history of chronic or recurrent upper abdominal pain or discomfort as assessed by a standardised questionnaire, and Helicobacter pylori status was determined (ELISA and (13)C urea breath test). Eight H pylori negative, currently asymptomatic dyspeptic subjects who were non-consulters and eight asymptomatic age and sex matched H pylori negative controls were enrolled. With a barostat bag in the proximal part of the stomach, visceral perception thresholds were determined by random tracking. Thereafter, standardised ramp distensions were performed (2 mm Hg increments, duration of each pressure step 30 seconds, maximum pressure 35 mm Hg (or occurrence of pain)) and tracking of sensory thresholds and ramp distension repeated every 30 minutes for a total of two hours. RESULTS: Overall, thresholds for first perception were significantly lower in dyspeptic subjects compared with asymptomatic controls (12.5 (0.6) mm Hg v 17.5 (1.0) mm Hg; p<0.02). After repeated ramp distensions, thresholds for first perception significantly increased by 3.6 (0.7) mm Hg in healthy subjects compared with 0.1 (1.4) mm Hg in subjects with dyspepsia (p<0.05 dyspeptics v controls). CONCLUSIONS: (1) Repeated mechanical stimulation increases visceral sensory thresholds in asymptomatic subjects while thresholds remain unchanged in dyspeptics. (2) Visceral hyperalgesia occurs in dyspeptic subjects who are not health care seekers.
Adult↗
[Significance of esophagocardiac reflexes for inducing thoracic pain].
In the clinical setting the cardiologists' interest is focussed on the esophagus as a potential source of thoracic pain as a differential diagnosis of angina pectoris. However, visceral afferences originating in the mucosal wall of the esophagus activated by acid exposure may also influence cardiac function. The available data convincingly demonstrate a reduction of the exertional angina threshold and changes of the ECG (ST segment depression and arrhythmia). These effects are most likely due to a reduced coronary blood flow.
Afferent Pathways↗
Gastric Helicobacter pylori infection accelerates healing of reflux esophagitis during treatment with the proton pump inhibitor pantoprazole.
BACKGROUND & AIMS: In previous studies an exaggerated effect of proton pump inhibitors (PPIs) on intragastric pH in Helicobacter pylori-infected patients was observed. Because healing and improvement of symptoms in patients with gastroesophageal reflux disease (GERD) is directly associated with an increase of intragastric pH during treatment, we hypothesized that the response to treatment with a PPI in patients with reflux esophagitis would be better in H. pylori-infected patients than in patients without H. pylori infection. METHODS: We recruited 971 patients with endoscopically verified reflux esophagitis grades II and III (Savary/Miller). At study entry, H. pylori status was assessed by a 13C-urea breath test and baseline characteristics were recorded. Physicians and patients were not notified about the results of the breath test until completion of the study. All patients underwent treatment with pantoprazole, 40 mg orally once daily for 4 weeks. Healing was verified by endoscopy after 4 or 8 weeks of treatment. If the esophagitis had not completely healed at this time, treatment was continued for a further 4-week period. Healing rates and symptom relief were compared for patients with and without H. pylori infection. RESULTS: The prevalence of H. pylori was 39.9% (95% confidence interval [CI], 36.9-42.9), and neither gender, smoking, nor alcohol consumption were associated with the H. pylori infection (P > 0.4). The trial was completed by 846 patients without protocol violation. Overall healing rates of reflux esophagitis were 80.4% (95% CI, 77.7-83.1) and 93.6% (95% CI, 91.8-95.2) after 4 and 8 weeks, respectively. In H. pylori-positive patients, healing rates were significantly higher after 4 (86.6% vs. 76.3%; P = 0.0005) and 8 weeks (96.4% vs. 91.8%; P < 0.004). Relief of symptoms after 4 weeks was also significantly (P < 0.05) better in H. pylori-infected patients than in uninfected patients. CONCLUSIONS: Patients with reflux esophagitis and H. pylori infection respond significantly better than H. pylori-negative patients to the PPI pantoprazole.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Development of a new dyspepsia impact scale: the Nepean Dyspepsia Index.
BACKGROUND: There is not at present a suitable disease-specific health-related quality of life instrument for uninvestigated dyspepsia and functional (non-ulcer) dyspepsia. AIM: To develop a new multi-dimensional disease-specific instrument. METHODS: The Nepean Dyspepsia Index (NDI) was designed to measure impairment of a subject's ability to engage in relevant aspects of their life and also their enjoyment of these aspects; in addition, the individual importance of each aspect is assessed. A 42-item quality of life measure was developed and tested, both in out-patients presenting to general practice with upper gastrointestinal complaints (n = 113) and in a randomly chosen population-based sample (n = 347). RESULTS: Adequate face and content validity was documented by an expert panel. Factor analysis identified four clinically relevant subscales: interference with activities of daily living, work, enjoyment of life and emotional well-being; lack of knowledge and control over the illness; disturbance to eating or drinking; and disturbance to sleep because of dyspepsia. These scales had high internal consistency. Both symptoms and the quality of life scores discriminated dyspepsia from health. CONCLUSION: The Nepean Dyspepsia Index is a reliable and valid disease-specific index for dyspepsia, measuring symptoms and health-related quality of life.
Adult↗
Management of uninvestigated and functional dyspepsia: a Working Party report for the World Congresses of Gastroenterology 1998.
BACKGROUND: The management of dyspepsia is controversial. METHODS: An international Working Party was convened in 1998 to review management strategies for dyspepsia and functional dyspepsia, based on a review of the literature and best clinical practice. RESULTS: Dyspepsia, defined as pain or discomfort centred in the upper abdomen, can be managed with reassurance and over-the-counter therapy if its duration is less than 4 weeks on initial presentation. For patients with chronic symptoms, clinical evaluation depends on alarm features including patient age. The age cut off selected should depend on the age specific incidence when gastric cancer begins to increase, but in Western nations 50 years is generally an acceptable age threshold. In younger patients without alarm features, Helicobacter pylori test and treatment is the approach recommended because of its value in eliminating the peptic ulcer disease diathesis. If, after eradication of H. pylori, symptoms either are not relieved or rapidly recur, then an empirical trial of therapy is recommended. Similarly, in H. pylori-negative patients without alarm features, an empirical trial (with antisecretory or prokinetic therapy depending on the predominant symptom) for up to 8 weeks is recommended. If drugs fail, endoscopy should be considered because of its reassurance value although the yield will be low. In older patients or those with alarm features, prompt endoscopy is recommended. If endoscopy is non-diagnostic, gastric biopsies are recommended to document H. pylori status unless already known. While treatment of H. pylori is unlikely to relieve the symptoms of functional dyspepsia, the long-term benefits probably outweigh the risks and treatment can be considered on a case-by-case basis. In H. pylori-negative patients with documented functional dyspepsia, antisecretory or prokinetic therapy, depending on the predominant symptom, is reasonable, assuming reassurance and explanation are insufficient, unless patients have already failed this approach. Other treatment options include antidepressants, antispasmodics, visceral analgesics such as serotonin type 3 receptor antagonists, and behavioural or psychotherapy although these are all of uncertain efficacy. Long-term drug treatment in functional dyspepsia should be avoided; intermittent short courses of treatment as needed is preferred. CONCLUSION: The management of dyspepsia recommended is based on current best evidence but must be tailored to local factors such as practice setting, the background prevalence of H. pylori and structural disease, and costs.
Decision Trees↗