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G Holtmann

Publications and source records attributed to G Holtmann.

At least 37 records · Page 2Linked to original sources

Review article: management of peptic ulcer bleeding-the roles of proton pump inhibitors and Helicobacter pylori eradication.

Peptic ulcer bleeding is associated with substantial morbidity and mortality. The goals of management are to control any active bleeding and prevent re-bleeding and then to heal the ulcer and prevent its recurrence. Initial management strategies are guided by the patient's clinical condition and endoscopic findings. Thus, treatment may consist of endoscopic and medical therapy and, sometimes, surgery. Control of acid secretion, preferably with proton pump inhibitor therapy in the initial management continues to evolve; it has also been used as both an adjunct to endoscopic therapy and as primary treatment. These agents have been found to be effective in some trials in the reduction of re-bleeding and the need for surgery, although there is no clear benefit demonstrated for overall mortality. Proton pump inhibitors have been administered either intravenously or orally in different trials. The long-term management of patients with peptic ulcer, after the initial bleeding episode, should include patient stratification based upon risk factors for ulcer recurrence (i.e. Helicobacter pylori infection, use of aspirin or nonsteroidal anti-inflammatory drugs). Elimination or modification of these risk factors reduces the risk of ulcer recurrence and, hence, of recurrent ulcer bleeding.

Anti-Ulcer Agents↗

Review article: the patient with gastro-oesophageal reflux disease--lifestyle advice and medication.

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%.

Cytochrome P-450 Enzyme System↗

Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease.

The major oesophageal complications associated with persistent gastro-oesophageal reflux disease (GERD) include erosive oesophagitis, ulceration, strictures and gastrointestinal (GI) bleeding. Although the causes of these complications are uncertain, studies indicate that erosive oesophagitis may progress to the development of ulcers, strictures and GI bleeding. Pharmacological treatment with proton pump inhibitors is favoured over that with H(2)-receptor antagonists for the treatment of strictures. The treatment of strictures is accomplished with dilation and many favour the concomitant use of proton pump inhibitors. Most gastroenterologists are seeing far fewer oesophageal strictures these days since the introduction of proton pump inhibitors. In addition, research has shown that oesophageal complications have a greater impact on patients suffering from night-time GERD than on those suffering from daytime GERD. Barrett's oesophagus is a significant complication associated with persistent GERD and those at risk generally experience a longer duration of symptoms, especially those with a high degree of severity. In addition, there is a strong relationship between Barrett's oesophagus and oesophageal adenocarcinoma. This is in part due to the association of obesity and the development of hiatal hernias. Furthermore, endoscopic screening is being used to detect Barrett's oesophagus and oesophageal adenocarcinoma in persons suffering from chronic GERD, even though screening may not have an impact on outcomes (Sharma P, McQuaid K, Dent J, et al. A critical review of the diagnosis and management of Barrett's esophagus: The AGA Chicago Workshop. Gastroenterology 2004; 127: 310-30.).

Adenocarcinoma↗

Symptom patterns in functional dyspepsia and irritable bowel syndrome: relationship to disturbances in gastric emptying and response to a nutrient challenge in consulters and non-consulters.

BACKGROUND: Our aim was to assess the relationship between gastric motor and sensory function and symptom patterns in community subjects and patients with functional dyspepsia (FD) or irritable bowel syndrome (IBS). METHODS: We recruited 291 asymptomatic blood donors, 151 symptomatic blood donors (recurrent abdominal pain or discomfort), and 40 patients with FD or IBS. Abdominal symptoms were assessed using the bowel disease questionnaire (BDQ) and, in addition, the most bothersome symptom complex identified (dysmotility-type, ulcer-type dyspepsia, or IBS). Gastric emptying time (GET (t(1/2), min)) was measured by (13)C-octanoic breath test and a nutrient challenge performed. Twenty randomly selected asymptomatic blood donors, 48 symptomatic blood donors (30 FD, 18 IBS), and 40 patients (23 FD, 17 IBS) had additional function testing. RESULTS: GET (t(1/2)) was significantly (p<0.05) longer in blood donors with FD symptoms (99 (6) min) and FD patients (110 (12) min) compared with asymptomatic controls (76.7 (7) min), but was not significant in IBS blood donors or patients. Overall, 25 of 48 blood donors with symptoms and 18 of 40 patients had slow gastric emptying. GET was most delayed in subjects with predominantly dysmotility-type symptoms (167 (36) min v controls; p<0.01). Symptom intensities after a nutrient challenge were significantly higher in FD patients and symptomatic blood donors compared with asymptomatic controls; 14 of 48 blood donors with symptoms and 16 of 40 patients had a symptom response to the nutrient challenge exceeding the response (mean (2SD)) of healthy asymptomatic controls. CONCLUSION: Gastric emptying and the global symptom response to a standardised nutrient challenge are abnormal in population based (non-health care seeking) subjects with dyspepsia.

Adolescent↗

Real time high resolution magnetic resonance imaging for the assessment of gastric motility disorders.

BACKGROUND: The aim of this study was to evaluate whether patients with increased or decreased gastric motility can be differentiated from healthy volunteers by means of real time magnetic resonance imaging (MRI). PATIENTS AND METHODS: Ten healthy volunteers, 10 patients with gastroparesis, and 10 patients with functional pylorospasm/peptic pyloric stenosis underwent real time MRI. All patients were examined on two separate days; once prior to therapy and once after adequate therapy. Antral motility was quantified by calculating the gastric motility index. RESULTS: Patients with gastroparesis showed a lower motility index compared with the reference volunteer group while the mean motility index of the patient group with pylorospasm was more than three times higher than that of the reference value of the volunteer group. However, the gastric motility index in the patient group with gastroparesis increased, and in the group with functional pylorospasm/peptic pyloric stenosis it decreased significantly after therapy. CONCLUSION: Real time MRI is a reliable tool for assessment of gastric motion. Furthermore, differences in gastric motility index in patients with increased or decreased gastric motility could be evaluated and quantified. Due to the non-invasive character of MRI, this imaging modality may be an attractive alternative to conventional invasive diagnostic tools for gastric motility disorders and therapeutic monitoring.

Adult↗

Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome.

Appropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations. This consensus report highlights the following points. (a) A 4-week period is considered to be adequate to assess drug efficacy for the control of symptoms. (b) For the cyclic and non-life-threatening nature of the disease, a long-term study of 4-6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients. (c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow-up period prolonged for a sufficient time (4-8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome. (e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome. (f) The main efficacy outcome of the treatment should be based on one primary end-point. (g) The primary efficacy end-point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms. (h) A 50% improvement in the primary efficacy end-point seems to be a reasonable definition of a responder.

Clinical Trials as Topic↗

Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six-week placebo-controlled, double-blind, multicentre trial.

BACKGROUND: This study aimed to assess the efficacy of artichoke leaf extract (ALE) in the treatment of patients with functional dyspepsia (FD). METHODS: In a double-blind, randomized controlled trial (RCT), 247 patients with functional dyspepsia were recruited and treated with either a commercial ALE preparation (2 x 320 mg plant extract t.d.s.) or a placebo. The primary efficacy variable was the sum score of the patient's weekly rating of the overall change in dyspeptic symptoms (four-point scale). Secondary variables were the scores of each dyspeptic symptom and the quality of life (QOL) as assessed by the Nepean Dyspepsia Index (NDI). RESULTS: Two hundred and forty-seven patients were enrolled, and data from 244 patients (129 active treatment, 115 placebo) were suitable for inclusion in the statistical analysis (intention-to-treat). The overall symptom improvement over the 6 weeks of treatment was significantly greater with ALE than with the placebo (8.3 +/- 4.6, vs. 6.7 +/- 4.8, P < 0.01). Similarly, patients treated with ALE showed significantly greater improvement in the global quality-of-life scores (NDI) compared with the placebo-treated patients (- 41.1 +/- 47.6 vs. - 24.8 +/- 35.6, P < 0.01). CONCLUSION: The ALE preparation tested was significantly better than the placebo in alleviating symptoms and improving the disease-specific quality of life in patients with functional dyspepsia.

Adolescent↗

Reflux disease and Barrett's esophagus.

Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders. The key feature of GERD is reflux of gastric contents into the esophagus. Medical treatment with proton-pump inhibitors (PPIs) is well established and is considered the standard treatment. Given the high prevalence of the condition and the excellent response to medical therapy, antireflux surgery is an option for patients with volume reflux that is not properly controlled by medical therapy. Adenocarcinoma is a rare but life-threatening complication of GERD. The only known precursor lesion for esophageal adenocarcinoma is Barrett's esophagus. In recent years, a clearer understanding of the development of Barrett's and of its progression toward invasive cancer has developed. Genetic factors almost certainly determine the individual risk. The length of the Barrett's esophagus segment and the size of a hiatal hernia are associated with the risk of developing high-grade dysplasia and esophageal adenocarcinoma.With regard to the clinical management of GERD patients with Barrett's, endoscopic surveillance at 3-year intervals is now considered appropriate in the absence of dysplasia. In patients with high-grade dyspepsia, the situation is more difficult. While a considerable proportion of these patients may already have invasive cancers, there is also the possibility that there is only focal dysplasia. For this reason, it is justifiable to carry out curative endoscopic resection. Mucosal ablation procedures may also be appropriate, but these still need to be properly investigated in clinical trials.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Persistently altered visceral perception after resection of an esophageal granular cell myoblastoma: a therapeutic concept revisited.

Granular cell tumors (GCTs) are rare and usually benign gastrointestinal tumors. Their most frequent symptoms are dysphagia and epigastric or retrosternal discomfort. We here report a case of esophageal GCT with continued symptoms of retrosternal discomfort, postprandial feeling of fullness, and early satiety despite complete thoracoscopic resection of the tumor. In contrast, all functional tests were in the normal range. We thus suggest that, due to their neuroectodermal origin, GCTs may affect neuronal alterations leading to a persistently disturbed visceral mechanosensory perception. Consequently, this case also cautions the therapeutic concept to solely relieve GCT symptoms by resection if the tumor is less than 20 mm in diameter.

Adult↗

[Epidemiology and clinical phenomenology of visceral pain].

Visceral pain is characterized by a subjectively painful perception located in the abdominal area. Distinct structural lesions or biochemical abnormalities which could serve as explanation for these painful sensations can be only detected in a proportion of patients. In the absence of precise causes for visceral pain, the symptoms are attributed to functional disorders. The two major single entities among functional disorders of the gut are functional dyspepsia and irritable bowel syndrome. Patients with functional dyspepsia characteristically localize the symptoms in the upper abdomen. Functional gastrointestinal disturbances which are localized in the lower abdomen are summarized as irritable bowel syndrome. Interestingly,both functional dyspepsia and irritable bowel syndrome may overlap.

Dyspepsia↗

[Diagnostic criteria and therapeutic strategies of abdominal pain syndromes].

Abdominal pain syndromes can be categorised into acute or chronic manifestations. In general, diagnostic work-up is targeted upon identification of structural lesions that cause the symptoms and allows therapeutic measures that permanently cure the cause of symptoms. If no structural or biochemical abnormality can be identified upon utilising the necessary diagnostic measures, a functional disorder as the cause of symptoms is assumed. For these disorders no cure is currently available and treatment is targeted towards relief of symptoms only.

Abdominal Pain↗

A randomized, double-blind, comparative study of standard-dose rabeprazole and high-dose omeprazole in gastro-oesophageal reflux disease.

BACKGROUND: Rabeprazole has a faster onset of antisecretory action than omeprazole, and it is of interest to determine whether this translates into faster symptom relief in patients with gastro-oesophageal reflux disease. AIMS: To assess the relief from heartburn after 3 days of treatment with standard-dose rabeprazole or high-dose omeprazole (primary end-point). Secondary end-points included the decrease in score for other symptoms of gastro-oesophageal reflux disease, healing rates and quantification of antacid use. METHODS: Patients with endoscopically confirmed erosive oesophagitis were randomized to receive 4 weeks of double-blind treatment with rabeprazole (20 mg) or omeprazole (40 mg). Patients who were not healed after 4 weeks received a further 4 weeks of treatment. RESULTS: Two hundred and seventy-four patients were screened, 251 patients were randomized and 230 patients completed the trial. The numbers of patients with relief from heartburn on day 4 were similar in the two groups (84% for rabeprazole; 95% confidence interval, 76-90%; 83% for omeprazole; 95% confidence interval, 75-89%). There were no significant differences between the treatments in the relief from other gastro-oesophageal reflux disease symptoms or in healing rates. The number of reports of severe heartburn during the first 3 days was higher in the omeprazole group (daytime heartburn: 4.7% for rabeprazole vs. 10.3% for omeprazole, P=0.005; night-time heartburn: 4.7% for rabeprazole vs. 9.8% for omeprazole, P=0.01; statistical comparisons defined post hoc). CONCLUSIONS: Standard-dose rabeprazole was as effective as high-dose omeprazole in relieving symptoms by day 4 of treatment and in healing oesophageal lesions, but had a faster onset of action in patients with severe heartburn. This suggests that the improved pharmacological properties of rabeprazole translate into a clinically relevant advantage.

2-Pyridinylmethylsulfinylbenzimidazoles↗

A randomized placebo-controlled trial of simethicone and cisapride for the treatment of patients with functional dyspepsia.

AIM: To compare the efficacy of simethicone with placebo and the prokinetic cisapride in patients with functional dyspepsia. METHODS: One hundred and eighty-five patients with functional dyspepsia were randomized and treated in a double-dummy technique with simethicone (105 mg t.d.s.), cisapride (10 mg t.d.s.) or placebo (t.d.s.). The primary outcome measure was the O'Brien global measure of the patients' rating of 10 upper gastrointestinal symptoms (graded as absent = 0, moderate = 1, severe = 2 or very severe = 3). Outcome measures were assessed at baseline and after 2, 4 and 8 weeks of treatment (intention-to-treat). RESULTS: At 2, 4 and 8 weeks, treatment with simethicone and cisapride yielded significantly (all P values < 0.0001) better improvement of symptoms compared to placebo. Simethicone was significantly better than cisapride after 2 weeks (P = 0.0007), but the differences were not statistically significant after 4 and 8 weeks. Patients treated with simethicone judged the efficacy of their treatment as very good in 46% of cases, compared to 15% and 16% receiving cisapride and placebo, respectively. CONCLUSIONS: Simethicone and cisapride were significantly better than placebo for symptom control in patients with functional dyspepsia after 2, 4 and 8 weeks of treatment. Simethicone was also superior to the prokinetic cisapride in the first 2 weeks of treatment.

Adult↗

[Gastrocolic fistula - a rare cause of cachexia and polyneuropathy].

Gastrocolic fistula is a rare clinical disorder which in the past most often occurred after gastric surgery or carcinoma of the gastrointestinal tract. However, during the last decade an increasing number of cases after benign gastric ulcers have been described. Most common symptoms have been weight loss, abdominal pain, diarrhea and copremesis. A 49-year-old cachectic patient presented with a 2-year history of abdominal discomfort and diarrhea. He reported a weight loss of 32 kg during this period and was finally unable to move because of exhaustion. Furthermore, he suffered of burning paresthesia of the legs and the abdomen. His medical history included a Billroth II operation because of recurrent ulcer disease in 1987. Barium enema revealed a gastrocolic fistula which caused small bowel bacterial overgrowth with villous atrophy and malabsorption and development of polyneuropathy. The fistula was surgically resected, and postoperatively, the patient improved and regained his weight. Gastrocolic fistula is a rare cause of diarrhea and should be considered in clinical practice. Barium enema is superior to endoscopy in detecting gastrocolic fistula.

Cachexia↗

Capsaicin-sensitive nerve fibres induce epithelial cell proliferation, inflammatory cell immigration and transforming growth factor-alpha expression in the rat colonic mucosa in vivo.

BACKGROUND: Capsaicin-sensitive nerve fibres protect gastrointestinal mucosa in animal models of mucosal injury by modulation of mucosal blood flow and mucus secretion. The aim of our study was to evaluate the effects of capsaicin-sensitive nerve fibres in rat colonic mucosa on epithelial cell proliferation and transforming growth factor-alpha (TGFalpha) expression, which is important in mucosal defence, protection and repair. METHODS: Male Wistar rats received either a capsaicin enema with or without giving antagonists to calcitonin-gene-related-peptide (CGRP) or substance P (SP) i.v. immediately prior to the capsaicin enemas; a capsaicin enema after sensory desensitization as described previously; or a vehicle enema. In all experiments, animals received 50 mg/kg BrdU i.v. and were killed at 2, 4, 8, 12, 24 and 48 h after the various treatments. Colonic mucosal specimens were evaluated microscopically for mucosal damage, changes in the numbers of inflammatory cells and BrdU-immunoreactive epithelial cell nuclei. In the same specimens, TGFalpha-mRNA and -protein expression were evaluated by RT-PCR and Western blot analysis using standardized procedures. RESULTS: A significant increase in the number of mucosal inflammatory cells and an increase in BrdU-immunoreactive nuclei were detected following mucosal exposure to capsaicin. A 2-fold increase of TGFalpha mRNA and a 10-fold increase of TGFalpha protein expression were obtained 2-12 h after capsaicin enemas. The effects on the invading number of inflammatory cells and on the increase in BrdU immunoreactive epithelial cell nuclei were significantly reduced by both CGRP and SP antagonists and were abolished in rats previously sensory-desensitized. CONCLUSION: Capsaicin-sensitive nerve fibres modulate epithelial cell proliferation and TGFalpha expression in colonic mucosa as well as a migration of inflammatory cells into the colonic mucosa. These effects are mediated by the neurotransmitters CGRP and SP.

Animals↗

[Chronic intestinal pseudo-obstruction. Clinical symptomatology and course].

BACKGROUND AND OBJECTIVE: Chronic intestinal pseudoobstruction (CIP) is a motility disorder clinically characterized by recurrent symptoms of small intestinal or large bowel obstruction without organic stenosis. The aim of the present study was to assess the clinical presentation and course of the disease. PATIENTS AND METHODS: During a four year period all available data including the symptoms as assessed by the bowel disease questionnaire (BDQ) of all patients with newly established diagnosis of CIP were analyzed including duration of symptoms and previous surgical interventions due to the abdominal symptoms. RESULTS: Data of nine patients (five females, four males, age 20 - 64 years) with newly diagnosed CIP were available for analysis. Median age at initial onset of symptoms were 24 years. The final diagnosis of CIP was established after a median of 7 years (range 1 - 20). Initially, the majority of patients suffered from uncharacteristic symptoms such as abdominal fullness and abdominal pain. All patients had undergone repeated abdominal surgical interventions for suspected mechanical bowel obstruction. On average, the first surgical intervention was performed 5 years after the onset of symptoms and there was a median number of 10 treatments as in-patients. Suspected acute bowel obstruction occurred between 1 and 14 times and laparotomies were performed in 50 % of these events. CONCLUSION: The diagnosis of CIP is usually preceded by several years with uncharacteristic abdominal symptoms. During this time, most patients undergo multiple surgical interventions. Thus, in patients with repeated suspected acute bowel obstruction without definite proof of mechanical obstruction, CIP has to be taken into consideration as differential diagnosis. In this context, small bowel manometry is an important diagnostic tool.

Adult↗