[What is your diagnosis? Severe celiac disease (endemic sprue)].
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Biomedical subjects
Publications and source records attributed to P Netzer.
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The acute upper gastrointestinal bleeding continues to represent one of the most frequent gastrointestinal emergencies both in hospital and out-patient settings. While the underlying etiology is widespread, the leading causes for such bleeding events are gastro-duodenal ulcers and esophageal or gastric varices. Given the potential life-threatening character of the bleeding, the first step in treating such a patient is the assessment of the severity of the bleeding based upon clinical and laboratory parameters. This translates into the time point of performing an endoscopy of the upper gastrointestinal tract. The role of gastro-esophago-duodenoscopy is defined by its dual function for the diagnosis of the exact origin of the bleeding and the therapy of the bleeding during the same examination. Drug administration has to accompany this endoscopic intervention. Effective acid suppression is in the focus of conservative treatment. In case of varices, additional medication has to be given to lower the portovenous pressure. Following persistent bleeding after endoscopic intervention, radiological and surgical treatment options have to be discussed in time.
BACKGROUND AND STUDY AIMS: The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach. PATIENTS AND METHODS: A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1. RESULTS: In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %). CONCLUSIONS: In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.
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Abdominal pain can result from a variety of different intra- and extra-abdominal disorders. Given the wide variety of etiological triggers for this pain, the primary task during the first stage of the diagnostic work-up is to determine as soon as possible the underlying cause and the degree of emergency. The aim of this evaluation is to adapt the therapeutic measures which are necessary for a causal treatment to the individual situation. Contrary to somatic causes of abdominal pain, the availability of such a causal therapy for functional bowel disorders is still very limited. Given this dilemma, the therapeutic focus of abdominal pain associated with these functional syndromes has to be placed on symptom-oriented treatment.
Dysphagia is a rare manifestation in a patient with Crohn's disease. We report on the case of a patient with long-standing Crohn's disease who developed progressive dysphagia over 3 years. Endoscopy showed minimal distal oesophagitis with non-specific histological findings. Further investigation with cinematography, barium swallow and manometry established an achalasia-like motility disorder. Biopsies obtained from the oesophagus were non-specific. Balloon dilatation was performed. Initial success was followed by recurrent dysphagia. At repeat endoscopy, an oesophageal fistula was detected. An attempt at conservative medical management failed and oesophagectomy was successfully performed. Pathology results of the resected specimen confirmed the suspected diagnosis of oesophageal Crohn's disease. Even if achalasia is suspected in a Crohn's patient, it should be taken into consideration that the motility disorder could be the result of a transmural inflammation with or without fibrosis caused by Crohn's disease.
BACKGROUND: In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5-hydroxytryptamine-3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans. AIM: To evaluate the effect of ondansetron on gastric half-emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers. METHODS: In a placebo-controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post-prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin. RESULTS: The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron. CONCLUSIONS: Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides.
AIM: The effect of ABT-229, a new macrolide with no antibacterial activity, on gastro-oesophageal reflux, oesophageal motility and gastric emptying in patients with gastro-oesophageal reflux disease was investigated. METHODS: Twenty-one patients were treated with a placebo and ABT-229 (2.5, 5 or 10 mg b.d.) in a randomized, incomplete crossover study design. Ambulatory 24-h pH manometry was performed and gastric emptying was assessed by the 13C-octanoic acid breath test on the seventh day of treatment. RESULTS: A significant decrease was found in the mean (+/- s.e.) percentage of reflux time (intra-oesophageal pH < 4) for ABT-229 5 mg b.d. and 10 mg b.d., but not for 2.5 mg b.d., compared with placebo. For ABT-229 5 mg, it was 8.5 +/- 0.5% vs. 10.7 +/- 0.7% (P < 0.038) and, for ABT-229 10 mg, it was 6.6 +/- 0.5% vs. 8.4 +/- 0.5% (P < 0.019). There were no significant differences in any of the analysed manometric parameters. In addition, the gastric half-emptying time for all doses of ABT-229 did not differ significantly from that after placebo. CONCLUSIONS: ABT-229 is able to reduce slightly, but significantly, acid reflux in patients with gastro-oesophageal reflux disease. This effect does not appear to be due to a measurable improvement in oesophageal motility or gastric emptying.
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There is considerable evidence that opioid mechanisms are involved in the mediation of pyloric motor responses that in turn regulate gastric emptying. The purpose of this randomized, placebo-controlled crossover study was to investigate the effect of naloxone on gastric emptying of a solid meal, gastric myoelectrical activity and the postprandial release of gastrointestinal peptides and neuropeptides in 20 healthy volunteers. Naloxone was administered as an intravenous bolus, followed by continuous infusion according to an intravenous dosing nomogram. Gastric emptying time was evaluated by scintigraphy and gastric myoelectrical activity was evaluated by cutaneous electrogastrography. Naloxone did not significantly alter gastric half-emptying time and postprandial dominant gastric electrical frequency compared with placebo. It also did not significantly change the plasma levels of several peptide hormones with the exception of neuropeptide Y, which was significantly increased (P = 0.001). In conclusion, in doses that influence human intestinal motility, naloxone had no effect on gastric motility and release of several peptide hormones in healthy male volunteers. The importance of the isolated increased neuropeptide Y plasma level needs further investigation.
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BACKGROUND: The introduction of total mesorectal excision (TME) has been shown to improve local recurrence rates in rectal cancer. The present study investigated the impact of this more extensive and radical procedure with regard to autonomic pelvic nerve function. METHODS: Patients with resected primary rectal cancer were interviewed by means of a questionnaire asking about preoperative and postoperative urinary bladder and genital function. The results in patients after rectal cancer surgery without TME (group 1; n = 29) were compared with those obtained after introduction of the TME technique (group 2; n = 31). Patients in group 2 were older and had a lower level of anastomosis than patients in group 1. Other patient, treatment and tumour characteristics were comparable between the groups. RESULTS: : Newly acquired and permanent symptoms of bladder dysfunction after rectal excision were present as follows (group 1 versus group 2): difficulty in bladder emptying 7 versus 19 per cent; sensation of incomplete bladder voiding 17 versus 17 per cent; urgency 17 versus 14 per cent; incontinence 10 versus 3 per cent; dysuria 7 versus 7 per cent; and dribbling 14 versus 8 per cent. Male patients stated the following sexual functions before operation/after operation in group 1 versus group 2: interest in sex 80 per cent/40 per cent versus 63 per cent/37 per cent; sexually active 67 per cent/7 per cent versus 53 per cent/22 per cent; impotence 75 per cent/6 per cent versus 58 per cent/26 per cent; ability to have intercourse 75 per cent/13 per cent versus 67 per cent/29 per cent; ability to achieve orgasm 88 per cent/13 per cent versus 76 per cent/47 per cent; and orgasm with ejaculation 88 per cent/9 per cent versus 76 per cent/53 per cent. CONCLUSION: While both conventional rectal cancer surgery and TME result in similarly favourable postoperative bladder function, both techniques decrease sexual function. However, TME offers a significant advantage with regard to preservation of postoperative sexual function in men and constitutes a true advance in rectal cancer surgery compared with conventional techniques.
BACKGROUND: Reflux of duodeno-gastric juice into the oesophagus appears to be involved in the pathogenesis of both reflux oesophagitis and oesophageal adenocarcinoma. Although proton pump inhibitors have been shown to decrease acid reflux and heal oesophagitis, their effect on biliary reflux and motility is less clear. AIM: To investigate whether pantoprazole also reduces bile reflux and whether this is paralleled by a change in oesophageal motility. METHODS: Combined 24-h measurements of intraoesophageal bilirubin concentration, pH and pressure were performed in 18 symptomatic patients with endoscopically proven reflux oesophagitis before and on day 28 of treatment with pantoprazole, 40 mg/day, under standardized conditions. A reflux symptom score was determined initially and every 2 weeks thereafter. After 56 days on medication, a control endoscopy was performed. RESULTS: The symptom score and the acid and bile reflux improved significantly, whereas the motility parameters did not change during the study period. Helicobacter pylori-positive patients had a significantly higher bile reflux time (32.1 +/- 4.3%) than H. pylori-negative patients (16.3 +/- 3.1%) (P=0.009). The endoscopic healing rate was 89%. The cough symptoms disappeared in three of four patients. CONCLUSIONS: The proton pump inhibitor pantoprazole decreases both acid and bile reflux. The decrease of bile reflux cannot be explained by increased oesophageal clearance as oesophageal motility did not improve with therapy. Interestingly, H. pylori infection of the stomach was associated with higher levels of oesophageal bile reflux.
BACKGROUND: Basic fibroblast growth factor has been shown to be mitogenic in colon cancer cell lines. In human malignant melanoma cells, antisense oligodeoxynucleotides targeted against basic fibroblast growth factor messenger RNA significantly inhibit cell growth. However, the efficacy of such an antisense oligodeoxynucleotide strategy has not been evaluated for colon cancer cells. AIM: To investigate whether basic fibroblast growth factor can stimulate the growth of HT-29 human colon cancer cells and whether antisense oligodeoxynucleotides can inhibit growth of these cells at baseline. METHODS: Western blotting analyses were used to confirm the presence of basic fibroblast growth factor protein in this cell line. Cell growth was assessed after 2, 4 and 6 days of treatment by cell counting using the trypan blue exclusion method. Phosphorothioate-modified oligodeoxynucleotides (10 microM) were used, complementary to codon 60 of the basic fibroblast growth factor messenger RNA. Cationic liposomes (DOTAP) were used to enhance the cellular uptake of the oligodeoxynucleotides. RESULTS: Western blotting demonstrated the presence of basic fibroblast growth factor protein in this cell line. Basic fibroblast growth factor (1-40 ng/mL) dose-dependently stimulated cell growth and peak values were obtained at a dose of 20 ng/mL. By contrast, antisense oligodeoxynucleotide treatment significantly inhibited cell growth compared with the sense oligodeoxynucleotide-treated cells (P=0.007). This inhibition was reversed by the addition of basic fibroblast growth factor, 20 ng/mL. CONCLUSION: Treatment targeted against basic fibroblast growth factor messenger RNA inhibits growth of HT-29 human colon cancer cells. This finding may provide a rationale for the therapeutic use of antisense oligodeoxynucleotides targeted at basic fibroblast growth factor for the treatment of colon cancer.
BACKGROUND: The pathway by which Helicobacter pylori induces apoptosis in gastric epithelial cells is not known. The aim of this study was to determine whether H. pylori-induced apoptosis is associated with SAPK/JNK activity in human gastric cancer KATO III cells. MATERIALS AND METHODS: H. pylori VacA toxin positive strain was incubated with KATO III cells for 0.5, 1, 2 or 24 hours. The SAPK/JNK protein was harvested from the KATO III cell lysate by precipitation with a C-jun fusion protein and its activity was measured by C-jun phosphorylation utilizing transblotting and phosphoserine antibody. Cellular apoptosis was demonstrated by DNA fragmentation. In addition, cell growth in coculture with H. pylori was determined over 72 hours. RESULTS: H. pylori significantly stimulated SAPK/JNK activity in KATO III cells with a peak at the 0.5 hour time point (3.6-fold vs. control, p <.05), but a return to basal levels by 2 hours. In addition, significant DNA fragmentation was observed after 24 hours in these cells but not in the control KATO III cells. Cell growth was inhibited in a dose dependent fashion in coculture with H. pylori. CONCLUSION: These results show that H. pylori triggers an increase in apoptosis in KATO III cells as reflected by DNA fragmentation. This effect was preceded and correlated with an increase in SAPK/JNK activity suggesting that the H. pylori-induced apoptosis in human gastric epithelial cells may be mediated by the SAPK/JNK pathway.
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Eosinophilic gastroenteritis is a rare disease of the gastrointestinal tract in which the eosinophils seem to play an important role in the inflammation of the gut wall. We report on a case with a synchronous first manifestation of eosinophilic gastroenteritis and bronchial asthma, which also occurred synchronously in all further episodes. The diagnosis was first made at the end of the second episode during which the patient lost more than 13 kg in weight. Under steroid therapy, symptoms of both diseases disappeared quickly in the third episode. We assume that participation of the gastrointestinal tract in patients with bronchial asthma occurs more frequently than expected. In asthma patients with abdominal symptomatology, eosinophilic gastroenteritis should also be considered.
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