The effects of omeprazole on healing and appearance of small gastric and duodenal lesions during dosing with diclofenac in healthy subjects.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal mucosal damage. Omeprazole prevents the formation, and accelerates the healing, of NSAID-induced ulcers. AIM: To test whether omeprazole accelerates healing of standardized gastroduodenal lesions in the presence of diclofenac. METHODS: In a double-blind, double-dummy, placebo-controlled, crossover study, 12 healthy volunteers received consecutive, 2-week courses of omeprazole (40 mg o.d.) and placebo, in random order, with an intervening, 4-week washout period; diclofenac (50 mg t.d.s.), was given for the second week of each course. Five endoscopies were performed, one at the outset and the others before and after each course of diclofenac. Biopsies were taken from the endoscopically normal mucosa of the corpus, antrum and duodenum and also from any new mucosal lesion that developed after diclofenac. The sites of biopsies taken before each course of diclofenac were evaluated endoscopically after each course to assess the extent of healing according to a predetermined healing score scale. RESULTS: The healing scores observed after administration of placebo/diclofenac (median=0; range 0-6) and after omeprazole/diclofenac (median=0; range 0-6; P=0.17) did not differ. Small gastroduodenal lesions developed de novo in six subjects during placebo/diclofenac and in seven during omeprazole/diclofenac. Focal chemical gastropathy was observed only in close proximity to macroscopic lesions. CONCLUSIONS: In healthy subjects, omeprazole does not accelerate the healing of pre-existing mucosal lesions or prevent the development of small diclofenac-induced mucosal lesions.

Pathophysiological studies of sheep during the build-up of immunity against Ostertagia leptospicularis and after a challenge infection.

Four groups of three lambs were used to investigate the pathophysiological changes during the development of a protective immunity against Ostertagia leptospicularis induced by a trickle infection. Three groups (A, B and C) were infected daily with 1000 third-stage larvae (L3) for a period of 26 weeks; group D remained uninfected until challenged. Egg excretion ceased after about 10 weeks in groups A, B and C and at the end of the trickle infection no parasites were found in group A sheep after slaughter. The sheep of groups B and C were highly refractory to two challenge infections, with 100,000 and 200,000 L3, given four and 17 weeks after the end of the trickle infection. Both challenge infections were followed by short term increases in the concentrations of gastrin and pepsinogen in the serum. Group C sheep were immunosuppressed with flumethasone during the second larval challenge and had higher pepsinogen concentrations but similar gastrin concentrations to the untreated sheep of group B.

[Gastrointestinal hormone profile in medullary thyroid carcinoma]. / Gastrointestinales Hormonprofil beim medullären Schilddrüsenkarzinom.

Medullary thyroid carcinoma (MTC) can be important for gastroenterologists because 20-30% of patients with MTC suffer from chronic diarrhea and the tumor is capable of producing--besides other bioactive substances--a multitude of gastroenteropancreatic hormones. Gastrointestinal hormone profiles of 5 patients with MTC were determined both basally and after intravenous stimulation with secretin and calcium respectively. Diagnosis of MTC was confirmed histologically or cytologically and by demonstration of elevated serum concentration of calcitonin both basally and after calcium stimulation. 4/5 patients had chronic diarrhea. Normal values or only borderline increases were found for the following hormones: vasoactive intestinal polypeptide (VIP), neurotensin, substance P, growth hormone releasing hormone (GRH), glucagon, neurokinin A, peptide YY, and pancreatic polypeptide. Somatostatin was elevated after calcium stimulation in 1/5 patients only. The main findings were increased basal concentrations for GAWK in 5/5 patients and elevated concentrations for gastrin-releasing peptide (GRP, human bombesin) after calcium stimulation in 4/5. Probably as a consequence of the GRP increase, an increase in gastrin occurred in parallel, indicating bioactivity of the GRP released from the tumor. Besides calcitonin as the main tumor marker for MTC, determination of GAWK and GRP seems to provide helpful additional markers in laboratory diagnosis of MTC. GRP determination after i.v. calcium infusion allowed identification of patients with normal basal plasma GRP concentration.

[Comparison of the efficacy of omeprazole/bismuth subcitrate or triple therapy in Helicobacter pylori gastritis. A prospective controlled study]. / Vergleich der Wirksamkeit von Omeprazol/Bismutsubcitrat oder Tripletherapie bei Helicobacter-pylori-Gastritis. Eine prospektive kontrollierte Studie.

UNLABELLED: In a controlled, prospective, randomized trial, 10 patients with Helicobacter pylori positive gastritis were treated either with triple therapy (tetracycline, ornidazole, bismuth subcitrate; T, Or, CBS), or omeprazole/CBS (O/CBS) to test the eradication rate of each treatment, its effect on gastritis and meal stimulated gastrin release. METHOD: 6 patients were treated with triple therapy and 4 patients with O/CBS for 2 weeks. Initially, and 0.5, 1, 3, 6, and 12 months after therapy, patients were investigated by a highly specific, quantitative Helicobacter serology, 13C-urea breath test and measurement of meal-stimulated gastrin release. After 3 and 12 months antral biopsies were taken endoscopically for rapid urease testing and culture. Activity of histological gastritis was graded. RESULTS: Eradication for at least 12 months was achieved in 5 out of 6 patients with triple therapy. Serology normalized and gastritis activity improved. In all patients treated with O/CBS, HP was suppressed only temporarily. No eradication was achieved. Urease testing and histology proved to be reliable tests for detecting HP. Culturing of HP was successful in only 66% due to technical problems. The 13C-urea breath test was correct in all cases. The initially, increased meal-stimulated gastrin release was normalized after eradication of HP. CONCLUSION: (1) Triple therapy is also successful in short term treatment in up to 80% of patients with HP gastritis and improves gastritis activity. (2) The combination O/CBS failed to eradicate HP in all treated patients. (3) The 13C-urea breath test and HP serology are reliable non-invasive parameters during follow-up. (4) Normalization of meal stimulated gastrin release after eradication of HP supports the hypothesis that HP induces increased gastrin release and hyperacidity.

[Ultrasonic study of gastric emptying of various oral rehydration solutions]. / Die Magenentleerung verschiedener oraler Rehydrationslösungen gemessen mit dem Ultraschall.

Gastric emptying of 4 different oral rehydration solutions was investigated by ultrasound in 7 healthy volunteers in a randomized double-blind study. The final gastric emptying times were 32.9 +/- 4.72 minutes for the glycine solution, 55.1 +/- 9.85 minutes for the glucose (WHO) solution. 60.8 +/- 11.58 minutes for the polycose solution and 58.6 +/- 10.12 minutes for the rice-flour solution (p less than 0.05). Gastric emptying times showed considerable person-to-person variability. Based on identical gallbladder volumes before and 60 minutes after ingestion of the rehydration solutions, there was no indication of cholecystokinin stimulation by any of the solutions tested.

[Well-differentiated papillary mesothelioma of the peritoneum. Rare, but prognostically important differential diagnosis]. / Gut differenziertes papilläres Mesotheliom des Peritoneums. Rarität, aber prognostisch wichtige Differentialdiagnose.

A 35-year-old man who presented with ascites and multiple small peritoneal nodules is still in good health after a follow-up of 6 years despite the fact that two different former histologic sections were interpreted as malignant mesothelioma. The present histologic finding is a well differentiated papillary mesothelioma. We review the literature and discuss the significance of this uncommon finding. It is generally associated with an excellent prognosis. Chemotherapy should be withheld.

Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome.

In patients with multiple endocrine neoplasia type 1 (MEN-1), gastrinomas are common and thought to occur predominantly in the pancreas. We describe eight patients with MEN-1 and hypergastrinemia (seven with the Zollinger-Ellison syndrome) in whom we searched for neuroendocrine tumors in the pancreas and duodenum. Tumors were found in the proximal duodenum in all eight patients: solitary tumors (diameter, 6 to 20 mm) in three patients and multiple microtumors (diameter, 2 to 6 mm) in the other five. Paraduodenal lymph-node metastases were detected in four patients. Immunocytochemical analysis revealed the presence of gastrin in all the duodenal tumors and in their lymph-node metastases. In contrast, no immunoreactivity for gastrin was present in the endocrine tumors found in the seven pancreatic specimens available for study, except for one tumor with scattered gastrin-positive cells. In four of the six patients whose duodenal gastrinomas were removed, serum gastrin levels returned to normal; in the other two patients gastrin concentrations decreased toward normal. We conclude that in patients with MEN-1 and the Zollinger-Ellison syndrome, gastrinomas occur in the duodenum, but the tumors may be so small that they escape detection.

[Endoprosthesis in the palliative treatment of malignant esophageal stenosis]. / Endoprothesen in der palliativen Behandlung maligner Osophagusstenosen.

31 patients with inoperable malignancies of the esophagus were treated for severe dysphagia or fistula by endoscopic placement of an endoprosthesis. The mortality rate was 4%. 56% of the patients with dysphagia and 55% with fistulation experienced relief of symptoms. Complications occurred in about one third of all patients. Median patient survival after diagnosis was 9 months. Median survival after placement of the endoprosthesis was 25 days (25 and 75% quartiles 10 and 50 days, minimum and maximum 1 and 371 days respectively). Prior to placement of an endoprosthesis 66% of the patients had already been treated by chemotherapy, radiotherapy, repeated bougienage or laser photocoagulation. Almost all patients died as a result of their primary illness with the tube still in place. In patients with neoplastic fistulation palliative intubation is the therapy of choice. In addition to intubation, alternative methods are available today for treatment of severe dysphagia. However, further investigation is needed to determine the patients who will benefit most from the placement of a prosthesis.

[Campylobacter pylori colonization of the antrum: effect of gastrin, somatostatin, pancreatic polypeptide and neurotensin]. / Campylobacter-pylori-Besiedelung des Antrums: Einfluss auf Gastrin, Somatostatin, pankreatisches Polypeptide und Neurotensin.

Campylobacter pylori (C.p.) infection is often found in patients with antral gastritis and peptic ulcer disease. Pathophysiological links are still unclear, and we therefore tested the hypothesis whether C.p. affects the gastrointestinal peptides and thus influences gastric acid secretion and protective factors. 94 patients were examined by upper GI endoscopy and blood analyzed for gastrin, somatostatin, pancreatic polypeptide and neurotensin. Biopsies of antral mucosa were investigated for C.p. in urease testing, culture and microscopy. C.p. was found in 42 patients (45%). In microscopy all of these patients had chronic gastritis (100%). A significant increase in gastrin uninfluenced by C.p. was found in patients with antral gastritis (normal: 6.4 +/- 0.7, [n = 27]; gastritis without C.p.: 18.4 +/- 5.9 [p less than 0.02], [n = 7]; gastritis with C.p.: 10.7 +/- 2.2, [n = 22]). Somatostatin, pancreatic polypeptide and neurotensin showed no difference.

Localization of proinsulin and insulin in human insulinoma: preliminary immunohistochemical results.

We have carried out an immunohistochemical investigation of 15 human insulinomas applying monoclonal antibodies specifically recognizing proinsulin and insulin. Our results demonstrate that the epitopes unique to proinsulin and insulin can be detected with the respective monoclonal antibodies using the protein A-gold technique after routine formaldehyde fixation and paraffin embedding of the tissues. The immunostaining pattern for proinsulin and insulin in the insulinomas was different from the observed in B cells of pancreatic islets present in the adjacent normal pancreas. Furthermore, the pattern of immunostaining was found to vary from tumor to tumor. These findings strongly suggest the possibility of a disturbed proinsulin to insulin conversion in human insulinomas.

Presence of neurotensin and neuromedin-N within a common precursor from a human pancreatic neuroendocrine tumor.

An acid extract of a human neuroendocrine pancreatic adenoma was found to contain very high concentrations of immunoreactive neurotensin (iNT; approximately 130 mumol/L) as well as immunoreactive neuromedin-N (iNMN; approximately 40 mumol/L), portions of which (iNT, 0.2%; iNMN, 30%) were found in large molecular forms. Processing of the large forms could be mimicked by treatment with pepsin, which increased their immunoreactivity 15- to 20-fold (iNT) and 1- to 2-fold (iNMN), liberating a peptide similar to NMN and 2 fragments of NT [primary product, NT-(4-13)]. Biochemical characterizations using gel electrophoresis, isoelectric focusing, and high pressure liquid chromatography indicated that the large forms were highly basic (pI 8.5-9.5) proteins with a mol wt of about 20K (78% of the total), 45K (8%), and 60K (4%). The 20K protein contained iNT and iNMN in a 1:1 ratio, while a slightly smaller species contained only NMN. These results are in agreement with cDNA studies of canine intestinal mRNA, indicating the presence of a 170-amino acid precursor containing 1 copy each of NT and NMN. They further indicate that within this tumor differential processing of precursor occurred, resulting in a NT to NMN ratio of about 3:1, with additional NMN stored in large molecular forms.

[Endoscopic therapy of acute upper gastrointestinal bleeding. A breakthrough in non-variceal bleeding?]. / Endoskopische Therapie der akuten oberen Gastrointestinalblutung. Ein Durchbruch bei der Nichtvarizenblutung?

Endoscopic therapy adds a new tool to the management of acute upper gastrointestinal hemorrhage. Endoscopic sclerotherapy being now a well established therapy for acute variceal bleeding, a simple and effective therapy for nonvariceal bleeding was missing. Recently coagulation therapy with laser, electric current or thermocouples has come into use, but injection therapy with hemostatic and sclerosing agents seems a simple, costeffective and relatively safe method. In uncontrolled trials the overall success rate in achieving hemostasis was over 90% and the need for emergency surgery was dramatically reduced. Injection therapy appears to be a major advance in the treatment of nonvariceal bleeding, especially in high risk patients.

Hormone-producing gastrointestinal tumors contain a high density of somatostatin receptors.

Fourteen hormone-producing gastrointestinal tract tumors were tested for their content of somatostatin (SRIH) receptors, using receptor autoradiography and in vitro binding assay with tumor homogenates. All four gastrinomas tested had high levels of SRIH receptors, as did two of five insulinomas and four of five vasoactive intestinal peptide-producing tumors. Receptor visualization was obtained with two different radioligands, either a SRIH-28 analog, [125I]-[Leu8,D-Trp22,Tyr25]SRIH-28, or a SRIH octapeptide, the [125I]Tyr3 derivative of SMS 201-995 [H-DPhe-Cys-Phe-DTrp-Lys-Thr-Cys-Thr(ol)], [125I]204-090. In both cases receptors were localized over the tumor cell area only. Biochemical and pharmacological analyses of one insulinoma and two vipomas revealed saturable, high affinity binding sites with pharmacological specificity for SRIH. However, differences in receptor affinity of selected SRIH analogs, in particular SRIH-28 and SRIH octapeptides, were found between the insulinomas and the two other tumor types, vipoma and gastrinoma. The presence of SRIH receptors on various hormone-producing gastrointestinal tumors suggests that at least part of the beneficial effects of chronic therapy with SRIH analogs may be mediated through such membrane-bound receptors located on the tumor itself. SRIH receptor measurement may be of prognostic value in assessment of the therapeutic efficacy of SRIH analogs. They may also be of diagnostic value, if used as in vivo markers for the localization of small hormone-producing gastrointestinal tumors or their metastases.

[Liver apudoma simulating cystic liver]. / Leber-Apudom unter dem Bild einer Zystenleber.

A 36-year-old man in otherwise good general condition and with completely normal laboratory results suffered from right upper abdominal pain. Hepatomegaly was diagnosed as due to cystic liver disease after ultrasound, computed tomography and magnetic resonance imaging. Recurrent abdominal pain continued over several months. Open liver biopsy eventually revealed trabecular-tubular carcinoma (APUDoma). Silver reaction was positive in many tumour cells. Electronmicroscopy demonstrated membrane-bound granules typical for endocrine cells. Immunohistological examinations of various hormones and of neurone-specific enolase were negative, but repeatedly measured high serum levels of pancreatic polypeptide and of beta-HCG nonetheless suggested an endocrine tumour. This case demonstrates that nonparasitic cystic changes in the liver, especially multiple ones, should have a firm diagnosis established by invasive means. Endocrine tumours can be mistaken for polycystic liver disease.

[Radiation proctocolitis following gynecologic radiotherapy: an endoscopic study]. / Strahlenproktokolitis nach gynäkologischer Radiotherapie: eine endoskopische Studie.

The prevalence of radiation injuries was assessed in 155 of 206 surviving patients who had had radiation therapy for carcinoma of the uterus or vagina. The patients were examined according to a standardized protocol. 51 (32.9%) exhibited endoscopic proctitis, and in 10 of them sigmoid colon was also affected. The prevalence of colitis was 31 of 66 (47%) in patients treated for carcinoma of cervix and 19 of 86 (47%) in those treated for carcinoma of corpus. 41 (80.4%) had clinical symptoms (bleeding and diarrhea in 53% each). The mean time lag between radiation therapy and beginning of symptoms was 9 months. Histology was positive in only 24 (47.1%) of 51 endoscopically documented cases of proctocolitis. There was no increase in the prevalence of radiation injury after previous surgery of any kind. Nor was higher risk found in patients with hypertension, diabetes, or congestive heart failure. However, patients with low body mass were at increased risk (p less than 0.01). There was a dose-response relationship between total dose and endoscopic proctitis (p less than 0.001). The incidence was 0% below 40 Gy, 20% at 60 Gy and 50% at 90 Gy.

Treatment of distal ulcerative colitis with beclomethasone enemas: high therapeutic efficacy without endocrine side effects. A prospective, randomized, double-blind trial.

Sixteen patients with 18 attacks of distal ulcerative colitis were treated randomly with either 0.5 mg topically administered beclomethasone dipropionate (BDP) or 5 mg betamethasone phosphate (BMT). The effect of the steroid enemas on adrenocortical function was examined by ACTH tests, which were performed before and 20 days after treatment. At completion of the trial, a marked suppression of the adrenocortical function was found in seven of eight patients treated for nine attacks with BMT but not in any patients in the BDP group (P less than 0.01). The mean posttreatment basal and stimulated plasma cortisol levels in the BMT group were significantly lower as compared with the BDP group. The overall therapeutic response assessed by score systems was comparable in the two treatment groups. It is concluded that, in the topical treatment of ulcerative colitis, BDP is preferable to BMT because it exerts an equal anti-inflammatory action without affecting adrenocortical function.

[Binding of bile salts and lysolecithin by various antacids in biological media]. / Bindung von Gallensalzen und Lysolecithin in physiologischen Medien durch verschiedene Antazida.

The in vitro capacity of several commercial antacids to bind bile acids and lysolecithin was measured in three different test media: 0.1 n HCl, natural human gastric juice and human gastric juice enriched with 5% protein. Antacids bind bile salts variably. In HCl and in natural and protein-enriched gastric juice the capacity to bind conjugated bile salts was higher (47-72%) for antacids with high aluminium content, such as Alucol, Andursil, Muthesa than for antacids with less aluminium such as Calamox and Riopan (17-18%). Binding of unconjugated bile salts did not show any corresponding difference. The test medium had little effect on binding capacity when pH was comparable. Natural gastric juice was slightly better with regard to binding of conjugated bile salts. The addition of protein had only minimal effect. Lysolecithin was equally heavily adsorbed by all tested antacids and in all three test conditions (85-100%). Since duodenogastral reflux contains mainly unconjugated bile salts, our results suggest that antacids with higher aluminium content should be preferred if binding of bile salt reflux is attempted.

[Esophageal obstruction in tube feeding: a result of protein precipitation caused by antacids?]. / Osophagusobstruktion während Sondenernährung: Folge von Eiweissfällung durch Antazida?

A complication of tube feeding, i.e. thickening of nutrient solution in the presence of an antacid leading to obstruction of the esophagus, is reported. Three patients on artificial breathing where fed by tube with Fresubin liquid. At intervals, Alucol liquid was given for stress ulcer prevention through the tube. After 2, 4, and 50 days respectively, reflux of nutrient solution into the mouth occurred. On removal of the tube a compact, yellowish-white substance was extracted. Endoscopically, residual particles were found in the upper part of the esophagus and in the hypopharynx which obstructed the esophagus completely and in one case could only be extracted through a rigid esophagoscope. In vitro studies showed that thickening of the nutrient solution was due to interaction with antacids administered simultaneously with the nutrient.

Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I. An immunocytochemical study of nine patients.

Pancreatic specimens of nine patients suffering from multiple endocrine neoplasia type I (MEN I) were investigated with regard to tumor frequency and growth pattern, islet hyperplasia and endocrine cell neoformation, immunocytochemical hormone profile of the tumors, and correlation to clinical symptoms. The majority of the 201 tumors were microadenomas (diameter less than 0.5 cm), which frequently displayed a trabecular growth pattern. Microadenomatosis was considered the most distinct feature of the MEN I pancreas. Additional larger tumors (diameter greater than 1.0 cm) were found in five patients. Whereas islet hyperplasia appears not to belong to the spectrum of the pancreatic lesions in MEN I, nesidioblastosis was occasionally observed. Immunocytochemical screening revealed that among hormone-positive tumors (approximately 80% of the tumors), pancreatic polypeptide tumors (PPomas), glucagonomas, and insulinomas were the most frequent. The high incidence of PPomas in these pancreases probably accounts for the elevated serum PP levels found in many MEN I patients. Somatostatinomas, gastrinomas, vasoactive intestinal polypeptide tumors (VIPomas), and neurotensinomas were rare. Clinically overt hyperinsulinism, observed in two patients and associated with a large insulinoma, was cured by tumor resection. Eight of nine patients presented a Zollinger-Ellison's syndrome (ZES), but only in two patients were gastrin-producing tumors found. The source of gastrin in MEN I patients with a ZES, in whom no gastrinoma could be detected, remains unclear.