Somatostatin compared with cimetidine in the treatment of bleeding peptic ulcer without visible vessel.

In a randomized double-blind trial 100 patients with severe bleeding peptic ulcers were treated with an intravenous (i.v.) infusion of cimetidine or somatostatin. Only those patients in whom endoscopy performed within 6 h of admission showed non-arterial bleeding or signs of recent haemorrhage without a visible vessel entered the trial. The two treatment groups were well matched for age, sex, presence of underlying disease, prior ingestion of ulcerogenic drugs, tobacco habits, type of bleeding, haematocrit at admission, presence of hypovolaemic shock, source of bleeding and endoscopic findings. Four patients in each group were excluded after randomization. Further haemorrhage occurred in eight (17.3%) patients in the somatostatin group and in 10 (21.7%) in the cimetidine group, but the difference was not statistically significant. The number of surgical procedures, blood transfusion requirement, duration of hospitalization and mortality rates were similar in the two treatment groups. These results suggest that somatostatin does not improve the results obtained with cimetidine in patients with bleeding peptic ulcer, in whom the endoscopy discloses non-arterial bleeding or signs of recent haemorrhage without a visible vessel.

Potent inhibition of gastric acid secretion and ulcer formation by centrally and peripherally administered interleukin-1.

IL-1 beta is one of the most potent centrally acting inhibitors of gastric acid secretion in rats. Sites of action have been located in the anterior/preoptic area and paraventricular nucleus of the hypothalamus where other biological activities of IL-1 have also been described. IL-1 beta action is, so far, quite unique to this cytokine and its action is not reproduced by IL-2 or TNF alpha. The IL-1 effect involves prostaglandin pathways and is unrelated to CRF. Similarly, systemic injection of IL-1 induces a long lasting inhibition of acid secretion through prostaglandin-dependent mechanisms. Several findings support the possibility that the effect of systemic IL-1 can be CNS-mediated and/or exerted at the periphery through local release of PG in the stomach. Exogenous IL-1 given into either the circulation or the cerebrospinal fluid also inhibits gastric injury induced by a variety of experimental models (stress, aspirin, ethanol). Such a protective effect is mediated through the inhibition of acid secretion and prostaglandin release, although other mechanisms may also contribute. Whether endogenously released IL-1 beta exerts a protective role in the gastric mucosa is still to be investigated.

Potent inhibition of gastric acid secretion by intravenous interleukin-1 beta and -1 alpha in rats.

The influence of human and rat recombinant interleukin-1 (hIL-1 beta and -1 alpha and rIL-1 beta) on acid secretion was investigated in conscious pylorus-ligated rats. Intravenous injection of either hIL-1 beta, hIL-1 alpha or rIL-1 beta dose dependently inhibited gastric acid output with an ED50 of 0.05 microgram, 0.5 microgram and 2.2 micrograms, respectively. The antisecretory action of IL-1 beta was associated with an increase in circulating levels of gastrin. hIL-1 beta-induced inhibition of acid secretion was dose dependently reversed by peripheral injection of the IL-1 receptor antagonist, IL-RA, with a dose ratio of 1:10(3) for complete reversal. The inhibitory effect of hIL-1 beta was blocked by indomethacin and was not modified by IV injections of the CRF receptor antagonist, alpha-helical CRF(9-41), or the monoclonal somatostatin antibody CURE.S6, or by systemic capsaicin pretreatment. These results show that systemic hIL-1 beta-induced inhibition of gastric acid secretion is mediated through IL-1 receptors and prostaglandin pathways, and does not involves CRF receptors, afferent fibers, or changes in circulating gastrin or somatostatin levels.

Role of central prostaglandin E2 in the regulation of gastric acid secretion in the rat.

The central action of prostaglandin E2 (PGE2) on gastric acid secretion was investigated in rats by comparing the effects of intracisternal (i.ci.) and i.v. administration of PGE2 and the influence of i.ci. injection of indomethacin on acid secretion and PGE2 generation in the brain and stomach. I.ci. injections of PGE2 (1-10 micrograms) or the stable analog, 16,16-dimethyl PGE2, (0.01-0.1 micrograms) induced a dose dependent inhibition of baclofen-stimulated gastric acid secretion by 0-82% and by 7-87% respectively. I.v. infusion of PGE2 also induced a dose related inhibition of baclofen-stimulated acid secretion, but 10 fold higher doses were required. I.ci. or i.v. injection of indomethacin in doses ranging from 50 to 500 micrograms/rat, produced a similar dose dependent inhibition of the PGE2 generation in both the gastric mucosa and brain cortex measured 1 h post injection. I.ci. injection of indomethacin (500 micrograms) increased within 10 min acid secretion with a peak response at 20-30 min; 60-120 min post injection, when prostaglandin synthesis was inhibited by 90%, basal and baclofen-stimulated acid output were not altered. These results further establish that PGE2 acts in the brain to inhibit vagally stimulated gastric acid secretion in rats, and do not support a tonic inhibitory influence of endogenous brain PGE2 in the regulation of gastric acid secretion. In addition, these data showed that indomethacin injected i.ci. at 500 micrograms does not induce a selective inhibition of prostaglandin synthesis in the brain.

Central interleukin-1 beta-induced inhibition of acid secretion in rats: specificity of action.

It is well established that IL-1 beta acts in the brain to potently inhibit gastric acid secretion in pylorus-ligated rats. The present study was designed to further investigate the specificity and mechanisms of the centrally mediated antisecretory action of IL-1 beta in conscious rats. Intracerebroventricular injection of IL-1 beta (100 ng) decreased acid secretion in pylorus-ligated rats and inhibited basal and pentagastrin-stimulated acid secretion in rats with chronic gastric fistula. The antisecretory effect of IL-1 beta (100 ng) injected into the lateral ventricle of pylorus ligated rats was completely reversed by prior intracerebroventricular injection of the IL-1 receptor antagonist, IL-1ra, (100 micrograms). Peripheral administration of the somatostatin monoclonal antibody, CURE.S6, did not modify intracisternal IL-1 beta-induced inhibition of acid secretion in pylorus ligated rats. IL-6 and tumor necrosis factor-alpha (100 ng) injected intracisternally did not influence gastric acid secretion in pylorus-ligated rats. These data show that IL-1 beta action in the CNS is mediated through interaction with specific IL-1 receptors and is selective to this cytokine. IL-1 beta antisecretory action can be observed under basal and pentagastrin-stimulated conditions and is independent from somatostatin release in the periphery.

Helicobacter pylori eradication prevents recurrence from peptic ulcer haemorrhage.

BACKGROUND: Successful eradication of Helicobacter pylori infection clearly modifies the natural history of peptic ulcer disease and prevents further recurrences of duodenal and gastric ulcers. However, there are few prospective studies about actual rates of rebleeding after H. pylori eradication, a highly relevant aspect of management as re-infection, relapse of ulcer disease for other reasons (i.e. anti-inflammatory agents) or idiopathic ulcers unrelated to H. pylori may develop and cause further bleeding episodes. OBJECTIVE: To determine the incidence of bleeding episodes after eradication of H. pylori infection in patients who had bled from an H. pylori-positive peptic ulcer. PARTICIPANTS AND INTERVENTIONS: H. pylori-positive patients who bled from a gastric or duodenal ulcer were treated with appropriate triple and/or quadruple therapy. H. pylori eradication was confirmed by urea breath test 4 weeks after treatment. Patients received no further treatment but were followed clinically and additional urea breath tests were performed every 6 months. Endoscopy with antral and corpus biopsies and urea breath test were repeated as soon as patients manifested any dyspeptic symptoms that might signal recurrence. RESULTS: A total of 103 patients with bleeding duodenal ulcer were included in the study; H. pylori was successfully eradicated in 93 of these patients, who were followed for a median interval of 27 months. The yearly re-infection rate was calculated to be 0.6%. There were no instances of rebleeding in any patients during the follow-up period. CONCLUSIONS: Even after prolonged follow-up, successful H. pylori eradication prevents rebleeding.

[Massive hemorrhage due to nodular hyperplasia of Brunner's glands in antiphospholipid syndrome]. / Hemorragia masiva por hiperplasia nodular de glándulas de Brunner en el síndrome antifosfolipídico.

Gastrointestinal hemorrhage is an exceptional complication of antiphospholipid syndrome and most reported cases are secondary to ischemic lesions. Brunner's gland hyperplasia is an infrequent and usually asymptomatic condition that has been associated with chronic renal failure. We report a patient with primary antiphospholipid syndrome who, after mechanic heart valve replacement and while in a state of drug-induced anticoagulation, experienced a life-threatening upper gastrointestinal hemorrhage due to nodular hyperplasia of Brunner's glands. This entity may be considered in the differential diagnosis of upper gastrointestinal bleeding in patients with antiphospholipid syndrome, most of whom are treated with oral anticoagulatory drugs, and particularly in patients with chronic renal failure.

[Gastric ulcers as the only manifestation of infection by cytomegalovirus in immunocompetent patients]. / Ulceras gástricas como única manifestación de infección por citomegalovirus en pacientes inmunocompetentes.

Gastritis is an infrequent manifestation of infection by cytomegalovirus (CMV) in a healthy host. This complication is usually associated to a mononucleosic syndrome during the course of a disseminated infection. Macroscopically, it presents with edema and mucosal congestion, multiple erosions or ulcers. Histologic examination of the endoscopic biopsies allows the etiologic diagnosis to be established in most cases. In immunocompetent patients the clinical course of gastritis by CMV is usually self-limited. We herein present two immunocompetent patients with gastric ulcerous disease as the only manifestation of CMV infection. Both patients required antiviral treatment due to refractoryness to the antisecretor treatment and one case evolved to pyloric stenosis requiring surgery.

[Estrogen and progestagen treatment in digestive hemorrhage caused by vascular malformations]. / Tratamiento con estrógenos y progestágenos en la hemorragia digestiva por malformaciones vasculares.

The efficacy of an association of estrogens and progestagens in the treatment of gastrointestinal bleeding by angiodysplasia was analyzed. Thirty-three patients with gastrointestinal bleeding due to vascular malformations were admitted from January 1986 to December 1993. Fifteen of the 33 patients were submitted to surgical or endoscopic treatment. The remaining 18 patients underwent daily oral treatment with a combination of estrogens-progestagens containing 2.5 mg of lynestrenol and 0.075 mg of mestranol. One patient presented a venous thrombosis leading to suppression of treatment at one month of initiation. The 17 remaining patients were treated for a mean of 22 +/- 4 months (range: 3-60). During treatment 13 of the 17 patients (76%) did not present evidence of hemorrhage. Likewise, the number of hemorrhagic episodes per year decreased from 4.4 +/- 1.2 prior to treatment to 0.7 +/- 0.5 during treatment (p < 0.05) with transfusional requirements decreasing from 7.9 +/- 2.8 erythrocyte concentrates per year prior to treatment to 1.2 +/- 1.0 during treatment (p < 0.05). In conclusion, the combined treatment with estrogens and progestagens prevents recurrence of gastrointestinal bleeding by angiodysplasia.

[The attitude of primary health care physicians in the metropolitan area of Barcelona about the diagnosis and treatment of Helicobacter pylori infection in gastroduodenal diseases]. / Actitud de los médicos de atención primaria del área metropolitana de Barcelona frente al diagnóstico y tratamiento de la infección por Helicobacter pylori en enfermedades gastroduodenales.

AIM: To evaluate the attitude of primary health care physicians versus the diagnosis and treatment of infection by Helicobacter pylori in patients with dyspepsia and gastroduodenal ulcer. DESIGN: An observational, transversal study was performed by a self administered questionnaire from June to October, 1997. PARTICIPANTS: Primary health care physicians from 38 reformed Medical Centers in the metropolitan area of Barcelona were included in the study. RESULTS: Of the 359 doctors to whom the questionnaire was sent, 283 responded (78.8%). In a patient with dyspepsia 95.4% would first request endoscopy. If they knew of the presence of infection by Helicobacter pylori 96.1% would administer eradication treatment in patients with gastric and duodenal ulcer and 15% would also do so if the endoscopy were normal. If the presence of infection by Helicobacter pylori were unknown in a patient with gastroduodenal ulcer, 65.3% would treat with anti-H2 or proton pump inhibitors associated with a diagnostic test of infection by Helicobacter pylori. If the physician decided to carry out eradication treatment of Helicobacter pylori infection, 98.6% would use one of the regimes recommended by different scientific societies. If confirmation of eradication of Helicobacter pylori infection were requested, 89% would do so one and three months after completion of treatment. In patients with gastric ulcer, 69.3% would request endoscopy on completion of treatment. The percentage of physicians specialized in Family and Community Medicine who would carry out eradication treatment in patients with duodenal ulcer and Helicobacter pylori infection and who would request endoscopies in patients with dyspepsia was found to be statistically significant in comparison with physicians without this specialty. CONCLUSIONS: The attitude of primary care physicians in the metropolitan area of Barcelona with regard to the diagnosis and treatment of infection by Helicobacter pylori in gastroduodenal diseases largely reflects the recommendations recently made by several scientific societies. In general there are no significant differences with respect to this attitude in regard to the age and sex of the physician, although their training was found to influence in some of the responses analyzed.

Interleukin-1 receptor antagonist does not prevent endotoxin-induced inhibition of gastric acid secretion in rats.

The underlying mechanisms involved in endotoxin-induced inhibition of gastric acid secretion were investigated in conscious rats with pylorus ligation for 2 hr. Intraperitoneal injection of endotoxin (0.1, 1, and 5 micrograms/rat) inhibited gastric acid output by 31%, 80%, and 84% respectively. Intraperitoneal endotoxin (1 microgram/rat) -induced inhibition of gastric acid secretion was not altered by pretreatment with the interleukin-1 receptor antagonist, IL-1RA, indomethacin, naloxone, or capsaicin. Treatments were injected peripherally at doses previously shown to antagonize the antisecretory effect of exogenous interleukin-1 beta, to inhibit prostaglandin synthesis in the stomach and brain, to block opiate receptors, and to alter functioning of unmyelinated afferent nerve fibers. These results indicate that the antisecretory effect of endotoxin can be expressed by factors other than interleukin-1, prostaglandins, or opioid peptides that do not require the integrity of capsaicin-sensitive afferent pathways.

Interleukin-1 beta acts at hypothalamic sites to inhibit gastric acid secretion in rats.

It has been established that interleukin-1 beta (IL-1 beta) injected into the cerebrospinal fluid inhibits gastric acid secretion in rats. Brain sites of action of IL-1 beta were investigated in conscious rats implanted unilaterally with chronic hypothalamic cannula. Gastric acid secretion was monitored 2 h after pylorus ligation. Human recombinant IL-1 beta (10 ng) microinjected into the medial preoptic area, anterior hypothalamus, and paraventricular nucleus inhibited gastric acid secretion by 76-83%. IL-1 beta microinjected into the ventromedial hypothalamus and other hypothalamic sites outside of responsive sites had no effect. IL-1 beta inhibitory action in the medial preoptic area was dose related (0.1-10 ng), prevented by indomethacin (5 mg/kg ip), and mimicked by prostaglandin E2. These results show that IL-1 beta acts in the medial preoptic area/anterior hypothalamus and paraventricular nucleus to inhibit acid secretion in pylorus-ligated rats and that IL-1 beta action is likely to involve prostaglandin E2.

Colitis induces CRF expression in hypothalamic magnocellular neurons and blunts CRF gene response to stress in rats.

We investigated hypothalamic neuronal corticotropin-releasing factor (CRF) gene expression changes in response to visceral inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNB) and acute stress. Seven days after TNB, rats were subjected to water-avoidance stress (WAS) or restraint for 30 min and euthanized. Hypothalamic CRF primary transcripts (heteronuclear RNA, hnRNA) and CRF and arginine vasopressin (AVP) mRNAs were assessed by in situ hybridization. Antisense (35)S-labeled cRNA probes against CRF mRNA intronic and exonic sequences and an oligonucleotide probe against the AVP mRNA were used. TNB induced macroscopic lesions and a fivefold elevation in myeloperoxidase activity in the colon. Colitis increased CRF hnRNA and mRNA signals in the magnocellular part of the paraventricular nucleus of the hypothalamus (PVN) and supraoptic neurons, whereas AVP mRNA was not altered. Colitis did not modify CRF hnRNA signal in the parvocellular part of the PVN (pPVN), plasma corticosterone, and serum osmolarity levels. However, CRF hnRNA expression in the pPVN and the rise in corticosterone and defecation induced by WAS or restraint were blunted in colitic rats. These data show that colitis upregulates CRF gene synthesis in magnocellular hypothalamic neurons but dampens CRF gene transcription in the pPVN and plasma corticosterone responses to environmental acute stressors.