Postoperative death in sows as a result of gastric mucosal de-gloving at the pars oesophagea

It is well documented that pigs frequently die from postoperative acute gastric dilatation, and proximal gastric 'stress' ulceration. Three cases of gastric mucosal 'de-gloving' are reported. This was secondary to acute gastric dilatation and resulted in death from acute haemorrhage. All animals had undergone major abdominal surgery. Histology confirmed that the proximal gastric mucosa had been 'de-gloved', or torn from the gastro-oesophageal junction, leaving exposed muscle fibres. This syndrome has not been reported previously. The postmortem appearances of this mechanical injury could easily be mistaken for extensive oesophago-gastric peptic ulceration. This has major implications for prevention.     

Comparative studies on starvation - and indomethacin - induced ulcerations in albino rats.

Experimental models of chronic and acute peptic ulcerations were produced in the albino rats by means of prolonged starvation and indomethacin administration. In the case of acute indomethacin-induced peptic ulceration, the effects of anticholinergic drugs on the ulcers produced were also studied. Starving the rats for a period of seven days produced gastric ulceration in all the rats used while indomethacin produced gastric ulceration within five hours in all the rats used. Severe ulceration of the degree found in human peptic ulcer disease was produced only by chronic starvation. Anticholinergic drugs ameliorated indomethacin-induced gastric ulceration, partly at least, by reducing intra-gastric acidity.     

Effect of prostaglandin 15 (R) 15 methyl-E2-methyl ester on the gastric mucosa in patients with peptic ulceration — An endoscopic and histological study

Endoscopic and Histological study of the locally administered prostaglandin 15 (R) 15 methyl-E₂-methyl ester on the gastric mucosa in patients with peptic ulceration was carried out. The results show that the Prostaglandin analogue in a single oral dose of 150 μg possesses a powerful stimulant effect on the mucus-secreting cells of the gastric mucosa. The implications of these finding in the healing of gastric ulceration is discussed.     

Helicobacter pylori: therapeutic targets.

Helicobacter pylori is now considered a major pathogen of the upper gastrointestinal tract. It is seen as an important cause of peptic ulceration not associated with NSAID use. It is also increasingly linked to other diseases of the GI tract, although the relationship between the organism and conditions such as gastric cancer, non-ulcer dyspepsia and gastroesophageal reflux disease is not as clear as is the case in peptic ulcer disease. This is probably because of a lack of well-performed, statistically powerful, prospective therapeutic trials that indicate that H. pylori eradication is of benefit in these diseases. The high infection rate without overt disease seen in many populations, especially from developing countries, probably contributes to this "credibility gap." While we have excellent therapeutic regimens available at this time, rational targeting requires that the objective evidence in favor of therapeutic intervention in upper GI disease, as well as the local H. pylori epidemiology, needs to be considered.     

Helicobacter pylori--a timeless source of lessons and research initiatives

The beginning of the H. pylori era was characterized by objections and even refusal to accept the new H. pylori-related theories. The shift from peptic ulcer disease as an acid-driven disease to a disease with an infectious etiology had to overcome major obstacles and the dogma of the stomach as a sterile organ. Strong effort and commitment of several medical disciplines with a large collection of scientific data gave decisive support to it. However what had started as a revolutionary and completely opposing concept to the one pre-existing evolved to a novel but integrative concept. The new theories were able to reconcile the new critical factor H. pylori with pre-existing knowledge carefully build up during several decades of intensive studies reserved to mechanisms regulating gastric physiology. On its way to full recognition and praise the difficult story of H. pylori has allowed the collection of many lessons which have allowed the medical and scientific profession to progress, and these lessons are also valuable for life beyond scientific boundaries.     

Prostaglandin E in peptic ulcer disease

Prostaglandin E₁ and E₂ inhibit gastric secretion in vivo and in vitro under a variety of conditions. It is not known whether these compounds may play a role in normal gastric secretory physiology or in the pathophysiology of peptic ulcer disease. Six normal adults and six patients with documented duodenal ulcer disease were studied under basal conditions and during gastric secretory stimulation with betazole. Prostaglandin E in plasma and gastric juice was measured by radioimmunoassay. Prostaglandin E was significantly higher in the plasma of normal volunteers both in the basal state and during stimulation. Gastric juice prostaglandin E was also significantly higher in normal volunteers during the basal state but the difference disappeared during stimulation. The relative deficiency of prostaglandin E in the ulcer group may indicate a role for prostaglandins in the pathophysiology of gastric hypersecretion.     

Cellular localization of intrinsic factor in pancreas and stomach of the dog

Summary A cobalamin (vitamin B₁₂)-binding protein has recently been identified in canine pancreatic juice which is biochemically, immunochemically and functionally similar to canine gastric intrinsic factor. However, the cellular sources of both this pancreatic intrinsic factor and gastric intrinsic factor in the dog are not known. Antisera raised against canine gastric intrinsic factor have been used to examine the distribution of intrinsic factors in the canine pancreas and stomach. Immunoreactivity was demonstrated in duct cells but not acinar or endocrine cells in the pancreas, and in fundic peptic and pyloric gastric pit cells in stomach. All immunostaining was abolished by preabsorption of the antisera with purified canine gastric and pancreatic intrinsic factors. A cellular source of pancreatic intrinsic factor has not been previously described, and the demonstration of intrinsic factor-like immunoreactivity in two cell types in the canine stomach contrasts with its localization in a single cell type in the gastric mucosa of other mammalian species. Furthermore, immunoreactivity in pancreatic duct cells was detected at much higher dilutions of antisera than those required for staining of peptic and gastric pit cells. This suggests a higher concentration of antigen, and supports previous evidence that the pancreas is a major source of intrinsic factor in the dog.     

Necropsy survey of gastric ulcers in a population of aged donkeys: prevalence, lesion description and risk factors

There is no information about the prevalence of gastric ulceration in donkeys or potential risk factors for its presence in donkeys. The donkey is a stoic, hardy animal that has not previously been thought to suffer from this disease. However, gastric ulceration was found to be a problem in a population of non-working UK donkeys resident at the Donkey Sanctuary and its prevalence was estimated by examining necropsy data over a 2-year period during 2005 to 2006. Associations with clinical and management factors were determined. In total, 426 donkeys were examined at necropsy to determine the presence of gastric ulceration. Lesions were described and scored according to a four-point scale. Management and clinical data from these donkeys were analysed to identify potential risk factors for the presence of gastric ulceration. Terminal blood samples were also studied to determine whether animals were exhibiting hyperlipaemia prior to death. Results showed that 41% (n = 174) of the donkeys studied had evidence of gastric ulceration at necropsy. Most (49%) of the ulcers were of a medium size (area of 2 cm2 - <10 cm2) and the most common site for ulcers was the margo plicatus. Of the donkeys examined, 18% had hyperlipaemia prior to or death or euthanasia and this was a risk factor for donkeys developing gastric ulceration; 62% of hyperlipaemia cases also displayed gastric ulceration (P < 0.001). Kidney disease was a potential risk factor (P = 0.02), with 74% of these animals having gastric ulceration. Donkeys that died or were euthanased due to respiratory disease were at a decreased risk of developing ulceration (P = 0.01) Donkeys fed a carbohydrate-based diet were more likely (P < 0.001) to have gastric ulceration than those fed a fibre-only diet, with 55% having gastric ulceration compared with 33% in the fibre-only group. This study has shown that gastric ulceration is commonly observed in donkeys at necropsy and may be extensive.     

Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine.

OBJECTIVE: To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients. DESIGN: Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks. SETTING: Multicentre outpatient study at secondary referral centres in five European countries. PATIENTS--297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal anti-inflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial. INTERVENTIONS: Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal anti-inflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator''s discretion. END POINT: Frequency of gastric and duodenal ulceration or lesions, or both. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of peptic ulceration by eight weeks was 10.3% (27/263); 2 out of 135 (1.5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency of gastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection. CONCLUSIONS: Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.     

Helicobacter pylori and peptic ulcer disease.

Medical therapy for duodenal or gastric ulcer disease has traditionally involved gastric acid antisecretory therapy for 4 to 8 weeks to promote initial healing and indefinitely to prevent recurrences of ulcer. The discovery of Helicobacter pylori in most patients with peptic ulcer disease has led to a change in this approach. Therapy designed to eradicate H pylori may facilitate ulcer healing with acid antisecretory agents and, more important, may greatly reduce the incidence of ulcer recurrence, obviating the need for maintenance antisecretory therapy. Regimens designed to eradicate H pylori are difficult to comply with, however, and are associated with adverse effects in some patients. In this article we review the diagnosis and treatment of H pylori infection in patients with peptic ulcer disease and make recommendations regarding the use of conventional ulcer therapies and therapies designed to eradicate H pylori.     

Comparison of the results of the treatment with pirenzepine combined with cimetidine and sucralfate of stomach ulcer resistant to cimetidine

Increased inhibition of gastric acid release through simultaneous blockade of H2-receptors and muscarine-receptors or administration of gastroprotective agent is theoretically justified in patients with peptic ulcer unresponsive to cimetidine. The study involved 70 patients with peptic ulcer previously treated with cimetidine in daily dose 1000 mg for 6 weeks without an effect. Patients were divided into two groups: group 1 treated with cimetidine plus pirenzepine, and group 2 given sucralfate in daily dose 4.0 g. Pirenzepine to patients of group 1 was given in a single dose of 50 mg before bedtime. Both groups were comparable in age, sex, disease onset, smoking, gastric acid secretion, and ulcer size. Healing was evaluated with endoscopic technique following 2 and weeks of therapy. Ulceration healed up within 2 weeks in 40% of patients treated with cimetidine combined with pirenzepine and in 31.4% patients treated with sucralfate. After 4 weeks, healing of ulceration was 71.4% and 68.6%, respectively. Large ulcers (over 1 cm in diameter) and previous partial gastrectomy did not affect healing rate. The obtained results suggest that administered therapies enable recovery in over 2/3 of patients with peptic ulcer unresponsive to a 6-week therapy with cimetidine alone.     

Potential animal models of Helicobacter pylori infection in immunological and vaccine research

Abstract Presence of Helicobacter pylori in the human gastric mucosa is associated with chronic gastritis and promotes the formation of peptic ulceration. Furthermore, long-term gastritis caused by the bacteria represents an increased risk of developing gastric cancer. Much controversy remains about the pathogenic mechanisms by which H. pylori can induce disease because of the limitations of animal models and the relevance of in vitro observations to the in vivo disease process. Studies of putative pathogenic factors such as induction of inflammatory mediators and immune evasion are required to understand how to design a vaccine against the infection. Vaccine adjuvants, delivery systems and therapeutic vaccination are likely to be the areas of major progress in the future. Data related to immunological aspects and vaccine development in potential animal models are reviewed.     

Helicobacter pylori infection and disease: from humans to animal models

Informative and tractable animal models that are colonized by well-defined microbial pathogens represent ideal systems for the study of complex human diseases. Helicobacter pylori colonization of the stomach is a strong risk factor for peptic ulceration and distal gastric cancer. However, gastritis has no adverse consequences for most hosts and emerging evidence suggests that H. pylori prevalence is inversely related to gastroesophageal reflux disease and allergic disorders. These observations indicate that eradication may not be appropriate for certain populations due to the potentially beneficial effects conferred by persistent gastric inflammation. Animal models have provided an invaluable resource with which to study H. pylori pathogenesis and carcinogenesis, and have permitted the development of a focused approach to selectively target human populations at high-risk of disease.Helicobacter pylori is a bacterium that colonizes gastric epithelium and represents the most common bacterial infection worldwide (Peek and Blaser, 2002). H. pylori has colonized human stomachs for over 58,000 years (Linz et al., 2007), and virtually all persons infected by this organism develop co-existing gastritis, a signature feature of which is the capacity to persist for decades. Owing to its co-evolution with humans, H. pylori can send and receive signals from gastric epithelium, allowing host and bacteria to participate in a dynamic equilibrium. However, there are biological costs to these long-term relationships.Epidemiological studies in humans and experimental infections using a variety of animal models have clearly demonstrated that sustained interactions between H. pylori and its host significantly increase the risk for peptic ulcer disease, distal gastric adenocarcinoma, and non-Hodgkin’s lymphoma of the stomach (Peek and Blaser, 2002). Eradication of H. pylori significantly decreases the risk of developing peptic ulceration or gastric adenocarcinoma in infected individuals without pre-malignant lesions (Wong et al., 2004), providing evidence that this organism influences early stages in gastric carcinogenesis. However, only a fraction of colonized persons ever develop ulcers or neoplasia, and disease risk involves well-choreographed interactions between pathogen and host, which, in turn, are dependent upon strain-specific bacterial factors and/or host characteristics.     

Deaths from peptic ulceration.

Deaths due to peptic ulceration can be prevented only by curing the ulcer and preventing the ulcer diathesis permanently by either medical or surgical means. Recurrence of ulcers after drug treatment is a major problem, so continuous treatment is often necessary, but there is no evidence that this decreases mortality. Surgery is the only means of permanently removing the ulcer diathesis in most patients, and subsequent mortality is low. A reasonable balance has to be achieved between the two kinds of treatment to prevent most deaths from peptic ulcer.     

The Helicobacter pylori vacuolating cytotoxin: from cellular vacuolation to immunosuppressive activities

Helicobacter pylori is a highly successful bacterial pathogen of humans, infecting the stomach of more than half of the worlds population. The H. pylori infection results in chronic gastritis, eventually followed by peptic ulceration and, more rarely, gastric cancer. H. pylori has developed a unique set of virulence factors, actively supporting its survival in the special ecological niche of the human stomach. Vacuolating cytotoxin (VacA) and cytotoxin-associated antigen A (CagA) are two major bacterial virulence factors involved in host cell modulation. VacA, so far mainly regarded as a cytotoxin of the gastric epithelial cell layer, now turns out to be a potent immunomodulatory toxin, targeting the adapted immune system. Thus, in addition to the well-known vacuolating activity, VacA has been reported to induce apoptosis in epithelial cells, to affect B lymphocyte antigen presentation, to inhibit the activation and proliferation of T lymphocytes, and to modulate the T cell-mediated cytokine response.     

Helicobacter pylori survival in gastric mucosa by generation of a pH gradient.

Helicobacter pylori has been established as the major causative agent of human active gastritis and is an essential factor in peptic ulcer disease and gastric cancer. The mechanism that has been proposed for H. pylori to control its inhospitable microenvironment happens to coincide with the pH control technique developed by us. This technique was developed to separate an acidic environment from a basic environment for a sequential enzymatic reaction by the hydrolysis of urea within a thin layer of immobilized urease. In this paper, a mathematical model is presented to consider how H. pylori survives the gastric acidity. The computed results explain well the experimental data available involving H. pylori.     

The effect of orally administered prostaglandins A1, A2 and 15 Epi-A2 on human gastric acid secretion

Prostaglandins A₁, A₂ and 15 Epi-A₂ were administered orally to human male volunteers. Prostaglandin A₁ and 15 Epi-A₂ did not consistently affect gastric acid secretion either in terms of the pH values within individual tests or in respect of comparative control test data. Prostaglandin A₂ administration resulted in a transient inhibition of secretion in all 6 subjects tested, with the pH rising above 6 in every case.It is concluded that none of these compounds is likely to have therapeutic application to the peptic ulceration problem.     

Twenty five years since the first prospective study by Forman et al. (1991) on Helicobacter pylori and stomach cancer risk

Stomach cancer is one of the leading causes of cancer death worldwide, despite its incidence and mortality falling in many places. The discovery in 1984 that a bacterial infection with Helicobacter pylori could cause stomach and duodenal ulcers prompted work in its role in causing gastritis, and led to the first prospective study in 1991 by Forman et al., showing that infection with H.pylori increased the risk of stomach cancer in those infected by almost three-fold. Prior to then, it was hypothesized that stomach was caused by poor diets. While diets may still play a role, the falls in stomach cancer incidence have been associated with reductions in population prevalence of H. pylori. Discovery of the link was accelerated by the use of stored sera from other unrelated studies, and the use of serological assays.Since those discoveries the treatment landscape of gastric disorders has changed significantly, with a rapid uptake of antibiotic and proton pump inhibitors (triple) therapies in those who are H. pylori positive. Over time we have seen falls in gastric cancer, peptic and duodenal ulcers and in many of the procedures previously used to cure peptic ulcer disease, such as vagotomies and gastrectomies.Further still, an oral vaccine against H. pylori, first trialled in China, holds much promise of being the third vaccine against a cancer causing infection. If successful this would lead to a further reduction in H. pylori related conditions, and ultimately gastric cancer, an otherwise lethal disease.