Biomedical subjects

A Hamlet

Publications and source records attributed to A Hamlet.

18 recordsLinked to original sources

PubMed2000

[When is H pylori a cause of duoenal ulcer? Hypersecretion of gastric acid, active duodenitis and reduced bicarbonate secretion are links in the chain].

Helicobacter pylori infection engaging mainly the gastric antrum causes hypersecretion of gastric acid. The increased duodenal acid load gives rise to islands of gastric mucosa in the proximal duodenum. As these bacteria thrive only on gastric mucosa it presents an opportunity for Helicobacter pylori to colonize the duodenum. A much higher density of virulent Helicobacter pylori has been found in the duodenum of duodenal ulcer patients in comparison to infected subjects without duodenal ulcer. The high density of virulent Helicobacter pylori in the proximal duodenum results in a strong inflammatory reaction with active duodenitis and impaired bicarbonate secretion. These characteristics of duodenal ulcer patients, together with the acid hypersecretion, seem to be the key factors in evoking a duodenal ulcer.

Bicarbonates↗

PubMed2000

Conceivable mechanisms by which Helicobacter pylori provokes duodenal ulcer disease.

A conceivable concept for the development of duodenal ulcers in Helicobacter pylori (H. pylori) infected subjects is presented in this chapter. The concept includes an explanation of the fact that only a minority of all H. pylori-infected subjects will develop a duodenal ulcer. Helicobacter pylori infection of the antrum induces a hypersecretion of gastric acid secretion, giving rise to gastric metaplasia in the duodenal bulb. This gastric metaplasia is a prerequisite for H. pylori colonization of the bulb. These events are common to all H. pylori-infected subjects. However, a much higher density of H. pylori bacteria and colonization with virulent organisms has been found in the bulb of duodenal ulcer patients, resulting in a much stronger inflammatory reaction with active duodenitis and an impaired bicarbonate secretion. These characteristics, together with acid hypersecretion, seem to be the important factors in evoking a duodenal ulcer.

Antigens, Bacterial↗

PubMed2000

Differences in surface-exposed antigen expression between Helicobacter pylori strains isolated from duodenal ulcer patients and from asymptomatic subjects.

We have analyzed possible qualitative and quantitative differences in antigen expression between Helicobacter pylori strains isolated from the antrum and different locations in the duodenum of 21 duodenal ulcer (DU) patients and 20 asymptomatic subjects (AS) by enzyme-linked immunosorbent assay (ELISA) and inhibition ELISA. Almost all antral and duodenal strains grown in vitro expressed the N-acetyl-neuroaminyllactose-binding hemagglutinin, flagellins (subunits FlaA and FlaB), urease, a 26-kDa protein, and a neutrophil-activating protein. In 75% of both the DU patients and the AS, antral H. pylori strains expressed either the blood group antigen Lewis y (Le(y)) alone or together with the Le(x) antigen. However, duodenal H. pylori strains of DU patients expressed Le(y) antigen more frequently than corresponding strains of AS (P < 0.05). Presence of Le(y) on H. pylori was related to the degree of active duodenitis (P < 0.05). Duodenal H. pylori strains isolated from AS were significantly more often Lewis nontypeable than duodenal strains of DU patients (P < 0.01). Presence of H. pylori blood group antigen-binding adhesin (BabA) was significantly higher on both antral and duodenal strains isolated from DU patients than on corresponding strains isolated from AS (P < 0.05). BabA-positive duodenal H. pylori strains isolated from DU patients were associated with active duodenitis more frequently than corresponding strains isolated from AS (P < 0.01). Infection with H. pylori strains positive for Le(y) and BabA in the duodenum is associated with development of duodenal ulcer formation.

ABO Blood-Group System↗

PubMed1999

Duodenal Helicobacter pylori infection differs in cagA genotype between asymptomatic subjects and patients with duodenal ulcers.

BACKGROUND & AIMS: It is unclear why only a minority of subjects infected by Helicobacter pylori develop duodenal ulcers (DU). The aim of this study was to investigate whether the number and type of H. pylori strains in the duodenum of patients with DU may play a critical role. METHODS: Twenty-one patients with DU and 20 asymptomatic subjects with antral H. pylori infection were studied. Paired biopsy specimens were taken from the antrum and from each quadrant of the duodenal bulb. Analyses included extent of duodenal gastric metaplasia, severity of duodenitis, bacterial density, presence of the cagA gene, and vacuolating cytotoxin activity. RESULTS: H. pylori was cultured from duodenal biopsy specimens in 95% of patients with DU and 80% of asymptomatic subjects. Both groups had a similar bacterial density and proportion of cagA-positive strains in the antrum (86% vs. 75%), but patients with DU had a 20-fold higher density of H. pylori and a higher proportion of cagA-positive strains in the duodenal bulb (81% vs. 30%). Active duodenitis was present only in patients with DU infected by cagA positive strains in the duodenum. CONCLUSIONS: The results suggest that a high density of cagA-positive strains in the duodenum with severe duodenitis are important determinants of DU disease.

Adult↗

PubMed1999

A novel tablet-based 13C urea breath test for Helicobacter pylori with enhanced performance during acid suppression therapy.

BACKGROUND: The urea breath test (UBT) can still be improved in terms of user-friendliness and accuracy during acid-suppression therapy. This study was designed to evaluate a novel, rapidly disintegrating 13C UBT tablet, which was supplemented with citric acid to facilitate diagnosis of Helicobacter pylori in the hypochlorhydric stomach. METHODS: The efficacy of a fasting 13C tablet-based UBT (TUBT) was compared with that of a standard 13C UBT (SUBT) during 40 min after dosing, and optimal sampling points were determined. The single-point TUBT was validated against a 'gold standard' (GS) including a TUBT, culture, histology, and a CLO test in 134 dyspeptic patients, and its optimal cut-off point was determined by means of a biometric method. In addition, 20 SUBT-positive patients were randomized to perform either the TUBT or the SUBT after 7 days of omeprazole therapy (20 mg twice daily). RESULTS: Compared with a SUBT, the TUBT gave a quicker and wider separation between positive and negative results and an earlier optimal sampling point (10 versus 40 min). At 10 min the TUBT correctly classified 40 of 42 GS-positive subjects (sensitivity, 95%) and all of 92 GS-negative patients (specificity, 100%), and the optimal cut-off point was 1.8 delta per mil. Furthermore, when optimal sampling points were used, the TUBT (t = 10 min) proved to be more accurate than the SUBT (t = 40 min) during omeprazole treatment, correctly identifying all of 10 and 3 of 9 H. pylori-infected patients, respectively. CONCLUSIONS: By supplying 13C urea and citric acid as a rapid-release tablet, it is possible to shorten the duration of the 13C UBT to 10 min, omit the test meal, and still maintain excellent accuracy, even during acid suppression therapy.

Anti-Ulcer Agents↗

PubMed1999

Role of local cytokines in increased gastric expression of the secretory component in Helicobacter pylori infection.

Using immunohistochemical staining, we examined the presence of secretory component (SC) on epithelial cells in gastric and duodenal biopsy specimens collected from Helicobacter pylori-infected individuals and healthy controls. Gastric epithelial cells from healthy volunteers expressed low, but detectable, levels of SC. In contrast, significantly higher level of expression of SC (P < 0.001) was observed on epithelial cells in the antra of H. pylori-infected individuals. The antral SC expression correlated with staining for gamma interferon of intraepithelial and lamina propria lymphocytes (r(s) = 0.76 and 0.69, respectively, P < 0.001) and correlated weakly with production of tumor necrosis factor alpha (r(s) = 0.43, P < 0.05), but it did not correlate at all with interleukin-4 production.

Adult↗

PubMed1998

Aspirin-induced gastritis, like Helicobacter pylori-induced gastritis disinhibits acid secretion in humans: relation to cytokine expression.

BACKGROUND: Helicobacter pylori infection contributes to hypergastrinemia and hypersecretion of acid by blocking inhibitory reflex pathways to gastrin and parietal cells normally activated by antral distention. Our aim was to investigate whether a similar blockade of inhibitory responses could be provoked by inducing gastritis with aspirin, thus implicating a common inflammatory component, possibly a proinflammatory cytokine(s). METHODS: We studied the effects of antral distention on stimulated acid secretion and gastrin release in H. pylori-negative volunteers, before and after 3 days of aspirin therapy (2 g daily). Immediately before the examinations, the severity of gastric mucosal injury was evaluated macroscopically and histologically, and the production of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma was determined by immunohistochemistry. RESULTS: Most subjects had severe gastric injury after aspirin therapy, resulting in a substantially increased production of IL-1beta, IL-6, and IL-8 but not of TNF-alpha and IFN-gamma in the antral mucosa. In these subjects the acid-inhibitory response was abolished or markedly reduced. Conversely, aspirin therapy failed to affect the gastrin release in all subjects studied. CONCLUSIONS: The disinhibition of acid secretion in response to antral distention is a joint feature of the gastritis induced by aspirin and H. pylori infection, possibly related to the increased production of IL-1beta, IL-6, and IL-8. The H. pylori-related hypergastrinemia apparently has a different background.

Adult↗

PubMed1998

Specific antibodies in sera and gastric aspirates of symptomatic and asymptomatic Helicobacter pylori-infected subjects.

In this study we have determined systemic and local antibody responses against different Helicobacter pylori antigens in H. pylori-infected and noninfected subjects. In addition, we studied whether differences in antibody responses between patients with duodenal ulcers and asymptomatic H. pylori carriers might explain the different outcomes of infection. Sera and in most instances gastric aspirates were collected from 19 duodenal ulcer patients, 15 asymptomatic H. pylori carriers, and 20 noninfected subjects and assayed for specific antibodies against different H. pylori antigens, i.e., whole membrane proteins (MP), lipopolysaccharides, flagellin, urease, the neuraminyllactose binding hemagglutinin HpaA, and a 26-kDa protein, by enzyme-linked immunosorbent assay. The H. pylori-infected subjects had significantly higher antibody titers against MP, flagellin, and urease in both sera and gastric aspirates compared with the noninfected subjects. Furthermore, the antibody titers against HpaA were significantly elevated in sera but not in gastric aspirates from the infected subjects. However, no differences in antibody titers against any of the tested antigens could be detected between the duodenal ulcer patients and the asymptomatic H. pylori carriers, either in sera or in gastric aspirates.

Adult↗

PubMed1998

Local cytokine response in Helicobacter pylori-infected subjects.

The host immune response to Helicobacter pylori infection might be of importance with regard to the outcome of infection by this organism, e.g., to explain why only a proportion of infected subjects develop peptic ulcers. In this study we have analyzed the local response of different cytokines-i.e., the proinflammatory interleukin-1beta, (IL-1beta), IL-6, tumor necrosis factor alpha, and IL-8; the immunoregulatory gamma interferon (IFN-gamma); and IL-4; and the anti-inflammatory transforming growth factor beta (TGF-beta)-in antral biopsy specimens from H. pylori-infected duodenal ulcer (DU) patients and asymptomatic (AS) carriers (i.e., with chronic gastritis only). For comparison, biopsy specimens from uninfected healthy individuals were also analyzed. An immunohistochemical technique was used to allow quantification of the cytokine responses as well as identification of the cell types associated with the cytokine expression. We found that the levels of all of the studied cytokines except IL-4 were increased in the H. pylori-infected subjects compared to the levels in the healthy individuals. Our results indicate that the antral cytokine response is of the Th1 type since IFN-gamma, but not IL-4, was up-regulated both in H. pylori-infected DU patients and in AS carriers. However, there were no significant differences in either proinflammatory or immunoregulatory cytokine levels when H. pylori-infected subjects with and without peptic ulcers were compared. Some of the cytokines, particularly IL-1beta and TGF-beta, were also found in the gastric mucosae of healthy, uninfected subjects. We also showed that the gastric epithelium contributes substantially to the antral cytokine response of the proinflammatory cytokines IL-1beta and IL-6 in addition to IL-8.

Adult↗

PubMed1998

Antibody-secreting cells in the stomachs of symptomatic and asymptomatic Helicobacter pylori-infected subjects.

In this study we analyzed whether infection with Helicobacter pylori gives rise to specific B-cell responses against a number of putative virulence factors of H. pylori, e.g., urease, flagellin, and different bacterial surface antigens, locally in the gastric mucosa. This was studied in antrum and corpus biopsies collected from 11 H. pylori-infected patients with duodenal ulcers, 11 asymptomatic H. pylori carriers, and 13 noninfected, healthy controls. Mononuclear cells were isolated from the biopsies and assayed for frequencies of total and H. pylori-specific antibody-secreting cells (ASCs) by means of the enzyme-linked immunospot technique. The H. pylori-infected subjects had remarkably higher frequencies of total immunoglobulin A (IgA)- and IgM-secreting cells than the noninfected subjects, while the frequencies of IgG-secreting cells were virtually the same in the different groups. In addition, most of the infected subjects had IgA ASCs reacting with H. pylori membrane proteins, flagellin, and urease, while none of the noninfected subjects had any detectable H. pylori-reactive ASCs. Furthermore, half of the infected subjects also had ASCs reacting with a Helicobacter-specific 26-kDa protein, while only a few of them had ASCs reacting with neutrophil-activating protein, the neuraminyllactose-binding hemagglutinin HpaA, or lipopolysaccharides purified from different H. pylori strains. The frequencies of H. pylori-specific ASCs in the antrum and corpus were almost identical, and no differences in either antigen specificity or magnitude of the B-cell response in the stomach could be detected between the ulcer patients and the asymptomatic H. pylori carriers. This study demonstrates that H. pylori infection induces strong antibody responses in the human gastric mucosa, both in asymptomatic carriers and in duodenal ulcer patients. However, the outcome of infection could not be explained by differences in the local B-cell response to any of the antigens used in this study.

Adult↗

PubMed1997

Local and systemic immune responses in humans against Helicobacter pylori antigens from homologous and heterologous strains.

The capacity of Helicobacter pylori to induce strain specific immune responses was studied in adult Swedish volunteers. Sera and gastric aspirates from 11 H. pylori-infected subjects were tested for specific antibody levels against, respectively, lipopolysaccharides (LPS) and total membrane preparations (MPs) prepared from the study subjects' own strains, as well as with corresponding antigens from two reference H. pylori strains or heterologous strains collected from other subjects within the study. It was found that sera from five of the 11 subjects had significantly higher IgA antibody titres against LPS from the homologous strain than against LPS from either of the reference strains and in five cases sera reacted with higher IgG titres against the homologous LPS than with LPS preparations from the reference or heterologous patient strains. Analyses of specific titres against MPs revealed that six sera had higher IgA titres and four sera had higher IgG titres against MPs prepared from the subjects' own strains than against MPs from either of the two reference strains. Determination of specific antibodies in gastric aspirates revealed significantly higher IgA titres against LPS from the homologous H. pylori isolate than against LPS from the two reference strains in five cases, and six aspirates reacted in higher IgA titre with the homologous H. pylori MPs. Results from immunoblotting analyses of sera support induction of strain specific immune responses against H. pylori LPS. By means of specific monoclonal antibodies against H. pylori LPS, antigenic heterogeneity between the different LPS preparations tested was confirmed.

Adult↗

PubMed1996

A mechanism by which Helicobacter pylori infection of the antrum contributes to the development of duodenal ulcer.

BACKGROUND & AIMS: Helicobacter pylori infection and duodenal ulcer disease are firmly correlated. However, the bacteria do mainly colonize the antrum, indicating an indirect pathogenic mechanism. The aim of this study was to test a concept claiming that H. pylori infection of the antrum selectively blocks normal inhibitory reflex pathways to gastrin and parietal cells. METHODS: The effect of antral distention was studied on gastric acid secretion stimulated by pentagastrin and on gastrin release stimulated by gastrin-releasing peptide in H. pylori-infected and noninfected patients with and without duodenal ulcer disease, as well as after eradication of the bacteria. RESULTS: The inhibitory effect on gastric acid secretion induced by antral distention was absent in H. pylori-infected patients irrespective of whether or not they had duodenal ulcer disease. The inhibitory mechanism was restituted in 8 of 10 patients within 9 months after successful eradication of H. pylori infection. Similar results were obtained in studies on gastrin release. CONCLUSIONS: H. pylori infection blocks normal, physiological inhibitory mechanisms from the antrum to both the gastrin cells and to the parietal cell region, resulting in increased gastrin release and impaired inhibition of gastric acid secretion, which will probably lead to an increased duodenal acid load as a general prerequisite for the development of duodenal ulcer disease.

Adult↗

PubMed1996

The influence of Helicobacter pylori infection on postprandial duodenal acid load and duodenal bulb pH in humans.

BACKGROUND & AIMS: Recently, we postulated a new concept of duodenal ulcer pathogenesis suggesting that antral Helicobacter pylori infection blocks inhibitory pathways to the gastrin and parietal cells, resulting in an increased and prolonged postprandial acid secretion. the aim of this study was to examine duodenal acid load and duodenal bulb pH after a meal before and after eradication of H. pylori. METHODS: Using a marker-dilution method and a pH electrode in the duodenal bulb, gastric emptying, acid secretion, gastrin release, duodenal acid load, and duodenal bulb pH were studied during 2 hours after peptone meals of pH 7.0 and 2.0 in 8 H. pylori-negative controls and 8 H. pylori-infected subjects before and 6 months after eradication. RESULTS: The H. pylori-infected subjects had an increased gastric emptying, gastrin release, and acid secretion, higher duodenal acid load, and lower duodenal bulb pH after the meals. These responses were normalized after eradication. CONCLUSIONS: H. pylori-infected subjects have an increased and prolonged postprandial acid secretion, partly caused by an impaired low pH inhibition of acid secretion, gastrin release, and gastric emptying, resulting in an increased duodenal acid load and a prolongation of low pH in the duodenal bulb, as a general prerequisite for the development of duodenal ulcer disease.

Adult↗

PubMed1995

Sympatho-adrenergic inhibition of basal and acid-induced changes in duodenal motility, mucosal net fluid and alkaline secretion in the anaesthetized cat.

Experiments were performed on chloralose anaesthetized cats. A 2-cm segment of the proximal duodenum was isolated between two luminally situated balloons and perfused with isotonic saline containing [14C]-PEG 4000 as a non-absorbable marker. The perfusate was analysed with regard to alkalinity (back titration) and concentration of marker (liquid scintillation). Net alkalinization and net fluid transport were calculated with conventional equations. Motor activity in the duodenal wall was recorded as changes in volume of the proximal balloon. In presence of sympathetic neural activity (spontaneous or electrically stimulated) basal motor activity and mucosal alkaline secretion was low and increased minimally in response to luminal HCl (30 mM). Net fluid transport was in an absorptive state and shifted to a small secretion upon the acid-exposure. Subsequent to bilateral acute splanchnicotomy, or the administration of the adrenolytic guanethidine (3-4 mg kg-1, i.v.), spontaneous duodenal contractions occurred and the alkaline secretion was increased. Furthermore, both parameters were then markedly stimulated by luminal perfusion with 30 mM HCl. Basal net fluid transport was zero and turned into secretion upon the acid-exposure. No morphological changes of the duodenal surface epithelium could be detected. The study demonstrates the existence of splanchnic nerve-mediated, adrenergic inhibition of basal, as well as of acid-induced duodenal motility, fluid and alkaline secretion.

Animals↗

PubMed1994

Duodenal wall motility, mucosal net fluid and alkaline secretion in response to luminal acid: role of the vagal nerves and cholinergic transmission.

Experiments were performed on chloralose anaesthetized cats. Biliary and pancreatic secretions were diverted by separate cannulation of each duct. A 2-cm segment of the proximal duodenum was isolated between two luminally situated balloons and perfused with isotonic saline containing 14C-PEG 4000 as a non-absorbable marker. The perfusate was analysed with regard to alkalinity (back titration) and concentration of marker (liquid scintillation). Net alkalinization and net fluid transport were calculated with conventional equations. Motor activity in the duodenal wall was recorded as changes in volume of the proximal balloon. Exposing the duodenal segment of 30 mM HCl induced duodenal contractions, net fluid secretion and an increased alkaline secretion, responses which were insensitive to acute truncal vagotomy. The acid-induced increase in contraction frequency was inhibited by hexamethonium, but not by atropine. Alkaline secretion in response to luminal acid was blocked by hexamethonium and inhibited by atropine, whereas the net fluid secretion was insensitive to these compounds. It is concluded that luminal exposure to hydrochloric acid changes the duodenal functional state by mechanisms which are independent of the extrinsic neural supply. Duodenal contractions during luminal acid exposure, and the alkalinization after such acid exposure, are mediated via local neural pathways, involving a nicotinic cholinergic step and, to some degree, muscarinic transmission. The mucosal volume secretion, however, appears to be mediated by non-conventional mechanisms.

Alkalies↗

PubMed1993

Does antral distension inhibit gastric acid secretion or stimulate bicarbonate secretion in 'healthy' subjects?

The effects of a 150-ml antral balloon distension on pentagastrin-stimulated gastric acid secretion and bicarbonate secretion were studied in nine healthy subjects and eight duodenal ulcer (DU) patients. The gastric secretions were simultaneously measured, using a luminal perfusion and pH/PCO2 measurements. Two of the healthy subjects and six of the DU patients were positive for Helicobacter pylori. When H. pylori-positive and -negative subjects were compared, basal gastric acid and bicarbonate outputs did not differ significantly. In H. pylori-infected subjects the bicarbonate transport increased by about 70% on pentagastrin stimulation. In the H. pylori-negative group pentagastrin had no effect on the bicarbonate secretion. Antral distension elicited a 30-35% inhibition of pentagastrin-stimulated gastric acid secretion in the group of H. pylori-negative subjects, whereas the acid secretory level remained essentially unchanged in the positive group. Bicarbonate secretion decreased transiently by the distension in the negative subjects, whereas a slight increase was observed in the infected group. We conclude that antral distension inhibits pentagastrin-stimulated gastric acid output in healthy H. pylori-negative subjects. Our results strongly suggest that the underlying mechanism is a direct inhibition of gastric parietal cell function and not an increased gastric bicarbonate secretion. Furthermore, the results indicate that this defective distension-induced acid inhibition may be correlated to H. pylori infection rather than to duodenal ulcer disease.

Adult↗

PubMed1992

The mediation of increased duodenal alkaline secretion in response to 10 mM HCl in the anaesthetized rat. Support for the involvement of capsaicin-sensitive nerve elements.

Experiments were performed on chloralose-anaesthetized rats. Bicarbonate secretion by the duodenal mucosa was continuously recorded by use of an in situ-titration technique. Exposing the duodenal segment to 10 mM HCl over 5 min increased the bicarbonate transport by about 65%. This acid-induced secretory response was resistant to neural decentralization by means of bilateral cervical vagotomy and/or splanchnicotomy. Furthermore, in the decentralized state, serosal application of the local anaesthetic lidocaine or tetrodotoxin (TTX) lowered basal duodenal bicarbonate secretion. Despite the presence of lidocaine or TTX, exposure of the duodenal mucosa to 10 mM HCl induced a net increase in secretion with a magnitude similar to that observed in the control situation with intact nerves. A 5-min exposure period of the decentralized duodenal segment to capsaicin (1.2 mg ml-1) raised bicarbonate secretion, a response which also occurred in the presence of lidocaine (serosa). Tachyphylaxis to capsaicin blocked the secretory response to 10 mM HCl and inhibited the response to luminal prostaglandin E2 (1.5 10(-5) M) by 80%. The present results indicate that luminal exposure to 10 mM HCl activates capsaicin-sensitive primary afferents which, locally within the submucosa or epithelium, activate the bicarbonate secretion.

Animals↗

PubMed1991

Hypovolaemia inhibits acid-induced alkaline transport in the rat duodenum via an alpha-2 adrenergic mechanism.

Acid exposure of the duodenal mucosa is a well-known stimulant of the mucosal alkaline secretion. We have previously reported that a minor blood loss inhibits this secretory increment via activation of the splanchnic nerves. In the present study the pharmacological characteristics of the splanchnic neural inhibition of the alkaline secretion were investigated. Duodenal HCO3- secretion was measured by in-situ titration in chloralose-anaesthetized rats. Exposure of the duodenal mucosa to hydrochloric acid (0.01 M, 5 min) increased the secretion by approximately 60%. A 10% decrease in blood volume simultaneously to the luminal acidification abolished the secretory increase, as previously reported. Treatment with either guanethidine or yohimbine blocked the bleeding-induced inhibition of the secretion after acid-exposure. Neither prazosin nor propranolol did prevent such hypovolaemia-induced inhibition of duodenal alkaline secretion. The present results suggest that the splanchnic neural inhibition of acid-induced duodenal HCO3- secretion is mediated via adrenergic nerve fibres and alpha-2 adrenoceptors.

Animals↗