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Biomedical subjects

R H Hunt

Publications and source records attributed to R H Hunt.

At least 109 records · Page 6Linked to original sources
PubMed1995

Helicobacter pylori and gastric neoplasia: evolving concepts.

There is evidence that Helicobacter pylori infection is associated with gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma and possibly with non-ulcer dyspepsia. Eradication therapy for confirmed H. pylori infection may therefore become mandatory in patients with non-ulcer dyspepsia severe enough to warrant endoscopy and in first-degree relatives of patients with gastric cancer. However, routine treatment of asymptomatic carriers awaits confirmation of the association with cancer.

Adenocarcinoma↗
PubMed1995

Optimizing acid suppression for treatment of acid-related diseases.

Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacological reduction of acid secretion is, therefore, the mainstay of current treatment, but the optimal degree of acid suppression remains incompletely understood. This paper considers the ideal ways of assessing and reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intragastric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been successfully correlated with healing rates for duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Three primary determinants of healing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, and the duration of treatment. The order of importance of these determinants varies depending on the disease. Data on 24-hr intragastric acidity should be accompanied whenever possible by data on 24-hr plasma gastrin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any other measurement of intragastric acidity. Comparative data sets in groups of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. However, in view of the importance of duration of treatment, healing rates with the H2-receptor antagonists approach those obtained with proton pump inhibitors if treatment is continued for a longer time. In gastroesophageal reflux disease in particular, although the optimal degree of acid suppression is not yet defined, the consistently superior performance of proton pump inhibitors demonstrates that increased suppression of acidity is clinically beneficial.

Duodenal Ulcer↗
PubMed1995

Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vitro.

BACKGROUND/AIMS: Helicobacter pylori is associated with neutrophil infiltrates, although the mechanism of their recruitment is only partially defined. The aim of the study was to determine if Kato III, a human gastric epithelial cell line, expressed cytokines and the intercellular adhesion molecule 1 (ICAM-1), which could contribute to the initiation of inflammation during infection with H. pylori. METHODS: Kato III cells were stimulated with H. pylori and were examined for evidence of infection, cytokine production, and the expression of ICAM-1. RESULTS: The expression of interleukin 8 messenger RNA and immunoreactive protein by Kato III cells was significantly increased over constitutive levels within 3 hours of infection with H. pylori. Infected Kato III supernatants activated neutrophils as evidenced by increased CD11b/CD18 and decreased L-selectin that could be blocked by anti-interleukin 8. In contrast, Campylobacter jejuni, lipopolysaccharide, killed H. pylori, and supernatants from cultures of H. pylori did not increase interleukin 8. Interleukins 2 and 6; interferons alfa, beta, and gamma; and tumor necrosis factor were not produced by resting or H. pylori-stimulated Kato III cells. In addition to producing interleukin 8, Kato III constitutively expressed surface ICAM-1, which acts as an intercellular adhesion molecule for neutrophils. CONCLUSIONS: Our results indicate that H. pylori stimulates the gastric epithelium to initiate inflammation and neutrophil recruitment and activation.

Base Sequence↗
PubMed1995

The effect of indomethacin-induced gastric mucosal injury on 24-h intragastric acidity and plasma gastrin concentration in healthy volunteers.

AIMS: To determine the influences of prostaglandin inhibition by indomethacin on 24-h intragastric acidity and plasma gastrin concentration, related to gastric mucosal injury. METHODS: A pre- and post-treatment study design was employed in 10 Helicobacter pylori negative healthy male subjects. All subjects underwent upper gastrointestinal endoscopy at least 3 days before and after 7 days dosing with indomethacin 50 mg t.d.s. Mucosal damage was scored according to the Lanza method, and biopsies were taken for H. pylori status and assay of mucosal concentrations of prostaglandin (PG)E2 and leukotriene (LT)B4. Before and on the last day of dosing, intragastric acidity was measured by continuous 24-h pH monitoring, and plasma gastrin levels determined by radioimmunoassay in blood samples collected over the same period. RESULTS: All subjects completed the study and no serious adverse events were reported. The mucosal injury score increased significantly from 0 (0-2) to 3.4 (0-8) (mean and range of values, P < 0.05) after dosing with indomethacin. No differences were observed in 24-h mean pH or meal stimulated plasma gastrin concentrations. Mucosal PGE2 and LTB4 were unchanged 8-10 h after the last indomethacin dose. CONCLUSIONS: Endogenous prostaglandins do not appear to alter intragastric acidity or gastrin secretion, in contrast to the PGE analogues, whose effects must be more pharmacological than physiological.

Adult↗
PubMed1995

The relationship between the control of pH and healing and symptom relief in gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GERD) is generally considered to be the result of a motility disorder which permits the abnormal and prolonged exposure of the lumen of the oesophagus to the acidic gastric contents. This view is supported by experimental data, intra-oesophageal pH measurement, and the dramatic results of symptom relief and healing seen with effective antisecretory treatment. Oesophageal mucosal injury is determined by the pH of the refluxate and duration of acid exposure. Most patients experience meal-stimulated reflux during the day and the more severe cases experience 24-h acid exposure. In contrast to the H2-receptor antagonists (H2RAs), the proton pump inhibitors (PPIs) are more effective at controlling meal-stimulated acid secretion when each is given in standard doses. Therefore, the degree and duration of acid suppression throughout 24 h is greater. Treatments which maintain intra-oesophageal pH > 4 for 96% or more of the 24 h normalize acid exposure and are associated with the highest healing rates. Peptic activity is minimized at or above pH 4. The time above pH 4 is significantly longer with the PPIs than with the H2RAs. Thus, the healing-time curves for GERD (grades II-IV) are shifted to the left for the PPIs which heal a significantly greater proportion of patients earlier than the H2RAs or sucralfate. Symptoms in GERD are related to the degree and duration of oesophageal acid exposure. Symptom relief is more rapid and complete with the PPIs than with the H2RAs or other treatments in standard doses.

Double-Blind Method↗
PubMed1995

Malaria infection potential of anopheline mosquitoes sampled by light trapping indoors in coastal Tanzanian villages.

Anopheline mosquito populations were studied during 1992 in seven villages south of Bagamoyo, coastal Tanzania, prior to malaria control intervention using insecticide treated bednets. To collect mosquitoes, CDC light traps were used in ten houses per village fortnightly for 12 months. Anopheles females were identified and checked by ELISA for the presence of malaria sporozoite antigen and source of bloodmeal. An.funestus peaked in June-July after the long rains. Three members of the An.gambiae complex had different seasonality: An.arabiensis, An.gambiae and small numbers of An.merus were collected. In most villages transmission was extremely high and perennial with the entomological inoculation rate reaching three to eleven infective bites per person per night in July and persisting at around 0.1 and 1 for most of the remainder of the year. Sporozoite infection rates within the An.gambiae complex ranged from 2% to 25%, with the peaks in January and July following the two rainy periods. An.funestus showed a similar pattern. The light traps were reliable, simple to operate, and proved to be satisfactory to study the mosquito vector population.

Animals↗
PubMed1995

Critical reappraisal of mucosal repair mechanisms.

The repair of the mucosal surface of the stomach is a complex process involving a number of different cell systems. These include mucosal enterocytes, matrix proteins, and cells responsible for angiogenesis. The regulation of each of these systems is as yet poorly defined and the interaction between the different components remains to be characterized. The signal system involved in recognition of damage initiates a cascade of events which broadly comprise cell migration, cell proliferation, lineage determination, matrix reconfiguration, and angiogenesis. Critical regulators of this process include the trefoil peptides, specific adhesion molecules, and the modulators of cell lineage. The utility of specific pharmacotherapeutic probes, whether responsible for surface protection, growth factor delivery, acid inhibition, or growth factor amplification, remains to be rigorously defined. The repair of the mucosal defect is critical in establishing the functional integrity of the gastric luminal surface. In order to facilitate rapid and long-lasting repair of mucosal injury, a precise understanding of the specific biological events participant in the repair process is required. At this time, there is only a paucity of such information available.

Extracellular Matrix↗
PubMed1995

The current role of Helicobacter pylori eradication in clinical practice.

Helicobacter pylori is probably the commonest bacterial infection worldwide and is now accepted as the cause of chronic active type B gastritis. It is increasingly accepted as having a critical role in duodenal ulcer, where the prevalence of infection is 90 to 100%. More important is the dramatic reduction in duodenal ulcer recurrence after successful eradication of the organism to about 4% in a year compared to recurrences of up to 80% in those whose ulcers have been healed but in whom the infection persists. There is increasing evidence that what is now clear for duodenal ulcers may also hold true for patients with a gastric ulcer who are infected with H. pylori. Moreover, evidence is accumulating that the risk of a duodenal ulcer complication, such as, bleeding, is reduced following successful eradication of H. pylori. The treatment of duodenal ulcer patients with H. pylori eradication treatment has been advocated by an international working party who met first in Sydney at the 1990 World Congress and subsequently in Athens during the First European Gastroenterology Week. The most recent recommendation suggests that the infection should be treated in any duodenal ulcer patient after the first recurrence, and that a triple therapy regimen or a proton pump inhibitor combined with either amoxicillin or clarithromycin may be prescribed. The combination of a proton pump inhibitor and an antibiotic can eradicate H. pylori in over 80% of cases and simultaneously offers the advantage of rapid symptom relief and the highest rates of duodenal ulcer healing.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastritis↗
PubMed1995

Helicobacter pylori eradication: a critical appraisal and current concerns.

Helicobacter pylori is now well recognized as a critical factor in the majority of patients with peptic ulcer disease and successful treatment of the infection results in cure of the disease. However, treatment of this infection has proved difficult, involving a combination of drugs, and has usually involved complex treatment regimens. Triple therapy involving a bismuth compound in combination with metronidazole and tetracycline or amoxicillin have been most widely used and achieve successful cure of the infection in about 90% of cases when the tetracycline combination is used. More recently, the use of the proton-pump inhibitors in combination with amoxicillin have been widely advocated to combine effective symptom relief with high ulcer healing rates and an opportunity to cure the disease. However, all these treatments have some disadvantages due to unpredictability, adverse events, complex regimens making compliance difficult, or cost. This article reviews the results of current treatments for the eradication of H. pylori infection and identifies opportunities for the development of optimal approaches to the cure of this infection.

Anti-Bacterial Agents↗
PubMed1995

Critical issues in the pathophysiology and management of peptic ulcer disease.

OBJECTIVE: To discuss some of the critical issues in the pathophysiology and management of peptic ulcer disease. OPINION: Peptic ulcer disease has multiple causes, although gastric acid has traditionally been considered the primary aggressive factor. Helicobacter pylori infection is established as a major causative factor, but some aspects of the mechanisms by which H. pylori causes peptic ulceration remain unclear. Treatment with proton pump inhibitors (PPIs) is the most effective means of healing peptic ulcers. In addition to healing a higher proportion of ulcers than H2-receptor antagonists, PPIs provide faster healing and relief of symptoms. The ability of PPIs to produce effective and sustained inhibition of gastric acid secretion suggests that they may also become the treatment of choice for gastric ulcers caused by non-steroidal anti-inflammatory drugs. However, eradication of H. pylori infection is more effective than maintenance therapy with antisecretory agents in reducing the rate of recurrence of peptic ulcers initially healed using antisecretory therapy. H. pylori eradication is therefore the optimal, and almost certainly the most cost-effective, approach to the long-term management of patients with peptic ulcer disease. Despite the fact that 90-95% of patients with demonstrable duodenal ulceration are probably infected with H. pylori, it is recommended that, in routine clinical practice, infection is diagnosed before eradication therapy is instituted. H. pylori testing 4-6 weeks after the completion of eradication therapy is also recommended to check that the infection has been successfully cured. For routine clinical practice, the highly sensitive and specific rapid urease test is probably the most useful diagnostic approach. The most appropriate H. pylori eradication regimen remains to be defined. However, 1-2 weeks of treatment with a combination of a PPI and two antimicrobial agents achieves eradication rates in excess of 90%, which are similar to those attained using standard triple therapy, but with the advantage of better patient compliance and greater tolerability. Preliminary evidence also suggests that H. pylori eradication prevents the recurrence of peptic ulcer bleeding, although further studies are required. CONCLUSION: H. pylori eradication by 1-2 weeks' treatment with a combination of a PPI and two antimicrobial agents appears to be the optimal (and probably the most cost-effective) approach to the long-term management of patients with peptic ulcer disease, and represents a major advance in the management of such patients.

Antacids↗
PubMed1994

Adenosine A1 receptors are not involved in contraction of canine gastric muscularis mucosae by adenosine analogues.

In vitro contractility studies were conducted in canine gastric muscularis mucosae muscle strips with the adenosine analogues 2-chloroadenosine (CIAD), 5'-N-ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), S-PIA, N6-cyclohexyladenosine (CHA) and (2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine (CGS21680) as well as the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). Adenosine analogues contracted the muscle strips with the following rank order of potency: CPCA > NECA > CIAD > R-PIA > CHA > S-PIA > CGS21680. CPCA, R-PIA, and CHA were partial agonists. At a concentration selective for adenosine A1 receptors (50 nM), DPCPX did not alter the concentration-response curves to CIAD or CHA. However, at higher concentrations (1-10 microM), DPCPX antagonized CIAD-mediated contractions in a competitive manner (pA2 = 6.96; slope = 0.93). CIAD-mediated contraction was not altered by treatment of the muscle strips with tetrodotoxin (1 microgram/ml) or mepyramine (1 microM). Our results indicate that adenosine A1 receptors, nerves or mast cells are not involved in contraction of canine gastric muscularis mucosae by adenosine analogues.

2-Chloroadenosine↗
PubMed1994

Biting pattern and host-seeking behavior of Anopheles arabiensis (Diptera: Culicidae) in northeastern South Africa.

Biting rhythm as well as vertical and horizontal distribution of host-seeking Anopheles arabiensis Patton was studied at a remote warm-water spring in the Kruger National Park, South Africa, which usually is devoid of human presence. An. arabiensis seeking hosts were collected throughout the night with several peaks, often with greatest biting activity during the predawn period. Abundance did not decline linearly as a function of distance from the breeding area, but was related to vegetation patterns. Most bites occurred on the ankles or feet and decreased rapidly above that height. Wearing closed shoes or raising feet off the ground could reduce vector contact and therefore the risk of malaria infection.

Animals↗
PubMed1994

The rationale of acid suppression in the treatment of acid-related disease.

Acid-related disorders such as gastric and duodenal ulcers and gastro-oesophageal reflux disease have a high prevalence. Traditionally, acid suppression has proved to be the most effective means by which to heal these disorders, but relapse rates are high after cessation of treatment. Recently, Helicobacter pylori infection has been shown to modify several aspects of gastric function. Eradication of H. pylori infection virtually abolishes duodenal ulcer recurrence, implicating this organism in the pathogenesis of peptic ulcers and initiating a whole new strategy in the management of these acid-related disorders. More potent degrees of acid suppression result in faster healing. Moderate acid suppression, as occurs with H2-receptor antagonists, can heal just as many ulcers if treatment is continued for longer. The combination of proton pump inhibitors and antibiotics have successfully eradicated H. pylori in duodenal ulcer patients. Both H2-receptor antagonists and the proton pump inhibitors have satisfactory safety profiles. Due to their superiority in symptom relief, and in the healing of duodenal and gastric ulcers and erosive oesophagitis, and due to their ability to eradicate H. pylori infection in combination with antibiotics, the proton pump inhibitors will probably become accepted as first-line therapy for the treatment of acid-related diseases.

Anti-Bacterial Agents↗
PubMed1994

Appropriate acid suppression for optimal healing of duodenal ulcer and gastro-oesophageal reflux disease.

Comparisons of the effectiveness of treatments for healing duodenal ulcer are essential to determine optimal management strategies for both economic analysis and quality-of-life evaluation. Differences are usually made on the basis of the proportion of ulcers healed at varying time intervals. It has been shown by meta-analysis that healing of duodenal ulcers with antisecretory drugs is directly correlated to the degree of acid suppression. More recently, sophisticated meta-analysis of 24-hour intragastric acidity data and clinical trials of antisecretory drugs has demonstrated that the optimal degree and duration of gastric acid suppression for healing duodenal ulcer can be achieved by an aggregate time above pH 3 of 18-20 hours/day. These conditions predict 100% ulcer healing at 4 weeks. Antisecretory drug regimens that approach these criteria should achieve faster healing than other agents, with a concomitant acceleration of symptom resolution. Regression analysis was performed on the healing-time curves for each drug class to determine the rate of ulcer healing per week. The mean proportion of ulcers healed, irrespective of treatment duration, was highest for omeprazole, which also provided a significantly faster rate of duodenal ulcer healing than all other drug classes (p < 0.001). It has recently been shown that healing of erosive oesophagitis with antisecretory drugs is directly correlated with both the duration of acid suppression over the 24-hour period (p < 0.05) and the elevation of intra-oesophageal pH above 4. Furthermore, oesophageal acid exposure time can be normalized by maintaining the intra-oesophageal pH above 4 for at least 96% of the 24-hour period.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs and Cost Analysis↗
PubMed1994

Hp and pH--the relevance of gastric acid to the treatment of Helicobacter pylori infection.

Helicobacter pylori infection causes inflammation of the gastric and duodenal mucosa, which results in a disturbance of the regulation of gastrin, gastric acid, and pepsin secretion. Acid secretion may be diminished, normal, or increased, depending on the stage of H. pylori infection, although the meal-stimulated gastrin response is invariably elevated. The exact mechanisms involved are not known, but probably involve the release of cytokines in response to bacterial products initiating mucosal inflammation. Helicobacter pylori is suppressed, although not eradicated, by proton pump inhibitors. In various dose combinations with amoxycillin, omeprazole in a twice daily dose of up to 40 mg b.i.d. eradicates the organism in up to 82% of patients. This synergistic effect may be due to the direct effects of omeprazole, the protection of amoxycillin from acid degradation, or the enhancement of host defense mechanisms accompanying acid suppression.

Amoxicillin↗
PubMed1994

NSAID--induced gastroduodenal ulcers: exploring the silent dilemma.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective medications and are very commonly prescribed. They are used by a large proportion of elderly persons who are most prone to adverse events. NSAID gastropathy is the commonest side effect. The relative risk of adverse events is high, but the absolute risk for any individual patient is low. Individualizing the risk/benefit ratio would lead to cost effective care.

Age Factors↗
PubMed1993

Effects of chronic NSAIDs on gastric mucosal injury related to mucosal prostanoids, and plasma drug concentrations in human volunteers.

The relationship between endoscopically observed gastric mucosal damage, elicited following repeated oral intake for 7 d of four NSAIDs, to their effects on antral and fundic production of PGE2, 6-keto-PGF1 alpha and TxB2 (assayed by GC-MS), mucosal histology and plasma concentration profiles was studied in 40 normal males. Subjects received azapropazone (APZ) 600 mg b.i.d., indomethacin (IND) 50 mg t.i.d., naproxen (NAP) 500 mg b.i.d., piroxicam (PIR) 20 mg qq.d., or one placebo capsule t.i.d. (N = 8/group). Plasma NSAIDs (HPLC) levelled at 7 d. Mucosal damage occurred in the antrum region with IND and NAP. APZ and PIR exhibited no differences compared to placebo. NAP and IND reduced all three prostanoids in the antrum while APZ and PIR were ineffective. Fundic PGE2 was reduced by IND, NAP and PIR; APZ had no effects. Thus, mucosal damage relates to effects on prostanoid production in the antrum but not in the fundus.

6-Ketoprostaglandin F1 alpha↗