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Biomedical subjects

K E McColl

Publications and source records attributed to K E McColl.

At least 19 recordsLinked to original sources
PubMed2002

In vitro studies indicate that acid catalysed generation of N-nitrosocompounds from dietary nitrate will be maximal at the gastro-oesophageal junction and cardia.

BACKGROUND: Dietary nitrate increases saliva nitrite levels and swallowed saliva is the main source of nitrite entering the acidic stomach. In acidic gastric juice, this nitrite can generate potentially carcinogenic N-nitrosocompounds. However, ascorbic acid secreted by the gastric mucosa can prevent nitrosation by converting the nitrite to nitric oxide. METHODS: To study the potential for N-nitrosocompound formation in a model simulating salivary nitrite entering the acidic stomach and the ability of ascorbic acid to inhibit the process. Concentrations of ascorbic acid, total vitamin C, nitrite, nitrosomorpholine, oxygen and nitric oxide were monitored during the experiments. RESULTS: The delivery of nitrite into HCl containing thiocyanate resulted in nitrosation of morpholine, with the rate of nitrosation being greatest at pH 2.5. Under anaerobic conditions, ascorbic acid converted the nitrite to nitric oxide and prevented nitrosation. However, in the presence of dissolved air, the ascorbic acid was ineffective at preventing nitrosation. This was due to the nitric oxide combining with oxygen to reform nitrite and this recycling of nitrite depleting the available ascorbic acid. Further studies indicated that the rate of consumption of ascorbic acid by nitrite added to natural human gastric juice (pH 1.5) was extremely rapid with 200 micromol/l nitrite consumed 500 micromol/l ascorbic acid within 10 s. CONCLUSIONS: The rapid consumption of ascorbic acid in acidic gastric juice by nitrite in swallowed saliva indicates that the potential for acid nitrosation will be maximal at the GO junction and cardia where nitrite first encounters acidic gastric juice. The high incidence of mutagenesis and neoplasia at this anatomical location may be due to acid nitrosation arising from dietary nitrate.

Ascorbic Acid↗
PubMed2001

Problems associated with the clinical use of proton pump inhibitors.

Proton pump inhibitors have proven to be important in the treatment of acid/peptic diseases. However, their therapeutic uses have extended over time, which may alter their risk:benefit ratio. Significant rebound acid hypersecretion has been demonstrated, which persists for at least two months. Its clinical significance remains unknown. Enhanced oxyntic gastritis may be responsible for the increased acid suppressive effects of proton pump inhibitors in H. pylori-infected patients. It remains unclear whether either H. pylori eradication or diminishing rates of infection in the developed world will therefore decrease the efficacy of proton pump inhibitors. Problems with carcinoids in rodents have not been found in man. However, the consequences of very long-term use of proton pump inhibitors remain unknown. Similarly, the development of atrophic gastritis in H. pylori-positive patients treated with proton pump inhibitors, with the long-term concern of gastric carcinoma development, remains controversial.

Animals↗
PubMed2001

Review article: tackling the "dyspeptic problem".

Dyspepsia, and the issue of Helicobacter pylori status, can present significant controversies in clinical management. Both primary physicians and gastroenterologists should be aware of options for the treatment of patients with dyspepsia. This article reviews information gathered about the eradication of H. pylori in non-ulcer dyspepsia (NUD), therapy for NUD not associated with H. pylori, and whether H. pylori testing should replace routine endoscopy in uncomplicated dyspepsia. The benefits of eradicating H. pylori in NUD include superior, cost-effective resolution of symptoms, compared to placebo; reduction of ulcer and gastric cancer risk; and removal of risk of certain adverse effects should long-term proton pump inhibitor therapy become necessary. In patients with normal endoscopy and no evidence of H. pylori, proton pump inhibitor therapy is superior to placebo in controlling symptoms. This benefit is confined to patients with symptoms and/or oesophageal pH-metry indicative of GORD. Non-invasive H. pylori testing may be appropriate for younger dyspeptic patients with no alarm symptoms who are not taking non-steroidal anti-inflammatory drugs (NSAIDs). In conclusion, eradication of H. pylori is advisable in patients with NUD. Proton pump inhibitor therapy is superior to placebo in NUD patients without H. pylori, especially if symptoms indicate GORD. H. pylori testing may replace endoscopy in young dyspeptics with no alarm symptoms or NSAID use.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Alterations in intragastric nitrite and vitamin C levels during acid inhibitory therapy.

Most nitrite entering the healthy acid-secreting stomach is derived from dietary nitrate. The latter is absorbed from the small intestine, 25% then being secreted by the salivary glands into the mouth. Buccal organisms subsequently convert 20% of this nitrate to nitrite. When this nitrite is swallowed, the ascorbic acid in the acidic gastric juice reduces it to nitric oxide, which is absorbed by the mucosa. In the process, the ascorbic acid is oxidized to dehydroascorbic acid. When the intragastric pH is elevated by powerful anti-secretory agents, this gastric chemistry is profoundly modified. At a neutral pH, the swallowed nitrite does not react with ascorbic acid but accumulates in the stomach. The level of nitrite in the gastric juice during treatment with anti-secretory medication is particularly high after a nitrate-containing meal. Powerful anti-secretory medication also lowers the intragastric concentration of ascorbic acid and total vitamin C, probably because of the relative instability of the vitamin at a higher pH. These changes in the intragastric concentrations of nitrite and ascorbic acid are most marked in Helicobacter pylori -infected subjects on proton pump inhibitor therapy. It is recognized that an elevated nitrite-to-ascorbic acid ratio predisposes to the formation of potentially carcinogenic N -nitroso compounds. It is, however, unclear at present whether such compounds are formed within the human stomach.

Anti-Ulcer Agents↗
PubMed2001

Problems related to acid rebound and tachyphylaxis.

Rebound acid hypersecretion after taking histamine H(2)-receptor antagonists is a now well-established class phenomenon. It has been demonstrated both basally and in response to meal and gastrin-releasing peptide stimulation, but not in response to peak pentagastrin stimulation. It is present by 3 days after treatment but has resolved by 10 days. A recent study in previously asymptomatic healthy volunteers has suggested that this phenomenon may be clinically relevant. Tachyphylaxis/tolerance after the use of H(2)-receptor antagonists is also now well established. It manifests as a loss of acid inhibitory efficacy and is also a class effect. It is present within a few doses but is not progressive after 29 days. Rebound acid hypersecretion after proton pump inhibitors has been shown for both basal and maximal acid output by 14 days after treatment. It is found in Helicobacter pylori -negative, but not positive, subjects, probably owing to the influence of the enhanced oxyntic gastritis that occurs during proton pump inhibitor therapy. It is a prolonged phenomenon, lasting for at least 2 months after a 2-month treatment course. This duration is likely to reflect its development as a result of trophic effects on the oxyntic mucosa. This trophism is caused by the marked hypergastrinaemia that occurs secondary to the profound acid suppression during proton pump inhibitor treatment. The clinical relevance of this phenomenon remains at present unknown. Tachyphylaxis/tolerance has not yet been shown in several short-term studies after taking proton pump inhibitors. A recent clinical study has, however, suggested that this phenomenon may merit longer-term evaluation.

Animals↗
PubMed2001

Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal.

BACKGROUND & AIMS: Gastroesophageal reflux typically occurs after meals. During dual gastric and esophageal pH monitoring, we observed that postprandial refluxate was often more acidic than the gastric contents. This study aimed to investigate this phenomenon. METHODS: Dual gastric and esophageal pH tracings were analyzed from 40 dyspeptic patients. Dual pH electrode pull-through studies were performed in healthy volunteers to document regional variation in intragastric pH under both fasting and postprandial conditions. The squamocolumnar junction was identified using radio-opaque endoscopic clips. We also examined in vitro partitioning of gastric juice added to a homogenized fatty meal. RESULTS: The dual pH traces confirmed that esophageal refluxate was frequently more acidic than the body of the stomach after meals but not during fasting. The pull-through studies showed a pocket of acid at the gastroesophageal junction that escaped the buffering effect of meals, remaining highly acidic (median pH 1.6) compared with the body of the stomach (pH 4.7; P < 0.001). This proximal acid pocket extended from the cardia across the squamocolumnar junction 1.8 cm into the distal esophagus. The in vitro studies showed that acidic gastric juice could partition on top of a homogenized fatty meal. CONCLUSIONS: After eating, highly acidic unbuffered gastric juice is present at the gastroesophageal squamocolumnar junction and is likely to contribute to the high prevalence of disease at this site.

Adult↗
PubMed2000

Interleukin-1 polymorphisms associated with increased risk of gastric cancer.

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not.

Alleles↗
PubMed2000

Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori.

BACKGROUND & AIMS: Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. METHODS: H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. RESULTS: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. CONCLUSIONS: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects.

Achlorhydria↗