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Biomedical subjects

B Cryer

Publications and source records attributed to B Cryer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Influence of H. pylori infection on meal-stimulated gastric acid secretion and gastroesophageal acid reflux.

Gastric acid secretion, gastrin release, gastric emptying, and gastroesophageal acid reflux were measured in asymptomatic individuals before and after elimination of Helicobacter pylori gastritis. After basal gastric acid secretion and serum gastrin concentrations were measured, meal-stimulated gastric acid secretion and gastrin release were assessed during in vivo intragastric titration to pH 3. Experiments were repeated 4 wk after treatment with lansoprazole, amoxicillin, and clarithromycin. Esophageal pH was also monitored for 24 h before and after therapy. Basal gastric acidity increased approximately 20 mmol/l in subjects whose infection was eradicated (P < 0.05) but not in those with persistent infection. Basal and meal-stimulated gastric acid secretion did not change after H. pylori eradication, despite a 41% reduction in meal-stimulated gastrin release (P < 0.05). Gastroesophageal acid reflux increased two- to threefold after successful treatment (P < 0. 05) but did not change in subjects with persistent infection. Thus elimination of H. pylori gastritis increases gastric acidity, probably by reducing nonparietal alkaline secretion, and this may facilitate gastroesophageal acid reflux.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Gastrointestinal side effects of nonsteroidal anti-inflammatory drugs.

The gastrointestinal (GI) tract is the most common location for side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs may cause problems in any part of the GI tract, from the esophagus to the rectum. The severity of these side effects ranges from nuisance symptoms such as dyspepsia to life-threatening ulcer complications. The diagnosis, treatment, and prevention of the various GI side effects of these commonly prescribed drugs are reviewed in this article.

Animals↗
PubMed1998

Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs.

PURPOSE: Both isoforms of cyclo-oxygenase, COX-1 and COX-2, are inhibited to varying degrees by all of the available nonsteroidal anti-inflammatory drugs (NSAIDs). Because inhibition of COX-1 by NSAIDs is linked to gastrointestinal ulcer formation, those drugs that selectively inhibit COX-2 may have less gastrointestinal toxicity. We measured the extent to which NSAIDs and other anti-inflammatory or analgesic drugs inhibit COX-1 and COX-2 in humans. SUBJECTS AND METHODS: Aliquots of whole blood from 16 healthy volunteers were incubated ex vivo with 25 antiinflammatory or analgesic drugs at six concentrations ranging from 0 (control) to 100 microM (n = 5 for each). Blood was assayed for serum-generated thromboxane B2 synthesis (COX-1 assay) and for lipopolysaccharide-stimulated prostaglandin E2 synthesis (COX-2 assay). In addition, gastric biopsies from the same volunteers were incubated with each drug ex vivo and mucosal prostaglandin E2 synthesis measured. RESULTS: Inhibitory potency and selectivity of NSAIDs for COX-1 and COX-2 activity in blood varied greatly. Some NSAIDs (eg, flurbiprofen, ketoprofen) were COX-1 selective, some (eg, ibuprofen, naproxen) were essentially nonselective, while others (eg, diclofenac, mefenamic acid) were COX-2 selective. Inhibitory effects of NSAIDs on gastric prostaglandin E2 synthesis correlated with COX-1 inhibitory potency in blood (P < 0.001) and with COX-1 selectivity (P < 0.01), but not with COX-2 inhibitory potency. Even COX-2 "selective" NSAIDs still had sufficient COX-1 activity to cause potent inhibitory effects on gastric prostaglandin E2 synthesis at concentrations achieved in vivo. CONCLUSION: No currently marketed NSAID, even those that are COX-2 selective, spare gastric COX activity at therapeutic concentrations. Thus, all NSAIDs should be used cautiously until safer agents are developed.

Adult↗
PubMed1998

The advent of highly selective inhibitors of cyclooxygenase--a review.

Cyclooxygenase (COX) exists in two isoforms, COX-1 and COX-2, COX-1 is present and is constitutively expressed in most cells and tissues, whereas COX-2 is felt to principally mediate inflammation. However, this distinction appears to be challenged by recent observations. This review addresses the roles of COX-1 and COX-2 isoforms in physiologic and pathophysiologic states and reviews potential therapeutic roles for selective COX inhibitors.

Adenocarcinoma↗
PubMed1998

Effects of Helicobacter pylori gastritis on gastric secretion in healthy human beings.

Helicobacter pylori gastritis is common, but effects on gastric secretion are not well understood. We measured basal and pentagastrin-stimulated gastric acidity, pepsin activity, and fluid output, as well as serum gastrin concentrations and H. pylori antibody levels, before and after treatment of H. pylori gastritis in 28 men and women. Subjects were studied before and 1 and 3 mo after a course of bismuth, metronidazole, and tetracycline. Elimination of H. pylori gastritis, accomplished in 14 subjects, increased basal and pentagastrin-stimulated gastric acidity (by 15 meq/l) and basal acid output significantly (by 2.1 meq/h 1 mo after therapy). Elimination of H. pylori had an opposite effect on pepsin secretion, significantly decreasing pepsin output by 30%. Elimination of H. pylori significantly reduced nonparietal fluid output by 35%, without affecting fluid output from parietal cells. Serum gastrin and H. pylori antibody levels declined significantly after elimination of H. pylori. None of these changes was observed in 14 subjects whose H. pylori gastritis was resistant to antimicrobial therapy. In summary, eradication of H. pylori infection increases gastric acidity by reducing nonparietal gastric secretion from peptic and other cells.

Adult↗
PubMed1998

Effects of age on gastric alkaline and nonparietal fluid secretion in humans.

Little is known about the effect of age on gastric alkaline and nonparietal secretion. Using a previously validated technique, we prospectively measured gastric HCO3- and nonparietal volume secretion, as well as secretion of H+, Na+, K+, and Cl-, in 114 healthy human beings over a wide age range (18-82 years). Each subject had normal oxyntic mucosal histology, was on no medication known to affect gastric secretion, and was studied under both basal (fasting) conditions and following stimulation of gastric H+ secretion by pentagastrin. There was a significant (p < 0.05) decline in gastric HCO3-, Na+, and nonparietal fluid secretion with advancing age, but not in H+, K+, Cl- or parietal fluid secretion. As a consequence of reduced gastric HCO3- and nonparietal fluid secretion, mean H+ concentrations in gastric juice increased significantly with advancing age. Thus, in healthy subjects with normal gastric histology, advancing age was associated with a significant decline in gastric HCO3-, Na+, and nonparietal fluid secretion, resulting in an increase in gastric acidity (H+ concentration).

Adolescent↗
PubMed1996

Effects of aging and gastritis on gastric acid and pepsin secretion in humans: a prospective study.

BACKGROUND & AIMS: Recent studies suggesting that gastric secretion does not decrease with aging included few elderly individuals and measured only acid secretion. The aims of this study were to measure gastric acid and pepsin output in 206 health Americans (age range, 18-98 years) and to compare secretion rates with gastric histology. METHODS: Immediately after basal and pentagastrin-stimulated acid and pepsin outputs were measured, oxyntic biopsy samples were obtained. RESULTS: Gastric acid and pepsin output rates were similar in young (age range, 18-34 years) and middle-aged (age range, 35-64 years) groups. Stimulated acid output was reduced approximately 30% in the elderly (age range, 65-98 years). However, after adjustment for histology, Helicobacter pylori infection, and other variables, age had no independent effect on acid output. The decline in acid secretion in the elderly was primarily related to a higher prevalence of chronic atrophic gastritis and a lower prevalence of smoking. Pepsin output was reduced by approximately 40% in the elderly. After adjustment for other variables, age remained a robust predictor of reduced pepsin output. CONCLUSION: Although advancing age has no independent effect on gastric acid secretion, it is associated with reduced pepsin output independent of atrophic gastritis, H. pylori infection, and smoking.

Adolescent↗
PubMed1996

Racial differences in gastric function among African Americans and Caucasian Americans: secretion, serum gastrin, and histology.

We measured gastric juice fluid output, acidity, tonic strength (osmolality), and pepsin concentrations basally and after the injection of pentagastrin in 120 healthy African Americans and 60 Caucasian Americans of similar age and gender. Sera for basal gastrin concentration and IgG for antibody to Helicobacter pylori (Hp) organisms also were obtained, as were gastric body mucosal biopsies to ascertain the presence or absence of Hp or gastritis. Gastric juice hydrogen ion concentrations and osmolality were significantly lower in African Americans than in Caucasians. At the same time, African Americans had significantly higher gastric juice fluid outputs than did Caucasians. From measurements of gastric juice fluid output, acidity, and osmolality, we used a previously validated method for calculating gastric HCO3- and H+ secretion, as well as nonparietal and parietal fluid secretion. Gastric HCO3 secretion and nonparietal fluid were significantly higher in African Americans, while H+, parietal fluid, and pepsin secretion rates were nearly identical in the two racial groups. Basal serum gastrin concentrations and antibody titers to Hp also were significantly higher in African Americans (p < .001). Mucosal biopsies demonstrated a much higher prevalence of Hp infection and chronic active superficial gastritis in African Americans than Caucasians (p < .001). When only Hp-negative subjects were considered, racial differences in gastric secretion and basal serum gastrin concentration were still present. The mechanism or mechanisms causing higher gastric bicarbonate and nonparietal fluid secretion and for higher serum gastrin concentrations in African Americans remains to be elucidated.

Adult↗
PubMed1994

Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury.

OBJECTIVE: To determine if a dose of aspirin exists that might inhibit thromboxane-dependent platelet function without causing gastric mucosal injury, we studied the effects of a wide range of doses of aspirin (3 mg/d to 2600 mg/d) on gastric juice prostaglandins (PGE2 and PGF2 alpha), on serum thromboxane B2, and on stomach mucosal injury as reflected by gastric juice hemoglobin and DNA concentrations. DESIGN: A randomized, placebo-controlled study. SETTING: Research laboratory at a Veterans Affairs medical center. PARTICIPANTS: 16 healthy volunteers (5 men and 11 women). INTERVENTION: In the first part of the study, volunteers received placebo; aspirin, 324 mg/d; 1300 mg/d; or 2600 mg/d for 2 days. In the second part, volunteers received placebo; aspirin, 3 mg/d; 10 mg/d; 30 mg/d; or 81 mg/d for 8 days. MEASUREMENTS: Gastric juice PGE2 and PGF2 alpha, hemoglobin and DNA concentrations; gastric juice volume and acidity; and serum salicylate and thromboxane B2 concentrations. RESULTS: In the first part, significant and similar (approximately 50%) inhibition of gastric juice prostaglandin output was observed with daily aspirin doses of 324 to 2600 mg. However, a significant increase in gastric juice hemoglobin output occurred only with 2600 mg/d. In the second part, significant inhibition (approximately 50%) of gastric PGE2 output was noted at a daily aspirin dose of 30 mg. Lower aspirin doses did not reduce PGE2 output significantly, although these doses did significantly reduce serum thromboxane B2 in a dose-related manner. CONCLUSIONS: Aspirin can significantly reduce serum thromboxane B2 at doses of 3 mg/d or 10 mg/d, which are significantly below the threshold dose for significant gastric prostaglandin inhibition and acute stomach mucosal injury.

Adult↗
PubMed1992

Factors influencing gastroduodenal mucosal prostaglandin concentrations: roles of smoking and aging.

OBJECTIVE: To evaluate behavioral, demographic, clinical, and histologic variables that independently influence gastroduodenal mucosal prostaglandin concentrations. DESIGN: Prospective study. SETTING: A clinical research laboratory located in a Department of Veterans Affairs hospital. PATIENTS: Fifty-two healthy adults who had no history of peptic ulcer disease and who were not receiving nonsteroidal anti-inflammatory drugs. MEASUREMENTS: Mucosal biopsy specimens were obtained endoscopically from the stomach (body and antrum) and the duodenum (bulb and postbulbar area). Mucosal extracts from each of these four regions were assessed by radioimmunoassay to determine prostaglandin E2 and prostaglandin F2 alpha concentrations. Specimens were also examined histologically for inflammation and the presence of Helicobacter pylori. A multivariate linear regression model was used to determine which behavioral, demographic, and histologic variables significantly and independently influenced gastroduodenal mucosal prostaglandin concentrations. RESULTS: Smoking and older age were independently associated with lower prostaglandin concentrations in all four mucosal regions (P = 0.0001 to P = 0.05). Compared with results in young nonsmokers, mucosal prostaglandin concentrations were reduced by 70% to 80% in older smokers. Gender, alcohol use, endoscopic appearance, dyspeptic symptoms, mucosal inflammation, and the presence of H. pylori had no consistent effect on prostaglandin content. CONCLUSION: Smoking and older age are associated with significantly reduced gastric and duodenal prostaglandin concentrations. These observations may help explain the predisposition to ulcer disease in smokers and older persons.

Adult↗
PubMed1992

Gastric and duodenal mucosal prostaglandin concentrations in gastric or duodenal ulcer disease: relationships with demographics, environmental, and histological factors, including Helicobacter pylori.

We measured gastric and duodenal mucosal prostaglandin concentrations in 69 patients with active or inactive duodenal or gastric ulcer disease and 26 non-ulcer controls. Each underwent endoscopy enabling us to obtain multiple biopsies from the gastric body and antrum and from the duodenal bulb and postbulbar duodenum for measurement of mucosal prostaglandin concentrations, as well as a single biopsy from each region for mucosal histology. Using a multivariate linear regression model, we found that neither gastric nor duodenal ulcer disease significantly affected gastric or duodenal mucosal prostaglandin concentrations. Mucosal prostaglandin concentrations were similar at the edge of the ulcer and in the adjacent non-ulcerated mucosa. Neither gender symptoms, smoking, use of H2-receptor antagonists, disease activity, nor Helicobacter pylori infection had an independent effect on mucosal prostaglandins in any region. Gastritis in the body of the stomach was associated with significantly higher prostaglandins, while older age was associated with significantly lower gastric and duodenal prostaglandins. Gastroduodenal mucosal prostaglandins are thus not altered in patients with active or inactive peptic ulcer disease, even when multiple demographic and histologic variables are taken into consideration.

Age Factors↗
PubMed1992

Effect of aging on gastric and duodenal mucosal prostaglandin concentrations in humans.

The effect of aging on gastric and duodenal mucosal prostaglandins has not been reported. Gastric and duodenal mucosal prostaglandin concentrations were measured in 46 healthy adults, 35 of whom were relatively young (21-40 years old) and 11 of whom were considerably more elderly (aged 52-72 years). Mucosal biopsy specimens were obtained endoscopically from the fundus, antrum, duodenal bulb, and postbulbar duodenum, and extracts were assayed for prostaglandin F2 alpha and E2 concentrations by radioimmunoassay. Older age was associated with significantly lower fundic, antral, and post-bulbar duodenal prostaglandin concentrations. A second experiment was performed in 20 additional subjects (9 younger, 11 older) to determine whether lower mucosal concentrations in older subjects were reproducible and, if so, whether reduced gastric mucosal prostaglandins would have a physiological counterpart, namely increased gastric acid secretion. As in the original experiment, fundic, antral, and postbulbar mucosal prostaglandin levels were significantly lower in older subjects than in younger subjects. Mean basal acid output was significantly higher in older than younger subjects (9.8 +/- 2.5 vs. 4.8 +/- 1.6 mmol/h). It is concluded that gastric and duodenal prostaglandin concentrations decline with aging in humans and that the decline in fundic mucosal prostaglandins is associated with an increase in gastric acid secretion.

Adult↗
PubMed1992

Effects of nonsteroidal anti-inflammatory drugs on endogenous gastrointestinal prostaglandins and therapeutic strategies for prevention and treatment of nonsteroidal anti-inflammatory drug-induced damage.

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for pain relief and treatment of arthritis, they can induce gastric and duodenal ulcers and life-threatening complications. The mechanisms of their anti-inflammatory action and their gastroduodenal toxic effects are related, in part, to inhibition of prostaglandin synthesis. This review article discusses prostaglandins, their functions in the gastrointestinal tract, anti-inflammatory actions of NSAIDs, and mechanisms by which NSAIDs produce gastroduodenal ulcers. Also reviewed are risk factors associated with the development of NSAID-related ulcers and pharmacologic strategies for the prevention and treatment of NSAID-induced ulcers.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Comparison of salsalate and aspirin on mucosal injury and gastroduodenal mucosal prostaglandins.

The effects of a 7.5-day course of orally administered salsalate (3.0 g/day), aspirin (3.9 g/day), or placebo on gastroduodenal mucosal injury, mucosal prostaglandin content, and plasma prostaglandin concentrations in healthy, asymptomatic human volunteers were examined. Mean serum salicylate concentrations after these doses of salsalate and aspirin were nearly identical (approximately 15 mg/dL). When the gastroduodenal mucosa was assessed endoscopically 1 hour after the final dose of medication, there was minimal mucosal injury in placebo-treated or salsalate-treated subjects and considerable injury in the stomach and duodenum of aspirin-treated subjects (P less than 0.001, aspirin vs. salsalate or placebo). In both the stomach and duodenum, aspirin lowered mucosal prostaglandin F2a and E2 content by greater than 90% (P less than 0.001), whereas salsalate produced no significant change. Aspirin also lowered plasma prostaglandin F2a concentrations by 58% +/- 6%, whereas salsalate lowered them by only 11% +/- 9% (P less than 0.001). Thus, the nonacetylated salicylate, salsalate, produced much less gastroduodenal mucosal damage than aspirin at equivalent serum salicylate concentrations, possibly because salsalate did not inhibit mucosal prostaglandin synthesis.

Adult↗
PubMedDate not supplied

Role of seroconversion in confirming cure of Helicobacter pylori infection.

CONTEXT: The role of serologic testing to confirm cure of Helicobacter pylori infection after antimicrobial therapy is not completely defined. OBJECTIVE: To determine the utility of serologic testing in confirming cure of H pylori infection more than 1 year after therapy. DESIGN: A prospective, before-after interventional trial. SETTING: An outpatient clinical research laboratory in an academic, urban Veterans Affairs medical center. PARTICIPANTS: Twenty-three otherwise healthy men and women with active H pylori infection demonstrated by gastric biopsy and with positive H pylori serologic findings. INTERVENTION: A 14-day course of bismuth, tetracycline, and metronidazole. MAIN OUTCOME MEASURES: Determination of IgG serum antibodies to H pylori at baseline, 1 month, 3 months, and approximately 18 months after completion of therapy compared with serial gastric mucosal biopsy specimens with stains for H pylori and for histologic examination as the criterion standard. RESULTS: Fifteen (65%) of 23 subjects were cured of their H pylori infection as assessed by gastric biopsy, with elimination of gastritis; median antibody levels declined from 92.5 U/mL at baseline to undetectable levels at 18 months. The other 8 subjects (35%) were not cured and had persistent gastritis at 18 months; median antibody levels declined from 130.6 U/mL at baseline to 89.7 U/mL at 18 months. Sensitivity and specificity of seroconversion (from a positive to negative test result) in detecting cure of H pylori infection were 60% and 100%, respectively. CONCLUSION: Undetectable antibody levels beyond the first year of therapy accurately confirm cure of H pylori infection in initially seropositive healthy subjects, with reasonable sensitivity.

Adult↗