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Biomedical subjects

B Cryer

Publications and source records attributed to B Cryer.

At least 19 recordsLinked to original sources
PubMed2006

Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions.

BACKGROUND: Zollinger-Ellison syndrome and idiopathic hypersecretion are gastrointestinal hypersecretory conditions requiring long-term maintenance. AIMS: The safety and efficacy data for short-term (6-month) treatment of Zollinger-Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were previously published. This study extends the initial observations to 3 years. METHODS: The primary efficacy end point for this report was the control of gastric acid secretion in the last hour before the next dose of oral pantoprazole (acid output of <10 mmol/h; <5 mmol/h in subjects with prior acid-reducing surgery). Dose titration was permitted to a maximum of 240 mg per 24 h. RESULTS: Twenty-four subjects completed the study. The acid output of 28 of 34 subjects was controlled at initial enrolment. The mean acid output rates were <10 mmol/h throughout the 36 months of treatment for 90-100% of the patients. The majority of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36 months (acid output was controlled in 24 of 24 subjects). Pantoprazole was generally well tolerated with minimal adverse events reported. CONCLUSIONS: Maintenance oral pantoprazole therapy up to 3 years at dosages of 40-120 mg b.d. was effective and well tolerated in patients with Zollinger-Ellison syndrome and other hypersecretory conditions.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Upper gastrointestinal tolerability of once weekly alendronate 70 mg with concomitant non-steroidal anti-inflammatory drug use.

BACKGROUND: Both oral bisphosphonates and non-steroidal anti-inflammatory drugs have the potential to irritate the upper gastrointestinal mucosa, and are frequently used by the same patient population. AIM: To determine the rate of upper gastrointestinal adverse events with once weekly alendronate 70 mg and concomitant non-steroidal anti-inflammatory drug use. METHODS: A post hoc analysis was performed on 222 patients who received both medications concomitantly during a 3-month placebo-controlled study. A total of 450 (224 alendronate; 226 placebo) postmenopausal women and men with osteoporosis were randomized. Concomitant non-steroidal anti-inflammatory drug users were defined as patients who received > or =7 continuous days of any dose of a dual cyclo-oxygenase-1 and cyclo-oxygenase-2 inhibiting non-steroidal anti-inflammatory drug, a selective cyclo-oxygenase-2 inhibitor, or aspirin. A survival analysis was performed, and significance assessed. Logistic regression was used to assess consistency of treatment effect on rate of upper gastrointestinal adverse events across non-steroidal anti-inflammatory drug subgroups. RESULTS: Similar percentages of alendronate (52.7%) and placebo (46.0%) patients used non-steroidal anti-inflammatory drugs regularly. Among concomitant non-steroidal anti-inflammatory drug users, 11 alendronate and 11 placebo patients experienced upper gastrointestinal adverse events (9.3% and 10.8%, respectively, P = 0.744). Logistic regression revealed no significant interaction (P = 0.722) between alendronate and concomitant non-steroidal anti-inflammatory drug use. CONCLUSION: Based on this subgroup analysis, once weekly alendronate 70 mg used concomitantly with non-steroidal anti-inflammatory drugs, did not increase upper gastrointestinal adverse events relative to placebo over 3-months.

Aged↗
PubMed2003

Effect of cyclooxygenase-2 inhibition on human Helicobacter pylori gastritis: mechanisms underlying gastrointestinal safety and implications for cancer chemoprevention.

UNLABELLED: Cyclooxygenase (COX)-2 expression and prostaglandin production is increased by Helicobacter pylori infection. Non-selective COX inhibitors reduce prostaglandins and mucosal proliferation in infected mucosa and may reduce gastric cancer risk, but ulceration precludes their use. COX-2 inhibitors cause fewer ulcers and may be chemopreventive. Physiological studies of COX-2 inhibitors in humans with H. pylori infection have not been performed. AIM: To study the impact of COX-2 specific inhibition on gastric prostaglandin levels, H. pylori gastritis and proliferation. METHODS: Twenty infected (eight males, 12 females; age 38 +/- 1.8) and six uninfected (four males, two females; age 36 +/- 3.5) healthy volunteers received rofecoxib 25 mg daily for 14 days. Endoscopic biopsies were evaluated for prostaglandin E2 (PGE2) content, gastritis and proliferation. RESULTS: Before drug therapy, compared to uninfected, H. pylori-infected subjects had significantly higher: (a) gastric mucosal PGE2 (pg/mg tissue) in the gastric body and antrum, (b) H. pylori score in body and antrum and (c) mid-gland proliferation index in antrum and body. The COX-2 inhibitor did not significantly affect PGE2 levels, gastritis scores or proliferation indices in the body or antrum in the H. pylori-positive or -negative subjects. CONCLUSION: The predominant source of increased gastric PGE2 in H. pylori infection appears to be COX-1-derived. In non-ulcerated H. pylori gastritis, COX-2 inhibition does not affect cellular proliferation. Rofecoxib's lack of effect on gastric prostaglandin levels and proliferation in H. pylori-infected mucosa may explain the absence of an increased ulcer risk among COX-2 inhibitor users with H. pylori infection. The lack of significant effect on intermediate biomarkers raises uncertainty regarding the potential of specific COX-2 inhibitors for chemoprevention of gastric cancer.

Adult↗
PubMed2003

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

OBJECTIVE: Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. RESEARCH DESIGN AND METHODS: We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. RESULTS: Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. CONCLUSION: Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Alendronate↗
PubMed2001

Effects of low-dose aspirin on serum C-reactive protein and thromboxane B2 concentrations: a placebo-controlled study using a highly sensitive C-reactive protein assay.

OBJECTIVES: We performed a placebo-controlled study to evaluate the effect of low-dose aspirin on serum C-reactive protein (CRP) levels. BACKGROUND: Elevated circulating concentrations of CRP, an inflammatory marker, increase the risk of thrombotic cardiovascular diseases such as myocardial infarction (MI). Moreover, low-dose aspirin therapy has been reported to be more effective in preventing MI in men with higher CRP levels than it is in those with lower levels, raising the possibility that aspirin prevents thrombosis by reducing vascular inflammation. The effect of low-dose aspirin therapy on serum CRP levels in men has been addressed recently, but the results of the two studies conflict. METHODS: Effects of aspirin (81 mg every day or 325, 81 or 40 mg every-third-day given for 31 days) on serum CRP, using a highly-sensitive assay, and on serum platelet-cyclo-oxygenase (COX)-1-derived thromboxane (Tx) B2 concentrations were studied simultaneously in 57 healthy volunteers (30 men and 27 women). RESULTS: Trough platelet COX-1-derived serum Tx B2 concentrations decreased by 100% with daily aspirin and by 90%, 84% and 78% with 325, 81 and 40 mg aspirin every-third-day (p < 0.001). However, there were no significant changes in serum CRP levels from baseline with daily low-dose aspirin therapy, with any of the every-third-day aspirin regimens or with placebo treatment. CONCLUSIONS: Low doses of aspirin that markedly inhibit platelet COX-1 activity, as manifested by a profound decline in platelet-derived serum Tx B2 concentrations, have no detectable effect on serum CRP levels in healthy men and women.

Adult↗
PubMed2001

Peptic ulcer disease.

Peptic ulcer disease is a common gastrointestinal disease whose management and treatment has changed dramatically over the last 25 years. Treatment of peptic ulcer disease has evolved from dietary modifications and antacids to gastric acid suppression with H2-receptor antagonists and proton pump inhibitors to eradication of Helicobactor pylori infection. Treatment of patients infected with H pylori using antibiotics has changed the natural history of peptic ulcer disease. As a result of H pylori treatment and other unknown factors ulcer disease is declining and complications from ulcer disease have diminished significantly.

Antacids↗
PubMed2001

Mucosal defense and repair. Role of prostaglandins in the stomach and duodenum.

When considering the diseases of the stomach and duodenum, peptic ulcer disease has been the one of greatest clinical impact. Although there are several components that contribute mechanistically to ulcer disease, it is recognized that gastroduodenal mucosal prostaglandins play a central pathogenic role, especially in ulcers related to the use of NSAIDs. As a result of understanding the mechanisms of NSAID-induced ulceration, the crucial function that gastroduodenal mucosal prostaglandins have in mucosal defense and repair is appreciated. It now is held widely that mucosal prostaglandin deficiency increases susceptibility to ulcer formation and that exogenous administration of supplemental prostaglandins reduces ulcer risk. This article reviews the role that mucosal prostaglandins play in defense of the gastric and duodenal mucosa against injury and ulceration.

Age Factors↗
PubMed2001

Nonsteroidal anti-inflammatory drug gastrointestinal toxicity.

Toxic effects in the upper gastrointestinal tract, primarily complicated gastric and intestinal ulcers, are the most common undesirable effects of the nonsteroidal anti-inflammatory drugs. During the last several years, there have been several advances, both in the laboratory and clinically, toward reducing nonsteroidal anti-inflammatory drugs' gastrointestinal toxicity. Some of these important developments are the delineation of mechanisms of nonsteroidal anti-inflammatory drug-induced gastrointestinal toxicity, identification of groups at highest risk for development of nonsteroidal anti-inflammatory drug-induced gastrointestinal complications, recognition of co-therapies that could reduce nonsteroidal anti-inflammatory drug toxicity, and, most recently, development of classes of nonsteroidal anti-inflammatory drugs with improved gastrointestinal safety profiles. Many of these advances have occurred during the last year. This review focuses on several of the important recent observations that have improved understanding and safety of nonsteroidal anti-inflammatory drugs in the gastrointestinal tract.

Journal Article↗
PubMed2001

Role of Helicobacter pylori infection in gastroduodenal injury and gastric prostaglandin synthesis during long term/low dose aspirin therapy: a prospective placebo-controlled, double-blind randomized trial.

OBJECTIVES: Whether gastric infection with Helicobacter pylori increases the risk of gastric mucosal injury during long term/low dose aspirin therapy is unknown. We examined whether H. pylori infection enhances upper GI mucosal damage, assessed endoscopically, in volunteers given low dose aspirin. We studied 61 healthy men and women, 29 with and 32 without active H. pylori infection. METHODS: We treated volunteers for 45 days with a placebo or aspirin (either 81 mg every day or 325 mg every 3 days). Gastroduodenal mucosal damage was then assessed by endoscopy, as was gastric histology and ex vivo gastric mucosal prostaglandin E2 and F2alpha synthesis rates. RESULTS: Erosive disease from low dose aspirin (erosions and/or ulcers) occurred in 50% of H. pylori-infected volunteers and in 16% of their noninfected counterparts (p = 0.02). Aspirin caused a significantly higher average mucosal injury score in the gastric antrum in H. pylori-infected participants than in noninfected subjects (p = 0.03), and two H. pylori-infected subjects developed antral gastric ulcers. Subjects with H. pylori gastritis treated with the placebo had nearly 50% higher gastric mucosal prostaglandin (E2 plus F2alpha) synthesis rates than their noninfected counterparts (108 +/- 6 ng/g/min versus 75 +/- 6 ng/g/min, p < 0.001). Aspirin reduced mucosal prostaglandin synthesis to similar levels in infected and noninfected participants. CONCLUSIONS: Long term/low dose aspirin therapy led to more gastric mucosal damage when H. pylori gastritis was present than when it was absent, despite similar degrees of gastric mucosal prostaglandin depletion.

Adolescent↗
PubMed2001

A comparison of every-third-day versus daily low-dose aspirin therapy on serum thromboxane concentrations in healthy men and women.

Aspirin's antithrombotic effect is mediated predominately by inhibition of platelet cyclooxygenase-1, leading to a decline in serum thromboxane A2 concentrations. We performed a placebo-controlled, randomized, double-blind trial to determine whether aspirin could be given at 3-day intervals and still achieve potent serum thromboxane inhibition. One hundred nine healthy men and women with no recent exposure to aspirin and no contraindications to its use participated. Subjects received 325 mg, 81 mg, or 40 mg of plain aspirin every third day, with placebo on other days; 81 mg of aspirin every day; or placebo every day. Serum concentrations of thromboxane B2 (the metabolite of thromboxane A2) were measured at 3-day intervals during a 31-day treatment period, as well as 4, 7, and 14 days after treatment ended. Serum thromboxane B2 concentrations were nearly identical during treatment with 325 mg of aspirin every third day or 81 mg of aspirin per day (86% inhibition [84%, 89%] and 85% inhibition [73%, 96%], respectively). An aspirin dose of 81 mg every third day was nearly as potent (74% inhibition [70%, 79%]), whereas 40 mg of aspirin every third day achieved only 50% inhibition (40%, 60%). Every-third-day low-dose aspirin regimens (325 and 81 mg) deserve comparison with daily low-dose aspirin regimens in controlled clinical trials because the former regimens could prove to have equal efficacy with reduced toxicity.

Adolescent↗
PubMed2000

Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells.

Adenocarcinoma in Barrett's esophagus has been increasing in incidence at a rapid rate for more than two decades. Cyclooxygenase (COX)-2 appears to play an important role in gastrointestinal carcinogenesis, and COX-2 overexpression has been demonstrated both in esophageal adenocarcinomas and in the metaplastic epithelium of Barrett's esophagus. The aim of our study was to determine whether selective inhibition of COX-2 by NS-398 would alter the rates of cell growth and apoptosis in human Barrett's-associated esophageal adenocarcinoma cell lines. COX-1 and COX-2 expression in adenocarcinoma cell lines was determined using reverse transcription-PCR and Western blotting for mRNA and protein, respectively. Esophageal adenocarcinoma cell lines were treated with various concentrations of NS-398 (selective for COX-2 inhibition) and flurbiprofen (selective for COX-1 inhibition). Cell growth was compared in flurbiprofen-treated and untreated tumor cell lines; cell growth and apoptosis were compared in NS-398-treated and untreated tumor cell lines. COX-2 mRNA and protein were detected in two of three cell lines (SEG-1 and FLO); the third cell line, BIC-1, did not express COX-2 mRNA or protein under basal conditions or after stimulation with phorbol 12-myristate 13-acetate. Treatment with COX-1-selective concentrations of flurbiprofen did not affect cell growth in any of the three tumor cell lines. In contrast, treatment with COX-2-selective concentrations of NS-398 significantly suppressed cell growth and increased apoptosis in the cell lines that expressed COX-2 (SEG-1 and FLO), but not in the cell line that did not express COX-2 (BIC-1). We conclude that the administration of a selective inhibitor of COX-2 significantly decreases cell growth and increases apoptosis in Barrett's-associated adenocarcinoma tumor cells that express COX-2. These observations suggest a potential role for selective COX-2 inhibitors in the prevention and treatment of esophageal adenocarcinoma for patients with Barrett's esophagus.

Adenocarcinoma↗
PubMed2000

NSAID gastrointestinal toxicity.

Toxic effects in the upper gastrointestinal tract, primarily complicated gastric and intestinal ulcers, are the most common undesirable effects of the nonsteroidal antiinflammatory drugs (NSAIDs). During the last several years there have been several advances, both in the laboratory and clinically, toward reducing NSAIDs' gastrointestinal toxicity. Some of these important developments have been the delineation of mechanisms of NSAID-induced GI toxicity, identification of groups at highest risk for development of NSAID-induced gastrointestinal complications, recognition of co-therapies that could reduce NSAID toxicity, and, most recently, development of classes of NSAIDs that have an improved gastrointestinal safety profile. Many of these advances occurred during the last year. This review focuses on several of the important recent observations that have improved our understanding and the safety of NSAIDs in the gastrointestinal tract.

Journal Article↗
PubMed2000

Time course inhibition of gastric and platelet COX activity by acetylsalicylic acid in humans.

Aspirin causes peptic ulcers predominately by reducing gastric mucosal cyclooxygenase (COX) activity and prostaglandin synthesis. Because aspirin circulates for only a few hours, we hypothesized that aspirin's inhibitory effect on gastric COX activity must be prolonged. We performed a placebo-controlled experiment in healthy humans to determine the duration of inhibition of aspirin on gastric mucosal COX activity (PGE(2) and PGF(2alpha) synthesis rates). Recovery of gastric COX activity after stopping aspirin was slow and linear. Seventy-two hours after 325-mg aspirin, gastric COX activity was still reduced by 57% (P < 0.001). Duration of inhibition of gastric COX activity was estimated to be 7-8 days after 325-mg aspirin and 5 days after 81-mg aspirin. Recovery of gastric prostaglandin synthesis after 325-mg but not after 81-mg aspirin occurred at slower rates in subjects with Helicobacter pylori-associated gastritis than in those with normal histology. In conclusion, aspirin inhibits gastric COX activity for much longer than predicted from its pharmacokinetic profile, explaining why aspirin at widely spaced intervals is ulcerogenic.

Adolescent↗
PubMed1999

Aspirin absorption rates and platelet inhibition times with 325-mg buffered aspirin tablets (chewed or swallowed intact) and with buffered aspirin solution.

Large clinical trials such as the second International Study of Infarct Survival routinely gave patients with myocardial infarction a chewed aspirin, yet there are no data to show whether chewing of aspirin is better, or worse, than swallowing a whole tablet. We performed a randomized, placebo-controlled study to determine whether chewing aspirin or administering it in solution accelerates its absorption and antiplatelet activity. On separate days, 12 fasting volunteers ingested 325 mg of buffered aspirin, either by chewing a tablet for 30 seconds before swallowing it with 4 ounces of water, swallowing a whole tablet with 4 ounces of water, or drinking 4 ounces of Alka Seltzer. Frequent blood samples were obtained for serum aspirin, salicylate, and thromboxane B2 (TxB2) concentrations. With all formulations of aspirin, serum TxB2 decreased 50% when the plasma aspirin concentration reached approximately 1,000 ng/ml. A 50% and 90% decrease in serum TxB2 occurred more quickly after chewing a tablet than after a tablet was swallowed whole. For example, the t 50% for serum TxB2 inhibition was 5.0 +/- 0.6 minutes with the chewed tablet versus 12.0 +/- 2.3 minutes when the tablet was swallowed (p = 0.01). A 50% decrease in serum TxB2 occurred 7.6 +/- 1.2 minutes after Alka Seltzer solution (p = 0.04 vs chewing a tablet; p = 0.13 vs swallowing a whole tablet). Chewing an aspirin tablet is the most effective way of accelerating absorption of aspirin into the blood and shortening the time required for an antiplatelet effect.

Absorption↗
PubMed1999

Effects of very low dose daily, long-term aspirin therapy on gastric, duodenal, and rectal prostaglandin levels and on mucosal injury in healthy humans.

BACKGROUND & AIMS: The safety of low-dose daily aspirin therapy in the gastrointestinal tract is uncertain. Our objectives were to evaluate the long-term effects of very low daily aspirin doses in the gastrointestinal tract and effects on platelet-derived serum thromboxane levels in volunteers. METHODS: Subjects were randomized to receive 10 mg (n = 8), 81 mg (n = 11), or 325 mg (n = 10) aspirin daily for 3 months. Before administration of aspirin, all subjects underwent gastroduodenoscopy, and most underwent proctoscopy for assessment of mucosal injury and prostaglandin content. After 1.5 and 3 months, subjects again underwent gastroduodenoscopy and, at 3 months, another proctoscopy. RESULTS: Each aspirin dose (even 10 mg) significantly reduced gastric mucosal prostaglandin levels, to approximately 40% of the baseline value. All three doses also induced significant gastric injury, and 325 mg caused duodenal injury. Three subjects developed gastric ulcers, 1 while taking 10 mg/day of aspirin. Furthermore, aspirin at 81 mg/day and 325 mg/day (but not 10 mg/day) significantly reduced duodenal mucosal prostaglandin levels to approximately 40% of the baseline value. Only 325 mg of aspirin per day significantly reduced rectal mucosal prostaglandin levels to approximately 60% of the baseline value. Serum thromboxane levels were inhibited 62%, 90%, and 98% with 10, 81, and 325 mg of aspirin. CONCLUSIONS: The findings explain aspirin's predominant gastric toxicity and question the safety of even 10 mg of aspirin daily.

Adult↗
PubMed1999

Nonsteroidal anti-inflammatory drug gastrointestinal toxicity.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently the most widely used class of therapeutic agents. By inhibiting cyclooxygenase (COX) and reducing gastrointestinal prostaglandins, they provide effective analgesia and suppress inflammation in a variety of conditions. However, through the same mechanism of COX inhibition, they also cause significant gastrointestinal toxicity. One of the most common methods to reduce NSAID-induced gastrointestinal toxicity has been to co-prescribe prophylactic therapies such as acid-reducing agents or the synthetic prostaglandin analogue, misoprostol. More recently safer NSAIDs, such as the COX-2 specific NSAIDs or the nitric oxide-releasing NSAIDs, have been developed or are currently in development. This article reviews mechanisms of NSAID-induced gastrointestinal toxicity. Also reviewed are data on the gastrointestinal consequences of the prophylatic co-therapies, COX-2 specific NSAIDs and nitric oxide-releasing NSAIDs.

Journal Article↗