Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It remains controversial whether the harmful effects of Helicobacter pylori (Hp) and nonsteroidal antiinflammatory drugs (NSAIDs) are additive. We studied the effects of Hp (virulent and nonvirulent strains) and NSAIDs, alone or in combination, on apoptosis and proliferation of gastric epithelial cells in nonulcer dyspepsia (NUD) patients. Forty-four (25 Hp-positive and 19 Hp-negative) consecutive Chinese NUD patients with rheumatoid arthritis who had taken continuously NSAIDs for more than three months were recruited for this study. Another 41 (20 Hp-positive and 21 Hp-negative) NUD patients not on any NSAIDs were included as controls. All patients underwent a gastroscopy examination and gastric biopsies. Hp infection was confirmed by CLOtest, anti-Hp ELISA, and [13C]urea breath test. The CagA status was determined by the anti-CagA antibody assay. The degree of gastritis, apoptosis, and proliferation indices were determined with H&E staining, terminal uridine deoxynucleotidyl nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) immunostaining methods, respectively. A significantly higher apoptosis was observed in subjects who had Hp infection or had been consuming NSAIDs when compared with the controls. Unlike NSAID-treated subjects, patients with Hp infection were shown to have significantly enhanced cell proliferation. However, the increased apoptosis and proliferation in Hp-positive subjects were reversed by also taking NSAIDs. No correlation was found between apoptosis and proliferation in all the study groups. There was no association found between CagA expression or degree of gastritis with cell proliferation or apoptosis. It was demonstrated at the cellular level that NSAIDs could abrogate apoptosis or proliferation effects induced by Hp. Furthermore, the latter effects appeared not to be influenced by the virulent nature of the Hp strains.
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PMID:Nonsteroidal antiinflammatory drugs could reverse Helicobacter pylori-induced apoptosis and proliferation in gastric epithelial cells. 975 58

In this review, we provide a conceptual framework of the ideal pharmacoeconomic model for nonsteroidal anti-inflammatory drug (NSAID) use in rheumatoid arthritis, together with a review of selected literature focusing on those areas identified in our model. An ideal pharmacoeconomic model fully accounts for the benefits and costs of this therapy. The benefits include: decreased pain and swelling; increased functional status, which may in turn lead to increased earnings potential; and decreased use of adjunctive therapies. The costs include costs for drug acquisition and administration, monitoring and treatment for adverse effects, as well as preventive measures. Noneconomic 'costs' (i.e. losses in quality of life and/or functional status) must also be included in this equation. Our literature review led to the following conclusions. NSAIDs are highly effective agents for the control of musculoskeletal pain and inflammation, and as such are among the most widely used drugs worldwide. It is well recognised that marked improvements in quality of life occur among arthritic patients receiving NSAIDs. Although careful patient selection and monitoring for potential adverse effects is essential, these drugs are well tolerated by most patients. NSAID-induced gastrointestinal events, ranging from dyspepsia to severe complications that can lead to hospitalisation, surgery and death, are reported more commonly than adverse effects from any other class of drugs. These events represent a substantial economic burden to society and have well documented negative effects on quality of life. Although misoprostol (a prostaglandin analogue) prevents the development of clinically defined NSAID-associated ulcers, its effectiveness on clinically important outcomes such as haemorrhage and perforation is somewhat more modest. Furthermore, there is evidence that some patients may experience substantial losses in quality of life because of the adverse effects of medication (particularly diarrhoea). Therefore, the widespread use of misoprostol prophylaxis not only has important economic consequences, but has important consequences for quality of life. More research is needed to address the critical trade-offs between cost and quality of life that are inherent in the use of NSAIDs.
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PMID:Economic and quality-of-life impact of NSAIDs in rheumatoid arthritis: A conceptual framework and selected literature review. 1016 78

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used successfully by many patients for the treatment of the signs and symptoms of arthritis, and other painful and inflammatory disorders. However, traditional nonselective NSAIDs that inhibit COX-1 and COX-2 lead to a state of propensity for gastric and duodenal ulcer disease and ulcer complications. The point prevalence of endoscopic ulcers ranges from 14 to 44% of patients using NSAIDs. Moreover, it is estimated that 1.46-1.90% of chronic NSAID users develop serious upper gastrointestinal (UGI) toxicity annually, most notably UGI bleeding, gastric/duodenal obstruction or ulcer perforation. In the USA, it has been estimated that 107,000 hospitalisations and 16,500 deaths occur annually related to the use of nonselective NSAIDs. Because these ulcer complications are often not heralded by chronic symptoms of dyspepsia, symptoms alone are not sufficient to guide long-term management of NSAID-related toxicity. Instead, prophylactic and preventive therapies are recommended in patients at above-average and high risk. Epidemiological data have identified that patients with a past history of ulcer disease, past history of UGI bleeding, greater age, concomitant corticosteroid use, and those who use higher doses and multiple NSAIDs fall into this category. Other risk factors of lesser importance have also been identified. A controversial issue remains regarding the possible increased risk of NSAID-associated ulcers and ulcer complications in patients who are infected with Helicobacter pylori. Prophylactic therapies have been evaluated primarily in randomised clinical trials, with the rate of endoscopic ulcers as the primary endpoint. It is assumed, but not proven, that these endoscopic ulcer rates are surrogate markers for gastrointestinal toxicity and are predictive of the rate of significant UGI adverse events. In the only outcomes trial to date, it was reported that misoprostol (200 microg 4 times daily) caused an approximately 50% reduction in serious UGI adverse events in a large 6-month trial involving rheumatoid arthritis patients. In parallel, this approximates the 50% reduction of endoscopic ulcers seen in randomised controlled trials using misoprostol. While H2 receptor antagonists are ineffective agents at traditional doses, proton pump inhibitors have been clearly shown to reduce the rate of endoscopic ulcers in several trials. In fact, the efficacy approximates to the efficacy seen with misoprostol. Beyond efficacy and in practical terms, the choice of optimal prophylaxis should take into consideration patient compliance, patient satisfaction, side-effects and cost.
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PMID:Who needs prophylaxis of nonsteroidal anti-inflammatory drug-induced ulcers and what is optimal prophylaxis? 1092 93

Rheumatoid arthritis and osteoarthritis are prevalent and costly conditions. A large proportion of the direct costs associated with these conditions relates to management of iatrogenic side effects. The cyclooxygenase (COX)-2-specific inhibitors lead to equivalent control of pain and disability compared with traditional NSAIDs. However, the COX-2-specific inhibitors have significant potential to reduce health-care costs, principally through the reduction of side effects. These cost savings are most likely to be realized through reductions in costs associated with dyspepsia and upper gastrointestinal ulcers and bleeding. Reduced indirect costs through improved disability scores and improved health-related quality of life are also predictable with the use of COX-2-specific inhibitors. This is accomplished without the attendant increase in risk to the gastrointestinal tract associated with traditional NSAIDs.
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PMID:The economic implications of cyclooxygenase-2-specific inhibitors. 1117 51

Our goal was to evaluate the state of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis (RA), before the introduction of the coxibs. The prerequisite for inclusion was the presence of RA (ACR criteria) plus therapy with an NSAID with or without a disease modifying antirheumatic drug (DMARD). A total of 368 consecutive RA patients (81% women) from the outpatient clinic at the Vienna General Hospital were included. Rheumatoid factor was positive in 62%, the patients' mean age was 60 +/- 14 years. The period of observation was 1972-1998. Seventy-seven per cent of the patients had DMARD and NSAID therapy. NSAID therapy was dominated by diclofenac, accounting for 60% of all therapies. Eighteen other substances were applied more rarely. All NSAIDs together were given for 768 patient years (with a mean duration of therapy of 17 years +/- 21 months). Seventy-two per cent of the patients received GI-protective therapy mainly with histamine antagonists and sucralfate while on nonsteroidal therapy. NSAID toxicity mostly affected the GI tract. There was a similar incidence of GI-related adverse events between patients with and patients without GI protection, mainly dyspepsia and nausea. NSAIDs have the potential to cause adverse events in the GI tract. Therapy with histamine antagonists or sucralfate did not reduce the patients' rate of gastrointestinal adverse events.
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PMID:Advances in anti-inflammatory therapy. 1189 47

BACKGROUND: Patients with rheumatoid arthritis (RA) frequently develop dyspepsia which may be due to peptic ulceration. There have been conflicting published data on the possible interactive roles of nonsteroidal anti-inflammatory drugs (NSAIDs) and colonisation of the gastric antrum with Helicobacter pylori in the development of peptic ulceration. METHODS: We have prospectively assessed the prevalence of peptic ulcers in dyspeptic RA patients and investigated the factors responsible. We endoscoped 100 RA patients comparing the endoscopic findings to those in 100 age- and sex-matched dyspeptic control subjects. Data on NSAID consumption and Helicobacter colonisation were collected for each patient. RESULTS: Endoscopic evidence of peptic ulceration was found in 29 RA patients and in 16 of the control subjects (P=0.03). Multiple ulcers (>2) were found in significantly more RA patients than in controls (10 vs. 2). NSAIDs were being used by 60 RA patients and 22 controls (P<0.001). Helicobacter was found in 41 RA patients and in 33 controls (P=NS). The consumption of NSAIDs conferred a relative risk (RR) of ulceration of 8.67 (1.19-62.87), while the presence of Helicobacter gave a RR for ulcers of 3.71 (0.37-37.35) in RA patients. The RR for the combination of NSAID consumption and Helicobacter colonisation was 14.44 (2.05-101). The corresponding RRs for the dyspeptic controls were 2.13, 1.57 and 1.42 (all P=NS). CONCLUSIONS: Rheumatoid patients have more major and more multiple pathology than age-, sex- and symptom-matched controls. This is due mainly to their increased consumption of NSAIDs. The prevalence of Helicobacter was no greater in RA patients than in controls, but Helicobacter infection increased the risk of NSAID-induced ulceration.
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PMID:What effect does Helicobacter pylori infection have on the risk of peptic ulceration in patients receiving NSAIDs for rheumatoid arthritis? 1206 24

Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic conditions requiring long-term therapy for pain relief. Currently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) provide symptomatic efficacy, but are frequently associated with gastrointestinal (GI) toxicities such as dyspepsia and ulcerations. In a small but significant number of cases, complications including perforations and massive bleeding develop and these may be fatal. A desirable therapeutic strategy would maintain efficacy while minimizing gastric intolerance. Two potential approaches have been suggested: (i) administration of NSAIDs in combination with gastroprotective compounds; or (ii) administration of potentially safer anti-inflammatory compounds which act via selective inhibition of cyclooxygenase-2 (COX-2). The selective COX-2 inhibitors rofecoxib and celecoxib consistently demonstrate efficacy comparable to conventional NSAIDs in patients with RA and OA, but have a significantly reduced propensity to cause GI toxicity. In many cases, the gastric effects of therapeutically active doses of COX-2 inhibitors are indistinguishable from placebo. The safety benefits of COX-2 inhibitors given alone appear similar to combined therapy with conventional NSAIDs and gastroprotective agents. Findings warrant the consideration of COX-2 inhibitors as first-line therapy in patients requiring long-term pain relief.
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PMID:Clinical experience with cyclooxygenase-2 inhibitors. 1217 76

To appraise the efficiency of complemental antacid administration in preventing and reducing digestive disturbances during prolonged treatment with prednisone and prednisolone, 100 patients with active rheumatoid arthritis who were maintained on combined antacid and prednisone or prednisolone therapy for periods of one year or longer, were studied clinically and roentgenographically. Antacid therapy consisted of 300 mg. of dried aluminum hydroxide gel and 50 mg. of magnesium trisilicate taken with each 2.5 mg. dose of the steroids. Digestive symptoms, such as indigestion, heartburn, sour eructations, gnawing epigastric distress and the like, were experienced by 18 per cent of patients during treatment with prednisone or prednisolone combined with antacids. Among patients who had been maintained on the steroids without antacids beforehand, the incidence of digestive complaints was reduced from 38 per cent to 17 per cent by the addition of alkali therapy, and the severity of the distress decreased in others. Active peptic ulcers were detected roentgenographically in three of the 100 patients. In two instances the ulcers were asymptomatic and in two instances they were considered as reactivations of previously healed lesions. The incidence of active ulcers in this series was substantially lower than that reported by several investigators among patients treated with prednisone and prednisolone without the concomitant administration of alkalis. The size of dosage and individual susceptibility appeared to be important factors in the development of digestive disturbances from steroids. Results of the study indicated that the complemental use of antacids with each divided dose of steroid is highly effective in reducing the frequency and severity of digestive symptoms during prednisone and prednisolone administration. The low incidence (3 per cent) for roentgenographically demonstrable active lesions in the series suggests that the addition of acid-neutralizing agents during prolonged treatment with these steroids may afford at least partial protection against the development and reactivation of peptic ulcers.
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PMID:Effectiveness of antacids in reducing digestive disturbances in patients treated with prednisone and prednisolone. 1358 44

Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation, reduction of the ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield acetic acid derivatives. Essentially no unchanged nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces. Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with other COX inhibitors, nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA, nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic properties in patients with arthritis and there is no evidence of excess GI or other forms of complications to date.
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PMID:Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. 1545 29

The recent identification of tissue transglutaminase (tTG) as the autoantigen for celiac disease-associated anti-endomysial antibodies (EMA) has allowed the use of rapid immunoassay to detect the presence of autoantibodies, anti-tTG, in the serum of patients. In this study, we examined the prevalence of IgG or IgA anti-tTG in sera from patients with elevated levels of IgM rheumatoid factors, which are autoantibodies reactive with the Fc portion of IgG. We report here on four cases of anti-tTG positivity for patients with elevated IgM rheumatoid factor (RF) without evidence of celiac sprue. The study population consisted of 65 patients (26 men, 39 women; mean age, 49 years; range 4 - 92 years) with elevated RF (>20 U/ml ), and 23 healthy subjects (12 men, 11 women; mean age, 46 years; range, 21 - 54 years). IgG and IgA anti- tTG levels were detected using a commercially available ELISA kit (Immuno-Biological Laboratories, Germany). Out of 65 patients, one (1.5%) and three (4.6%) patients were positive for IgG and IgA anti-tTG antibodies, respectively, and this was a higher frequency than occurred in healthy subjects (0/23). The clinical features of the four cases positive for IgG or IgA anti-tTG were as follows: The first case (female, 63 yrs) positive for IgA anti-tTG antibody suffered from rheumatoid arthritis, type II diabetes mellitus, iron deficiency anemia and gastric indigestion without symptoms of malabsorption. She denied any gluten sensitivity on her diet. Her esophagogastroduodenoscopic biopsy showed mucosal atrophy with no elongated crypts or infiltration of inflammatory cells in the lamina propria. The remaining three cases positive for anti-tTG antibodies had interstitial pneumonia, a herniated lumbar disc, and mild scoliosis, respectively. They all denied any malabsorption symptoms or gluten sensitivity. Jejunal biopsy could not be performed in all four cases.
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PMID:Tissue transglutaminase autoantibodies in patients with IgM rheumatoid factors. 1551 14


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