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Title: Non-steroidal anti-inflammatory drugs and peptic ulcers
Author: Taha, Ali S. A.
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1993
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This Thesis addresses several issues related to the pathogenesis of peptic ulcers in patients receiving non-steroidal anti-inflammatory drugs (NSAID). Section I discusses the background of Thesis with respect to the mechanisms of mucosal damage by NSAID, the interaction between NSAID and H pylori, and the interaction between NSAID and anti-rheumatoid second-line drugs. Suppression of mucosal prostaglandin synthesis is central to the mode of action of the vast majority of NSAID, and yet several studies have failed to find a correlation between the degree of prostaglandin inhibition and that of mucosal damage. This emphasizes the importance of other mechanisms of toxicity by NSAID such as stimulation of gastric acid secretion, interference with the mucus layer, reduction of mucosal blood flow, and the histological manifestation of chronic NSAID intake. Details of such mechanisms, in the presence or absence of H pylori, and their therapeutic implications are all discussed in Chapters 1 and 2. It becomes clear, as shown in Chapter 2, that NSAID and H pylori share several pathogenetic mechanisms which might ultimately lead to an increase in the prevalence of peptic ulcers in NSAID patients infected with H pylori. In addition to taking NSAID and the possibility of being infected with H pylori, the prevalence of ulcers in rheumatoid arthritis patients might be influenced by the concurrent treatment with anti-rheumatoid second-line drugs such as gold compounds and sulphasalazine. This is described in Chapter 3, which attempts to explain the interesting observation that patients on long term gold injections appear to have a lower prevalence of both H pylori and peptic ulcers, suggesting that gold may have a toxic effect on this organism and thus protect against NSAID - induced gastric damage. With the increasing evidence for an interaction between NSAID and H pylori, which is damaging to the gastric mucosa, the accurate diagnosis of H pylori in chronic NSAID users becomes of crucial importance. Almost all diagnostic tests for H pylori were previously evaluated in patients not taking NSAID. This subject is studied in Chapter 4, which assesses the efficacy of histology, urease enzyme activity (CLO-test), latex agglutination (Pyloriset), and an enzyme-linked immunosorbent assay, ELISA (Helico-G) in diagnosing H pylori in the presence or absence of NSAID, using culture as standard. The sensitivity and specificity of the three biopsy-related tests (culture, histology and CLO-test) were greater than 90% and not affected by NSAID intake. However, the sensitivity and specifity of Pyloriset and Helico-G were lower than those of the biopsy-related tests, and the specifity was even lower in the presence of NSAID. These results should not lead to abandoning the search for more effective serological tests because of the potential benefits of serodiagnosis, such as convenience, low cost, and early diagnosis. Such characteristics can be very helpful especially in screening for H pylori and in monitoring the response to therapeutic regimes. Taking such benefits into consideration, and having accepted the validity of culture, histology and CLO-test in diagnosing H pylori in NSAID patients. Chapter 5 moves on to evaluate the efficacy of Biolab Malakit and Bio-Rad GAP tests, in comparison with Pyloriset and Helico-G, taking all the biopsy-related tests as standard. Bio-Rad GAP test had the highest sensitivity but the lowest specificity. The sensitivity and specificity of the other three serological tests were low, and the specificity of all the serological tests was also lower in patients taking NSAID. The performance of the serological tests studied in Chapters 4 and 5 would limit their value in predicting peptic ulcers in patients treated with NSAID, unlike the situation in dyspeptic patients not on NSAID. The Health Assessment Questionnaire (HAQ) is an established method of assessing physical disability in patients with chronic arthritis. The prevalence of peptic ulcers might be higher in patients with debilitating arthritis because, it could be argued, their advanced disease requires more aggressive use of NSAID. This hypothesis was tested in Chapter 6, which used HAQ to classify chronic arthritic patients according to their physical disability. Patients with high HAQ scores (greater than 2.0, severely disabled by arthritis) had the highest prevalence of ulcers despite taking comparable types and doses of NSAID. The explanation for this is not fully clear, but the results might help in the process of selecting patients for prophylactic therapy against NSAID - related peptic ulcers. Active chronic inflammation of the upper gastrointestinal tract has, for a long time, been thought to play an important role in the pathogenesis of peptic ulceration. The situation is not clear in chronic NSAID users, who are known to have a higher risk of developing ulcers. This issue is addressed in Section IV, which aims at identifying any specific histological features in the stomach, duodenum, or oesophagus of patients receiving NSAID.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available