Simon Smale

King's College London, Londinium, England, United Kingdom

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Publications (11)49.93 Total impact

  • Clinical Gastroenterology and Hepatology 02/2006; 4(2):121-122. · 6.65 Impact Factor
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    ABSTRACT: It has been variably suggested that nonselective NSAIDs and cyclooxygenase (COX)-2 selective inhibitors aggravate or ameliorate clinical disease activity in patients with inflammatory bowel disease. We assessed the effect of these drugs in patients with inflammatory bowel disease (n = 209) and the possible mechanisms. First, patients with quiescent Crohn's disease and ulcerative colitis received the non-NSAID analgesic acetaminophen (n = 26) and the conventional NSAIDs naproxen (n = 32), diclofenac (n = 29), and indomethacin (n = 22) for 4 weeks. The Harvey-Bradshaw index was used to define relapse. Second, to assess the mechanism of relapse, intestinal inflammation was quantitated (fecal calprotectin) before and during treatment (20 patients/group) with acetaminophen, naproxen (topical effect, COX-1 and -2 inhibitor), nabumetone (COX-1 and -2 inhibitor), nimesulide (selective COX-2 inhibitor), and low-dose aspirin (selective COX-1 inhibition). Nonselective NSAIDs were associated with a 17%-28% relapse rate within 9 days of ingestion. No patient had an early relapse on acetaminophen, nimesulide, or aspirin, whereas those on naproxen and nabumetone (20%) experienced relapse. These clinical relapses were associated with escalating intestinal inflammatory activity. NSAID ingestion is associated with frequent and early clinical relapse of quiescent inflammatory bowel disease, and the mechanism appears to be due to dual inhibition of the COX enzymes. Selective COX-2 inhibition with nimesulide and COX-1 inhibition with low-dose aspirin appear to be well-tolerated in the short-term.
    Clinical Gastroenterology and Hepatology 02/2006; 4(2):196-202. · 6.65 Impact Factor
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    Simon Smale, Ingvar Bjarnason
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    ABSTRACT: Intestinal integrity is maintained by a delicate balance between mucosal defence and luminal aggressors that cause damage if exposed to the mucosa. The intestinal barrier function appears to be the gatekeeper for controlling this balance. It is becoming increasingly clear that if the intestinal barrier is disrupted the consequences are low grade intestinal inflammation which carry with it the risk of significant blood and protein loss both of which may cause clinical management problems. We review the strength and weaknesses of methods for assessing small bowel function that are useful for assessing drug-induced intestinal toxicity. There are a number of imaging methods for assessing intestinal integrity but these do not provide functional information. Intestinal permeability measurements have been optimized for specificity and there are now ways of measuring intestinal permeability regionally, but marker analyses continue to be cumbersome. Recent developments of faecal inflammatory markers make it a matter of routine to assess this in any routine chemical pathology laboratory. Bleeding, protein loss and other complications of inflammation can also be measured with good specificity, but again the methods are cumbersome. Using a combination of functional and imaging techniques it is now possible to characterize and define with precision, the small bowel side-effects of drugs, the best example being the small bowel side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs).
    British Journal of Clinical Pharmacology 10/2003; 56(3):284-91. · 3.69 Impact Factor
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    ABSTRACT: Previous researchers have shown that non-medical endoscopists can perform lower gastrointestinal endoscopy as safely and effectively as medical staff. However, it is not known if upper gastrointestinal endoscopy performed by medical and non-medical endoscopists in clinical practice yields similar results in terms of performance, patient discomfort, and satisfaction. To determine differences in the yield of diagnosis for significant disease during upper gastrointestinal endoscopy performed by nurse and medical endoscopists and to measure patient discomfort, satisfaction, and attitudes towards future endoscopy. This two part study included 3009 patients in a retrospective analysis and 480 in a prospective study. The first part of the study assessed indications for endoscopy, diagnoses, and procedures performed by medical and nurse endoscopists. In a second prospective study, 480 patients were included to determine the association between endoscopist type and sedation, patient anxiety, discomfort, satisfaction, and attitudes towards future sedation. No patient refused endoscopy by either a nurse or medical endoscopist and there were no complications in either group. Nurses performed 1487 procedures and reported fewer endoscopies as "normal" than medical staff (p=0.006). Multivariate analysis showed that male sex, older age, inpatient status, dysphagia, and gastrointestinal bleeding, but not endoscopist type, were all associated with significant disease. In relation to discomfort and satisfaction, a similar proportion of patients received sedation in both groups (p=0.81). There were no differences in pre-procedure anxiety (p=0.61), discomfort during intubation (p=0.97), discomfort during examination (p=0.90), or post-procedure examination rating (p=0.79) in patients examined by medical or nurse endoscopists. Experienced nurses perform routine diagnostic gastroscopy safely in everyday clinical practice and with as little discomfort and as much patient satisfaction as medical staff.
    Gut 09/2003; 52(8):1090-4. · 10.73 Impact Factor
  • Arthritis & Rheumatology 01/2002; 44(12):2728-36. · 7.48 Impact Factor
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    Arthritis & Rheumatology 12/2001; 44(12):2728 - 2736. · 7.48 Impact Factor
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    ABSTRACT: Non-steroidal anti-inflammatory drugs cause small-bowel inflammation in about 60% of patients receiving these drugs long-term. The inflammation is associated with small intestinal bleeding, protein loss, ulcers and occasionally strictures. Treatment options for NSAID enteropathy include metronidazole, sulphasalazine and misoprostol, and some patients may require surgery. The diagnosis of NSAID enteropathy is not always straightforward. It is especially difficult to differentiate it from the ileitis associated with spondylarthropathy and, at times, that of Crohn's disease. An investigational algorithm is suggested for this purpose. In the last decade a number of small-bowel diseases have been identified, where none were thought to exist, because of the increasing use of enteroscopy and new sensitive tests for intestinal inflammation. Optimal treatments of these conditions are still to be studied.
    Bailli√®re&#x027 s Best Practice and Research in Clinical Gastroenterology 11/2001; 15(5):723-38. · 3.16 Impact Factor
  • S Smale, J Tibble, I Bjarnason
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    ABSTRACT: The noninvasive assessment of small intestinal permeability in humans is now within the capability of any routine biochemistry laboratory. There remain however, many pitfalls for the unwary when performing these tests. Importantly, it has now been shown that normal intestinal permeability relates to geographical location rather than race. Recent studies show that it may be possible to simplify the procedure even further. The main recent focus of interest in measuring intestinal permeability relates to patients with AIDS and inflammatory bowel disease, the effects of nonsteroidal anti-inflammatory drugs on the small bowel, and the use of these tests in the pediatric population and critically ill. Some groups have now started to focus their attention on the possible systemic consequences of increased intestinal permeability, whereas others have shown that increased small bowel permeability results in small intestinal inflammation that may in turn be associated with blood and protein loss.
    Current Opinion in Gastroenterology 04/2000; 16(2):134-9. · 4.10 Impact Factor
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    ABSTRACT: The small intestine is a rather neglected site of adverse effects, but can be important. Inflammation caused by non-steroidal anti-inflammatory drugs can lead to loss of blood and protein, ulcers, and strictures. Neomycin and alcohol also cause inflammation, and arsenic and potassium preparations can induce ulcers. Small bowel diarrhoea, constipation, and malabsorption can also be drug-induced. (C) 1999 Lippincott Williams & Wilkins, Inc.
    Adverse Drug Reaction Bulletin 09/1999; 198(1).