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R Brimblecombe

Publications and source records attributed to R Brimblecombe.

4 recordsLinked to original sources
PubMed1990

Mesalazine: a global safety evaluation.

The potential benefit of sulphasalazine in inflammatory bowel disease is limited by the wide variety of side effects that occur in about one-third of treated patients. Most of the side effects of sulphasalazine are due to the sulphapyridine moiety. Claversal has the advantage of delivering the active ingredient of sulphasalazine--mesalazine--without the undesirable effects of sulphapyridine. Four international multicentre trials involving 932 patients with ulcerative colitis or Crohn's disease compared 0.75 g/day or 1.5 g/day mesalazine, 1.5 g/day or 3.0 g/day sulphasalazine, or placebo. Forty-seven (14%) of 331 patients receiving mesalazine reported adverse events, whereas 33 (23%) of 144 patients receiving sulphasalazine and 23 (19%) of 123 patients receiving placebo reported adverse effects. When lower doses of both mesalazine (0.75 g/day) and sulphasalazine (1.5 to 2.0 g/day) were evaluated in a maintenance trial, the percentage of adverse events was similar for both drugs--14% and 12%, respectively. In these trials the incidence of adverse effects was similar with both doses of mesalazine; however, doubling the sulphasalazine dose resulted in a twofold increase in adverse effects. In contrast, mesalazine appeared not to induce dose-related effects, suggesting that patients may be able to tolerate even higher mesalazine doses than those studied. The withdrawal rate owing to adverse events in all four controlled trials was similar for patients treated with mesalazine (6%) and sulphasalazine (8%). Results of an open postmarketing sampling trial of just over 1700 patients in Germany showed a low overall incidence of adverse effects (3%) with mesalazine and none of the rare, more serious effects, such as hepatoxicity, agranulocytosis, or pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminosalicylic Acids↗
PubMed1986

Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.

A 24 hour gastric aspiration study was carried out on nine Polya gastrectomy, eight pernicious anaemia, and nine matched control subjects. Intragastric pH, bacteria, nitrite, and N-nitroso compounds were assessed half hourly whilst ambulant and hourly when in bed. Both total and nitrate reducing bacterial counts were positively related to pH (chi 2 = 279.3; p less than 0.001), as was nitrite concentration (F = 19.1; p less than 0.0001). By contrast, total (F = 40.6; p less than 0.0001) and stable (F = 257.4; p less than 0.0001) N-nitroso compound concentrations were negatively related to pH. Clear differences in these gastric juice factors were not apparent between matched control and either pernicious anaemia, or Polya gastrectomy because the Polya gastrectomy and matched control groups were heterogeneous for gastric acidity. Thus, although eight of eight pernicious anaemia subjects were hypoacidic (defined as intragastric pH greater than 4 for greater than 50% of both daytime and night time periods), only five of nine Polya gastrectomy and two of nine matched control subjects were hypoacidic. When subjects were rearranged into hypoacidic (n = 15) and acidic (n = 11) groups, bacterial counts (p less than 0.01) and nitrite concentrations (p less than 0.01) were higher, whereas N-nitroso compounds tended to be lower (NS) in the hypoacidic group. These data suggest that, although hypoacidity predisposes to bacterial overgrowth and nitrite generation, it does not enhance nitrosation. Instead, this is maximal at low pH, suggesting chemical rather than bacterial nitrosation, contrary to the nitrosamine hypothesis of gastric carcinogenesis.

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