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Biomedical subjects

R I Russell

Publications and source records attributed to R I Russell.

At least 109 records · Page 6Linked to original sources

Evaluation of the efficacy and comparative effects on gastric and duodenal mucosa of etodolac and naproxen in patients with rheumatoid arthritis using endoscopy.

The therapeutic efficacy and upper gastrointestinal side effects of a twice daily dose of 300 mg etodolac and 500 mg naproxen were compared in 30 hospital out-patients with active rheumatoid arthritis. Drugs were taken for 4 weeks in a double-blind, randomized, parallel group, single centre study. Rheumatological, endoscopic and laboratory assessments were performed at the start and on completion of the study. Mucosal lesions developed in only three (20%) patients of the etodolac group and they all had low endoscopy scores, compared to eight (53%) patients of the naproxen group with significantly worse endoscopy scores (p less than 0.05). Lesions were asymptomatic in all but one patient (on naproxen), and the gastric antrum was the commonest region involved. Of the 11 patients who developed endoscopic abnormalities in both groups, seven (64%) were moderate to heavy smokers. Etodolac had a similar antiarthritic effect to naproxen, but it appears to be better tolerated by the upper gastrointestinal mucosa as shown by endoscopy.

Adult↗

Comparison of the effect of aspirin and choline magnesium trisalicylate on thromboxane biosynthesis in human platelets: role of the acetyl moiety.

Parameters of platelet thromboxane biosynthesis were measured 24 h after ingestion of equivalent salicylate doses (500 mg) of aspirin (ASA) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate. In random order, 10 healthy volunteers received these drugs on 2 separate days, 2 weeks apart. While ASA significantly prolonged bleeding time, and decreased plasma thromboxane generation and serum thromboxane B2 levels, CMT failed to produce such effects. Thus CMT, which lacks an acetyl moiety in its structure, has no inhibitory effect on platelet thromboxane biosynthesis, and may therefore be considered safer than ASA for therapeutic use, when inhibition of platelet function can be hazardous.

Adult↗

Campylobacter pylori associated gastritis in patients with rheumatoid arthritis taking nonsteroidal anti-inflammatory drugs.

Fifty-two patients with rheumatoid arthritis taking nonsteroidal anti-inflammatory drugs were studied in order to assess the carriage rate of Campylobacter pylori (C. pylori) with reference to dyspeptic symptoms, endoscopic appearance and antral histology. All patients were interviewed using a standard gastrointestinal symptom scoring questionnaire and underwent endoscopy at which two antral biopsies were obtained. Sections were examined for the presence and severity of gastritis and of C. pylori. Forty-four of 52 patients (85%) had histological evidence of gastritis. Twenty-six of 44 (59%) patients with gastritis were positive for C. pylori. Twenty-six of 28 patients with 'active' (polymorph infiltration) chronic gastritis were positive for C. pylori (p less than 0.002). Sixteen of 26 bacteria-positive patients had gastrointestinal symptoms compared with eight of 26 bacteria-negative patients (p less than 0.05) and this may have therapeutic implications. There was no correlation between the presence of organisms and the appearances at endoscopy.

Adult↗

Plasma kinin-precursor levels in clinical intestinal inflammation.

Plasma kinin-precursor (kininogen) concentrations were measured in the peripheral venous blood of 7 untreated patients with inflammatory bowel diseases, 12 healthy subjects, and 5 uncomplicated fracture cases. The mean plasma kininogen levels were significantly raised (P less than 0.025) in patients with intestinal inflammation (7.0 +/- 1.0 micrograms BK Eq/ml), as compared with the value found in healthy subjects (5.7 +/- 0.7 micrograms BK Eq/ml), and in fracture cases (5.0 +/- 1.2 micrograms BK Eq/ml). The packed cell volume did not differ (P greater than 0.05) between patients and control groups. Thus, the raised plasma kininogen levels observed in patients were not the result of nonspecific changes in plasma volume. It is suggested that raised plasma kininogen might be due to increased synthesis to provide substrate for excessive kinin-formation, to a potent inflammatory agent, or to high synthesis of acute-phase reactants. The possible significance of this observation is discussed.

Acute-Phase Reaction↗

Peptic ulcer in rheumatoid arthritis.

In a study of patients attending a rheumatology clinic 230 unselected patients, 185 with rheumatoid arthritis (RA) and 45 with other rheumatic disorders (non-RA), were examined by endoscopy and a detailed history of symptoms referable to the gastrointestinal tract was taken. A peptic ulcer was found in 67 (36%) of the patients and in 13 (29%) of the non-RA group. Gastric ulceration was more common in the group with RA (32 patients (17%) compared with three patients (7%) in the non-RA group); 17/32 (53%) patients with RA and gastric ulcer were asymptomatic. In the group with RA, of those with gastric ulcer 20/32 (63%) were smokers, compared with only 40/118 (34%) of the non-ulcer group. There was no difference in the duration of rheumatic disease or non-steroidal anti-inflammatory drug (NSAID) treatment between the ulcer and non-ulcer groups. Treatment with H2 receptor antagonist and maintenance of NSAID treatment resulted in healing in 26 out of 29 (90%) patients with gastric ulcer and 23 out of 27 (85%) patients with duodenal ulcer.

Adult↗

Effect of intragastric pH on mucosal protective action of sucralfate.

Acid intragastric pH is believed to be mandatory for mucosal protective action of sucralfate, but evidence for its efficacy at neutral pH is lacking. The effect of sucralfate on gastric mucosal erosions induced by oral administration of aspirin and bile acids at acidic pH of 1.5 and 3.9, and near neutral pH of 6.5 was investigated in 320 rats. The effect of sucralfate on the intragastric pH four hours after the ingestion of test solutions was also examined. The incidence and severity of mucosal erosions induced by aspirin and bile acids were lower in animals treated with sucralfate at acidic (p less than 0.001) and near neutral (p less than 0.01) intragastric pH. Mucosal protection was greater with ingestion of sucralfate 300 mg/kg and 200 mg/kg, than with 100 mg/kg. The intragastric pH was higher (p less than 0.001) in sucralfate treated groups at pH 3.9 and 6.5. This study provides evidence that sucralfate protects against mucosal injury at near neutral, as well as at acidic pH.

Animals↗

Antacid maintenance therapy in the prevention of duodenal ulcer relapse.

The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p less than 0.01) and bedtime Maalox TC (p less than 0.04). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo.

Adult↗

Can 111indium autologous mixed leucocyte scanning accurately assess disease extent and activity in Crohn's disease?

111Indium autologous mixed leucocyte scanning has recently been used for the investigation of Crohn's disease. Nineteen patients had indium scans to assess disease extent and activity. The scans were compared with conventional imaging techniques and indices of disease activity including clinical scores, ESR, CRP, and GI protein loss. In five patients with active disease the scans were negative and overall there was poor correlation between the scan scores and the other indices of disease activity. Indium scanning correctly located extent of disease in only 58% of patients. 111Indium mixed leucocyte scanning may be more suited for the assessment of disease extent and activity in severely ill patients with Crohn's disease.

Adolescent↗

Does non-acetylated salicylate inhibit thromboxane biosynthesis in human platelets?

Ingestion of aspirin (acetyl salicylic acid: ASA) may promote bleeding complications due to inhibition of thromboxane biosynthesis, which results in the prolongation of bleeding time. The effect is believed to be achieved by the irreversible acetylation of the enzyme cyclooxygenase by aspirin. This alteration in platelet function by aspirin prohibits its use in patients with bleeding disorders such as haemophiliacs. Choline magnesium trisalicylate (CMT; Napp Laboratories Ltd) is a non-acetylated salicylate with analgesic and anti-inflammatory effects similar to that of aspirin. However, despite a comparable salicylate absorption from the two drugs, CMT is found to have no inhibitory action in platelet aggregation and to cause less gastric mucosal damage and gastrointestinal blood loss than aspirin. To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.

Administration, Oral↗

Is an acid pH medium required for the protective effect of sucralfate against mucosal injury?

It has been suggested that an acidic medium is required for the action of sucralfate in providing mucosal protection. We have examined the effect of sucralfate (300 mg/kg) at an acidic pH of 1.5 and a near-neutral pH of 6.5 on the occurrence of mucosal damage induced in rats by aspirin alone and aspirin combined with bile acids. Fasting Sprague-Dawley rats received test solutions by oral intubation, and their stomachs were examined four hours later for the presence of hemorrhagic erosions. Sucralfate significantly reduced mucosal erosions induced by aspirin alone and aspirin combined with bile acids at pHs of both 1.5 and 6.5. These results indicate that the protective effect of sucralfate against mucosal injury induced by aspirin and bile acids is not dependent on an acidic medium.

Animals↗

Replacing the acetyl linkage in aspirin with choline and magnesium moieties reduces the occurrence of gastric mucosal injury.

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA-induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non-acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered by per oral intubation to five groups of fasting Sprague-Dawley rats (n = 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion-scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg-1) compared with 17% and 0 (0:0) for CMT (128 mg kg-1) (P less than 0.001 and P less than 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P less than 0.001) and P less than 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre-1 for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA-induced mucosal injury, without affecting blood salicylate concentrations.

Animals↗