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Background and purpose: Aspirin reduces the risk of myocardial infarction and stroke by inhibiting thromboxane production in platelets. This inhibition can be competitively antagonized by some non-steroidal anti-inflammatory drugs (NSAIDs). Experimental approach: By measuring thromboxane B2 production in healthy volunteers, we investigated whether ibuprofen (800 mg three times daily for 7 days) or diclofenac (50 mg three times daily for 7 days) taken concurrently with aspirin 80 mg (once daily for 7 days) influenced the inhibitory effect of aspirin. The effects were compared with aspirin 30 mg (once daily for 7 days), which is the lowest dose of aspirin with a proven thromboprophylactic effect. Key results: The median percentage inhibition of thromboxane B2 levels by 30 mg or 80 mg aspirin was 90.3% (range 83.1–96.0%) and 98.0% (range 96.8–99.2%) respectively. The inhibition by concurrent administration of slow release diclofenac and 80 mg aspirin was 98.1% (range 97.2–98.9%), indicating no interference between aspirin and diclofenac. The inhibition decreased significantly by concurrent administration of immediate release ibuprofen and 80 mg aspirin (86.6%; range 77.6–95.1%) to a level less than 30 mg aspirin. Conclusions and implications: As alternatives are easily available, NSAIDs such as diclofenac should be preferred to ibuprofen for combined use with aspirin.

Aims To compare the effects of nabumetone and meloxicam, two cyclo-oxygenase-2 (COX-2) preferential nonsteroidal anti-inflammatory drugs (NSAIDs), on platelet COX-1 activity and platelet function. Methods Twelve healthy volunteers (3 male, 9 female, median age 22 years) participated in an open, randomized, cross-over trial of nabumetone 1000 mg twice daily vs meloxicam 7.5 mg twice daily during 1 week with 2 weeks wash-out. After a second 2 week wash-out period, one dose of indomethacin 50 mg was given as a positive control to check for NSAID induced inhibition of platelet function. COX-1 inhibition was measured as percentage inhibition of serum TXB2 generation in clotting whole blood, and as closure time with use of the platelet function analyser PFA-100. Data are reported as median with range. Paired variables were analysed using Wilcoxons signed rank test. Results TXB2 levels decreased significantly after all three medications, but percentage inhibition after nabumetone and indomethacin (88% and 97%, respectively) was significantly higher than after meloxicam (63%) (P

Pefloxacin (400 mg twice daily) was administered orally for infection prophylaxis in neutropenic patients. Diffusible fecal pefloxacin concentration was determined by bioassay during 24 neutropenic periods. The median diffusible fecal pefloxacin concentration was 187 micrograms/g. This concentration was comparable with those found in volunteers following oral and intravenous administration of pefloxacin (400 mg twice daily) (median of 171 and 155 micrograms/g, respectively). From this study, it is concluded that pefloxacin administered orally results in a predictable high diffusible fecal concentration which leads to effective elimination of susceptible aerobic gram-negative bacilli from the colonic flora.

Sir, Sevelamer hydrochloride (Renagel) is a calcium-free nonabsorbable phosphate-binding cationic polymer marketed for the treatment of hyperphosphataemia in patients undergoing renal function replacement [1]. Furosemide is a loop diuretic. Large doses of furosemide have been employed as an adjunct to other therapies in patients with acute and chronic renal failure. In some patients, the use of furosemide may permit a slightly more liberal fluid intake. This is very important for the quality of life of these patients. A 64-year-old female on haemodialysis thrice weekly started with sevelamer for hyperphosphataemia. Her urine production was 950 ml/day with furosemide 250 mg twice daily. Upon starting sevelamer, 800 mg with breakfast, 800 mg at lunchtime and 1600 mg with dinner, she noticed that her urine production stopped within 24 h after taking the first sevelamer capsule. After sevelamer withdrawal, her urine production increased within 24 h to her previous level. Her urine production stopped again within 24 h after resumption of sevelamer and increased after withdrawal. Unfortunately, we do not know if the patient gained weight or if there were any blood pressure fluctuations during the time the urine production stopped. At present the patient takes furosemide 500 mg once daily in the morning and sevelamer twice daily 1600 mg at lunch and dinner. Her urine production is stable as before.

Cephradine has been described as one of the antimicrobials that do not impair microbial colonisation resistance. However, this view was based on data obtained in animals, and has not been proven in man. In this study we investigated the influence of cephradine, 500 mg twice daily, on microbial colonisation resistance in six healthy volunteers. Increase in the faecal concentrakion of gram-negative bacilli, aerobic gram-positive cocci or yeasts, and increase in secondary colonisation by strains acquired spontaneously or administered deliberately (challenge), were used as indicators for disturbance of the flora that provides colonisation resistance. In two of six volunteers none of these indicators was found to be positive. In the other four volunteers one or more indicators became positive. It is concluded that even this low dosage of cephradine may impair colonisation resistance. Therefore the view that cephradine does not impair colonisation resistance in a dosage of up to 9 g daily is probably incorrect. Keywords: Colonisation resistance; Cephradine; Indigenous aerobic flora.

The effects of various types of 3 d antibiotic treatment of mice on the presence of segmented filamentous bacteria (SFBs) in the ileum were measured in order to further characterise these microorganisms. To assess any specific effects of the antimicrobial drugs on SFBs, relative caecal weight, relative number of fusiform-shaped bacteria in the caecum and the number of faecal Enterobacteriaceae were also determined. All drugs tested, i.e. amoxycillin, doxycyclin, gentamicin, vancomycin, ciprofloxacin, trimethoprim, metronidazole, clindamycin, streptomycin and cefotaxim, reduced the presence of SFBs in the ileum, although to different degrees. None of the drugs affected body weight of the mice. There was no correlation of the drug effects on SFBs and those on either relative caecal weight, percentage of caecal fusiforms or faecal Enterobacteriaceae. Thus, the effects of the antimicrobial drugs on SFBs can be considered rather specific. The sensitivity pattern of SFBs suggests that they are facultatively anaerobic bacteria with relatively high sensitivity to antimicrobial drugs. Keywords: Segmented filamentous bacteria; Intestinal bacteria; Small intestine; Mouse; Antibiotics.