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Biomedical subjects

A Knifton

Publications and source records attributed to A Knifton.

At least 19 recordsLinked to original sources
PubMed1999

Protection against aspirin-induced human gastric mucosal injury by bosentan, a new endothelin-1 receptor antagonist.

BACKGROUND: Gastric ulceration induced by aspirin and by non-steroidal anti-inflammatory drugs (NSAIDs) is a major clinical problem. The mechanism of injury is unclear. There is evidence that NSAID-induced injury may cause endothelin activation. Endothelin-induced vasoconstriction has been shown to be capable of causing gastric ulceration. AIM: To investigate whether acute gastroduodenal injury induced in humans by aspirin can be prevented by the endothelin-1 antagonist, bosentan. METHODS: Eighteen healthy volunteers each received 5 x 900 mg aspirin every 12 h on three separate occasions (with either placebo, bosentan 700 mg or misoprostol 400 mg). Treatment order was randomized by Latin square design. Subjects were endoscoped and erosions counted before and 90 min after the first and last dose of aspirin. Plasma concentrations of bosentan were measured up to 5 h post-dose. RESULTS: There was a significant reduction in the mean number of erosions in the aspirin plus bosentan and aspirin plus misoprostol groups after the first dose of aspirin, compared with controls (aspirin plus placebo) (P<0.05). This was not sustained after the fifth dose of aspirin in the aspirin plus placebo and aspirin plus bosentan groups, but was still present in the aspirin plus misoprostol group. The mean plasma concentration of bosentan measured 3.5 h post-dose fell from 4510 (95% CI: 2791-6230) ng/mL after the 1st dose to 2508 (95% CI: 1733-3283) ng/mL after the 5th dose (P = 0.02). CONCLUSION: Endothelin receptor antagonism by bosentan can protect the gastric mucosa against aspirin damage. After five doses, bosentan levels fell, possibly because of enzyme induction, and protection was no longer evident. Further investigation is needed to assess whether higher doses would be effective.

Adult↗
PubMed1998

Safety and efficacy of rabeprazole in combination with four antibiotic regimens for the eradication of Helicobacter pylori in patients with chronic gastritis with or without peptic ulceration.

OBJECTIVES: Rabeprazole is a new fast acting proton pump inhibitor that has recently been proven to be effective in the treatment of peptic ulceration and reflux esophagitis. The aim of this study was to evaluate rabeprazole in combination with antibiotics for the eradication of Helicobacter pylori (H. pylori) in patients with chronic active gastritis with or without peptic ulcer disease. METHODS: Seventy-five H. pylori-infected patients were randomized in a double-blind fashion to receive a 7-day treatment regimen consisting of: RAC, RAM, RCM, or RC (R=rabeprazole 20 mg b.d., A=amoxycillin 1 g b.d., C=clarithromycin 500 mg b.d., M=metronidazole 400 mg b.d.). Randomized patients were H. pylori-positive by gastric biopsy urease test, histology and 13C urea breath test (13C-UBT). H. pylori eradication was assessed by 13C-UBT, 4 and 8 wk after finishing treatment. Endoscopy with histology and culture for antibiotic sensitivity testing was performed pretreatment and if treatment failed. RESULTS: On an intention-to-treat analysis, treatment success was: RCM 100%, RAC 95%, RAM 90%, and RC 63%. The most common side effects were loose stools, headache, and taste disturbance, but there were no serious adverse events related to the study medication. The two patients failing RAM treatment had metronidazole-resistant strains before and after treatment. None of the pretreatment H. pylori isolates from six patients failing RC were clarithromycin resistant, but three of five successfully cultured posttreatment had developed clarithromycin resistance. CONCLUSION: Rabeprazole-based triple therapy with two antibiotics for 1 wk is safe and effective in eradicating H. pylori. Dual therapy with clarithromycin is less successful, and the majority of treatment failures develop clarithromycin resistance.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Healing with basic fibroblast growth factor is associated with reduced indomethacin induced relapse in a human model of gastric ulceration.

BACKGROUND: Acid stable basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats and reduces subsequent non-steroidal anti-inflammatory drug (NSAID) induced relapse. AIMS: To test in a double blind, placebo controlled, three way crossover study whether bFGF promotes healing and reduces subsequent relapse in a human model of gastric ulceration. SUBJECTS: Twelve healthy volunteers. METHODS: Subjects took aspirin 900 mg twice daily (days 1-3) with bFGF 0.1 mg twice daily or cimetidine 400 mg twice daily or placebo (days 1-14) and then indomethacin 50 mg thrice daily (days 15-21). Endoscopy was performed on days 1, 4, 8, 15, and 22 during each treatment period. Eight antral biopsy specimens were taken on day 1 and the number of unhealed biopsy induced mini-ulcers and NSAID induced erosions counted during subsequent endoscopies. RESULTS: Basic FGF and cimetidine were protective against aspirin and indomethacin induced duodenal (but not gastric) injury compared with placebo. There was significant relapse of biopsy induced mini-ulcers after indomethacin only in the placebo group (0 (0-0) before v 1 (0-4.5) after; p > 0.05). TGP-580 was detected in serum of one volunteer. CONCLUSIONS: Healing with bFGF (and cimetidine) was associated with reduced NSAID induced ulcer relapse in this model of gastric ulceration.

Adult↗
PubMed1986

Forthcoming changes in the misuse of drugs legislation.

The effects of the new regulations on veterinary practice are minimal. Veterinarians are mainly concerned with drugs in schedules 2 and 3 to the regulations and the requirements relating to these drugs are virtually unchanged. Pentazocine (Fortral) has been added to schedule 3 and from April 1, 1986, veterinarians must comply with the following additional requirements with respect to this drug or any other in schedule 3: use of written requisition for purchase of supplies and the prescription requirements for controlled drugs. Further details of the legislation applying to the labelling and dispensing of medicinal products and the requirements relating to schedule 2 controlled drugs, can be found in 'Legislation Affecting The Veterinary Profession in the United Kingdom', 4th edn (1984) Royal College of Veterinary Surgeons. For details of the legislation relating to schedule 3 drugs, see VR, December 22/29, 1984, p649.

Animals↗
PubMed1984

The effect of furazolidone on fertility of male chickens.

In mature chickens, furazolidone (0.4% w/w, 10 days) decreased the weight of the testes, but did not affect significantly the concentrations of testosterone in testes and plasma, nor the concentrations of ascorbic acid, protein or cholesterol in the testes. Feeding furazolidone at a concentration of 0.08% w/w for 10 days decreased significantly the weights of the testes, wattles and combs. Treatment also produced significant reductions in the concentration of testosterone in plasma and testes, and some reductions in ascorbic acid, protein and cholesterol concentrations in the testes. Administration of furazolidone by crop tube at doses of 40 or 80 mg/kg for five days caused significant decreases in the concentrations of testicular and plasma testosterone, and reductions in ascorbic acid, protein and cholesterol concentrations in the testes. The sizes of the testes, wattles and combs were also significantly reduced. Monoamine oxidase activity in the testes was significantly inhibited by furazolidone. In all the treated birds testicular concentrations of 5-hydroxy-tryptamine were significantly raised, except in those fed the drug at a dose of 0.04% w/w for 10 days.

Animals↗
PubMed1981

Oxytocin-induced oestrus in the goat.

Subcutaneous administration of oxytocin between days 3-6, inclusive, significantly reduced the length of the oestrous cycle in goats. Concomitant oral administration of the prostaglandin synthetase inhibitor, meclofenamic acid, completely prevented this effect. Oxytocin treatment did not affect the duration of the posttreatment cycles.

Journal Article↗
PubMed1981

Bioavailability of oxytetracycline dihydrate tablets in dogs.

Plasma oxytetracycline concentrations were studied in four healthy beagles after oral administration of four different commercial preparations of oxytetracycline dihydrate tablets. Although no statistically significant differences were found in the biological availability between the four tablets, assessed by the peak plasma level and the area under the plasma concentration--time curve, there was great variation in the plasma concentrations of oxytetracycline achieved in the sixteen experiments. This variation was not related to the in vitro dissolution properties of the tablets. As the amount of oxytetracycline dihydrate administered in the experiments was almost the maximum recommended dose and the mean peak plasma concentrations were either below or at the lower end of the therapeutic concentration range, it is suggested that higher oral doses than those officially recommended are required to attain effective plasma levels.

Animals↗