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Biomedical subjects

G A Mogg

Publications and source records attributed to G A Mogg.

13 recordsLinked to original sources

Comparative in vitro and in vivo bioavailability of naproxen from tablet and caplet formulations.

A 500 mg dose of naproxen in a caplet formulation (product A) or a tablet (Naprosyn 500, product B) was administered to 14 fasting healthy subjects on two separate occasions, separated by a 1-2 week washout period in an open, randomized crossover. Blood samples were drawn periodically and plasma naproxen concentrations measured by HPLC. The median time Tmax to reach peak concentration for product A was shorter than that for product B (1.025 h versus 1.5 h) but A and B were similar with respect to median peak plasma concentration Cmax (77.9 mg l-1 versus 71.4 mg l-1), and average area AUC0-infinity under the plasma concentration-time curve (1210.2 mg l-1 h versus 1211.0 mg l-1 h). In vitro parameters (A versus B) of mean dissolution time MDT (5.03 min versus 15.0 min), and time for 70% dissolution T70 (6.67 min versus 20.2 min), differed significantly.

Adolescent

The disposition of bupivacaine following a 72 h interpleural infusion in cholecystectomy patients.

The disposition of bupivacaine and degree of analgesia following a 72 h interpleural infusion was investigated in 12 adult patients undergoing elective cholecystectomy. The infusion regimen of an initial interpleural bolus dose of 20 ml of 0.5% bupivacaine HCl with adrenaline (1:200,000) followed by continuous infusion at a rate of 8 ml h-1 of 0.25% plain bupivacaine HCl was designed to achieve continuous post-operative pain relief for 72 h. In practice an additional bolus dose (identical to the first) administered 5 h after infusion commencement was required to achieve adequate pain relief on the first postoperative day. The mean measured steady-state plasma bupivacaine concentration was 2.1 mg l-1 (s.d. +/- 0.54, range 1.3-3.2 mg l-1). Disposition parameters for bupivacaine measured for the infusion were calculated by non-compartmental methods and compared with previous values obtained after single and multiple interpleural bolus dose administration. No statistically significant differences were noted and, in particular, the systemic clearance of bupivacaine (mean 10.2 l h-1 s.d +/- 3.0; range 6.3-16.0 1 h-1) remained unchanged following the long-term interpleural infusion. Analgesia was deemed satisfactory throughout the entire post-operative period.

Adult

Interpleural bupivacaine infusion compared with intravenous pethidine infusion after cholecystectomy.

Twenty-six cholecystectomy patients received either an interpleural infusion of bupivacaine (Group B, n = 12) or an intravenous infusion of pethidine (Group P, n = 14) for management of postoperative pain over a three-day period. Patients in Group P experienced a significantly (P less than 0.05) greater incidence of total side-effects (146) than patients in Group B (66). Pain scores (VAS) and responses to a pain questionnaire were similar for both groups; however, within Group B improvement in mean VAS scores at rest with time were more sustained. Similar reductions in FEV1 and FVC from preoperative values occurred for both groups, while for Group P there were significant (P less than 0.05) changes in arterial blood gases (increase in PCO2, decrease in PO2) over two days postoperatively. Patients in Group P recorded longer times to passing flatus and unaided mobilisation (P less than 0.05), and required a significantly greater number of additional medications (anti-emetics and analgesics) over the postoperative period (41 vs 29, P less than 0.05).

Adult

Pharmacokinetics of interpleural bupivacaine in patients undergoing cholecystectomy.

Arterial and venous plasma concentrations of bupivacaine were measured following interpleural administration of 20 ml of 0.5% solution with adrenaline in patients undergoing cholecystectomy. Mean maximum arterial and venous concentrations in eight of 11 patients were 1.90 (SD 0.36) and 1.65 (0.48) mg litre-1 and occurred at 22 (10) min and 25 (10) min, respectively. An arteriovenous difference for bupivacaine of approximately 20% was noted during the first 45-60 min after administration. Mean systemic venous plasma clearance (0.15 (0.08) litre h-1 kg-1) was less and the mean elimination half-life (6.85 (2.29) h) and mean body residence time (9.99 (3.00) h) were longer than reported previously for interpleural bupivacaine--possibly because of continued slow absorption of the drug from its absorption site.

Adult

Steady-state pharmacokinetics of interpleural bupivacaine in patients after cholecystectomy.

Venous plasma concentrations of bupivacaine were determined in eight cholecystectomy patients following multiple interpleural bolus instillations of bupivacaine 20 ml 0.5% with adrenaline (5 mg/l) administered at six- to eight-hour intervals. The mean steady-state peak plasma concentration was 2.3 mg/l (range 1.2-3.1 mg/l); however, in three of the eight patients peak plasma concentrations were greater than 3 mg/l. The mean accumulation ratio was found to be 1.6 (range 0.99-2.49), with steady-state occurring within the first 24 hours of drug administration. Mean apparent systemic plasma clearance was 0.16 +/- 0.07 l/kg/h with a mean terminal half-life of 5.8 +/- 2.3 hours measured at steady-state, values which were not significantly different (P greater than 0.05) from those values obtained following single interpleural bolus dose administration.

Adult

Randomized controlled trial of colestipol in antibiotic-associated colitis.

Thirty-eight patients with severe antibiotic-associated postoperative diarrhoea were entered into a randomized controlled trial to compare colestipol (an ion exchange resin) in 17 patients with placebo (sherbet) in 21 patients. Clostridium difficile or its toxin was present before treatment in 12 of the colestipol group, compared with only 5 in the placebo group. Because of the low incidence of Cl. difficile or its toxin, the placebo group data from 22 patients receiving placebo in a previous trial (9 of whom had Cl. difficile or toxin) were included for comparison. Neither colestipol nor placebo had any influence on the faecal excretion of Cl. difficile or its toxin. Colestipol was clinically no better than placebo. In view of the persistent faecal excretion of Cl. difficile toxin, ion exchange resins cannot be recommended for the treatment of antibiotic-associated colitis.

Anti-Bacterial Agents

Faecal toxin and severity of antibiotic-associated pseudomembranous colitis.

The relationship between faecal toxin titre, histological evidence of pseudomembrane in the rectum, and severity of antibiotic-associated colitis has been analysed from data on 62 patients whose faeces contained Clostridium difficile toxin. There was a significant correlation between a toxin titre of 6400 or more and the presence of pseudomembrane (p less than 005). There was no correlation between toxin titre, duration of diarrhoea, total white cell count, temperature, serum albumin or serum orosomucoid concentrations. There was, however, a significant correlation between the presence of rectal pseudomembrane and duration of diarrhoea (p less than 0.005). Exposure to clindamycin or lincomycin was also associated with a significantly higher toxin titre than that seen in patients who were given other antibiotics. The duration of diarrhoea of diarrhoea was not longer and rectal pseudomembrane did not occur more often in the patients who had received clindamycin or lincomycin.

Anti-Bacterial Agents

Relationship of proctitis and rectal capacity in Crohn's disease.

In patients with Crohn's disease involving the rectum (n=25), there was an inverse relationship between rectal capacity and the degree of proctitis. However, in patients with Crohn's disease not involving the rectum (n=22) the rectal capacity was similar to that of normal controls (n=20). The frequency of defaecation was not related to the degree of proctitis or to the pressure of a colectomy and ileorectal anastomosis. Control subjects had a significantly lower frequency of defaecation than patients with Crohn's disease irrespective of involvement of the rectum.

Adolescent

Therapeutic trials of antibiotic associated colitis.

Since September 1977 we have seen 63 patients with Clostridium difficile and a faecal toxin, but only 33 had histological evidence of pseudomembranous colitis. We have conducted separate double blind trials of an antibiotic, vancomycin and an anion-exchange resin, colestipol, in patients with post-operative diarrhoea. Vancomycin was extremely effective at eradicating the organism and its faecal toxin. These changes were associated with a marked symptomatic improvement. Colestipol proved ineffective in absorbing the faecal toxin and caused no change in numbers of Clostridial difficile. There was no associated symptomatic response. Neither drug had any effect on diarrhoea not related to Clostridium difficile. A carrier state was created by those patients who continued to excrete the organism after Colestipol or placebo treatment. This was eradicated by subsequent treatment with vancomycin. Our brief experience with metronidazole is discussed and a rational basis for treatment advocated.

Anti-Bacterial Agents

Antibiotic-associated colitis--a review of 66 cases.

We have reviewed 66 cases of antibiotic-associated colitis since March 1975, which have been associated with a 27 per cent mortality. We believe antibiotics may predispose patients to this condition which is caused by a toxin produced by Clostridium difficile. Although the disease is rare, it is more common than previously reported. The presentation, methods of diagnosis and treatment are discussed.

Adolescent

Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea.

The efficacy of vancomycin in pseudomembranous colitis was assessed in a prospective randomised controlled trial. Forty-four patients with postoperative diarrhoea were allocated to five days' treatment with either 125 mg vancomycin six-hourly or a placebo. Sixteen patients had high titres of the neutralised faecal toxin characteristic of pseudomembranous colitis; nine received vancomycin and seven placebo. At the end of treatment faecal toxins were present in one patient given vancomycin compared with five of the controls. Vancomycin caused the disappearance of Clostridum difficile from the stool in all except one patient, whereas toxicogenic strains of Cl difficile persisted in all but one of the controls. Histological evidence of psuedomembranous colitis had disappeared by the end of treatment in six out of seven patients given vancomycin compared with only one out of seven patients given vancomycin compared with only one out of five patients given placebo. In patients with faecal toxins bowel habit had returned to normal in seven of the vancomycin group compared with only one of the controls, but there was no significant difference in clinical response among patients without faecaal toxins. The results suggest that vancomycin eliminates toxin-producing Cl difficile from the colon and is associated with rapid clinical and histological improvement in patients with pseudomembranous colitis.

Bacterial Toxins