Biomedical subjects
R O Day
Publications and source records attributed to R O Day.
The effect of various drugs on adenosine triphosphate content and histamine release from rat peritoneal cell suspensions rich in mast cells.
1. Iopanoic acid and iophenoxic acid were potent inhibitors of compound 48/80-induced histamine release from rat peritoneal cell suspensions rich in mast cells and caused a parallel dose-related reduction in ATP content of these cells. 2. Lignocaine was less potent and ouabain and probenecid were ineffective in inhibiting histamine release and reducing cellular ATP content. 3. Various drugs can inhibit 48/80-induced histamine release from rat peritoneal cells and this activity may result from depletion of cellular ATP. It is apparent that little structural specificity is required for activity in this cell system.
Effects of various drugs on the osmotic lysis of rat mast cells.
1. Rat mast cells were exposed to low osmotic pressures to produce a 'non-specific' disruption of the mast cell, with release of histamine along with other intracellular contents. 2. The effect of non-steroidal anti-inflammaotry drugs and various other drugs upon osmotically induced histamine release was examined. 3. Representative non-steroidal anti-inflammatory drugs indomethacin, phenylbutazone and flufenamic acid, the acidic compounds ethacrynic acid, iopanoic acid and probenecid, and the local anaesthetic lignocaine, all caused a dose-dependent facilitation of osmotically induced histamine release compared to controls. All drugs were active at 0.1 mmol/l. 4. The previously observed inhibition of compound 48/80 and the antigen-induced histamine release from rat mast cells by similar concentrations of the drugs used in the present study are unlikely to be due to mast cell plasma membrane stabilization.
Induction of salicyluric acid formation in rheumatoid arthritis patients treated with salicylates.
Average steady-state serum salicylate concentrations and salicyluric acid (SU) formation rates were measured in 4 subjects with rheumatoid arthritis. After a salicylate washout period (1 month), the mean observed maximum formation rate of SU was determined by collecting frequent urine samples after a single oral dose of salicylate (35 mg/kg). The patients were then commenced on appropriate high dose salicylate therapy. Two and 5 weeks later, the mean observed maximum rates of SU formation were re-determined along with the average steady-state serum salicylate concentrations. Mean observed maximum SU excretion rates increased significantly between the single-dose study (0.96 +/- 0.22 mg/kg/h) and the last dose of the high dose therapy at 2 weeks (1.65 +/- 0.30 mg/kg/h; p less than 0.01); however, there was no further increase at week 5. Similar increases in the theoretical maximum rate of SU formation (Vmax) were observed between the single-dose study and after 2 weeks of high dose salicylate therapy. Average steady-state serum salicylate concentrations showed no decline between weeks 2 and 5. High dose salicylate therapy leads to acceleration of the rate of SU formation in patients with rheumatoid arthritis and this occurs largely during the first 2 weeks of therapy.
Overdose with chloral hydrate: a pharmacological and therapeutic review.
The purpose of this review is to highlight the toxicity of chloral hydrate and to review the management of overdoses with chloral hydrate. Three patients are presented in whom life-threatening cardiac arrhythmias dominated the clinical presentation. These arrhythmias were resistant to standard antiarrhythmic therapy. Also, we have reviewed selected features in eight patients who took overdoses of chloral hydrate who were admitted to an intensive care unit between 1981 and 1988. The pharmacology and toxicology of chloral hydrate are discussed with particular reference to the cardiac arrhythmias that are seen with overdosage. A proposed management scheme is detailed, including intravenously-administered propranolol as the preferred first-line antiarrhythmic agent. A case may be made for the discontinuation of the usage of chloral hydrate.
Non-steroidal anti-inflammatory drug induced upper gastrointestinal haemorrhage and bleeding.
Explore the source record for details and available documents.
Pharmacokinetic and pharmacodynamic aspects of the ideal COX-2 inhibitor: a rheumatologist's perspective.
The ideal cyclooxygenase-2-specific inhibitor (coxib) would demonstrate efficacy comparable or superior to the best non-steroidal anti-inflammatory drug (NSAID) and, in addition to being substantially less gastrotoxic than the safest conventional NSAID, would have limited or no cardiovascular or renal toxicity and be generally tolerated as well as placebo. The contribution of the pharmacokinetic properties of a coxib to achieving this goal has been overlooked to some degree for available coxibs. Maximizing synovial compartment exposure while minimizing systemic exposure may deliver tolerability benefits, particularly with respect to rates of hypertension and cardiovascular and thrombotic adverse effects.
The pharmacokinetics of albumin conjugates of D-penicillamine in humans.
D-penicillamine (D-PEN) is incompletely recovered during short-term balance studies, despite rapid elimination of D-PEN and its low molecular weight metabolites. Urinary excretion of metabolites of D-PEN also persists long after cessation of chronic therapy. A study was performed to determine whether the formation and later breakdown of a stable disulfide between D-PEN and plasma albumin could explain these aspects of D-PEN pharmacokinetics. Five human volunteers received D-penicillamine, 250 mg orally, daily for 21 days. Plasma concentration-time profiles for D-PEN and D-PEN-albumin disulfide (D-PEN-albumin) were determined during the first day and pre-dose concentrations were measured on five further occasions. The pharmacokinetics of D-PEN on the first day were similar to those reported previously. No D-PEN was found in any of the pre-dose specimens. The concentration of D-PEN-albumin rose rapidly during the first day, with an estimated 8.6% of the bioavailable D-PEN being transformed to D-PEN-albumin. Pseudo-steady-state concentrations of D-PEN-albumin were achieved in three subjects at between 14 and 21 days. The mean trough concentration of D-PEN-albumin at 21 days (19.5 microM) exceeded the peak concentration of D-PEN (during the first day) by 5.7-fold. The terminal elimination half-life of D-PEN-albumin was 1.65 +/- 0.29 days, which compared with an elimination half-life of 59 +/- 8.4 min for D-PEN.(ABSTRACT TRUNCATED AT 250 WORDS)
Corticosteroid injection for osteoarthritis of the knee: peripatellar compared to intra-articular route.
Intra-articular injection of micro-crystalline corticosteroid is used to treat symptomatic osteoarthritis (OA) of the knee, but its duration of effect and efficacy are uncertain. From the observation that pain in OA of the knee can often be blocked by infiltration of the soft tissues at the patella margin with local anaesthetic, this study investigated an injection technique in which corticosteroid was infiltrated around the patella. Thirty-eight patients with radiologically demonstrable and painful OA of the knee were treated either with peripatellar or intra-articular methylprednisolone in a randomised double blind study. Assessments of response to either injection were made at one week, one month and three months. Eleven of 15 measures improved significantly over time in both groups, but the differences between groups were not statistically significant. Analysis of individual responses showed that the majority of good outcomes were in the peripatellar group. Five patients receiving intra-articular injections but only one receiving a peripatellar injection withdrew because of treatment failure. Peripatellar injection is an alternative method of local administration of corticosteroid which is highly effective in a proportion of patients and merits further evaluation.
Auranofin in rheumatoid arthritis.
Explore the source record for details and available documents.
Terminations of treatment with gold sodium thiomalate in rheumatoid arthritis.
Treatment terminations with gold sodium thiomalate (GST) in 200 patients with rheumatoid arthritis (RA) were analyzed using the life table method. The termination rate was 27% at 6 months, 48% at 12 months and 84% at 48 months. The major reason for termination was mucocutaneous reaction. Pretreatment clinical and laboratory status of the RA did not influence terminations significantly. Concurrent administration of oral corticosteroids had no significant effect on gold terminations. Complete control of synovitis was achieved in 38% of patients by a median time of 6 months but sustained for greater than 12 months in only 19%.