Search PubMed⌕ Search

Biomedical subjects

M D Rawlins

Publications and source records attributed to M D Rawlins.

At least 127 records · Page 7Linked to original sources
PubMed1985

Opiate-induced rhabdomyolysis.

Three patients with opiate self-poisoning developed acute muscle damage with elevated serum aspartate aminotransferase and creatine kinase activities, increased serum myoglobin concentrations, raised plasma creatinine concentrations, hypocalcaemia and hyperphosphataemia. These abnormalities gradually resolved over 7-10 days, but recovery was complicated due to the development of acute renal failure (requiring haemodialysis) in one patient. Plasma drug concentrations, shortly after admission, in the patients taking dihydrocodeine and morphine were grossly elevated (184 and 60 micrograms/l respectively). Clinical evidence of myopathy was minimal in all three patients and muscle biopsy of one patient was normal at 7 days.

Acute Kidney Injury↗
PubMed1985

2,5-Diphenyloxazole as a probe for microsomal mono-oxygenation in human and rat liver.

2,5-Diphenyloxazole (PPO) is metabolized to one major fluorescent product by human liver and rat liver microsomes. PPO metabolism by human-liver microsomes involves more than one cytochrome P-450 isozyme, termed low-affinity and high-affinity components. At a substrate concentration of 0.1 microM, 95% of activity is due to the high-affinity component whereas at 100 microM 69% of activity is due to the low-affinity component. Inhibition studies with metyrapone and alpha-naphthoflavone at 0.1 microM and 100 microM suggest that the high-affinity component may reflect a 3-methylcholanthrene-inducible form of cytochrome. Therefore studies at low substrate concentrations may be a useful tool for cytochrome P-450 studies in man. Rat liver microsomes show linear kinetics indicating the involvement of one major form of cytochrome P-450.

Animals↗
PubMed1985

Pharmacokinetics and clinical toxicity of quinine overdosage: lack of efficacy of techniques intended to enhance elimination.

We report clinical details in 16 cases of quinine poisoning. Plasma quinine concentrations above 15 mg/l were associated with increased risks of permanent visual damage and of cardiac arrhythmias from which one of our patients died. The rate of quinine elimination was not significantly altered by forced acid diuresis in five patients (t 1/2 25.1 +/- SEM 4.6 h) as compared to eight patients treated conservatively (t 1/2 26.5 +/- SEM 5.78 h). Neither urinary pH or flow rate correlated consistently with urinary quinine clearance. In three other patients charcoal column haemoperfusion, haemodialysis and exchange transfusion were performed. These were also ineffective in increasing quinine elimination. It is concluded that techniques advocated to increase quinine elimination are ineffective in the management of quinine poisoning.

Adolescent↗
PubMed1984

A comparative study of the effects of aspirin and paracetamol (acetaminophen) on platelet aggregation and bleeding time.

In a double blind, randomised trial, the effects of 1 g aspirin and 1 g paracetamol were compared on bleeding time and platelet aggregation in 40 volunteers (20 females). Also investigated was the relationship between plasma aspirin esterase activity and both bleeding time and platelet aggregation after aspirin. Following 1 g aspirin there was a significant increase in bleeding time at 24 h (p less than 0.01). A significant reduction (P less than 0.01) in platelet aggregation with collagen was observed at 1, 6 and 24 h after aspirin, but no significant reduction (P greater than 0.05) was observed with ADP. Paracetamol had no effect on bleeding time or platelet aggregation. Plasma aspirin esterase activity ranged from 0.26-0.6 mumol/ml/min. A significant negative correlation (R = -0.55, P less than 0.001) was observed between percentage increase in bleeding time (24 h) and plasma aspirin esterase activity. Further significant correlations were observed between plasma aspirin esterase activity and change in platelet aggregation with collagen at 1 h (R = 0.68, P less than 0.001), 6 h (R = -0.73, P less than 0.001) and 24 h (R = -0.67, P less than 0.001). These results suggest that it might be possible to predict an individual's haemostatic response to aspirin from knowledge of their plasma aspirin esterase activity.

Acetaminophen↗
PubMed1984

The effect of alcoholic cirrhosis on the two kinetic components (high and low affinity) of the microsomal 0-deethylation of 7-ethoxycoumarin in human liver.

The activities of the two kinetic components (high and low affinity) of the microsomal 0-deethylation of 7-ethoxycoumarin have been measured in liver from patients with alcoholic cirrhosis and in normals. The activity (expressed as pmol 7-OH coumarin formed/mg microsomal protein/min) of both components of the enzyme was significantly lower in alcoholic cirrhosis (high affinity = 3.27 +/- 1.18, low affinity 60.9 +/- 11.6) than in normals (high affinity 9.43 +/- 2.37, low affinity 111.3 +/- 9.2). These results are further evidence that there is a broad impairment of hepatic microsomal mono-oxygenase activity in alcoholic cirrhosis.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1984

The effect of age on pathways of drug metabolism in human liver.

The effect of age on some important pathways of drug metabolism in human liver biopsy specimens was examined. Five parameters were investigated: two microsomal mono-oxygenases; aldrin epoxidation and 7-ethoxycoumarin-O-de-ethylation; microsomal protein recovery; epoxide hydrolase activity and concentrations of reduced gluthatione. No correlation was observed between age and any of these measurements. It is concluded that, contrary to conventionally held views, impaired clearance of some drugs in the elderly is unlikely to be due to decreased hepatic microsomal enzyme specific activity. Any increase in adverse drug reactions in the elderly liver is unlikely to be due to impaired detoxification of reactive metabolites.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1984

The efficacy and pharmacokinetics of sodium salicylate in post-operative dental pain.

Sodium salicylate, 537 mg and 1074 mg were compared in a double-blind cross-over study in 24 patients with post-operative pain following removal of impacted lower third molars. No significant analgesic effect was observed after either dose of sodium salicylate, either overall or at any time point during the 5 h investigation period. Peak plasma concentrations of salicylate after 537 mg were observed at 30 min after dosage, whereas peak plasma salicylate concentrations after 1074 mg sodium salicylate occurred at 45 min after dosage.

Dose-Response Relationship, Drug↗
PubMed1984

Reduction of antipyrine clearance in psoriasis.

Antipyrine clearance was determined in 41 psoriatics and age-sex matched controls, using sequential measurements of salivary concentration. Antipyrine clearance and elimination rate constant were less in psoriatics (P less than 0.05) and apparent volumes of distribution were similar. These differences were greater between female psoriatics and controls (P less than 0.025; P less than 0.05) and the differences between male psoriatics and controls were not significant. Correlation of simultaneous measurements of saliva and plasma antipyrine concentration in six psoriatics and age-sex matched controls showed no differences between the two groups. We conclude that antipyrine clearance is reduced in psoriasis but the underlying mechanism is unclear.

Adolescent↗
PubMed1984

Aspirin metabolism and efficacy in postoperative dental pain.

Aspirin 1200 mg was compared with placebo in a randomised, double-blind, crossover study in 15 patients with postoperative pain after removal of impacted lower third molars. Over a 5 h investigation period, patients reported significantly less pain (P less than 0.01) after treatment with aspirin, than after treatment with placebo. Peak concentrations of aspirin occurred at 15 min after dosage. Significant negative correlations were observed between plasma aspirin esterase activity and both AUC aspirin (r = -0.904, P less than 0.001) and AUC analgesia (r = -0.91, P less than 0.001). Similarly, a significant correlation was observed between AUC aspirin and AUC analgesia (r = 0.96, P less than 0.001). Evidence from this study would suggest that an individual's pain relief in postoperative dental pain is determined by the rate of aspirin hydrolysis to salicylate.

Adolescent↗
PubMed1984

"Therapeutic" serum concentration of phenytoin: the influence of seizure type.

Serum phenytoin concentrations were monitored prospectively in 26 patients with previously untreated partial epilepsy, during monotherapy with phenytoin. Only six remained entirely seizure-free, although only four experienced further tonic-clonic seizures. There was no correlation between serum phenytoin concentrations and freedom from partial seizures in those patients in whom such seizures recurred. There did appear to be a correlation between serum phenytoin concentration and freedom from tonic-clonic seizures.

Adolescent↗
PubMed1984

Adverse reactions to N-acetylcysteine.

Clinical details of seven patients who suffered adverse reactions to N-acetylcysteine as Parvolex are documented. Skin testing was carried out to diluted Parvolex, and its individual components N-acetylcysteine and ethylenediaminetetra-acetate, in five reacting patients and five patients who had received Parvolex with no ill-effects. Weal responses to high concentrations (20 mg/ml) of acetylcysteine as Parvolex were significantly greater (p less than 0.02) in reactors. There were no other significant differences between the groups. In two patients who reacted, the effects of intradermal Parvolex could be inhibited by prior therapy with the antihistamine terfenadine. These results suggest a 'pseudo-allergic' rather than an immunological aetiology for adverse reactions to Parvolex.

Acetaminophen↗
PubMed1983

Aryl hydrocarbon hydroxylase activity and psoriasis.

Aryl hydrocarbon hydroxylase (AHH) has been measured in the skin, jejunum and liver of normal and psoriatic individuals. We have been unable to confirm previous reports of an abnormality in AHH activity in patients with psoriasis. Re-examination of the laboratory records on which the original reports were based leads us to doubt their veracity and validity.

Animals↗