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Biomedical subjects

P Walson

Publications and source records attributed to P Walson.

9 recordsLinked to original sources

Strychnine poisoning in an adolescent.

One half hour following the ingestion of a possibly tainted antibiotic capsule, a 14 year-old female experienced acute onset of stiffness and weakness in her lower extremities. She subsequently survived despite the development of convulsions, severe lactic acidosis (pH 6.86), hyperthermia (Temp 40.5 degrees C) and rhabdomyolysis. Toxicology testing confirmed the presence of strychnine in blood, gastric aspirate, and urine. Her course, history and outcome are presented and the pharmacokinetics, the mechanism of action, signs and symptoms and treatment of strychnine poisoning are reviewed.

Adolescent

Carbamazepine plasma concentration. Relationship to cognitive impairment.

Neuropsychological function was assessed before and after carbamazepine monotherapy in children with newly diagnosed complex partial epilepsy. Simultaneous video-electroencephalographic monitoring examined the influence of subclinical abnormal electrical discharges on performance. Total and unbound plasma carbamazepine concentrations were examined in relation to changes in performance at low (carbamazepine level, less than or equal to 32 mumol/L [less than or equal to 7.5 mg/L]) and moderate (carbamazepine level, greater than 34 mumol/L [greater than 8.0 mg/L]) drug levels. The data suggest a mild beneficial effect of carbamazepine on speeded eye-hand coordination and, at low drug levels, more rapid processing of items in memory. Efficiency of learning new information and memory-scanning rate displayed a concentration-dependent relationship with carbamazepine level, with poor performance significantly associated with higher carbamazepine plasma concentrations. Carbamazepine free levels were equivalent to total levels in predicting cognitive side effects.

Carbamazepine

Kinetics of clonazepam in relation to electroencephalographic and clinical effects.

The aim of this study was to see if the immediate EEG and clinical response to an intravenous dose of clonazepam was predictive for the effect of oral clonazepam maintenance therapy. Four children with petit mal epilepsy were given clonazepam intravenously during continuous EEG recording. Clonazepam plasma concentrations were determined repeatedly with a high performance liquid chromatographic method using a reversed phase system. The day after the intravenous dose the patients were given oral therapy with clonazepam. Repeated long-term EEG recordings were made and plasma concentrations of clonazepam were determined. There was no clinically satisfactory effect of clonazepam during oral maintenance treatment in three of the children who responded well to the intravenous dose of clonazepam. Thus, the immediate response to intravenous clonazepam was not a good predictor of the long-term effects in our patients.

Adolescent

Regional epidural analgesia: kinetics of pethidine.

Low intrathecal doses of opiates produce dose-dependent long-wasting elevation of the pain threshold in rats. The effect is postulated to be mediated by a direct action on the substantia gelatinosa of the spinal cord. Eight uncontrolled and two controlled studies in man showed a long duration of analgesia for most patients in the postoperative period. The duration of effect differs widely within and between studies. Using a double-blind design, we compared the relative efficacy of epidural and parenteral pethidine to control postoperative pain after total hip replacement. Preliminary pharmacokinetic data from six patients show that epidural doses of 20 or 60 mg pethidine give a similar pattern of absorption and elimination in plasma as 2 mg pethidine/kg body weight intramuscularly. The terminal elimination half-lives of pethidine in plasma are 5-7 h for all routes of administration. The possibility cannot be excluded that the analgesic effect of epidural pethidine is partly systemically mediated.

Anesthesia, Conduction

Effect of dose on phenytoin absorption.

To determine the effect of dose on phenytoin bioavailability, a single intravenous 15-mg/kg dose, single oral doses of 400, 800, and 1,600 mg, and 1,600 mg in divided doses (400 mg every 3 hr) were given to six healthy male subjects. Values of Vmax (maximum elimination rate) and Km (serum concentration at which rate of elimination is one half the maximum rate) from the intravenous dose were used to determine the extent of absorption. Although no statistically significant difference in extent of phenytoin absorption was detected, the time to reach maximum phenytoin serum concentrations increased from 8.4 hr for the 400-mg dose and 13.2 hr for the 800-mg dose to 31.5 hr for the 1,600-mg dose. After the 400, 800, and 1,600-mg doses and 1,600-mg divided doses, the serum concentration peaks were 3,9, 5.7, 10.7, and 15.3 mg/l. It is suggested that the prolonged, but complete, absorption of large phenytoin doses is due to slow dissolution and continued absorption from the colon. Due to prolonged absorption of phenytoin, it may be necessary to use larger oral than intravenous loading doses to achieve the same maximum phenytoin serum concentrations.

Administration, Oral

Levodopa and childhood amblyopia.

A pilot study was undertaken to address the tolerance and efficacy of levodopa/carbidopa treatment for amblyopia in older amblyopic children who failed to respond to conventional occlusion therapy. Five amblyopic children, between the ages of 7 and 12 years, and two normal adults were given between 100 mg/25 mg and 400 mg/100 mg of levodopa/carbidopa, respectively, depending on body weight. A symptoms questionnaire was completed, with temperature, respiration, heart rate, and blood pressure taken periodically to assess tolerance. Blood samples were taken, via a heparin well, to assess the pharmacokinetics of levodopa, dopamine, noradrenaline, and DOPAC. Snellen visual acuity, contrast sensitivity, stereo acuity, and pattern VERs were measured periodically to assess efficacy. The results revealed a high prevalence of side effects including emesis and nausea (four of seven subjects). Pharmacokinetics revealed that maximum serum levels of levodopa occurred 30 minutes to 1 hour after drug ingestion and decreased by 50% after 2 to 4 hours. One hour after drug ingestion, Snellen visual acuity temporarily improved from an average of 20/159 to 20/83 in the amblyopic eyes. Contrast sensitivity and pattern VERs (10-minute checks) temporarily improved in both dominant and amblyopic eyes, whereas visual function remained stable in normal eyes. The improvements in visual function started to decrease 5 hours after drug ingestion. The results are discussed in the context of developing a therapeutic trial of levodopa/carbidopa for childhood amblyopia.

Adult