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Biomedical subjects

S Dany

Publications and source records attributed to S Dany.

10 recordsLinked to original sources
PubMed1995

Differentiation between organophosphate and carbamate poisoning.

We propose a novel and simple assay for the real-time differentiation between carbamate and organophosphate inhibition of cholinesterase, based on our observations of the kinetic behavior of inhibited enzyme. The assay of carbamylated cholinesterase activity over time follows a non-linear kinetic pattern, whereas that of phosphorylated enzyme activity is linear. This feature can be exploited to differentiate between carbamate and organophosphate cholinesterase inhibition. The non-linear pattern characteristic of carbamates is easily discernible at degrees of inhibition of 40% or more. In this setting, cholinesterase activity ought to be measured continuously for about 1 h to obtain the kinetic pattern of enzyme activity. The initial activity, measured during the first 5 min of assay, represents the activity of enzyme in vivo. In vitro reactivation of inhibited cholinesterase allows the estimation of full potential activity of enzyme prior to poisoning, so that percentage of inhibition can be calculated. Reactivation of carbamylated cholinesterase is obtained by the incubation of diluted enzyme at 37 degrees C for 2.5 h prior to assay, whereas phosphorylated (non-aged) enzyme is reactivated by a 30 min incubation with oximes. In cases of mild exposure to cholinesterase inhibitors (< 40% inhibition), the response of enzyme to in vitro reactivation serves as a complementary test for exposure and for the nature of the inhibitor. All the results presented in this work refer to plasma cholinesterase. Erythrocyte cholinesterase was found to behave very similarly to plasma enzyme and its results have not been reported here.

Adolescent↗
PubMed1992

Computer assisted design of a theophylline dosing regimen in acute bronchospasm: serum concentrations and clinical outcome.

The effect of intravenous theophylline on the outcome of inhospital treatment of acute bronchospasm has been assessed, comparing the results achieved by computer-assisted dosing, designed to achieve and maintain a serum theophylline level of 16 micrograms.ml-1 (10 patients) with those of unaided physicians (15 control patients). The outcome measures compared were clinical improvement, peak expiratory flow rate and serum theophylline concentration. Loading doses of theophylline in the control and computer groups were: 167 and 437 mg, respectively. Initial serum theophylline concentrations, measured 20 min after the loading dose, were 13.6 and 17.0 micrograms.ml-1 in the control and computer groups, respectively. In patients who had not received theophylline prior to admission, loading doses and initial concentrations were: 200 mg and 9.4 micrograms.ml-1 in the control group (n = 5) versus 613 mg and 15.7 micrograms.ml-1 in the computer group (n = 4), respectively. During maintenance therapy, serum theophylline concentrations were kept in the therapeutic range (10-20 micrograms.ml-1) throughout 51% and 77% of the hospitalisation period, in the control and computer groups, respectively. There were no differences between the two groups in the rate or extent of clinical improvement or in change in peak expiratory flow rate. The computer assisted theophylline dosing regimen outperformed that of the unaided physicians in achieving and maintaining therapeutic serum theophylline concentrations in acute bronchospasm. There was no correlation between clinical outcome and serum theophylline concentration, but this may have been due to the small sample size and modest difference in serum theophylline between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Sodium cromoglycate in asthma: correlation between response and serum concentrations.

The clinical response to sodium cromoglycate treatment was compared with its concentration in serum. Twenty five children with asthma entered a 10 week trial of two baseline weeks followed by eight weeks of treatment by the inhalation of 20 mg of sodium cromoglycate spincaps four times a day. Individual clinical response was determined by the differences between baseline and treatment periods of: (a) percentage of symptomless days (delta score 0); (b) diary derived daily score for four symptoms (delta DS); and (c) peak expiratory flow rate (delta PEFR). At the end of the treatment period, patients inhaled a 20 mg spincap of sodium cromoglycate and the technique of inhalation was graded. Concentrations of sodium cromoglycate in serum were measured by radioimmunoassay in samples withdrawn 5 to 120 minutes after inhalation. Delta Score 0, delta DS, and delta PEFR correlated significantly with the area under the concentration time curve. Both the area under the sodium cromoglycate concentration time curve and clinical response correlated significantly with inhalation technique score. We suggest that response of children with asthma to inhalation treatment with sodium cromoglycate is correlated to its serum concentrations.

Administration, Inhalation↗
PubMed1985

Phenytoin bioavailability assessed by steady state serum concentrations.

The effect of a change in bioavailability of phenytoin sodium formulations on steady state serum concentrations was assessed in two groups of neurosurgical patients (n = 20 and 12). One group was studied in 1980 while on the old formulation, the other in 1983 while on the new formulation. Data were also obtained from routine therapeutic-level monitorings in 85 ambulatory patients receiving the new formulation during 1984. Phenytoin levels on the 400-mg/day dose were 10.9 +/- 4.1 (SD) and 16.1 +/- 5.6 micrograms/ml on the old and new formulations, respectively (P less than 0.01) in the neurosurgical patients. Routinely monitored levels on the 300-mg/day dose were 6.9 +/- 4.9 and 12.1 +/- 6.8 micrograms/ml, respectively (P less than 0.01). The maximum elimination rate of phenytoin, estimated from steady state dose-concentration pairs, was significantly higher on the old formulation (9.5 +/- 2.8 vs. 7.2 +/- 1.1 mg/kg per day, P less than 0.025) even though there was no difference in the estimates of the Michaelis-Menten constant. The proportion of subtherapeutic levels on ostensibly equal doses fell from 85 to 45% on 300 mg/day of the two formulations (P less than 0.01), and to 28% on 400 mg/day of the new formulation. Steady state concentrations may be used to assess increased bioavailability of drugs with capacity-limited metabolism, such as phenytoin.

Adult↗
PubMed1984

Kinetics of intravenous phenytoin in children.

Single-dose intravenous phenytoin (9.4-21.3 mg/kg) effectively eradicated seizures within 3 minutes in 12 out of 13 patients in status epilepticus. Eleven additional patients were treated prophylactically. No adverse effects were observed and neurological status was unaltered in all 24 cases. Phenytoin volume of distribution was found to decline significantly with age from 1.6 L/kg at 1 year to 0.6 at 10 years (P less than 0.01). Estimates of Vmax, the maximal rate of phenytoin metabolism, were obtainable in 8/24 patients and were in the expected range (10.6 +/- 4.2 mg/kg/day) for their age (6.6 +/- 2.8 years). Therapeutic serum concentrations (initial post distribution values 17.9 +/- 9.0 micrograms/ml) were maintained for more than 10 hours in 15/24 patients. Single-dose intravenous phenytoin is both effective and safe in the treatment and prevention of epileptic seizures in pediatric patients.

Adolescent↗
PubMed1980

Colchicine kinetics in patients with familial Mediterranean fever.

Serum colchicine levels were determined by radioimmunoassay after a 1-mg bolus injected intravenously in 4 patients with familial Mediterranean fever and in 6 normal subjects. Mean elimination half-life (t1/2) (+/- SEM) was 157 +/- 20 min in the patients and 65 +/- 15 min in the normal subjects (p less than 0.005). Total clearance was 239 +/- 50 ml/min in the patients and 601 +/- 155 ml/min in the normal subjects (p less than 0.05). Volume of distribution (Vdarea) was 76 +/- 16 and 49 +/- 91 and did not differ significantly. In 8 patients receiving colchicine prophylactically with good clinical response, serum colchicine ranged from 0.3 to 2.4 ng/ml after daily doses of 1 mg orally. In 2 responding patients 2-mg doses orally induced levels from 4 to 10 ng/ml, and in one (a nonresponder) a 3-mg dose induced levels of 7.5 to 13 ng/ml. Of 3 patients receiving 2 mg daily with unsatisfactory clinical responses, serum levels were not detectable in one and in the low range of 1.5 to 5.4 ng/ml in the others. It is suggested that lack of response to colchicine orally in some nonresponders could result from inadequate absorption or altered disposition of colchicine.

Adult↗
PubMed1980

Inadequacy of reported intake in assessing the potential hepatotoxicity of acetaminophen overdose.

No evidence of liver damage was found in a series of 22 patients with acute acetaminophen overdose, 13 of whom reported ingesting doses of 10 to 25 g, which is within the accepted hepatotoxic range. Serum acetaminophen concentrations did not exceed 160 micrograms/ml, an amount well below the minimal hepatotoxic level. Moreover, mean serum concentrations of acetaminophen in patients reporting the ingestion of less than 10 g [74 +/- 48 (SD) micrograms/ml) were similar. Throughout the study, no correlation was found between serum concentrations and the reported dose ingested. Poor bioavailability of local acetaminophen formulations was ruled out as a factor in the dose-concentration discrepancy by comparison with a British formulation ingested by four volunteers. We conclude that information regarding dose ingestion given by patients admitted to hospital for self-poisoning is inaccurate and often exaggerated. Management of acute acetaminophen overdose must be based on serum concentrations of acetaminophen and not on the reported dose.

Acetaminophen↗