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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 379 records · Page 21Linked to original sources

Clinical pharmacology of edrophonium in infants and children.

The dose-response relationship, onset, duration of action, atropine requirement, and pharmacokinetic variables of edrophonium were determined in infants and children during N2O-halothane anesthesia. The technique of steady state infusion of d-tubocurarine anesthesia. The technique of steady state infusion of d-tubocurarine (dTc) was used to determine the ED50 for edrophonium (i.e., the dose producing 50% antagonism of 90% neuromuscular depression) in 4 infants (145 micrograms/kg) and 12 children (233 microgram/kg). The reported values for ED50 for edrophonium (obtained under similar anesthetic conditions) is 128 micrograms/kg for adults. These three dose-response curves do not differ statistically; however, there was greater variability among infants and children than adults. Time to peak antagonism was similar for all three age groups. Duration of antagonism was determined in six infants and six children and did not differ from the reported value for adults. The optimal dose and time of administration of atropine were established by administering edrophonium (1 mg/kg) and atropine (10-20 micrograms/kg) to 24 infants and children. The smallest changes in heart rate and systolic blood pressure occurred when atropine (10 micrograms/kg) was given 30 s before edrophonium. The pharmacokinetics of edrophonium (1 mg/kg) were studied in four infants and four children and were compared with published values for adults: distribution and elimination half-lives and distribution volumes were similar for the three groups. Total clearance (ml.kg-1.min-1) was greatest for infants (17.8 +/- 1.2) compared with children (14.2 +/- 7.3) and adults (8.3 +/- 2.9). The authors conclude that the dose of edrophonium required toantagonize dTc-induced neuromuscular blockade is similar or possibly greater for infants and children than for adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Metabolites of neostigmine and pyridostigmine do not contribute to antagonism of neuromuscular blockade in the dog.

The authors sought to determine whether the metabolites of neostigmine and pyridostigmine contribute to antagonism of neuromuscular blockade. Accordingly, the dose-response relationship, onset and duration of action (n = 60), and pharmacokinetics (n = 22) of neostigmine, pyridostigmine, their metabolites 3-hydroxyphenyltrimethylammonium (PTMA) and 3-hydroxy-N-methylpyridinium (MP), and edrophonium were determined in dogs anesthetized with sodium pentobarbital. The force of contraction of the anterior tibialis muscle was maintained at constant 90% depression by infusing pancuronium. Then, a single iv bolus dose of one of the drugs under study was injected while the pancuronium infusion was continued. Venous blood, urine, and bile were sampled for four hours. Concentrations were determined by liquid chromatographic techniques; a three-compartment pharmacokinetic model was fitted to the serum concentration data. The doses producing 50% antagonism were 6.5, 52, 69, and 40 micrograms/kg for neostigmine, pyridostigmine, edrophonium, and PTMA, respectively. MP was inactive as an antagonist. By comparing approximately equipotent doses, time to peak antagonism (onset) and until 30% of peak antagonism remained (duration) were shorter for both edrophonium and PTMA than for neostigmine and pyridostigmine. Slow distribution and elimination half-lives, volume of distribution at steady state (VDss), and total plasma clearance (Cl) were similar for the drugs except for a smaller Vdss and lower Cl for MP. More than 60% of the dose of each drug was recovered unchanged from urine; less than 1% was recovered from bile. Less than 10% of the dose of neostigmine was recovered as PTMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The pharmacokinetics and pharmacodynamics of atracurium in patients with and without renal failure.

To determine the influence of renal function on the pharmacology of atracurium, 10 patients with normal renal function and 10 with renal failure (scheduled for cadaver kidney transplant) were anesthetized with nitrous oxide and halothane. Atracurium besylate, 0.5 mg . kg-1, was given as an iv bolus and plasma samples were collected over a 4-h period. These samples were assayed for atracurium (all patients) and laudanosine, one of the principal metabolites (eight of the normal group), using an ion-exchange liquid chromatographic assay. The plasma concentrations of atracurium for each patient were fitted to a two-compartment pharmacokinetic model. The onset time, duration of action, and recovery time of atracurium neuromuscular blockade were measured. There were no differences found in the pharmacokinetics or pharmaco-dynamics of atracurium between patients with normal renal function and those with renal failure. There were measurable levels of laudanosine following atracurium administration with peak levels of 199 +/- 31 ng . ml-1 at 2 min. The authors conclude that the pharmacokinetics and pharmacodynamics of atracurium are not altered by renal failure.

Anesthesia, General↗

The biological approach to the radiotherapy of the oral cancers of South India.

Two-thirds of all cancers in South India are squamous cell carcinomas, of which 78% to 93% are late cases requiring radiotherapy. Oral cancers, which constitute the majority of these, provided an excellent clinical model for studies in radiotherapeutic biology. Their characteristics made them ideally suited for our clinical trials. The paper reviews the special biology of these lesions, the factors involved in their radiation non-response, the therapeutic postulations that suggested themselves, the implementation of these therapeutic protocols and the mixed story of failure and success that has marked the two decades of these studies. It discovers the fact that radiation response is not just a factor of tumor extent but involves several biological subtleties in both tumor and its host environment. It also discusses possible future approaches to bridge a gap of about 30% failure in these lesions, especially in the context of a poor economy.

Bleomycin↗

Serum zinc levels in subtypes of leprosy.

Serum zinc levels were estimated in 146 patients with different types of leprosy and 40 control subjects. Tuberculoid patients were found to have normal serum zinc levels. A gradual reduction in serum zinc levels was observed from TT to LL. Serum zinc levels were not significantly higher in patients treated with dapsone for approximately 18 months. The cause of hypozincemia is not clear, but the findings suggest that there are correlations among bacillary load, immune status, and serum zinc. Zinc deficiency could be one of the factors involved in the nonspecific suppression of cell-mediated immunity in lepromatous leprosy.

Adolescent↗

Irradiation, bleomycin and hyperbaric oxygen in the treatment of oral carcinoma.

The present report is the sixth in a series of combination therapy trials in oral carcinoma in South India conducted since 1960. In the fifth trial a combination of bleomycin (BLM) and irradiation was compared with irradiation alone. The results gained and the subsequent experience in an unselected series demonstrated in buccal mucosal squamous cell carcinomas a highly superior effect with the irradiation-BLM combination, but still revealed a failure rate around 30 per cent. The present clinical trial--irradiation + BLM was compared with irradiation + BLM + hyperbaric oxygen (HbO) and irradiation + placebo + HbO--was undertaken in an attempt to eliminate or at least reduce these failures. The results were unexpectedly disappointing in that the irradiation combined with BLM + HbO proved to be inferior to irradiation + BLM. An attempt has been made to elucidate the possible reasons for this surprising outcome.

Bleomycin↗

Serology of Aspergillus granuloma.

A total of 21 cases of granuloma caused by Aspergillus species were encountered during the period 1972-79. The organs involved were nasal and paranasal sinuses, brain, orbit, subcutaneous tissue of check, lungs and endocardial valve in the decreasing order of their frequency. Aspergillus flavus was the main etiological agent. Immunodiffusion tests with various Aspergillus species as antigen showed a positively of 17 out of 18 (94.4 per cent) cases. The role of precipitins in diagnosis and prognosis of the disease has been discussed.

Adolescent↗