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Biomedical subjects

J T Callaghan

Publications and source records attributed to J T Callaghan.

26 records · Page 2Linked to original sources

Correlation of in vivo and in vitro expression of cell-mediated immunity to mumps skin test antigen.

The simplest functional assay of cell mediated immunity, skin testing, is not always possible to do in every patient. A variety of in vitro assays, including lymphocyte transformation (LT), have been developed as possible alternatives to skin testing. In this report studies were undertaken to determine whether LT induced by mumps skin test antigen (MSTA) correlated with skin test sensitivity. LT stimulated by MSTA was performed with cells obtained from 43 normal subjects. Each subject was subsequently skin-tested with up to four concentrations of MSTA. LT results correlated well with skin test reactions. Lymphocytes from all subjects were responsive in LT assays. A less pronounced correlation was observed between the concentration of MSTA used for skin testing and LT. The results of these experiments suggest that LT assays with MSTA provide an adequate substitute for MSTA skin tests.

Antigens, Viral↗

CSF perfusion to treat intraventricular penicillin toxicity.

A shunt infection and meningitis developed in a patient receiving methotrexate intravenously for CNS leukemia. Convulsions and respiratory failure followed the intraventricular administration of 300,000 units of penicillin G potassium. Perfusion with 900 mL of Ringer's lactate removed an amount of penicillin equal to that injected intraventricularly plus some from systemic treatment.

Adult↗

Pergolide, a potent long-acting dopamine-receptor agonist.

After single doses (100 to 400 microgram orally), pergolide, a synthetic ergot, reduced basal plasma prolactin levels in normal subjects in a dose-related manner. This effect persisted for more than 24 hr. Multiple doses of pergolide (150 to 250 microgram daily for 7 days) resulted in a plasma prolactin decrease of more than 80%. A single dose of pergolide (150 microgram orally) suppressed plasma prolactin and abolished the plasma prolactin diurnal rhythm, i.e., suppression of sleep-induced elevation in plasma prolactin during a 40-hr period. Perphenazine (5 mg intramuscularly)-induced plasma prolactin elevation was inhibited by pergolide; the effect was dose dependent. After single or multiple doses, pergolide had no effect on plasma follicle-stimulating hormone, luteinizing hormone, cortisol, growth hormone, and thyroid-stimulating hormone. Pergolide appears to have specificity at the pituitary level for the dopamine receptors that mediate prolactin secretion.

Adult↗

In-flight medical emergencies. One year of experience with the enhanced medical kit.

Recent regulations require commercial US aircraft to carry an enhanced medical kit. We reviewed kit use on United Airlines during the initial year of the regulations. We also surveyed passengers who became ill during flight and health care providers who used the new kit. The medical kit was used 362 times on 361 flights (once in every 1900 flights or one use for every 150,000 air travelers). Health care providers indicated that the kit was useful in more than 80% of emergencies and was occasionally lifesaving. In the emergencies in which the kit was used, 70% fell into one of seven major diagnostic groupings, including syncope/near syncope (29%), cardiac/chest pain (16%), asthma/lung disease/shortness of breath (10%), and allergic reactions (5%). With 450 million domestic air travelers per year, we would expect 3000 in-flight medical emergencies annually, and conclude that the enhanced medical kit is beneficial and propose that its effectiveness would be improved by the addition of a bronchodilator for inhalation.

Adult↗

Disposition in humans of racemic picenadol, an opioid analgesic.

Racemic picenadol is being tested clinically as an analgesic. The (+)-enantiomer of picenadol is an opioid agonist and the (-)-enantiomer is a weak agonist/antagonist. The disposition of racemic [14C] picenadol was studied in healthy men after a single dose was administered im (N = 3) and orally (N = 5). After the dose, virtually none of the radioactivity that appeared in blood was associated with the red cells. In plasma, approximately 4% of the radioactivity was attributable to the parent drug, the remainder being picenadol glucuronide (approximately 35%) and other metabolites. The t1/2 for total radioactivity was 6 hr, that for the unchanged drug was 3.5 hr. Picenadol was present in plasma almost exclusively as the (+)-enantiomer. However, after incubation with glucuronidase and sulfatase, plasma contained 2 to 4 times more (-)- than (+)-picenadol, indicating that more conjugated (-)-picenadol than conjugated (+)-picenadol was in the plasma. After im and oral administration of [14C]picenadol, plasma levels of radioactivity were generally 10 and 70 times higher than those in saliva, respectively. More than 90% of the administered radioactivity was excreted in the urine, mostly as picendol glucuronide, and lesser amounts of picenadol sulfate and N-desmethylpicenadol sulfate. Only about 1% of the administered dose of picenadol appeared unchanged in urine. The disposition of racemic picenadol in humans was stereoselective, the (-)-picenadol apparently being metabolized preferentially over the (+)-enantiomer. This finding was of particular interest in view of the dissimilar pharmacologic activities of the enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Nizatidine, an H2-blocker. Its metabolism and disposition in man.

The disposition of a single oral dose of about 150 mg of nizatidine, an H2-blocker, was studied in five men. Plasma levels of both parent drug and radioactivity peaked in 1-3 hr. Nizatidine accounted for about 60% of the plasma radioactivity. The t1/2 of nizatidine was 1.6 hr. About 35% of nizatidine became bound to plasma proteins in vitro, particularly to alpha-1-glycoprotein. Warfarin, acetaminophen, phenobarbital, propantheline, diazepam, and propranolol did not notably affect the amount of nizatidine bound. Two to 3 times more radioactivity was in plasma than in blood cells or saliva. Greater than 90% of the dose of nizatidine was excreted in urine, probably by glomerular filtration and active tubular secretion. Nizatidine accounted for about 65% of the urinary radioactivity. The major metabolite of nizatidine was N2-monodesmethylnizatidine; it represented about 7% of the nizatidine dosage. Another metabolite, constituting about 5% of the dose, is proposed to be nizatidine N2-oxide. Nizatidine sulfoxide also may be a minor metabolite of nizatidine.

Adult↗

Lack of effect of olanzapine on the pharmacokinetics of a single aminophylline dose in healthy men.

STUDY OBJECTIVE: To test whether olanzapine, an atypical antipsychotic, is an inhibitor of cytochrome P450 (CYP) 1A2 activity, we conducted a drug interaction study with theophylline, a known CYP1A2 substrate. DESIGN: Two-way, randomized, crossover study. SETTING: Clinical research laboratory. SUBJECTS: Nineteen healthy males (16 smokers, 3 nonsmokers). INTERVENTIONS: Because the a priori expectation was no effect of olanzapine on theophylline pharmacokinetics, a parallel study using cimetidine was included as a positive control. In group 1, 12 healthy subjects received a 30-minute intravenous infusion of aminophylline 350 mg after 9 consecutive days of either olanzapine or placebo. In group 2, seven healthy subjects received a similar aminophylline infusion after 9 consecutive days of either cimetidine or placebo. MEASUREMENTS AND MAIN RESULTS: Concentrations of theophylline and its metabolites in serum and urine were measured for 24 and 72 hours, respectively. Plasma concentrations of olanzapine and its metabolites were measured for 24 hours after the next to last dose and 168 hours after the last olanzapine dose. Olanzapine did not affect theophylline pharmacokinetics. However, cimetidine significantly decreased theophylline clearance and the corresponding formation of its metabolites. Urinary excretion of theophylline and its metabolites was unaffected by olanzapine but was reduced significantly by cimetidine. Steady-state concentrations of olanzapine (15.3 ng/ml), 10-N-glucuronide (4.9 ng/ml), and 4'-N-desmethyl olanzapine (2.5 ng/ml) were observed after olanzapine 10 mg once/day and were unaffected by coadministration of theophylline. CONCLUSION: As predicted by in vitro studies, steady-state concentrations of olanzapine and its metabolites did not affect theophylline pharmacokinetics and should not affect the pharmacokinetics of other agents metabolized by the CYP1A2 isozyme.

Adult↗