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Biomedical subjects

D A Powell

Publications and source records attributed to D A Powell.

At least 127 records · Page 7Linked to original sources

Naloxone induces multiple effects on aversive Pavlovian conditioning in rabbits.

A series of experiments examined the effects of intravenous naloxone treatment on aversive Pavlovian conditioning of eye-blink and heart rate responses, and related unconditioned behaviors, in rabbits. Naloxone treatment before testing attenuated bradycardiac orienting responses to tones used as conditioning stimuli. Naloxone also attenuated conditioned bradycardia when administered either before or after training sessions, but it potentiated conditioned bradycardia during extinction of discriminative conditioning. Naloxone did not influence acquisition or extinction of discriminative eye-blink conditioning or somatic or cardiac responses to shocks used as unconditioned stimuli, but it did decrease locomotor activity. Naloxone treatment immediately after training sessions facilitated acquisition of eye-blink responses. It was concluded that naloxone influences aversive Pavlovian conditioning in more than one way: (a) During training, it appears to alter reception and processing of signals but does not affect subsequent development of somatic responses to the Pavlovian conditioning contingency. (b) After training sessions, naloxone apparently affects consolidation of both somatic and autonomic conditioning. (c) Naloxone also appears to delay extinction of Pavlovian conditioning; this effect may similarly involve changes in a stimulus-processing mechanism or in memory functions, but it apparently does not involve changes in somatomotor responsitivity.

Animals↗

Chloramphenicol serum concentration falls during chloramphenicol succinate dosing.

Chloramphenicol succinate and chloramphenicol kinetics were examined on two occasions at steady state, separated by 2 to 17 days, in 10 pediatric patients on the same intravenous dose of chloramphenicol succinate. The steady-state peak serum concentration of chloramphenicol succinate fell from an average of 77.1 micrograms/ml during the first study to 42.2 micrograms/ml during the second. The steady-state peak serum concentration of chloramphenicol also decreased from an average of 27.8 micrograms/ml to 24.9 micrograms/ml. There was a marked decrease in the steady-state trough serum concentration of chloramphenicol, which averaged 8.4 micrograms/ml during the first and 5.3 micrograms/ml at the time of the second study. Mean area under the serum concentration-time curve (AUC) of chloramphenicol succinate decreased from 59.7 micrograms . hr/ml to 24.0 micrograms . hr/ml. The AUC of chloramphenicol averaged 105.7 micrograms . hr/ml at the time of the first and decreased to 79.5 micrograms . hr/ml during the second study. Mean percent decrease in the AUC of chloramphenicol was about 28% and occurred most substantially in patients with high AUCs during the first study. Mean elimination chloramphenicol half-life was 3.0 hr during the first study and fell to 2.3 hr at the time of the second study. Our data indicate that chloramphenicol serum concentration should be monitored frequently, especially in patients not responsive to a set dose.

Adolescent↗

Comparative bioavailability and pharmacokinetics of chloramphenicol after intravenous chloramphenicol succinate in premature infants and older patients.

The bioavailability of chloramphenicol and the pharmacokinetics of chloramphenicol and chloramphenicol succinate were studied in 5 premature infants (group A), 8 full-term infants (group B) and 4 children (group C) receiving intravenous chloramphenicol succinate at steady-state. Although the total body clearances of chloramphenicol succinate were similar in the three groups, its renal clearance, 0.78 +/- 1.13 ml/min/kg, in group A was markedly lower than 4.11 +/- 2.41 ml/min/kg in group B (p less than 0.05) and 7.31 +/- 2.85 ml/min/kg in group C (p less than 0.05). The bioavailability of chloramphenicol, 0.93 +/- 0.10, in group A was considerably higher as compared to 0.71 +/- 0.14 in group B (p = 0.06) and 0.64 +/- 0.13 in group C (p less than 0.05). The elimination half-life of chloramphenicol, 10.08 +/- 6.88 h, in group A was longer than 3.48 +/- 1.52 h in group B (p less than 0.05) and 4.86 +/- 2.41 h in group C (p = 0.06). The increased bioavailability of chloramphenicol in premature infants was a result of the decreased renal clearance of chloramphenicol succinate causing a greater fraction of the chloramphenicol succinate dose to be hydrolyzed to chloramphenicol.

Biological Availability↗

A solid-phase radioimmunoassay for detection of antibodies against Mycoplasma pneumoniae.

A solid-phase radioimmunoassay (RIA) for the detection of Mycoplasma pneumoniae antibodies is described. This method uses M. pneumoniae organisms grown in microtiter plate wells as a solid-phase antigen that is economical and easy to prepare. Results obtained from our studies indicate this RIA method is highly sensitive and reproducible. This is a more specific assay than the popular complement fixation (CF) method because the glycolipid haptens employed in the CF test are not unique to M. pneumoniae. Data on 34 serum samples from 12 patients indicate the applicability of this diagnostic method for clinical use. In addition, this method measures the immunoglobulin class-specific antibody activities which may be important in differentiating recent and past infections.

Adult↗

Cingulate damage attenuates conditioned bradycardia.

New Zealand albino rabbits received either sham, midline cortical, lateral cortical, or combined medial-lateral cortical lesions, and were subjected to differential pavlovian conditioning in which tones of different frequencies served as the conditioning stimulus and a brief paraorbital electric shock train served as the unconditioned stimulus. Heart rate conditioned responses were recorded.d Damage to medial but not lateral neocortex abolished the heart rate conditioned response. These data suggest that midline cortical structures may modulate higher level processing of stimulus information.

Animals↗

Pharmacokinetics of theophylline in infants with bronchiolitis.

Theophylline pharmacokinetics were studied in 12 infants (age 3 weeks-6.5 months) with bronchiolitis. 9 of the 12 patients received a single dose of aminophylline (5.0-8.5 mg/kg) whereas the remainder were at steady-state receiving multiple doses (2.5-5.0 mg/kg) of aminophylline. The dose was administered IV over 0.5-1.0 h. An HPLC method was used to measure theophylline concentrations in serum and urine. Peak serum concentrations of theophylline measured by HPLC ranged from 8.48-21.6 micrograms/ml. Total, renal and nonrenal clearance of theophylline ranged from 4.66 to 19.25, 1.07 to 5.76 and 3.59 to 16.83 ml/min/m2, respectively. Mean apparent volume of distribution and elimination half-life were 8.75 l/m2 and 11.38 h, respectively. Although no significant correlation was observed between age and theophylline kinetic parameters, clearance appeared to increase and half-life decrease with age. Our patients had a substantially lower clearance and longer half-life as compared to published data in children greater than 1 year of age. A five-fold variation in theophylline clearance demonstrates the need for monitoring theophylline serum concentration to minimize the risk of potential toxicity.

Aminophylline↗

Cingulate cortex: its role in Pavlovian conditioning.

Three experiments with New Zealand albino rabbits examined the role of anterior and posterior cingulate cortex in Pavlovian conditioning. Tones served as conditioned stimuli, and paraorbital electric shock served as the unconditioned stimulus. Anterior cingulate lesions attenuated conditioned heart rate (HR) decelerations, relative to posterior cingulate or sham lesions, but enhanced the magnitude of the bradycardiac component of the orienting reflex. Posterior cingulate lesions enhanced the bradycardiac component of the conditioned response, particularly late in training, relative to anterior or sham lesions. Somatomotor eye-blink conditioning, shock thresholds, and HR unconditioned responses were unaffected by cingulate lesions. Electrical stimulation of cingulate cortex revealed effective sites for eliciting heart rate and blood pressure (BP) changes only in anterior cingulate cortex. Relatively large (70-100 beats per minute) HR decelerations accompanied by small (1-5-mm Hg) BP depressor responses were elicited by stimulation of this area; the HR decreases were abolished by atropine methyl nitrate but were unaffected by either propranolol hydrochloride or phentolamine hydrochloride. These results are discussed in terms of cingulate involvement in the mediation of the cardiovascular component of a response pattern related to stimulus processing.

Animals↗

Lateral septal lesions enhance conditioned bradycardia in the rabbit.

New Zealand albino rabbits received sham lesions or complete, medial, lateral, or posterior septal lesions and were subjected to differential conditioning in which tones of different frequencies served as conditioned stimuli and paraorbital electric shock was the unconditioned stimulus. Electromyographic (EMG), heart rate (HR), and blood pressure (BP) conditioned responses (CRs) as well as hippocampal rhythmic slow wave activity (RSA) were recorded. Lateral or complete septal lesions enhanced the bradycardiac HR CR but had no effect on the BP depressor response. Both unconditioned and conditioned EMG responses occurred infrequently and were unaffected by any lesion. Unconditioned HR responses and somatomotor threshold determinations to unsignaled electric shock were also unaffected by the lesions. Complete septal lesions increased locomotor activity relative to sham or other septal lesions. Little hippocampal RSA was detected in animals with medial lesions, but the HR CR was unimpaired in these animals. These data implicate the septo-hippocampal circuit in classical conditioning of cardiovascular changes and further suggest that diencephalic forebrain structures may modulate forebrain processing of sensory stimulation, perhaps in terms of assessing its biological significance.

Animals↗

Adverse effects of methicillin, nafcillin and oxacillin in pediatric patients.

68 patients (from newborns to 18 years of age) were studied prospectively for adverse effects associated with methicillin, nafcillin and oxacillin. Hematologic, liver and renal function tests were monitored before and during therapy. 3 of 28 patients receiving methicillin developed eosinophilia within 5-8 days. Of 32 patients on nafcillin, 2 had neutropenia within 4-13 days, 3 had eosinophilia within 1-4 days and 1 elevated liver enzymes on day 3. Of 8 patients receiving oxacillin, 1 developed neutropenia on day 11 and another showed elevation of liver enzymes on day 15. All abnormalities were reversible with the discontinuation of therapy. Appropriate laboratory tests should be monitored to detect an occurrence of adverse reaction to methicillin, nafcillin and oxacillin.

Adolescent↗

Chloramphenicol: new perspectives on an old drug.

Chloramphenicol is an old antibiotic being used with increasing frequency in serious childhood infections largely due to the emergence of ampicillin-resistant Hemophilus influenzae type b. Because of this renewed popularity and the recent availability of accurate analytical techniques for measurement of chloramphenicol, there have been many recent articles examining the pharmacokinetics of chloramphenicol and its two major prodrug esters, chloramphenicol succinate and chloramphenicol palmitate. New data from these studies include the incomplete bioavailability of chloramphenicol succinate, the possible superior bioavailability of chloramphenicol palmitate vs. chloramphenicol succinate, and the wide interpatient variability in chloramphenicol clearance. These observations, coupled with the known serious hematologic toxicity (reversible bone marrow suppression or irreversible aplastic anemia) and metabolic toxicity (gray baby syndrome) associated with chloramphenicol use, require that initial antibiotic doses be selected by age and be carefully individualized by measurement of peak serum chloramphenicol concentrations.

Bacteria↗

Sarcoidosis and ocular disease in a young child. A case report and review of the literature.

Uveitis in the very young child may be a manifestation of sarcoidosis. A case of sarcoidosis with intraocular inflammation that occurred in a child 2 years 7 months old is reported. The diagnosis was supported by biopsy of uncommon bulbar conjunctival nodules. Knowledge by the ophthalmologists that this disease can occur in children younger than 5 years of age may be crucial to the establishment of proper diagnosis.

Biopsy↗