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Biomedical subjects

D A Powell

Publications and source records attributed to D A Powell.

At least 145 records · Page 8Linked to original sources

Effect of intravenous flow rate and injection site on in vitro delivery of chloramphenicol succinate and in vivo kinetics.

The delivery rates of chloramphenicol succinate from a standard pediatric intravenous infusion set were studied in vitro at varying flow rates and injection sites of the infusion set. The pharmacokinetic properties of CAPS and chloramphenicol were then studied in 15 children given intravenous injections of CAPS via the infusion set at the flashball and Buretrol sites in a crossover fashion on successive days. In vitro, the actual times required for 95% delivery of CAPS from the infusion set were two- to fourfold longer than the predicted infusion times at flow rates of 5, 15, and 29 ml/min and at all three available injection sites. In vivo, flashball injections vs Buretrol injections resulted in significantly higher mean peak serum concentrations of CAPS and CAP, with peaks occurring significantly sooner after the beginning of the intravenous infusion. These results suggest a need for considering characteristics of CAPS infusion when monitoring and interpreting serum concentration values.

Adolescent↗

Forebrain norepinephrine and serotonin concentrations and cardiac conditioning in normal rabbits and rabbits with septal lesions.

Septal lesioned or sham operated rabbits were subjected to two days of differential Pavlovian (classical) heart rate (HR) conditioning in which tones served as the conditioned stimuli and paraorbital electric shock served as the unconditioned stimulus. After completion of training, norepinephrine (NE) and serotonin (5-HT) concentrations were determined in the hippocampus and neocortex to determine if lesion-induced amine depletion was related to changes in HR conditioned response (CR). The magnitude of the bradycardiac CR was increased by septal lesions during the initial session but during the second session. several lesioned animals revealed accelerative HR changes resulting in an attenuated HR CR in the septal damaged group. The more accelerative HR responding in the septal lesioned animals was accompanied by increased EMG activity which appeared to be related to damage to more posteroventral areas of the septum. Septal lesions produced a depletion of forebrain NE of approximately 30%, but NE concentrations did not appear to be specifically related to lesion-induced changes in the HR CR. However, both NE and 5-HT concentrations were correlated with the magnitude of the HR CR in intact, but not in lesioned, animals.

Animals↗

Lateral hypothalamic lesions: effects on Pavlovian cardiac and eyeblink conditioning in the rabbit.

Rabbits received either bilateral lesions of the far lateral hypothalamus (LH), or sham-operate lesions. After recovery from surgery the animals were exposed to Pavlovian conditioning in which eyeblink (EB), electromyographic (EMG), and heart rate (HR) conditioned responses (CRs) were recorded. Adaptation, acquisition and extinction training were studied. Subsequent to conditioning, free-field activity, paraorbital electric shock thresholds, and HR unconditioned responses (URs) were measured. At the end of behavioral testing forebrain norepinephrine (NE), dopamine (DA), an serotonin (5-HT) concentrations were assessed. Animals with LH lesions did not differ from controls on EB responding during either adaptation or acquisition. However, lesioned animals revealed more EB CRs during extinction than control animals. EMG CRs were minimal in both groups of animals. Lesioned animals showed smaller HR changes than control animals during all phases of training, although HR CRs tended to consist of bradycardia in all animals. No differences were observed in either shock thresholds or open field activity as a result of LH lesions. Cortical and hippocampal 5-HT and NE concentrations were significantly depleted in lesioned as compared to control animals. These findings were interpreted within the framework of the phasic control of attention by midbrain modulation of forebrain structures; however, the interruption of downward going fibers which mediate brain stem cardiac control cannot be ruled out.

Animals↗

Bioavailability and clearance of chloramphenicol after intravenous chloramphenicol succinate.

Bioavailability of chloramphenicol and kinetics of chloramphenicol succinate and chloramphenicol were studied in 12 patients. Chloramphenicol succinate, 25 mg/kg, was injected intravenously every 6 hr over 0.5 to 1 hr. Both the drug and the prodrug were analyzed by high-pressure liquid chromatography. Bioabailability of chlorampenicol ranged from 0.55 to 0.92 and total, renal, and nonrenal clearance from 6.81 to 98.22, 2.54 to 26.90, and 3.73 to 87.38 ml/m2/min, while clearances of chloramphenicol succinate ranged from 84.75 to 916.00 28.40 to 312.00, and 26.06 to 760.93 ml/m2/min. Urinary recovery of chloramphenicol was 3% to 25% and that of chloramphenicol succinate was 7% to 45%. Mean apparent volumes of distribution were 0.71 l/kg for chloramphenicol and 2.10 l/kg for chloramphenicol succinate and elimination half-lifes were 4.03 and 2.65 hr, respecitively. There were relationships between patient age and clearance of both drugs. Incomplete bioavailability of chloramphenicol and the more than 10-fold variability in clearance of both chloramphenicol and chloramphenicol succinate explain the need for individualizing doses to achieve thrapeutic effect and minimize the risk to toxicity.

Adolescent↗

Age-related changes in classical (Pavlovian) conditioning in the New Zealand albino rabbit.

The groups of New Zealand albino rabbits of approximately six and forty months of age respectively were subjected to Pavlovian conditioning in which a 1216 Hz, 75 dB tone served as the conditioning stimulus and a brief paraorbital electric shock train served as the unconditioned stimulus. Eyeblink and heart rate responses were assessed. Older animals revealed acquisition deficits in the somatomotor eyelid conditioning task compared to the young animals: however, the magnitude of the concomitantly occurring heart rate change was greater in older than in younger animals. These age-related changes appeared to be enhanced in males and were unrelated to general activity differences, or to the unconditioned response to unpaired tones or electric shocks.

Aging↗

Learning and reaction time performance in older veterans: relationship to attitudes and life satisfaction.

Young (age 20-35) and old (age 55-70) veterans were tested on serial learning and reaction time tasks. Life satisfaction, attitudes toward older people, and physical and mental status were also assessed. Younger veterans showed better performance on both learning and psychomotor tasks than did older veterans. However, positive attitudes toward aging, and greater life satisfaction were associated with better performance on the behavioral tasks in the older group. Certain aspects of physical and mental status were also associated with better learning and reaction time scores in the elderly. These results suggest that age-related behavioral decrements may be related to psychosocial variables but that physio-medical factors may play a mediating role.

Adult↗

Structural studies of the capsular polysaccharide from Streptococcus pneumoniae type 1.

The capsular polysaccharide from Streptococcus pneumoniae type 1 is composed of D-galactopyranosyluronic acid residues and 2-acetamido-4-amino-2,4,6-trideoxy-D-galactopyranosyl residues. The latter sugar, previously unknown in Nature, was not isolated but was identified from the products obtained on deamination of the polymer. Using n.m.r. spectroscopy, methylation analysis, and Smith degradation as the principal methods of structural investigation, it is concluded that the polysaccharide is composed of trisaccharide repeating-units having the structure: leads to 3)-alpha-Sugp-(1 leads to 4)-alpha-D-GalpA-(1 leads to 3)-alpha-D-GalpA-(1 leads to, in which Sug denotes the new sugar.

Carbohydrate Sequence↗

Peripheral 6-hydroxydopamine administration in the rabbit (Oryctolagus cuniculus): effects on Pavlovian conditioning.

The present experiment studied the effects of 6-hydroxydopamine (6-OHDA) administration and adrenal enucleation on differential classical conditioning of somatic and cardiovascular changes in the rabbit. Heart rate and blood pressure conditioned responses (CRs) were relatively large decreases in rate and slight depressor responses, respectively, which were both attenuated by 6-OHDA administration and adrenal demedullation. Frequency of eye-blink response to the reinforced conditioned stimulus was diminished by sympathetic interference during the middle sessions of conditioning, thus producing a decrement in eye-blink discrimination. Electromyographic CRs, on the other hand, were not affected by peripheral catecholamine reduction. These results are discussed in terms of the role of afferent autonomic feedback in influencing the acquisition of somatomotor behaviors.

Adrenal Medulla↗

Peripheral autonomic mechanisms and Pavlovian conditioning in the rabbit (Oryctolagus cuniculus).

The present experiments examined the effects of peripheral administration of atropine methyl nitrate and 6-hydroxydopamine hydrobromide on differential classical conditioning or eye-blink (EB) and heart rate (HR) responses in the rabbit. Atropine decreased HR conditioned response (CR) magnitude and increased baseline HR, although the latter declined somewhat over the first few sessions of the experiment. As baseline HR declined, EB CRs increased in animals treated with atropine. However, the acquisition of the EB response was impaired in these subjects compared with animals treated with saline. The administration of 6-hydroxydopamine produced an impairment of the HR response early and late during acquisition but had no effect on EB conditioning. Control experiments suggested that the impairments produced by methyl atropine were not due to general somatomotor deficits or to a differential sensitivity to the electric shock unconditioned stimulus. The conditioning data are consistent with the Laceys' peripheral afferent feedback hypothesis of autonomic-somatic relations.

Adrenal Medulla↗

Peripheral autonomic changes accompanying learning and reaction time performance in older people.

Heart rate, blood pressure, and electrodermal activity were assessed in old (55 to 70) and young (20 to 35) veterans during their performance on serial learning and reaction time tasks. More older than younger subjects exhibited systolic blood pressure increases during the tasks; baseline heart rate was also slower in the older subjects. However, the phasic electrodermal response of the older Ss during the reaction time task was of smaller magnitude than that of the young Ss, and there were no phasic HR differences between the groups. Learning and psychomotor performance of the older subjects who revealed systolic BP pressor responses was significantly better than that of those who showed depressor responses, but this relationship was not obtained in the younger subjects. These relationships were more pronounced on easier than on more difficult tasks.

Adult↗

Experimental infection of the respiratory tract with Mycoplasma pneumoniae.

M. pneumoniae, a common human respiratory pathogen, has been studied experimentally for years using intranasal inoculation of the golden Syrian hamster. Because of recent evidence outlining the role in pulmonary immune development of particle size and depth of mycoplasma deposition in the hamster lung, we developed an aerosol chamber for the reproducible aerosolization of radiolabeled M. pneumoniae. Organisms were labeled to high specific activity by the incorporation of 3H-oleic acid and aerosolized under airflow and humidity conditions creating a mean particle diameter of 2.0 micrometers. Under these conditions, viable mycoplasmas were reproducibly and evenly distributed to all major lobes of the lung. Examination of radioactive clearance and organism viability within the lung during the first 48 hr after aerosolization have suggested a minimal role for macrophage mycoplasmacidal activity and a more prominent role for ciliary clearance. Data from aerosol infections of hamsters with radio-labeled M. pneumoniae should provide a unique opportunity to examine in a highly controlled manner the effects of air pollutants on the initial stages of infection as well as effects on the development of pulmonary immunity and histologic alterations.

Aerosols↗

Phagocytic dysfunction in monocytes of normal newborn infants.

The kinetics of phagocytosis by monocytes isolated from cord blood and from the blood of adult volunteers was studied. Monocytes attached to glass coverslips were incubated with polystyrene spheres (1.1 mu diameter) for up to 120 minutes. In this system, the rate of phagocytosis was considerably slower in newborn monocytes than in those from adults. By the time phagocytosis had occurred in virtually all of the adult cells, only 38% of the neonatal monocytes had engulfed particles. However, this defect was not absolute, since ultimately all of the newborn cells contained engulfed spheres. Levamisole had no effect on normal adult monocytes but accelerated phagocytosis of newborn cells to a rate identical with that of adult cells. These data demonstrate that newborn monocytes are less efficient in the early stages of phagocytosis than are comparable cells from adults, raising the question of the impact of phagocytic kinetics in the development of neonatal sepsis. The correction of this defect by levamisole suggests that the differences in neonatal and adult monocytes may be evaluated more thoroughly by similar pharmacologic probes.

Humans↗

Adrenal demedullation and peripheral 6-OHDA administration in the rabbit: effects on body weight, general activity and cardiovascular responsivity.

Two experiments were undertaken to determine the effects of systemic 6-hydroxydopamine (6-OHDA) administration and adrenal enucleation on body weight, brain and heart norepinephrine, general activity, and cardiovascular responsivity in the rabbit. 6-Hydroxydopamine produced long lasting, dose related decreases in baseline blood pressure (BP) and in pressor responses following electric shock. Partial reversal of the BP changes was observed in nonenucleated animals tested 20 days after 6-OHDA administration but not in enucleated animals tested 5, 10 or 20 days post-injection or in control animals tested 5, 10 or 15 days after vehicle injection. Although 6-OHDA administration produced transient weight loss and activity decrements, no long term weight or activity changes were observed.

Adrenal Medulla↗