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Biomedical subjects

A Campbell

Publications and source records attributed to A Campbell.

At least 199 records · Page 11Linked to original sources

Continuous infusion epidural analgesia in obstetrics. A comparison of 0.08% and 0.25% bupivacaine.

The effects of 0.08% (Group A) and 0.25% (Group B) solutions of bupivacaine were compared in a random manner, to assess continuous pump infusion epidural analgesia in labour. Both solutions were infused at a dose rate of 20 mg bupivacaine/hour. The results in all the mothers who had received infusions lasting more than 4 hours were studied. There were 25 in Group A and 28 in Group B. Any treatment during the infusion epidural for inadequate analgesia, hypotension, etc., was recorded as an intervention. The mean of the intervention-free intervals was significantly greater in Group A than in Group B, and significantly fewer top-up injections were required in Group A. The results show that the administration of a 0.08% solution of bupivacaine into the epidural space by continuous pump infusion is more labour saving than the infusion of a 0.25% solution. The concept that a greater volume infusion rate maintains a more extended liquid sleeve of local anaesthetic in the epidural space is supported.

Adult↗

Late changes in cerebral monoamine metabolism following focal ventrolateral cerebrocortical lesions in rats.

Twelve weeks after focal ventrolateral cerebrocortical suction lesions (ca. 12 X 4 mm) were made in rats, concentrations of the monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their metabolites were measured in several cortical and subcortical brain regions using high performance liquid chromatography with electrochemical detection. Widespread changes in the concentrations of monoamines, their metabolites, and metabolite:monoamine ratios were found in the hemisphere ipsilateral to unilateral (right) lesions, and bilaterally in animals with bilateral lesions. NE was decreased in undamaged dorsolateral cortex and hippocampus, and tended to be increased in striatum and midbrain ipsilateral to lesions. DA was increased in the hypothalamus of bilaterally lesioned animals, and also tended to be increased in striatum and midbrain. The changes of greatest magnitude and anatomical extent were found in the serotonin system: 5-HT was generally increased, and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA:5-HT ratio were decreased throughout the cerebral hemispheres ipsilateral to lesions. These widespread changes in cerebral 5-HT metabolism were qualitatively different and smaller than those previously found at 6 days after cortical lesions, and suggest a biphasic response of the ipsilateral 5-HT system to ventrolateral cortical injury.

3,4-Dihydroxyphenylacetic Acid↗

Prolonged antidopaminergic actions of single doses of butyrophenones in the rat.

Rats were treated once with doses of haloperidol or of droperidol below and above the acute ID50 vs the dopamine agonist apomorphine; they were later challenged with an acute dose of apomorphine (0.3 mg/kg, SC) and rated for stereotyped behavioral responses. The two neuroleptics were similar in acute anti-apomorphine potency (ID50 = 0.12 and 0.18 mg/kg for haloperidol and droperidol, respectively). The antidopaminergic effects of droperidol persisted for nearly 1 week and those of haloperidol lasted for 20-40 days, depending on the dose given. The computed half-time of disappearance of their antidopaminergic effects was 7.6 +/- 1.0 days and 0.59 +/- 0.17 days for haloperidol and droperidol, respectively, following a dose of 0.3 mg/kg, and these indices of duration of action did not vary significantly at doses between 0.1 and 1.0 mg/kg. Haloperidol reduced the acute entry of 3H-apomorphine into brain by 21.5% 1 week later. Treatment with apomorphine alone just prior to haloperidol (both at 0.3 mg/kg) prevented the prolonged antidopaminergic effects of the neuroleptic evaluated 1 week later. These results indicate that some neuroleptics may have very prolonged activity or retention in tissue at sites of action, even after moderate, single doses. Caution is recommended in the interpretation of studies which assume "neuroleptic-free" conditions of subjects previously exposed to a neuroleptic agent.

Animals↗

S(+)Apomorphines. Selective inhibition of excitatory effects of dopamine injected into the limbic system of the rat.

Dopamine (DA) injected unilaterally into the corpus striatum of the brain of the rat after pretreatment with a monoamine oxidase inhibitor, induced contralateral deviation of the head (ED50 = 23 micrograms). Dopamine, administered similarly into the nucleus accumbens septi, induced strong locomotor arousal effects (ED50 = 32 micrograms), as reported by others. Systemic administration of the S(+) isomers of apomorphine (APO) and its N-n-propyl analog (NPA) had no significant action on the effects on posture of DA given intrastriatally, even in large doses. In striking contrast, both agents selectively inhibited the locomotor-arousal effects of DA injected into the accumbens, but (+)NPA was seven times more potent (ED50 = 0.5 mg/kg vs 16 micrograms of DA) and its effects lasted for about 70 min. The dose-effect curves for (+)NPA against two doses of DA demonstrated parallel, lateral displacement, indicating a competitive interaction. These results support the impression that enantiomers and analogs of apomorphine, and especially S(+)N-propylnorapomorphine, have potent antidopaminergic actions that may be selective for limbic areas of the forebrain.

Animals↗

gamma-Aminobutyric acid esters. 2. Synthesis, brain uptake, and pharmacological properties of lipid esters of gamma-aminobutyric acid.

Two lipid esters of U-14C-labeled and unlabeled gamma-aminobutyric acid (GABA) were synthesized to test the possibility that natural lipid analogues, which resemble normal components of lipid bilayer membranes, can penetrate the blood-brain barrier and transport exogenous GABA to the brain. The uptake of 1-linolenoyl-2,3-bis(4-aminobutyryl)propane-1,2,3-triol and 1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol into mouse brain relative to liver was found to be, respectively, 75- and 127-fold greater than that of free GABA. The results indicate that there is little or no blood-brain barrier for the GABA ester molecules at doses up to 0.36 mmol/kg. Both ester compounds, but neither free GABA nor the lipid components delivered systemically, demonstrated central nervous system depressant properties by inhibiting the general motor activity of mice. Brain tissue has esterase activity which can release GABA from these compounds. This suggests that these compounds function as "prodrugs" to release GABA in the CNS.

Animals↗

Bacteriuria in pregnancy.

In a racially mixed community in Gisborne, New Zealand, the prevalence of asymptomatic (covert) bacteriuria of pregnancy was 9.6%. The prevalence in Maori women was 17.1% and in non-Maori women 4.7%. There was a higher prevalence of bacteriuria in the younger women. Escherichia coli was the infecting organism in 58 of the 72 women with bacteriuria. Twenty-five (44%) of the E. coli were resistant to ampicillin and amoxycillin. Fifty-eight (81%) of the women with bacteriuria also had pyuria. In 37 of the 44 women (84%) who received antimicrobial therapy, the infection was cured. Single dose therapy was just as effective as a course of treatment. In 14 of the 28 untreated women, the infection cleared spontaneously. Four of the 28 (14%) patients in the untreated bacteriuric group developed acute pyelonephritis. More patients with bacteriuria had anaemia and a low fetal birth-weight.

Adolescent↗

Predicting our own aggression: person, subculture or situation?

Using a self-report technique, teenaged subjects (stratified by sex and social class) were asked to report their predicted behaviour over 24 conflict scenarios involving 12 male and 12 female targets. In terms of degree of aggression predicted, there was a strong effect of situation. Towards male targets, lower middle-class subjects were more aggressive than upper middle-class subjects and males were more aggressive than females. With respect to female targets, the social class difference again appeared but there was no simple sex difference. The interaction of sex and social class indicated that lower middle-class females were most aggressive toward female targets. Cross-situational consistency was low even controlling for class and sex, indicating little support for a generalized 'aggressive personality'. The most powerful single effect was the situation being judged. Feature analysis of situations tending to produce fight vs. flight responses suggested that flight is associated with perceived high risk encounters whereas fighting is the modal response in 'fair fight' situations where the risk of injury is lower. It is suggested that impression management concerns operate only in these low risk situations.

Adolescent↗

Extracellular matrix promotes the growth and differentiation of murine hematopoietic cells in vitro.

We have developed a long-term culture system in which murine marrow cells are cultured on a complex extracellular matrix (ECM) that is derived from marrow and extracted with guanidine hydrochloride and dithiothreitol. Marrow cultures were established with fresh murine marrow cells and recharged at 2 wk (week 0). Phase microscopy showed a dramatically increased adherent cell layer development on ECM compared with controls within a week after recharge. By electron microscopy, this adherent layer was composed of numerous reticular cells apparently attached to the ECM which extended cytoplasmic projections to the surrounding hematopoietic cells. Adherent cellularity on ECM-coated dishes increased to 30 times the control values by week 2. Cumulative suspension cells on ECM dishes were eight times controls. ECM influenced both hematopoietic progenitor cell proliferation and differentiation. Adherent colony-forming unit-granulocyte/macrophage and colony-forming unit-megakaryocyte were greater than 30 and 15 times the control values, respectively, by week 2 (P less than or equal to 0.05). There were more mature granulocytic and megakaryocytic cells in ECM-coated dishes than in controls at all time points. This new culture system directly demonstrates that ECM is an important component of the hematopoietic microenvironment.

Animals↗

Effects of N-substituted phenyltetrahydropyridines on cerebral high-affinity synaptosomal uptake of dopamine and other monoamines in several mammalian species.

Effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (N-methyl-PTP) and its N-propyl congener (N-propyl-PTP) on the high-affinity uptake of tritiated dopamine (DA), norepinephrine, and serotonin by striatal or cerebral cortical synaptosomes were evaluated in several species (rat, guinea pig, rabbit, calf, and man). Both compounds inhibited uptake of 0.1 microM labeled amines at IC50s of 5-10 microM. Effects of N-methyl-PTP were competitive, reversible, somewhat more potent, and more selective for serotonin than were actions of N-propyl-PTP. Similar effects were found in all species. Neither agent inhibited binding of 3H-labeled spiperone or ADTN to DA receptor sites. 3H-N-methyl-PTP did not appear to be taken up selectively into DA neurons. N-methyl-PTP was highly toxic to the rat in doses that did not alter the metabolism of DA or serotonin in brain. These results, overall, do not provide strong support for the hypothesis that reported neurotoxic actions of N-methyl-PTP are mediated by neuron-specific local transport and intracellular accumulation, or account for species differences in the actions of this toxin, but do suggest interactions with brain monoamine neurons. The actions of the neurotoxic effects of N-methyl-PTP remain unclear.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effect of age on behavioral responses and tissue levels of apomorphine in the rat.

Rats of several ages between 2 and 24 months were tested for stereotyped behavioral responses to R(-)apomorphine-HCl (APO), a potent and selective dopamine agonist. Between 2 and 24 months, the ED50 for apomorphine decreased 2.5-fold (0.14-0.06 mg/kg, i.p.), as assessed by a microcomputer-assisted technique. Not only were older rats more sensitive to apomorphine, but the duration of the behavioral effects increased with age and showed a greater change at doses which were greater than the ED50. When levels of apomorphine in brain were assayed by liquid chromatography and electrochemical detection, there was a progressive increase in peak levels of the agent in the tissue as well as a delay in its elimination from brain, with increasing age. Moreover, there was a highly significant correlation between increased behavioral effect and the level of apomorphine in brain with increasing age (r greater than 0.8). These results indicate that increased levels in brain or decreased elimination of apomorphine may be an important factor contributing to a marked increase in behavioral sensitivity to apomorphine with age in the rat.

Aging↗

Spontaneous motor activity increases after portacaval anastomosis in rats.

Spontaneous motor activity was monitored in rats at various times, up to 14 weeks, after portacaval anastomosis (PCA) or sham operation. Total 24 hour activity scores rose significantly after PCA and remained significantly higher than those of sham operated rats for twelve weeks. After PCA, activity during the twelve hour lighted period was greatly increased, whereas dark period activity was unchanged. Increased activity in the light period was found to be well correlated with the degree of elevation in brain concentrations of tryptophan, tyrosine, phenylalanine and glutamine. These results are consistent with previously reported EEG studies and suggest that motor-activity measurement may facilitate the correlation of biochemical changes with behaviour in rats with portal systemic shunting.

Amino Acids↗

Gamma-aminobutyric acid esters. 1. Synthesis, brain uptake, and pharmacological studies of aliphatic and steroid esters of gamma-aminobutyric acid.

Labeled and unlabeled aliphatic and steroid esters of gamma-amino[U-14C]butyric acid (GABA) were synthesized and tested for their capacity to penetrate the blood-brain barrier and for evidence of central neuropharmacological activity in rodents. The uptake of the labeled 9,12,15- octadecatrienyl ( linolenyl ), 3-cholesteryl, 1-butyl, and the 9-fluoro-11 beta,17-dihydroxy-16 alpha-methyl-3,20- dioxopregna -1,4-dien-21-yl (dexamethasone) esters of GABA into mouse brain increased 2-, 25-, 74-, and 81-fold over GABA, respectively. The cholesteryl ester of GABA depressed the general motor activity of mice and rats in a dose-dependent manner, whereas the 1-butyl, linolenyl , and dexamethasone esters were inactive by this test. Studies of the rates of hydrolysis, GABA receptor binding capacity, and octanol/water partition coefficients indicated that pharmacological activity of the esters after entry into the central nervous system (CNS) was dependent on their capacity to release GABA by enzymatic hydrolysis and their lipid solubility.

Animals↗

Hepatic artery infusion: surgical approach.

Hepatic artery infusion chemotherapy for the treatment of nonresectable liver cancer is gaining popularity among the medical community. A lack of knowledge of the variants in the anatomy of the arterial blood supply to the liver may lead to inadequate hepatic perfusion, or inadvertent perfusion of extrahepatic organs. A review of 70 hepatic artery angiograms on patients referred to the liver program at the Creighton Cancer Center was performed to integrate angiographic findings, surgical techniques, and clinical decision making.

Angiography↗

In vitro and in vivo studies of cellular lysis of oral bacteria by a lysozyme-protease-inorganic monovalent anion antibacterial system.

Compared with anion-activated cell lysis of oral bacteria damaged with either lysozyme or trypsin, cells which were treated with both of these enzymes showed a far greater degree of lysis. This was true regardless of whether turbidimetric, DNA release, or electron microscopic assays were used to monitor the lytic process. At an acidic pH of 5.2 and an NaHCO3 concentration of 100 mM, the kinetics of lysis for two different serotype c strains of Streptococcus mutans were similar. At 0 to 100 mM bicarbonate, however, differences in the lytic susceptibilities of the two strains were evident. At pH 5.2, NaHCO3, but not NaSCN, NaCl, or NaF, was effective in promoting cell lysis of the oral bacteria. At apparent sublytic concentrations of NaHCO3, lysis was achieved by adding appropriate concentrations of NaSCN, NaCl, or NaF to the lysozyme-protease-damaged cells. In in vivo studies, hamsters given a combination of NaHCO3, NaCl, and NaSCN were found to have significantly reduced levels of S. mutans on their molar teeth compared with that found in controls or animals exposed to any one of the salts alone or to a combination of chloride and thiocyanate only. The results suggest that bicarbonate is an essential anion which, together with the other major salivary inorganic monovalent anions, plays an active role in the lysis and ultimate elimination of cariogenic bacteria.

Actinomyces↗