Influenza vaccine--the effect of virus strain and dosage on antibody response.
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Antibodies, Viral↗
Biomedical subjects
R A Moore
Publications and source records attributed to R A Moore.
Influences on prescribing practices.
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Drug Utilization↗
A novel form of dependency of hepatic extraction ratio of opioids in vivo upon the portal vein concentration of drug: comparison of morphine, diamorphine, fentanyl, methadone and buprenorphine in the chronically cannulated cow.
In the chronically cannulated cow, the hepatic extraction ratio for intravenous boluses of morphine, diamorphine, fentanyl, methadone and buprenorphine increased towards a plateau value as portal vein drug concentration increased. An extraction ratio close to zero for morphine was observed at a portal vein plasma drug concentration of about 200 nanomol per litre, which is within the range for significant pharmacodynamic effects. The similar concentrations extrapolated for the other narcotics would be of less pharmacodynamic importance. The phenomenon did not depend with morphine on the history of drug delivery to the liver; measurement of hepatic blood flow showed the effect was not an artifact of unrepresentative blood sampling, and was not related to any action of the narcotics on hepatic blood flow. The existence of this novel type of concentration dependent hepatic extraction ratio in vivo can explain a number of anomalous observations on narcotic pharmacokinetics, especially for morphine. Furthermore, similar behaviour may be expected for non-opioid drugs having similar pharmacokinetic properties.
Animals↗
Nuclear chromatin changes in hepatocytes of soman treated rats.
Cytochemical and morphometric indices of DNA metabolism and nuclear transcriptional-translational capabilities were used to monitor liver responses in Sprague-Dawley X Wistar rats subcutaneously injected with 0.9 LD50 soman, a highly toxic acetylcholinesterase-inhibiting organophosphate. Thirty minutes post-soman the following were evident: (1) increased polyploidization; (2) expansion of the nuclear envelope; and (3) elevated deoxyribonucleoprotein (DNP) complex lability to acid hydrolysis. Nuclear changes were accompanied by cytoplasmic correlates of impaired hepatocyte function, i.e., vacuolation and depressed basophilia. The overall data suggest that with acute soman toxication there are concomitant adaptive and maladaptive responses occurring within liver parenchymal elements. It is postulated that nuclear changes represent an early proliferative response and DNP activation to enhance detoxification capabilities, whereas cytoplasmic changes reflect the disruption of normal function and hepatotoxic injury.
Animals↗
Brain neuronal RNA metabolism during sustained low-level soman toxication.
Quantitative azure B-RNA cytophotometry was used to monitor metabolic responses of cholinergic elements of the rat brain during sustained low-level administration of soman (0.25-0.50 LD50, sc). RNA contents of caudate and cerebrocortical (Layers III and V) neurons were measured 60 min following 1-5 soman dosages given at 24 h intervals. Marked and progressive RNA depletion was evidenced after 1-4 soman injections, whereas partial or complete restitution of RNA levels was observed following the fifth injection. These data indicate that repetitive soman toxication is associated with metabolic correlates of impaired rather than accentuated activation of CNS cholinergic systems, and that tolerance is developed to CNS actions of the agent. It is postulated that impaired neuronal activation is related to soman or ACh-induced transmission block, and that the same adaptive processes responsible for recovery during acute poisoning may underlie the development of tolerance during repetitive administration of organophosphates.
Acetylcholinesterase↗
Soman toxication in hypoxia acclimated rats: alterations in brain neuronal RNA and survival.
Effects of prior hypoxia acclimation (14-day at 380 mm Hg) on soman (pinacolyl methylphosphonofluoridate) induced brain neuronal RNA and acetylcholinesterase (AChE) depletion and lethality were monitored in rats following their return to ambient oxygenation. Quantitative cytochemical techniques were used to measure RNA and AChE changes in individual cerebrocortical (Layer III) and striatal (caudate plus putamen) neurons. In ambient Po2 controls, soman eventuated in a moderate diminution of neuronal RNA in both brain regions and severe, dose-dependent suppression of AChE activity. Hypoxia acclimation per se induced RNA alterations as manifested in cortical RNA depletion and increased variability of striatal neuron RNA contents. In hypoxia acclimated rats, the extent of neuronal RNA depletion following soman injection was attenuated in both brain regions, yet there were no discernible differences in saline control AChE levels or in the extent of soman-induced AChE inhibition in ambient control versus hypoxia acclimated treatment groups. Hypoxia acclimated rats, however, were found to be even more susceptible to lethal actions of soman as assessed using 24- and 48-hour survival following a three-point treatment regimen. These data indicate that while compensatory systemic and central metabolic adjustments associated with 14d acclimation to reduced oxygen availability may retard soman-induced neuronal RNA depletion, resistance to lethal or near-lethal soman exposure is not enhanced. It is postulated that hypoxia acclimation is associated with complex adaptive and maladaptive neurophysiological alterations influencing CNS responsiveness to soman toxication, and that detrimental consequences exceed protection afforded by metabolic adaptation.
Acclimatization↗
Cytochemical correlates of atherosclerosis-resistant and susceptible lesions of the normal rabbit aorta.
Quantitative cytochemical and microfluorimetric techniques were employed to compare mural intermediary metabolism--endothelial macromolecular uptake changes in spontaneous aortic-arteriosclerotic lesions of normolipemic New Zealand White rabbits. Specifically, mural succinic (SDH), lactic (LDH), and glucose-6-phosphate (G-6-PDH) dehydrogenase activities and luminal surface uptake of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) were measured in lesion sites abnormally resistant (calcified) and susceptible (proliferative) to dietary hypercholesterolemia. Calcified lesions exhibited severe (55-66%) diminution of SDH, LDH, and G-6-PDH activities within the involved inner mural zone and a comparable (68%) decline in luminal FITC-BSA uptake. Concomitant reductions in FITC-BSA uptake (30%) and marker enzymes of the predominant energy transducing pathways in arterial tissue, i.e., SDH (30%) and LDH (31%), were evidenced in proliferative foci, whereas G-6-PDH was augmented (52%) in comparison to nonlesioned aortic segments. These data lend additional support to the concept that endothelial uptake of plasma-borne macromolecules is coupled to oxidizable substrate requirements of inner avascular compartments of the arterial wall. It is postulated that diminished macromolecular transport in these degenerative lesions stems from reduced mural metabolic demands, and that pharmacologic reduction of vascular smooth muscle metabolism may depress uptake of sclerogenic macromolecules.
Animals↗
Cytophotometric analyses of brain neuronal RNA in soman intoxicated rabbits.
Quantitative azure B-RNA cytophotometry was used to monitor metabolic responses of individual neurons of the motor cortex (layer V) and caudate nucleus of soman (pinacolyl methylphosphonofluoridate) poisoned rabbits. Time- and dose-dependent RNA responses were related to the extent of acetylcholinesterase (AChE) inactivation of these 2 brain regions and to overt behavioral manifestations of toxication. A complex pattern of RNA responses was evidenced, with RNA depletion occurring at both arousal and convulsive doses of soman. In general, RNA changes paralleled previously reported metabolic responses observed in soman toxicated rats and mice: (1) linear dose-dependent suppression of RNA was evidenced during the depressant phase but not in the acute excitatory phase of toxication; and (2) RNA depletion was more severe following than during the appearance of excitatory symptoms. These data indicate that soman poisoning results in metabolic correlates of impaired rather than excessive CNS activation. It is postulated that metabolic disturbances are related to blockade of central cholinergic excitation, and that disruption of functionally integrated synaptic activity forms a critically important aspect of toxication.
Acetylcholinesterase↗
The effect of hypothermic cardiopulmonary bypass on patients with low-titer, nonspecific cold agglutinins.
The effect of hypothermic cardiopulmonary bypass (CPB) was studied in 5 patients with strongly positive cold agglutination at 4 degrees C (experimental group) and in 10 controls. In the in vitro part of the study, the characteristics of the cold agglutinin antibodies in the experimental group included a low thermal amplitude (28 degrees C or less), a low 4 degrees C agglutination titer (1:32 or less), and nonspecificity (non-anti-I and non-anti-i). The in vivo portion of the study revealed a fall in total urine and serum free hemoglobin in both groups on going on bypass, followed by a rise for the remainder of bypass. Statistical comparison between observed and expected total free hemoglobin for both groups showed a significant rise (p less than 0.05) after bypass, thereby indicating ongoing hemolysis. No statistically significant difference between preoperative and post-operative blood urea nitrogen and creatinine levels and gross neurological status was observed in the experimental group. It was concluded that the patient with nonspecific cold agglutinins whose antibody is characterized by a low titer, a low thermal amplitude, and a lack of clinical symptomatology can undergo hypothermic CPB without increased threat of a hemolytic or vascular occlusive crisis.
Aged↗
Plasma morphine concentrations and clinical effects after thoracic extradural morphine or diamorphine.
Twenty-seven patients undergoing thoracotomy received either morphine sulphate 2 mg or diamorphine hydrochloride 2 mg by thoracic extradural injection for postoperative analgesia. Arterial plasma morphine concentrations were measured by specific radioimmunoassay, and the analgesic, respiratory and biochemical effects noted. The plasma morphine concentrations were significantly greater after extradural diamorphine than after extradural morphine in the first 30 min after injection. The maximum increase in plasma morphine concentration was significantly (P less than 0.02) greater after extradural diamorphine, and mean peak values occurred at 5 and 10 min for diamorphine and morphine, respectively. There were significant decreases in respiratory rate and plasma cortisol concentration with maximum effects between 90 and 180 min after the extradural injection. The analgesia produced by these doses was inadequate. The role of lipophilicity is discussed.
Adult↗
Controlled comparison of intrathecal cinchocaine with intrathecal cinchocaine and morphine. Clinical effects and plasma morphine concentrations.
Twenty patients scheduled for elective total hip replacement were given either intrathecal cinchocaine with morphine hydrochloride 2.5 mg or intrathecal cinchocaine alone before general anaesthesia. Arterial plasma morphine concentrations were measured and analgesic, respiratory and biochemical effects compared. Plasma morphine concentrations increased to 19.3 nmol litre-1 at 210 min. PaCO2 concentrations increased significantly only in those patients who received morphine as well as cinchocaine. Patients receiving cinchocaine alone, but not those given cinchocaine and morphine, had significant (P less than 0.01) increases in plasma cortisol concentrations' in the period after operation. Median time to next analgesic in patients receiving cinchocaine with intrathecal morphine was 22 h, significantly (P less than 0.01) longer than in patients receiving intrathecal cinchocaine alone (7.8 h).
Aged↗
Mandatory sublingual buprenorphine for postoperative pain.
This study examined the analgesic effect, vital signs and side effects when 0.4 mg doses of buprenorphine were given pre-emptively for the treatment of postoperative pain after elective total hip replacement. Pain intensity, pain relief, retrospective peak pain intensity and pain relief, sedation, vital signs and side effects were measured 1 hour after surgery and then in the morning and evening of the first 2 postoperative days. There was a significant improvement in pain measured over the 3 days, with concomitant reduction in side effects and sedation. However, there was a significant increase in the number of patients with a pulse rate greater than 100 beats per minute. No particular benefit for postoperative pain relief was observed in patients receiving buprenorphine premedication in comparison with those who had received morphine or placebo.
Administration, Oral↗
Intradural morphine and diamorphine. Dose response studies.
This open study of 81 patients having major orthopaedic surgery reviews the duration of analgesia and side-effects of 0.625, 1.25 or 2.5 mg of morphine or 1.25 or 2.5 mg of diamorphine given intradurally in combination with 7.5 mg of cinchocaine at induction of anaesthesia. A significant dose-response relationship for duration of analgesia measured by time to first requirement of postoperative analgesic was found with morphine; 1.25 and 2.5 mg of morphine produced analgesia of longer duration than 0.625 mg. No such dose-response was found for side-effects. There was no significant difference in duration of analgesia between diamorphine 1.25 and 2.5 mg, and the duration was similar to that seen with the higher doses of morphine. An intradural dose of between 0.625 mg and 1.25 mg of either morphine or diamorphine used with cinchocaine and without additional parenteral opiate, may be appropriate.
Aged↗
Evidence for two distinct mechanisms of resistance to polymyxin B in Pseudomonas aeruginosa.
Pseudomonas aeruginosa H181 and H185 are resistant to initial exposure to polymyxin B and continue to grow in its presence. Growth of the strains in the presence of 50 U of polymyxin B per ml was characterized by a doubling time of 120 min, whereas the doubling time in the absence of polymyxin was 60 min. Growth for two generations in the presence of polymyxin caused a 23 to 31% increase in lipopolysaccharide content. In addition, a marked increase in susceptibility to the detergents sodium deoxycholate, Triton X-100, and sodium dodecyl sulfate was observed. The resistant mutants had a small but significant reduction in their levels of dodecanoic acid as compared with the parent strain; however, this was the only consistent alteration observed in levels of fatty acids or readily extractable lipids. Polymyxin was fluorescently labeled by coupling to 1-dimethylaminonaphthalene-5-sulfonyl chloride (dansyl chloride). Growth of strains H181 and H185 in the presence of dansylated polymyxin resulted in a stable association between the fluorescent antibiotic and the outer membrane. We postulate that these alterations are part of an adaptive response by the strains to the presence of polymyxin in the growth medium and reflect a resistance mechanism distinct from the mechanism affording polymyxin B resistance when these strains are initially exposed to the antibiotic.
Bacterial Proteins↗
HPLC of morphine with electrochemical detection: analysis in human plasma.
A method is described for the measurement of morphine in human plasma by ion-paired reverse-phase liquid chromatography. It includes a novel solid-phase extraction of morphine from plasma which is simple, rapid and complete. No known morphine metabolites could be shown to interfere with the measurements. Determination of morphine pharmacokinetics in patients undergoing heart surgery with 1 mg/kg intervenous morphine produced plasma morphine clearances which agreed with established estimates.
Cardiac Surgical Procedures↗
Sensitive and specific morphine radioimmunoassay with iodine label: pharmacokinetics of morphine in man after intravenous administration.
Analysis of morphine in plasma by radioimmunoassay is complicated by interference from morphine metabolites, particularly morphine-3-glucuronide. This interference makes radioimmunoassay a poor technique to study the pharmacokinetics of morphine in man. The method described here is one which uses commercially available anti-morphine antiserum and separating reagent with a simply prepared iodinated morphine derivative. Cross-reactivity to morphine metabolites is negligible and the method correlates well with HPLC. Results obtained for pharmacokinetic parameters after intravenous administration in man are in agreement with published data using GLC or HPLC. The method is inexpensive, simple and rapid; choice of a different antiserum could allow the method to be used for screening for drugs of abuse such as morphine, diamorphine, codeine and dihydrocodeine.
Chromatography, High Pressure Liquid↗
Studies on the peripheral action of opioids in postoperative pain in man.
Using simultaneous measurements of pain in both limbs after bilateral orthopaedic surgery, peripheral and central components of regionally administered drugs can be separated. Perineural local anesthetic action is readily shown in both upper and lower limbs. Perineural morphine had no effect in ankle blocks, although an effect superior to that of local anesthetics has been claimed in man. Similarly, no effect was seen from morphine or buprenorphine given by intravenous regional administration in the upper limbs, although opioids have shown local antinociceptive action in animal models. There is little evidence to suggest that the usual parenteral opioids have any significant peripheral action clinically, but further human studies are needed because of the theoretical importance of even a small peripheral component.
Analgesics, Opioid↗
Scrotal lymphocele complicating renal transplantation.
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Adult↗