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R J Summers

Publications and source records attributed to R J Summers.

177 records · Page 10Linked to original sources

An uptake mechanism for L-noradrenaline in the cat spleen, associated with the nerves but distinct from uptake.

1. The characteristics of the uptake of [(3)H]L-noradrenaline from 1 mug pulses injected close arterially to the isolated blood perfused cat spleen are described.2. The spleen took up 355.0+/-16.0 ng from a first pulse and 321.1+/-43.6 ng from a second.3. Uptake from a second pulse was 254.0+/-30.3 ng in the presence of the Uptake(1) inhibitor desmethylimipramine (DMI) (3.3 x 10(-5)M) and the Uptake(2) inhibitor 17-beta-oestradiol (17beta0) (1.8 x 10(-4)M).4. Uptake from small 10 ng pulses was also insensitive to DMI and 17beta0.5. Uptake from pulses was abolished by surgical denervation of the spleen, or pre-treatment with phenoxybenzamine (PBA) (8.8 x 10(-5)M).6. The pulse uptake process was impaired by omission of red cells from the perfusate.7. Stimulation of the splenic nerves at 3Hz halved the pulse uptake.8. Uptake from infusion in the presence of DMI and 17beta0 occurred only during the first few minutes of the infusion.9. It is concluded that an uptake process for L-noradrenaline distinct from Uptakes(1) and (2) is present in the spleen and this might be important physiologically.

Animals↗

The effects of pargyline on overflow of transmitter and uptake of noradrenaline in the cat spleen.

1. Twenty minutes after the addition of pargyline (5 x 10(-4)M) to blood perfusing the isolated spleen of the cat, the overflow of transmitter resulting from stimulation of the sympathetic nerves increased 2.3-3-fold. Lower doses of pargyline did not significantly affect overflow.2. Monoamine oxidase activity, measured with either radioactively labelled tyramine or noradrenaline as substrate, was almost completely inhibited by doses of pargyline in the range of 10(-4)M to 5 x 10(-4)M. Inhibition of enzyme activity was not correlated with the effect on overflow. Pargyline had only a slight inhibitory effect on catechol-O-methyl transferase.3. Uptake of a 1 mug injection (pulse) of labelled noradrenaline, following pargyline (5 x 10(-4)M), was increased to 199.1% of that found in control experiments.4. Pargyline significantly reduced the vascular responses to nerve stimulation but had no significant effect on capsular responses.5. The inhibitor had no effect on resting overflow of labelled noradrenaline from the spleen but doubled the overflow of labelled noradrenaline following nerve stimulation.6. It is suggested that the effect of pargyline on overflow is due to increased release of transmitter during nerve stimulation.7. The possible clinical significance of these findings is discussed.

Animals↗

Cat assay for the emetic action of digitalis and related glycosides (digitoxin, digoxin, lanatoside C, ouabain and calactin).

1. A titration assay with two end points is described for comparison of the emetic and lethal potencies of digitalis-like drugs.2. A drug was infused at constant rate to a conscious, unrestrained cat, through an indwelling venous cannula. At the moment of vomiting the cat was rapidly anaesthetized and infusion continued at the same rate until the moment of cardiac arrest.3. With very slow and very fast infusions, the emetic and lethal doses tended to rise. In the range between these extremes (which varied from drug to drug) they were independent of time.4. The observations could be accounted for by analogue computation, assuming that the drugs entered an initial pool and were distributed at finite rates to receptors in the CNS (vomiting centre) and heart.5. Half times of metabolic loss derived from this computation for digitoxin, digoxin and ouabain (17, 9.9 and 1.8 h, respectively) were in the same ratio as the threefold longer half times reported for these drugs in man.6. When measured with infusion rates in the time independent range, the ratio of lethal to emetic doses did not vary between the drugs studied. All caused vomiting at 40% of the lethal dose.7. From a review of the literature, the emetic and cardiotoxic actions of digitalis-like drugs appear inseparable and probably share a common biochemical mechanism.8. It is concluded that foreseeable improvements in digitalis-like drugs are small and would depend on the elimination of any local emetic effect on gut receptors which they may have.

Animals↗

Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane.

1. In cats, the effects of intraperitoneal injections of four monoamine oxidase (MAO) inhibitors, tranylcypromine, pheniprazine, pargyline, and nialamide, were examined on rectal temperature and on the hypothermia during anaesthesia produced by a 2 hr period of halothane inhalation.2. A 2 hr period of halothane inhalation produced a steady fall in temperature amounting to between 2 degrees and 3.5 degrees C. After discontinuation of halothane inhalation, temperature quickly returned to the pre-anaesthetic level but no pyrexia developed. A peculiar stiffness of the leg muscles occurred in several experiments either at the beginning of the inhalation or after its discontinuation.3. An injection of tranylcypromine (5 mg/kg) caused a rise in rectal temperature and prevented the hypothermia of halothane anaesthesia. This effect lasted for at least 4 hr; 20 hr after the injection, halothane again caused hypothermia.4. An injection of pheniprazine (10 mg/kg) usually caused a small rise in temperature which was not sustained. Pheniprazine not only prevented the hypothermia of halothane anaesthesia during the subsequent 20 hr, but during the first few hours after the injection halothane inhalation actually produced a steep rise in temperature.5. An injection of pargyline (50 mg/kg) had no effect on temperature but the hypothermia due to halothane inhalation was prevented 1 hr after the injection and attenuated after 20 hr. Injection of 200 mg/kg caused a steady rise in temperature which was accelerated when halothane was administered 1 hr later.6. An injection of nialamide (10, 25 or 50 mg/kg) had no immediate effect on temperature, but pyrexia developed overnight after the two larger doses. The effect on the hypothermia due to halothane inhalation was greater 20 hr after the injection than it was after 1 to 2 hr. Twenty hours after injection of the two larger doses, halothane no longer produced hypothermia but caused a lethal rise in temperature either during or after its inhalation.7. In rabbits, the effect on temperature of halothane inhalation varied. Either temperature rose slightly or it fell, but not as much as in cats. In one rabbit in which the inhalation had produced a transient rise, pyrexia developed 40 min after discontinuation of halothane.

Anesthesia, Inhalation↗

Lidocaine and surgical modification reduces mortality in a rat model of cardiac failure induced by coronary artery ligation.

Coronary artery ligation in the rat provides a useful experimental model of cardiac failure; however, this procedure carries with it a high mortality rate (50%). In this study, we used lidocaine (10 mg/kg, i.m.) before coronary artery ligation and 2 h after surgery to minimise the incidence of ventricular fibrillation (VF) that leads to sudden death in this model. We found that coronary artery ligation, using lidocaine in conjunction with a modified surgical procedure, had a mortality rate of 15%, much lower than reported in previous studies using this model. These modifications allow for the production of larger infarcts with 29% of animals having an infarct size > 50% of the epicardial surface. Infarct size in our myocardial infarction (MI) group varied between 5% and 75% of the left ventricular (LV) surface area resulting in a mean infarct size of 41.3 +/- 1.3% for the epicardial surface and 40.0 +/- 1.3% for the endocardial surface.

Animals↗

Characterization and localization of [3H]-clonidine binding in membranes prepared from guinea-pig spleen.

1. [3H]-Clonidine binds to membranes prepared from guinea-pig spleen with high affinity. 2. Kinetic experiments indicated that [3H]-clonidine associates rapidly to the binding site and that the binding is reversible. A study of the dissociation of [3H]-clonidine from splenic membranes revealed two components. The slowly dissociating component corresponded to a high affinity process (Kd = 2.1 nmol/l) in good agreement to that obtained by saturation analysis. 3. Over the concentration range used, saturation experiments revealed only a single population of sites with a dissociation constant (Kd) of 2.4 nmol/l and a density of 5.1 pmol/g wet weight tissue. 4. Examination of the relatively potency of a series of alpha-adrenoceptor agonists and antagonists indicates that [3H]-clonidine binding is to alpha 2-adrenoceptors. 5. High levels of binding were obtained to lymphocytes prepared from guinea-pig spleen and to membranes from the splenic capsule. Pretreatment of animals with 6-hydroxydopamine produced changes in apparent affinity of binding with little change in the number of receptor sites. 6. It is concluded that [3H]-clonidine labels is a site resembling the alpha 2-adrenoceptor in guinea-pig spleen. Few if any of these sites are located prejunctionally and a significant fraction are associated with lymphocytes.

Animals↗

Immunization outreach using individual need assessments of adults at an army hospital.

A comprehensive assessment of the immunization status of 2,451 adults was carried out at Walter Reed Army Medical Center's Allergy-Clinical Immunology Service, Washington, DC, during an influenza immunization program from October 1985 through February 1986. More than 66 percent of those screened needed either immunization other than for influenza, or an immunologic test, a decline from 72 percent noted during a 1984-85 influenza immunization program. The mean number of interventions was 2.00 per patient in the 1985-86 program and 2.26 during the previous program. Of patients screened in the period 1985-86, 20.5 percent received diphtheria-tetanus toxoids, 15.7 percent received pneumococcal vaccine, and 23.1 percent received a tuberculin skin test. Vaccination or titers for measles were ordered for 10.4 percent, for rubella for 10.9 percent, and for hepatitis B for 20.3 percent. Assessment of those who came to the clinic for influenza vaccination in the second program demonstrated that the needs of some patients had been met in the first program. However, a general lack of immune protection existed in the majority of patients screened in the second program. In both programs, those older than 59 years needed pneumococcal vaccine and diphtheria-tetanus toxoids more frequently than the general population. The means of the numbers of interventions and the percentages of patients needing intervention other than influenza vaccine declined from the first program to the second, suggesting progress in meeting some individual immunization needs in a large and changing ambulatory population.

Adult↗