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Biomedical subjects

J Coyle

Publications and source records attributed to J Coyle.

35 records · Page 2Linked to original sources
PubMed1986

The effect of propranolol on catecholamine clearance.

Normal subjects given propranolol increased their plasma t1/2 for infused isoproterenol from 2.68 to 6.25 minutes. Propranolol increased plasma norepinephrine (NE) levels only slightly. Propranolol increased the t1/2 of isoproterenol but not that of NE in men with autonomic nervous system degeneration. This suggests that propranolol acts on nonneuronal uptake-2 processes, rather than on uptake-1 mechanisms. alpha-Blockers slow uptake-1 and beta-blockers slow uptake-2 processes. When 27 subjects exercised, those who attained the highest plasma levels of the alpha- and beta-receptor agonist NE also had the briefest apparent t1/2 for NE. Adrenergic receptor blocking drugs slow catecholamine clearance. NE may stimulate its own clearance.

Blood Pressure↗
PubMed1986

Interpretation of pulmonary artery wedge pressure and pullback blood gas determinations during positive end-expiratory pressure ventilation and after exclusion of the bronchial circulation in the dog.

Left atrial pressure (LAP) and pulmonary artery wedge pressure (PWP) were measured at different heights during graded increases in positive end-expiratory pressure (PEEP). Six healthy anesthetized dogs were placed in lateral decubitus positions with a balloon-tipped pulmonary artery catheter inserted in each lung. PWP in the gravitationally superior lung overestimated LAP at 15 and at 20 cm H2O PEEP (p less than 0.05). PWP in the dependent lung was virtually identical to LAP at all degrees of PEEP. Wedge blood could be aspirated through the distal lumen of the pulmonary artery catheters during balloon inflation at all degrees of PEEP except for 3 attempts. PCO2 in wedge blood in both the nondependent and dependent lungs at all degrees of PEEP was consistently lower than PCO2 in arterial blood (p less than 0.05). Wedge blood was arterialized, i.e., oxygen saturation greater than 95%, in all but 4 specimens. Surgical elimination of the bronchial artery supply to the lung in 3 dogs did not affect PWP or blood gas measurements. We conclude that in this animal model: (1) the tip of a pulmonary artery catheter must be below the level of the left atrium, Zone III location, to accurately reflect LAP at high degrees of PEEP; (2) arterialization of wedge blood samples does not guarantee that PWP reflects LAP; (3) bronchial artery blood supply does not affect PWP or wedge blood gas measurements, even at high degrees of PEEP.

Animals↗
PubMed1986

Relapse in chronic schizophrenics treated with fluphenazine decanoate is associated with low serum neuroleptic levels.

Seventy-three chronic schizophrenic outpatients were studied for 1 year to determine if neuroleptic drug levels could be useful in preventing relapse. All patients received fluphenazine decanoate i.m., and serum level of neuroleptic was determined by radioreceptorassay. Clinical improvement was measured using the Global Assessment Scale. Results indicate that serum neuroleptic drug levels may be useful in the outpatient management of chronic schizophrenics.

Adolescent↗
PubMed1985

Dipeptides of glutamate and aspartate may be endogenous neuroexcitants in the rat hippocampal slice.

The dipeptide N-acetylaspartylglutamate (NAAG), and possibly the related dipeptide aspartylglutamate (AG), have been found in high concentrations in rat brain, and have been shown to bind avidly and selectively to a subset of glutamate (GLUT) receptors. Certain observations regarding GLUT and aspartate might be explained if the endogenous transmitter were a compound composed of both amino acids. We therefore examined the electrophysiological actions of NAAG and AG in the rat in vitro rat hippocampal slice model. NAAG or AG and GLUT were applied locally to cells by a dual-barrel pressure technique. Intracellular recordings from 34 CA1 pyramidal neurons showed depolarizations and conductance increases resembling evoked excitatory postsynaptic potential in 15 of 20 cells exposed to NAAG, and 14 of 14 exposed to AG. Many GLUT-responsive sites did not respond to AG, and most did not respond to NAAG. Responses to NAAG were usually too small to induce cell firing; they were best detected, therefore, by intracellular recording. With extracellular unit recordings, GLUT was equally excitatory in stratum radiatum and pyramidale of CA1 (N = 19; p greater than 0.10, one-way analysis of variance). In contrast, AG was considerably more potent (N = 21; p less than 0.01) in stratum radiatum. NAAG was not noted to excite cells when applied to stratum pyramidale. The region of maximal responsiveness to AG in CA1 coincided with the area of the dendritic tree receiving Schaffer collateral-commissural afferents. This spatial profile, together with other neuropharmacological evidence, support the candidacy of glutamate-containing peptides as endogenous excitatory compounds in certain pathways of hippocampus.

Animals↗
PubMed1984

DNA polymerase alpha inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes.

Aphidicolin, a specific inhibitor of DNA polymerase alpha, is known to induce chromosomal aberrations. At concentrations that did not greatly affect mitotic index, aphidicolin induced a striking number of chromosome gaps and breaks distributed in a highly nonrandom manner in cultured human lymphocytes. Specific chromosome bands, especially 2q31, 3p14, 6q26, 7q32, 16q23, and Xp22 were preferentially damaged in lymphocytes from each of 12 subjects studied. Total and site-specific damage was dose dependent and greatly increased when folic acid was removed from the medium. The sites most sensitive to aphidicolin damage include the "hot spots" seen under conditions of thymidylate stress and in studies of spontaneous chromosomal damage. The fragile X site, which can also be induced by thymidylate stress, was not induced by aphidicolin in lymphocytes, suggesting a separate mechanism for its induction. Aphidicolin represents a novel tool for detection of hot spots on human chromosomes through the mechanism of DNA polymerase alpha inhibition. The hot spots induced by aphidicolin represent a new class of fragile sites which we term common fragile sites.

Aphidicolin↗
PubMed1984

Serum neuroleptic concentrations and clinical response: a radioreceptor assay investigation of acutely psychotic patients.

Twenty-two acutely psychotic patients were rigorously assessed for psychopathology at baseline and after 14 days of neuroleptic treatment. The neuroleptic radioreceptor assay (NRRA) was used to determine serum neuroleptic concentrations. Serum neuroleptic concentration was significantly, nonlinearly related to changes in BPRS Total Score, and BPRS Factor Scores for Thought Disturbance and Anxiety-Depression. Clinical improvement was associated with intermediate (11-50, 51-126 ng/ml haloperidol equivalents) while poor clinical outcome was related to both low (less than or equal to 10 ng/ml) or high (greater than 125 ng/ml) serum levels. The results are discussed in terms of a possible "therapeutic window" for the neuroleptics and the implications this might have for clinical practice.

Adolescent↗
PubMed1983

Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine.

A patient with chronic schizophrenia treated with fluphenazine developed neuroleptic malignant syndrome, characterized by fever, obtundation, rigidity, and tremulousness. Hyperthermia and elevated serum creatine kinase were successfully corrected by parenteral treatment with dantrolene. Obtundation, rigidity, and tremulousness responded to high doses of bromocriptine.

Adult↗
PubMed1983

Fenfluramine lowers plasma norepinephrine in overweight subjects.

The effect of fenfluramine on sympathetic nervous system activity was determined in 12 normotensive, obese men. Supine plasma norepinephrine (NE) concentrations decreased (p less than 0.001) from pretherapy levels (298 +/- 39 pg/ml) after one (166 +/- 30 pg/ml) and four weeks (171 +/- 28 pg/ml) of fenfluramine (60 mg daily). Fenfluramine did not alter the sympathetic nervous system responses to orthostasis or exercise. Fenfluramine-induced decreases in heart rate (72 +/- 3 to 67 +/- 4 beats/min, p less than 0.01) and mean arterial blood pressure (90 +/- 2 to 81 +/- 2 mmHg; p less than 0.005) were observed after only one week of therapy despite no significant change in body weight. We conclude that fenfluramine may be a useful agent in the treatment of patients with sympathetic hyperactivity. The effects of fenfluramine on given subsets of patients and control subjects are also defined.

Adult↗
PubMed1982

Effects of premature depolarization on refractoriness of ischemic canine myocardium.

In 25 pentobarbital anesthetized dogs we measured refractory periods (RPs) of regularly driven complexes and premature ventricular depolarizations (PVDs) with a range of coupling intervals or of regularly driven complexes and the complex following the PVD, i.e. the postextrasystolic depolarization (PED). Measurements were made during control periods and during occlusion of a branch of the left anterior descending coronary artery. The difference in control and occlusion RPs was less following some PVDs with short coupling intervals than following other PVDs with longer coupling intervals. Variations in the coupling interval of PVDs had less effect on RPs of the PVDs in ischemic than in nonischemic tissue. RPs of PEDs were prolonged with respect to RPs of regularly driven complexes in both ischemic and nonischemic tissue, but the prolongation in ischemic tissue was significantly greater than that in nonischemic tissue, 8 +/- 4 msec and 2 +/- 2 msec respectively, p less than .001. The difference in effect of PVDs on RPs of ischemic and nonischemic tissue results in greater disparity of refractoriness between ischemic and nonischemic tissue following some long coupling interval PVDs than following some PVDs with shorter coupling intervals. In addition the greater prolongation of RPs of PEDs in ischemic than in nonischemic tissue can result in increased disparity in RPs than the disparity between ischemic and nonischemic tissue present during regular drive.

Animals↗
PubMed1982

Plasma, urine, and CSF catecholamine concentrations during and after ketamine anesthesia.

Ketamine has been reported to increase plasma catecholamine concentrations. Prior investigations have only studied plasma catecholamine levels for short periods after iv ketamine. Because ketamine is one of the most frequently used anesthetic agents in critical care research, we evaluated ketamine's effect on catecholamines over a longer period of time. Plasma, urine, and CSF epinephrine (E) and norepinephrine (NE) concentrations were serially measured during a 2-h ketamine infusion and a subsequent 2-h "wake-up" period. No changes in heart rate, mean arterial blood pressure or urine, plasma, and CSF NE concentrations were noted during the 4-h study period, whereas there were significant (p less than 0.005) increases in urine, plasma, and CSF E levels during ketamine infusion but not during the wake-up period. An unexpected finding was that the baboons have very high basal plasma E levels versus those in humans. It is concluded that ketamine is a useful anesthetic agent for critical care research involving measurements of sympathetic nervous system activity. The interesting observation of high plasma levels in the baboon warrants further investigation.

Anesthesia↗
PubMed1976

The effect of a growing tumor and its removal on the cytotoxicity of macrophages from cultured bone marrow cells.

Previous investigations by us have demonstrated that there is a significant but transient (4 to 14 days) increase of colony-forming cells (CFC) in bone marrow following implanation of a syngeneic mammary tumor in C3H mice. Those CFC gave rise to enhanced macrophage colony production when cultured in semisolid medium. The present studies have for the first time demonstrated that macrophages from the colonies were cytotoxic to cells from the immunizing tumor, and they continued to possess that characteristic for as long as a tumor was present in the animal from which bone marrow was derived. By 21 days after tumor removal cytotoxicity was no longer evident. The findings provide evidence to suggest that the cytotoxicity displayed by the macrophage originates in its ancestral CFC or in the antecedent stem cell. They also suggest that receptor sites of the CFC (or stem cell) that respond to a stimulus for self-replication are probably different from those sites that, when activated, result in cytotoxic properties of their progeny. The present findings also indicate not only that quantitation of macrophage production is of relevance in determining the efficacy of a therapeutic regimen but also that knowledge concerning the specific properties, i.e., ctytotoxicity, of such cells is of equal or greater importance.

Animals↗
PubMed1975

Studies concerning the regional lymph node in cancer. VIII. Effect of two asynchronous tumor foci on lymph node cell cytotoxicity.

Results suggest that cytotoxicity by cells from nodes regional to a primary tumor is unique. While a primary tumor was present, A) cytotoxicity was displayed by cells from lymph nodes (RLNs) to that tumor, B) cells from nonregional lymph nodes regional (NRLNs) possessed lesser cytotoxicity which failed to increase in response to a second tumor focus in an area drained by those nodes, and C) the second focus attenuated cytotoxicity of cells from LNs regional to the primary tumor. Following removal of the primary tumor, cells from RLNs rapidly lost cytotoxicity and with passage of time were unable to regain that function in response to a second tumor focus. In contrast, cells from NRLNs demonstrated increased cytotoxicity at any time following removal of the primary tumor when exposed to a second focus. These observations suggest that nodes regional to a distant metastatic focus may be unable to react to it and thus contribute little to the host response generated by the primary tumor. In addition, since nodes regional to a primary tumor manifest diminished cytotoxicity in the presence of a distant tumor focus, tumor cells gaining access and lodging in those nodes subsequent to the development of other metastatic foci are likely to proliferate, resulting in the "positive" lymph node. The findings are in keeping with our contention that host factors responsible for metastases, and perhaps metastases themselves, are at least in part responsible for growth of tumor in RLNs. They also have relevance to the site of administration of specific immunotherapeutic agents and to the significance of the removal of RLNs with a primary tumor.

Amputation, Surgical↗
PubMedDate not supplied

Acute management of spinal cord injury.

Demographic trends in the occurrence of injury and improvements in the early management of spinal trauma are changing the long-term profile of patients with spinal cord injuries. More patients are surviving the initial injury, and proportionately fewer patients are sustaining complete injuries. While preventive efforts to reduce the overall incidence of spinal cord injury are important, a number of steps can be taken to minimize secondary injury once the initial trauma has occurred. Recent efforts have focused on understanding the biochemical basis of secondary injury and developing pharmacologic agents to intervene in the progression of neurologic deterioration. The Third National Acute Spinal Cord Injury Study investigators concluded that methylprednisolone improves neurologic recovery after acute spinal cord injury and recommended that patients who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone therapy is initiated 3 to 8 hours after injury, it should continue for 48 hours. In addition to the adoption of the guidelines of that study, rapid reduction and stabilization of injuries causing spinal cord compression are critical steps in optimizing patients' long-term neurologic and functional outcomes.

Chemoprevention↗
PubMedDate not supplied

Changing perceptions.

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Community Health Nursing↗