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Biomedical subjects

J G Webb

Publications and source records attributed to J G Webb.

At least 91 records · Page 5Linked to original sources
PubMed1986

Quantitative analysis of adenosine: statistical comparison of radioimmunoassay and gas chromatography-mass spectrometry-selected ion monitoring methods.

A new method for quantitating adenosine concentration by capillary gas chromatography-mass spectrometry-selected ion monitoring (GC-MS-SIM) has been developed and used as a reference method for evaluating a newly developed radioimmunoassay (RIA) for adenosine. Details of the GC-MS-SIM method are presented, along with the comparative results and uncertainties of both methods. General considerations in the statistical analysis of method comparison data are discussed with particular reference to studies using quantitative mass spectrometry as the standard method; the adenosine methods are used as specific examples in this discussion. Simultaneous estimation of the y-intercept and slope of the least squares regression line relating the results of the two methods using the 95% joint confidence ellipse demonstrated the absence of either constant or proportional error between the two methods. The relatively small uncertainty in the GC-MS-SIM measurements had no significant effect on the linear regression. Random error between the two methods was detected, and was estimated by the coefficient of variation in the RIA data as ten percent of the RIA value.

Adenosine↗
PubMed1986

Hypertrophic osteoarthropathy and pulmonary tuberculosis.

A case of hypertrophic osteoarthropathy associated with pulmonary tuberculosis is described. This appears to be a definite, although rare, complication of tuberculosis and may be associated with severe and fulminant disease.

Humans↗
PubMed1986

Central venous catheter malposition presenting as chest pain.

Erroneous positioning of central venous catheters in small tributaries of large central veins is a rare occurrence. We describe three such unusual incidents involving cannulation of the left internal mammary vein. Malposition was suspected when infusion of hypertonic parenteral nutrition led to persistent precordial pain. Unusual chest pain syndromes may indicate central venous catheter malposition and have not previously been described.

Adult↗
PubMed1985

Depolarization-induced release of propranolol and atenolol from rat cortical synaptosomes.

The accumulation and release of [3H]-propranolol and [3H]-atenolol were examined in synaptosomes from rat cerebral cortex. Synaptosomes accumulated 20 pmol propranolol and 0.6 pmol atenolol mg-1 protein when incubated at 30 degrees C with radiolabelled drugs (0.1 microM). Exposure of propranolol-loaded synaptosomes to elevated K+, Rb+ or Cs+ evoked a concentration-dependent increase in propranolol efflux. The action of these ions in releasing propranolol was highly correlated with their ability to produce synaptosomal membrane depolarization, as estimated with the voltage-sensitive dye diS-C3-(5). Elevated K+ also promoted atenolol release from synaptosomes in a concentration-dependent manner. Veratridine (10 microM) released propranolol and atenolol from synaptosomes and these effects were antagonized by tetrodotoxin (1 microM). Under Ca2+-free conditions, K+-induced release of propranolol was reduced by 37% and atenolol release was diminished by 68%. The results support the concept that both polar and non-polar beta-adrenoceptor blocking drugs may be accumulated by nerve endings for release by membrane depolarization and suggest that neural storage and release of these molecules may influence their concentrations at localized sites of action.

Animals↗
PubMed1985

Site and mechanism of the centrally mediated hypotensive action of propranolol.

Ventriculocisternal perfusion of propranolol (25 micrograms/kg/min for 30 min) throughout the entire brain ventricular system in anesthetized dogs decreased arterial pressure and increased cerebrospinal fluid (CSF) norepinephrine. Localized perfusion of propranolol into the fourth ventricle produced increased CSF norepinephrine levels and a hypotensive response comparable to that seen with whole-brain ventriculocisternal perfusion. In comparison, perfusion of propranolol through the forebrain (lateral-third) ventricles resulted in changes in CSF norepinephrine comparable to those observed with the administration of the drug into the fourth ventricle but resulted in a reduced hypotensive response. Increased CSF norepinephrine levels and a hypotensive response were also observed after peripheral i.v. infusion of propranolol (100 micrograms/kg/min for 45 min). Collectively, these results support the hypothesis that an interaction of propranolol at noradrenergic nerve terminals in the hindbrain area results in a hypotensive effect which may contribute to the antihypertensive action of the drug.

Animals↗
PubMed1984

Increased myocardial adenosine release in heart failure.

Volume overload congestive heart failure in dogs is associated with a reduced myocardial inotropic responsiveness to the exogenous administration of beta-adrenergic agonists [10, 11]. This same blunted inotropic responsiveness to beta-agonists has now been identified in the failing human myocardium [2]. Volume overload congestive heart failure in dogs is also associated with a reduced resting coronary vascular resistance [7, 12] suggesting the possibility of increased myocardial production of a metabolic vasodilator in the failing heart. Adenosine is a metabolic coronary vasodilator [1] and also has recently been shown to antagonize the inotropic action of beta-adrenergic agonists through a mechanism involving action on the sarcolemmal adenylate cyclase system [4, 13]. Given the findings of blunted inotropic responsiveness of the failing myocardium to beta-adrenergic agonists and reduced coronary vascular resistance in heart failure, we hypothesized that heart failure was associated with elevated myocardial production of adenosine. Accordingly we measured myocardial adenosine release in normal dogs and dogs with volume overload heart failure. Basal levels of myocardial adenosine release were found to be elevated three-fold above normal in dogs with heart failure. It is possible that elevated adenosine release in the failing myocardium contributes both to abnormalities of coronary blood flow and to the blunted inotropic responsiveness of the failing heart to catecholamines.

Adenosine↗
PubMed1984

Orthostatic hypotension with brainstem tumors.

Three patients with brainstem tumors had orthostatic hypotension as the major presenting manifestation. Two patients had primary tumors that involved the dorsal medulla, pons, and rostral spinal cord; one was a malignant astrocytoma and the other a hemangioblastoma. The third patient had an oat cell carcinoma of the lung with subependymal spread to the medulla, pons, hypothalamus, and thalamus. Evaluation of baroreceptor function in the patient with the malignant astrocytoma showed a defect in the efferent sympathetic limb of the baroreceptor reflex arc.

Adolescent↗
PubMed1984

Accumulation, subcellular localization and release of propranolol from synaptosomes of rat cerebral cortex.

Propranolol is accumulated at several adrenergic neuroeffector junctions after chronic oral administration in the dog, and is released subsequently during sympathetic nerve stimulation. In the present study, the accumulation, subcellular localization and release of propranolol was examined in rat cortical synaptosomes. Synaptosomal propranolol accumulation was rapid and attained equilibrium within 1 min. Propranolol uptake increased in a nonlinear manner with increasing drug concentration in the medium, but could not be fully saturated over the concentration range studied (10(-7) - 10(-3) M). Uptake was unaffected by cocaine or ouabain and showed no stereoselectivity. Subsynaptosomal fractionation of propranolol-loaded synaptosomes revealed that the drug was concentrated principally in fractions enriched in synaptic plasma membranes and synaptic storage vesicles. Exposure of propranolol-loaded synaptosomes to elevated potassium evoked a concentration-dependent increase in propranolol overflow, which was not seen in mitochondrial fractions, myelin fractions or in freeze-thawed synaptosomal preparations. Veratridine was also effective in promoting propranolol overflow in a concentration-dependent manner. The increase in propranolol overflow induced by elevated potassium was significantly reduced, but not completely inhibited, in a calcium-free, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-supplemented medium. These results indicate that propranolol may be accumulated by neuronal tissue and stored at sites from which release may occur in response to depolarizing stimuli. The data further suggest that propranolol release in the synaptosome preparation may occur by both calcium-dependent and calcium-independent processes.

Animals↗
PubMed1983

Exercise-induced increments in plasma levels of propranolol and noradrenaline.

Exercise-induced changes in the plasma levels of propranolol and noradrenaline were determined in nine volunteers. Total plasma propranolol levels were increased during submaximal treadmill exercise, with exercise-induced increments of 13 +/- 4% at 4 h after the last dose, 18 +/- 7% at 9 h and 41 +/- 5% at 16 h. Exercise-induced increments in plasma propranolol were observed after single as well as repeated doses. During exercise, increments in plasma propranolol were correlated temporally with changes in plasma noradrenaline. Exercise-induced increments in plasma noradrenaline were greater during propranolol administration than during placebo periods. The changes in plasma propranolol concentration during exercise may reflect a redistribution of propranolol at its site(s) of action.

Humans↗
PubMed1982

Persistence of myocardial failure following removal of chronic volume overload.

Length-contractile force curves and dose-response curves of heart rate, blood pressure, and contractile force were recorded from the left ventricle of six anesthetized dogs in a control state. These measurements were repeated at an average of 56 days following creation of an atrioventricular fistula when signs of heart failure were present. The fistula was then closed and the dogs restudied after an additional 57 days. Heart failure was associated with a shift up the ascending limb of a depressed length-contractile force curve and a depressed contractile response to isoproterenol. For instance, 0.1 micrograms/kg of isoproterenol produced a 173 +/- 8% increase in contractile force in control and 42 +/- 7% in failure. The contractile response to ouabain (30 micrograms/kg) was unchanged in heart failure, i.e., 36 +/- 5% in control vs. 39 +/- 4% in heart failure. When the dogs were restudied following fistula closure, the length-contractile force curve was still depressed as was the contractile response to isoproterenol, whereas the response to ouabain was again unchanged from control. Plasma norepinephrine and renin levels increased 5- and 10-fold, respectively, during heart failure and then returned to control following closure of the fistula. The data support the view that myocardial dysfunction associated with volume-overload heart failure is not reversible within the same time frame as its onset.

Animals↗
PubMed1981

Cerebroventricular propranolol elevates cerebrospinal fluid norepinephrine and lowers blood pressure.

Ventriculocisternal administration of dl- and d-propranolol produced dose-dependent increases in cerebrospinal fluid norepinephrine and reductions in blood pressure. A highly significant correlation was found between the increase in norepinephrine and the hypotensive effect. The propranolol-induced hypotension was prevented by intracisternal phentolamine. These data indicate that the hypotensive effect of centrally administered propranolol results from a drug-induced release of norepinephrine, which stimulates central alpha receptors to lower arterial pressure.

Animals↗
PubMed1981

A comparison of the inflammatory response produced by commercial eugenol and purified eugenol.

Eugenol "purified" by HPLC20 was compared to commercial USP eugenol to determine if any difference exists between the inflammatory response caused by each. Mixtures of each eugenol with zinc oxide were also compared. Each material was injected subcutaneously beneath the abdominal skin of 40 Walter Reed white rats. Ten animals were sacrificed at four different dates, and the degree of necrosis and inflammation was compared. The purified eugenol caused less necrosis and inflammation at all times than did the commercial eugenol. The purified ZOE mixture produced less necrosis and inflammation than the commercial ZOE mixture at each sacrifice date. The two mixtures of ZOE and the two samples of eugenol produced roughly parallel amounts of inflammation, suggesting that the degree of inflammation of ZOE mixtures is strongly influenced by the amounts of free eugenol in the mixtures. This study suggests that the impurities in commercial eugenol do cause an increase in the inflammatory response in the rat system studied. This increase is most evident at day two and after day ten.

Animals↗
PubMed1980

A differential inotropic responsiveness to isoprenaline and ouabain in dogs with heart failure.

We have previously shown that volume overload heart failure is associated with a depressed inotropic response to isoprenaline, noradrenaline, glucagon, and calcium. In these present experiments, the inotropic response of the failing heart to ouabain was examined because ouabain has a mechanism of action that is different from these other agents. The studies were conducted in dogs with heart failure resulting from an aortocaval fistula. The principal finding was that during heart failure the inotropic response to isoprenaline was markedly depressed while the inotropic response to ouabain was unaltered. These findings, coupled with our previous observations, suggest that heart failure is not associated with some common defect in the excitation-contraction coupling mechanism that reduces the response to inotropic agents. Additionally, we made the first measurements of plasma noradrenaline levels in this model of heart failure and found them to be elevated four-fold.

Animals↗