Search PubMed⌕ Search

Biomedical subjects

J G Webb

Publications and source records attributed to J G Webb.

At least 73 records · Page 4Linked to original sources
PubMed1990

Coronary angioplasty after coronary bypass surgery: initial results and late outcome in 422 patients.

From 1978 to 1988, coronary angioplasty was performed in 422 patients with prior coronary artery bypass surgery (264 patients with native coronary artery angioplasty and 158 patients with graft angioplasty). Angioplasty was successful in 84%, unsuccessful but uncomplicated in 11% and complicated by one or more major cardiac events in 5% (myocardial infarction 5%, emergency bypass surgery 2% and death 0.2%). Follow-up data were obtained in 99% of 356 patients with successful angioplasty. At a mean of 33 +/- 26 months, 92% were alive, 73% had improvement in angina and 61% were free of angina. One or more of the following late events occurred in 67 patients (19%): myocardial infarction (6%), elective reoperation (13%) and cardiac death (6%). Repeat angioplasty was performed in 27%, with a success rate of 89% and no deaths. Initial success rates were equal in native vessel versus graft angioplasty, but late outcome was less favorable with the latter because of a higher rate of infarction (11% versus 4%, p less than 0.05) and need for reoperation (19% versus 10%, p less than 0.05). The initial success rate was higher in vein grafts less than 1 year old compared with grafts 1 to 4 years or greater than 4 years after operation (92% versus 85% versus 83%, respectively) and adverse late events were less frequent after angioplasty in recent vein grafts (less than 1 year 13%, 1 to 4 years 35%, greater than 4 years 29%; less than 1 versus greater than 1 year, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1990

Chronic treatment with propranolol enhances the synthesis of prostaglandins E2 and I2 by the aorta of spontaneously hypertensive rats.

The effects of treatment with dl, d- or l-propranolol (subcutaneously for 1 week) on arterial blood pressure and on 6-keto prostaglandin (PG) F1 alpha (stable metabolite of PGI2) and PGE2 production by aorta, renal medulla and renal cortex were examined in spontaneously hypertensive rats. dl-Propranolol and l-propranolol significantly (P less than .05) lowered blood pressures from 148 +/- 9/113 +/- 5 (n = 6) and 133 +/- 4/100 +/- 2 (n = 12) mm Hg to 112 +/- 3/80 +/- 3 and 121 +/- 3/81 +/- 3 mm Hg, respectively. Comparable treatment of spontaneously hypertensive rats with inactive d-propranolol was without effect. Basal immunoreactive (i) i6-keto-PGF1 alpha and iPGE2 production by isolated aorta, renal medulla and cortex was not different in vehicle compared to the dl-propranolol-treated rats. In contrast, norepinephrine (1 microM)-stimulated synthesis of i6-keto PGF1 alpha and iPGE2 by the aorta in the dl-propranolol-treated group was significantly (P less than .05) enhanced compared with the vehicle-treated group. Aortic i6-keto-PGF1 alpha and iPGE2 synthesis stimulated by norepinephrine in l-propranolol-treated rats was also significantly (P less than .05) higher than that observed in vehicle and d-propranolol-treated rats. dl-Propranolol treatment did not alter norepinephrine-stimulated renal cortical or medullary i6-keto-PGF1 alpha or iPGE2 synthesis. Indomethacin (5 mg/kg i.p.) given on the last 2 days of dl-propranolol treatment, significantly inhibited aortic i6-keto-PGF1 alpha and iPGE2 production and blunted the antihypertensive effect of dl-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Myocarditis and myocardial hemorrhage associated with thrombotic thrombocytopenic purpura.

Four patients with thrombotic thrombocytopenic purpura (TTP) developed severe cardiac dysfunction. Endomyocardial biopsy in one patient demonstrated focal myocarditis associated with platelet microthrombi. Cardiac function and TTP improved after plasmapheresis therapy in this as well as in two other patients. A fourth patient died owing to extensive intramyocardial confluent hemorrhages. Cardiac involvement in TTP may be due to microvascular thrombosis, hemorrhage, or myocarditis. Severe myocardial dysfunction may improve with treatment aimed at the underlying hematologic disorder.

Adult↗
PubMed1989

Persistent desensitization of the heart to the inotropic action of isoproterenol by adenosine.

Isolated guinea pig hearts were perfused with Krebs buffer in the absence or presence of 10 microM adenosine for 60 to 120 min followed by a 15 min washout with adenosine-free buffer. The effects of isoproterenol on left ventricular dP/dt and heart rate were then determined. Perfusion with adenosine for a minimum of 90 min followed by washout resulted in a 40% depression of the dose-response curve of left ventricular dP/dt to isoproterenol. This depressed inotropic responsiveness persisted for at least 1 hr after cessation of adenosine perfusion. The heart rate response to isoproterenol was unaffected. Also, adenosine perfusion had no effect on ouabain inotropism. Measurement of adenosine in coronary effluent and in ventricular tissue by radioimmunoassay verified that no residual elevated adenosine remained following perfusion and washout. Moreover, isoproterenol-induced release of adenosine into the coronary effluent did not differ between control and adenosine-treated hearts. Addition of 100 microM theophylline, an adenosine receptor antagonist, to the adenosine containing buffer during perfusion prevented the depressed response to isoproterenol. In membrane fractions prepared from ventricles, beta receptors were assessed by (-) [125] iodocyanopindolol binding and neither the density of these receptors nor their affinity for agonists or antagonists was altered by adenosine perfusion. However, activation of adenylate cyclase by isoproterenol (10 microm) was significantly depressed in membranes from adenosine perfused hearts. These findings are consistent with a receptor mediated action of adenosine to produce persistent depression of catecholamine inotropism. Such an effect may be important in heart failure where myocardial levels of adenosine are elevated and circulating levels of catecholamines are high.

Adenosine↗
PubMed1989

Stereoselective uptake of atenolol into storage granules isolated from PC12 cells.

Atenolol has been shown to be stored and secreted from PC12 cells by calcium-dependent and stereoselective mechanisms. The present study was designed to determine if the cytoplasmic amine storage granule was the site for storage and release of atenolol and if the drug was, in fact, an enantiomeric selective substrate for the vesicular amine transport protein. Uptake of racemic [3H]atenolol and (-)-[3H]norepinephrine was studied in a vesicular preparation of storage granules isolated from PC12 cells. Uptake of both molecules was found to be ATP-dependent (80%) and to reach steady state in approximately 10 to 15 min. Uptake and storage was inhibited (95%) by either reserpine, an inhibitor of the vesicular amine carrier, or by nigericin which dissipates the proton gradient across the membrane. Uptake of neither compound was inhibited by desipramine, an inhibitor of uptake 1, or oligomycin, an inhibitor of mitochondrial adenosine triphosphatase. Furthermore, uptake of the (-)-enantiomer of atenolol was found to be approximately 5-fold greater than the (+)-enantiomer. Kinetic studies revealed a Km of 184 microM for (+/-)-atenolol and 79 microM for (-)-norepinephrine and Vmax values of 750 and 503 pmol/min/mg of protein for atenolol and norepinephrine, respectively. The interaction of the two compounds with the transport process was found to be kinetically competitive. In separate experiments, atenolol was also found to be transported stereoselectively into bovine adrenal chromaffin granule ghosts and to be ATP dependent (85%) and reserpine sensitive (44%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1988

Stereoselective delivery and actions of beta receptor antagonists.

These studies have revealed that the delivery and actions of beta receptor antagonist drugs are controlled by a cascade of stereoselective processes involving multiple enzymes, transport proteins and receptors. In essence, the free concentration of the pharmacologically active (-)-enantiomer species of these drugs presented to cell surface beta receptors appears to be a function of the stereoselective clearance by hepatic cytochrome P-450 isoenzymes, enantiomer selective binding to alpha 1-acid glycoprotein and albumin and perhaps predominantly by stereoselective sequestration (and release) by the vesicular amine transport protein within adrenergic neurons. Stereoselectivity in the clearance of beta blocking drugs, which can favor either the (+)- or (-)-enantiomer, only appears to be important for the lipophilic drugs which are cleared by hepatic metabolism. Such stereoselectivity is due to differential stereochemical substrate requirements of individual hepatic cytochrome P-450 isoenzymes. Interindividual variations in the stereoselectivity can occur as a result of differences in the amount and expression of cytochrome P-450 isoenzymes due to genetic predisposition or other factors. In the same context, we have observed a significant correlation between the extent and stereoselectivity of binding of beta blocking drugs to plasma proteins. This is another finding which suggests that variability in the expression of individual proteins involved in the beta blocking drug-protein cascade determines the free concentration of the pharmacologically active enantiomer. However, since most observations have been made in young normal subjects, the extent of stereoselectivity in metabolism, binding and other processes is unknown in the general population where steady-state plasma concentrations can vary widely due to multiple biological factors. The observations from neural studies support the concept that adrenergic nerve endings provide a depot for the stereoselective storage and release of the active enantiomer of beta receptor antagonists. The mechanism of this release appears to involve exocytotic secretion of drug that has been stereoselectively accumulated by the neurotransmitter storage vesicles. In terms of this idea, beta receptor antagonists released during nerve stimulation may achieve concentrations of the (-)-enantiomer within the adrenergic synapse greatly in excess of those found in plasma. Such a mechanism could significantly influence both the intensity and duration of beta receptor blockade in the heart, blood vessels, brain and other target tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Cardiac dysfunction associated with the acquired immunodeficiency syndrome (AIDS).

Five patients with acquired immune deficiency syndrome (AIDS) developed clinical evidence of mild to severe cardiac dysfunction confirmed by nuclear angiography and echocardiography. In 4 patients who were studied postmortem there was no evidence of myocarditis, valvular, or ischemic heart disease. Cardiac involvement in patients with AIDS may include pericardial and myocardial involvement by opportunistic pathogens or Kaposi's sarcoma, subclinical myocardial dysfunction, or an as-yet unexplained cardiomyopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Inhibitors of prostaglandin synthesis reverse the effects of chronic beta-receptor blockade to attenuate adrenergic neurovascular transmission in dogs.

The effects of acute and chronic treatment with beta-adrenergic receptor blocking drugs on peripheral adrenergic neurovascular transmission were investigated. Experiments were performed using the blood perfused gracilis muscle preparation in control dogs and in animals treated with single or repeated doses of beta-receptor antagonists. After 7 days of d,l-propranolol, l-propranolol, or atenolol administration, the arterial pressor response to sympathetic nerve stimulation was significantly reduced in treated dogs (p less than 0.05) when compared with control- or d-propranolol-treated animals. In comparison, acute beta blockade produced by a single intravenous dose of propranolol had no effect on the pressor response to nerve stimulation. Inhibition of fatty acid-cyclooxygenase activity by indomethacin or piroxicam enhanced the vasoconstrictor response to sympathetic nerve stimulation in chronic d,l-propranolol-, l-propranolol-, and atenolol-treated dogs, but had no effect on vascular neurotransmission in control-, chronic d-propranolol-, or acutely d,l-propranolol-treated animals. The vasoconstrictor response to intraarterial phenylephrine was not significantly altered by chronic propranolol treatment, and measurement of norepinephrine overflow during sympathetic nerve stimulation failed to reveal any difference in neurotransmitter release between control- and propranolol-treated dogs. The results indicate that chronic but not acute beta-adrenergic receptor blockade alters signaling at the neurovascular synapse to diminish adrenergic transmission. This effect does not appear to result from a change in postsynaptic alpha 1 receptors or from a decrease in norepinephrine release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Surgical therapy for sinoatrial reentrant tachycardia.

Sinoatrial reentry is an uncommon cause of paroxysmal supraventricular tachycardia. This paper presents a case of supraventricular tachycardia, refractory to medical therapy, in which the sinus node formed part or all of the reentrant circuit. The mechanism of the arrhythmia was confirmed by catheter mapping during electrophysiological study and by intraoperative epicardial mapping. Cryosurgical ablation of the right atrium in the region of the sinus node has led to cure of her arrhythmia and emergence of a stable ectopic atrial pacemaker rhythm.

Adult↗
PubMed1988

Direct endocardial recording and catheter ablation of an accessory pathway in a patient with incessant supraventricular tachycardia.

A patient presented with incessant supraventricular tachycardia due to a concealed accessory pathway. The His bundle electrocardiogram showed a large discrete accessory pathway potential following ventricular activation and resulting in retrograde atrial activation. Percutaneous catheter ablation in the region of the accessory pathway potential left nodal conduction intact but prevented retrograde activation of the atria. Symptomatic tachycardia has not recurred. Direct endocardial recording of accessory pathway potentials is rare but may offer the opportunity for catheter ablation.

Adult↗
PubMed1988

Enhanced exercise noradrenaline concentrations during propranolol treatment: a limiting factor in cardiac beta-adrenoceptor blockade.

Treatment with beta-adrenoceptor blocking drugs may result in augmented plasma concentrations of noradrenaline during exercise. The effect of propranolol on exercise heart rate and its relationship to plasma concentrations of propranolol and noradrenaline were examined in 10 hospitalized volunteers following treatment with propranolol, in doses of 80 mg and 320 mg daily. Responses to submaximal treadmill exercise during propranolol treatment and following discontinuation of the higher dose were compared to pre-drug and post drug placebo values. Exercise noradrenaline was increased by 67% over baseline values by treatment with the 320 mg daily dose of propranolol; this increment was present at 4 h and returned to baseline by 16 h after drug administration. Augmentation of exercise noradrenaline was correlated with plasma propranolol concentrations; the threshold concentration for this effect was 10-fold higher than the threshold for reduction in exercise heart rate. The effect of propranolol on heart rate was blunted in relation to the augmentation of exercise noradrenaline (P less than 0.001). These relationships suggest that, in patients taking high doses of propranolol, drug induced augmentation of plasma levels of noradrenaline during exercise may have physiologic importance. Enhanced effects on adrenergic receptors could have clinical relevance in certain groups of patients.

Adult↗
PubMed1988

Stereoselective secretion of atenolol from PC12 cells.

Stereoselective storage and release of the cardioselective beta adrenergic receptor antagonist atenolol was studied using cultured PC12 cells as a neural model. [3H]Atenolol efflux from preloaded PC12 cells was increased 4-fold in response to membrane depolarization by elevated extracellular potassium (50 mM). [3H]Norepinephrine release was enhanced 4.5-fold under the same conditions. Potassium-induced release of both [3H] atenolol and [3H]norepinephrine was inhibited completely in the absence of extracellular calcium. [3H]Atenolol release from PC12 cells was also reduced by the calcium channel antagonist nifedipine (IC50 = 1.6 +/- 0.5 nM). In addition, the calcium channel agonist BAY K8644 (1 microM) significantly enhanced potassium-induced [3H]atenolol efflux. After loading overnight, accumulation and storage of the (-)-enantiomer of atenolol by PC12 cells was found to be approximately 3-fold greater than that of the (+)-enantiomer. The (-)-enantiomer of atenolol was also preferentially released by 50 mM potassium with a (-)/(+)-enantiomer ratio of 3.6 to 1. The results support the existence within neurosecretory cells of storage and calcium-dependent release mechanisms which result in stereoselective secretion of the (-)-or active enantiomer of atenolol in response to membrane depolarization.

Animals↗
PubMed1987

Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin.

The effects of afferent vagal stimulation, cerebroventricular vasopressin, and intravenous nitroprusside on cerebrospinal fluid (CSF) kinin levels, mean arterial pressure (MAP), and heart rate (HR) were determined in anesthetized dogs in which a ventriculocisternal perfusion system (VP) was established. Following bilateral vagotomy, stimulation of the central ends of both vagi for 60 min significantly increased MAP and CSF perfusate levels of kinin and norepinephrine (NE). MAP was increased a maximum of 32 +/- 4 mmHg, and the rates of kinin and NE appearance into the CSF perfusate increased from 4.2 +/- 1.4 to 22.1 +/- 6.9 and from 28 +/- 5 to 256 +/- 39 pg/min, respectively. A significant correlation was found between CSF kinin and NE levels in these experiments. In other experiments the addition of arginine vasopressin to the VP system caused a significant increase in CSF perfusate kinin without affecting MAP or HR. Intravenous infusion of nitroprusside lowered MAP without affecting kinin levels in the CSF. However, on cessation of nitroprusside infusion, CSF kinin increased significantly in association with the return in MAP to predrug level. Collectively the data are consistent with the hypothesis that central nervous system kinins have some role in cardiovascular regulation, and furthermore that this role may involve an interaction between brain kinin and central noradrenergic neuronal pathways.

Afferent Pathways↗
PubMed1987

Multiple enteric pathogens in a patient with diarrhoea.

A woman who recently arrived in Canada from India developed a febrile, diarrhoeal illness. Stool culture revealed the presence of Salmonella typhi, Campylobacter fetus subspecies jejuni and Shigella flexneri. Concurrent infection with these three pathogens does not appear to have been previously reported. The possibility of multiple pathogens should be considered in travellers who fail to respond to treatment of a single organism.

Adult↗
PubMed1986

Malnutrition and the heart.

Earlier concepts that the heart is spared in malnutrition have been shown to be incorrect. Inadequate intake of protein and energy results in proportional loss of skeletal and myocardial muscle. As myocardial mass decreases, so does the ability to generate cardiac output; however, various compensatory factors come into play. Nutritional supplementation for malnourished patients reverses the compensatory factors and may increase the short-term potential for heart failure. Severe cardiac debility results in poor nutrition, which may in turn produce unsuspected but clinically significant myocardial atrophy. Nutritional support may play a role in improving cardiac function in selected patients with cardiac cachexia who are being prepared for cardiac surgery and in patients with rapid weight loss who are at risk for sudden death due to arrhythmias. Malnutrition is common in hospitalized patients, and many patients in hospital now receive nutritional supplementation; both facts have important cardiac implications.

Animals↗