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Biomedical subjects

P Sharkey

Publications and source records attributed to P Sharkey.

26 records · Page 2Linked to original sources
PubMed1986

Pharmacodynamics and side effects of flecainide acetate.

We compared side effects with flecainide trough levels and ECG intervals among 43 patients who received flecainide for up to 34 months. Flecainide plasma levels were higher when associated with cardiovascular side effects (mean 1063 ng/ml; range 296 to 2050 ng/ml) than when no side effects occurred (mean 609 ng/ml; range 89 to 1508 ng/ml; P less than 0.001). The PR interval (P less than 0.001), QRS interval (P less than 0.001), and the rate-corrected QT interval (P less than 0.001) were greater at the time of cardiovascular side effects, but the rate-corrected JT interval was not. The therapeutic-toxic window for flecainide plasma level was 381 ng/ml (at least 50% probability of efficacy) to 710 ng/ml (less than 10% probability of cardiovascular side effects). The risk of cardiovascular side effects increases at higher plasma levels of flecainide and is associated with greater increases in the PR and QRS intervals from baseline than are routinely observed during flecainide dosing.

Aged↗
PubMed1986

Pulmonary microvascular fluid flux in a large animal model of sepsis: evidence for increased pulmonary endothelial permeability accompanying surgically induced peritonitis in sheep.

To characterize some of the remote effects of systemic sepsis on the lung, we evaluated changes in pulmonary microvascular fluid flux before and during sepsis secondary to a peritoneal focus of inflammation in sheep. We induced peritonitis by cecal ligation, perforation, and devascularization. During a subsequent 72-hour study period, both the mean blood pressure and the pulmonary capillary wedge pressure were unchanged, while the cardiac index increased slightly. The PaO2 fell by 48 hours (98 +/- 8 to 84 +/- 10 mm Hg; p less than 0.05) (mean +/- SD) and subsequently remained low throughout the experiment. Simultaneously, pulmonary lymph flow increased by 24 hours (11.5 +/- 4.9 to 26.7 +/- 13 ml/hr; p less than 0.05) and remained elevated throughout the experiment while [L/P] total protein ratios remained unchanged at 24 hours (baseline: 0.59 +/- 0.15 at 24 hours: 0.65 +/- 0.16). Morphologic examination of the lung showed that this model of peritonitis was characterized by neutrophil emigration into the pulmonary interstitium by 24 hours and interstitial edema by 48 hours. Therefore this model of bacterial peritonitis in sheep demonstrates that one of the remote effects of surgically induced systemic sepsis is an increase in permeability of the pulmonary microvascular membrane.

Animals↗
PubMed1985

Microsurgical selective procedures in peripheral nerves and the posterior root-spinal cord junction for spasticity.

This review deals with the long-term results of selective peripheral neurotomy (SPN) of the tibial nerve and selective posterior rhizotomy (SPR) in 123 cases of severe spastic syndromes in the limbs. The microtechniques and preoperative electrostimulation for identification of the nervous structures responsible for the spastic components give to these methods an advantage of a substantial reduction of the harmful spasticity, without suppressing the useful muscle tone and impairing the residual motor and sensory functions. The results were effective, with a 1- to 13-year follow-up, in 89% of 47 SPN of the tibial nerve for spastic foot, in 92% of 53 SPR for paraplegia and in 87% of 23 SPR for hemiplegia.

Adolescent↗
PubMed1984

A controlled trial of propafenone for treatment of frequent and repetitive ventricular premature complexes.

The effectiveness of oral propafenone was evaluated for the treatment of ventricular premature complexes (VPCs) in 12 patients, using a single-blind, dose-ranging trial followed by a double-blind comparison with placebo, and then an open-label, long-term protocol. During dose ranging, 8 of 12 patients achieved greater than or equal to 80% suppression of total VPCs (mean 83%) (p less than 0.01 vs single-blind placebo). Paired VPCs were suppressed greater than or equal to 90% and ventricular tachycardia was eliminated in 11 of the 12 patients (p less than 0.01). The effectiveness of propafenone for treatment of VPCs was confirmed during the double-blind trial (p less than 0.05 vs double-blind placebo) and during treatment for 6 months (p less than 0.05 vs initial single-blind placebo). Propafenone prolonged the PR interval by 16% (p less than 0.01 vs single-blind placebo) and the QRS interval by 18% (p less than 0.001). Left ventricular systolic performance decreased as assessed by 2-dimensional echocardiography (p less than 0.01 vs single-blind placebo). Propafenone increased serum digoxin levels in 5 of 5 patients (mean increase of 83%). Side effects included exacerbation of congestive heart failure (1 patient) and conduction abnormalities (2 patients). Thus, propafenone is effective for treatment of total and repetitive VPCs. Although generally well tolerated, the drug reduces left ventricular systolic function and atrioventricular conduction and increases serum digoxin levels.

Adult↗
PubMed1984

The effect of an infusion of zymosan-activated plasma on hemodynamic and pulmonary function in sheep.

To assess the integrated cardiopulmonary response to acute microvascular lung injury, we infused zymosan-activated plasma (ZAP) into mature, awake sheep. ZAP infusion resulted in an immediate increase in the mean pulmonary artery pressure (PAP) from 17.5 +/- 4.5 mm Hg to a maximum of 33.0 +/- 5.4 mm Hg by 5 min (p less than 0.01) of a 90-min infusion. The pulmonary artery hypertension (PAH) was sustained throughout ZAP infusion, and for up to 30 min after infusion was completed (p less than 0.05). Lung lymph flow increased immediately, but lymph to plasma total protein ([L/P]) ratios remained unchanged, suggesting increased pulmonary microvascular permeability. The PaO2 fell to a minimum by 5 min (106.9 +/- 17 to 88.3 +/- 14 mm Hg; p less than 0.01), but recovered toward preinfusion values in the final 60 minutes of ZAP infusion. The cardiac index (CI) and stroke volume index (SVI) also fell significantly for 15 minutes (p less than 0.01), and then recovered to levels not different from baseline by 30 min. In parallel with all of these changes, the polymorphonuclear leukocyte count (PMN) in arterial blood fell immediately [baseline to 5 min, delta 4.9 +/- 2.5 (X 10(3))/mm3; (p less than 0.01)] due to sequestration within the pulmonary microvasculature, since a baseline PMNs were being released from the lung, -6.0 +/- 19%, while by 15 min the PMNs were being sequestered, +58.4 +/- 31% (p less than 0.01). Therefore, ZAP infusion reproduced the clinical picture of acute microvascular lung injury in humans, specifically acute PAH and increased pulmonary microvascular permeability. These two changes were due to a cascade of events associated with the pulmonary microvascular trapping of PMNs.

Animals↗
PubMed1983

Comparison of flecainide with quinidine for suppression of chronic stable ventricular ectopic depolarizations. A double-blind randomized study in ambulatory outpatients.

In a randomized placebo-controlled double-blind trial, we compared flecainide to quinidine for treatment of ventricular ectopic depolarizations in 19 patients. The mean percent suppression of total ventricular ectopic depolarizations was 95% for flecainide and 56% for quinidine (p less than 0.05). A greater than 80% reduction of total ventricular ectopic depolarizations was obtained in eight of nine patients given flecainide and in five of ten patients given quinidine (p = 0.09). After the randomized protocol, the patients who had received quinidine were given flecainide; 9 of the 10 patients had greater than 80% reduction of total ventricular ectopic depolarizations. Flecainide produced 100% suppression of nonsustained ventricular tachycardia and 99.5% suppression of paired ventricular depolarizations. Flecainide prolonged the PR and QRS intervals; quinidine prolonged the PR and JTC intervals. Side effects were commoner with quinidine than flecainide (p = 0.06). Three other patients failed to complete the protocol because of serious adverse experiences.

Adult↗