PubMed Health⌕ Search

Biomedical subjects

J F Lavelle

Publications and source records attributed to J F Lavelle.

8 recordsLinked to original sources
PubMed2001

Glycine antagonist (GV150526) in acute stroke: a multicentre, double-blind placebo-controlled phase II trial.

GV150526 is a novel glycine antagonist at the NMDA receptor complex. It is a potent neuroprotective agent in animal models of acute stroke including permanent middle cerebral artery occlusion in the rat. GV150526 was very well tolerated in early human studies. The purpose of this randomised, double-blind, multicentre, placebo-controlled trial was to assess the safety and population pharmacokinetics of GV150526 in patients with a clinical diagnosis of acute stroke. Exploratory assessment of efficacy, quality of life and resource utilisation was also undertaken. Upon clinical diagnosis of acute stroke within 12 h of onset of symptoms, patients were treated with a loading dose of 800 mg GV150526 (or placebo), followed by 5 maintenance doses of 400 mg GV150526 (or placebo) given every 12 h over 3 days. Following observation of asymptomatic hyperbilirubinaemia, the maintenance dose was reduced mid-study to 200 mg. CT/MRI scanning was not mandatory prior to treatment. The study treated 128 patients (38 with GV 800 mg/400 mg, 48 with GV 800 mg/200 mg and 42 with placebo). Fewer patients with mild stroke (NIH scores < or =5) were enrolled in the GV150526-treated groups than in the placebo group (placebo 38%, GV 800 mg/400 mg 18%, GV 800 mg/200 mg 15%). There was also an imbalance in the proportion of patients with haemorrhagic strokes (placebo 5%, GV 800 mg/400 mg 3%, GV 800 mg/200 mg 15%). Mortality at 1 month was unbalanced between treatment groups, being 10, 18 and 17% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively (no significant difference). Similarly, adverse events, though consistent with an acute stroke population, appeared more often in the GV 800 mg/200 mg group. Functional outcomes at 1 month also showed imbalances, the percentage of patients with a Barthel Index score of > or =95 at 1 month being 52, 39 and 27% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively. These results probably reflect a prognostically significant baseline difference between the groups rather than the effect of GV150526. GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified.

Aged↗
PubMed1982

Left ventricular geometry during partial and complete coronary occlusion in the conscious dog.

Seven dogs were instrumented with a left ventricular micromanometer and pairs of ultrasonic crystals to measure left ventricular wall thicknesses (control and ischemic regions) and short and long left ventricular axes; cuff occluders were placed around the left circumflex coronary artery and the inferior vena cava. Measurements were performed at rest, after 2 min of partial and complete coronary occlusion, and 1 and 10 min after release of partial and complete coronary occlusion. Left ventricular wall thickness in the ischemic region showed reduced systolic thickening during partial coronary occlusion and systolic thinning during complete coronary occlusion. During diastole, at zero pressure (inferior vena cava obstruction) the left ventricular short axis was unchanged during partial coronary occlusion but significantly increased (creep) during complete coronary occlusion (P less than 0.05), whereas after release of both partial and complete coronary occlusion the short axis at zero pressure decreased significantly (P less than 0.025). Left ventricular wall thickness at zero diastolic pressure in the ischemic region was significantly thinner during complete coronary occlusion than during control and significantly thicker (reactive hyperemia) 1 min after release of both partial and complete coronary occlusion. The long left ventricular axis remained unchanged during the entire experiment. At end-diastole, the long/short axis ratio was normal during partial (1.72; control 1.68; NS) and complete coronary occlusion (1.69; NS), but it decreased significantly from control of 2.10 to 1.99 with partial coronary occlusion and 1.85 with complete coronary occlusion (P less than 0.01). The changes in the L/S ratio during partial and complete coronary occlusion were proportional to changes in left ventricular chamber volume (correlation coefficient 0.94). Our data show that left ventricular shape remains normal at end-diastole during partial and complete coronary occlusion but becomes significantly more spherical at end-systole, with reduction of the normal tendency for the ventricle to become more elliptical during systole. These elliptical and spherical shape changes of the left ventricle during partial and complete coronary occlusion appear to be closely related to the chamber volume.

Animals↗
PubMed1981

[Determinants of the diastolic pressure-volume relationship of the left ventricle: significance of myocardial ischemia and vena cava occlusion].

Diastolic pressure-volume relations of the left ventricle were studied in 7 dogs during partial and complete coronary occlusion. The pericardium was widely opened and the dogs were instrumented with a left ventricular micromanometer, cuff occluders around the left circumflex coronary artery and inferior vena cava, and ultrasonic crystals to measure control and ischemic wall thickness as well as both left ventricular long and short axes. Measurements were performed at rest and after 2 minutes of partial and complete coronary occlusion. The first experiment was performed without caval occlusion and a second experiment was carried out a few days later with caval occlusion. During partial coronary occlusion, no shift of the diastolic pressure-volume relationship was observed. However, during complete coronary occlusion the pressure-volume curve was shifted significantly upwards but no shift was observed when occlusion of the inferior vena cava was carried out. These findings suggest that the shift of the diastolic pressure-volume relationship during coronary occlusions (1) depends on the extent of myocardial ischemia and (2) is related to ventricular interaction since the shift was prevented by caval occlusion.

Animals↗
PubMed1973

Early estimation of myocardial damage in conscious dogs and patients with evolving acute myocardial infarction.

To estimate the ultimate extent of myocardial damage during evolving myocardial infarction in conscious dogs and patients, we analyzed early serum creatine phosphokinase (CPK) changes with nonlinear curve-fitting techniques. In experiments with dogs, serial serum CPK changes were fit to a log-normal function by the least squares method; the extent of the completed infarct was calculated by analysis of observed serum CPK changes and verified by measurement of myocardial CPK depletion 24 h after coronary occlusion. Early prediction of myocardial damage was based on projected serum CPK values from best fit curves based on data obtained during the first 5 h after initial elevation of enzyme activity. The correlation between predicted and observed values was close (r > 0.96, n = 11). In 11 additional conscious animals subjected to coronary occlusion, isoproterenol was administered continuously as soon as damage had been estimated from projected serum CPK values. The extent of the completed infarct was assessed by analysis of all serial serum CPK values and verified by analysis of myocardial CPK depletion 24 h after coronary occlusion. In each experiment the calculated completed infarct size exceeded infarct size projected before administration of isoproterenol (average increase = 44+/-10 [SE]%). When similar calculations were applied in experiments with eight dogs treated with propranolol, myocardial salvage was detected in 50% of the animals. In 30 patients with uncomplicated acute myocardial infarction the extent of the completed infarct, measured by analysis of CPK activity in serum samples obtained every 2 h, was compared with damage estimated from CPK values projected by the best fit log-normal curve derived from data obtained during the first 7 h after the initial serum CPK elevation. The estimate of damage based on early data correlated closely with the extent of infarction calculated from all available serial serum CPK values (r = 0.93, n = 30). Thus, the extent of the completed infarct could be estimated accurately during the early evolution of infarction. In patients with spontaneous extension of infarction manifested by chest pain and electrocardiographic changes, the calculated extent of the completed infarct exceeded that predicted. Conversely, salvage of myocardium, after reduction of myocardial oxygen requirements by administration of trimethaphan, was reflected by reduction of the extent of the calculated completed infarct with respect to that predicted from early serum CPK changes.

Acute Disease↗