Multiple-dose plasma pharmacokinetic and safety study of LY450108 and LY451395 (AMPA receptor potentiators) and their concentration in cerebrospinal fluid in healthy human subjects.

The objective of this study was to measure the steady-state cerebrospinal fluid (CSF) concentration of LY450108 and LY451395 (positive modulators of AMPA receptors) in healthy subjects after the administration of 1 mg and 5 mg. Secondary objectives included the evaluation of safety, pharmacokinetics, and steady-state ratio of plasma:CSF concentrations of LY450108 and LY451395 after multiple dosing. This study was an open-label, multiple oral dose study evaluating 1 mg and 5 mg LY450108 and 1 mg and 5 mg LY451395 in 12 (3 subjects per dosing group) healthy subjects, aged 18 to 49 years. Twelve healthy male subjects completed the study. LY450108 and LY451395 were quantifiable in CSF after 1-mg and 5-mg multiple-dose administrations with plasma:CSF ratio of 82:1 and 44:1, respectively. LY450108 and LY451395 1 mg and 5 mg were measured in the CSF. Single and multiple oral doses of LY450108 and LY451395 were determined to be safe and well tolerated in healthy subjects.

Spontaneous rupture of a fenestrated aortic valve. Surgical treatment.

Fenestration of the aortic valve is a common anatomic finding. Although spontaneous rupture of the semilunar cusps is infrequent, it leads to rapidly progressive heart failure and death. We present, to our knowledge, the first case of successful treatment by valve reconstruction. A 2 year follow-up demonstrates excellent clinical results.

Ultrastructural myocardial preservation during coronary artery surgery: a controlled, prospective, randomized study in humans.

Potassium cardioplegia was compared with normothermic, intermittent ischemic arrest in 30 patients undergoing multiple coronary artery bypass grafts. Group 1 comprised 15 patients in whom cold potassium cardioplegia with St. Thomas' Hospital solution was used. In Group 2 were 15 patients who underwent intermittent ischemic arrest during the construction of the distal anastomoses. Two myocardial transmural left ventricular biopsies were done in each patient. There was no operative mortality. Electron microscopical examination showed normal myocardial ultrastructure in both groups. In particular, mitochondria were well preserved in all samples. The postoperative electrocardiogram demonstrated a new Q wave in 1 patient in Group 2 whose level of the myocardial isoenzyme of creatine phosphokinase (CPK-MB) was within the normal range. The peak CPK-MB release in Group 1 was 23.2 +/- 20.1 IU and in Group 2, 19.9 +/- 15.1 IU. This difference was not statistically significant. The mean period of anoxic arrest in Group 1 was 49.5 +/- 15 minutes and in Group 2, 25.5 +/- 8 minutes (p less than 0.001). Total cardiopulmonary bypass time in Group 1 was 114.5 +/- 20 minutes and in Group 2, 90.2 +/- 16 minutes (p less than 0.01). It is concluded that both techniques can preserve myocardial subcellular architecture during multiple coronary artery bypass grafting in patients with normal left ventricular function.

Predictors of radial artery patency for coronary bypass operations.

BACKGROUND: Few data exist regarding angiographic predictors of radial artery patency for coronary bypass grafting, and the benefit of calcium antagonists is not clear. METHODS: One hundred fifteen patients were studied who had myocardial revascularization with the radial artery plus internal mammary and vein grafts with 3.5 +/- 1.1 grafts per patient. Sixty-three patients received diltiazem and 52 patients did not. Base line and follow-up angiographies were analyzed 1 year postoperatively in 50 of these patients with a quantitative computerized method. RESULTS: One hundred fourteen patients survived and were followed for 30.1 +/- 12.6 months. Patency for mammary grafts was 100%, for radial grafts it was 80%, and for saphenous vein grafts it was 68%. Patent radial artery grafts had significantly greater degree of stenosis in the native vessels than occluded grafts (73% +/- 14% vs 40% +/- 24%), (p = 0.0007; confidence interval = 95%). Radial artery patency increased to 92% when arteries with 70% or more stenosis were considered. No differences were observed for clinical and angiographic end points in the patients that received diltiazem compared with the rest who had not. CONCLUSIONS: The degree of stenosis in the native coronary artery significantly influences the patency rate of radial artery grafts, independent of diltiazem.

Annoyance by aircraft noise and fear of overflying aircraft in relation to attitudes toward the environment and community.

If, as has been suggested, expressions of annoyance attributable to aircraft noise may reflect, in part, fear of aircraft overflights and possible crashes, then residents of areas where crashes have occurred should express more annoyance. To test this hypothesis, 50 residents of an Albany, New York area where an aircraft crash producing fatalities recently occurred, and 50 residents of a comparable nearby area without such a history, were asked to respond to a "Quality of Life" questionnaire. Among the items were some designed to test annoyance by noise and fear of aircraft overflights. It was predicted that those in the crash area would express more fear and would more often identify aircraft as a noise source. Factor analysis and discriminant analysis results sustained these hypotheses. A near-replication was carried out in Louisville, Kentucky; results were much the same. For the crash-area groups there was association of aircraft fear and noise annoyance responses; this was true to an apparently lesser extent for non-crash-area groups. The greater annoyance of crash groups by aircraft community noise apparently does not carry over to assessment of aircraft noise in the laboratory.

Comparison of two doses of aprotinin in patients receiving aspirin before coronary bypass surgery.

This study was designed to evaluate efficacy and tolerability of two different doses of aprotinin in patients receiving aspirin before undergoing coronary artery bypass grafting. Forty-two patients were randomized to receive either placebo (group I), or aprotinin in doses of 4,000,000 KIU (group II) or 6,000,000 KIU (group III). Drug efficacy was determined by measuring postoperative blood loss and transfusion of blood products. Both doses were effective in reducing blood loss and transfusion requirements. Blood loss through thoracotomy drainage was 450 +/- 224, 182 +/- 144, 142 +/- 98 ml, respectively, for control and treatment groups II and III (p = 0.0001). The numbers of patients with blood transfusions were seven (50%), two (17%) and two (17%) for group I and treatment groups II and III, respectively (p = 0.10). Tolerability was excellent and complications few and reversible. In conclusion, high and medium doses of aprotinin were well tolerated and reduced bleeding and transfusion requirements in patients submitted to coronary bypass surgery under the effects of aspirin.