Lumefantrine solid dispersions with piperine for the enhancement of solubility, bioavailability and anti-parasite activity.

Crystallinity and P-glycoprotein (P-gp) mediated efflux of drugs with low aqueous solubility collaboratively contributes to erratic absorption resulting in low/variable bioavailability. Herein, the amorphous solid dispersions (SD) of lumefantrine (LUMF) containing piperine (PIP), a P-gp and CYP3A4 inhibitor, were formulated with Soluplus (Sol), Klucel (Klu) and Lutrol F68 (Lut), polymeric carriers, to improve solubility and bioavailability of LUMF following oral administration. The LUMF-PIP-SD prepared with Sol exhibited higher aqueous solubility of LUMF in concentration dependent manner and LUMF-PIP-Sol demonstrating maximum aqueous LUMF solubility were characterized by DSC, FTIR and XRD. The DSC thermogram and XRD diffractogram of LUMF-PIP-SD confirmed the loss of crystallinity of LUMF ensuing improved dissolution while possible interaction of LUMF with PIP and /or Sol was evident in FTIR spectrum. DSC and dissolution studies confirmed the stability for LUMF-PIP-Sol SD stored for 90 days under stressed conditions of humidity and temperature. An in situ single-pass intestinal perfusion study in rats indicated 2.2-fold increase in intestinal permeation of LUMF co-administered with PIP. Improved bioavailability of LUMF was evidenced by increased AUC0-∞ and Cmax for LUMF in SD compared to alone LUMF or LUMF with PIP. Peter's four-day suppressive test indicated improved antimalarial activity for LUMF-PIP-Sol SD. Overall, the data suggest that the SD of LUMF incorporated with P-gp inhibitor PIP, improves the bioavailability as well as antimalarial efficacy of LUMF.

Arcanobacterium haemolyticum associated with pyothorax: case report.

Arcanobacterium haemolyticum has an established role in the etiology of human pharyngitis. There are increasing reports of systemic infections caused by this organism. From India, we report the first case of Arcanobacterium haemolyticum causing pyothorax in an immunocompetent adolescent male patient. The probable mode of infection is also discussed. The role of A. hemolyticum as an animal pathogen needs further study.

Long-term survival of patients with low ejection fraction: surgical versus medical management.

From May 1974 to December 1982, 3,592 patients underwent cardiac catheterization at the Buffalo Veterans' Administration Medical Center. Three hundred sixty-three patients (10.2%) presented with ejection fractions (EFs) < 40%. Of these, 194 had significant coronary artery disease. Follow-up data for retrospective analysis of survival rates were available for 173 of the 194 patients. Fifty-eight of these 173 had undergone coronary artery bypass surgery, while the remaining 115 had received medical treatment. The cumulative survival rates at 8 years for patients with EFs < 25% reveal a significantly better survival rate (61% vs. 29%, p <.03) for surgically treated patients. We conclude that coronary artery bypass surgery yields higher 8-year survival rates than does medical treatment for patients with compromised left ventricular function and significantly low EFs (< 25%).

Stress test evaluation of patients with poor left ventricular function before and after coronary artery bypass surgery.

Between May 1976 and December 1982 (104 months), 152 patients from a total of 3592 patients who had coronary angiography at the Buffalo Veterans Administration Medical Center had coronary artery disease with left ventricular ejection fractions of 40% or below. Sixty-three patients in this group had coronary bypass surgery. Thirty patients who had graded exercise tests done before and after surgery improved in their peak exercise double product and systolic blood pressure (p value <.05) accompanied by increased work capacity (p value < 0.02). Nineteen patients who had identical exercise protocols also showed increases in exercise time (p value <.05). We believe that coronary artery bypass surgery improves exercise capacity in selected patients with compromised left ventricular function.

Effect of left ventricular aneurysmectomy on exercise performance.

We performed pre- and post-operative exercise testing on 12 patients with coronary artery bypass surgery and ventricular aneurysmectomy and 2 patients with ventricular aneurysmectomy alone. Most patients showed better exercise performance, higher double product, better work capacity and were able to exercise longer. Two patients who had ventricular aneurysmectomy alone showed similar changes. Most patients showed improved New York Heart Association functional classification and exercise performance after surgery.

Improved exercise performance following single daily dose of atenolol in stable angina.

We administered atenolol to 10 patients with effort limiting angina pectoris. Doses of 50 mg, 100 mg and 200 mg provided significant improvement (P less than 0.05) in exercise tolerance tested 24 hours after the drug was given. Twenty-five milligrams was not significantly better than placebo in increasing work tolerance. Side effects were minimal, and treatment could be continued throughout the study. The beta-blocker atenolol is an effective drug in the treatment of exercise-induced angina.

Mitral regurgitation in coronary artery disease.

Over a period of 5.25 years, 1,530 patients with coronary artery disease (CAD) underwent catheterization; 104 had associated mitral regurgitation (MR), and 60 had no complications. Twelve patients underwent coronary artery bypass graft surgery (CABG), with both pre- and postoperative angiograms. Nine of the 12 patients (75 percent) were in functional class 3 or 4. Left ventricular ejection fraction ranged from 34 to 75. The MR was considered severe (3+) in three, moderate (2+) in six, and trivial (1+) in three patients. Following CABG, all except two patients were in class 1. Of the 43 patients medically treated, 31 patients (72 percent) were in functional class 3 or 4. Angiographic results showed that five patients had 3+ MR, 14 had 2+ MR, and 24 had 1+ MR. The EF was less than 30 in 23 patients and greater than or equal to 30 in 20 patients, and left ventricular filling pressure was elevated. Twenty patients died, with a mean follow-up period of 11 months. Our study demonstrates that the surgically treated patients showed angiographic improvement in MR, improved functional status, and relief of symptoms compared with medically treated patients. We believe that a subset of patients with MR and CAD would benefit with CABG.

Assessment of cardiac risk in surgical patients.

Fifty patients admitted to the hospital for elective noncardiac surgery were carefully assessed for cardiac risk by exercise stress testing. Twenty-five of 38 (66%) patients with adequate testing had abnormal stress test results. Patients with symptoms of angina had a high incidence of abnormal stress test results (15 of 20). In the majority of these patients, the exercise stress test was true-positive, so that on angiography, severe coronary artery disease was present. In patients with no cardiac symptoms, 33% (ten of 30) had abnormal stress test results and seven patients had significant coronary artery disease. Our preliminary data indicate that exercise stress testing is a good noninvasive screening test to detect asymptomatic coronary artery disease. Those patients who have an abnormal stress test or an abnormal ECG or angina should undergo coronary angiography to determine extent of coronary disease.