The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes

Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.     

Statistical aspects of early termination in the beta-blocker heart attack trial

The Beta-Blocker Heart Attack Trial was a randomized double blind controlled trial comparing propranolol with placebo in 3837 patients with a recent myocardial infarction. The trial was terminated on recommendation of the Policy and Data Monitoring Board 9 months before the scheduled closing date. The propranolol group, at the time of the decision, had a 26% lower mortality (z = 2.82). Many issues were considered in this decision. These included the magnitude of the overall results; consistency of results across subgroups, clinical centers, and cause of death; and completeness of follow-up. Two basic statistical methods were used in declaring the overall mortality results significant. The first method evaluated the current survival data taking into account the issue of repeated significance testing. The second method evaluated whether the observed trend was so impressive that the conclusion was unlikely to change even if the trial should continue to the scheduled end. These two methods, as well as other considerations led to the recommendation to discontinue the trial.     

Bone scintigraphy in chondroblastoma

Scintigraphy in 3 patients with chondroblastoma showed that the tumors were hyperemic and avidly accumulated the radionuclide. These changes were also present in adjacent normal bone, but to a lesser degree. This suggest that radionuclide uptake in chondroblastoma is a function of the blood supply to the tumor rather than primary matrix extraction.     

Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy

The relationship between hyperglycemia, measured by glycosylated hemoglobin at the initial examination, and the four-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Younger- (n = 891) and older-onset (n = 987) persons participating in baseline and follow-up examinations were included. Glycosylated hemoglobin was measured by microcolumn. Retinopathy was determined from stereoscopic fundus photographs. In the younger-onset group, comparing the highest with the lowest quartile of glycosylated hemoglobin, the relative risk for developing any diabetic retinopathy was 1.9; for proliferative retinopathy, 21.8; and for progression, 4.0. Among older-onset persons taking insulin, the corresponding relative risks were 1.9, 4.0, and 2.1. Among older-onset persons not taking insulin, relative risks were 4.0 for any retinopathy and 6.2 for progression. A positive relationship between incidence and progression of retinopathy and glycosylated hemoglobin remained after controlling for duration of diabetes, age, sex, and baseline retinopathy. These data suggest a strong and consistent relationship between hyperglycemia and incidence and progression of retinopathy.     

Congenital hepatic artery aneurysm simulating pancreatic carcinoma

The authors report a case of a hepatic artery aneurysm that simulated a mass in the head of the pancreas. The correct diagnosis was made preoperatively based on several findings: curvilinear calcification within the mass on CT, a well-defined cystic collection on ultrasound, absence of biliary duct dilatation or jaundice, and presence of other aneurysms.     

Training of the next generation of biostatisticians: a call to action in the U.S

Two workshops (2001, 2003) were held by the National Institutes of Health (NIH) to examine the need to train more biostatisticians in the U.S. to meet the increasing opportunities in the biomedical research enterprise. The supply of new PhD graduates in biostatistics in the U.S. has been relatively steady for the past two decades while the demand has increased dramatically. These workshops concluded that a renewed effort must be made in the U.S., led in part by the NIH, to add to and expand the existing training programs to increase the supply. This article summarizes those two workshops and their recommendations. Some progress has been made through a new biostatistics training program with emphasis in bioinformatics sponsored by the National Institute of General Medical Sciences (NIGMS).