A randomized, double-blind, parallel group comparison of disopyramide phosphate and quinidine in patients with cardiac arrhythmias

This report summarizes the results of a randomized, double-blind, parallel group, multicenter study which compared the antiarrhythmic activity and safety of oral disopyramide phosphate and oral quinidine sulfate. A total of 124 outpatients, whose pretreatment rates of ventricular and/or supraventricular arrhythmias were documented by ambulatory ECG recordings, were randomly assigned to receive either oral disopyramide or oral quinidine for the eight-week course of the study. Every two weeks, ten-hour ambulatory ECG recordings were obtained from each patient and blood was drawn to determine serum concentrations of assigned drug.     

In-hospital initiation of lipid-lowering therapy after coronary intervention as a predictor of long-term utilization: a propensity analysis

BACKGROUND: Despite multiple randomized trials demonstrating their efficacy for the secondary prevention of coronary disease, lipid-lowering agents remain underused. Few studies have examined the relationship between predischarge initiation of lipid-lowering therapy and long-term use. METHODS: Using data from patients at 69 centers from the United States and Canada enrolled in the Evaluation in PTCA to Improve Long-term Outcome With Abciximab GP IIb/IIIa Blockade (EPILOG) trial, we performed a retrospective propensity-analyzed cohort study. Patients underwent percutaneous coronary intervention for stable or recently unstable coronary disease and were older than 21 years, were not taking lipid-lowering therapy at the time of admission, and survived to hospital discharge; 175 were discharged taking lipid-lowering therapy and 1951 were not. RESULTS: After 6 months, 77% of patients who started taking lipid-lowering agents before hospital discharge continued taking therapy, compared with only 25% of those discharged without these agents (relative risk, 3.17; 95% confidence interval, 2.88-3.41; P<.001). After restricting the analysis to propensity-matched patients (n = 477) and adjusting for other potential confounders, initiation of a lipid-lowering agent during hospitalization was the strongest independent predictor of use at 6 months (relative risk, 2.50; 95% confidence interval, 2.29-2.65; P<.001). CONCLUSIONS: Inpatient initiation of lipid-lowering therapy is a strong and independent positive predictor of subsequent use, with patients who start taking lipid-lowering therapy before hospital discharge nearly 3 times as likely to be taking these agents 6 months later. Inpatient initiation of lipid-lowering therapy appears to be an effective strategy for bridging the gap between current medical knowledge and practice.     

Quantitation of aortic regurgitation by computer analysis of digital subtraction angiography

Digital subtraction angiography provides the potential to determine aortic regurgitant fraction by computer analysis of time-intensity curves generated from regions of interest positioned over the aorta and left ventricle after aortography. To validate this ability, we studied six dogs instrumented with an electromagnetic flow probe on the ascending aorta. Aortic regurgitation of varying severity was produced by a basket catheter introduced through the right carotid artery. Aortograms were performed using continuous fluoroscopy at 30 frames/s and stored in digital format in a 256 x 256 pixel matrix. An image-processing computer was utilized to plot summated pixel intensity versus time for both the aortic and the left ventricular regions of interest. Regurgitant fraction was calculated from the time-intensity curves using an algorithm analogous to that employed by dye-dilution methods. Regurgitant fraction determined from digital angiography was compared with that obtained by electromagnetic flow and was found to correlate well (r = 0.94, SEE = 7.4%) over a wide range of values. Thus, these data indicate that aortic regurgitant fraction can be accurately determined from computer analysis of digitally acquired aortograms in an animal model of acute aortic regurgitation.     

Is CURE a cure for acute coronary syndromes? Statistical versus clinical significance

Clopidogrel has been recently approved for treatment of non-ST-elevation acute coronary syndromes based on the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial. However, the trial's findings are confounded by issues that lessen its clinical significance. Clopidogrel did not reduce mortality; its benefit was limited to preventing myocardial infarction, which was defined less stringently than in previous trials. Clopidogrel led to an increase in major and minor bleeding. Furthermore, clopidogrel increased bleeding risk in early cardiac surgery. Thus, widespread usage of clopidogrel, especially in centers with an early revascularization strategy, will have limited clinical benefit with considerable risk.     

Repeated intravascular ultrasound imaging in cardiac transplant recipients does not accelerate transplant coronary artery disease

OBJECTIVES: This study was designed to examine the impact of repeated intravascular ultrasound (IVUS) examinations on transplant coronary artery disease (CAD). BACKGROUND: Serial IVUS is the most accurate method for early detection and surveillance of transplant CAD. However, the long-term safety of serial IVUS exams is not well described. Accordingly, we examined the impact of repeated IVUS examinations on transplant CAD. METHODS: We examined 226 transplant recipients who underwent one or more IVUS examinations and coronary angiography at least one year after the last IVUS exam. The coronary angiograms were analyzed using quantitative coronary angiography. Vessel diameters, frequency, and severity of stenoses in IVUS-imaged and nonimaged coronary arteries were compared. In a subgroup analysis of 31 patients, angiographic lumen diameters were measured at baseline (within eight weeks of transplantation) and during follow-up (after two, three, or four IVUS studies). RESULTS: In the 226 patients, 548 coronary arteries were previously imaged by IVUS and 130 arteries were not imaged by IVUS. On subsequent angiograms, stenoses were observed in 16.2% (21/130) of nonimaged arteries and 19.5% (107/548) of imaged arteries (p = 0.38). The arterial diameters of nonimaged and imaged arteries were not significantly different (p = 0.07), regardless of the number of IVUS exams and duration of follow-up. Subgroup analysis revealed a significant decrease in vessel lumen diameter over time in nonimaged as well as imaged arteries. The magnitude of the diameter decrease was not significantly different between the two groups. CONCLUSIONS: Repeated IVUS examinations following heart transplantation do not result in angiographically evident acceleration of transplant CAD. Therefore, serial IVUS imaging is a safe method for the detection and surveillance of transplant CAD.     

Stem cell factor stimulates the in vitro growth of bone marrow cells from aplastic anemia patients.

Aplastic anemia (AA) is a rare human bone marrow disorder of unknown etiology manifested by a strongly impaired growth of hematopoietic precursors. In this study, we examined the ability of recombinant human stem cell factor (SCF) to stimulate proliferation in vitro of bone marrow cells from 15 AA patients. All patients had been previously treated with antilymphocyte globulin (ALG). SCF, in combination with erythropoietin (Epo), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF), increased the number of hematopoietic colonies formed in a semisolid medium by AA marrows. Maximal colony numbers reached 30% of the numbers observed with normal bone marrow cells. Proliferation of AA cells cultured in a liquid medium containing SCF together with Epo, IL-3, GM-CSF, and G-CSF approached 70% of the control level, as measured by 3H-thymidine incorporation. The effect of the combination of SCF with the other growth factors was more than 10 times stronger than that of the growth factors alone. The most marked effect of SCF was on the generation of erythroid colonies by precursor cells. The results demonstrate synergism between CSF and other hematopoietic growth factors, resulting in the most efficient stimulation of the in vitro growth of AA bone marrow cells described to date. Use of SCF, either alone or in combination with other factors, may be of potential value in treatment of AA.     

Distinct and overlapping direct effects of macrophage inflammatory protein-1 alpha and transforming growth factor beta on hematopoietic progenitor/stem cell growth

Both transforming growth factor beta (TGF beta) and macrophage inflammatory protein 1 alpha (MIP-1 alpha) have been shown to be multifunctional regulators of hematopoiesis that can either inhibit or enhance the growth of hematopoietic progenitor cells (HPC). We report here the spectrum of activities of these two cytokines on different hematopoietic progenitor and stem cell populations, and whether these effects are direct or indirect. MIP-1 alpha enhances interleukin-3 (IL- 3)/and granulocyte-macrophage colony-stimulating factor (GM- CSF)/induced colony formation of normal bone marrow progenitor cells (BMC) and lineage-negative (Lin-) progenitors, but has no effect on G- CSF or CSF-1/induced colony formation. Similarly, TGF beta enhances GM- CSF/induced colony formation of normal BMC and Lin- progenitors. In contrast, TGF beta inhibits IL-3/ and CSF-1/induced colony formation of Lin- progenitors. The effects of MIP-1 alpha and TGF beta on the growth of Lin- progenitors were direct and correlate with colony formation in soft agar. Separation of the Lin- cells into Thy-1 and Thy-1lo subsets showed that the growth of Thy-1lo Lin- cells is directly inhibited by MIP-1 alpha and TGF beta regardless of the cytokine used to stimulate growth (IL-3), GM-CSF, or CSF-1). In contrast, two other stem cell populations (0% to 15% Hoechst 33342/Rhodamine 123 [Ho/Rh123] and Lin- Sca-1+ cells) were markedly inhibited by TGF beta and unaffected by MIP- 1 alpha. Furthermore, MIP-1 alpha has no effect on high proliferative potential colony-forming cells 1 or 2 (HPP-CFC/1 or /2) colony formation in vitro, whereas TGF beta inhibits both HPP-CFC/1 and HPP- CFC/2. Thus, MIP-1 alpha and TGF beta are direct bidirectional regulators of HPC growth, whose effects are dependent on other growth factors present as well as the maturational state of the HPC assayed. The spectrum of their inhibitory and enhancing activities shows overlapping yet distinct effects.     

The site‐specific epidemiology of hip fracture in the Australian Capital Territory with projections for the first half of the 21st century: Implications for clinical management and health services planning

Objectives: To analyse the site‐specific epidemiology of hip fracture (HF) for the ACT and to project HF up to 2051. Methods: Age‐ and sex‐specific rates of HF and projections of the number of HFs were calculated by applying the age‐ and sex‐specific rates to the median population projections. Results: Analysis of patterns of HF by anatomical site of fracture revealed a diverse relationship according to age and sex. Fracture rates were higher in men before age 60 (1.8 : 1), and thereafter in women (3.1 : 1). In the age group of 60–64 years, the female : male ratio was 8.2 : 1 for cervical versus 1.8 : 1 for trochanteric fractures. Treatment for osteoporosis was under‐utilised. HF in people aged > 60 years will almost double by 2011, and increase 2.5‐fold and 5.4‐fold by the years 2021 and 2051, respectively. The greatest increase will occur in older men. Conclusions: The number of HFs in the first half of the 21st century will increase dramatically. Aetiological and pathophysiological differences in HF emphasise the need to individualise preventative strategies.