Comparison of risk stratification with pharmacologic and exercise stress myocardial perfusion imaging: A meta-analysis

BACKGROUND: Although pharmacologic stress myocardial perfusion imaging (MPI) and exercise stress MPI have comparable diagnostic accuracy, their comparative value for risk stratification of patients with known or suspected coronary disease is not known. METHODS AND RESULTS: The data of 14,918 patients were combined from 24 studies evaluating prognosis in patients undergoing either pharmacologic stress or exercise stress MPI. Studies were included if a 2 x 2 table for hard cardiac events (cardiac death and myocardial infarction [MI]) could be constructed from the data available. Excluded were studies performed for post-MI, post-revascularization, or preoperative risk stratification. A weighted t test was used to compare the cardiac events, and a random effects model was used to calculate summary odds ratios. Summary odds ratios for hard cardiac events were similar for pharmacologic stress and exercise stress MPI. Summary receiver operating characteristic curves also showed no difference in discriminatory power between the stressors. The cardiac event rates were significantly higher with normal and abnormal test results with pharmacologic stress MPI than with exercise stress MPI (1.78% vs 0.65% [P < .001] for normal results and 9.98% vs 4.3% [P < .001] for abnormal results). Subgroup analysis revealed that both cardiac death and nonfatal MI were significantly higher with pharmacologic stress MPI. Patients undergoing pharmacologic stress MPI had a significantly higher prevalence of poor prognostic factors, and meta-regression revealed that exercise capacity was the single most important predictor of cardiac events. CONCLUSIONS: This meta-analysis shows that exercise stress MPI and pharmacologic stress MPI are comparable in their ability to risk-stratify patients. However, patients undergoing pharmacologic stress studies are at a higher risk for subsequent cardiac events. This is true even for those with normal perfusion imaging results.     

Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.     

Evaluation of myocardial function in patients with end-stage heart failure during support with the Jarvik 2000 left ventricular assist device.

In 2 patients with the Jarvik 2000 left ventricular assist device (LVAD), we assessed left ventricular systolic function through pressure-volume loops and E(max) at the beginning and end of the support period to potentially predict the possibility of pump removal without transplantation. Immediately before LVAD implantation and explantation, pressure and volume measurements were made with catheters and echocardiography, respectively, the E(max) being calculated from the slope of the pressure-volume loops, and the left ventricular ejection fraction (LVEF) being estimated by echocardiography. Transplantation was performed after 14 and 62 days, respectively, during which the LVEF increased by 75% (from 12% to 21%) in Patient 1 and remained unchanged (from 16% to 18%) in Patient 2, whereas the E(max) increased from 0.63 and 0.42 mm Hg/ml, respectively, to 1.31 and 1.07 mm Hg/ml, reflecting a 107% and 155% improvement. In these 2 cases, the E(max) was a more reliable indicator of intrinsic myocardial contractility than was the LVEF.     

Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.     

Consequences of misfilling contemporary vaporizers with desflurane

Desflurane is a volatile anaesthetic that combines low blood gas solubility (blood/gas partition coefficient =0.42 at 37° C), moderate potency (MAC = 6–7%), and high volatility (vapour pressure =681 mmHg at 20° C, boiling point = 23.5° C). The volatility and potency of desflurane prevent its safe use in vaporizers of traditional design. We present a mathematical model which demonstrates the potential for desflurane overdose if contemporary vaporizers are misfilled with desflurane. The most hazardous filling error occurs if an enflurane vaporizer is misfilled with desflurane. The calculated desflurane output of a misfilled enflurane vaporizer at a dial setting of 1% and a temperature of 22° C is 57.8%, or 9.6 MAC. For misfilled enflurane, isoflurane, and halothane vaporizers at dial settings equivalent to one MAC at 22° C, the calculated desflurane output is 14.0, 10.2, and 7.8 MAC, respectively. We conclude that the safe delivery of desflurane will require engineering safeguards, additional monitoring, and education of the anesthesia community.     

The use of a priori knowledge to quantify short echo in vivo 1h mr spectra

In vivo ¹H MR spectra of the prefrontal cortex acquired with the stimulated echo acquisition mode (STEAM) TE = 20 ms sequence were quantified to determine relative levels of cerebral metabolites. A priori knowledge of spectra from individual metabolites in aqueous solution was incorporated into a frequency domain quantification technique. The accuracy and precision of modeling these metabolites were investigated with simulated spectra of varying signal-to-noise ratios (SNRs) and relative metabolite levels. The efficacy of modeling in vivo data was tested by quantifying 10 repeated measures of two consecutively acquired in vivo spectra (an 8?cm³ volume of interest (VOI) and a 4?cm³ VOI positioned within the 8?cm³ VOI) on the same normal subject. The differences in levels of glutamate (Glu), phosphocreatine plus creatine (PCr+Cr) and choline-containing compounds (Cho₁ between spectra from the 8? and 4?cm³ VOIs corresponded with the expected differences observed in the proportions of gray matter within the VOIs (estimated from ¹H images). Correcting for the T₁ and T₂ relaxation, the estimated concentrations of N-acetylaspartate, PCr+Cr, Cho₁, Glu, and glutamine were consistent with previous in vivo and in vitro reports.     

Treatment of End-Stage Renal Disease in Central and Eastern Europe: Overview of Current Status and Future Needs

The situation of end-stage renal disease (ESRD) patients in central and eastern Europe was very poor for many years during the so called socialistic era. Economical and political liberation resulted in the significant growth of renal replacement facilities in this region. The number of hemodialysis units increased significantly (56%) during the period 1990–1996, and the number of patients treated with this modality has risen by 75%. More dramatic progress was achieved in peritoneal dialysis. The number of units performing this method of renal replacement therapy (RTT) increased by 277% and the number of patients by more than 300%. Not only quantitative but also qualitative changes were observed. More modern hemodialysis machines installed in the vast majority of units allow for the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium profile modeling. Also, a wider choice of biocompatible dialyzers has become available during the last few years. The number of centers performing renal transplantation has increased significantly, but the number of renal transplants has not followed this progress. Despite all the progress, further development of all RRT methods is necessary to achieve acceptance rates comparable to those observed in developed countries.     

Osteogenic differentiation of human bone marrow stromal cells on partially demineralized bone scaffolds in vitro

Tissue engineering has been used to enhance the utility of biomaterials for clinical bone repair by the incorporation of an osteogenic cell source into a scaffold followed by the in vitro promotion of osteogenic differentiation before host implantation. In this study, three-dimensional, partially demineralized bone scaffolds were investigated for their ability to support osteogenic differentiation of human bone marrow stromal cells (BMSCs) in vitro. Dynamic cell seeding resulted in homogeneous cell attachment and infiltration within the matrix and produced significantly higher seeding efficiencies when compared with a conventional static seeding method. Dynamically seeded scaffolds were cultured for 7 and 14 days in the presence of dexamethasone and evaluated on biochemical, molecular, and morphological levels for osteogenic differentiation. Significant elevation in alkaline phosphatase activity was observed versus controls over the 14-day culture, with a transient peak indicative of early mineralization on day 7. On the basis of RT-PCR, dexamethasone-treated samples showed elevations in alkaline phosphatase and osteocalcin expression levels at 7 and 14 days over nontreated controls, while bone sialoprotein was produced only in the presence of dexamethasone at 14 days. Scanning electron microscopy evaluation of dexamethasone-treated samples at 14 days revealed primarily cuboidal cells indicative of mature osteoblasts, in contrast to nontreated controls displaying a majority of cells with a fibroblastic cell morphology. These results demonstrate that partially demineralized bone can be successfully used with human BMSCs to support osteogenic differentiation in vitro. This osseous biomaterial may offer new potential benefits as a tool for clinical bone replacement.