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Biomedical subjects

D Eberhart

Publications and source records attributed to D Eberhart.

8 recordsLinked to original sources
PubMed2000

Impact of high transvalvular velocities early after implantation of Freestyle stentless aortic bioprosthesis.

BACKGROUND AND AIM OF THE STUDY: Stentless aortic bioprostheses have excellent hemodynamics, although heterogeneity in gradients has been observed. The present study was intended to determine whether high early postoperative transvalvular velocities correlate with other measures of left ventricular outflow obstruction, whether the phenomenon is transient, and whether high velocities observed early after surgery predict differences in subsequent valve performance or left ventricular remodeling. METHODS: Sixty-eight consecutive patients who underwent implantation of Freestyle stentless aortic bioprosthesis and survived to hospital discharge underwent early postoperative echocardiography. Peak transvalvular velocity was used to define a 'high-velocity' group, based on mean (+ 1 SD) for the group. Mean pressure gradient, ratio of peak to proximal velocities, and effective orifice area were assessed; change in peak velocity and evidence of left ventricular mass regression were studied at one-year follow up. RESULTS: Of 68 patients, 14 (21%) had 'high velocities' based on early postoperative peak transvalvular velocity >3.0 m/s. There was a higher prevalence of women (64% versus 33%, p = 0.04), and both body surface area (1.79+/-0.17 versus 1.95+/-0.20 m2, p = 0.01) and implanted valve size (22.9+/-2.0 versus 24.9+/-2.1 mm, p = 0.003) were smaller among the 'high-velocity' group. High velocity correlated with other measures of resistance to left ventricular outflow, including higher mean gradient (20.9+/-6.5 versus 8.3 +/-4.2 mmHg, p <0.001) and lower effective orifice area (1.15+/-0.36 versus 1.69+/-0.62 cm2, p <0.001). High early postoperative velocities persisted at one year in eight of 13 (62%) patients. Left ventricular mass regression occurred less often in the 'high-velocity' group (38% versus 77% of patients, p = 0.03) and was present in only one of eight (12%) patients in whom high velocity persisted at one year. CONCLUSION: High early postoperative transvalvular velocity suggests resistance to left ventricular outflow. High velocities are transient in some patients, although persistence of high transvalvular velocity suggests 'prosthesis-patient mismatch' with incomplete relief of left ventricular outflow obstruction.

Aged↗
PubMed1999

Impact of intraoperative post-pump aortic regurgitation with stentless aortic bioprostheses.

Stentless aortic bioprosthesis performance may be affected by geometric distortion, and intraoperative echocardiography typically is used to assess prosthetic valve function. The impact of minimal or mild post-pump aortic regurgitation has not been previously investigated. Intraoperative post-pump transesophageal echocardiograms and follow-up transthoracic echocardiograms (up to 3 years' postoperatively) were reviewed for 96 patients who underwent implantation of Freestyle (Medtronic) stentless aortic bioprostheses. Minimal or mild aortic regurgitation was present post-pump in 50 of 96 (52%) patients. On early follow-up examination (n = 80), no patient had more than mild aortic regurgitation. Aortic regurgitation had completely resolved in 24 of 39 (62%) patients with post-pump aortic regurgitation, including 15 of 19 (79%) patients with minimal paravalvular regurgitation. The incidence of mild aortic regurgitation at 2 and 3 years did not appear different between patients with and those without post-pump aortic regurgitation. Minimal or mild aortic regurgitation is common on intraoperative post-pump transesophageal echocardiography immediately after implantation of stentless aortic bioprostheses. Resolution is common, especially of small paravalvular jets. Minimal or mild post-pump aortic regurgitation infrequently results in even mild aortic regurgitation on early follow-up evaluation and does not appear to predict clinically significant progression of aortic regurgitation on long-term follow-up evaluation.

Adult↗
PubMed1995

Translational suppression by trinucleotide repeat expansion at FMR1.

Fragile X syndrome is the result of the unstable expansion of a trinucleotide repeat in the 5'-untranslated region of the FMR1 gene. Fibroblast subclones from a mildly affected patient, each containing stable FMR1 alleles with 57 to 285 CGG repeats, were shown to exhibit normal steady-state levels of FMR1 messenger RNA. However, FMR protein was markedly diminished from transcript with more than 200 repeats. Such transcripts were associated with stalled 40S ribosomal subunits. These results suggest that a structural RNA transition beyond 200 repeats impedes the linear 40S migration along the 5'-untranslated region. This results in translational inhibition by trinucleotide repeat expansion.

Centrifugation, Density Gradient↗
PubMed1992

Evidence for the involvement of a distinct form of cytochrome P450 3A in the oxidation of digitoxin by rat liver microsomes.

The preceding paper (B. Gemzik, D. Greenway, C. Nevins, and A. Parkinson (1992). Regulation of two electrophoretically distinct proteins recognized by antibody against rat liver cytochrome P450 3A1. J. Biochem. Toxicol., 7 (43-52).) described the regulation of two rat liver microsomal proteins (50- and 51-kDa) recognized by antibody against P450 3A1. It was also shown that changes in the levels of the 51-kDa 3A protein were usually paralleled by changes in the rate of testosterone 2 beta-, 6 beta-, and 15 beta-hydroxylation. The present study demonstrates that age- and sex-dependent changes in the 50-kDa protein were paralleled by changes in the rate of digitoxin oxidation to digitoxigenin bisdigitoxoside. Induction or suppression of the 50-kDa protein by treatment of rats with various xenobiotics were also paralleled by changes in the rate of digitoxin oxidation. These results suggest that, contrary to previous assumptions, the conversion of digitoxin to digitoxigenin bisdigitoxoside and the conversion of testosterone to 2 beta-, 6 beta-, and 15 beta-hydroxytestosterone are primarily catalyzed by different forms of P450 3A. Further evidence for this conclusion was obtained from studies in which the suicide inhibitor, chloramphenicol, was administered to mature female rats previously treated with pregnenolone-16 alpha-carbonitrile (PCN), which induces both the 50-kDa and the 51-kDa protein. Treatment of mature female rats with PCN alone caused a marked increase (16- to 18-fold) in the 6 beta-hydroxylation of testosterone and the rate of digitoxin oxidation. Treatment of PCN-induced rats with chloramphenicol caused a approximately 70% decrease in liver microsomal testosterone 6 beta-hydroxylation, but had no effect on the rate of conversion of digitoxin to digitoxigenin bisdigitoxoside. The oxidation of testosterone by purified 3A1 (a 51-kDa protein) was also inhibited by chloramphenicol in a time- and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent manner. In addition to testosterone and chloramphenicol, purified 3A1 also metabolized troleandomycin, but it was unable to convert digitoxin to digitoxigenin bisdigitoxoside. Testosterone inhibited the microsomal oxidation of digitoxin, but digitoxin did not inhibit testosterone oxidation. This suggests that testosterone is a substrate for the 3A enzyme that metabolizes digitoxin, but that this form of P450 3A does not contribute significantly to testosterone oxidation by rat liver microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1990

Reconstitution of testosterone oxidation by purified rat cytochrome P450p (IIIA1).

Cytochrome P450p (IIIA1) has been purified from rat liver microsomes by several investigators, but in all cases the purified protein, in contrast to other P450 enzymes, has not been catalytically active when reconstituted with NADPH-cytochrome P450 reductase and dilauroylphosphatidylcholine. We now report the successful reconstitution of testosterone oxidation by cytochrome P450p, which was purified from liver microsomes from troleandomycin-treated rats. The rate of testosterone oxidation was greatest when purified cytochrome P450p (50 pmol/ml) was reconstituted with a fivefold molar excess of NADPH-cytochrome P450 reductase, an equimolar amount of cytochrome b5, 200 micrograms/ml of a chloroform/methanol extract of microsomal lipid (which could not be substituted with dilauroylphosphatidylcholine), and the nonionic detergent, Emulgen 911 (50 micrograms/ml). Testosterone oxidation by cytochrome P450p was optimal at 200 mM potassium phosphate, pH 7.25. In addition to their final concentration, the order of addition of these components was found to influence the catalytic activity of cytochrome P450p. Under these experimental conditions, purified cytochrome P450p converted testosterone to four major and four minor metabolites at an overall rate of 18 nmol/nmol P450p/min (which is comparable to the rate of testosterone oxidation catalyzed by other purified forms of rat liver cytochrome P450). The four major metabolites were 6 beta-hydroxytestosterone (51%), 2 beta-hydroxytestosterone (18%), 15 beta-hydroxytestosterone (11%) and 6-dehydrotestosterone (10%). The four minor metabolites were 18-hydroxytestosterone (3%), 1 beta-hydroxytestosterone (3%), 16 beta-hydroxytestosterone (2%), and androstenedione (2%). With the exception of 16 beta-hydroxytestosterone and androstenedione, the conversion of testosterone to each of these metabolites was inhibited greater than 85% when liver microsomes from various sources were incubated with rabbit polyclonal antibody against cytochrome P450p. This antibody, which recognized two electrophoretically distinct proteins in liver microsomes from troleandomycin-treated rats, did not inhibit testosterone oxidation by cytochromes P450a, P450b, P450h, or P450m. The catalytic turnover of microsomal cytochrome P450p was estimated from the increase in testosterone oxidation and the apparent increase in cytochrome P450 concentration following treatment of liver microsomes from troleandomycin- or erythromycin-induced rats with potassium ferricyanide (which dissociates the cytochrome P450p-inducer complex). Based on this estimate, the catalytic turnover values for purified, reconstituted cytochrome P450p were 4.2 to 4.6 times greater than the rate catalyzed by microsomal cytochrome P450p.

Animals↗