Methodology of serial ECG classification using an adaptation of the NOVACODE for Q wave myocardial infarction in the Bypass Angioplasty Revascularization Investigation (BARI)

Serial electrocardiographic (ECG) changes are a critical component of the diagnostic algorithm for classification of myocardial ischemic events in large-scale clinical trials. This study describes a computerized serial ECG classification program developed at the St. Louis University Core ECG Laboratory for use in the Bypass Angioplasty Revascularization Investigation (BARI) trial, in which patients with multivessel coronary artery disease were randomized to receive either coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. The St. Louis University program detects and codes serial changes in Q, ST, and T wave items according to Minnesota code (MC) criteria using a modified NOVACODE hierarchical classification system. Measurements using a seven-power calibrated coding loupe are used to generate the MC from a customized software program. Significant minor or major changes are detected by the serial comparison program and referred to a physician coder for verification. Serial comparison coding rules are used to adjust for weaknesses in the standard MC classification system resulting from instability at decision boundaries. Of 4,244 BARI randomized and registry study participants with follow-up ECGs received at the Core ECG Laboratory as of March 1995, a grade 2 MC Q wave progression was noted in 568 participants (13.4%) using MC criteria alone, as compared with 367 (8.6%) after the St. Louis University coding rules were applied. The incidence of grade 1 MC Q wave progressions was 16.4% (697/4,244) versus 6.1% (259/4,244) when the St. Louis University program was applied. Intraobserver variability for grade 2 Q wave progression codes determined from a sample of 812 serial.     

Three-dimensional quantitative structure-activity relationship study of nonsteroidal estrogen receptor ligands using the comparative molecular field analysis/cross-validated r2-guided region selection approach

A newly developed comparative molecular field analysis (CoMFA) technique, the cross-validated r2-guided region selection (CoMFA/q2-GRS) method, has been used to build a quantitative structure-activity relationship (3D-QSAR) for nonsteroidal estrogen receptor (ER) ligands. Ligands included in this study belong to a series of diethylstilbestrol (DES) and indenestrol analogues whose affinities for the mouse ER (mER) have been determined in our laboratory. The final model utilized 30 compounds and yielded a q2GRS (cross-validated r2, guided region selection) of 0.796, as compared to a q2 of 0.720 for conventional CoMFA, with a standard error of prediction of 0.594 at 3 principal components. This model was used to visualize steric and electrostatic features of the ligands that correspond with ER binding affinity. Results obtained from the CoMFA steric and electrostatic plots of this model have also been compared to information from the ER binding affinities of substituted estradiol analogues. This is in an effort to determine structural features of compounds in the CoMFA analysis that may correspond to those of the estradiol analogues and to further clarify the mode of binding of nonsteroidal ER ligands.     

Clinimetrics of postural instability in Parkinson's disease

Judgement of the ability to recover balance after a sudden shoulder pull is used as a clinical measure of postural instability in Parkinson's disease. To further evaluate its merits, we compared this 'retropulsion test' with dynamic posturography in 23 Parkinson patients. Dynamic posturography involved 20 serial 'toe-up' support surface rotations, which induced backward body sway. We found a moderate correlation (Spearman's p = 0.54; P < 0.05) between the retropulsion test and body sway after platform rotations during the 'off' phase, but no correlation during the 'on' phase (Spearman's p = 0.43; P = 0.11). These results cast doubt on the use of the retropulsion test as a measure of postural instability in Parkinson's disease.     

Differential effects of myeloperoxidase-derived oxidants on Escherichia coli DNA replication

The microbicidal myeloperoxidase (MPO)-H2O2-chloride system strongly inhibits Escherichia coli DNA synthesis. Also, cell envelopes from MPO-treated E. coli cells lose their ability to interact with hemimethylated DNA sequences of oriC, the chromosomal origin of replication, raising the prospect that suppression of DNA synthesis involves impairment of oriC-related functions (H. Rosen, et al. Proc. Natl. Acad. Sci. USA, 87:10048-10052, 1990). To evaluate whether origin-specific DNA sequences play a role in the MPO effect on E. coli DNA synthesis, plasmid DNA replication was compared to total (chromosomal) DNA replication for six plasmids with three distinct origins of replication. Plasmid pCM700 replication, replicating from oriC, was as sensitive to MPO-mediated inhibition as was total (chromosomal) DNA replication. A regression line describing this relationship had a slope of 0.90, and the r2 was 0.89. In contrast, the replication activities of three of four non-oriC plasmids, pUC19, pACYC184, and pSC101, demonstrated significant early resistance to inhibition by MPO-derived oxidants. The exception to this resistance pattern was plasmid pSP102, which has an origin derived from P1 phage. pSP102 replication declined similarly to that of total DNA synthesis. The regression line for pSP102 replication versus total DNA synthesis had a slope of 0.95, and the r2 was 0.92. The biochemical requirements for P1-mediated replication are strikingly similar to those for oriC-mediated replication. It is proposed that one of these requirements, common to oriC and the P1 origin but not critical to the replication of the other non-oriC plasmids, is an important target for MPO-mediated oxidations that mediate the initial decline in E. coli chromosomal DNA synthesis.     

Structure of CheA, a signal-transducing histidine kinase

BACKGROUND/AIMS: After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown. METHODS: In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8.5 years). RESULTS: The actuarial 5-year patient and graft survival rates were 91% (+/-6%) and 83% (+/-8%). The actuarial 1-year rate of acute rejection was 50% (+/-10.2%), which was comparable to that of patients transplanted for primary biliary cirrhosis and primary sclerosing cholangitis. Autoantibodies persisted in 77% of patients, at a lower titer than before liver transplantation. Ten patients were excluded from the study of autoimmune hepatitis recurrence, one because of an early postoperative death and nine because of hepatitis C virus infection acquired before or after liver transplantation. In the remaining 15 patients, who were free of hepatitis C virus infection, 5-year patient and graft survivals were 100% and 87%, respectively. Despite triple immunosuppressive therapy, three patients (20%) developed chronic hepatitis with histological and serological features of autoimmune hepatitis in the absence of any other identifiable cause. The disease was severe in two patients, leading to graft failure and asymptomatic in another, despite marked histological abnormalities. In one of these three patients, autoimmune hepatitis recurred on the second liver graft as well. CONCLUSIONS: Patients undergoing liver transplantation for autoimmune hepatitis have an excellent survival rate although severe primary disease may recur, suggesting the need for stronger post-operative immunosuppressive therapy.     

High-performance energy-efficient D-flip-flop circuits

This paper investigates performance, power, and energy efficiency of several CMOS master-slave D-flip-flops (DFF's). To improve performance and energy efficiency, a push-pull DFF and a push-pull isolation DFF are proposed. Among the five DFF's compared, the proposed push-pull isolation circuit is found to be the fastest with the best energy efficiency. Effects of using a double-pass-transistor logic (DPL) circuit and tri-state push-pull driver are also studied. Last, metastability characteristics of the five DFP's are also analyzed