Significance of automated stenosis detection during quantitative angiography. Insights gained from intracoronary ultrasound imaging

BACKGROUND: Automated stenosis analysis is a common feature of commercially available quantitative coronary angiography (QCA) systems, allowing automatic detection of the boundaries of the stenosis, interpolation of the expected dimensions of the coronary vessel at the point of obstruction, and angiographically derived estimation of atheromatous plaque size. However, the ultimate meaning of this type of analysis in terms of the degree of underlying atherosclerotic disease remains unclear. We investigated the relationship between stenosis analysis performed with QCA and the underlying degree of atherosclerotic disease judged by intracoronary ultrasound (ICUS) imaging. METHODS AND RESULTS: In 40 coronary stenoses, automated identification of the sites of maximal luminal obstruction and the start of the stenosis was performed with QCA by use of curvature analysis of the obtained diameter function. Plaque size at these locations also was estimated with ICUS, with an additional ICUS measurement immediately proximal to the start of the stenosis. Crescentlike distribution of plaque, indicating an atheroma-free arc of the arterial wall, was recorded. At the site of the obstruction, total vessel area measured with ICUS was 16.65 +/- 4.04 mm2, whereas an equivalent measurement obtained from QCA-interpolated reference dimensions was 7.48 +/- 3.30 mm2 (P = .0001). Plaque area derived from QCA data was significantly less than that calculated from ICUS (6.32 +/- 3.21 and 13.29 +/- 4.22 mm2, respectively; mean difference, 6.92 +/- 4.43 mm2; P = .0001). At the start of the stenosis identified by automated analysis, ICUS plaque area was 9.38 +/- 3.17 mm2, and total vessel area was 18.77 +/- 5.19 mm2 (50 +/- 11% total vessel area stenosis). The arterial wall presented a disease-free segment in 28 proximal locations (70%) but in only 5 sites (12%) corresponding to the start of the stenosis and none at the obstruction (P = .0001). At the site of obstruction, all vessels showed a complete absence of a disease-free segment, and the atheroma presented a cufflike or all-around distribution with a variable degree of eccentricity. CONCLUSIONS: At the site of maximal obstruction, QCA underestimated plaque size as measured with ICUS. Atherosclerotic disease was consistently present at the start of the stenosis and was used as a reference site by automated stenosis analysis. At the start of the stenosis, ICUS demonstrated a mean 50 +/- 11% total vessel area stenosis, with a characteristic loss of disease-free arcs of arterial wall present in proximal locations. Thus, the site identified by automated stenosis analysis as the start of the stenosis does not represent a disease-free site but rather the place where compensatory vessel enlargement fails to preserve luminal dimensions, a phenomenon that seems related to the observed loss of a remnant arc of normal arterial wall.     

The N-terminal side of the origin-binding domain of simian virus 40 large T antigen is involved in A/T untwisting

We investigated the role of the N-terminal side of simian virus 40 (SV40) large T antigen's origin-binding domain in the initiation of virus DNA replication by analyzing the biochemical activities of mutants containing single point substitutions or deletions in this region. Four mutants with substitutions at residues between 121 and 135 were partially defective in untwisting the A/T-rich track on the late side of the origin but were normal in melting the imperfect palindrome (IP) region on the early side. Deletion of the N-terminal 109 amino acids had no effect on either activity, whereas a longer deletion, up to residue 123, greatly reduced A/T untwisting but not IP melting. These results indicate that the region from residue 121 to 135 is important for A/T untwisting but not for IP melting and demonstrate that these activities are separable. Two point substitution mutants (126PS and 135PL) were characterized further by testing them for origin DNA binding, origin unwinding, oligomerization, and helicase activity. These two mutants were completely defective in origin (form U(R)) unwinding but normal in the other activities. Our results demonstrate that a failure to normally untwist the A/T track is correlated with a defect in origin unwinding. Further, they indicate that some mutants with substitutions in the region from residue 121 to 135 interact with origin DNA incorrectly, perhaps by failing to make appropriate contacts with the A/T-rich DNA.     

Partitioning of the Golgi apparatus during mitosis in living HeLa cells

The Golgi apparatus of HeLa cells was fluorescently tagged with a green fluorescent protein (GFP), localized by attachment to the NH2-terminal retention signal of N-acetylglucosaminyltransferase I (NAGT I). The location was confirmed by immunogold and immunofluorescence microscopy using a variety of Golgi markers. The behavior of the fluorescent Golgi marker was observed in fixed and living mitotic cells using confocal microscopy. By metaphase, cells contained a constant number of Golgi fragments dispersed throughout the cytoplasm. Conventional and cryoimmunoelectron microscopy showed that the NAGT I-GFP chimera (NAGFP)-positive fragments were tubulo-vesicular mitotic Golgi clusters. Mitotic conversion of Golgi stacks into mitotic clusters had surprisingly little effect on the polarity of Golgi membrane markers at the level of fluorescence microscopy. In living cells, there was little self-directed movement of the clusters in the period from metaphase to early telophase. In late telophase, the Golgi ribbon began to be reformed by a dynamic process of congregation and tubulation of the newly inherited Golgi fragments. The accuracy of partitioning the NAGFP-tagged Golgi was found to exceed that expected for a stochastic partitioning process. The results provide direct evidence for mitotic clusters as the unit of partitioning and suggest that precise regulation of the number, position, and compartmentation of mitotic membranes is a critical feature for the ordered inheritance of the Golgi apparatus.     

Laboratory evaluation in the diagnosis of Lyme disease

PURPOSE: To provide a qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease and to use the resultant data to formulate guidelines for clinical diagnosis. DATA SOURCES: A MEDLINE search of English-language articles or articles with English-language abstracts published from 1982 to 1996. DATA EXTRACTION: Sensitivity, specificity, and likelihood ratios were calculated, and a random-effects model was used to combine the proportions from the eligible studies. Prespecified criteria were used to determine which studies were eligible for analysis. DATA SYNTHESIS: Laboratory testing in general is not clinically useful if the pretest probability of Lyme disease is less than 0.20 or greater than 0.80. When the pretest probability is 0.20 to 0.80, sequential testing with enzyme-linked immunosorbent assay and Western blot is the most accurate method for ruling in or ruling out the possibility of Lyme disease. CONCLUSIONS: Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease.     

Modulation of delta9-tetrahydrocannabinol-induced hypothermia by fluoxetine in the rat

We characterized the development of the anti-centromere antibody in a patient prior to the development of CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) symptoms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting (IgG and IgM) of cellular extracts enriched for centromere antigens and indirect immunofluorescence were used to study the anti-centromere immune response. The sera recognized 3 centromere antigens with molecular masses 18,000 (CENP-A), 50,000 (CENP-D), and 80,000 (CENP-B). For CENP-A, IgM was present before the appearance of the IgG response. Anti-CENP-D revealed an IgM response that decreased over time but no IgG, while CENP-B showed an IgG response that strengthened and then weakened over time. The appearance of an anti-centromere nuclear fluorescence pattern correlated with the appearance of IgG anti-CENP-A. Signs and symptoms typical of CREST began about 4 years after antibodies to centromere antigens were found. The development of the CREST syndrome in our patient was preceded by the appearance of anti-centromere autoantibodies. For at least one of the antigens (CENP-A), there was an immunoglobulin class switch from IgM to IgG.     

Rapid overdrive pacing of refractory tachyarrhythmias in patients after open-heart surgery

The efficacy of rapid ventricular pacemaker overdrive in the treatment of supraventricular and ventricular tachyarrhythmias is presented as a new approach to the management of these rhythm disorders inpatients after cardiac surgery. This mode of therapy is exemplified in the control of heart rate and return of normal sinus rhythm in patients with both types of tachyarrhythmias refractory to conventional antiarrhythmic agents. In addition, the pathogenesis and mechanisms of pacemaker overdrive in termination these rhythm disturbances are delineated.