Publications

OBJECTIVES

The aim of this study was to test the hypothesis that atherosclerotic plaque in the thoracic aorta detected by transesophageal echocardiography is a marker for coronary artery disease.

BACKGROUND

Previous pathologic and roentgenographic studies have suggested a relation between aortic plaque and coronary artery disease but have lacked clinical utility.

METHODS

We performed transesophageal echocardiography on 61 patients (30 women and 31 men aged 22 to 83 years [mean 60 +/- 14]) who had previously undergone cardiac catheterization with coronary angiography. The clinical indications for angiography were angina (n = 26), valvular heart disease (n = 17), positive noninvasive evaluation for ischemia without angina (n = 6), postmyocardial infarction (n = 5), familial hypercholesterolemia (n = 4), coronary cameral fistula (n = 1), atrial myxoma (n = 1) and suspected aortic dissection (n = 1). All patients underwent transesophageal echocardiography with imaging of the thoracic aorta. The criteria used to diagnose atherosclerotic plaque on transesophageal echocardiography were the presence of linear or focal increased echo-density with lumen irregularity and thickening or calcification of the aortic intima.

RESULTS

In 41 of the 61 patients, obstructive coronary artery disease was detected by angiography in at least one vessel (> 50% left main coronary artery stenosis or > 70% stenosis in the left anterior descending, right coronary or left circumflex artery distribution). In 37 of the 41, atherosclerotic plaque was detected in the thoracic aorta by transesophageal echocardiography. Twenty of the 61 patients had normal coronary angiographic findings or nonobstructive lumen irregularities. In 2 of these 20 patients, plaque was detected in the thoracic aorta on transesophageal echocardiography. The presence of aortic plaque on transesophageal study had a sensitivity of 90% and a specificity of 90% for angiographically proved obstructive coronary artery disease. The positive predictive value of aortic plaque for obstructive coronary artery disease was 95% and the negative predictive value was 82%.

CONCLUSIONS

The detection of atherosclerotic plaque in the thoracic aorta by transesophageal echocardiography appears to be a marker for the identification of obstructive coronary artery disease and deserves further investigation.

A 34-year-old chemical manufacturing worker had new onset of work-related asthma after several years of exposure to the fungicide, captafol. On specific bronchial challenge testing, he demonstrated a marked and persistent fall in FEV1. Cessation of exposure resulted in improved symptoms and pulmonary function. The delay in symptoms after several years of workplace exposure and the dual reaction demonstrated on specific bronchial challenge testing suggest sensitization to some component of technical-grade captafol, but an IgE response was not detected.

There is no gold standard for determining poisoning incidence. We wished to compare four measures of poisoning incidence: International Classification of Diseases 9th Revision (ICD-9) principal (N-code) and supplemental external cause of injury (E-code) designations, poison control center (PCC) reporting, and detection by the Drug Abuse Warning Network (DAWN). We studied a case series at two urban hospitals. We assigned ICD-9 N-code and E-code classifications, determining whether these matched with medical records. We ascertained PCC and DAWN system reporting. A total of 724 subjects met entry criteria; 533 were studied (74%). We matched poisoning N-codes for 278 patients (52%), E-code by cause in 306 patients (57%), and E-code by intent in 171 patients (32%). A total of 383 patients (72%) received any poisoning N-code or any E-code. We found that PCC and DAWN reporting occurred for 123 of all patients (23%) and 399 of 487 eligible patients (82%), respectively. In multiple logistic regression, factors of age, hospital admission, suicidal intent, principal poisoning or overdose type, and mixed drug overdose were statistically significant predictors of case match or report varying by surveillance measure. Our findings indicate that common surveillance measures of poisoning and drug overdose may systematically undercount morbidity.

Metal fume fever is a flulike illness caused by zinc oxide inhalation and accompanied by an impressive pulmonary cellular response. We hypothesized that the syndrome is mediated by cytokines released in the lung after exposure to zinc oxide fume. We carried out 26 experimental welding exposures in 23 volunteer subjects, performing postexposure bronchoalveolar lavage (BAL) 3 h (n = 6), 8 h (n = 11), or 22 h (n = 9) after exposure. We detected tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) varying in a time- and exposure-related manner. The concentration of TNF in the BAL fluid supernatant was significantly greater at 3 h than at 8 h or 22 h after exposure (p < 0.05), exhibiting a statistically significant exposure-response relationship to airborne zinc at each follow-up time period (p < 0.05). TNF concentrations were statistically correlated with those of IL-6 in BAL supernatant obtained at 22 h (r = 0.78, p = 0.01) and with concentrations of IL-8 in BAL 8 h after exposure (r = 0.85, p = 0.001). IL-6 displayed a significant exposure-response relationship to zinc (p < 0.05) at 22 h. IL-8 exhibited a significant exposure-response relationship to zinc (p < 0.05) at 8 h after exposure, a time at which IL-8 correlated with marked increases in BAL fluid polymorphonuclear leukocytes (PMN) (r = 0.7, p = 0.01). Although we also detected interleukin-1 (IL-1) in BAL samples, this cytokine did not demonstrate a statistically significant exposure response. TNF, IL-6, and IL-8 in BAL fluid supernatant concentrations increased in a time and exposure-dependent fashion after zinc oxide welding fume exposure. The time course of increased cytokines, their correlations with one another and with PMN in the BAL fluid, and the consistency of our findings with the known kinetics and actions of these cytokines support the hypothesis that a network of cytokines is involved in the pathogenesis of metal fume fever.

Matrix-assisted laser desorption ionization on a time-of-flight (MALDI/TOF) mass spectrometer provides a rapid and accurate method for molecular weight determination of hydrophobic cytochrome P450 proteins (P450s). A mass accuracy of 0.075% was achieved by analysis of dialyzed P450 2B1 using bovine serum albumin (BSA) as an internal standard. The measured mass of cytochrome P450 2B2 with MALDI/TOF resulted in an average molecular weight which was higher than reported values. Immobilization procedures proved extremely effective on samples containing high concentrations of phosphate buffers.

The frizzled (fz) locus of Drosophila encodes a protein (Fz) with a seven-transmembrane-domain profile characteristic of G-protein-coupled receptors. In Drosophila, genetic evidence suggests that Fz functions to transmit and transduce polarity signals in epidermal cells during hair and bristle development. We have isolated from a UMR 106 rat osteosarcoma cell library a cDNA (fz-1) encoding a predicted 641-residue protein (Fz-1) with 46% homology with Drosophila Fz. We also identified a second cDNA (fz-2) encoding a protein (Fz-2) of 570 amino acids that is 80% homologous with Fz-1, with divergence most evident in the extracellular domains. Southern blots of rat genomic DNA indicated that fz-1 and fz-2 represent distinct genes. Northern analysis revealed the presence of a single fz-1 mRNA (4.7 kilobases) and two fz-2 mRNAs (2.5 and 4.5 kilobases) in rat tissues. The fz-1 and fz-2 genes are widely expressed in rat tissues with the highest steady-state levels of mRNA in kidney, liver, heart, uterus, and ovary. fz-1 and -2 mRNA levels were greater in neonatal than in corresponding adult tissues. Treatment of UMR 106 cells with bone resorbing agents including parathyroid hormone, epidermal growth factor, and 1,25-dihydroxyvitamin D3 produced increases in fz-1 and -2 mRNA levels. We suggest that hormonal induction of Fz proteins in osteoblasts serves to promote intercellular signaling required for functional responses such as increased bone resorption. Fz-1 and Fz-2 may represent products of a gene family whose members serve as transducers or intercellular transmitters of signals required for normal morphogenesis and/or differentiated function in diverse tissues.