Biomedical subjects

S Byers

Publications and source records attributed to S Byers.

At least 19 recordsLinked to original sources

PubMed2005

The effect of recombinant human osteogenic protein-1 on growth plate repair in a sheep model.

Injuries to the growth plate in children can result in bone bridge formation, which ultimately lead to limb length and angular deformities. The histological and molecular changes associated with growth plate repair following the Langenskiöld procedure, a surgical technique used to remove impeding bone bridges, in conjunction with administration of recombinant human osteogenic protein-1 (rhOP-1) were examined using a sheep model. Following treatment with rhOP-1 there was an increase in the height of the growth plate immediately adjacent to the defect compared to untreated animals. The expression of type I collagen, osteopontin and decorin were observed in the growth plate adjacent to the defect in the untreated animals at day 56, but this response was accelerated in the rhOP-1 treated animals, with these molecules seen as early as day 7. Therefore, treatment with rhOP-1 initiated a complex response that was both chondrogenic and osteogenic in nature.

Animals↗

PubMed2001

Regulation of beta-catenin function by the IkappaB kinases.

Both the beta-catenin and the nuclear factor kappaB (NF-kappaB) proteins are important regulators of gene expression and cellular proliferation. Two kinases, IKKalpha and IKKbeta, are critical activators of the NF-kappaB pathway. Here we present evidence that these kinases are also important in the regulation of beta-catenin function. IKKalpha- and IKKbeta-deficient mouse embryo fibroblasts exhibited different patterns of beta-catenin cellular localization. IKKbeta decreases beta-catenin-dependent transcriptional activation, while IKKalpha increases beta-catenin-dependent transcriptional activity. IKKalpha and IKKbeta interact with and phosphorylate beta-catenin using both in vitro and in vivo assays. Our results suggest that differential interactions of beta-catenin with IKKalpha and IKKbeta may in part be responsible for regulating beta-catenin protein levels and cellular localization and integrating signaling events between the NF-kappaB and Wingless pathways.

Animals↗

PubMed2000

Beta-catenin affects androgen receptor transcriptional activity and ligand specificity.

beta-Catenin is a multifunctional molecule with important roles in intercellular adhesion and signal transduction. We reported previously that beta-catenin is mutated in human prostate cancer. In this study, we investigated the role of beta-catenin mutations on androgen receptor (AR) signaling. beta-Catenin significantly enhanced androgen-stimulated transcriptional activation by the AR. beta-Catenin also increased AR transcriptional activation by androstenedione and estradiol and diminished the antagonism of bicalutamide. Coimmunoprecipitation of beta-catenin with AR from LNCaP prostate cancer cells showed that the two molecules are present in the same complex. The amount of beta-catenin in complex with AR was increased by androgen. These findings implicate beta-catenin in the regulation of AR function and support a role for beta-catenin mutations in the pathogenesis of prostate cancer.

Androgen Antagonists↗

PubMed2000

Automated assay for nicotinamide adenine dinucleotide (NAD+).

Sulfur mustard (HD), a vesicating chemical warfare compound, has been shown to deplete the nicotinamide adenine dinucleotide (NAD+) content in several cell systems and tissues. This NAD+ depletion has been proposed as an indicator of HD exposure and can be used to evaluate potential antivesicant compounds. To examine NAD+ levels, an automated method based on the alcohol dehydrogenase cycling assay of Jacobson and Jacobson and utilizing a Cobas FARA clinical analyzer has been developed. Automation of this assay led to smaller sample volumes and more efficient use of personnel and resources. The usefulness of this automated method was tested by evaluating the protection, if any, by the topical application of vitamin D or betamethasone against HD-induced NAD+ depletion in skin punches from the hairless guinea pig. The results showed that the samples exposed to HD exhibited significant decreases in NAD+ levels when compared with controls. However, neither vitamin D nor betamethasone demonstrated protection against HD-induced NAD+ depletion. In fact, betamethasone exacerbated the NAD+ depletion when compared with the HD exposed group. This assay appears to be useful for testing potential antivesicant compounds using both in vivo and in vitro exposure systems.

Animals↗

PubMed2000

Spatial arrangement of physeal cartilage chondrocytes and the structure of the primary spongiosa.

Using laser confocal microscopy and 5-chloromethyl-fluoresceindiacetate (CMFDA) loading of chondrocytes we have investigated the structure of the ovine physis during late fetal development and its relationship to the structure observed in the primary spongiosa. Chondrocytes within the ovine growth plate form nests that together span the growth plate. We propose that all growth plates may be composed of nests of cells, but that the length of the individual nests changes between growth plates and with gestational age. The continuous column of cells seen within some growth plates is a nest of cells that is in the process of being absorbed by the invading metaphyseal front. Scanning electron microscopy of the mineralized portion of the primary spongiosa revealed structures that were consistent with the hypothesis that the cartilage surrounding the nest structure gives rise to the structure in the primary spongiosa. Although mineralization does not occur between cells within a nest, bands of mineral form between nests in the lower hypertrophic region and around the end of the nest as it reaches the hypertrophic region. This pattern of mineralization around and between nest termini yields the complex three-dimensional network of mineralized trabeculae observed in the primary spongosia.

Animals↗

PubMed2000

Metaphyseal factors promote calcium incorporation in physeal chondrocyte cultures.

Our hypothesis is that physiological mineralization within the mammalian growth plate is a consequence of communication between cartilage chondrocytes and cells within metaphyseal bone. To test this hypothesis, chondrocytes were isolated from the proliferative region of the fetal ovine physis and co-cultured with cells or conditioned medium from cells characteristic of those in metaphyseal bone. The mineralization potential of chondrocytes alone and in the presence of other cells or conditioned medium was determined by 45calcium incorporation. Co-culture of chondrocytes with a crude cell isolate from metaphyseal bone resulted in a stimulation of 45calcium incorporation of 93% above that observed in the individual cell populations alone. Conditioned medium from metaphyseal bone cultures also stimulated 45calcium incorporation. This response to conditioned medium was dose-dependent and stable to 90 degrees C. Vascular endothelial cells and conditioned medium from chondrocyte and osteoblast cultures did not stimulate 45calcium incorporation by physeal chondrocytes. Thus, cells found in the metaphyseal bone produce a soluble factor, which promote calcium incorporation by physeal chondrocytes. The source of this factor is not chondrocytic, osteoblastic, or endothelial in origin.

Animals↗

PubMed2000

Quantitative histomorphometric analysis of the human growth plate from birth to adolescence.

Longitudinal bone growth occurs via the transformation of growth plate cartilage into bone through a series of cell and matrix changes, termed endochondral ossification. In this study, we characterize the development of trabecular bone from growth plate cartilage in the human rib from birth to adolescence. The height of the proliferative and hypertrophic zones within the growth plate and the primary bone spongiosa decreased with increasing age, with the greatest change observed in the first year of postnatal life. Within these zones, an internal rearrangement of tissue structure occurred. The matrix volume fraction (either cartilage or bone) increased with age in each of the zones. A concomitant increase in cartilage septae thickness and bone trabecular thickness was observed. A decrease in cartilage septae number was seen in the proliferative zone and a decrease in bone trabeculae number was also observed in the primary spongiosa. However, no difference in cartilage septae number was noted in the hypertrophic zone, the region at which cartilage is transformed into bone. Together the proliferative and hypertrophic regions of the growth plate and the bone primary spongiosa appear to constitute the active growth region, with concomitant changes observed that result in longitudinal growth. In contrast, bone mineral volume in the secondary spongiosa was stable over the ages examined; however, trabecular architecture underwent consolidation as trabecular number decreased and trabecular thickness increased. The integration of the structural transformation from cartilage to bone is crucial in achieving the dual purposes of longitudinal growth and peak bone mass. The structure developed during childhood will have an important bearing on the response to bone-altering disease in later life.

Adolescent↗

PubMed2000

Identification and immunolocalization of decorin, versican, perlecan, nidogen, and chondroitin sulfate proteoglycans in bovine small-antral ovarian follicles.

Proteoglycans (PGs) consist of a core protein and attached glycosaminoglycans (GAGs) and have diverse roles in cell and tissue biology. In follicles PGs have been detected only in follicular fluid and in cultured granulosa cells, and the composition of their GAGs has been determined. To identify PGs in whole ovarian follicles, not just in follicular fluid and granulosa cells, small (1-3-mm) bovine follicles were harvested. A proportion of these was incubated with (35)SO(4) for 24 h to incorporate radiolabel into the GAGs. The freshly harvested and cultured follicles were sequentially extracted with 6 M urea buffer, the same buffer with 0.1% Triton X-100 and then with 0.1 M NaOH. Proteoglycans were subjected to ion-exchange and size-exclusion chromatography. The GAGs were analyzed by chemical and enzymic digestion, and on the basis of their composition, we chose a list of known PGs to measure by ELISA analyses. Versican, perlecan, decorin, but not aggrecan or biglycan, were identified. These, excluding decorin for technical reasons, as well as a basal lamina glycoprotein, nidogen/entactin, were immunolocalized. Versican was localized to the thecal layers, including externa and the interna particularly in an area adjacent to the follicular basal lamina. Perlecan and nidogen were localized to the follicular basal lamina of antral follicles, both healthy and atretic, but not to that of preantral follicles. Both were localized to subendothelial basal laminas, but the former was not readily detected in arteriole smooth muscle layers. This study has confirmed the presence of versican and perlecan, but not the latter as a component of follicular fluid, and identified decorin and nidogen in ovarian antral follicles.

Animals↗

PubMed2000

Enzyme replacement therapy in a feline model of MPS VI: modification of enzyme structure and dose frequency.

Enzyme replacement therapy (ERT) in the MPS VI cat is effective at reducing or eliminating pathology in most connective tissues. One exception is that cartilage and chondrocytes remained distended with extensive lysosomal vacuolation after long-term, high-dose ERT. In this study, we demonstrate that recombinant human N-acetylgalactosamine-4-sulphatase (4S) is taken up by chondrocytes via a mannose-6-phosphate-dependent mechanism and is effective at removing MPS storage. In vitro, the penetration of 4S into articular cartilage is low (partitioning coefficient = 0.06) and i.v. administered enzyme does not distribute significantly into articular cartilage in vivo. To alter the tissue distribution of 4S, the enzyme was coupled to ethylene diamine or poly-L-lysine, increasing its overall charge and diffusion into cartilage, and the dosing frequency of unmodified 4S was increased. Modification resulted in active 4S that maintained its ability to correct MPS storage and increased the partitioning coefficient of 4S into cartilage by 77% and 50% for ethylene diamine and poly-L-lysine, respectively. However, in vivo ERT studies demonstrated that response to therapy was not significantly improved by either the enzyme modifications or change to the dosing regimen, when compared with ERT with unmodified enzyme. Distribution experiments indicated the majority of enzyme is taken up by the liver irrespective of modification. To optimize therapy and improve the amount of enzyme reaching cartilage and other tissues demonstrating poor uptake, it may be necessary to bypass the liver or prolong plasma half-life so that proportionately more enzyme is delivered to other tissues.

Animals↗

PubMed1999

Expression and characterization of wild type and mutant recombinant human sulfamidase. Implications for Sanfilippo (Mucopolysaccharidosis IIIA) syndrome.

Mucopolysaccharidosis IIIA (MPS-IIIA) is an autosomal recessive lysosomal storage disorder caused by the deficiency of sulfamidase (NS; EC 3.10.1.1), resulting in defective degradation and storage of heparan sulfate. This paper reports the production and characterization of monoclonal and polyclonal antibodies against recombinant human sulfamidase (rhNS) to quantitate and characterize normal and mutant sulfamidase produced from the wild type NS expression vector. Glycosylation and phosphorylation studies of immunoprecipitated rhNS show that all five potential glycosylation sites are utilized, with three high mannose/hybrid oligosaccharides and two simpler chains, with at least one functional mannose 6-phosphate group. An NS quantification system was developed to determine the effect of the three most common and severe patient mutations: S66W (Italy), R74C (Poland), and R245H (The Netherlands). The quantity and specific activity of expressed mutant rhNS was significantly lower than expressed normal rhNS, with 0.3, 0.2, and 0.05% of normal rhNS produced and 15, 17, and 83% of normal specific activity for S66W, R74C, and R245H observed, respectively. The recent structural elucidation of N-acetylgalactosamine-4-sulfatase was utilized to postulate the effect on the structure-function relationship of NS. The characterization of normal and mutated rhNS has relevance for efficient diagnosis and therapeutic developments for MPS-IIIA patients.

Animals↗

PubMed1999

Cross-regulation of beta-catenin-LEF/TCF and retinoid signaling pathways.

Vitamin A derivatives (retinoids) are potent regulators of embryogenesis, cell proliferation, epithelial cell differentiation and carcinogenesis [1]. In breast cancer cells, the effects of retinoids are associated with changes in the cadherin-beta-catenin adhesion and signaling system [2] [3]. beta-catenin is a component of the Wnt signaling pathway, which regulates several developmental pathways [4]. Increases in cytoplasmic beta-catenin and beta-catenin signaling are also associated with numerous cancers, and are particularly important in colon cancer [5]. The oncogenic and developmental effects of beta-catenin are mediated by its interaction with and activation of members of the LEF/TCF family of transcription factors [6] [7] [8]. Here, we shown that retinoic acid (RA) decreases the activity of the beta-catenin-LEF/TCF signaling pathway. This activity of RA was independent of the adenomatous polyposis coli (APC) tumor suppressor and ubiquitination-dependent degradation of cytoplasmic beta-catenin. Consistent with this finding, beta-catenin interacted directly with the RA receptor (RAR) in a retinoid-dependent manner, but not with the retinoid X receptor (RXR), and RAR competed with TCF for beta-catenin binding. The activity of RA on RAR-responsive promoters was also potentiated by beta-catenin. The data suggest that direct regulation of beta-catenin-LEF/TCF signaling is one mechanism whereby RA influences development, cell differentiation and cancer.

Caco-2 Cells↗

PubMed1999

The ubiquitin-proteasome pathway and serine kinase activity modulate adenomatous polyposis coli protein-mediated regulation of beta-catenin-lymphocyte enhancer-binding factor signaling.

The tumor suppressor function of the adenomatous polyposis coli protein (APC) depends, in part, on its ability to bind and regulate the multifunctional protein, beta-catenin. beta-Catenin binds the high mobility group box transcription factors, lymphocyte enhancer-binding factor (LEF) and T-cell factor, to directly regulate gene transcription. Using LEF reporter assays we find that APC-mediated down-regulation of beta-catenin-LEF signaling is reversed by proteasomal inhibitors in a dose-dependent manner. APC down-regulates signaling induced by wild type beta-catenin but not by the non-ubiquitinatable S37A mutant, beta-catenin. Bisindoylmaleimide-type protein kinase C inhibitors, which prevent beta-catenin ubiquitination, decrease the ability of APC to down-regulate beta-catenin-LEF signaling. All these effects on LEF signaling are paralleled by changes in beta-catenin protein levels. Lithium, an inhibitor of glycogen synthase kinase-3beta, does not alter the ability of APC to down-regulate beta-catenin protein and beta-catenin-LEF signaling in the colon cancer cells that were tested. These results point to a role for beta-catenin ubiquitination, proteasomal degradation, and potentially a serine kinase other than glycogen synthase kinase-3beta in the tumor-suppressive actions of APC.

Adenomatous Polyposis Coli Protein↗

PubMed1999

Histomorphometric analysis of the tibial growth plate in a feline model of mucopolysaccharidosis type VI.

Mucopolysaccharidosis type VI (MPS VI) is a genetically inherited lysosomal storage disorder. Severely affected children exhibit a range of skeletal abnormalities including short stature, facial dysmorphia, and dysostosis multiplex. Naturally occurring and transgenic animal models of MPS VI are also found which exhibit pathology similar to the human disorder. In this paper we have characterized the formation of trabecular bone from growth plate cartilage in a feline model of MPS VI. Tibial trabecular bone was shown to be osteopenic in MPS VI animals with a bone mineral volume (BV/TV) of 4.51% compared with a BV/TV of 15.64% in normal animals. In addition to osteopenia, a rearrangement of trabecular bone architecture was also observed in MPS VI tibiae, with fewer, thinner trabeculae noted; bone formation rate was also decreased. These observations support those previously made in the L5 vertebrae of MPS VI animals. When the sequential formation of growth plate cartilage structural elements, their transition into primary bone spongiosa, and remodeling into secondary bone spongiosa was characterized, no difference between normal and MPS VI could be detected in the number of cartilage septae and their arrangement in the proliferative and hypertrophic regions of the growth plate or trabecular elements in the primary spongiosa. However, a deviation from normal was observed in the resting zone of the growth plate and in the secondary spongiosa of bone. Thus, the osteopenia observed in MPS VI bone appears to arise primarily from a defect in bone production within the metaphysis and diaphysis rather than the creation of an abnormal template in the preceding growth plate cartilage.

Animals↗

PubMed1998

Genotype-phenotype correlations in mucopolysaccharidosis type I using enzyme kinetics, immunoquantification and in vitro turnover studies.

Fibroblasts from 16 patients with known alpha-L-iduronidase gene mutations and different clinical phenotypes of mucopolysaccharidosis type I (MPS I) were investigated in order to establish genotype/phenotype correlations. Enzyme kinetic studies were performed using the specific alpha-L-iduronidase substrate iduronosyl anhydro[1-3H]mannitol-6-sulfate. Specific residual enzyme activities were estimated using the kinetic parameters and an immunoquantification assay which determines levels of alpha-L-iduronidase protein. Cells were cultured in the presence of [35S]sulfate and the in vivo degradation of accumulated labelled glycosaminoglycans measured after different chase times. Residual enzyme activity and different amounts of residual enzyme protein were present in extracts from 9 of 16 cell lines covering a wide spectrum of clinical severity. Catalytic capacity, calculated as the product of kcat/Km and ng iduronidase protein per mg cell protein, was shown in most cases to be directly related to the severity of clinical phenotype, with up to 7% of normal values for patients with the attenuated form of MPS I (Scheie) and less than 0.13% for severely affected patients (Hurler) In vitro turnover studies allowed further refinement of correlations between genotype and phenotype. Scheie disease compared to Hurler disease patients were shown to accumulate smaller amounts of glycosaminoglycans that were also turned over faster. A combination of turnover and residual enzyme data established a correlation between the genotype, the biochemical phenotype and the clinical course of this lysosomal storage disorder.

Cell Line↗

PubMed1998

Glycosaminoglycan accumulation and excretion in the mucopolysaccharidoses: characterization and basis of a diagnostic test for MPS.

A combination of anion-exchange chromatography and 30-40% gradient polyacrylamide gel electrophoresis (gradient-PAGE) was used to purify and characterize urinary glycosaminoglycans from various mucopolysaccharidoses (MPS). The urinary glycosaminoglycans from the different MPS displayed distinct patterns on gradient-PAGE and further confirmation of MPS types and subtypes was demonstrated by an electrophoretic shift in the banding pattern after digestion with the appropriate MPS enzyme. Thus each of the MPS accumulates a unique spectrum of glycosaminoglycans with a nonreducing terminal consisting of the substrate specific for the deficient enzyme in that particular MPS disorder. The absolute correlation of the nonreducing terminal structure with a particular MPS and the availability of recombinant lysosomal enzymes provide the means for a rapid and accurate diagnosis of individual MPS. Analysis of tissue glycosaminoglycans in one MPS type (feline MPS VI) indicated a tissue-specific pattern of glycosaminoglycan accumulation. Undegraded glycosaminoglycans had distinct banding patterns on gradient-PAGE and although dermatan sulfate was predominantly excreted in MPS VI urine, some tissues were observed to accumulate predominantly chondroitin sulfate glycosaminoglycans, e.g., bone and kidney. The spectrum of glycosaminoglycans excreted in the urine is therefore most likely a combination of glycosaminoglycans from various tissues.

Animal Diseases↗

PubMed1998

Recombinant caprine 3H-[N-acetylglucosamine-6-sulfatase] and human 3H-[N-acetylgalactosamine-4-sulfatase]: plasma clearance, tissue distribution, and cellular uptake in the rat.

The use of recombinant lysosomal enzymes for enzyme replacement therapy (ERT) is likely to be a necessary component of effective treatment regimens for lysosomal storage diseases (LSDs). The mechanism and rate of uptake into target cells, rate of disappearance of the enzyme from plasma, and its tissue distribution are important factors to assess the need for possible modifications to the enzyme, particularly for LSDs that affect the central nervous system (CNS). Two recombinant lysosomal enzymes, caprine N-acetylglucosamine-6-sulfatase (rc6S) and human N-acetylgalactosamine-4-sulfatase (rh4S), deficient in MPS IIID and MPS VI, respectively, were radiolabeled and purified. The major portion (>77%) of each recombinant enzyme contained the mannose-6-phosphate (M6P) recognition marker as demonstrated by their ability to bind to a M6P receptor affinity column. The uptake of 3H-rc6S and 3H-rh4S into cultured rat brain cells was also inhibited by the addition of 5 mM M6P to the culture medium. After iv administration of 0.4-0.5 mg/kg of 3H-rc6S and 1 mg/kg of 3H-rh4S to the rat, both enzymes were rapidly lost from the circulation in a biphasic fashion (t1/2 for 3H-rc6S = 1.25+/-0.15 min and 37.17+/-23.29 min; t1/2 for 3H-rh4S = 0.41 and 5.3 min). At this dose, about 6% of 3H-rc6S, but only 0.49% of 3H-rh4S, remained in the plasma 4 h after administration, whereas approx 30% of 3H-rc6S and more than 50% of 3H-rh4S was found in the liver. At doses of 1.6-2.0 mg/kg of 3H-rc6S and 1 mg/kg 3H-rh4S, but not at the lower dose of 3H-rc6S, trace levels of both 3H-rc6S and 3H-rh4S were detected in the brain. The low level of enzyme recovered from the brain suggests that modification of rc6S will be necessary to achieve sufficient enzyme uptake into the CNS for effective therapy of MPS IIID.

Animals↗

PubMed1997

Enzyme replacement therapy in Mucopolysaccharidosis VI: evidence for immune responses and altered efficacy of treatment in animal models.

Enzyme replacement therapy (ERT) can potentially result in an immunological response to the introduced protein. The immunological response by Mucopolysaccharidosis type VI (MPS VI) cats to recombinant human N-acetylgalactosamine 4-sulfatase (rh4S) ERT has been investigated. Plasma antibody titres to rh4S were detected in untreated MPS VI and normal control cats, but the antibody titres to rh4S were higher in ERT treated MPS VI cats. The reactivity by cats to rh4S did not appear to be just due to species cross reactivity, as plasma antibodies from normal control, MPS VI and MPS VI ERT cats reacted equally with feline and human 4-sulfatase. Normal control and MPS VI human plasma also had antibody titres to rh4S. Plasma antibodies to rh4S, from an ERT treated cat, could be temporarily removed from circulation by enzyme infusion, confirming specificity for rh4S and indicating a possible window for ERT in the absence of antibody. In enzyme distribution studies with 3H-rh4S, evidence of altered targeting, and enzyme inactivation and degradation were observed in high compared to low titre rats. In high titre rats, the observed loss of 3H-label from vacuolar organelles of the liver may represent either degradation of antibody bound 3H-rh4S for reutilisation within the liver, or antigen presentation. The development of high titre antibody may have a detrimental effect on the efficacy of ERT.

Animals↗

PubMed1997

Relation between ambulatory electrocardiographic monitoring and myocardial perfusion imaging to detect coronary artery disease and myocardial ischemia: an ACIP ancillary study. The Asymptomatic Cardiac Ischemia Pilot (ACIP) Investigators.

OBJECTIVES: This study sought to explore the relation between markers of ischemia detected by ambulatory electrocardiographic (AECG) monitoring and stress myocardial perfusion single-photon emission computed tomography (SPECT). BACKGROUND: Stress myocardial SPECT and AECG monitoring are both utilized in evaluating patients with coronary artery disease. However, information is limited regarding the relation between the presence and extent of ischemia as detected by these two modalities. METHODS: This was an ancillary study of the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial. One hundred six patients with previous coronary angiography underwent AECG monitoring and stress SPECT within a close temporal time period. The frequency and duration of ischemia as assessed by AECG monitoring and the total and ischemic stress-induced myocardial perfusion defect sizes as assessed by SPECT were quantified in separate core laboratories. Multivariate logistic regression and linear regression analysis were used to determine associations between AECG and SPECT abnormalities with regard to angiographic, demographic and treadmill exercise variables. RESULTS: Seventy-four percent of patients with significant (> or = 50%) coronary artery stenosis had SPECT abnormalities, whereas 61% had ischemia by AECG monitoring. The most important predictors of SPECT abnormalities were severity (p < 0.001) of coronary artery stenosis, followed by total exercise duration (p = 0.016) and patient age (p = 0.04). The only predictor of AECG abnormalities was the presence of ST segment depression on the initial exercise treadmill test (p = 0.021). Only a 50% concordance for normalcy or abnormalcy was observed between the SPECT and AECG results, and no relation was observed between the frequency or duration of AECG ischemia and the quantified total or ischemic myocardial perfusion defect size as assessed by SPECT. CONCLUSIONS: Ischemia as detected by AECG monitoring does not correlate with the presence and extent of ischemia as quantified by stress SPECT. Because these techniques appear to detect different pathophysiologic manifestations of ischemia, they may be complementary in more fully defining the functional significance of coronary artery disease and, in particular, which patients are at highest risk for adverse cardiac events.

Adult↗