Swine cysticercosis and associated risk factors in non-technified pig breeding in semi-arid region of Sergipe state, Brazil.

The aim of this study was to determine the frequency of Taenia solium anti-metacestode antibodies in slaughtered pigs in a semi-arid region of the "Alto Sertão" of Sergipe state, Brazil, and verify the risk factors associated with swine cysticercosis. For this, 230 samples of swine blood from two slaughterhouses were collected and analyzed by indirect ELISA. The pigs came from five non-technical properties in the semi-arid region of the Alto Sertão of Sergipe state. Searches for cysts in the skeletal muscles of the pigs were performed during slaughter. In addition, an epidemiological questionnaire was applied to the pigs' original properties to determine risk factors. Besides that, the official health services database was evaluated for confirmed cases of neurocysticercosis and taeniasis in humans in the last 5 years, living in the studied region. Seropositivity in pigs was 12.6%, with no significant difference between males and females. No cysts were found in the carcasses of the slaughtered pigs. A positive association was found for properties that discharge domestic sewage into the environment, in river or streams, increasing the risk of positivity by 5.72 times. When analyzing the database of official agencies, there were no records of cases of neurocysticercosis or taeniasis in the resident population in the last 5 years. However, there were frequent cases of idiopathic epilepsy. The results demonstrate that study area is endemic for swine cysticercosis and serves as a warning of the possibility of the occurrence of the taeniasis-cysticercosis complex.

Prevalence and antimicrobial susceptibility of Streptococcus equi isolated from horses in Santa Catarina state, Southern Brazil.

The objective of this study was to determine the prevalence of Streptococcus equi (S. equi subsp equi and S. equi subsp zooepidemicus) in the state of Santa Catarina and evaluate the antimicrobial susceptibility of the isolates. For this, 420 nasal swab samples were collected from randomly selected horses. Isolation and phenotypic characterization of the bacteria were performed by sowing on 5% sheep blood agar, followed by analysis of morphotinctorial characteristics and biochemical analysis. To differentiate the main beta-hemolytic Streptococcus in horses, the fermentation profiles of the sugar's lactose, maltose, sorbitol, and trehalose were used, which were confirmed at the subspecies level by the PCR technique. The antimicrobial susceptibility panel was defined by the disk diffusion method, testing 13 antimicrobials from ten different classes, all regularly used in equine medical clinics, followed by the calculation of the multiple antimicrobial resistance index. Ten strains of S. equi were isolated, with a prevalence of 2.38% (10/420). Of the total positive samples, 3% (3/10) were confirmed as belonging to S. equi subsp equi and 70% (7/10) were confirmed as belonging to S. zooepidemicus. Multidrug resistance was observed in 60% (6/10) of isolates. The antimicrobial with the greatest resistance was clindamycin with 70% (7/10), followed by beta-lactams, with 40% (4/10) resistance to penicillin and 30% (3/10) to ceftiofur. The isolates were 100% (10/10) sensitive to gentamicin, chloramphenicol, levofloxacin, and vancomycin. This was the first study carried out in the state, and based on these data, it can be said that Santa Catarina has a low prevalence of S. equi and the presence of multi-resistant strains of S. equi was confirmed in the equine herd in Santa Catarina.

Anti-inflammatory properties of doxycycline and minocycline in experimental models: an in vivo and in vitro comparative study.

AIMS AND METHODS: Minocycline (Mino) and doxycycline (Dox) are second generation tetracyclines known to present several other effects, which are independent from their antimicrobial activities. We studied in a comparative way the anti-inflammatory effects of Mino and Dox, on acute models of peripheral inflammation in rodents (formalin test and peritonitis in mice, and carrageenan-induced paw oedema in rats). Immunohistochemical assays for TNF-alpha and iNOS in rat paws of carrageenan-induced oedema were also carried out as well as in vitro assays for myeloperoxidase (MPO) and lactate dehydrogenase (LDH). Furthermore, antioxidant activities were evaluated by the DPPH assay. RESULTS: In the formalin test although Mino and Dox (1, 5, 10 and 25 mg/kg, i.p.) inhibited the first phase, they acted predominantly on the second phase of the test, where inhibition of the licking time close to 80% were observed. Mino and Dox were very efficacious in reducing the carrageenan-induced paw oedema in rats (10, 25 and 50 mg/kg, i.p.) and carrageenan-induced leucocyte migration (1 and 5 mg/kg, i.p.) to mice peritoneal cavities. Besides, they also significantly inhibited MPO and LDH releases at doses ranging from 0.001 to 1 µg/ml. Thus, in general, the anti-inflammatory activity of Dox was higher as compared to that of Mino, although the radical scavenging activity of Mino was of a magnitude 10 times higher. CONCLUSIONS: Our data indicate that anti-inflammatory and antioxidant effects, involve the inhibition of iNOS and TNF-alpha, among other properties, and these encourage clinical studies of these compounds for new therapeutic applications, especially those were inflammation plays a role.

[Disease activity assessment in large vessel vasculitis]. / Valutazione dell'attività di malattia nelle vasculiti dei grandi vasi.

Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive.

Inhibition of Escherichia coli invasion into bovine mammary epithelial cells previously infected by Mycobacterium avium subsp. paratuberculosis.

Background: The coinfection process of Escherichia coli, an etiological agent of clinical mastitis and Mycobacterium avium subsp. paratuberculosis (MAP), a non-mastitic etiological agent in the bovine mammary gland is not fully known.Objective: Verify the ability of MAP to interfere with the invasion and translocation of E. coli in bovine mammary epithelial cell line (MAC-T).Methods: For the invasion assay, MAC-T cells were challenged with MAP K10 for 2 h and then challenged with E. coli for 10, 30 and 120 min. For the translocation assay, the trans well plates were used and the challenge sequence was repeated as previously described. The amount of E. coli in the assays was determined by counting colony forming units (CFU) in Luria-Bertani medium. Quantitative real-time PCR was used to quantify MAP in MAC-T cells. To verify the viability of the MAC-T cells, the MTT assay was performed. MAP culture supernatant was also evaluated at different percentages for E. coli growth.Results: Previous MAP infection in MAC-T cells inhibited E. coli invasion in 10, 30 and 120 min. No significant interference of MAP in the translocation of E. coli from the apical-basal direction was verified. Quantity of MAP DNA inside the MAC-T cells was statistically similar. Neither reduction in MAC-T cells viability was detected during the experiment nor MAP-released factor in the supernatant inhibited E. coli invasion.Conclusion: These findings suggest that MAP-positive cows could be more resistant to E. coli infection, but when infected, could rapidly translocate E. coli to the subepithelial region.

Validation of real-time PCR technique for detection of Mycobacterium bovis and Brucella abortus in bovine raw milk.

Brucellosis and tuberculosis are diseases of great economic impact in cattle herds and are controlled by governmental programs in many countries. The validation of a diagnostic technique is fundamental for its application in official control programs of these diseases. The aim of the present study was to validate a polymerase chain reaction in real time (qPCR) for detection of Mycobacterium bovis and Brucella abortus in samples of artificially contaminated raw milk. The technique was evaluated using tests of analytical sensitivity and specificity, repeatability, internal reproducibility, and robustness. Initially, five DNA extraction methodologies were tested, and the DNeasy Mericon Food Kit-Qiagen and the Maxwell® 16 Tissue DNA Purification Kit-Promega presented the best analytical specificity of all the commercial kits tested and were used exclusively in subsequent tests. The lowest limits of detection obtained in the qPCR were 2.3 pg for M. bovis DNA and 20.7 fg for B. abortus DNA. The repeatability and reproducibility associated with the robustness indicate that the evaluated methods are applicable as rapid tools for the official in vivo diagnosis of bovine tuberculosis and brucellosis in raw milk from dairy herds in Brazil.

Critical Perspective of Animal Production Specialists on Cell-Based Meat in Brazil: From Bottleneck to Best Scenarios.

Recently, many studies regarding consumer perception of cell-based meat have been published. However, the opinion of the professionals involved in animal production also seems relevant. In particular, veterinarians and animal scientists may be important players in the new cell-based meat production, acting as proponents or barriers to this major improvement for farm animal welfare. Therefore, our aim is to analyse the knowledge and perspective of Brazilian veterinarians and animal scientists regarding cell-based meat. Veterinarians (76.8%; 209/272) and animal scientists (23.2%; 63/272) responded to an online survey. Logistic regression, latent class and logit models were used to evaluate objective answers, and the Discourse of the Collective Subject method was used to interpret open-ended answers. Specialists who were women (62.5%; 170/272), veterinarians (76.8%; 209/272), vegetarians (7.0%; 19/272) and vegans (1.1%; 3/272) were more supportive of cell-based meat. Lack of knowledge and the connection with artificiality, the most frequent spontaneous word associated with cell-based meat by all respondents, were the main negative points highlighted. Thus, it seems fundamental to offer higher education to veterinarians and animal scientists regarding cell-based meat, since engaging them with this novel technology may mitigate both the resistance and its negative consequences for the professionals, society, the animals involved and the environment.

Subclinical vascular alterations in young adults with type 1 diabetes detected by arterial tonometry.

BACKGROUND: Diabetes mellitus is characterized by a very high prevalence of atherosclerotic disease. Aims of this study were to determine arterial compliance parameters in type 1 diabetes (T1D) patients as an expression of early pre-clinical endothelial dysfunction and to evaluate the impact of glucose exposure parameters such as the duration of diabetes and glycosylated haemoglobin (HbA(1c)) on the risk of developing alterations in vascular compliance. METHODS: 23 patients with uncomplicated type 1 diabetes (mean age: 32.78 +/- 9.06 years, mean disease duration: 10.78 +/- 7.51 years, mean HbA(1c) levels: 7.7 +/- 1.9) and 26 age- and sex-matched healthy subjects (mean age: 32.3 +/- 8.51 years) were recruited. In these subjects, we evaluated arterial compliance by calibrated tonometry (HDI/Pulsewave() CR-2000). Parameters included the following: large artery elasticity (C1), small artery elasticity (C2), systemic vascular resistance (SVR) and total vascular impedance (TVI). RESULTS: Patients with longer duration of T1D (>10 years) showed significant alterations in C2 (4.97 +/- 2.7 mL/mmHg x 100) and in SVR (1464.67 +/- 169.16 dina x s x cm(-5)) when compared with both healthy individuals (C2: 8.28 +/- 2.67 mL/mmHg x 100, p = 0.001; SVR: 1180.58 +/- 151.55 dina x s x cm(-5), p = 0.01) and patients with recent-onset disease (

Ivabradine use in refractory unstable angina: a case report.

In this report, we describe the clinical results of ivabradine use in a patient with a serious form of unstable angina. For this patient, it was proposed that no other therapeutic, pharmacologic or surgical, option was available. The patient is a 75-year-old woman who presented with repeated episodes of retrosternal chest pain. She notably had a history of type II diabetes mellitus treated by insulin for several years and complicated by diabetic macro-angiopathy. ECG tracings recorded during these episodes showed abnormalities of the lateral repolarization phase of ischaemic nature. There was no measured increase in cardiac enzymes. She was transferred to our CCU with a diagnosis of unstable angina. In our CCU, the patient was treated with nitrates, metoprolol, aspirin, clopidogrel and atorvastatin at maximal sustainable doses. Following persistent clinical-instrumental instability, she was subjected to coronary angiography. This study revealed severe multi-vessel coronary artery disease not amenable to surgery or angioplasty revascularization. In addition to the therapy already provided, a beta-blocker (metoprolol 50 mgx2/die) and diltiazem (30 mgx2/die) were added despite their potentially dangerous and adverse chronotropic effects. Despite this treatment, the patients heart rate remained high (between 80 and 100 beats/min). This heart rate appeared to be the main driving cause of her anginal symptoms. At this point, the use of ivabradine seemed the only option, even though use would be off-label compared to current indications for the drugs use. We started with a low dose of 2.5 mg/b.i.d. and titrated up to 5 mg b.i.d. As we titrated, we witnessed a gradual reduction in heart rate. A consequent stabilization of her clinical pattern progressed into an almost unexpected asymptomatic state. After about a week of clinical observation, the patient recovered. After three months, she remains asymptomatic.

Polyphenols synergistically inhibit oxidative stress in subjects given red and white wine.

Aim of this study was to analyse the relationship between the plasma levels of polyphenols and the antioxidant activity of red and white wine. Twenty healthy subjects (HS) were randomly allocated to drink 300 ml of red (n = 10) or white n = 10 wine for 15 days. Ten HS who refrained from any alcohol beverage for 15 days were used as control. Urinary PGF-2alpha-III, a marker of oxidative stress and plasma levels of polyphenols were measured. Urinary PGF-2alpha-III significantly fell in subjects taking wine with a higher percentage decrease in subjects given red wine (-38.5 +/- 6%, p < 0.001) than in those given white wine (-23.1 +/- 6%). Subjects taking red wine had higher plasma polyphenols than those taking white wine (1.9 +/- 0.6 microM versus 1.5 +/- 0.33 microM, p < 0.001). Plasma polyphenols were inversely correlated with urinary PGF2alpha (r = 0.77, p < 0.001). No changes of urinary isoprostanes were observed in subjects who refrained from wine intake. In vitro study demonstrated that only a mixture of polyphenols, all in a range corresponding to that found in human circulation, inhibited LDL oxidation and PKC-mediated NADPH oxidase activation. Such inhibitory effects were more marked using the concentrations of polyphenols detected in human circulation after red wine intake. This study shows that red wine is more antioxidant than white wine in virtue of its higher content of polyphenols, an effect that may be dependent upon a synergism among polyphenols.

CREB engages C/EBPδ to initiate leukemogenesis.

cAMP response element binding protein (CREB) is frequently overexpressed in acute myeloid leukemia (AML) and acts as a proto-oncogene; however, it is still debated whether such overactivation alone is able to induce leukemia as its pathogenetic downstream signaling is still unclear. We generated a zebrafish model overexpressing CREB in the myeloid lineage, which showed an aberrant regulation of primitive hematopoiesis, and in 79% of adult CREB-zebrafish a block of myeloid differentiation, triggering to a monocytic leukemia akin the human counterpart. Gene expression analysis of CREB-zebrafish revealed a signature of 20 differentially expressed human homologous CREB targets in common with pediatric AML. Among them, we demonstrated that CREB overexpression increased CCAAT-enhancer-binding protein-δ (C/EBPδ) levels to cause myeloid differentiation arrest, and the silencing of CREB-C/EBPδ axis restored myeloid terminal differentiation. Then, C/EBPδ overexpression was found to identify a subset of pediatric AML affected by a block of myeloid differentiation at monocytic stage who presented a significant higher relapse risk and the enrichment of aggressive signatures. Finally, this study unveils the aberrant activation of CREB-C/EBPδ axis concurring to AML onset by disrupting the myeloid cell differentiation process. We provide a novel in vivo model to perform high-throughput drug screening for AML cure improvement.

Incremental prognostic value of post-stress left ventricular ejection fraction and volume by gated myocardial perfusion single photon emission computed tomography.

BACKGROUND: The incremental prognostic value of post-stress left ventricular ejection fraction (EF) and volume over perfusion has not been investigated. METHODS AND RESULTS: We identified 1680 consecutive patients who underwent rest Tl-201/stress Tc-99m sestamibi gated single photon emission computed tomography (SPECT) and who were followed-up for 569+/-106 days. Receiver-operator characteristics analysis defined an EF<45%, an end-systolic volume (ESV) >70 mL, and an end-diastolic volume >120 mL as optimal thresholds, yielding moderate sensitivity and high specificity in the prediction of cardiac death. Patients with an EF> or = 45% had mortality rates <1%/year, despite severe perfusion abnormalities, whereas patients with an EF<45% had high mortality rates, even with only mild/moderate perfusion abnormalities (9.2%/year; P<0.00001). Similarly, an ESV< or = 70 mL was related to a low cardiac death rate (<1.2%/year), even for patients with severe perfusion abnormalities, whereas patients with an ESV>70 mL and only mild/moderate perfusion abnormalities had high death rates (8.2%/year; P<0.00001). Patients with an EF<45% and an ESV< or = 70 mL had low cardiac death rates (1.7%/year); those with an EF<45% but an ESV>70 mL had high death rates (7.9%/year; P<0.02). Multivariate Cox proportional hazards regression showed that perfusion variables and ESV were independent predictors of overall coronary events, whereas EF and ESV demonstrated incremental prognostic values over prescan and perfusion information in predicting cardiac death and cardiac death or myocardial infarction. CONCLUSIONS: Post-stress EF and ESV by gated-SPECT have incremental prognostic values over prescan and perfusion information in predicting cardiac death, and they provide clinically useful risk stratification.

Incremental prognostic value of rest-redistribution (201)Tl single-photon emission computed tomography.

BACKGROUND: The incremental prognostic value of rest-redistribution (201)Tl compared with stress and rest perfusion abnormalities has not been defined. METHODS AND RESULTS: We identified 458 patients who underwent rest (201)Tl /stress (exercise or adenosine) (99m)Tc sestamibi single-photon emission computed tomography (SPECT) and had late (18 to 24 hours) (201)Tl imaging, were not revascularized within 60 days of SPECT, and were followed up at >1 year. SPECT images were visually analyzed with the use of a 20-segment model on a scale of 0 to 4. Thirty-seven cardiac deaths (CDs) and 17 nonfatal myocardial infarctions occurred. Univariate Cox proportional hazards analysis showed that the presence of a large amount of rest (201)Tl reversibility (rest-late summed difference score [SDS] of >8) was a significant predictor of CD (chi(2) = 5.77, P = 0.02) and CD or myocardial infarction (chi(2) = 5.3, P = 0.02). The CD rate was 9.3% y(-1) in patients with rest-late SDS of >8 compared with 3.6% y(-1) in patients with a mild/moderate amount of rest reversibility (rest-late SDS 3 to 8) and 3.4% y(-1) in patients with no rest reversibility (rest-late SDS <3) (P = 0.029). Kaplan-Meier survival analysis demonstrated significantly lower cumulative survival rates in patients with rest-late SDS of >8 (P = 0.01). Multivariate Cox proportional hazards analysis demonstrated that the presence of a large amount of resting reversibility was an independent and incremental predictor of CD after adjustment for stress and rest perfusion information. Multivariate logistic regression analysis demonstrated that resting reversibility was not an independent predictor of referral to coronary angiography and revascularization. CONCLUSIONS: The identification of a large amount of resting (201)Tl reversibility is an independent predictor of CD over stress and rest perfusion abnormalities.

Automatic quantitation of regional myocardial wall motion and thickening from gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: We developed an automatic quantitative algorithm for the measurement of regional myocardial wall motion and wall thickening from three-dimensional gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomographic images. BACKGROUND: The algorithm measures the motion of the three-dimensional endocardial surface using a modification of the centerline method, as well as wall thickening using both geometry (gaussian fit) and partial volume (counts). METHODS: The algorithm was tested using a "variable thickness" heart phantom, and the quantitative results were compared with visual segmental assessment of myocardial motion and thickening in 79 clinical patients with a wide range of ejection fractions (6% to 87%). RESULTS: Phantom measurements of simulated motion and thickening were accurate regardless of the camera used (dual or triple detector), the angular span of reconstructed data (180 degrees or 360 degrees), the amount of motion (3 or 6 mm) or the amount of thickening (33%, 50% or 100%). Quantitative measurements of segmental motion and thickening in the patients were correlated with visual scores (r = 0.668, exact agreement 72.6%, kappa 0.433 and r = 0.550, exact agreement 74.7%, kappa 0.408, respectively). Significant inverse linear relations exist between the global (summed) visual motion score and the average quantitative motion, and between the global (summed) visual thickening score and the average quantitative thickening. Automatic quantitative ejection fraction measurements correlated extremely well with average quantitative motion (r = 0.929) and thickening (r = 0.959). CONCLUSIONS: Our algorithm is accurate and may be the first automatic technique for the quantitative three-dimensional assessment of regional ventricular function in cardiology.

Gated technetium-99m sestamibi for simultaneous assessment of stress myocardial perfusion, postexercise regional ventricular function and myocardial viability. Correlation with echocardiography and rest thallium-201 scintigraphy.

OBJECTIVES: This study compares technetium-99m sestamibi (sestamibi) electrocardiographic (ECG) gated single-photon emission computed tomography (gated SPECT) and echocardiography for the evaluation of myocardial function and assesses the feasibility of single-injection, single-acquisition stress perfusion/rest function technetium-99m sestamibi-gated SPECT as an alternative to conventional stress/rest imaging for assessment of myocardial perfusion and viability. BACKGROUND: Simultaneous assessment of stress perfusion and rest function is possible with gated SPECT acquisition of stress-injected technetium-99m sestamibi. METHODS: Rest thallium-201 SPECT followed by stress sestamibi-gated SPECT (acquired 0.5 to 1 h after sestamibi injection) was performed in 58 patients. Echocardiography was performed immediately after or before gated SPECT in 43 of the patients. All studies were analyzed by semiquantitative visual scoring. Sestamibi-gated SPECT studies were read for stress perfusion and rest wall motion and thickening. Reversibility on sestamibi-gated SPECT was defined as the presence of a definite stress defect with normal or mildly impaired wall motion or thickening on gated SPECT: RESULTS: There was high segmental score agreement between gated SPECT and echocardiography for wall motion (91%, kappa = 0.68, p < 0.001) and thickening (90%, kappa = 0.62, p < 0.001). Correlation for global wall motion (r = 0.98, p < 0.001) and thickening (r = 0.96, p < 0.001) scores between the two modalities was excellent. In 32 patients without previous myocardial infarction, there was excellent agreement for reversibility between stress sestamibi-gated SPECT and rest thallium-201/stress sestamibi (98%, kappa = 0.93, p < 0.01). However, in 26 patients with previous infarction, discordance between the two approaches was frequent, with 26% (20 of 78) of nonreversible defects by stress sestamibi-gated SPECT being reversible by rest thallium-201/stress sestamibi and 21% (23 of 112) of reversible defects by stress sestamibi-gated SPECT being nonreversible by rest thallium-201/stress sestamibi. CONCLUSIONS: Gated SPECT of stress-injected sestamibi correlates well with echocardiographic assessment of regional function and thus adds information to perfusion SPECT: In patients without previous myocardial infarction, a single-injection stress perfusion/rest function approach using sestamibi-gated SPECT can substitute for conventional stress/rest myocardial perfusion imaging, adding a rest perfusion study only if there are nonreversible defects or consideration of attenuation artifacts. In patients with previous myocardial infarction, the gated SPECT approach does not replace the need for a rest perfusion study.

Separate acquisition rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion single-photon emission computed tomography: a clinical validation study.

OBJECTIVES: This study assessed the validity of a novel approach to myocardial perfusion scintigraphy that provides the opportunity to avoid the drawbacks of standard same-day rest/stress technetium-99m sestamibi myocardial perfusion studies by using separate-acquisition dual-isotope rest thallium-201 and exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT). BACKGROUND: Standard same-day rest/stress technetium-99m sestamibi myocardial perfusion studies are cumbersome, associated with a potential decrease in perceived stress defect severity compared with thallium-201 due to the presence of rest technetium-99m sestamibi and may be unable to differentiate hibernating from infarcted myocardium. METHODS: The dual-isotope procedure was performed in 63 patients without previous myocardial infarction undergoing coronary angiography to evaluate sensitivity and specificity for coronary artery disease and in 107 patients with a low (< 5%) likelihood of coronary artery disease to evaluate normalcy rate. To validate defect reversibility, the dual-isotope SPECT study was compared with stress/rest technetium-99m sestamibi SPECT studies in a separate group of 31 patients with previous documented myocardial infarction who underwent a rest technetium-99m sestamibi study in addition to the dual-isotope SPECT study. RESULTS: In angiographic correlations, dual-isotope SPECT demonstrated high sensitivity for detecting patients with > or = 50% stenosis (91%, 55 patients) and > or = 70% stenosis (96%, 52 patients). In a small group of patients, high specificity was also observed (75% for < 50% stenosis [8 patients] and 82% for < 70% stenosis [11 patients]). A very high normalcy rate of 95% was also found. In the patient group assessed for defect reversibility, in zones with no previous myocardial infarction, segmental agreement for defect type between rest thallium-201 and rest technetium-99m sestamibi studies was 97% (kappa = 0.79, p < 0.001). In myocardial infarct zones, segmental agreement for defect type was 98% (kappa = 0.93, p < 0.001). Image quality was generally good to excellent. CONCLUSIONS: Our findings demonstrate that separate-acquisition dual-isotope myocardial perfusion SPECT is accurate for coronary artery disease detection, correlates well with rest-stress sestamibi studies for assessment of defect reversibility and results in good to excellent image quality. This approach provides an excellent method for the combined assessment of stress myocardial perfusion and myocardial viability.

Identification of severe and extensive coronary artery disease by automatic measurement of transient ischemic dilation of the left ventricle in dual-isotope myocardial perfusion SPECT.

OBJECTIVES: This study sought to assess whether a transient ischemic dilation ratio, determined from automatically derived stress and rest left ventricular volumes during stress technetium-99m (Tc-99m) sestamibi/rest thallium-201 dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT), is useful for the identification of patients with severe and extensive coronary artery disease. BACKGROUND: Transient ischemic dilation of the left ventricle on stress/redistribution thallium-201 scintigraphy has been shown to be a clinically useful marker of severe and extensive coronary artery disease. However, in practice, its assessment is highly subjective. This study automatically assessed the transient ischemic dilation ratio on the basis of a previously described algorithm to estimate three-dimensional ventricular boundaries. METHODS: Normal limits for the transient ischemic dilation ratio were developed using data from 54 patients with a low likelihood (< 5%) of coronary artery disease, and criteria for abnormality were developed based on data from 97 who under-went catheterization, of whom 34 had severe and extensive coronary artery disease, defined as > or = 90% stenosis in the proximal left anterior descending coronary artery or in two or more coronary arteries, and 63 had no coronary artery disease (15 patients) or mild to moderate coronary artery disease (48 patients). The criteria were then tested in a validation cohort of 77 additional patients who underwent catheterization, of whom 36 had severe and extensive coronary artery disease. The quantitative results of the dilation ratio were compared with the visual results of the dilation ratio and perfusion defect analysis. RESULTS: For normal limits, receiver operating characteristic curve analysis showed that abnormal transient ischemic dilation ratio values corresponded to left ventricular endocardial volume ratios > 1.22 (mean +/- 2 SD). Transient ischemic dilation assessment using these criteria for abnormality showed high sensitivity (24 [71%] of 34) and very high specificity (60 [95%] of 63) for severe and extensive coronary artery disease. When the analysis was applied to the prospective catheterization group, similar sensitivity and specificity for severe and extensive coronary artery disease were observed (77% and 92%, respectively). Significant agreement (p = 0.0001) was found between the degree of transient ischemic dilation and the Tc-99m sestamibi defect extent, the latter assessed by semiquantitative visual analysis (summed stress score). CONCLUSIONS: The automatic measurement of transient ischemic dilation in dual-isotope myocardial perfusion SPECT is a clinically useful marker that is sensitive and highly specific for detection of severe and extensive coronary artery disease.

When to stress patients after coronary artery bypass surgery? Risk stratification in patients early and late post-CABG using stress myocardial perfusion SPECT: implications of appropriate clinical strategies.

OBJECTIVES: The study compared the prognostic significance of myocardial perfusion single-photon emission computed tomography (SPECT) (MPS) in patients early and late after coronary artery bypass graft surgery (CABG). BACKGROUND: The long-term effectiveness of CABG is limited by graft stenosis. The greatest incidence of graft occlusion occurs between five and eight years after surgery. However, little is known regarding the appropriate time to stress patients post-CABG with respect to risk stratification. METHODS: We identified 1,765 patients, who underwent MPS 7.1 +/- 5.0 years post-CABG. All patients underwent rest T1-201/stress Tc-99m sestamibi MPS and were followed up > or =1 year after testing. Patients with early CABG or PTCA (<60 days after MPS) were censored. The prognostic population consisted of 1,544 patients. A semiquantitative visual analysis employing a 20-segment model was used to define summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), and the number of nonreversible segments (NRS). RESULTS: During follow-up, 53 cardiac deaths (CD) occurred. There was a significant increase in annual CD rates as a function of SSS. A multivariate analysis identified age, ischemia (SDS), and infarct size (NRS) as independent predictors of CD. Nuclear variables added incremental value to prescan information. The annual CD rate was relatively low (1.3%) in patients < or =5 years post-CABG. In this subgroup only age and infarct size (NRS) were predictive of CD. CONCLUSION: MPS is strongly predictive of subsequent CD in post-CABG patients and adds incremental value over clinical and treadmill test information. Our data suggest that symptomatic patients < or =5 years and all patients >5 years post-CABG may benefit from testing.

Gender-related differences in clinical management after exercise nuclear testing.

OBJECTIVES: This study sought to determine the rate of referral to cardiac catheterization in men and women early after nuclear testing as a function of the magnitude of myocardial ischemia by radionuclide perfusion imaging. BACKGROUND: Although many previous studies have suggested that gender-related differences are present in the clinical management of coronary artery disease, the presence of such a difference with respect to referral to catheterization after noninvasive testing is disputed. METHODS: We examined 3,211 consecutive patients (1,074 women, 2,137 men) who underwent exercise dual-isotope single-photon emission computed tomography and had follow-up evaluation performed at least 1 year after nuclear testing (mean [+/- SD] follow-up 19 +/- 5 months) for "hard" events (cardiac death and myocardial infarction) and referral to cardiac catheterization or revascularization within 60 days of nuclear testing. Multiple logistic regression analysis was performed to determine the best predictors of referral to catheterization as well as to examine whether gender itself added further information to this model. RESULTS: Although men were referred to catheterization more frequently than women (10.6% vs 7.1%, p < 0.001) early after exercise nuclear testing, there were no differences in the rate of referral to catheterization or revascularization after stratification by the amount of abnormally perfused myocardium detected by the nuclear scan. Both men and women with normal scan results were infrequently referred to subsequent catheterization. In the setting of severe ischemia, women were referred to catheterization more frequently than men. This higher rate appears to be clinically appropriate because women with severely abnormal scan results had a significantly higher event rate than men (17.5% vs. 6.3%, p < 0.0001). This greater risk in women than in men appeared to be underappreciated because the increased rate of hard events in women with severely abnormal scan results was out of proportion to the smaller increase in their rate of referral to cardiac catheterization. Although gender added information to the multivariate model most predictive of referral to catheterization models when nuclear variables were not included, when nuclear variables were considered, the addition of gender added no further significant information. This finding suggests that adjusting for differences in perfusion scan abnormalities by the use of nuclear testing eliminated the apparent gender-related referral bias. CONCLUSIONS: After controlling for differences in perfusion scan abnormalities, no gender-related referral bias to catheterization was present. In the setting of severe ischemia, women had a greater rate referral to catheterization than men. As a function of risk, both men and women were appropriately referred to catheterization at a low rate when the scan result was normal. However, because women with severe perfusion abnormalities had a greater rate of cardiac death and myocardial infarction then men, women in this high risk subgroup were underreferred to catheterization relative to men. This finding points to the need to better identify women at high cardiac risk.

Incremental value of prognostic testing in patients with known or suspected ischemic heart disease: a basis for optimal utilization of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: This study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cost implications. BACKGROUND: The prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored. METHODS: We studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered "hard" events, and coronary angioplasty and bypass surgery > 60 days after testing were considered "soft" events. RESULTS: Of the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost-effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre-ETT likelihood of coronary artery disease. CONCLUSIONS: Normal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.