Expansion of immature, nucleated red blood cells by transient low-dose methotrexate immune tolerance induction in mice.

Biological treatments such as enzyme-replacement therapies (ERT) can generate anti-drug antibodies (ADA), which may reduce drug efficacy and impact patient safety and consequently led to research to mitigate ADA responses. Transient low-dose methotrexate (TLD-MTX) as a prophylactic ITI regimen, when administered concurrently with ERT, induces long-lived reduction of ADA to recombinant human alglucosidase alfa (rhGAA) in mice. In current clinical practice, a prophylactic ITI protocol that includes TLD-MTX, rituximab and intravenous immunoglobulin (optional), successfully induced lasting control of ADA to rhGAA in high-risk, cross-reactive immunological material (CRIM)-negative infantile-onset Pompe disease (IOPD) patients. More recently, evaluation of TLD-MTX demonstrated benefit in CRIM-positive IOPD patients. To more clearly understand the mechanism for the effectiveness of TLD-MTX, non-targeted transcriptional and proteomic screens were conducted and revealed up-regulation of erythropoiesis signatures. Confirmatory studies showed transiently larger spleens by weight, increased spleen cellularity and that following an initial reduction of mature red blood cells (RBCs) in the bone marrow and blood, a significant expansion of Ter-119+ CD71+ immature RBCs was observed in spleen and blood of mice. Histology sections revealed increased nucleated cells, including hematopoietic precursors, in the splenic red pulp of these mice. This study demonstrated that TLD-MTX induced a transient reduction of mature RBCs in the blood and immature RBCs in the bone marrow followed by significant enrichment of immature, nucleated RBCs in the spleen and blood during the time of immune tolerance induction, which suggested modulation of erythropoiesis may be associated with the induction of immune tolerance to rhGAA.

Alpha galactosidase A activity in Parkinson's disease.

Glucocerebrosidase (GCase, deficient in Gaucher disease) enzymatic activity measured in dried blood spots of Parkinson's Disease (PD) cases is within healthy range but reduced compared to controls. It is not known whether activities of additional lysosomal enzymes are reduced in dried blood spots in PD. To test whether reduction in lysosomal enzymatic activity in PD is specific to GCase, we measured GCase, acid sphingomyelinase (deficient in Niemann-Pick disease types A and B), alpha galactosidase A (deficient in Fabry), acid alpha-glucosidase (deficient in Pompe) and galactosylceramidase (deficient in Krabbe) enzymatic activities in dried blood spots of PD patients (n = 648) and controls (n = 317) recruited from Columbia University. Full sequencing of glucocerebrosidase (GBA) and the LRRK2 G2019S mutation was performed. Enzymatic activities were compared between PD cases and controls using t-test and regression models adjusted for age, gender, and GBA and LRRK2 G2019S mutation status. Alpha galactosidase A activity was lower in PD cases compared to controls both when only non-carriers were included (excluding all GBA and LRRK2 G2019S carriers and PD cases with age-at-onset below 40) [2.85 µmol/l/h versus 3.12 µmol/l/h, p = 0.018; after controlling for batch effect, p = 0.006 (468 PD cases and 296 controls)], and when including the entire cohort (2.89 µmol/l/h versus 3.10 µmol/l/h, p = 0.040; after controlling for batch effect, p = 0.011). Because the alpha galactosidase A gene is X-linked, we stratified the analyses by sex. Among women who were non-carriers of GBA and LRRK2 G2019S mutations (PD, n = 155; control, n = 194), alpha galactosidase A activity was lower in PD compared to controls (2.77 µmol/l/h versus 3.10 µmol/l/h, p = 0.044; after controlling for a batch effect, p = 0.001). The enzymatic activity of acid sphingomyelinase, acid alpha-glucosidase and galactosylceramidase was not significantly different between PD and controls. In non-carriers, most lysosomal enzyme activities were correlated, with the strongest association in GCase, acid alpha-glucosidase, and alpha galactosidase A (Pearson correlation coefficient between 0.382 and 0.532). In a regression model with all five enzymes among non-carriers (adjusted for sex and age), higher alpha galactosidase A activity was associated with lower odds of PD status (OR = 0.54; 95% CI:0.31-0.95; p = 0.032). When LRRK2 G2019S PD carriers (n = 37) were compared to non-carriers with PD, carriers had higher GCase, acid sphingomyelinase and alpha galactosidase A activity. We conclude that alpha galactosidase A may have a potential independent role in PD, in addition to GCase.

New TRAP1 and Hsp90 chaperone inhibitors with cationic components: Preliminary studies on mitochondrial targeting.

TRAP1 (Hsp75) is the mitochondrial paralog of the Hsp90 molecular chaperone family. Due to structural similarity among Hsp90 chaperones, a potential strategy to induce apoptosis through mitochondrial TRAP1 ATPase inhibition has been envisaged and a series of compounds has been developed by binding the simple pharmacophoric core of known Hsp90 inhibitors with various appendages bearing a permanent cationic head, or a basic group highly ionizable at physiologic pH. Cationic appendages were selected as vehicles to deliver drugs to mitochondria. Indeed, masses of new derivatives were evidenced to accumulate in the mitochondrial fraction from colon carcinoma cells and a compound in the series, with a guanidine appendage, demonstrated good activity in inhibiting recombinant TRAP1 ATPase and cell growth and in inducing apoptotic cell death in colon carcinoma cells.

Cisplatin plus paclitaxel and maintenance of bevacizumab on tumour progression, dissemination, and survival of ovarian carcinoma xenograft models.

BACKGROUND: Bevacizumab is being incorporated as first-line therapy with standard-of-care chemotherapy on epithelial ovarian carcinoma (EOC). We investigated bevacizumab combined with chemotherapy on tumour progression and mouse survival in EOC xenograft models. METHODS: Bevacizumab was administered concomitantly with cisplatin plus paclitaxel (DDP+PTX), continued after induction (maintenance) or started after chemotherapy. The effect on tumour progression was monitored by bioluminescence imaging (BLI) (1A9-luc xenograft). Tumour dissemination into the peritoneal organs and ascites formation (HOC22 xenograft) was evaluated by histological analysis at the end of treatment (interim) and at euthanasia (survival). The effects on overall survival (OS) were investigated in both EOC models. RESULTS: Bevacizumab with PTX+DDP delayed tumour progression in mice bearing EOC xenografts. OS was significantly extended, with complete responses, by bevacizumab continued after stopping chemotherapy in the HOC22 xenograft. Bevacizumab alone inhibited ascites formation, with only limited effect on tumour burden, but combined with PTX+DDP reduced ascites and metastases. Bevacizumab started after induction with PTX+DDP and maintained was equally effective on tumour progression and survival on 1A9-luc xenograft. CONCLUSION: Bevacizumab combined with chemotherapy not only affected tumour progression, but when administered as maintenance regimen significantly prolonged survival, reducing ascites, and tumour dissemination. We believe our findings are consistent with the clinical results and shed light on the potential effects of this kind of treatment on tumour progression.

Optimization of a customized simultaneous algebraic reconstruction technique algorithm for phase-contrast breast computed tomography.

Objective.To introduce the optimization of a customized GPU-based simultaneous algebraic reconstruction technique (cSART) in the field of phase-contrast breast computed tomography (bCT). The presented algorithm features a 3D bilateral regularization filter that can be tuned to yield optimal performance for clinical image visualization and tissues segmentation.Approach.Acquisitions of a dedicated test object and a breast specimen were performed at Elettra, the Italian synchrotron radiation (SR) facility (Trieste, Italy) using a large area CdTe single-photon counting detector. Tomographic images were obtained at 5 mGy of mean glandular dose, with a 32 keV monochromatic x-ray beam in the free-space propagation mode. Three independent algorithms parameters were optimized by using contrast-to-noise ratio (CNR), spatial resolution, and noise texture metrics. The results obtained with the cSART algorithm were compared with conventional SART and filtered back projection (FBP) reconstructions. Image segmentation was performed both with gray scale-based and supervised machine-learning approaches.Main results.Compared to conventional FBP reconstructions, results indicate that the proposed algorithm can yield images with a higher CNR (by 35% or more), retaining a high spatial resolution while preserving their textural properties. Alternatively, at the cost of an increased image 'patchiness', the cSART can be tuned to achieve a high-quality tissue segmentation, suggesting the possibility of performing an accurate glandularity estimation potentially of use in the realization of realistic 3D breast models starting from low radiation dose images.Significance.The study indicates that dedicated iterative reconstruction techniques could provide significant advantages in phase-contrast bCT imaging. The proposed algorithm offers great flexibility in terms of image reconstruction optimization, either toward diagnostic evaluation or image segmentation.

Quantitative phase retrieval with picosecond X-ray pulses from the ATF Inverse Compton Scattering source.

Quantitative phase retrieval is experimentally demonstrated using the Inverse Compton Scattering X-ray source available at the Accelerator Test Facility (ATF) in the Brookhaven National Laboratory. Phase-contrast images are collected using in-line geometry, with a single X-ray pulse of approximate duration of one picosecond. The projected thickness of homogeneous samples of various polymers is recovered quantitatively from the time-averaged intensity of transmitted X-rays. The data are in good agreement with the expectations showing that ATF Inverse Compton Scattering source is suitable for performing phase-sensitive quantitative X-ray imaging on the picosecond scale. The method shows promise for quantitative imaging of fast dynamic phenomena.

Relevance of biofilms in pediatric tonsillar disease.

In this investigation, we study the relation between chronic inflammation of the tonsils, clinical features, and the presence of biofilms in the crypts in patients presenting with obstructive hypertrophy and recurrent upper airway pathology. Thirty-six patients who needed to undergo a tonsillectomy for obstructive reasons (aged 1 to 6 years), among which none of them had taken any antibiotics 30 days prior to surgery, were included. Samples were examined with hematoxylin-eosin and Gram staining, fluorescent microscopy, and confocal laser microscopy. The predominance of symptoms were those related to obstructive pathology rather than infection (p < 0.01). All patients had tonsillar hypertrophy (grade III or IV), but an association with adenoids hypertrophy was detected in 66.66% of cases (p < 0.05). 77.28% of tonsils presented biofilms in their crypts, but hypertrophy and tonsillar follicle number were not related to the presence or absence of biofilms. Here, we demonstrated that symptoms like harsh raucous sound, tonsillar and adenoids hypertrophy, apnea, and cervical adenopathies are clearly related to the presence of biofilm in tonsils. Our results allow us to propose that biofilms are involved in the pathogenesis of tonsils and adenoids hypertrophy. The prevention of biofilms formation should be focused in the early stages, attempting to restrain bacterial attachment to the respiratory mucosa.

Compact x-ray sources for mammographic applications: Monte Carlo simulations of image quality.

Thomson scattering x-ray sources can provide spectral distributions that are ideally suited for mammography with sufficient fluence rates. In this article, the authors investigate the effects of different spectral distributions on the image quality in simulated images of a breast mammographic phantom containing details of different compositions and thicknesses. They simulated monochromatic, quasimonochromatic, and polychromatic x-ray sources in order to define the energy for maximum figure of merit (signal-difference-to-noise ratio squared/mean glandular dose), the effect of an energy spread, and the effect of the presence of higher-order harmonics. The advantages of these sources with respect to conventional polychromatic sources as a function of phantom and detail thickness were also investigated. The results show that the energy for the figure of merit peak is between 16 and 27.4 keV, depending on the phantom thickness and detail composition and thickness. An energy spread of about 1 keV standard deviation, easily achievable with compact x-ray sources, does not appreciably affect the image quality.

Involvement of the beta-adrenergic system in the cardiac chronic form of experimental Trypanosoma cruzi infection.

Changes in the cardiac beta-adrenergic system in early stages of Trypanosoma cruzi infection have been described. Here, we studied an early (135 days post-infection-p.i.) and a late stage (365 days p.i.) of the cardiac chronic form of the experimental infection (Tulahuen or SGO-Z12 strains), determining plasma epinephrine and norepinephrine levels, beta-receptor density, affinity and function, cardiac cAMP concentration and phosphodiesterase activity, cardiac contractility, and the presence of beta-receptor autoantibodies. Tulahuen-infected mice presented lower epinephrine and norepinephrine levels; lower beta-receptor affinity and density; a diminished norepinephrine response and higher cAMP levels in the early stage, and a basal contractility similar to non-infected controls in the early and augmented in the late stage. The Tulahuen strain induced autoantibodies with weak beta-receptor interaction. SGO-Z12-infected mice presented lower norepinephrine levels and epinephrine levels that diminished with the evolution of the infection; lower beta-receptor affinity and an increased density; unchanged epinephrine and norepinephrine response in the early and a diminished response in the late stage; higher cAMP levels and unchanged basal contractility. The SGO-Z12 isolate induced beta-receptor autoantibodies with strong interaction with the beta-receptors. None of the antibodies, however, acted a as beta-receptor agonist. The present results demonstrate that this system is seriously compromised in the cardiac chronic stage of T. cruzi infection.

Evaluation of the intra- and inter-method agreement of brain MRI segmentation software packages: A comparison between SPM12 and FreeSurfer v6.0.

PURPOSE: The lack of inter-method agreement can produce inconsistent results in neuroimaging studies. We evaluated the intra-method repeatability and the inter-method reproducibility of two widely-used automatic segmentation methods for brain MRI: the FreeSurfer (FS) and the Statistical Parametric Mapping (SPM) software packages. METHODS: We segmented the gray matter (GM), the white matter (WM) and subcortical structures in test-retest MRI data of healthy volunteers from Kirby-21 and OASIS datasets. We used Pearson's correlation (r), Bland-Altman plot and Dice index to study intra-method repeatability and inter-method reproducibility. In order to test whether different processing methods affect the results of a neuroimaging-based group study, we carried out a statistical comparison between male and female volume measures. RESULTS: A high correlation was found between test-retest volume measures for both SPM (r in the 0.98-0.99 range) and FS (r in the 0.95-0.99 range). A non-null bias between test-retest FS volumes was detected for GM and WM in the OASIS dataset. The inter-method reproducibility analysis measured volume correlation values in the 0.72-0.98 range and the overlap between the segmented structures assessed by the Dice index was in the 0.76-0.83 range. SPM systematically provided significantly greater GM volumes and lower WM and subcortical volumes with respect to FS. In the male vs. female brain volume comparisons, inconsistencies arose for the OASIS dataset, where the gender-related differences appear subtler with respect to the Kirby dataset. CONCLUSIONS: The inter-method reproducibility should be evaluated before interpreting the results of neuroimaging studies.

Trypanosoma cruzi: Cardiac mitochondrial alterations produced by different strains in the acute phase of the infection.

The parasite Trypanosoma cruzi is the causative agent of Chagas disease. T. cruzi invasion and replication in cardiomyocytes induce cellular injuries and cytotoxic reactions, with the production of inflammatory cytokines and nitric oxide, both source of reactive oxygen species. The myocyte response to oxidative stress involves the progression of cellular changes primarily targeting mitochondria. We studied the cardiac mitochondrial structure and the enzymatic activity of citrate synthase and respiratory chain CI-CIV complexes, in Albino Swiss mice infected with T. cruzi, Tulahuen strain and SGO Z12 isolate, in two periods of the acute infection. Changes in the mitochondrial structure were detected in both infected groups, reaching values of 71% for Tulahuen and 88% for SGO Z12 infected mice, 30 days post infection. The citrate synthase activity was different according to the evolution of the infection and the parasite strain, but the respiratory chain alterations were similar with either strain.

Comparison of two portable solid state detectors with an improved collimation and alignment device for mammographic x-ray spectroscopy.

We describe a portable system for mammographic x-ray spectroscopy, based on a 2 X 2 X 1 mm3 cadmium telluride (CdTe) solid state detector, that is greatly improved over a similar system based on a 3 X 3 X 2 mm3 cadmium zinc telluride (CZT) solid state detector evaluated in an earlier work. The CdTe system utilized new pinhole collimators and an alignment device that facilitated measurement of mammographic x-ray spectra. Mammographic x-ray spectra acquired by each system were comparable. Half value layer measurements obtained using an ion chamber agreed closely with those derived from the x-ray spectra measured by either detector. The faster electronics and other features of the CdTe detector allowed its use with a larger pinhole collimator than could be used with the CZT detector. Additionally, the improved pinhole collimator and alignment features of the apparatus permitted much more rapid setup for acquisition of x-ray spectra than was possible on the system described in the earlier work. These improvements in detector technology, collimation and ease of alignment, as well as low cost, make this apparatus attractive as a tool for both laboratory research and advanced mammography quality control.

A completely automated CAD system for mass detection in a large mammographic database.

Mass localization plays a crucial role in computer-aided detection (CAD) systems for the classification of suspicious regions in mammograms. In this article we present a completely automated classification system for the detection of masses in digitized mammographic images. The tool system we discuss consists in three processing levels: (a) Image segmentation for the localization of regions of interest (ROIs). This step relies on an iterative dynamical threshold algorithm able to select iso-intensity closed contours around gray level maxima of the mammogram. (b) ROI characterization by means of textural features computed from the gray tone spatial dependence matrix (GTSDM), containing second-order spatial statistics information on the pixel gray level intensity. As the images under study were recorded in different centers and with different machine settings, eight GTSDM features were selected so as to be invariant under monotonic transformation. In this way, the images do not need to be normalized, as the adopted features depend on the texture only, rather than on the gray tone levels, too. (c) ROI classification by means of a neural network, with supervision provided by the radiologist's diagnosis. The CAD system was evaluated on a large database of 3369 mammographic images [2307 negative, 1062 pathological (or positive), containing at least one confirmed mass, as diagnosed by an expert radiologist]. To assess the performance of the system, receiver operating characteristic (ROC) and free-response ROC analysis were employed. The area under the ROC curve was found to be Az = 0.783 +/- 0.008 for the ROI-based classification. When evaluating the accuracy of the CAD against the radiologist-drawn boundaries, 4.23 false positives per image are found at 80% of mass sensitivity.

Incidence and risk factors of superficial and deep vein thrombosis associated with peripherally inserted central catheters in children.

Essentials Pediatric studies on peripherally inserted central catheter (PICC)-related thrombosis are scarce. This study analyzes incidence and risk factors for PICC-related venous thrombosis in children. PICC-related thrombosis is a common, and nearly always, asymptomatic complication. Echo-guided insertion and a catheter to vein ratio < 0.33 may notably decrease this complication. SUMMARY: Background Upper-extremity venous thrombosis is associated with the use of peripherally inserted central catheters (PICCs). Few pediatric studies have focused on this issue. Objectives To determine the incidence and risk factors for PICC-related superficial vein thrombosis (SVT) and deep vein thrombosis (DVT) in children. Patients/methods An observational follow-up cohort study was conducted at a single hospital between June 2012 and June 2015. All patients receiving a PICC were enrolled and followed up, with weekly Doppler ultrasound examination of the catheterized limb until PICC removal. Patient, procedural and follow-up data were analyzed. Results In the study period, 265 PICCs were inserted (median age of patients 6.5 years, interquartile range [IQR] 2.4-13 years; median weight 20 kg, IQR 11-38 kg; 54% males; 67.9% chronically ill), and patients were followed up for a total of 9743 days. The median indwelling time was 21 days (IQR 12-37 days). During follow-up, 88 (33.2% of insertions) PICC-related thromboses (incidence rate [IR] 9.03 per 1000 catheter-days) were diagnosed, 66 (24.9%) as isolated SVT, seven (2.6%) as isolated DVT, and 15 (5.7%) as SVT with associated DVT (IR 6.78, 0.71 and 1.54 per 1000 catheter-days, respectively). Only 9.9% of patients with SVT and 18.2% of those with DVT were symptomatic. The main risk factors for PICC-related SVT and DVT were a catheter/vein ratio of > 0.33 and thrombosis of the catheterized superficial vein, respectively. Conclusions PICC-related thrombosis is a common and nearly always asymptomatic complication in children, the SVT rate being approximately three times higher than the DVT rate. Optimal vein and catheter selection, yielding the lowest possible catheter/vein ratio, may decrease the rate of PICC-related thrombosis.

Imaging performance of phase-contrast breast computed tomography with synchrotron radiation and a CdTe photon-counting detector.

PURPOSE: Within the SYRMA-CT collaboration based at the ELETTRA synchrotron radiation (SR) facility the authors investigated the imaging performance of the phase-contrast computed tomography (CT) system dedicated to monochromatic in vivo 3D imaging of the female breast, for breast cancer diagnosis. METHODS: Test objects were imaged at 38keV using monochromatic SR and a high-resolution CdTe photon-counting detector. Signal and noise performance were evaluated using modulation transfer function (MTF) and noise power spectrum. The analysis was performed on the images obtained with the application of a phase retrieval algorithm as well as on those obtained without phase retrieval. The contrast to noise ratio (CNR) and the capability of detecting test microcalcification clusters and soft masses were investigated. RESULTS: For a voxel size of (60µm)(3), images without phase retrieval showed higher spatial resolution (6.7mm(-1) at 10% MTF) than corresponding images with phase retrieval (2.5mm(-1)). Phase retrieval produced a reduction of the noise level and an increase of the CNR by more than one order of magnitude, compared to raw phase-contrast images. Microcalcifications with a diameter down to 130µm could be detected in both types of images. CONCLUSIONS: The investigation on test objects indicates that breast CT with a monochromatic SR source is technically feasible in terms of spatial resolution, image noise and contrast, for in vivo 3D imaging with a dose comparable to that of two-view mammography. Images obtained with the phase retrieval algorithm showed the best performance in the trade-off between spatial resolution and image noise.

Opportunities to improve antimicrobial use in paediatric intensive care units: a nationwide survey in Spain.

Improving antimicrobial use is a complex process that requires an accurate assessment of ongoing problems and barriers. Paediatric intensive care units (PICU) have seldom been assessed from this perspective. Two Internet-based, self-administered surveys were conducted nationwide in Spain between January and February 2014. The first survey aimed to assess those characteristics of Spanish PICUs that could influence antimicrobial prescribing or antimicrobial stewardship. The second survey targeted Spanish PICU physicians and pursued to assess their attitudes and perceptions regarding antimicrobial resistance and antimicrobial use. Information about 29/39 contacted PICUs was obtained. A total of 114/206 (55.3%) paediatric intensivists responded. PICUs were heterogeneous regarding years since foundation, number of beds, type of patients admitted and staffing. Only 11 (37.9%) PICUs had available e-prescribing systems. Procalcitonin was available in 24 (89.1%) PICUs, but there were no procalcitonin-based protocols in 14 (60.9%) of them. Half of surveyed PICUs had implemented antimicrobial stewardship activities. Ninety-eight of the 114 PICU physicians (86%) who participated considered that antimicrobial resistance was a significantly relevant problem for their daily and that improving antimicrobial use in their PICU should be a priority (103; 90.4%). The main perceived problems regarding antimicrobial use were the excessive use of antimicrobials in patients with nonconfirmed infections and excessive use of broad-spectrum antimicrobials. The most valued antimicrobial stewardship interventions were the implementation of protocols to guide antimicrobial therapy. Spanish PICU doctors are aware of the relevance of the problem of antimicrobial resistance and the need to improve antimicrobial use. Targeted interventions should take into account their difficulties and preferences when feasible.

Towards breast tomography with synchrotron radiation at Elettra: first images.

The aim of the SYRMA-CT collaboration is to set-up the first clinical trial of phase-contrast breast CT with synchrotron radiation (SR). In order to combine high image quality and low delivered dose a number of innovative elements are merged: a CdTe single photon counting detector, state-of-the-art CT reconstruction and phase retrieval algorithms. To facilitate an accurate exam optimization, a Monte Carlo model was developed for dose calculation using GEANT4. In this study, high isotropic spatial resolution (120 µm)(3) CT scans of objects with dimensions and attenuation similar to a human breast were acquired, delivering mean glandular doses in the range of those delivered in clinical breast CT (5-25 mGy). Due to the spatial coherence of the SR beam and the long distance between sample and detector, the images contain, not only absorption, but also phase information from the samples. The application of a phase-retrieval procedure increases the contrast-to-noise ratio of the tomographic images, while the contrast remains almost constant. After applying the simultaneous algebraic reconstruction technique to low-dose phase-retrieved data sets (about 5 mGy) with a reduced number of projections, the spatial resolution was found to be equal to filtered back projection utilizing a four fold higher dose, while the contrast-to-noise ratio was reduced by 30%. These first results indicate the feasibility of clinical breast CT with SR.

Cardiac rupture, a clinically predictable complication of acute myocardial infarction: report of 70 cases with clinicopathologic correlations.

OBJECTIVE: To test the hypothesis that certain clinical events may precede free wall myocardial rupture and allow its prediction, we conducted a retrospective and prospective study of 70 patients with rupture. BACKGROUND: Rupture of the left ventricular free wall develops in approximately 10% of patients with fatal acute transmural myocardial infarction. Clinically, its occurrence has been considered precipitous and unexpected. Pathologically, however, rupture appears to be a stuttering, progressive process characterized in many instances by an infiltrating intramural hemorrhage and a thrombus within the tear of > or = 1 day's duration. METHODS: The clinical course and evolutionary electrocardiographic (ECG) changes in 70 consecutive patients with rupture and 100 comparison patients with acute myocardial infarction but without rupture were reviewed to ascertain whether certain clinical symptoms, signs and ECG alterations occur in patients prone to develop rupture, allowing its anticipation. In addition, a correlation was established between the site of infarction indicated by the ECG and the site of rupture determined at autopsy or surgery. RESULTS: Patients with rupture had a significantly greater incidence of pericarditis, repetitive emesis and restlessness and agitation than did patients without rupture. More than 80% of patients with rupture had two or more symptoms compared with 3% of patients without rupture (p < 0.002). A deviation from the expected evolutionary T wave pattern occurred in 94% of patients with rupture and 34% of control patients (p < or = 0.02). An abrupt transient episode of hypotension and bradycardia, probably due to the initial tearing of the epicardium with a resultant small hemopericardium, was observed in 21% of patients with rupture. Rupture of the midlateral wall was most common (32%) and usually occurred in the setting of an inferoposterolateral infarction related to an acute left circumflex artery occlusion. On the basis of these clinical and ECG changes, rupture was confirmed by echocardiography and pericardiocentesis in the two most recent patients, and the defect was successfully repaired. CONCLUSIONS: Rupture is often preceded by particular symptoms, signs--namely, one or more episodes of abrupt, transient hypotension and bradycardia and unexpected alterations of the T waves, especially directional changes of the latter. Patients displaying these symptoms, signs and ECG changes require a bedside echocardiogram and echocardiographically guided pericardiocentesis if fluid is visualized. If the pericardiocentesis identifies the fluid as blood, immediate surgery is indicated.

T wave changes consistent with epicardial involvement in acute myocardial infarction. Observations in patients with a postinfarction pericardial effusion without clinically recognized postinfarction pericarditis.

OBJECTIVES: This study was designed to evaluate the presence or absence of atypical T wave evolution in patients with a postinfarction pericardial effusion but without clinically recognized postinfarction pericarditis. A second purpose was to evaluate the frequency of atypical T wave evolution in a previous study of postinfarction pericarditis. BACKGROUND: Electrocardiographic (ECG) criteria involving the evolution of the T wave after an acute myocardial infarction were recently described in patients with regional postinfarction pericarditis. Atypical T wave evolution was found to have a sensitivity of 100% and a specificity of 77% for clinically recognized regional postinfarction pericarditis with or without a pericardial effusion. METHODS: The hospital records and serial ECGs of 20 patients with clinically recognized postinfarction pericarditis (Group I) were reviewed. The records and serial ECGs of 20 additional patients with a postinfarction pericardial effusion without clinically recognized postinfarction pericarditis (Group II) were also examined. The type of postinfarction T wave pattern, typical or atypical, was recorded in both groups. RESULTS: All 20 patients in Group I had atypical T wave evolution. Among the 20 patients in Group II, every patient also had atypical T wave evolution. Fifteen percent of all 40 patients with atypical T wave evolution had a non-Q wave infarction with definite or inferred postinfarction pericarditis. CONCLUSIONS: The high sensitivity of atypical T wave evolution in diagnosing regional postinfarction pericarditis was confirmed. However, similar T wave alterations were also observed when a postinfarction pericardial effusion existed in the absence of clinically recognized pericarditis. Fifteen percent of patients with atypical T wave evolution had a non-Q wave infarction with definite or inferred pericardial involvement. Thus, the presence of atypical T wave evolution may be a more sensitive indicator of a transmural infarction than the development of a Q wave.