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Introduction: The coronavirus disease 2019 (COVID-19) pandemic has increased the use of technology for communication including departmental conferences, working remotely, and distance teaching. Methods to enable these activities should be developed and promulgated. Objective: To repurpose a preexisting educational website to enable the development of a COVID-19 autopsy biorepository to support distance teaching and COVID-19 research. Methods: After consent was obtained, autopsies were performed on patients with a confirmed positive severe acute respiratory syndrome coronavirus-2 reverse-transcriptase-polymerase-chain reaction test. Autopsies were performed according to a COVID-19 protocol, and all patients underwent both gross and microscopic examination. The H and E histology slides were scanned using a Leica Biosystems Aperio CS ScanScope whole slide scanner and the digital slide files were converted to deep zoom images that could be uploaded to the University of Alabama at Birmingham (UAB) Pathology Educational Instructional Resource website where virtual microscopy of the slides is available. Results: A total of 551 autopsy slides from 24 UAB COVID-19 cases, 1 influenza H1N1 case and 1 tuberculosis case were scanned and uploaded. Five separate COVID-19 research teams used the digital slides remotely with or without a pathologist on a Zoom call. The scanned slides were used to produce one published case report and one published research project. The digital COVID-19 autopsy biorepository was routinely used for educational conferences and research meetings locally, nationally and internationally. Conclusion: The repurposing of a pre-existing website enabled telepathology consultation for research and education purposes. Combined with other communication technology (Zoom) this achievement highlights what is possible using pre-existing technologies during a global pandemic.

Context.—The health care industry is growing rapidly and is continually seeking more-innovative ways to deliver patient care. The growing demands of clinicians seeking faster and more-efficient ways of providing care to their patients presents challenges to clinical laboratory services. Point-of-care testing (POCT) is frequently seen as a viable solution to address this dilemma. The role of POCT is widely established and accepted in many circumstances provided certain criteria are met.Objectives.—To discuss the Cleveland Clinic Abu Dhabi experience—the challenges faced and the solutions found—during the process of establishing a POCT service in a greenfield hospital, and to share this experience to support health care professionals wishing to establish or expand POCT services.Data Source.—First-hand expert opinion relating to setting up a POCT service, which was guided and informed by national and international standards and regulatory bodies, provide the basis for this review.Conclusions.—Point-of-care testing is a fast growing and unique discipline of pathology. The establishment of a new POCT service creates distinctive and unique challenges compared with traditional laboratory services. The difficulties experienced are compounded in a greenfield hospital but the process of multidisciplinary collaboration and information exchange among peer groups allows the efficient development of a highly effective POCT department.

Context.—Opening a new hospital is a once in a lifetime experience and can be very inspiring for those involved in its activation. However, establishing a safe transfusion practice in a greenfield environment comes with unique challenges and opportunities.Objective.—To highlight critical activation components such as on-boarding of new personnel, establishing clinical practices, and integrating critical laboratory software.Design.—Our staff initially faced challenges in standardizing transfusion medicine clinical practice inside the laboratory. Our efforts were mainly focused on the appropriate use of various transfusion orders, creating comprehensive policies for type and screening, cost effective utilization of blood products, and establishment of the maximum surgical blood order schedule. The transfusion service was launched with 2 information technology programs that separately facilitated steps in the transfusion process, but did not provide centralized access to the entire process. In these circumstances, we partnered with the laboratory information system team to create a series of interfaces that streamlined each system's functionality and implemented the existing infrastructure with upgrades that enable remote location and management of blood products.Results.—The transfusion medicine team spent more than a year training and monitoring workflows to avoid individual variations between technologists and to adopt our own standards of practice. Participation in a structured training plan was also necessary between clinical caregivers to know the safe and efficient use of these standards.Conclusions.—Although laboratory and clinical staff are knowledgeable in care delivery, it is always a learning experience to establish a new system because of the natural tendency of resorting to previous practices and resistance to new approaches.

Context.—This review examines challenges and opportunities in preparing laboratories in a startup phase for accreditation by both the College of American Pathologists (CAP) and International Organization for Standardization (ISO) 15189 in an international setting as it relates to our experience at Cleveland Clinic Abu Dhabi Laboratory. It also discusses some of the strategies used in executing those projects and the added advantages in pursuing both types of accreditations.Objectives.—To share our experience with CAP and ISO 15189 accreditations in a startup international operation in relation to the challenges encountered and implementation strategy success factors.Data Sources.—MEDLINE (PubMed) database was used to review this topic as well as peer-reviewed articles and World Health Organization publications on the topic.Conclusions.—Accreditation is a perfect means toward building quality medical laboratories in a diverse workforce environment and improving patient safety. Further, it establishes a strong foundation on which any new operation can build a sustainable quality improvement culture. Accreditations by CAP and/or ISO are among the most reputable and well-established accreditation systems that clinical laboratories could aim for. As a result of both accreditations offering synergistic and complementing features, we recommend that any laboratory seeking excellence in quality and performance should consider exploring both. Key elements to success include having dedicated project management and change management support while preparing for accreditation. Laboratories seeking accreditation in early operational stages may face a number of challenges; however, significant opportunities will also be present to optimize various operational components from the beginning.

Preliminary studies have revealed that some stents undergo corrosion and fatigue-induced fracture in vivo, with significant release of metallic ions into surrounding tissues. A direct link between corrosion and in-stent restenosis has not been clearly established; nonetheless in vitro studies have shown that relatively high concentrations of heavy metal ions can stimulate both inflammatory and fibrotic reactions, which are the main steps in the process of restenosis. To isolate the mechanical effects from the local biochemical effects, accelerated biomechanical testing was performed on single and overlapping Nickel-Titanium (NiTi) stents subjected to various degrees of curvature. Post testing, stents were evaluated using Scanning Electron Microscopy (SEM) to identify the type of surface alterations. Fretting wear was observed in overlapping cases, in both straight and curved configurations. Stent strut fractures occurred in the presence of geometric curvature. Fretting wear and fatigue fractures observed on stents following mechanical simulation were similar to those from previously reported human stent explants. It has been shown that biomechanical factors such as arterial curvature combined with stent overlapping enhance the incidence and degree of wear and fatigue fracture when compared to single stents in a straight tube configuration. In Press

A study has been carried out on the effect of the optical density of inks on the specular reflectance of a printed surface. Samples of cyan, magenta, and yellow ink were printed with a liquid electrophotographic, an offset lithographic, and a thermal transfer printer. Specular reflectance was measured using a goniophotometric instrument to produce the bidirectional reflectance distribution function. The results clearly demonstrated that the amount of specular light reflected from a printed surface depends strongly on the optical density of the ink. A linear correlation was observed between the total amount of specular light reflected from the surface and the square of the transmittance of the ink layer. A highly transparent ink (e.g., yellow ink measured with red light) reflected approximately twice as much specular light than a highly absorbing ink (e.g., yellow with blue or cyan with red). It is suggested that specular reflections from surfaces below the ink layer can contribute significantly to overall specular reflectance of a printed image.

The development of allograft vascular disease (AVD) may be related to altered expression of the fibrinolytic system. We determined the extent to which plasminogen activator inhibitor type 1 (PAI-1) expression in donor tissue influences intimal proliferation (IP) in a mouse model of AVD.We utilized an end-to-end abdominal aortic transplant model in mice to investigate the development of IP in 3 groups of 6 recipients. Group A (negative control) utilized C57BL/6J strain mice as both donors and recipients. In Groups B (positive control) and C, C57BL/6J mice were vessel donors and CBA/J mice were recipients. Both groups received intraperitoneal anti-CD4 and anti-CD8 monoclonal antibodies (250 microg/week for 5 weeks). Group C recipients, however, were transplanted with vessels from C57BL/6J PAI-1 knockout mice. Animals were killed at 50 days. Transplanted aortas were removed and intimal areas calculated using morphometric analysis.Group A (mean intimal area 6421 +/- 8507 microm(2)) demonstrated very little IP in comparison to the other groups. IP was significantly higher in Group B (mean intimal area 56357 +/- 35629 microm(2)) than Group A (p = 0.008). Group C (mean intimal area 288195 +/- 123279 microm(2)) demonstrated significantly more intimal proliferation than either Groups A or B (vs B, p = 0.003; vs A, p0.001). The significance of these results is maintained if intimal thickness is measured as a stand-alone reference for the intimal response.Lack of PAI-1 expression in donor tissue greatly exaggerates the extent of IP after allogeneic transplantation and suggests that PAI-1 is important in limiting the early phase of AVD.

In-stent restenosis (ISR) remains a significant limitation despite the considerable previous clinical and investigative emphasis on the problem. Complications arising from the interaction of stent materials with the surrounding vessel wall as well as from the mechanical forces developing after implantation, play an important role in the development of ISR. To investigate the relation between mechanical factors and stent structural integrity, and to identify any structural weakness points on the geometry of commercially available Stainless Steel and Cobalt-Chromium stents, accelerated pulsatile durability tests were carried out in a simulated physiological environment. Potential spatial variations in the mechanical properties on stent struts and their role in the observed premature failures of the stent devices during operation were also examined. Fretting wear and fatigue-induced fractures were found on stent surfaces after exposure to cyclic loading similar to that arising in vivo. Nanoindentation studies performed on various locations along the stent struts have shown that the hardness of specific stent locations significantly increases after mechanical expansion. The increase in hardness was associated with a reduction of the material's ability to dissipate energy in plastic deformations, therefore an increased vulnerability to fracture and fatigue. We conclude that the locations of fatigue fractures in stent struts are controlled not only by the geometrically-driven stress concentrations developing during cyclic loading but also by the local material mechanical changes that are imparted on various parts of the stent during the deployment process.

Previously, we reported that elevated extracellular potassium concentration in vitro inhibited proliferation and migration of vascular smooth muscle cells, formation of free radical compounds by macrophages, and reduced platelet sensitivity to agonists. More recently, we described a reduction in neointimal proliferation after balloon angioplasty injury in the carotid arteries of rats associated with an elevation of dietary potassium intake during a 4-week experiment. In the present study we conducted a similar investigation in the swine coronary artery balloon angioplasty model.Two groups of seven castrated male swine were studied; for 28 days the normal potassium group consumed a diet containing 0.25% potassium and the high potassium group ate diet containing 2.0% potassium. After 14 days on the diet, balloon angioplasty was performed. After an additional 14 days on the same diets the hearts were removed, and normal and lesioned sections of the artery were analyzed histologically.The neointimal area was markedly less in the high potassium group than in the normal potassium group, 0.33+/-0.04 mm2 v 0.74+/-0.10 mm2 (P.004). Neointimal area-to-total wall area ratio in the normal potassium group averaged 0.199+/-0.018, significantly greater than the ratio computed for the elevated potassium group, 0.120+/-0.015 (P.006).These results support the hypothesis that a high level of dietary potassium intake inhibits neointimal proliferation after balloon angioplasty in the swine coronary artery.

— Adaptations of the aging left ventricle (LV) to hemodynamic overload are functionally and structurally distinct from those of the young organism. This study describes the influence of aging on LV hemodynamics and remodeling late after myocardial infarction (MI) in Fischer 344 Brown Norway rats. In sham rats at 23 mo, LV weight, myocyte cross-sectional area (CSA), and myocardial fibrosis were increased, whereas LV dP/d t, LV relaxation, and maximal LV systolic function declined with respect to younger rats (7, 12, and 18 mo of age). Isometric myocardial function was evaluated in papillary muscles of 12- and 23-mo-old sham rats. Myocardial systolic function was decreased in older rats. To determine how aging affects LV function and remodeling after MI, rats were infarcted at 7 and 18 mo of age and were studied 5 mo later. Infarct size was similar in each group. Right ventricular weight, LV end-diastolic pressure, and volume index were increased, whereas LV dP/d t, peak cardiac index, and peak developed LV pressure declined after MI. However, there were no significant differences between young and older rats in any variable of LV systolic function or remodeling after MI. Myocyte CSA increased in younger rats after MI but was unchanged in 23-mo-old rats. After MI, myocardial fibrosis was significantly increased from baseline only in younger rats. The negative interaction of aging and MI on myocyte hypertrophy and fibrosis was highly significant. The findings indicate that baseline LV and myocardial function decline with age. In the aging rat after MI, despite limited compensatory hypertrophy and more advanced baseline myocardial fibrosis, the long-term functional and structural adaptations to MI are similar to those of the mature adult heart.

To determine the role of angiotensin II-receptor blockade on cardiovascular remodeling in a pressure-overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult male Sprague-Dawley rats. Aortic-banded (AB) rats were left untreated or were losartan (Los; 250 mg/l) treated (AB-Los). Sham-operated (S) controls were either left untreated or treated with Los (S-Los). After 4 wk, rats were catheterized for measurement of mean arterial pressures [carotid (CMAP) and femoral (FMAP), in mmHg]. Hearts were perfused on a modified Langendorff system, and minimal coronary resistance (MCR) was determined. Hearts were then perfusion fixed, total and regional heart weights were recorded, and sections were processed for morphology. Changes in coronary artery medial thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Los than in S or S-Los (P < 0.05). There was no difference in FMAP in AB vs. S, but AB-Los and S-Los had lower FMAPs than S. Total heart weight and left ventricular weight-to-body weight ratios were increased in AB and AB-Los compared with S and S-Los (P < 0.05). MCR of AB was greater than S and S-Los. MCR of AB-Los was significantly lower than AB and was not significantly different from S and S-Los. In coronary vessels, medial thickness was greatest in AB, whereas there was no difference among AB-Los, S, and S-Los. Similarly, the increase in perivascular fibrosis was greatest in AB, and there was no difference among AB-Los, S, and S-Los. These data suggest that angiotensin II, independent of increased arterial pressure, is critical for the development of the vascular and fibrotic changes that occur in this model of pressure-overload hypertrophy.

Covered stents are the standard of care when coronary perforations complicate percutaneous coronary interventions (PCIs) and have also been utilized in the treatment of coronary aneurysms. We present the clinical and histologic features of a patient who developed a coronary perforation and pseudoaneurysm four years following deployment of intracoronary stents. Although the covered stent successfully sealed the perforation, subsequent thrombosis led to a fatal acute myocardial infarction.

With individuals either living longer with the disease or contracting it at a later stage in life, HIV/AIDS can no longer be regarded as just a young person’s disease. In fact, people older than 50 will represent 50% of HIV/AIDS cases by 2015. The intersection of aging and HIV/AIDS is explored in this article through the use of an individual example highlighting typical age-related issues encountered in living with a chronic HIV infection and two of the more common comorbid conditions. Nursing implications for managing these conditions—depression and dyslipidemia—as well as other considerations for providing care to older adults with HIV/AIDS are addressed.

Traditional approaches for in-vitro pulsatile and fatigue testing of endovascular stents do not take into consideration the pathologies of the stented vessel and their associated biomechanical effects. One important pathology is calcification, which may be capable of inducing changes in the vessel wall leading to inhomogeneous distribution of stresses combined with wall motion during the cardiac cycle. These local property changes in the region adjacent to stents could directly influence in-vivo stent performance. Seven cases containing a total of 18 stents were obtained from autopsy. Radiographs were evaluated and vessels were sectioned for histology and stent topographical analysis. Stents were retrieved by chemical removal of surrounding tissue and surfaces were evaluated using 3D digital optical and scanning electron microscopy for biomechanical abrasion and fracture features. Pathologic complications such as restenosis and thrombus formation were assessed from histological sections. Direct evidence of fracture was found in 6 of the 7 cases (in 12 out of 18 stents; 9 drug eluting and 3 bare metal). The degree of stent alterations was variable, where separation of segments due to fracture occurred mostly in drug-eluting stents. All fracture surfaces were representative of a high cycle fatigue mechanism. These fractures occurred in complex lesions involving the presence of diffuse calcification alone, or in combination with vessel angulations and multiple overlapping stents. Morphologic analysis of tissue at or near some fracture sites showed evidence of thrombus formation and/or neointimal tissue growth.

BACKGROUND: We have previously shown that lack of plasminogen activator inhibitor-1 (PAI-1) expression in donor tissue greatly increases intimal proliferation (IP) after allogeneic transplantation. We sought to determine the relative role of PAI-1 and other fibrinolytic proteins in the development of IP. METHODS: We used an abdominal aortic transplant model in mice to investigate IP in 3 groups of 6 recipients. In the isograft group, CBA/J strain mice were donors and recipients, donors for allograft group were C57BL/6J mice, and for the allograft/knockout group, C57BL/6J PAI-1 knockout mice. All groups received weekly injections of anti-CD8/CD4 monoclonal antibodies. IP was calculated at 50 days, and sections were analyzed for fibrinolytic proteins, messenger RNA (mRNA) and PAI-1 activity using immunohistochemistry (IHC), in situ hybridization (ISH), reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis. RESULTS: Significantly more IP developed in the allograft/knockout group vs the isograft (p 0.001) and the allograft groups (p 0.003). There was marked intimal expression of tissue plasminogen activator (tPA), urokinase PA (uPA), and uPA receptor (uPAR) proteins and mRNA in the allograft and allograft/knockout groups vs the isograft group. Allografts also showed significant intimal staining for PAI-1 protein and mRNA. RT-PCR demonstrated a stepwise increase in profibrinolytic protein mRNA from isograft to allograft to allograft/knockout groups, particularly uPA (p 0.02) and uPAR (p 0.016). Western blot data showed complementary findings. PAI-1 activity was persistently present in isograft and allograft animals, only. Intimas in allograft and allograft/knockout groups were primarily smooth muscle cells. CONCLUSIONS: PAI-1 reduces IP by limiting smooth muscle cell activity, with little change in matrix composition likely by modulating profibrinolytic protein expression. J Heart Lung Transplant 2011;30:935‐44 © 2011 International Society for Heart and Lung Transplantation. All rights reserved.

The morphologic changes in atherosclerotic coronary arteries and saphenous vein bypass grafts after placement of a balloon-expandable flexible coil stent (Cook) are described. In each case, the vessels were patent despite morphologic evidence of injury and dissection in the vessel wall. The stented region was reendothelialized and the tissue overlying the stent wires consisted primarily of smooth muscle cells. There was minimal inflammatory reaction to the stent wires. These findings suggest that the balloon-expandable flexible coil stent can effectively maintain vessel patency even in the setting or postangioplasly lumen disruption. In addition, the vessels tolerate the metal prosthesis with little evidence of tissue inflammatory reaction.

The purpose of this study is to present data comparing the penetration of cryolesions created by various sizes and shapes of cryoprobes in human cadaveric myocardium, fat, and tissue of the central fibrous body. Ten cryolesions were made for each combination of tissue and cryoprobe studied. All cryolesions enlarged most rapidly during the first minute of cryothermia (p less than 0.01). Maximal cryothermic penetration into nontrabeculated myocardium was 8.5 +/- 0.5 mm (15-mm flat probe) and 6.1 +/- 1.0 mm (5-mm small probe). Maximal cryothermic penetration into trabeculated myocardium was 9.4 +/- 1.0 mm (10-mm cone-tipped probe) and 7.4 +/- 0.5 mm (10-mm flat probe). Maximal cryothermic penetration into fat was 4.7 +/- 0.7 mm (15-mm flat probe) and 3.9 +/- 0.7 mm (5-mm flat probe). The deeper penetration of cryothermia into myocardium as compared with fat (p less than 0.05) is related to the lower thermal conductivity of fat. Maximal cryothermic penetration of the central fibrous body was similar to that of the myocardium with transmural freezing of the central fibrous body after 4.4 +/- 0.3 minutes of cryothermia. These data can be used when determining the optimal cryothermic exposure for ablation of arrhythmogenic tissue.

The selective infusion of ethanol into the coronary circulation supplying the site of origin of incessant ventricular tachycardia has been demonstrated to abolish this arrhythmia in selected patients. The present study was designed to evaluate the efficacy and safety of the intracoronary ethanol ablation technique in patients with paroxysmal ventricular tachycardia related to prior myocardial infarction. Twenty-three patients with sustained monomorphic ventricular tachycardia that was refractory to conventional antiarrhythmic drug therapy were prospectively studied. After induction of ventricular tachycardia by programmed electrical stimulation, the response of the arrhythmia to the infusion of radiographic contrast medium or saline solution into the ostia of the native coronary arteries and coronary artery bypass grafts was assessed. If ventricular tachycardia was reliably interrupted by injections into the proximal coronary artery or bypass graft, the vessel was cannulated with a steerable guide wire and 2.7F infusion catheter to determine the smallest arterial branch that would result in termination of the arrhythmia with selective injections. If reliable interruption of ventricular tachycardia was observed with saline or contrast injections, ethanol (2 ml) was then delivered through the infusion catheter. Ventricular tachycardia could be terminated by injections of saline solution or contrast medium in 11 of 21 patients in whom the protocol could be completed. Ethanol was infused in 10 of these patients. Ventricular tachycardia was inducible in only 1 of 10 patients immediately after ethanol infusion. At a follow-up electrophysiologic study performed 5 to 7 days after ablation, ventricular tachycardia became inducible in two other patients, in one of whom the arrhythmia substrate was successfully ablated after three sessions. The mean left ventricular ejection fraction was 0.33 +/- 0.1 before and 0.35 +/- 0.11 after ablation. Complications of the procedure included complete atrioventricular block in four patients and pericarditis in one patient. Thus, intracoronary ethanol ablation is associated with a moderate degree of efficacy but the potential for important complications. Despite these limitations, this technique may provide effective long-term control of ventricular tachycardia for some patients.

In this paper we describe a method to evolve biologically inspired motion detection systems utilizing artificial neural networks (ANN's). Previously, the evolution of neural networks has focused on feed-forward neural networks or networks with predefined architectures. The purpose of this paper is to present a novel method for evolving neural networks with no predefined architectures to solve various problems including motion detection models. The neural network models are evolved with genetic algorithms using an encoding that defines a functional network with no restriction on recurrence, activation function types, or the number of nodes that compose the final ANN. The genetic algorithm operates on a population of potential solutions where each potential network is represented in a chromosome. The structure of each chromosome in the population is defined with a weight matrix which allows for efficient simulation of outputs. Each chromosome is evaluated by a fitness function that scores how well the actual output of an ANN compares to the expected output. Crossovers and mutations are made with specified probabilities between population members to evolve new members of the population. After a number of iterations a near optimal network is evolved that solves the problem at hand. The approach has proven to be sufficient to create biologically realistic motion detection neural network models with results that are comparable to results obtained from the standard Reichardt model.

This paper introduces a hybrid face recognition model that combines biologically inspired features and Local Binary Features. The structure of the model is mainly based on the human visual ventral pathway. Previously, object-centered models focus on extracting global view-invariant representation of faces (I. Biederman, 1987) while feed-forward view-based models (HMAX model by Riesenhuber and Poggio, 1999) extract local features of faces by simulating responses of neurons in the human visual system. In this paper we first review the current main face recognition algorithms: Local Binary Pattern model and R&P model. This is followed by a detailed description of their implementation and advantages in overcoming intra-class variance. Results from our model are compared to the original Riesenhuber and Poggio model and Local Binary Pattern model (T. Ahonen et al, 2005). Then the paper will focus on our hybrid biological model which takes advantages of both structural information and biological features. Our model shows improved recognition rates and increased tolerance to intra-personal view differences.

This paper presents a new approach for the design of feature-extracting recognition networks that do not require expert knowledge in the application domain. Feature-Extracting Recognition Networks (FERNs) are composed of interconnected functional nodes (feurons), which serve as feature extractors, and are followed by a subnetwork of traditional neural nodes (neurons) that act as classifiers. A concurrent evolutionary process (CEP) is used to search the space of feature extractors and neural networks in order to obtain an optimal recognition network that simultaneously performs feature extraction and recognition. By constraining the hill-climbing search functionality of the CEP on specific parts of the solution space, i.e., individually limiting the evolution of feature extractors and neural networks, it was demonstrated that concurrent evolution is a necessary component of the system. Application of this approach to a handwritten digit recognition task illustrates that the proposed methodology is capable of producing recognition networks that perform in-line with other methods without the need for expert knowledge in image processing.

BACKGROUND Previous studies have shown that hypertrophy of surviving myocytes after myocardial infarction (MI) is limited. Progressive ventricular dilatation after MI may occur when compensatory hypertrophy cannot restore left ventricular (LV) wall stress to normal. METHODS AND RESULTS To test whether induction of additional myocyte hypertrophy might prevent pathological LV remodeling after large MI, we administered 2-tetradecylglycidic acid (TDGA) 20 mg/kg/day to sham-operated (n = 12) and MI (n = 10) rats for 10 days, beginning the third day after infarction. We have previously shown that chronic inhibition of long-chain fatty acid oxidation with TDGA in rats results in myocardial hypertrophy without any apparent impairment of LV systolic function. When compared with untreated MI rats (n = 9), we found that TDGA-treated MI rats had increases in LV weight/body wt, myocyte cross-sectional area, and peak developed LV pressure during abrupt aortic occlusion. MI rats treated with TDGA had lower LV end-diastolic pressures and smaller end-diastolic volumes, whereas stroke volume was maintained. The ex vivo passive LV pressure-volume relation was shifted toward the pressure axis compared with untreated infarct rats. In sham-operated rats, TDGA caused increases in LV weight/body wt, myocyte size, peak developed LV pressure, cardiac index, and stroke volume index, and a shift of the passive LV pressure-volume relation toward the pressure axis. CONCLUSIONS Induction of myocardial hypertrophy with an inhibitor of long-chain fatty acid oxidation retarded the process of LV dilatation and produced beneficial effects on systolic function after large myocardial infarction. These data support the hypothesis that inadequate hypertrophy of residual myocardium after infarction may contribute to LV dilatation and the development of congestive heart failure.

Purpose of the study: We aimed to determine if there is any relationship between long term exposure to ambient air pollution and the blood pressure and inflammatory processes among young subjects. Methods: We recruited permanent residents of two Polish major cities, Krakow and Lublin, with very similar urban structure characteristics, which significantly differ in mean 10-year ambient air pollution levels: PM2.5 (22.4 vs. 41.7mg/m3) and PM10 (29.4 vs. 56.9 mg/m3) respectively. Data regarding BMI, lifestyle, ethnics and family history was collected. Measurements of blood pressure (BP) and heart rate (HR) were performed and blood tests, including inflammatory markers were studied. Results: 826 subjects (558 females, 268 males) aged 18.02 1.12 were randomly recruited, 382 in Lublin, 444 in Krakow. There were no differences between groups in BMI (median: 20,80 kg/m2), age, ethnic. We found no significant differences in BP parameters, pulse pressure (PP) between subjects differing in exposure to air pollution. Lublin vs. Krakow: DBP (70.3; IQR 10.5 vs. 69.7; IQR 9.3 mmHg), SBP (122.3; IQR 16.3 vs. 121.3; IQR 16.6 mmHg), PP (50.8; IQR 12.8 vs. 51.3; IQR 12.7 mmHg). Moreover we found lower PP (51.0; IQR 13.0 vs. 53.1; IQR 12.0 mmHg) in subjects drinking energy drinks more frequent than several times a week. We found significantly higher inflammatory parameters in inhabitants of highly polluted city. Lublin vs. Krakow: CRP (0.4; IQR 0.5 vs. 0.77; IQR 0.6 mg/ml, p

Summary: The Internet has revolutionized the computer and communications world. It has grown to become a worldwide mechanism for information exchange without regard for geographic boundaries. The tremendous growth in this wealth of information poses several questions regarding the utility of this powerful tool in pathology practice and education. This article reviews the advantages and disadvantages of using the Internet in pathology resident education, in general, and how it has impacted the repertoire of educational opportunities at our own institution. The various Internet resources of educational value for pathology trainees are outlined. Basic Internet concepts are also elucidated.

Abstract —Arterial smooth muscle cells undergo phenotypic and proliferative changes in response to balloon catheter injury. Nitric oxide (NO) and cGMP have been implicated in the inhibition of vascular smooth muscle cell proliferation and phenotypic modulation in cultured-cell studies. We have examined the expression of the major cGMP receptor protein in smooth muscle, cGMP-dependent protein kinase I (PKG), in response to balloon catheter injury in the swine coronary artery. On injury, there was a transient decrease in the expression of PKG in neointimal smooth muscle cells when compared with medial smooth muscle cells. The decrease in PKG expression was observed in the population of proliferating cells expressing the extracellular matrix protein osteopontin but not in cells present in the uninjured portion of the media. Coincident with the suppression of PKG expression in neointimal cells after injury, there was a marked increase in the expression of type II NO synthase (inducible NOS [iNOS], NOS-II) in the neointimal cells. These results suggest that PKG expression is transiently reduced in response to injury in the population of coronary arterial smooth muscle cells that are actively proliferating and producing extracellular matrix proteins. The reduction in PKG expression is also correlated temporally with increases in inflammatory activity in the injured vessels as assessed by iNOS expression. Coupled with our current knowledge regarding the role of PKG in the regulation of cultured cell phenotypes, these results imply that PKG may also regulate phenotypic modulation of vascular smooth muscle cells in vivo as well.

Recently, we reported that elevated extracellular potassium concentration in vitro inhibited proliferation and migration of vascular smooth muscle cells, formation of free radical compounds by macrophages, and reduced platelet sensitivity to agonists. In the present study we analyzed the effects of long-term, in vivo elevation of extracellular potassium concentration resulting from changes in dietary potassium intake on the vascular response to injury. The rat carotid artery balloon injury model was employed in 70 adult Sprague Dawley rats assigned to three groups. Beginning 14 days before surgical placement of the carotid lesion and continuing until death, the animals were fed diets containing either low (0.1% potassium, n = 25), normal (1.5% potassium, n = 19), or high potassium (4.0% potassium, n = 26). Fourteen days postsurgery the animals were killed and the arteries were analyzed to determine quantitatively the ratio of neointimal to medial area. Dietary potassium had a significant effect on arterial plasma potassium concentration (one-way analysis of variance, P.01). Group mean and standard errors were 4.26+/-0.12 mmol/L for the low-potassium group, 5.22+/-0.19 mmol/L for normal, and 5.80+/-0.23 mmol/L for the high-intake group. Increases in dietary potassium attenuated neointima formation significantly (P.05, one-way analysis of variance), with the mean ratio of neointimal area to medial area being 0.447+/-0.106 for the low-intake animals, 0.384+/-.116 for normal, and 0.240+/-.046 for the high-intake group. These results are consistent with a hypothesis that a high level of potassium intake is effective in inhibiting neointima formation in vivo.

Digital halftoning is used to render continuous gray-scale images to a device, such as a laser printer or video display, that is only capable of binary output (black and white). Other applications include image transmission and storage where the gray-scale to binary data reduction translates to reduced transmission and storage costs. The idea is that the local density of dots mimics the original gray-scale and appears nearly the same to a viewer. This method works because the human visual system acts like an averaging or low-pass filtering device when presented with the relatively high frequency dot pattern. The challenge is to optimize the appearance by minimizing side effects such as undesirable texture artifacts and false contours, that can be produced by the pattern. The general issues that must be addressed are those concerned with the original image relative to dynamic range and spatial resolution of the grayscale and those concerned with the visibility of the halftone pattern.

Background —Although the effects of epicardial implantable cardioverter-defibrillator (ICD) leads on underlying cardiac tissue have been reported, the gross and microscopic changes associated with endocardial ICD leads are less well described. This study describes the gross and microscopic changes associated with endocardial ICD leads in humans. Methods and Results —The hearts from 8 patients were examined. At the time of ICD implantation, the patients’ mean age was 47±11 years, and the left ventricular ejection fraction was 0.24±0.10. Four patients had ischemic heart disease, and 4 had dilated cardiomyopathy. Five hearts were examined after transplantation; 3, after death. The electrode-myocardial interfaces were characterized by intense endocardial fibrosis and were remarkably consistent. Each lead was encased by a ring of fibroelastic tissue, and there was fibrosis of the right ventricular myocardium adjacent to the leads. Fibrosis involved the tricuspid valve in 5 patients, and 1 had perforation of the valve by the lead. Microscopically, interstitial fibrosis was adjacent to each lead in the current path of ICD shocks. Acute cell injury was present only in the hearts that had received recent shocks. Conclusions —The ICD electrode-myocardial interface is characterized by intense fibrosis. The fibrosis associated with endocardial ICD leads and the cumulative acute damage produced by defibrillation discharges may explain changes in the defibrillation and pacing thresholds and the difficulty of lead extraction that can be encountered with transvenous ICD systems.

Background Smooth muscle cell (SMC) hyperplasia is an important mechanism of restenosis after coronary angioplasty and the primary mechanism of restenosis within coronary stents. Ethanol has been shown to reduce the response of SMCs to local growth stimulants in vitro. This study was carried out to determine whether local delivery of ethanol solution could reduce intimal hyperplasia induced by balloon injury. Methods and Results Three groups of juvenile domestic pigs underwent oversized balloon dilation injury of the left anterior descending and left circumflex coronary arteries. Immediately after the balloon injury, one of the arteries was randomized to local delivery of 15% ethanol with a local delivery balloon catheter, and the other received no further treatment. Histological and morphometric studies were carried out at 2 weeks in group 1 (n=16) and at 4 weeks in group 2 (n=10). In the third group (n=15), animals were killed at days 4, 8, and 14 after balloon injury, and coronary artery segments were studied by immunohistochemical staining against proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU). Histological injury scores were not different between the ethanol-treated and untreated arterial segments in either group 1 or 2. The neointimal areas were significantly smaller in the ethanol-treated arterial segments than in the untreated segments (0.25±0.08 versus 0.57±0.08 mm 2 , P =.004, at 2 weeks; 0.33±0.05 versus 0.54±0.07 mm 2 , P =.03, at 4 weeks). SMC proliferative activity was significantly lower in ethanol-treated arteries than in untreated arteries at 4 and 8 days after injury by BrdU and PCNA staining. Conclusions Local delivery of 15% ethanol solution to pig coronary arteries significantly decreased the SMC proliferative activity and neointimal formation induced by balloon dilation injury.

BACKGROUND The proposed mechanisms of restenosis after coronary angioplasty include neointima formation, vessel wall remodeling and mural thrombus. Poloxamer 188 does not inhibit coagulation factors, but was shown to reduce mural thrombus formation in pig coronary arteries after intracoronary stenting in an acute study. This study was performed to examine whether this agent may reduce neointima formation. METHODS Thirty domestic juvenile pigs of weight 20-30 kg were anesthetized. A left angiogram was performed via a femoral artery. Proximal left anterior descending and circumflex arteries were dilated three times with a 20-30% oversized coronary angioplasty balloon catheter. Fifteen animals were allocated randomly to receive intravenous infusions of poloxamer 188, starting 30 min before angioplasty and continuing for 24 h. The remaining 15 received intravenous 0.45% saline and served as controls. The animals were killed 2 weeks after the angioplasty. Histologic studies of the arteries were performed. The severity of the injury and the amount of thrombus material incorporated in the neointima were assessed by semiquantitative methods. RESULTS There was no significant difference between injury scores in the two groups. Thrombus material in the neointima in the treatment group was significantly less than that in those of the control group (thrombus areas 0.013 +/- 0.004 compared with 0.029 +/- 0.006 mm2, P < 0.02), but there were no significant differences between the neointimal (0.60 +/- 0.08 and 0.60 +/- 0.13 mm2) and luminal (2.51 +/- 0.21 and 2.44 +/- 0.26 mm2) areas in treatment and control groups. CONCLUSION Continuous 24 h intravenous infusion of poloxamer 188 after balloon injury in pig coronary arteries may reduce mural thrombus formation significantly, but did not reduce neointima formation.

Abstract To clarify the role of Na + i , pH i , and high-energy phosphate (HEP) levels in the initiation and maintenance of ischemia-induced ventricular fibrillation (VF), interleaved 23 Na and 31 P nuclear magnetic resonance spectra were collected on perfused rat hearts during low-flow ischemia (51 minutes, 1.2 mL/g wet wt). When untreated, 50% of the hearts from normal (sham) rats and 89% of the hypertrophied hearts from aortic-banded (band) rats ( P + i accumulation was greater in hearts that eventually developed VF than in hearts that did not develop VF for both band and sham groups (144% versus 128% of control in sham; P + -H + exchange inhibitor 5-( N , N -hexamethylene)-amiloride prevented VF in sham and band hearts; reduced Na + i accumulation but similar HEP depletion were observed compared with VF hearts before the onset of VF. Rapid changes in Na + i , pH i , and HEP began with VF, resulting in intracellular Na + i overload (≈300% of control) and increased HEP depletion. A delayed postischemic functional recovery occurred in VF hearts, which correlated temporally with the recovery of Na + i . In conclusion, alterations in Na + i were associated with spontaneous VF transitions, consistent with involvement of excess Na + i accumulation in VF initiation and maintenance and with previously reported alterations in Ca 2+ i with VF. Hypertrophied band hearts exhibited enhanced susceptibility to ischemia-induced VF, possibly linked to a lower HEP reserve.

The predominant role of geometric remodeling in restenosis after percutaneous coronary angioplasty (PTCA) has recently been described. In this study, Cytochalasin B (CB), a compound which reversibly blocks actin polymerization and thereby inhibits smooth muscle contraction and geometric remodeling, was tested for its ability to inhibit restenosis after balloon trauma in a swine coronary model. The left circumflex artery was traumatized with a torquable embolectomy catheter and treated with either saline, 0.1 μ g/ml or 1.5 μ g/ml CB applied directly to the arterial wall with a Cordis Microporous Infusion Catheter (MIC). Pigs were sacrificed 3 weeks post-surgery and the left coronary artery was processed for histopathology. Histologically, traumatized and treated coronary arteries in all groups were characterized by tears in the internal elastic lamina which occasionally extended into the tunica media, reorientation of the inner myofibers of the tunica media perpendicular to the lumen, occasional dissecting aneurysms, and intimal hyperplasia. Morphometric evaluation of vascular lumenal area demonstrated a significant difference between treatment groups and the saline control. Saline control pigs had a mean lumenal area of 55.8% (44.2% stenosis) compared to the mean of the proximal and distal vessel lumen areas. Pigs treated with 0.1 μ g/ml CB had lumenal areas of 92.1% (7.9% stenosis, p l 0.01), and pigs treated with 1.5 μ g/ml CB had lumenal areas of 112.4% (12.4% dilation, p = 0.001). Treatment with 0.1 μ g/ml CB markedly inhibited restenosis and treatment with 1.5 μ g/ml CB actually resulted in increased in lumenal area. In this model of vascular injury, treatment with CB resulted in increased lumenal patency which appears to be associated with chronic geometric remodeling despite concurrent intimal proliferation. Treatment of traumatized coronary arteries with CB may be useful in diminishing restenosis in patients undergoing PTCA.

The success of methods that ablate atrioventricular (AV) node reentry demonstrates that extranodal tissue is part of the reentry circuit. The hypothesis of this study is that atrial tissue approaching the posterior AV node is part of the AV node reentry circuit and is especially suitable for complete division with sparing of AV conduction. This study measured AV node function after either an anterior or posterior perinodal incision. The only significant change noted in antegrade function was a lengthening of the Wenckebach point after the posterior incision. Retrograde AV conduction and ventricular echoes were abolished by the posterior incision, whereas the anterior incision had no discernible effect on retrograde AV node function. Anatomic analysis of the two incisions showed that the posterior incision completely interrupted the posterior atrial input to the AV node, whereas the anterior incision spared the medial input to the AV node. The atrial tissue posterior to the AV node is anatomically suited for complete interruption. Ablation of atrial tissue posterior to the AV node is proposed for abolishing AV node reentrant tachycardia.

We have constructed a linear discriminator for handprinted character recognition that uses a (binary) vector of 1, 500 features based on an equidistributed collection of products of pixel pairs. This classifier is competitive with other techniques, but faster to train and to run for classification.

We present a pattern recognition algorithm for handprinted and machine-printed characters, based on a combination of the classical least squares method and a neural-network-type supervised training algorithm. Characters are mapped, nonlinearly, to feature vectors using selected quadratic polynomials of the given pixels. We use a method for extracting an equidistributed subsample of all possible quadratic features.

The pathology associated with an invesrigational transvenous defibriliating and sensing lead is described. The lead system had delivered a total of 865 J from the time of implantation to the time of patient death from a noncardiac cause 7 months after implantation and 1 month after his last defibrillator shock. There was mild, superficial fibrous thickening on the endothelial surface of the superior vena cava adjacent to the proximal spring electrode, which did not extend into the vessel wall. The distal portion of endocardial lead was embedded in the interventricular septum near the apex of the right ventricle, surrounded by fibrous thickening, and partially covered by endocardial tissue. Microscopically, there was a thick bed of fibrous connective tissue surrounding the lead with extensive interstitial fibrous connective tissue radiating into the adjacent myocardium. Since this pattern is different from the more generalized fibrotic scarring produced by myocardial infarction, we speculate that the mechanism for the observed interstitial fibrosis is replacement fibrosis following acute myocyte injury that resulted from prior defibrillator shocks and possibly from the trauma produced by the lead compressing adjacent myocardium during systole. Potential effects on device efficacy of these fibrotic changes at the bioelectric interface include their representing a new arrhythmia substrate, the possibility that fibrosis could increase both defibrillation and pacing thresholds, and that the inflammatory reaction may cause deterioration of intracardiac electrograms and interfere with sensing and tachycardia recognition.

The purpose of this study was to compare the degree of ischemic and hypoxic injury in normal versus hypertrophied rat hearts to investigate basic mechanisms responsible for irreversible myocardial ischemic injury. Hearts from rats with bands placed on the aortic arch at 23 days of age (BAND) and sham-operated rats (SHAM, 8 weeks postoperative) were isolated, perfused with Krebs buffer, and had a left ventricular balloon to measure developed pressure. Hearts were made globally ischemic until they developed peak ischemic contracture and were reperfused for 30 minutes. Additional hearts were perfused for 15 minutes with glucose-free hypoxic buffer followed by 20 minutes of oxygenated perfusion. There was an 87% increase in heart weight of BAND compared with SHAM (p less than 0.01). During ischemia, lactate levels increased faster in BAND compared with SHAM, ischemic contracture occurred earlier in BAND than in SHAM despite no difference in ATP levels, and postischemic recovery of left ventricular pressure was less in BAND (26.8 +/- 5.6% of control left ventricular pressure, mean +/- SEM) compared with SHAM (40 +/- 4.6%, p less than 0.05). During hypoxic perfusion, lactate release was greater in BAND than in SHAM (48.8 +/- 1.2 versus 26.6 +/- 0.97 mumols/g, p less than 0.01), and with reoxygenation, lactate dehydrogenase release was less in BAND than in SHAM (13.2 +/- 0.7 versus 19.5 +/- 0.2 IU/g, p less than 0.01). After hypoxia and reoxygenation, left ventricular pressure recovery was greater in BAND than in SHAM (93 +/- 8.4% versus 66 +/- 5.3%, p less than 0.01). Thus, this study suggests that hypertrophied hearts have a greater potential for glycolytic metabolism, resulting in an increased rate of by-product accumulation during ischemia, which may be responsible for the increased susceptibility of hypertrophied hearts to ischemic injury.

To provide an integrated assessment of changes in systolic and diastolic function in diabetic rats, we measured conscious hemodynamics and performed ex vivo analysis of left ventricular passive-elastic properties. Rats given streptozotocin (STZ) 65 mg/kg i.v. (n = 14) were compared with untreated age-matched controls (n = 15) and rats treated with insulin after administration of STZ (n = 11). After 7 d, diabetic rats exhibited decreases in heart rate and peak developed left ventricular (LV) pressure during aortic occlusion. After 26 d of diabetes there were significant decreases in resting LV systolic pressure, developed pressure, and maximal +dP/dt, whereas LV end-diastolic pressure increased and the time constant of LV relaxation was prolonged. The passive LV pressure-volume relationship was progressively shifted away from the pressure axis, and the overall chamber stiffness constant was decreased. However, "operating chamber stiffness" calculated at end-diastolic pressure was increased at 7 d, and unchanged at 26 d. LV cavity/wall volume and end-diastolic volume were increased after 26 d of diabetes. Myocardial stiffness was unchanged at both time intervals. All of the above abnormalities were reversed by the administration of insulin. We conclude that the hemodynamic and passive-elastic changes that occur in diabetic rats represent an early dilated cardiomyopathy which is reversible with insulin.