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Introduction: To improve the quality of Higher Education, the use of information and communication technologies (ICTs) have been integrated, with the aim of improving the meaningful learning of students and teachers within the teaching-learning process. With the use of Tics through an open educational resource (Rea) that deals with vaginal cytology as a method of studying Pathological Anatomy, the student will be able to know the main elements related to it. Objective: To design an open educational resource for the teaching and learning of vaginal cytology in the Pathological Anatomy subject. Methodology: A technological development project (quasi-experimental) was carried out between the 2018 and 2020 academic years. A sample of 141 2nd-year medical students, 2018-2019 academic year, was used; 16 permanent and part time professors of Anatomical Pathology; 14 specialists carried out the subsequent evaluation of the Rea, and contributed to its evaluation. Results: An open educational resource was created for the teaching and learning of vaginal cytology with the generalities of this method. The evaluation by the specialists was positive from the pedagogical, technological and axiological point of view. Conclusions: A Rea was designed for the teaching-learning of vaginal cytology, which inserts elements that contribute to the study of this method both individually and collectively, favors the development of intellectual abilities, the motivation of the students, the construction of their own knowledge, which contributes to the improvement of the Pathological Anatomy subject., Introducción: Para mejorar la calidad de la Educación Superior se han integrado el uso de las tecnologías de la información y las comunicaciones (Tics), con el objetivo de mejorar el aprendizaje significativo de los estudiantes y docentes dentro del proceso enseñanza aprendizaje. Con la utilización de las Tics a través de un recurso educativo abierto (Rea) que aborde la citología vaginal como método de estudio de la Anatomía Patológica, el estudiante podrá conocer los principales elementos relacionados con este. Objetivo: Diseñar un Recurso educativo abierto para la enseñanza aprendizaje de la citología vaginal en la asignatura Anatomía Patológica. Metodología: Se realizó un proyecto de desarrollo tecnológico (cuasi experimental) entre los cursos 2018 al 2020. Se utilizó una muestra de 141 estudiantes de 2do año de la carrera de medicina, curso 2018-2019; 16 profesores fijos y a tiempo parciales de Anatomía Patológica; 14 especialistas realizaron la evaluación posterior del Rea, y contribuyeron a la valoración de este. Resultados: Se confeccionó un recurso educativo abierto para la enseñanza aprendizaje de la citología vaginal con las generalidades de este método. La valoración por los especialistas fue positiva desde el punto de vista pedagógico, tecnológico y axiológico. Conclusiones: Se diseñó un Rea para la enseñanza aprendizaje de la citología vaginal, el cual inserta elementos que contribuyen al estudio de este método tanto de forma individual como colectiva, favorece el desarrollo de habilidades intelectuales, la motivación de los estudiantes, la construcción de su propio conocimiento, lo que contribuye, al perfeccionamiento de la asignatura Anatomía Patológica.

The diversity of ovarian tumors cannot be explained only by the difference in the degree of maturity and the directions of differentiation.

The diversity of ovarian tumors cannot be explained only by the difference in the degree of maturity and the directions of differentiation.

The diversity of ovarian tumors cannot be explained only by the difference in the degree of maturity and the directions of differentiation.

Introduction The training and development of research skills in students is a process that will allow the mastery of the method of science in the process of professional training in undergraduate from the Pathological Anatomy. Currently, it is more important with the implementation of the "D" study plan, which requires graduating physicians prepared with solid knowledge and a scientific approach that allows them to diagnose and solve human health problems. Objective: The objective of this work is to carry out a bibliographic review and to base some theoretical considerations related to the importance of the development of investigative skills in the initial formation of students in the teaching-learning process from the Pathological Anatomy subject. Development: The initial training of the student is understood as a process of appropriation of knowledge, skills, values and working methods that prepare him / her for the exercise of scientific research functions and that is expressed through the mode of action throughout the career. The formation and development of research skills is fundamental in the teaching-learning process of all disciplines and subjects, Pathological Anatomy is no exception. Conclusions: A literature review on the training and development of research skills in the undergraduate program was carried out and the importance of the training and development of research skills in the subject Pathological Anatomy at the Latin American School of Medicine was argued., Introducción La formación y el desarrollo de habilidades investigativas en los estudiantes es un proceso que permitirá el dominio del método de la ciencia en el proceso de formación profesional en el pregrado desde la Anatomía Patológica. En la actualidad cobra mayor importancia con la implementación del plan de estudio “D”, que exige egresar médicos preparados con sólidos conocimientos y un enfoque científico que les permita diagnosticar y solucionar problemas de la salud humana. Objetivo: El objetivo de este trabajo consiste en realizar una revisión bibliográfica y fundamentar algunas consideraciones teóricas relacionadas con la importancia del desarrollo de habilidades investigativas en la formación inicial de los estudiantes en el proceso de enseñanza- aprendizaje desde la asignatura Anatomía Patológica. Desarrollo: La formación inicial del estudiante es entendida como un proceso de apropiación de conocimientos, habilidades, valores y métodos de trabajo que lo prepara para el ejercicio de las funciones profesionales científicas investigativas y que se expresa mediante el modo de actuación a lo largo de la carrera. La formación y desarrollo de las habilidades investigativas resulta fundamental en el proceso de enseñanza aprendizaje de todas las disciplinas y asignaturas, la Anatomía Patológica no resulta un excepción. Conclusiones: Se efectuó una revisión bibliográfica sobre la formación y desarrollo de habilidades investigativas en el pregrado y se argumentó la importancia de la formación y desarrollo de habilidades investigativas en la asignatura Anatomía Patológica en la Escuela Latinoamericana de Medicina.

The pathophysiology of coronary atherosclerosis is multifaceted. Plaque initiation and progression are governed by a complex interplay between genetic and environmental factors acting through processes such as lipid accumulation, altered haemodynamics and inflammation. There is increasing recognition that biomechanical stresses play an important role in atherogenesis, and integration of these metrics with clinical imaging has potential to significantly improve cardiovascular risk prediction. In this review, we present the calculation of coronary biomechanical stresses from first principles and computational methods, including endothelial shear stress (ESS), plaque structural stress (PSS) and axial plaque stress (APS). We discuss the current experimental and human data linking these stresses to the natural history of coronary artery disease and explore the future potential for refining treatment options and predicting future ischaemic events.Copyright © 2020 Elsevier B.V.

Emerging evidence suggests voice dysfunction is the earliest sign of motor impairment in Parkinson's disease (PD). The complexity and fine motor control involved in vocalization may result in dysfunction here before the limbs. The voice in PD demonstrates characteristic changes on perceptual and acoustic analyses. The physiological and anatomical correlates of these have been investigated through laryngoscopy, stroboscopy, photoglottography, laryngeal electromyography, computed-tomography, pulmonary function testing and aerodynamic assessments. These have revealed numerous abnormalities including incomplete glottic closure and vocal fold hypoadduction/bowing to account for these voice changes. Many of these phenomena are likely related to rigidity or bradykinesia of the laryngeal muscles. The early onset of voice changes is resonant with the pathophysiological insights offered by Braak's hypothesis and murine models of the disease. These physiological abnormalities and pathological models largely stand to support dopaminergic and non-dopaminergic mechanisms being implicated in the pathogenesis of voice dysfunction. This review focuses on characterizing the voice changes in PD. These stand as a promising area of enquiry to further our understanding of the pathophysiology of the disease and offer potential to be utilized as an early diagnostic biomarker or marker of disease progression.Copyright © 2020 Elsevier Ltd

The pathophysiology of coronary atherosclerosis is multifaceted. Plaque initiation and progression are governed by a complex interplay between genetic and environmental factors acting through processes such as lipid accumulation, altered haemodynamics and inflammation. There is increasing recognition that biomechanical stresses play an important role in atherogenesis, and integration of these metrics with clinical imaging has potential to significantly improve cardiovascular risk prediction. In this review, we present the calculation of coronary biomechanical stresses from first principles and computational methods, including endothelial shear stress (ESS), plaque structural stress (PSS) and axial plaque stress (APS). We discuss the current experimental and human data linking these stresses to the natural history of coronary artery disease and explore the future potential for refining treatment options and predicting future ischaemic events.Copyright © 2020 Elsevier B.V.

Emerging evidence suggests voice dysfunction is the earliest sign of motor impairment in Parkinson's disease (PD). The complexity and fine motor control involved in vocalization may result in dysfunction here before the limbs. The voice in PD demonstrates characteristic changes on perceptual and acoustic analyses. The physiological and anatomical correlates of these have been investigated through laryngoscopy, stroboscopy, photoglottography, laryngeal electromyography, computed-tomography, pulmonary function testing and aerodynamic assessments. These have revealed numerous abnormalities including incomplete glottic closure and vocal fold hypoadduction/bowing to account for these voice changes. Many of these phenomena are likely related to rigidity or bradykinesia of the laryngeal muscles. The early onset of voice changes is resonant with the pathophysiological insights offered by Braak's hypothesis and murine models of the disease. These physiological abnormalities and pathological models largely stand to support dopaminergic and non-dopaminergic mechanisms being implicated in the pathogenesis of voice dysfunction. This review focuses on characterizing the voice changes in PD. These stand as a promising area of enquiry to further our understanding of the pathophysiology of the disease and offer potential to be utilized as an early diagnostic biomarker or marker of disease progression.Copyright © 2020 Elsevier Ltd

A search for updated material related to the topic was carried out, based on Internet search engines and the review of textbooks and other articles, for a total of 37, of which 15 references were selected. The concept of Open Educational Resource was defined and its main characteristics, also the concept of necropsy, its types and importance as a method of study of the Pathological Anatomy subject. The use of educational resources in the subject was found, but none specific for clinical necropsy. Therefore, the objective of this work is to design an Open Educational Resource for the study of clinical necropsy, specifying its components and characteristics from the theoretical point of view. For the design of the resource, interviews will be carried out with computer scientists, methodologists and pathology specialists, to know the contents and tools necessary for the resource. A digital platform will be used to insert in it the glossary of terms, texts, images, videos and selfassessments. As an indispensable element will be the development of the ethical values of the profession with the realization of this method. The recommendation is given in extending the use of the Open Educational Resource to other universities in the country., Se realizó una búsqueda de material actualizado relacionado con el tema, a partir de buscadores de internet y la revisión de libros de textos y otros artículos, para un total de 37, de los cuales fueron seleccionadas 15 referencias. Se definió el concepto de Recurso Educativo Abierto y sus principales características, igualmente el concepto de necropsia, sus tipos e importancia como método de estudio de la asignatura Anatomía Patológica. Se encontró el uso de los recursos educativos en la asignatura, pero ninguno específico para la necropsia clínica. Por lo que el objetivo del presente trabajo es diseñar un Recurso Educativo Abierto para el estudio de la necropsia clínica, especificándose sus componentes y características desde el punto de vista teórico. Para el diseño del recurso se realizarán entrevistas a informáticos, metodólogos y especialistas de anatomía patológica, para conocer los contenidos y herramientas necesarias para el recurso. Se utilizará una plataforma digital para insertar en ella el glosario de términos, los textos, las imágenes, los videos y las autoevaluaciones. Como elemento indispensable estará el desarrollo de los valores éticos de la profesión con la realización de este método. La recomendación está dada en extender a otras universidades del país el uso del Recurso Educativo Abierto

Information and Communication Technologies have impacted all areas of educational activity to establish new ways of teaching and learning. The Learning Teaching Process aims to contribute to the student’s training through the fulfillment of the instructional and educational objectives which, in the medical career, in the graduate’s profile, appears as the need for the formation of values for that are transmitted in his medical activity and as a future teacher, based on ethical medical knowledge and the history of our country and the profession. In contradiction with the proposal in the graduate model, there is a deficit in the teaching of the history of Medicine, as there is no specific subject or educational resource that includes it, which transcends its comprehensive medical training; Therefore, it was determined to carry out the design of an open educational resource, which contributes to enrich the knowledge of the history of Medicine and its most relevant personalities, from the Pathological Anatomy course. With this resource an integral education will be favored, which contributes to a general culture necessary for the development of the professional future, the incorporation of ethical values of the profession in students will be stimulated through the life stories of their predecessors and the resource It could be applied in other disciplines, Las Tecnologías de la Información y la Comunicación han impactado en todas las áreas de la actividad educativa para establecer nuevas formas de enseñar y aprender. El Proceso de Enseñanza Aprendizaje tiene como propósito contribuir a la formación del estudiante a través del cumplimiento de los objetivos instructivos y educativos lo que, en la carrera de Medicina, en el perfil del egresado, aparece como la necesidad de la formación de los valores para que se trasmitan en su accionar médico y como futuro docente, basado en los conocimientos médicos éticos y de la historia de nuestro país y la profesión. En contradicción con lo propuesto en el modelo del egresado, se aprecia un déficit en cuanto a la enseñanza de la historia de la Medicina, al no existir una asignatura específica o un recurso educativo que la incluya, lo que trasciende en su formación médica integral; por lo que se determinó realizar el diseño de un recurso educativo abierto, que contribuya a enriquecer el conocimiento de la historia de la Medicina y sus personalidades más relevantes, desde la asignatura Anatomía Patológica. Con este recurso se favorecerá una educación integral, lo cual tributa a una cultura general necesaria para el desarrollo del futuro profesional, se estimulará la incorporación de valores éticos de la profesión en los estudiantes a través de las historias de vida de sus predecesores y el recurso pudiera ser aplicado en otras disciplinas

The quality of human resources training for health is a requirement of postgraduate medical education.Objective: to design a didactic modeling of the pathological Anatomy resident's training to perform the perinatal autopsy.Method: an observational and pedagogical study was carried out during the 2016-2018 period. The objective was met and the modeling that was done with the participation of 7 teachers and through a pre-experiment with 6 residents was validated.Results: 100% of the residents showed inadequacies in performing the perinatal autopsy, but these were corrected ostensibly after the application of a system of teaching tasks for this purpose. 100% of teachers showed conformity with the proposed modeling.Conclusions: the didactic modeling of the pathological anatomy resident's preparation to perform the perinatal autopsy contributes to a qualitatively superior didactic-methodological change in the training process of these residents., A qualidade da formação de recursos humanos em saúde é um requisito da educação médica de pós-graduação.Objetivo: projetar uma modelagem didática do treinamento do residente em Anatomia Patológica para realização da autópsia perinatal.Método: foi realizado um estudo observacional e pedagógico no período 2016-2018. O objetivo foi alcançado e a modelagem realizada com a participação de 7 professores e validada por meio de um pré-experimento com 6 residentes.Resultados: 100% dos residentes apresentaram inadequações na realização da autópsia perinatal, mas estas foram corrigidas ostensivamente após a aplicação de um sistema de tarefas de ensino para esse fim. 100% dos professores mostraram conformidade com a modelagem proposta.Conclusões: a modelagem didática da preparação do residente em anatomia patológica para realização da autópsia perinatal contribui para uma mudança didático-metodológica qualitativamente superior no processo de treinamento desses residentes., La calidad de la formación de los recursos humanos para la salud es una exigencia de la educación médica de postgrado.Objetivo: diseñar una modelación didáctica de la formación del residente de Anatomía Patológica para realizar la autopsia perinatal.Método: se realizó un estudio observacional y de corte pedagógico durante el periodo de 2016-2018. Se satisfizo el objetivo y se validó la modelación que se hizo con la participación de 7 profesores y mediante un pre-experimento con 6 residentes.Resultados: el 100 % de los residentes mostró insuficiencias para la realización de la autopsia perinatal, pero estas se corrigieron ostensiblemente después de la aplicación de un sistema de tareas docentes para este fin. El 100 % de los profesores mostraron conformidad con la modelación propuesta.Conclusiones: la modelación didáctica de la preparación del residente de Anatomía Patológica para realizar la autopsia perinatal contribuye a un cambio didáctico-metodológico cualitativamente superior en el proceso de formación de estos residentes.

A clinical-pathological case was reported, diagnosed at the "Joaquín Albarrán" Clinical Surgical Teaching Hospital in Havana. In this entity, an 85-year-old female patient with a history of type 2 diabetes mellitus was presented, admitted due to arterial insufficiency of the lower left limb, for which she underwent supracondylar amputation and died on the third day of her hospital stay. At the autopsy, the pathological diagnosis of Mönckeberg arteriosclerosis of vessels of the uterus was reached. This is a form of arteriosclerosis closely related to old age, but risk factors such as diabetes mellitus and chronic kidney disease can directly contribute to its development and progression. Its diagnosis is an incidental finding in histopathological samples., Um caso clínico-patológico foi relatado, diagnosticado no Hospital de Clínica Cirúrgica "Joaquín Albarrán" em Havana. Nessa entidade, apresentou-se uma paciente de 85 anos, com história de diabetes mellitus tipo 2, internada por insuficiência arterial do membro inferior esquerdo, para a qual sofreu amputação supracondiliana e faleceu no terceiro dia de internação. Na autopsia, o diagnóstico patológico da arteriosclerose de Mönckeberg de navios do útero foi conseguido. Essa é uma forma de arteriosclerose intimamente relacionada à velhice, mas fatores de risco como diabetes mellitus e doença renal crônica podem contribuir diretamente para seu desenvolvimento e progressão. Seu diagnóstico é um achado incidental em amostras histopatológicas., Se realizó la comunicación de un caso clínico-patológico, diagnosticado en el Hospital Docente Clínico Quirúrgico “Joaquín Albarrán” de La Habana. En dicha entidad se presentó en una paciente femenina de 85 años de edad con antecedentes de diabetes mellitus tipo 2, ingresada por cuadro de insuficiencia arterial de miembro inferior izquierdo por lo cual se le realizan amputación supracondilia y al tercer día de su estadía hospitalaria, fallece. En la autopsia se arribó al diagnóstico anatomopatológico de arterioesclerosis de Mönckeberg de vasos del útero. Esta es una forma de arterioesclerosis muy relacionada con la senectud, pero factores de riesgo como diabetes mellitus y la enfermedad renal crónica pueden contribuir de forma directa en su desarrollo y progresión. Su diagnóstico es un hallazgo incidental en muestras histopatológicas.

Objective: to determine the behavior of Medulloblastoma in the Pediatric Teaching Hospital “Juan Manuel Márquez” in the period from 2011 to 2017. Method: a descriptive, retrospective and cross-sectional study related to the diagnosis of Medulloblastoma carried out at the “Juan Manuel Márquez” Pediatric Teaching Hospital was carried out in the period from 2011 to 2017, taking into account the behavior of the variables: frequency of occurrence in relation to the rest of the malignant tumors of the central nervous system, gender, age, location, and histological pattern. Data were obtained from the medical records and biopsies of patients with final histological diagnosis of Medulloblastoma. Results: Medulloblastoma was the second malignant tumor of the central nervous system diagnosed in the period studied, preceded by the different variants of Astrocytoma. The most affected age group was between 1 and 5 years, the male gender prevailed, the location of the midline of the cerebellar vermis and the classical histological pattern. Conclusions: Medulloblastoma was the second malignant tumor of the central nervous system diagnosed in the Department of Pathological Anatomy of the “Juan Manuel Márquez” Pediatric Teaching Hospital, its behavior regarding sex, the most affected age group, location and histological pattern, coincided with what was stated in the literature reviewed, Objetivo: determinar el comportamiento del Meduloblastoma en el Hospital Pediátrico Docente “Juan Manuel Márquez” en el período comprendido desde el año 2011 hasta el año 2017. Método: se realizó un estudio descriptivo, retrospectivo y transversal relacionado con los diagnósticos de Meduloblastoma efectuados en el Hospital Pediátrico Docente “Juan Manuel Márquez” en el período comprendido desde el año 2011 hasta el año 2017, teniendo en cuenta el comportamiento de las variables: frecuencia de aparición con relación al resto de los tumores malignos del sistema nervioso central, el género, la edad, la localización, y el patrón histológico. Los datos se obtuvieron de las historias clínicas y biopsias de los pacientes con diagnóstico histológico final de Meduloblastoma. Resultados: el Meduloblastoma fue el segundo tumor maligno del sistema nervioso central diagnosticado en el periodo estudiado, precedido por las diferentes variantes de Astrocitoma. El grupo de edades más afectado fue entre 1 y 5 años, prevaleció el género masculino, la localización de la línea media del vermis cerebeloso y el patrón histológico Clásico. Conclusiones: el Meduloblastoma fue el segundo tumor maligno del sistema nervioso central diagnosticado en el Departamento de Anatomía Patológica del Hospital Pediátrico Docente “Juan Manuel Márquez”, su comportamiento referente al sexo, al grupo de edad más afectado, la localización y el patrón histológico, coincidió con lo planteado en la literatura revisada.

The posterior tibialis is a muscle in the deep posterior compartment of the calf that plays several key roles in the ankle and foot. Posterior tibialis tendon dysfunction is a complex but common and debilitating condition. Degenerative, inflammatory, functional, and traumatic etiologies have all been proposed. Despite being the leading cause of acquired flatfoot, it is often not recognized early enough. Knowledge of the anatomical considerations and etiology of posterior tibialis tendon dysfunction, as well as key concepts in its evaluation and management, will allow health care professionals to develop appropriate intervention strategies to prevent further development of flatfoot deformities.Copyright © SLACK Incorporated.

The posterior tibialis is a muscle in the deep posterior compartment of the calf that plays several key roles in the ankle and foot. Posterior tibialis tendon dysfunction is a complex but common and debilitating condition. Degenerative, inflammatory, functional, and traumatic etiologies have all been proposed. Despite being the leading cause of acquired flatfoot, it is often not recognized early enough. Knowledge of the anatomical considerations and etiology of posterior tibialis tendon dysfunction, as well as key concepts in its evaluation and management, will allow health care professionals to develop appropriate intervention strategies to prevent further development of flatfoot deformities.Copyright © SLACK Incorporated.

Hydropic villi in products of conception continue to pose a diagnostic problem for the anatomical pathologist. It is important to distinguish between complete hydatidiform mole (CM), partial hydatidiform mole (PM) and hydropic degeneration (HD), as hydatidiform moles (especially CM) have a tendency to develop persistent trophoblastic disease. Several studies have demonstrated interobserver variability in the diagnosis of the three conditions, but there have been no studies testing the accuracy of the consensus diagnosis of pathologists experienced in the field. In this study four anatomical pathologists with experience in diagnosing hydatidiform moles selected five cases of HD, seven cases of PM and ten cases of CM on the basis of consensus diagnosis using established criteria. Ploidy studies were done on these 22 cases using fluorescent in situ hybridisation. The 15 cases of HD and CM were diploid, confirming the histological diagnosis. However only five of the seven cases of PM were triploid, the other two being diploid. Review of these two diploid cases showed a mixture of small and large villi with moderate to marked trophoblastic proliferation. On the basis of the significant trophoblastic proliferation and the DNA information, the two cases were reclassified as early complete moles. This study demonstrates that even pathologists experienced in the field have difficulty separating PM from CM. The findings suggest that, in the absence of DNA information, a lesion with hydropic villi showing moderate to marked trophoblastic proliferation should be classified as a complete mole, even if there is a mixture of small and large villi. Ploidy studies are an important adjunct to histological diagnosis, especially when there is an overlap of features.

Hydropic villi in products of conception continue to pose a diagnostic problem for the anatomical pathologist. It is important to distinguish between complete hydatidiform mole (CM), partial hydatidiform mole (PM) and hydropic degeneration (HD), as hydatidiform moles (especially CM) have a tendency to develop persistent trophoblastic disease. Several studies have demonstrated interobserver variability in the diagnosis of the three conditions, but there have been no studies testing the accuracy of the consensus diagnosis of pathologists experienced in the field. In this study four anatomical pathologists with experience in diagnosing hydatidiform moles selected five cases of HD, seven cases of PM and ten cases of CM on the basis of consensus diagnosis using established criteria. Ploidy studies were done on these 22 cases using fluorescent in situ hybridisation. The 15 cases of HD and CM were diploid, confirming the histological diagnosis. However only five of the seven cases of PM were triploid, the other two being diploid. Review of these two diploid cases showed a mixture of small and large villi with moderate to marked trophoblastic proliferation. On the basis of the significant trophoblastic proliferation and the DNA information, the two cases were reclassified as early complete moles. This study demonstrates that even pathologists experienced in the field have difficulty separating PM from CM. The findings suggest that, in the absence of DNA information, a lesion with hydropic villi showing moderate to marked trophoblastic proliferation should be classified as a complete mole, even if there is a mixture of small and large villi. Ploidy studies are an important adjunct to histological diagnosis, especially when there is an overlap of features.

Background: Information about lymphatics and lymphangiogenesis in the human endometrium is limited. We investigated the distribution of endometrial lymphatic vessels during the normal menstrual cycle and in association with endometrial adenocarcinoma and investigated the expression of lymphangiogenic growth factors, vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor-3 (VEGF-R3). Methods and Results: Full thickness uterine samples (n = 23 proliferative; n = 23 secretory) and endometrial adenocarcinoma samples (n = 7 grade I; n = 10 grade III) were collected for the study and analysed by immunohistochemistry and western blotting. Lymphatic vessels of the functionalis were significantly reduced compared with basalis (P = 0.001) across the menstrual cycle with lymphatics of the basalis sometimes intimately associated with spiral arterioles. Lymphatic vessels of endometrial adenocarinomas were located intra-tumoural and peri-tumoural with significant increases in the peri-tumoural lymphatic vessels compared with normal basalis (P = 0.02). Interestingly, high-grade adenocarcinoma vessels containing tumour emboli demonstrated a mixed blood/lymphatic endothelial cell phenotype. VEGF-C and VEGF-D were immunolocalized in glandular epithelium and some stromal cells with the staining intensity of this localization increasing in endometrial adenocarcinoma. Protein analysis identified VEGF-C (58, 41, 31 and 21 kD) and VEGF-D (56, 41, 31 and 21 kD) and VEGF-R3 (148 and 65 kD) peptides in normal endometrium, with significant increases in several of these peptides for VEGF-C and VEGF-D and no changes in protein expression for VEGF-R3 in endometrial adenocarcinoma. Conclusion(s): Endometrial lymphatics are significantly reduced in the functionalis, and increases in endometrial adenocarcinoma peri-tumoural lymphatics are associated with increases in VEGF-C and VEGF-D peptides. © The Author 2007. Published by Oxford University Press on behalf of the European Society

Polycythemia vera is a rare hematological disease of chronic myeloid ieukemia group, Characteristics of evolution of the notion of polycythemia vera during the last four decades was presented in the paper. Bone marrow biop-tates of 34 patients (16 men and 18 women) at the stages of stable course of disease (24 cases) and postpoiycythemic myeloid metaplasia (10 observations) were studied Histological preparations were prepared using the generally accepted method for bone marrow. All cases revealed high cellularity of bone marrow. Erythroid samples were mainly iarge, did not have precise boarders, fiue between each other. Among the cells of myeloid appendix, there dominated mature and maturating forms. Megakaryocytes in all cases were multiple, polymorphic, formed clusters from some cells, had lobulous nuclei. Collagenic fibrosis was absent, reticular one occurred more oftea The authors suggested that in the majority of cases, sternal puncture material is sufficient for pathologoanatomic diagnosis of polycythemia vera.

Background: Information about lymphatics and lymphangiogenesis in the human endometrium is limited. We investigated the distribution of endometrial lymphatic vessels during the normal menstrual cycle and in association with endometrial adenocarcinoma and investigated the expression of lymphangiogenic growth factors, vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor-3 (VEGF-R3). Methods and Results: Full thickness uterine samples (n = 23 proliferative; n = 23 secretory) and endometrial adenocarcinoma samples (n = 7 grade I; n = 10 grade III) were collected for the study and analysed by immunohistochemistry and western blotting. Lymphatic vessels of the functionalis were significantly reduced compared with basalis (P = 0.001) across the menstrual cycle with lymphatics of the basalis sometimes intimately associated with spiral arterioles. Lymphatic vessels of endometrial adenocarinomas were located intra-tumoural and peri-tumoural with significant increases in the peri-tumoural lymphatic vessels compared with normal basalis (P = 0.02). Interestingly, high-grade adenocarcinoma vessels containing tumour emboli demonstrated a mixed blood/lymphatic endothelial cell phenotype. VEGF-C and VEGF-D were immunolocalized in glandular epithelium and some stromal cells with the staining intensity of this localization increasing in endometrial adenocarcinoma. Protein analysis identified VEGF-C (58, 41, 31 and 21 kD) and VEGF-D (56, 41, 31 and 21 kD) and VEGF-R3 (148 and 65 kD) peptides in normal endometrium, with significant increases in several of these peptides for VEGF-C and VEGF-D and no changes in protein expression for VEGF-R3 in endometrial adenocarcinoma. Conclusion(s): Endometrial lymphatics are significantly reduced in the functionalis, and increases in endometrial adenocarcinoma peri-tumoural lymphatics are associated with increases in VEGF-C and VEGF-D peptides. © The Author 2007. Published by Oxford University Press on behalf of the European Society

Breast cancer is the most common form of malignancy affecting women in the Western world. Today, anticancer treatment can control primary breast tumors, but treatment and prevention of metastatic disease still represents a major challenge in the management of breast cancer patients. It has been shown that Wnt-5a plays an important role in breast cancer, since loss of that protein is associated with a higher frequency of metastasis. The findings presented in this thesis show that Wnt-5a inhibits the metastatic behaviour of breast cancer cells by blocking Ca2+-induced NFAT activation. This inhibition is mediated through activation of Yes, Cdc42 and CK1?. Furthermore, based on sequence analysis of the Wnt-5a protein, I identified two peptides with Wnt-5a mimicking ability. One of the peptides was shortened and modified to yield the formylated hexapeptide, Foxy-5, which was able to copy the effects of Wnt-5a on the intracellular signaling, adhesion and migration of breast epithelial cells. Experiments were performed in which the mammary fat pads of athymic (immunodeficient) BALB/c mice and normal BALB/c mice were inoculated with 4T1 breast cancer cells. Administration of Foxy-5 every fourth day did not lead to any difference in primary tumor growth, whereas it did radically reduce the level of metastasis to lung and liver compared to controls. The mechanism behind the inhibited metastasis formation seemed to be impaired migration and invasion in the breast cancer cells. In addition, the Wnt-5a coreceptor Ror2 was found to be involved in regulation of breast cancer cell migration and to associate with DDR1, a tyrosine kinase receptor that participates in Wnt-5a signaling. These results further emphasize the importance of Wnt-5a in breast cancer metastasis, and they identify a novel potential treatment strategy.

Estrogen receptor (ER) status can define breast cancer patients who would benefit from adjuvant tamoxifen therapy. However, resistance to tamoxifen is often observed and possible mechanisms may be loss or reduction of ER, dysfunctional ER- signaling and ligand independent activation of the receptor. Hypoxia and hypoxia inducible factor-1? (HIF-1) expression has been correlated to loss of ER in breast tumors. Cyclin D1, initially described as a cell cycle regulator, might also function as a cofactor to ER inducing ligand independent activation of the receptor. We therefore determined the relation between ER, cyclin D1 and HIF-1 expression in primary breast tumors and cell lines. Further, the prognostic and treatment predictive value of cyclin D1 and HIF-1 was analyzed in breast cancer patients receiving two years of tamoxifen versus no adjuvant treatment. The results indicated that ER heterogeneity in primary breast tumors was associated with cyclin D1 and HIF-1 expression. Further, breast cancer patients with cyclin D1 high tumors did not benefit from tamoxifen treatment. The survival for untreated patients with cyclin D1 high tumors was nevertheless slightly better than for patients with cyclin D1 low tumors. Hypoxia was also strongly linked to ER downregulation in DCIS and invasive breast cancer and caused ER downregulation in breast cancer cell lines. Interestingly, hypoxic cells were less differentiated, showing changes in morphology, proliferation and cytokeratin 19 expression. The hypoxia induced ER reduction was due to both proteasomal degradation and decreased transcription and active extracellular regulated kinase (ERK1/2)was involved in the transcriptional regulation of ER. Consequently, tamoxifen treatment did not affect proliferation as efficiently in hypoxia as in normoxia, but ERK1/2 inhibitors efficiently increased the tamoxifen effect in hypoxia. Unexpectedly, tumor specific HIF-1 expression was not a predictive marker for tamoxifen response in preme

Dementia is a state of permanent loss of cognitive function, most commonly affecting the elderly. With a rapidly growing aged population, the spectrum of disorders that lead to dementia is exerting an ever-increasing toll on patients, families and society alike. The most common dementing disorders are Alzheimer's disease and vascular dementia. Although Alzheimer's disease is very common and was described almost a century ago, the pathomechanisms are imperfectly understood, and mainly symptomatic therapy is available. Treatment options are even more meagre in vascular dementia, but in many cases, this disorder can possibly be prevented by risk factor management. Since both Alzheimer's disease and vascular dementia are common in the elderly population, it is not uncommon for both diseases to be present to some degree in the same patient. Increasing evidence suggests that the disease mechanisms not only coexist, but that they interact synergistically, further exacerbating the clinical disorder. The purpose of this thesis was to explore features of vascular pathology in Alzheimer's disease and vascular dementia, to improve basic understanding of the disease processes in play. We have shown that one of the major hallmarks of Alzheimer's disease, deposition of amyloid protein in the cerebrovasculature (cerebral amyloid angiopathy), is surprisingly common in vascular dementia, and frequently more severe than in Alzheimer's disease. In Alzheimer's disease, cerebral amyloid angiopathy is associated with ischemic white matter disease, but in vascular dementia, cerebral amyloid angiopathy is associated with cortical microinfarctions. Furthermore, the interrelationship between the amyloid beta (A-beta) peptide species deposited is affected by the presence of cerebrovascular disease, which is associated with a relative increase in deposition of the more fibrillogenic and toxic variant of the Ab peptide, and more severe degeneration of vascular components.

Microvessel density (MVD) is a widely used surrogate measure of angiogenesis in pathological specimens and tumour models. Measurement of MVD can be achieved by several methods. Automation of counting methods aims to increase the speed, reliability and reproducibility of these techniques. The image analysis system described here enables MVD measurement to be carried out with minimal expense in any reasonably equipped pathology department or laboratory. It is demonstrated that the system translates easily between tumour types which are suitably stained with minimal calibration. The aim of this paper is to offer this technique to a wider field of researchers in angiogenesis.