Medical support system for continuation of care based on XML web technology.

In this paper, the implementation of an Internet-based telematic service for medical support is presented, which was developed and operated in pilot form within the INTRANET HEALTH CLINIC project--a 2-year project supported by the European Commission under the Health Telematics Programme. The aim of the application is to offer high quality care to users of health services over inexpensive communication pathways, using Internet-based, interactive communication tools, like remote access to medical records and transmission of multimedia information. The XML technology was employed to achieve customised views on patient data, according to the access rights of different user profiles. Strict security and access control policy were implemented to ensure secure transmission of medical data through the Internet. The system was designed to collaborate with existing clinical patient record systems and to be adjustable to different medical applications. Current implementations include the fields of Oncology, Lupus Erythrematosis, Obstetrics and Chronic Obstructive Pulmonary disease. The results of the pilot operation with oncological patients in Greece were encouraging, so that the refining of the system and its expansion to a large number of patients is already in progress.

Intranet health clinic: Web-based medical support services employing XML.

In this paper, the implementation of an Internet-based telematic service for medical support is presented, which operates in pilot form within the INTRANET HEALTH CLINIC project--a two-year project supported by the European Commission under the Health Telematics Programme. The aim of the application is to offer high quality care to users of health services over inexpensive communication pathways, using Internet-based, interactive communication tools, like remote access to medical records and transmission of multimedia information. The XML technology was employed to achieve customised views on patient data, according to the access rights of different users. Strict security and access control policy were implemented to ensure secure transmission of medical data through the Internet. The system is designed to collaborate with existing clinical patient record systems and to be adjustable to different medical applications. Current pilot implementations are under clinical evaluation and include oncological patients (Greece), Lupus Erythrematosis (Canada), Obstetrics (Belgium) and Chronic Obstructive Pulmonary disease (Spain).

A cytomorphological scheme of differentiating neuronal phenotypes in cerebellar medulloblastomas based on immunolocalization of class III beta-tubulin isotype (beta III) and proliferating cell nuclear antigen (PCNA)/cyclin.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III) to that of the proliferating cell nuclear antigen (PCNA)/cyclin in 46 cerebellar neuroblastic tumors (medulloblastomas). Both class III beta-tubulin (beta III) and PCNA/cyclin reactivities were present in all tumors, but the topographic distribution and cytomorphologic features of stained cells varied considerably between classic and desmoplastic medulloblastomas. Four neoplastic phenotypes, representing gradations of neuronal differentiation, were identified: [Allegranza 1991] apolar, blast-like PCNA/cyclin(+) cells devoid of beta III reactivity (Nb1); [Bravo et al. 1987] apolar, often binucleated and/or fusiform, PCNA/cyclin (+) cells with pronounced beta III staining in their protoperikarya and their growth cones (Nb2); [Burger et al. 1987] beta III-immunoreactive immature polar neurons with varying degrees of neuritic development, reading to significant neuritogenesis in the "pale islands" of desmoplastic medulloblastomas (Nb3). The majority of Nb3 phenotypes were PCNA/cyclin (-), although subpopulations of such polar tumor cells exhibiting PCNA staining were also identified; and [Burger et al. 1991] beta III-immunoreactive, PCNA/cyclin (-) mature ganglion-like cells (Nb4). A high PCNA/cyclin labeling index (> 80%) was obtained in 20 poorly differentiated classic medulloblastomas while, significant intratumoral staining heterogeneity was observed in 23 cases of desmoplastic medulloblastomas and 3 cases of "medulloblastomas with ganglion cells": A high labeling index (LI)(> 80%) in the reticulin-impregnated poorly differentiated areas of tumor contrasted with sharp decline of PCNA staining and a very low LI (< 10%) in areas of overt neoplastic neuritogenesis ("pale islands") displaying strong beta III reactivity. Neoplastic ganglion cells were beta III (+)/PCNA (-). Our findings indicate that the majority of differentiating neuronal phenotypes undergoing cytomorphological changes of neuritic development (Nb3), and all neoplastic ganglion cells (Nb4 phenotypes) are PCNA (-), in contrast to actively proliferating, poorly differentiated, tumor cells that are PCNA (+). Although PCNA staining corresponded in part, to beta III (-) blast-like elements (Nb1), a co-expressive pattern of staining for beta III and PCNA/cyclin also was observed in subpopulations of poorly differentiated tumor cells (Nb2), indicating that transformed neuroblasts are capable of expressing differentiation-associated neuronal cytoskeletal proteins while still remaining in the proliferative compartment of the cell cycle. Our observations suggest that only neuritogenesis and acquisition of ganglionic phenotype are significant maturational events in medulloblastomas (indicating entry into the quiescent phase of the cell cycle) and provide further support for the neuronal lineage and differentiation potential of these cerebellar embryonal tumors.

The stromal Schwann cell during maturation of peripheral neuroblastomas. Immunohistochemical observations with antibodies to the neuronal class III beta-tubulin isotype (beta III) and S-100 protein.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III; analogous to the beta' 1-/beta 2-tubulin isoform) to the Schwann cell-associated S-100 protein focusing on topographic relationships of Schwann-like cells to differentiating neuronal phenotypes during stromal development in human peripheral neuroblastomas. The earliest appearance of Schwann cells in poorly differentiated (classical) neuroblastomas is heralded by S-100 protein-immunoreactive cells in close association with tumor blood vessels. In subsequent stages of maturation, i.e. maturing neuroblastoma (ganglioneuroblastoma and gangliocytoma), S-100 protein-positive cells are mostly confined to the connective tissue septa dividing tumor into lobules, and are not freely interspersed with beta III-immunoreactive neoplastic neurons. Significant ensheathment of individual axon-like processes by Schwann cells occurs only in mature ganglioneuromas. beta III is localized in a full spectrum of neoplastic neuronal phenotypes, ranging from poorly-differentiated apolar neuroblasts (often signaling ensuing neuritogenesis) to mature ganglion cells, but not in Schwann cells, or other cell types of the stroma. Our observations suggest that Schwann cells in peripheral neuroblastomas are stroma-derived cells and not an expression of divergent neoplastic differentiation.

Differential localization of class III, beta-tubulin isotype and calbindin-D28k defines distinct neuronal types in the developing human cerebellar cortex.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III) to that of calbindin-D28k in 40 human fetal and postnatal cerebella ranging from 12 weeks gestation to adulthood. In the external granule layer of the developing cerebellar cortex, beta III staining was present in the premigratory (postmitotic) zone of horizontal neurons but was absent in "epithelioid" cells of the subpial proliferative mitotic zone. In the molecular layer, intense beta III staining was associated with parallel fibers, stellate/basket neurons and migrating fusiform granule neurons. beta III staining was also present in internal granule neurons. In contrast, beta III was not detectable in fetal and neonatal Purkinje neurons and Golgi II neurons, but was evident in these neurons from juvenile and adult cerebella. Calbindin-D28k staining was present in Purkinje neurons also delineating their somatic spines ("pseudopodia"), lateralizing and apical dendrites (including dendritic spines), subpopulations of small to intermediate-sized Golgi II neurons in the internal granule layer ("synarmotic cells" of Landau), large to medium-sized subcortical Golgi II neurons and neurons of cerebellar roof nuclei, at various gestational stages and postnatally. It was absent in the external granule layer, parallel fibers, stellate/basket and internal granule neurons. Variable degrees of beta III and calbindin-D28k staining were detected in subpopulations of immature neuroepithelial cells of the ventricular matrix at the roof of the fourth ventricle. Glial (including Bergmann glia) and mesenchymal cells were not stained for either antigenic determinants. The differential expression of calbindin-D28k and beta III defines distinct populations of neurons in the developing human cerebellar cortex and supports the ontogenetic concept of Ramon y Cajal.