Karl Rokitansky: his Bohemian years and his relationship with Jan Evangelista Purkyne: on the occasion of bicentenary of birth

Karl Rokitansky was born on 19th February 1804 in the historic Czech town of Hradec Králové (K?niggr?tz). During 1821-1824 he studied for 3 years at the medical faculty of Prague University. In the archives of Charles University there is a record of Rokitansky's performance during these three years. At the university he met J. E. Purkyne who was teaching anatomy at that time. Relationship between the two world--renowned medical scientists of Czech origin is discussed.     

Competition-based cellular peptide binding assays for 13 prevalent HLA class I alleles using fluorescein-labeled synthetic peptides

We report the development, validation, and application of competition-based peptide binding assays for 13 prevalent human leukocyte antigen (HLA) class I alleles. The assays are based on peptide binding to HLA molecules on living cells carrying the particular allele. Competition for binding between the test peptide of interest and a fluorescein-labeled HLA class I binding peptide is used as read out. The use of cell membrane-bound HLA class I molecules circumvents the need for laborious biochemical purification of these molecules in soluble form. Previously, we have applied this principle for HLA-A2 and HLA-A3. We now describe the assays for HLA-A1, HLA-A11, HLA-A24, HLA-A68, HLA-B7, HLA-B8, HLA-B14, HLA-B35, HLA-B60, HLA-B61, and HLA-B62. Together with HLA-A2 and HLA-A3, these alleles cover more than 95% of the Caucasian population. Several allele-specific parameters were determined for each assay. Using these assays, we identified novel HLA class I high-affinity binding peptides from HIVpol, p53, PRAME, and minor histocompatibility antigen HA-1. Thus these convenient and accurate peptide-binding assays will be useful for the identification of putative cytotoxic T lymphocyte epitopes presented on a diverse array of HLA class I molecules.     

Standard atlas space for C57BL/6J neonatal mouse brain

A standard atlas space with stereotaxic co-ordinates for the postnatal day 0 (P0) C57BL/6J mouse brain was constructed from the average of eight individual co-registered MR image volumes. Accuracy of registration and morphometric variations in structures between subjects were analyzed statistically. We also applied this atlas coordinate system to data acquired using different imaging protocols as well as to a high-resolution histological atlas obtained from separate animals. Mapping accuracy in the atlas space was examined to determine the applicability of this atlas framework. The results show that the atlas space defined here provides a stable framework for image registration for P0 normal mouse brains. With an appropriate feature-based co-registration strategy, the probability atlas can also provide an accurate anatomical map for images acquired using invasive imaging methods. The atlas templates and the probability map of the anatomical labels are available at .     

Adequacy and support of physiological functions in the acutely ill cirrhotic patient

The cirrhotic condition is characterized by a series of changes in physiological functions and of subclinical alterations that imply an abnormal and fragile adaptive pattern with reduced resistance to superimposed distress. In the care of the critically ill cirrhotic patient, the supportive measures aimed at maintaining physiological stability through the control of such debilitating factors have a key role and are not secondary in importance to the more obvious measures needed to treat clinically evident and specific alterations or complications. The relationship between hepatic malfunction and the development of these physiological abnormalities is not fully understood. Our knowledge of the problem, however, has been recently improved and the need for supportive measures motivated by a series of notions on cardiorespiratory and metabolic abnormalities and interactions in hepatic decompensation.

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Resumen La condición cirrótica se caracteriza por una serie de cambios en las funciones fisiológicas y por alteraciones subclinicas que implican un patrón de adaptación anormal y fragil de resistencia reducida al estrés. Estas incluyen disfunción respiratoria con tendencia a la hipoxemia arterial en presencia de elevados indices cardiacos, una situatión crónica de hiperdinamismo cardiovascular pero con precaria eficacia miocárdica y latente riesgo de falla de alto débito, y cambios metabólicos que se traducen en un estado de fallas multisistémicas interrelacionadas características del cirrótico. En el cuidado del paciente cirrótico en estado crítico, las medidas de soporte orientadas al mantenimiento de la estabilidad fisiológica mediante el control de tales factores debilitantes tienen una importancia capital y no son secundarias frente a aquellas muy obvias que se requieren para tratar alteraciones o complicaciones específicas y clínicamente evidentes. La relación entre la disfunción hepática y el desarrollo de las mencionadas anormalidades fisiológicas no está totalmente aclarada, sin embargo, el estado de nuestro conocimiento sobre el problema ha sido enriquecido recientemente y se ha fortalecido la necesidad de establecer medidas de soporte por una serie de nociones relativas a las anormalidades e interacciones cardiorrespiratorias y metabólicas de la descompensación hepática.

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Résumé La cirrhose est caractérisée par des séries de variations des fonctions physiologiques et de modifications cliniques qui impliquent des modalités d'adaptation anormale et fragile se traduisant par une résistance réduite à l'état de détresse ou peut se trouver le cirrhotique. Des mesures appropriées pour maintenir la stabilité physiologique ont un rôle principal en présence de ces facteurs défavorables. Elles ne doivent pas être considérées comme moins importantes que les mesures essentielles qui sont nécessaires pour traiter les complications et les modifications cliniques spécifiques. La relation entre l'altération des fonctions du foie et le développement des anomalies physiologiques précitées n'est pas parfaitement élucidée, cependant, nos connaissances de ce problème ont été récemment améliorées et le besoin de mesures adéquates de soutien est devenu manifeste en raison de séries acquises de notions concernant les anomalies cardio-respiratoires et métaboliques ainsi que les interactions de la décompensation hépatique.

     

Structure-intestinal transport and structure-metabolism correlations of some potential cancerostatic pyrimidine nucleosides in isolated rat jejunum

Summary Both transport and biotransformation processes for a series of pyrimidine nucleobases, ribonucleosides, 2-deoxyribonucleosides, and acetyl and 5-substituted derivatives of the cancerostatic agent araC were studied in the isolated everted rat jejunum with a continuous perfusion technique. Metabolic alterations during penetration were assessed by HPLC. 5-Halogeno and 5-deoxy derivatives of cytosine nucleosides exhibited higher transport rates and higher stability towards the deamination reaction than did unsubstituted derivatives. Octanol-buffer partition coefficients were estimated for the study compounds, and fragmental constants for the sugar moieties of nucleosides were assessed. With the present study compounds there was no correlation between lipophilicity and transport rate, as previously reported, but there was a correlation between lipophilicity and metabolic alteration of araC derivatives (r=0.99, n=5).     

Reported disease and psychological well-being in Swiss adults

Summary In Switzerland, and in many other countries as well, the distribution of morbidity and perceived health in the general population and their determining factors have not been systematically studied so far. This article reports an exploratory study of prevalence of two complex health indicators, longstanding disease (Disease) and psychological well-being (Well-being) and of their environmental, person-specific and behavioural determinants. Data from a health survey conducted in five cantons and three language regions as part of the Swiss Intercantonal Health Indicators Project were used. Whereas distributions of prevalence of Disease according to gender, age, level of education and place of living confirm results of other studies, unexpected prevalence patterns were found for Well-being, especially with regard to gender differences. Multivariate analyses by general linear models (independent sub-samples of the study population were used to develop and validate models) showed different sets of environmental, person-specific and behavioural factors to explain inter-individual differences of Disease and Well-being, both in the total validation sample and in sub-samples of women and men. The results are discussed with regard to implications for socioepidemiological health research.

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Zusammenfassung Wie in zahlreichen anderen Ländern so sind bisher in der Schweiz die Verteilung und die Determinanten von Morbidität und wahrgenommener Gesundheit in der Gesamtbevölkerung nicht systematisch untersucht worden. Die vorliegende Arbeit berichtet über eine explorative Studie über die Prävalenz zweier komplexer Gesundheitsindikatoren, länger andauernde Krankheit (Disease) und psychisches Wohlbefinden (Well-being), und über deren jeweilige umweltbedingte, personale und verhaltensbezogene Einflußfaktoren. Grundlage dafür waren Daten, die in einer Bevölkerungsbefragung in 5 Kantonen und 3 Sprachregionen im Rahmen des Interkantonalen Gesundheitsindikatorenprojekts (IGIPPROMES) erhoben wurden. Während die Verteilung der Prävalenz von Krankheit nach Geschlecht, Alter, Bildungsstatus und Wohnortgrösse den Ergebnissen anderer Studien entspricht, ergaben sich bei der Prävalenz von Wohlbefinden unerwartete Verteilungsmuster, insbesondere Unterschiede zwischen Frauen und Männern. Eine Analyse interindividueller Unterschiede von Krankheit und Wohlbefinden mit Hilfe eines allgemeinen linearen Modells (Modellentwicklung und Validierung an unabhängigen Teilstichproben) zeigte, dass diese durch jeweils spezifische Konstellationen von Umwelt-, Personen- und Verhaltensfaktoren erklärt werden können, sowohl in der gesamten Validierungsstichprobe als auch in den Teilstichproben für Frauen und Männer. Die Ergebnisse der Studie werden in Hinblick auf die Weiterentwicklung der sozialepidemiologischen Gesundheitsforschung diskutiert.

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Résumé En Suisse, comme dans beaucoup d'autres pays, la morbidité et le bien-être psychologique de la population générale n'ont presque pas été étudiés jusqu'à présent. Dans ce rapport, les résultats d'une étude exploratoire sur deux indicateurs complexes de santé, maladie chronique (Disease) et bien-être psychologique (Well-being) et sur les facteurs de l'environnement, de la personnalité et du comportement qui influencent ces deux indicateurs sont présentés. Cette étude faisait part du projet intercantonal sur les indicateurs de santé (IGIP-PROMES) et se base sur les données tirées d'une enquête auprès des populations de cinq cantons et trois régions linguistique de la Suisse. Tandis que la prévalence de l'indicateur «maladie» par sexe, age, degré de formation et dimension du lieu de résidence était conforme aux résultats d'autres études, des distributions inattendues de la prévalence de «bien-être psychologique», notamment des différences entre hommes et femmes ont été trouvées. Une analyse des différences entre individue de «maladie» et «bien-être» au moyen d'un modèle linéaire généralisi — le développement et l'évaluation duquel ont été faits à l'aide de deux échantillons d'occasion indépendents — a montré que des constellations spécifiques constituées de facteurs de l'environnement, de la personnalité et du comportement, peuvent expliquer ces différences, soit dans l'échantillon d'évaluation totale, soit dans les échantillons partiels de femmes et d'hommes. Ces résultats sont discutés par rapport à l'évolution de la recherche socio-épidémiologique.

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Paper presented at a symposium on The Public Health Perspective of Social and Preventive Medicine, in celebration of the 20th anniversary of the Department of Social and Preventive Medicine, University of Berne, 25 June 1992 in Berne.     

Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies.

PURPOSE: To discuss the absolute benefits from adjuvant systemic therapy knowledge of long-term outcomes and baseline risks of relapse and disease-specific survival are required. We assessed the 10-year outcomes in a population-based cohort of node-negative (N-) lymphovascular negative (LV-) early breast cancers diagnosed from 1989 to 1991 who did not receive adjuvant systemic therapy. METHODS: One thousand one hundred eighty-seven cases of pT(1-2)N(0) LV- breast cancers with a median follow-up of 10.4 years were reviewed. Kaplan-Meier survival curves for relapse free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) were compared with log-rank tests with cohorts stratified for tumor size and grade. RESULTS: The median age of this series was 62 years. Four hundred thirty tumors were < or = 1 cm in diameter (cohort 1), 507 were 1.1-2 cm (cohort 2), and 250 were 2.1 to 5 cm in diameter (cohort 3). The 10-year outcomes for cohorts 1, 2, and 3, respectively, were significantly different: RFS, 82%, 75%, and 66%; BCSS, 92%, 90%, and 77%; and OS, 79%, 78%, and 66%. Tumor grade significantly altered outcome within size cohorts, particularly in pT(1)N(0) breast cancers. CONCLUSION: This study provides detailed information on the continued relapse and breast cancer death rate to 10 years of follow-up. Specifically, without adjuvant systemic therapy, patients with LV-, N - breast cancer had a > or = 25% 10-year risk of relapse and a corresponding 10-year breast cancer death rate of > or = 10% if they had either a grade 3 tumor < or = 1 cm, a grade 2 to 3 tumor from 1.1 to 2 cm, or any grade tumor greater than 2 cm.