21585
2020
deu
doctoralthesis
1
2020-11-07
--
2020-10-15
Analyse der B-Zell-Entwicklung und -Differenzierung bei Patienten mit chronischer Immunthrombozytopenie
Analysis of B-cell development and differentiation in patients with chronic immune thrombocytopenia
Die Immunthrombozytopenie (ITP) ist eine erworbene Autoimmunerkrankung, bei der sich Autoantikörper gegen Thrombozyten bilden. Dadurch werden diese, unter anderem in der Milz, vermehrt abgebaut und es treten Blutungskomplikationen auf. Der fehlgeleiteten Immunabwehr wird versucht mit medikamentösen Therapien wie z. B. mit Glucocorticoiden und Rituximab bis hin zur Splenektomie entgegenzuwirken.
Im Rahmen dieser Arbeit untersuchte ich durchflusszytometrisch die Verteilung der B-Zell-Subpopulationen bei Patienten mit chronischer, primärer ITP und Gesunden hinsichtlich einer möglichen Störung in der B-Zell-Entwicklung und -Differenzierung. Dabei wurden 7 Knochenmark-, 28 Blut- und 12 Milzproben von ITP-Patienten sowie 5 Knochenmark- und 10 Milzproben von Gesunden aufbereitet. Anschließend wurden die B-Zell-Subpopulationen mittels immunphänotypischer Marker gefärbt um die Proben danach durchflusszytometrisch zu vermessen und zu charakterisieren. Zusätzlich erfolgte der Vergleich zu laboreigenen, bereits etablierten Referenzwerten von 220 Blutproben von Gesunden.
Bei den Knochenmarkproben konnten keine signifikanten Unterschiede in der Verteilung von Vorläufer-B-Zellen zwischen den ITP-Patienten und den Gesunden beobachtet werden, d. h. die frühe B-Zell-Entwicklung im Knochenmark erscheint bei der ITP auf zellulärer Ebene nicht beeinträchtigt. Die Analyse der Blutproben zeigte, dass auch keine signifikanten Unterschiede in der Verteilung von naiven B-Zellen zwischen den ITP-Patienten und den Gesunden vorzufinden sind. Dies bekräftigt, dass bei der ITP auf zellulärer Ebene keine Abweichungen in der frühen pre-immunen B-Zell-Entwicklung vorzuliegen scheinen und eine intakte B-Zell-Reifung bis hin zur naiven B-Zelle stattfindet. Es zeigte sich jedoch bei den ITP-Patienten ein erhöhter Anteil an anergen B-Zellen und atypischen Gedächtnis-B-Zellen, von denen allgemein angenommen wird, dass sie aus einer chronischen bzw. dysregulierten antigen-abhängigen B-Zell-Aktivierung entstammen. Aus der Untersuchung der Milzproben zeigte sich zudem, dass bei den ITP-Patienten der Anteil der antikörperproduzierenden Plasmablasten im Vergleich zu den Gesunden erhöht ist. Folglich lassen sich bei der ITP auf zellulärer Ebene vor allem Abweichungen in der späten Phase der B-Zell-Differenzierung nachweisen. Es kann somit angenommen werden, dass Störungen der B-Zell-Entwicklung, wie sie auf zellulärer Ebene bei verschiedenen mit sekundärer ITP einhergehenden Erkrankungen (systemischer Lupus erythematodes, variables Immundefektsyndrom) beschrieben wurden, bei der primären ITP nicht für die Produktion von antithrombozytären Antikörpern notwendig sind. Eine weitere detaillierte Aufarbeitung, auf welcher Ebene der B-Zell-Differenzierung der Toleranzverlust gegenüber thrombozytären Antigenen auftritt, ist entscheidend für die zukünftige Entwicklung spezifischer, zellgerichteter Therapien.
Immune thrombocytopenia (ITP) is an acquired autoimmune disease in which autoantibodies against platelets are produced. As a result, the platelets are increasingly reduced in the spleen, and bleeding disorders occur. The misdirected immune defense is tried to counteract with drug therapies such as glucocorticoids and rituximab up to surgery with splenectomy.
In this study, I used flow cytometry to investigate the distribution of B-cell subpopulations in patients with chronic, primary ITP and healthy individuals regarding possible disruptions in B-cell development and differentiation. 7 bone marrow, 28 blood and 12 spleen samples from ITP patients as well as 5 bone marrow and 10 spleen samples from healthy individuals were processed. The B-cell subpopulations were stained using immunophenotypic markers to measure and characterize the samples by flow cytometry. In addition, the results were compared with the laboratory's own established reference values of 220 blood samples from healthy individuals.
No significant differences in the distribution of precursor B cells between the ITP patients and the healthy subjects could be observed in the bone marrow samples. Therefore, the early B-cell development in the bone marrow does not appear to be impaired in ITP at the cellular level. The analysis of the blood samples showed that there were no significant differences in the distribution of naive B cells between the ITP patients and the healthy individuals. This confirms that in ITP at the cellular level there seem to be no deviations in the early pre-immune B-cell development and that intact B-cell maturation takes place up to naive B-cells. However, ITP patients revealed an increased proportion of anergic B-cells and atypical memory B-cells, which are generally assumed to originate from chronic or dysregulated antigen-dependent B-cell activation. The examination of the spleen samples also displayed that the proportion of antibody-producing plasmablasts in ITP patients is higher than in healthy individuals. Consequently, in ITP at the cellular level especially deviations in the late phase of B-cell differentiation can be detected. It can thus be assumed that disorders of B-cell development, as described at the cellular level in various diseases associated with secondary ITP (systemic lupus erythematosus, variable immunodeficiency syndrome), are not necessary for the production of anti-platelet antibodies in primary ITP. A further detailed investigation at which stage of the B-cell differentiation a loss of tolerance to platelet antigens occurs is crucial for the future development of specific, cell-directed therapies.
urn:nbn:de:bvb:20-opus-215854
10.25972/OPUS-21585
publish
X 129015
Deutsches Urheberrecht mit Print on Demand
Daniel Schuster
deu
swd
Essenzielle Thrombozytopenie
deu
swd
B-Zelle
deu
swd
B-Lymphozyt
deu
swd
Durchflusscytometrie
deu
uncontrolled
Immunthrombozytopenie
deu
uncontrolled
ITP
deu
uncontrolled
B-Zelle
deu
uncontrolled
Durchflusszytometrie
eng
uncontrolled
immune thrombocytopenia
eng
uncontrolled
b-cell
eng
uncontrolled
b-lymphocyte
eng
uncontrolled
flow cytometry
Krankheiten
open_access
Kinderklinik und Poliklinik
Universität Würzburg
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/21585/Schuster_Daniel_Immunthrombozytopenie.pdf
9623
2013
eng
article
1
--
--
--
Evaluation of suspected malignant hyperthermia events during anesthesia
Background
Malignant hyperthermia (MH), a metabolic myopathy triggered by volatile anesthetics and depolarizing muscle relaxants, is a potentially lethal complication of general anesthesia in susceptible patients. The implementation of modern inhalation anesthetics that research indicates as less potent trigger substances and the recommended limitations of succinylcholine use, suggests there may be considerable decline of fulminant MH cases. In the presented study, the authors analyzed suspected MH episodes during general anesthesia of patients that were referred to the Wuerzburg MH unit between 2007 and 2011, assuming that MH is still a relevant anesthetic problem in our days.
Methods
With approval of the local ethics committee data of patients that underwent muscle biopsy and in vitro contracture test (IVCT) between 2007 and 2011 were analyzed. Only patients with a history of suspected MH crisis were included in the study. The incidents were evaluated retrospectively using anesthetic documentation and medical records.
Results
Between 2007 and 2011 a total of 124 patients were tested. 19 of them were referred because of suspected MH events; 7 patients were diagnosed MH-susceptible, 4 MH-equivocal and 8 MH-non-susceptible by IVCT. In a majority of cases masseter spasm after succinylcholine had been the primary symptom. Cardiac arrhythmias and hypercapnia frequently occurred early in the course of events. Interestingly, dantrolene treatment was initiated in a few cases only.
Conclusions
MH is still an important anesthetic complication. Every anesthetist must be aware of this life-threatening syndrome at any time. The rapid onset of adequate therapy is crucial to avoid major harm and possibly lethal outcome. Dantrolene must be readily available wherever MH triggering agents are used for anesthesia.
BMC Anesthesiology
10.1186/1471-2253-13-24
http://www.biomedcentral.com/1471-2253/13/24
urn:nbn:de:bvb:20-opus-96231
In: BMC Anesthesiology (2013) 13: 24, doi:10.1186/1471-2253-13-24
Frank Schuster
Stephan Johannsen
Daniel Schneiderbanger
Norbert Roewer
eng
uncontrolled
Malignant hyperthermia
eng
uncontrolled
In vitro contracture test
eng
uncontrolled
Succinylcholine
eng
uncontrolled
Volatile anesthetics
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9623/Schuster_1471-2253-13-24.pdf
28647
2022
deu
doctoralthesis
1
2022-09-08
--
2022-07-11
„Da schleicht hinein ein böser Gast“ - Körper- und Krankheitsmetaphern in der medizinischen Ratgeberliteratur des 16. und 17. Jahrhunderts
"An Evil Guest Is Creeping In" - Metaphors for Illness and the Body in 16th and 17th Century Health Guides
Metaphern prägen unser Verständnis des Körpers und seiner Krankheiten. Die Kommunikation zwischen Heilkundigen und Kranken basiert daher maßgeblich auf Metaphern. Dieser Beitrag untersucht deutschsprachige Gesundheitsratgeber des 16. und 17. Jahrhunderts, die von gelehrten Ärzten für ein Laienpublikum verfasst wurden. Mit den Methoden der qualitativen Metaphernanalyse soll das Bild einer kommunikativen Praxis vor dem Hintergrund ihrer kulturhistorischen Rahmenbedingungen gezeichnet werden. Metaphern erweisen sich als wichtiges Werkzeug, um die sprachliche und intellektuelle Kluft zwischen Laien- und Gelehrtenwelt zu überbrücken. Geschickt lenken die ärztlichen Autoren mit Hilfe von Metaphern den Blick des Lesers. Dabei bieten sie ihm auch sinnstiftende Erkenntnisse und Ansätze zur Teilhabe am therapeutischen Prozess.
Metaphors can shape our conception of the body and our understanding of its diseases. Communication between medical practitioners and patients, therefore, has often relied on metaphors. This study examines 16th and 17th century health guides written in German vernacular by university-trained medical practitioners. Using qualitative metaphor analysis, a communications practice and its historical background are explored [for insights into patient-practitioner communications]. Metaphors emerge to create a linguistic and intellectual common ground between experts in medicine and the lay reading public. They could serve to manipulate the patient but also to facilitate participation in the therapeutic process and to satisfy the patients’ need for understanding.
urn:nbn:de:bvb:20-opus-286477
10.25972/OPUS-28647
publish
X 130160
CC BY-SA: Creative-Commons-Lizenz: Namensnennung, Weitergabe unter gleichen Bedingungen 4.0 International
Daniel Schuster
deu
swd
Metaphernanalyse
deu
swd
Ratgeber
deu
swd
Medizin
deu
swd
Frühe Neuzeit
deu
swd
Volkssprache
deu
uncontrolled
Gesundheitsratgeber
eng
uncontrolled
Gout
eng
uncontrolled
Early Modern
deu
uncontrolled
Vernakularisierung
deu
uncontrolled
Gicht
deu
uncontrolled
Podagra
deu
uncontrolled
Pest
eng
uncontrolled
health guide
eng
uncontrolled
metaphor analysis
eng
uncontrolled
vernacular medicine
Medizin und Gesundheit
Geschichte Mitteleuropas; Deutschlands
open_access
Institut für Geschichte der Medizin
Universität Würzburg
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28647/Schuster_Daniel_Krankheitsmetaphern.pdf
23434
2021
eng
14
article
1
--
--
--
International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)
Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.
Frontiers in Human Neuroscience
1662-5161
10.3389/fnhum.2020.568051
urn:nbn:de:bvb:20-opus-234346
2021-04-12T16:08:35+00:00
sword
swordwue
attachment; filename=deposit.zip
7c32ee28b56dfb62089aa3c20ca8ef11
Frontiers in Human Neuroscience 2021, 14:568051. DOI: 10.3389/fnhum.2020.568051
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Adam D. Farmer
Adam Strzelczyk
Alessandra Finisguerra
Alexander V. Gourine
Alireza Gharabaghi
Alkomiet Hasan
Andreas M. Burger
Andrés M. Jaramillo
Ann Mertens
Arshad Majid
Bart Verkuil
Bashar W. Badran
Carlos Ventura-Bort
Charly Gaul
Christian Beste
Christopher M. Warren
Daniel S. Quintana
Dorothea Hämmerer
Elena Freri
Eleni Frangos
Eleonora Tobaldini
Eugenijus Kaniusas
Felix Rosenow
Fioravante Capone
Fivos Panetsos
Gareth L. Ackland
Gaurav Kaithwas
Georgia H. O'Leary
Hannah Genheimer
Heidi I. L. Jacobs
Ilse Van Diest
Jean Schoenen
Jessica Redgrave
Jiliang Fang
Jim Deuchars
Jozsef C. Széles
Julian F. Thayer
Kaushik More
Kristl Vonck
Laura Steenbergen
Lauro C. Vianna
Lisa M. McTeague
Mareike Ludwig
Maria G. Veldhuizen
Marijke De Couck
Marina Casazza
Marius Keute
Marom Bikson
Marta Andreatta
Martina D'Agostini
Mathias Weymar
Matthew Betts
Matthias Prigge
Michael Kaess
Michael Roden
Michelle Thai
Nathaniel M. Schuster
Nicola Montano
Niels Hansen
Nils B. Kroemer
Peijing Rong
Rico Fischer
Robert H. Howland
Roberta Sclocco
Roberta Sellaro
Ronald G. Garcia
Sebastian Bauer
Sofiya Gancheva
Stavros Stavrakis
Stefan Kampusch
Susan A. Deuchars
Sven Wehner
Sylvain Laborde
Taras Usichenko
Thomas Polak
Tino Zaehle
Uirassu Borges
Vanessa Teckentrup
Vera K. Jandackova
Vitaly Napadow
Julian Koenig
eng
uncontrolled
transcutaneous vagus nerve stimulation
eng
uncontrolled
minimum reporting standards
eng
uncontrolled
guidelines & recommendations
eng
uncontrolled
transcutaneous auricular vagus nerve stimulation
eng
uncontrolled
transcutaneous cervical vagus nerve stimulation
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Institut für Psychologie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23434/fnhum-14-568051.pdf
https://opus.bibliothek.uni-wuerzburg.de/files/23434/fnhum-14-568051-g0001.tif
https://opus.bibliothek.uni-wuerzburg.de/files/23434/fnhum-14-568051-g0002.tif
21983
2020
eng
7
article
1
--
--
--
COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study
Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS).
Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included.
Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay.
Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.
Frontiers in Medicine
2296-858X
10.3389/fmed.2020.599533
urn:nbn:de:bvb:20-opus-219834
2021-01-01T05:11:16+00:00
sword
swordwue
attachment; filename=deposit.zip
e4eda77d78955daddda68def2a39aa11
Frontiers in Medicine 2020, 7:599533. DOI: 10.3389/fmed.2020.599533
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Johannes Herrmann
Elisabeth Hannah Adam
Quirin Notz
Philipp Helmer
Michael Sonntagbauer
Peter Ungemach-Papenberg
Andreas Sanns
York Zausig
Thorsten Steinfeldt
Iuliu Torje
Benedikt Schmid
Tobias Schlesinger
Caroline Rolfes
Christian Reyher
Markus Kredel
Jan Stumpner
Alexander Brack
Thomas Wurmb
Daniel Gill-Schuster
Peter Kranke
Dirk Weismann
Hartwig Klinker
Peter Heuschmann
Viktoria Rücker
Stefan Frantz
Georg Ertl
Ralf Michael Muellenbach
Haitham Mutlak
Patrick Meybohm
Kai Zacharowski
Christopher Lotz
eng
uncontrolled
COVID-19
eng
uncontrolled
ARDS (acute respiratory distress syndrome)
eng
uncontrolled
intensive care medicine
eng
uncontrolled
pandemia
eng
uncontrolled
Germany
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Medizinische Klinik und Poliklinik I
Institut für Klinische Epidemiologie und Biometrie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/21983/fmed-07-599533-g0001.tif
https://opus.bibliothek.uni-wuerzburg.de/files/21983/fmed-07-599533.pdf
https://opus.bibliothek.uni-wuerzburg.de/files/21983/Table_1.docx