Institutes
Refine
Year of publication
- 2021 (767)
- 2022 (493)
- 2020 (318)
- 2023 (220)
- 2019 (78)
- 2024 (62)
- 2018 (48)
- 2013 (39)
- 2012 (34)
- 2017 (34)
- 2004 (32)
- 2014 (29)
- 2015 (26)
- 2010 (23)
- 2011 (23)
- 1991 (22)
- 2008 (20)
- 1993 (19)
- 1994 (18)
- 2005 (18)
- 2009 (18)
- 1998 (15)
- 2016 (15)
- 2003 (14)
- 2001 (13)
- 2000 (12)
- 2006 (12)
- 1988 (10)
- 1990 (10)
- 2002 (10)
- 2007 (10)
- 1992 (9)
- 1995 (9)
- 1996 (9)
- 1999 (9)
- 1983 (7)
- 1984 (6)
- 1989 (5)
- 1997 (5)
- 1977 (4)
- 1981 (4)
- 1985 (4)
- 1975 (3)
- 1986 (3)
- 1953 (2)
- 1959 (2)
- 1961 (2)
- 1963 (2)
- 1982 (2)
- 1954 (1)
- 1958 (1)
- 1960 (1)
- 1962 (1)
- 1971 (1)
- 1987 (1)
Document Type
- Article (1779)
- Doctoral Thesis (433)
- Preprint (157)
- Conference Proceeding (104)
- Review (32)
- Book (17)
- Part of Periodical (12)
- Contribution to a Periodical (9)
- Part of a Book (7)
- Report (3)
Has Fulltext
- yes (2555)
Is part of the Bibliography
- no (2555)
Keywords
- COVID-19 (43)
- SARS-CoV-2 (36)
- inflammation (30)
- Epilepsy (19)
- Video (19)
- Inflammation (17)
- prostate cancer (16)
- ADHD (13)
- Cancer (12)
- autophagy (12)
Institute
- Medizin (2555)
- Biowissenschaften (32)
- Biochemie und Chemie (30)
- Biochemie, Chemie und Pharmazie (29)
- Georg-Speyer-Haus (25)
- Buchmann Institut für Molekulare Lebenswissenschaften (BMLS) (19)
- Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) (19)
- Präsidium (17)
- Frankfurt Institute for Advanced Studies (FIAS) (16)
- Ernst Strüngmann Institut (12)
Background and objectives: Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS).
Methods: We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)–based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]).
Results: The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max = − 0.65; RA patients: g*max = 0.72).
Conclusion: As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment.
Die Ergebnisse der Studie und die Diversität der Datenbanken ist groß.
Für 12 Datenbanken wurde ein Punktesystem mit elf Items entworfen, um die Qualität der einzelnen Datenbanken zu objektivieren. Keine Datenbank konnte alle Bewertungskriterien erfüllen. Der insgesamt schlechte Punktedurchschnitt ist ein Indikator für die Mängel der aktuell verfügbaren Datenbanken. Außerdem konnten wir einen Qualitätsunterschied zwischen kostenpflichtigen und kostenfreien Datenbanken beweisen und mussten im Zuge dieser Ergebnisse die Frage stellen, ob kostenfreie Datenbanken überhaupt nützlich sind. Zwischen den kostenpflichtigen Datenbanken fallen die Qualitätsunterschiede weniger gravierend aus, wenngleich Stärken und Schwächen sich deutlich unterscheiden. Die häufigsten Wechselwirkungen wurden in allen Datenbanken mit großem Abstand zwischen rein psychiatrischen Interaktionspaaren erfasst. Dieses zeigt, wie wechselwirkungsreich Psychopharmaka sind und dass psychiatrische Patienten besonders vulnerabel sind. Die Nutzung digitaler Hilfsmittel scheint bei Betrachtung der hohen Anzahl ausgegebener Warnmeldungen unabdingbar zu sein, dennoch existiert große Uneinheitlichkeit bei der Bewertung der einzelnen Interaktionen. Die Vorstellung, dass zwei Kliniker bei Nutzung zweier unterschiedlicher Datenbanken zu völlig unterschiedlichen Empfehlungen kommen, fällt nicht schwer. Gleichzeitig könnte die Kooperation von Heilberuflern, die unterschiedliche Datenbanken verwenden, die Chance auf zusätzlichen Informationsgewinn und Austausch erhöhen, was im Umkehrschluss in einer erhöhten Arzneimitteltherapiesicherheit resultiert. In Studien konnte der positive Effekt interdisziplinärer Zusammenarbeit bereits bewiesen werden.
Zusammenfassend konnten umfangreiche Differenzen zwischen allen untersuchten Datenbanken aufgezeigt werden. Um den Anforderungen des klinischen Alltags zu genügen, müssen digitale Unterstützungssysteme weiterentwickelt werden.
Die „ideale Datenbank“ gibt es bisher nicht – das lässt sich durch unser Punktesystem beweisen. Um im klinischen Alltag Patientensicherheit zu gewährleisten ist die Nutzung einer einzelnen Datenbank bisher nicht ausreichend.
Die Gewährung der Patientensicherheit sollte unser oberstes Ziel sein und um dieses zu erreichen, bedarf es vieler Komponenten. Neben der Nutzung und vor allem Weiterentwicklung digitaler Unterstützungssysteme sollte auch der zwischenmenschliche Austausch weiter gefördert werden. Interdisziplinäre Zusammenarbeit im Sinne pharmazeutischer Dienstleistungen zur Medikationsanalyse könnten ein zusätzliches Instrument zur Vermeidung arzneimittelbezogener Probleme werden.
Zukünftig werden unsere Patienten am meisten von optimaler Nutzung weiterentwickelter Technologien, sowie wachsendem zwischenmenschlichem Austausch profitieren.
Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome2,3,4,5,6,7. Earlier studies concluded that FLVCR1 may function as a haem exporter8,9,10,11,12, whereas FLVCR2 was suggested to act as a haem importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14,15,16. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation–π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.
Background: Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy.
Results: We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model.
Conclusion: PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.
We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti-seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates. Results were summarized with meta-analyses that pooled logit-transformed proportions or rates. Subgroup analyses and univariable and multivariable meta-regressions were performed to examine the influence of covariates. We included 38 studies (2 controlled and 5 uncontrolled prospective; 31 retrospective) involving 1152 patients. Meta-analysis of aggregate data for the primary outcomes of seizure response and reduction of electroencephalography (EEG) spikes at the end of treatment yielded pooled proportions (PPs) of 0.60 (95% confidence interval [CI] 0.52–0.67) and 0.56 (95% CI 0.43–0.68). The relapse rate was high (PP 0.33, 95% CI 0.27–0.40). Group analyses and meta-regression showed a small benefit of ACTH and no difference between all other corticosteroids, a slightly better effect in electric status epilepticus in slow sleep (ESES) and a weaker effect in patients with cognitive impairment and “symptomatic” etiology. Obesity and Cushing's syndrome were the most common adverse effects, occurring more frequently in trials addressing continuous ACTH (PP 0.73, 95% CI 0.48–0.89) or corticosteroids (PP 0.72, 95% CI 0.54–0.85) than intermittent intravenous or oral corticosteroid administration (PP 0.05, 95% CI 0.02–0.10). The validity of these results is limited by the high risk of bias in most included studies and large heterogeneity among study results. This report was registered under International Prospective Register of Systematic Reviews (PROSPERO) number CRD42022313846. We received no financial support.
Key points
* Systematic review resulting in low to moderately solid evidence on the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroid treatment in children with epilepsy other than infantile spasms.
* Meta-analysis based on aggregate data from 2 controlled prospective, 5 uncontrolled prospective, and 31 retrospective studies.
* Pooled data showing a seizure response in 60% and electroencephalography (EEG) response in 56% of patients, with no major differences between drugs. However, 30%–40% of patients relapse after the cessation of treatment.
* The most frequent adverse effects are obesity and Cushing's syndrome, occurring in 70% of patients under continuous treatment for some weeks, but in less than 10% undergoing pulsed, intermittent regimens.
* More prospective, randomized-controlled studies are needed to improve the level of evidence and define the optimal doses and treatment duration.
Diese Arbeit hatte das Ziel, die Größe einer DVT-Aufnahme (FOV) mit der Größe der durch die Indikationsstellung definierten Region (ROI) zu vergleichen. Durch eine speziell dafür entwickelte Software sollten Messungen in den Datensätzen ermöglicht werden. Die dazu verwendeten 332 Datensätze wurden zufallsverteilt aus den mit einem Orthophos SL-3D DVT-Gerät der Firma Dentsply Sirona in der Poliklinik für zahnärztliche Chirurgie und Implantologie des ZZMK (Carolinum) in Frankfurt angefertigten Röntgenaufnahmen selektiert.
Es wurde die Auswertungssoftware ExRoi entwickelt, mit der die Werte des axialen Durchmessers, die Höhe (vertikale Dimension) sowie die Distanz der Mittelpunkte von FOV und ROI direkt in den Datensätzen bestimmt werden konnten. Zusätzlich wurde festgehalten, welche rechtfertigenden Indikationen gestellt und welche Auflösungsmodi verwendet wurden.
Die Stichprobe bestand aus Aufnahmen mit einem axialen Durchmesser von 8 cm [VOL 1] (n= 76, entsprechend 46,39%), 5 cm Durchmesser [VOL 2] (n = 102, entsprechend 30,72%) und 11 cm Durchmesser [VOL 3] (n= 154, entsprechend 22,89%). 95,18% der Aufnahmen wurden im HD-Modus mit laut Herstellerangaben vier Mal so vielen Aufnahmen im Vergleich zum SD-Modus angefertigt. Hauptindikationen waren Implantat Planung (45,1%) und Planungen komplizierter Zahn-Extraktionen (25,5%).
Die Messungen zum Vergleich des axialen Durchmessers zeigten, dass bei Verwendung des VOL 2 die ROI im Mittel den größten Anteil der FOV nutzt (78,52 %), den kleinsten Anteil nutzt durchschnittlich VOL 1 (56,04 %). Dazwischen liegt VOL 3 (69,12 %). In der Vertikalen nutzt die ROI von VOL 3 mittelwertig den größten Anteil der FOV (81,87 %), den kleinsten Mittelwert hat VOL 1 (58,76 %). VOL 2 liegt zwischen diesen Werten (64,47 %).
In allen Fällen war das FOV größer als die ROI und die ROI lag im Bereich des gewählten FOV.
Die Mittelpunkte von FOV und ROI lagen im Mittel in der axialen Ebene in Abhängigkeit vom gewählten Volumen um rund 9-13 mm auseinander, in der coronalen und sagittalen Ebene um rund 5-6mm.
Aus diesen Ergebnissen kann für das verwendete Gerät eine gute Trefferquote für die ROI abgeleitet werden. Höhe und Durchmesser des FOV hätten in den meisten Fällen kleiner gewählt werden können, liegen aber angesichts der vorhandenen Auswahl-Optionen des Röntgengeräts zur Dimensionierung der Volumina in einem akzeptablen Bereich.
Background: Epilepsy surgery is an established treatment for drug-resistant focal epilepsy (DRFE) that results in seizure freedom in about 60% of patients. Correctly identifying an epileptogenic lesion in magnetic resonance imaging (MRI) is challenging but highly relevant since it improves the likelihood of being referred for presurgical diagnosis. The epileptogenic lesion’s etiology directly relates to the surgical intervention’s indication and outcome. Therefore, it is vital to correctly identify epileptogenic lesions and their etiology presurgically.
Methods: We compared the final histopathological diagnoses of all patients with DRFE undergoing epilepsy surgery at our center between 2015 and 2021 with their MRI diagnoses before and after presurgical diagnosis at our epilepsy center, including MRI evaluations by expert epilepsy neuroradiologists. Additionally, we analyzed the outcome of different subgroups.
Results: This study included 132 patients. The discordance between histopathology and MRI diagnoses significantly decreased from 61.3% for non-expert MRI evaluations (NEMRIs) to 22.1% for epilepsy center MRI evaluations (ECMRIs; p < 0.0001). The MRI-sensitivity improved significantly from 68.6% for NEMRIs to 97.7% for ECMRIs (p < 0.0001). Identifying focal cortical dysplasia (FCD) and amygdala dysplasia was the most challenging for both subgroups. 65.5% of patients with negative NEMRI were seizure-free 12 months postoperatively, no patient with negative ECMRI achieved seizure-freedom. The mean duration of epilepsy until surgical intervention was 13.6 years in patients with an initial negative NEMRI and 9.5 years in patients with a recognized lesion in NEMRI.
Conclusions: This study provides evidence that for patients with DRFE—especially those with initial negative findings in a non-expert MRI—an early consultation at an epilepsy center, including an ECMRI, is important for identifying candidates for epilepsy surgery. NEMRI-negative findings preoperatively do not preclude seizure freedom postoperatively. Therefore, patients with DRFE that remain MRI-negative after initial NEMRI should be referred to an epilepsy center for presurgical evaluation. Nonreferral based on NEMRI negativity may harm such patients and delay surgical intervention. However, ECMRI-negative patients have a reduced chance of becoming seizure-free after epilepsy surgery. Further improvements in MRI technique and evaluation are needed and should be directed towards improving sensitivity for FCDs and amygdala dysplasias.
Background: Patients with epilepsy often require a specialized treatment, which may differ because of the responsibility of the federal states for healthcare policy in Germany.
Objective: State-specific differences in healthcare structures based on inpatient hospital cases of epilepsy patients between 2000 and 2020 in relation to specialized treatment offers.
Material and methods: The inpatient hospital cases of the German federal states were evaluated using the Friedman test and time series trend analysis. A state-specific inpatient undertreatment or overtreatment of inpatient hospital cases outside the registered state was analyzed by comparing residence-related and treatment site-related case numbers with a threshold of ±5%.
Results: After age adjustment, significantly more inpatient cases were found in the “new states” compared to the “old states” (p < 0.001); the highest number of cases nationwide was found in Saarland with 224.8 ± 11.5 cases per 100,000 inhabitants. The trend analysis showed an increase in cases until the end of 2016 with a trend reversal from 2017 and a further significant decrease in hospital cases in the COVID year 2020. A relative inpatient undertreatment was shown for Brandenburg, Lower Saxony, Rhineland-Palatinate, Saxony-Anhalt, Schleswig-Holstein and Thuringia. Additional, possibly compensatory, inpatient care was found for all city states (Hamburg, Bremen and Berlin) and Baden-Wuerttemberg. In federal states with a relative inpatient undertreatment and/or high inpatient hospital case numbers, there was often a lower availability of specialized epilepsy centers, specialized outpatient clinics and epilepsy outpatient clinics.
Conclusion: In Germany there are state-specific differences in the structure of care, with higher inpatient hospital care in the “new states” and Saarland. In addition, there were federal states with disproportionately higher treatment of patients not registered in this federal state. A potential influencing factor may be the availability of centers with specialized treatment for epilepsy patients.