We will present a 42-year-old woman with acute myeloid leukemia and pulmonary aspergillosis. She was treated with several antifungal agents, including three triazoles. Voriconazole, posaconazole, and isavuconazole all led to hepatocellular liver injury. Voriconazole administration led to a peak alanine aminotransferase (ALT) value of 1,793 U/L (normal range, 9–59 U/L). After posaconazole and isavuconazole treatment, ALT rose over 500 U/L. The typical course of events, exclusion of differential diagnoses, and normalization of the liver function tests (LFTs) after stopping the triazoles were highly suspicious for a drug-induced liver injury (DILI). Interestingly, our patient carries a rare HLA B allele (HLA B*35:02), which occurs in less than 1% of the population and is known to be associated with minocycline-induced liver injury. Over the course of 4 months, the patient received two induction chemotherapies and afterward underwent a successful allogenic hematopoietic stem cell transplantation. Her liver function recovered rapidly and favorable clinical findings concerning the aspergillosis led to a de-escalation of the antifungal treatment to prophylactic dose fluconazole. Delayed hepatotoxicity suggested a dose dependency and a cumulative effect. The question of a common pathophysiology and a cross-toxicity was raised. At the present time, only a few case reports describe cross-toxicity or its absence after rechallenge with different azoles. The pathophysiology is not well understood. Ketoconazole was found to impair rat mitochondrial function in vitro . Further investigations showed cell membrane toxicity and ATP depletion in isolated human liver cancer cells. Our case report suggests a cross-toxicity, dose-dependency, and a possible genetic predisposition of triazole-induced liver injury.
A 'sense of self' is essentially the ability to distinguish between self-generated and external stimuli. It consists of at least two very basic senses: a sense of agency and a sense of ownership. Disturbances seem to provide a basic deficit in many psychiatric diseases. The aim of our study was to manipulate those qualities separately in 28 patients with schizophrenia (14 auditory hallucinators and 14 non-hallucinators) and 28 healthy controls (HC) and to investigate the effects on the topographies and the power of the event-related potential (ERP). We performed a 76-channel EEG while the participants performed the task as in our previous paper. We computed ERPs and difference maps for the conditions and compared the amount of agency and ownership between the HC and the patients. Furthermore, we compared the global field power and the topographies of these effects. Our data showed effects of agency and ownership in the healthy controls and the hallucinator group and to a lesser degree in the non-hallucinator group. We found a reduction of the N100 during the presence of agency, and a bilateral temporal negativity related to the presence of ownership. For the agency effects, we found significant differences between HC and the patients. Contrary to the expectations, our findings were more pronounced in non-hallucinators, suggesting a more profoundly disturbed sense of agency compared to hallucinators. A contemporary increase of global field power in both patient groups indicates a compensatory recruitment of other mechanisms not normally associated with the processing of agency and ownership.
We report the case of a 20-year-old male complaining of sudden-onset, severe headaches, fever, chills, and generalized arthralgia. He had no symptoms of a respiratory tract infection. Blood examination revealed severe leukopenia and mild to moderate thrombocytopenia. Onset of symptoms was rapid, intense, and occurred only a few hours after routine tick-borne encephalitis (TBE) booster vaccine. The question of a relationship between booster vaccine administration and the febrile illness with bicytopenia was raised. A broad range of diagnostics excluded infections and other causes for bicytopenia. Symptoms resolved within a few days, and blood counts normalized within two weeks. Due to the close temporal relationship, a transient benign bicytopenia and febrile illness as a systemic reaction to TBE vaccination was assumed. Review of the literature and adverse event reporting systems suggest that this is a very rare reaction.
Zusammenfassung. Im Alltag stellen K.o.-Mittel die praktizierenden Ärzte nicht selten vor Herausforderungen. Besteht der Verdacht einer Substanzbeibringung, steht in erster Linie die Frage nach einer Involvierung der Rechtsmedizin im Raum. Bei unklaren Situationen oder fraglichen Delikten kann jedoch seitens der Patientinnen und Patienten der Wunsch einer Erstdiagnostik auf der Notfallstation bzw. in der Sprechstunde geäussert werden. Der Kliniker ist dabei mit einer Vielzahl möglicher involvierter Substanzen, begrenzten analytischen Methoden und oftmals schwierig zu interpretierenden Resultaten konfrontiert. Im folgenden Artikel wird ein Überblick über die diagnostischen Möglichkeiten sowie ihre Limitationen gegeben. Häufig involvierte Substanzen, ihre Nachweisbarkeit und pharmakokinetische Besonderheiten werden vorgestellt. Besondere Aufmerksamkeit soll den im Alltag relevanten, praktischen Aspekten gelten.
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