A middle-aged woman began experiencing spells of profound anterograde amnesia several months after beginning intrathecal baclofen treatment for generalized dystonia. Her spells met criteria for transient global amnesia, but were unusual because of their frequent recurrence and because their frequency was somewhat dose-dependent on baclofen. Fludrocortisone decreased the frequency of these episodes, and sublingual nitroglycerin both prevented and terminated them. Baclofen-induced amnesia in rodents is a reliable model of memory impairment. In contrast, baclofen-induced memory impairment in humans is uncommon. Baclofen- associated transient global amnesia has not previously been reported.
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http://dx.doi.org/10.1213/ane.0b013e318165e1c6 | DOI Listing |
Int J Toxicol
January 2025
Chemical and Preclinical Safety Department, Global Chemical and Preclinical Safety, Merck KGaA, Darmstadt, Germany.
The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan.
View Article and Find Full Text PDFSci Bull (Beijing)
December 2024
NOAA/Pacific Marine Environmental Laboratory, Seattle, Washington DC 20005, USA.
El Niño-Southern Oscillation (ENSO) exhibits a strong asymmetry between warm El Niño and cold La Niña in amplitude and temporal evolution. An El Niño often leads to a heat discharge in the equatorial Pacific conducive to its rapid termination and transition to a La Niña, whereas a La Niña persists and recharges the equatorial Pacific for consecutive years preconditioning development of a subsequent El Niño, as occurred in 2020-2023. Whether the multiyear-long heat recharge increases the likelihood of a transition to a strong El Niño remains unknown.
View Article and Find Full Text PDFMol Cell
January 2025
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia. Electronic address:
Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export.
View Article and Find Full Text PDFAnn Neurol
January 2025
Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Objective: Monoallelic variants in the transient receptor potential melastatin-related type 3 gene (TRPM3) have been associated with neurodevelopmental manifestations, but knowledge on the clinical manifestations and treatment options is limited. We characterized the clinical spectrum, highlighting particularly the epilepsy phenotype, and the effect of treatments.
Methods: We analyzed retrospectively the phenotypes and genotypes of 43 individuals with TRPM3 variants, acquired from GeneMatcher and collaborations (n = 21), and through a systematic literature search (n = 22).
Am J Med Genet A
January 2025
Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Aicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy. Janus kinase (JAK) inhibition has emerged as a potential treatment for AGS. RNU7-1 is one of the most recently discovered genes for AGS, and the clinical effects of JAK inhibition in these patients have not been reported.
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