RESUMO
The advent of immunotherapy in oncology has led to the emergence of a new spectrum of adverse effects. A number of these have the potential to contribute to life-threatening outcomes; and therefore require prompt identification and aggressive treatment to optimise management. In this report, we describe a case of pembrolizumab-induced CTCAE (common toxicity criteria for adverse events) grade 4 myositis in a non-small cell lung cancer patient.
Assuntos
Adenocarcinoma de Pulmão , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Miosite , Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Miosite/induzido quimicamenteRESUMO
OBJECTIVE: To investigate the association between brain amyloid load in Alzheimer disease (AD) measured by [11C]PIB-PET, regional cerebral glucose metabolism (rCMRGlc) measured by [18F]FDG-PET, and cognition. METHODS: Nineteen subjects with AD and 14 controls had [11C]PIB-PET and underwent a battery of psychometric tests. Twelve of those subjects with AD and eight controls had [18F]FDG-PET. Parametric images of [11C]PIB binding and rCMRGlc were interrogated with a region-of-interest atlas and statistical parametric mapping. [11C]PIB binding and rCMRGlc were correlated with scores on psychometric tests. RESULTS: AD subjects showed twofold increases in mean [11C]PIB binding in cingulate, frontal, temporal, parietal, and occipital cortical areas. Higher cortical amyloid load correlated with lower scores on facial and word recognition tests. Two patients fulfilling the clinical criteria for AD had normal [11C]PIB at baseline. Over 20 months this remained normal in one but increased in the cingulate of the other. Mean levels of temporal and parietal rCMRGlc were reduced by 20% in AD and these correlated with mini mental scores, immediate recall, and recognition memory test for words. Higher [11C]PIB uptake correlated with lower rCMRGlc in temporal and parietal cortices. CONCLUSION: [11C]PIB-PET detected an increased amyloid plaque load in 89% of patients with clinically probable Alzheimer disease (AD). The high frontal amyloid load detected by [11C]PIB-PET in AD in the face of spared glucose metabolism is of interest and suggests that amyloid plaque formation may not be directly responsible for neuronal dysfunction in this disorder.
Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Amiloide/metabolismo , Encéfalo/metabolismo , Cognição , Glucose/metabolismo , Idoso , Doença de Alzheimer/diagnóstico , Compostos de Anilina , Benzotiazóis/farmacocinética , Radioisótopos de Carbono , Face , Feminino , Fluordesoxiglucose F18 , Humanos , Idioma , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Reconhecimento Psicológico , TiazóisRESUMO
OBJECTIVE: To evaluate the relationship between clinical improvement and in vivo synaptic dopamine (DA) release after a single oral dose of levodopa (LD) in patients with advanced Parkinson disease (PD). METHODS: We studied 16 patients with advanced PD with [(11)C]raclopride (RAC) PET. Each patient had RAC PET twice: once when medication had been withdrawn and once after an LD challenge. On the day of the LD challenge scan, oral 250 mg LD/25 mg carbidopa was given before scanning. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were rated in an "off" state before LD and again at the end of PET. RESULTS: All the patients were still in "on" state at the end of their LD challenge RAC PET scans. Following LD, mean caudate and putamen RAC binding potentials (BPs) were significantly lower vs baseline, consistent with increased synaptic DA. Individual LD-induced improvements in UPDRS score correlated significantly with reductions in putaminal BP. Additionally, large putaminal RAC BP changes were associated with higher dyskinesia scores. When motor UPDRS subitems were examined, improvements in rigidity and bradykinesia, but not in tremor or axial symptoms, correlated with putamen DA release. CONCLUSION: In advanced Parkinson disease, the improvement of rigidity and bradykinesia and the presence of dyskinesias after a single dose of oral levodopa are governed by the level of dopamine generated at striatal D2 receptors. In contrast, relief of parkinsonian tremor and axial symptoms is not related to striatal synaptic dopamine levels and presumably occurs via extrastriatal mechanisms.