RESUMO
This study reviews the case of a 67-year-old man who initially presented with high fever and dyspnea. He was subsequently admitted for treatment of pneumonia. On admission, severe leucopenia and thrombopenia were observed in the peripheral blood, with significant phagocytosis of hematopoietic cells including erythroblasts and leukocytes by macrophages in the bone marrow. Following the administration of antibiotic therapy, an improvement in pneumonia and cytopenia symptoms was noted. Clinically, we diagnosed this case as bacteria-associated hemophagocytic syndrome (BAHS) with community-acquired pneumonia. In general BAHS is seen following severe hematologic disease or pneumonia, and so the treatment of BAHS is quite difficult. This particular case had no additional hematologic disorder, and all presenting symptoms of BAHS were resolved immediately following the improvement in pneumonia with post-antibiotic therapy.
Assuntos
Histiocitose de Células não Langerhans/etiologia , Pneumonia Bacteriana/complicações , Idoso , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/tratamento farmacológico , Citocinas/fisiologia , Quimioterapia Combinada , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Histiocitose de Células não Langerhans/diagnóstico , Histiocitose de Células não Langerhans/tratamento farmacológico , Humanos , Mediadores da Inflamação/fisiologia , Masculino , Meropeném , Pneumonia Bacteriana/tratamento farmacológico , Tienamicinas/administração & dosagem , Resultado do TratamentoRESUMO
The erythropoietin receptor (EPOr) is activated by ligand-induced homodimerization, which leads to the proliferation and differentiation of erythroid progenitors. Through the screening of combinatorial libraries of dimeric iminodiacetic acid diamides, novel small molecule binders of EPOr were identified in a protein binding assay. Evaluation of a series of analogues led to optimization of binding subunits, and these were utilized in the synthesis of higher order dimer, trimer, and tetramer libraries. Several of the most active EPOr binders were found to be partial agonists and induced concentration-dependent proliferation of an EPO-dependent cell line (UT-7/EPO) while having no effect on a cell line lacking the EPOr (FDC-P1). An additional compound library, based on a symmetrical isoindoline-5,6-dicarboxylic acid template and including the optimized binding subunits, was synthesized and screened leading to the identification of additional EPO mimetics.