ABSTRACT
Syncope is common in the pediatric population and occurs in up to 15 percent of children prior to the end of adolescence. While the etiology of syncope in children is often benign and the majority of cases can be explained by isolated changes in vasomotor tone, a thorough evaluation is warranted to rule out more serious, life-threatening causes of syncope. Here, we present three atypical cases of syncope: a young judo player with recurrent syncope and dizziness, a teenage boy with syncopal episodes always preceded by stretching, and a child who experienced urticaria before losing consciousness. Herein, we review the pathophysiology, diagnosis, and management of syncope in children and adolescents.
ABSTRACT
End-stage liver disease is a common cause of non-AIDS-related mortality in HIV+ patients, despite effective anti-retroviral therapies (ARTs). HIV-1 infection causes gut CD4 depletion and is thought to contribute to increased gut permeability, bacterial translocation, and immune activation. Microbial products drain from the gut into the liver via the portal vein where Kupffer cells (KCs), the resident liver macrophage, clear translocated microbial products. As bacterial translocation is implicated in fibrogenesis in HIV patients through unclear mechanisms, we tested the hypothesis that HIV infection of KCs alters their response to LPS in a TLR4-dependent manner. We showed that HIV-1 productively infected KCs, enhanced cell-surface TLR4 and CD14 expression, and increased IL-6 and TNF-α expression, which was blocked by a small molecule TLR4 inhibitor. Our study demonstrated that HIV infection sensitizes KCs to the proinflammatory effects of LPS in a TLR4-dependent manner. These findings suggest that HIV-1-infected KCs and their dysregulated innate immune response to LPS may play a role in hepatic inflammation and fibrosis and represent a novel target for therapy.
