Efficacy of anterior gastric fundoplication in the treatment of gastroesophageal reflux in infants and children

Anterior gastric fundoplication (AGF) has been performed at the University of Michigan since 1988. To objectively evaluate the long-term efficacy of the AGF, the authors performed a study of children who had undergone AGF between June 1988 and June 1990 (n = 46). Six of them died of unrelated causes. Twenty-two consented to follow-up evaluation that included parental interview, physical examination, upper gastrointestinal series (UGI), 24-hour esophageal pH probe monitoring (EpH), and a liquid-phase gastric emptying study. Twenty patients (74%) remained asymptomatic, patients exhibited gastroesophageal reflux (GER) by UGI, and three others by EpH. Three children were noted to have delayed gastric emptying. These results compare favorably with data previously reported from this institution of a 5-year follow-up of children after Nissen fundoplication. There is a trend toward improved efficacy (87% v 74%; P = .12), decreased reoperation rate (4% v 14%; P = .11), and less severe complications. The present study shows that AGF is effective treatment for GER when evaluated by objective studies and is comparable in therapeutic efficacy and safety to the Nissen fundoplication.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31949/1/0000902.pd

Immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice

Type 1 diabetes (T1D) is an autoimmune disease that is caused by the destruction of insulin-producing β cells. Viral infections induce immune responses that can damage β cells and promote T1D or on the other hand prevent the development of the disease. However, the opposing roles of viral infections in T1D are not understood mechanistically. We report here that viruses that do not inflict damage on β cells provided protection from T1D by triggering immunoregulatory mechanisms. Infection of prediabetic NOD mice with Coxsackie virus B3 or lymphocytic choriomeningitis virus (LCMV) delayed diabetes onset and reduced disease incidence. Delayed T1D onset was due to transient upregulation of programmed cell death–1 ligand 1 (PD-L1) on lymphoid cells, which prevented the expansion of diabetogenic CD8+ T cells expressing programmed cell death–1 (PD-1). Reduced T1D incidence was caused by increased numbers of invigorated CD4+CD25+ Tregs, which produced TGF-β and maintained long-term tolerance. Full protection from T1D resulted from synergy between PD-L1 and CD4+CD25+ Tregs. Our results provide what we believe to be novel mechanistic insight into the role of viruses in T1D and should be valuable for prospective studies in humans

Expression level of a pancreatic neo-antigen in beta cells determines degree of diabetes pathogenesis

It is not fully understood how the expression level of autoantigens in beta cells impacts autoimmune diabetes (T1D) development. Earlier studies using ovalbumin and also insulin had shown that secreted antigens could enhance diabetes development through facilitated presentation by antigen presenting cells. Here we sought to determine how the expression level of a membrane bound, non-secreted or cross-presented neo-antigen, the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), would influence T1D. We found that a RIP-LCMV transgenic mouse line exhibiting higher levels of beta cell GP expression developed more severe diabetes after LCMV infection or transfer of high numbers of activated autoreactive T cells. Importantly, all beta cells were lost and a significant increase in morbidity and mortality from T1D was noted. Insulitis and accumulation of autoaggressive CD8 cells was more profound in the RIP-LCMV-GP high-expressor line. Interestingly, the additional introduction of neo-antigen-specific CD4(+) helper or regulatory T cells was able to influence diabetogenesis positively or negatively. We conclude that a higher degree of autoantigen expression results in increased diabetes susceptibility. Therefore, autoantigens such as insulin that are expressed at higher levels in beta cells might have a more profound impact on diabetes pathogenesis