Gastroparesis after combined heart and lung transplantation.

GOALS: To determine the prevalence, severity, and outcome of gastroparesis after heart and lung transplantation (HLT). STUDY: Ten patients (five women; age range, 27-57 years) underwent HLT at Temple University Hospital from 1996 to 1999. The charts of these patients were reviewed, including results from gastric emptying scans and upper endoscopies. Symptoms were assessed with a standardized questionnaire. RESULTS: The indications for HLT included pulmonary hypertension in six patients, Eisenmenger syndrome in two, and dilated cardiomyopathy and congenital heart disease in two. Four patients died before the start of this clinical analysis. The six surviving patients constituted our study population. The patients' posttransplantation follow-up period ranged from 1.4 to 4.4 years (average, 2.6 years). Five patients (83%) were symptomatic with nausea, vomiting, and postprandial abdominal distension. Solid phase gastric emptying was delayed in all five patients with mean gastric retention of 93% at 2 hours (normal <50%). Patients generally did not respond to prokinetic agents. Four patients required pyloroplasty with J tube placement for symptom control, nutrition, and delivery of immunosuppressive medication. CONCLUSIONS: There is a high prevalence of symptomatic gastroparesis in patients after HLT. The gastroparesis is severe and often resistant to prokinetic agents.     

TLR2- and Dectin 1–Associated Innate Immune Response Modulates T-Cell Response to Pancreatic β-Cell Antigen and Prevents Type 1 Diabetes

The progression of autoimmune diseases is dictated by deviations in the fine balance between proinflammatory versus regulatory responses, and pathogen recognition receptors (PRRs) play a key role in maintaining this balance. Previously, we have reported that ligation of Toll-like receptor 2 (TLR2) and Dectin 1 on antigen-presenting cells by zymosan results in a regulatory immune response that prevents type 1 diabetes (T1D). Here, we show that TLR2 and Dectin 1 engagement by zymosan promotes regulatory T-cell (Treg) responses against the pancreatic β-cell–specific antigen (Ag). Unlike the TLR4 ligand, bacterial lipopolysaccharide, which induced proinflammatory cytokines and pathogenic T cells, zymosan induced a mixture of pro- and anti-inflammatory factors and Tregs, both in vitro and in vivo. Ag-specific T cells that are activated using zymosan-exposed dendritic cells (DCs) expressed Foxp3 and produced large amounts of IL-10, TGF-β1, and IL-17. NOD mice that received β-cell-Ag–loaded, zymosan-exposed DCs showed delayed hyperglycemia. Injection of NOD mice at the prediabetic age and early hyperglycemic stage with β-cell-Ag, along with zymosan, results in a superior protection of the NOD mice from diabetes as compared with mice that received zymosan alone. This therapeutic effect was associated with increased frequencies of IL-10–, IL-17–, IL-4–, and Foxp3-positive T cells, especially in the pancreatic lymph nodes. These results show that zymosan can be used as an immune regulatory adjuvant for modulating the T-cell response to pancreatic β-cell-Ag and reversing early-stage hyperglycemia in T1D.     

Nodal Langerhans cell histiocytosis with prominent eosinophilic emperipolesis

Multinucleated giant cells of osteoclastic type are known to occur in nodal and extranodal lesions of Langerhans cell histiocytosis (LCH). These giant cells are thought to be derived from phagocytic histiocytes, which correlate with the degree of necrosis in LCH lesions. Emperipolesis commonly seen in Rosai–Dorfman disease is a distinct phenomenon characterized by intact phagocytosed cells in an intracytoplasmic vacuole protected from proteolytic digestion. We present a case of emperipolesis of inflammatory cells especially of eosinophils by multinucleated giant cells of Langhans type in a lymph node involved by LCH—a finding that has not been described previously in the literature. Diagn. Cytopathol. 2015;43:1000–1002. © 2015 Wiley Periodicals, Inc.