Black oesophagus in a patient with peritoneal carcinomatosis

Acute oesophageal necrosis (AEN) is a rare disorder that presents like \u201cblack oesophagus\u201d on endoscopy. The main risk factors include age, male sex, cardiovascular disease, gastric outlet obstruction, diabetes, malnutrition and alcohol ingestion. Malignancy is associated to AEN in about 20% of cases. Case Report: A 78-year-old man presented with ascites, anorexia, nausea and weight loss. His alcohol intake was about 50 g daily and he had hypertension, ischemic cardiopathy and chronic obstructive pulmonary disease. Laboratory and imaging investigations oriented towards biliary malignancy with peritoneal carcinomatosis. Twenty days after admission, the patient had an episode of hematemesis. At upper gastrointestinal endoscopy, the entire oesophagus was black with superimposed pseudomembranes. Additional fi ndings included cardial and duodenal ulcers with pyloric involvement. After treatment with omeprazole and parenteral nutrition, the endoscopic fi ndings disappeared but the patient died in two weeks because of malignant cachexia. Conclusions: AEN should be considered in the differential diagnosis of upper gastrointestinal bleeding. Malnutrition in malignancy, together with other risk factors, fi rst of which cardiovascular disease and gastric outlet obstruction, can contribute to mucosal necrosis

Polyneuropathy in hypereosinophilic syndrome.

We investigated two patients with the idiopathic hypereosinophilic syndrome and peripheral neuropathy. Clinical, EMG, and pathological findings were consistent with axonal polyneuropathy. Morphologic changes of the nerve biopsies suggested axonal damage secondary to increased endoneurial pressure from leakage of capillaries. We postulate that endothelial cell damage, followed by nerve edema, is the first step in the pathogenesis of peripheral neuropathy in these patients

Dendritic cells in the healthy and inflamed brain: A two photon microscopy investigation.

Dendritic cells (DCs) are professional antigen-presenting cells, derived from a bone marrow progenitor, which modulate the balance between suppression and induction of the immune response. DCs have been widely characterized in peripheral organs, especially in lymph nodes where antigen presentation mostly occurs. DCs have also been identified in the meninges and choroid plexus, as well as within the brain parenchyma. Several key aspects of DCs function in the brain are, however, still unexplored. Transgenic mice expressing fluorescent proteins in cell subsets provide valuable tools for in vivo investigations by two-photon fluorescence (TPF) microscopy. We recently demonstrated that in thy1GFP-M mice, engineered for green fluorescent protein (GFP) expression in neurons, also DCs express GFP. This murine line is, therefore, suited for the visualization of brain DCs. We here analyzed with TPF microscopy GFP-tagged brain DCs in healthy thy1GFP-M mice and during infection with Trypanosoma brucei (Tb). This parasite is the etiological agent of human African trypanosomiasis or sleeping sickness, whose encephalitic stage is fatal if untreated, and in which pathogenetic mechanisms of the neuroimmune response remain to be clarified. Our in vivo observations showed, in normal conditions, GFP-DCs in the subarachnoid space and meninges, where these cells were mainly static and occasionally in a probing-like motion. A motile behavior of GFP-DCs was also observed in the upper cortical layers, supporting a role of immunosurveillance of DCs in the healthy brain. Striking changes of motility and quantity of GFP-DCs were observed in the brain of Tb-infected thyGFP-M mice. During the early meningoencephalitic stage, GFP-DCs invaded the parenchyma with rapid and wide displacements, and also occurred in static adhesion to or crawling on the inflamed endothelium. With disease progression, a drastic decrease in the number of GFP-DCs was observed at the brain surface, and GFP-DCs appeared arranged in static clusters of cells exhibiting numerous processes, likely to increase the cell membrane surface on which antigens are exposed. Preliminary in vivo observations of thy1GFP-M mice infected with transgenic fluorescent Tb have shown direct interactions between GFP-DCs and the parasites; further analyses are ongoing. Taken together, the present in vivo investigations not only reveal a motile behavior of DCs at the brain surface and in the upper cortical layers, but also suggest a relevant role of brain DCs in African trypanosome infection. In particular, these cells could play a role in the transition from immune resistance to immune tolerance during this severe brain infection

Watching in vivo dendritic cells in action in the brain

Dendritic cells (DCs) present self or no-self antigens to T cells, to modulate the immune response. DCs are widely studied in peripheral organs, but little is known about their function in the brain. We recently demonstrated (Laperchia et al., 2013) that DCs can be monitored in vivo by two-photon microscopy in thy1GFP-M transgenic mice, in which a subset of DCs is tagged by green fluorescent protein (GFP-DCs). Here we investigated by two-photon microscopy the migratory pattern of brain GDP-DCs both in basal condition and during the meningo-encephalitic stage of an experimental model of African trypanosomiasis, also known as sleeping sickness, induced by the infection with parasites Trypanosome brucei brucei. Trough a chronically implanted brain window in thy1GFP-M mice we found, in basal conditions, GFP-DCs floating in the cerebrospinal fluid or static at the pia mater/parenchyma interface. At an early stage of the meningoencephalitis, circulating GFP-DCs were in contact with the parasites, maybe representing an antigen capture process. Subsequently, DCs roll and crawl on the inflamed endothelium and were massively recruited from the blood stream to the brain parenchyma, where exhibited rapid and wide displacements. At a late stage, the number of motile GFP-DCs was significantly reduced and, interestingly, GFP-DCs were mainly arranged in static clusters that incorporate the parasite. Our results show for the first time the migratory pattern of DCs during invasion of the inflamed brain and suggest a role of brain DCs in the passage from brain immune-resistance to immune-tolerance during a parasitic infection

Two-photon microscopy investigation of brain dendritic cells in inflamed brain

Human African trypanosomiasis, also known as sleeping sickness, is a severe disease caused by the parasite Trypanosoma brucei (T.b.), in which systemic infection evolves into meningoencephalitis1. One of the most effective strategies adopted by several parasites to attack the host immune system is to interfere with dendritic cells (DCs)2, which play a key role of immune surveillance. In African trypanosomiasis, DCs have been analyzed in peripheral organs3,4 but have not been hitherto examined in the brain. We recently demonstrated that thy1GFP-M transgenic mice represent a novel tool for the study of brain DCs because they express green fluorescent protein (GFP) not only in neurons but also in DCs5. Here, we investigated in vivo, by two-photon microscopy, DCs and their interaction with T.b. in infected thy1GFP-M mice at different time points during the meningoencephalitic stage of the disease