A case of AIDS-complicated lung infection mimicking acute eosinophilic pneumonia]

A 34-year-old man was admitted with dyspnea and low grade fever. Chest radiograph and computed tomography (CT) showed bilateral, ground glass opacities and perihilar consolidation. Bronchoalveolar lavage (BAL) was performed. The percentage of eosinophils in the BAL fluid (BALF) was elevated (20.5%). BALF smear and culture showed normal flora. Acute eosinophilic pneumonia was diagnosed and steroid therapy was performed. Afterwards he was transferred to our hospital. The HIV antibody was positive and peripheral blood CD-4 positive lymphocytes decreased to 10/microl, cytomegalovirus (CMV) antigenemia was positive and beta-D-glucan increased. CMV infection and pneumocystis pneumonia (PCP) complicated with AIDS was diagnosed. Trimethoprim/sulfamethoxazole, ganciclovir, and antifungal drugs were administered, but he suffered pneumothorax on the 18th day after admission and died. Histopathologic findings from an autopsy lung specimen revealed CMV infection and PCP. It is known that the percentage of eosinophils in the BALF increases in some cases of PCP complicated with AIDS. We emphasize that it is necessary to consider PCP when the percentage of eosinophils in the BALF increase.     

Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI 3-kinase-Akt signaling pathway

Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive (PHT) gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury. However, the signaling mechanisms for eNOS activation in PHT gastric mucosa and the role of TNF-alpha in this signaling remain unknown. In PHT gastric mucosa we studied (1) eNOS phosphorylation (at serine 1177) required for its activation; (2) association of the phosphatidylinositol 3-kinase (PI 3-kinase), and its downstream effector Akt, with eNOS; and, (3) whether TNF-alpha neutralization affects eNOS phosphorylation and PI 3-kinase-Akt activation. To determine human relevance, we used human microvascular endothelial cells to examine directly whether TNF-alpha stimulates eNOS phosphorylation via PI 3-kinase. PHT gastric mucosa has significantly increased (1) eNOS phosphorylation at serine 1177 by 90% (P <.01); (2) membrane translocation (P <.05) and phosphorylation (P <.05) of p85 (regulatory subunit of PI 3-kinase) by 61% and 85%, respectively; (3) phosphorylation (P <.01) and activity (P <.01) of Akt by 40% and 52%, respectively; and (4) binding of Akt to eNOS by as much as 410% (P <.001). Neutralizing anti-TNF-alpha antibody significantly reduced p85 phosphorylation, phosphorylation and activity of Akt, and eNOS phosphorylation in PHT gastric mucosa to normal levels. Furthermore, TNF-alpha stimulated eNOS phosphorylation in human microvascular endothelial cells. In conclusion, these findings show that in PHT gastric mucosa, TNF-alpha stimulates eNOS phosphorylation at serine 1177 (required for its activation) via the PI 3-kinase-Akt signal transduction pathway.     

EB virus-associated peripheral T cell lymphoma presenting with hemophagocytic syndrome and hepatic cell necrosis

A 72-year-old woman was admitted with left cervical lymphadenopathy, high fever, pancytopenia and liver dysfunction. Bone marrow aspiration showed infiltration of large atypical lymphoid cells and hemophagocytic histiocytes, thus suggesting a diagnosis of lymphoma associated hemophagocytic syndrome (LAHS). An abdominal CT scan revealed multiple low-density areas in the liver, and the patient's liver function rapidly deteriorated. Histologically, the cervical biopsy showed lymphoma cell infiltration with prominent necrosis and karyorrhectic debris. The lymphoma cells expressed CD3+, CD4-, CD8+, CD20-, CD56+/-, TIA-1+, granzyme B+, and EBER was positive using in situ hybridization. DNA analysis of the TCR beta and gamma chain gene with the Southern blot showed rearranged bands. These findings were compatible with those of EB-virus associated peripheral T-cell lymphoma. After chemotherapy with the THP-COP regimen, the patient's liver dysfunction improved rapidly, but she died from bacterial peritonitis due to perforation of a recurrent duodenal ulcer. Post-mortem examination of the liver showed multiple irregular massive necroses of the hepatocytes, where no lymphoma cell infiltration was present. Hemophagocytic histiocytosis was remarkable in the bone marrow, spleen, lymph nodes, and liver. Marked elevation of serum levels of cytokines such as TNF-alpha or IFN-gamma suggests that these cytokines played an important role in the pathogenesis of the hepatic cell necrosis.     

Impairment of angiogenic activity in the serum from patients with coronary aneurysms due to Kawasaki disease.

BACKGROUND: The inflammatory mediators play an important role in the progression of coronary vasculitis in Kawasaki disease (KD), but effects of KD serum including inflammatory mediators on endothelial cells remain unknown. We hypothesized that serum activity to stimulate in vitro human umbilical vein endothelial cells (HUVEC) tube formation might be impaired in KD. METHODS AND RESULTS: Serum from patients with coronary aneurysms was less active in stimulating HUVEC tube formation than serum from patients without coronary aneurysms or febrile controls. In patients with coronary aneurysms, the reduction in the serum angiogenic activity was documented already before KD treatment (p=0.03 vs healthy controls, p=0.08 vs febrile controls) and enhanced after intravenous immune globulin plus aspirin (p<0.001 vs healthy controls, p=0.002 vs febrile controls); both drugs did not affect the assay studied. This reduction was greater in patients who later developed giant aneurysms >8 mm compared with those who developed small to moderate aneurysms (p=0.01). The reduced serum angiogenic activity was partly caused by the reduction in the serum activity of stimulating HUVEC proliferation. CONCLUSIONS: Serum activity to stimulate HUVEC tube formation was impaired in KD patients who later developed larger coronary aneurysms, which may be associated with the severity of vascular injury.     

Clinical significance of the accessory pancreatic duct

BACKGROUND/AIMS: The accessory pancreatic duct is the smaller and less constant pancreatic duct in comparison with the main pancreatic duct. We investigated the patency of the accessory pancreatic duct and its role in pancreatic pathophysiology. METHODOLOGY: Dye-injection endoscopic retrograde pancreatography was performed in 411 patients. In patients in whom the main pancreatic duct could be selectively cannulated, contrast medium with indigo carmine was injected through the catheter. Excretion of the dye from the minor duodenal papilla was observed endoscopically. RESULTS: Patency of the accessory pancreatic duct was 43% of the 291 control cases. In the 46 patients with acute pancreatitis, 8 (17%) had a patent accessory pancreatic duct. The difference in patency between this group and the normal group was significant (p < 0.01). Especially, patency of the accessory pancreatic duct was only 8% of the 13 patients with acute biliary pancreatitis. In the patients with pancreaticobiliary maljunction, biliary carcinoma occurred in 72% of patients with a nonpatent accessory pancreatic duct, but in contrast, it occurred only in 30% of those with a patent accessory pancreatic duct. This difference was significant (p < 0.05). Lower amylase level in the bile of patients with pancreaticobiliary maljunction with a patent accessory pancreatic duct was frequently observed than those with a nonpatent accessory pancreatic duct. CONCLUSIONS: A patent accessory pancreatic duct may prevent acute pancreatitis by lowering the pressure in the main pancreatic duct. In cases of pancreaticobiliary maljunction with a patent accessory pancreatic duct, the incidence of carcinogenesis of the bile duct might be lower, as the reflux of the pancreatic juice to the bile duct might be reduced by the flow of the pancreatic juice into the duodenum through the accessory pancreatic duct.