Delayed haemolytic and serologic transfusion reactions: pathophysiology, treatment and prevention.

PURPOSE OF REVIEW: The aim of this study was to summarize the basic epidemiology, pathophysiology and management of delayed serologic and delayed haemolytic transfusion reactions (DHTRs), as well as recent developments in our understanding of these adverse events. RECENT FINDINGS: Several studies have identified risk factors for DHTRs, including high alloantibody evanescence rates among both general patient groups and those with sickle cell disease (SCD). Antibody detection is also hampered by the phenomenon of transfusion record fragmentation. There have also been enhancements in understanding of what may contribute to the more severe, hyperhaemolytic nature of DHTRs in SCD, including data regarding 'suicidal red blood cell death' and immune dysregulation amongst transfusion recipients with SCD. With growing recognition and study of hyperhaemolytic DHTRs, there have been improvements in management strategies for this entity, including a multitude of reports on using novel immunosuppressive agents for preventing or treating such reactions. SUMMARY: Delayed serologic and haemolytic reactions remain important and highly relevant transfusion-associated adverse events. Future directions include further unravelling the basic mechanisms, which underlie DHTRs and developing evidence-based approaches for treating these reactions. Implementing practical preventive strategies is also a priority.

Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival.

Angiogenesis is one of the hallmarks of tumor growth and metastasis. Identification of tumor angiogenic factors has been a critical component in understanding cancer biology and treatment. Intermedin (IMD) has been reported to promote angiogenesis in a rat ischemic model and human umbilical vascular endothelial cells. Our study sought to determine the role of IMD in human hepatocellular carcinoma tumor progression. High IMD mRNA expression levels were observed in human hepatocellular carcinoma tumors, even in early stage disease, by real-time RT-PCR. Immunohistochemical analysis of hepatocellular carcinoma clinical samples demonstrated that the tumor regions were significantly more immunoreactive for IMD than adjacent benign liver. Inhibition of IMD expression using RNA interference reduced cell proliferation in SK-Hep-1 and SNU-398 cells. Blockage of IMD signaling using either an antagonist peptide or a neutralizing antibody inhibited growth in a dose-dependent manner with concomitant induction of apoptosis, causing cleavage of caspase-8 and downregulation of Gli1 and Bcl2. Conversely, addition of IMD active peptide increased the phosphorylation level of extracellular signal-regulated kinase. Thus, IMD might play an important role in cell proliferation and survival of hepatocellular carcinoma. Our data suggests that IMD is a potential biomarker and therapeutic target for hepatocellular carcinoma.

Identification of lymphatics within the colonic lamina propria in inflammation and neoplasia using the monoclonal antibody D2-40.

CONTEXT: Lymphatic vessels are believed to be absent in the colon above the level of the mucularis mucosae. However, in our experience, lymphatic vessels are sometimes identifiable within the lamina propria in the setting of inflammation and neoplasia. OBJECTIVE: We sought to assess the presence of lymphatics within the colonic lamina propria in neoplastic and inflammatory conditions using the lymphatic endothelium-specific immunohistochemical marker D2-40. DESIGN: Representative sections of normal colon, inflamed colon, hyperplastic polyps, inflammatory polyps, adenomatous polyps, adenomatous polyps containing intramucosal carcinoma, and invasive colonic adenocarcinomas were subjected to immunohistochemical staining with D2-40. The presence of immunopositive lymphatic vessels was assessed. Lymphatic density within the lamina propria was calculated quantitatively, and the presence of inflammation was graded subjectively on a four-tiered scale (0-3). RESULTS: Lymphatics were not identified within the lamina propria of normal colon. However, lymphatics were identified within the lamina propria in the majority of cases with neoplasia and/or inflammation. Additionally, there was a non-significant trend toward higher lymphatic vessel density in cases with increasing inflammation. CONCLUSIONS: Lymphatic vessels are present within the lamina propria of colon in pathologic states, including cases of intramucosal carcinoma. This "aberrant" lymphangiogenesis is likely to be driven by inflammation and/or neoplasia.