Multiple main pancreatic duct stones in tropical pancreatitis: safe clearance with extracorporeal shockwave lithotripsy

BACKGROUND AND AIM: Extracorporeal shockwave lithotripsy (ESWL) has an established role in the management of pancreatic ductal stones. Its efficacy in management of multiple stones in tropical pancreatitis is unknown. The aim of this study was to prospectively evaluate: (i) the efficacy of main pancreatic duct stone clearance; and (ii) associated complications with ESWL therapy in tropical pancreatitis. METHODS: Consecutively recruited patients with tropical pancreatitis underwent fragmentation of main pancreatic duct stones using ESWL. Endoscopic retrograde cholangiopancreatography (ERCP) using standard techniques was performed to manage residual stones. Complete, partial and unsatisfactory clearance was defined as >90%, 50-90% and <50% of stone clearance, respectively. Clinical and technical data were collected on a pre-formatted data sheet. Statistical analysis was performed on an intention-to-treat basis. RESULTS: A total of 250 patients (mean+/-SD age 35.2+/-11.9 years; 66% men), 86.8% with multiple radio-opaque stones, underwent ESWL between February 2004 and May 2005. Of the 250 patients, 149 (59.6%) achieved complete clearance and 59 (23.6%) achieved partial clearance of pancreatic calculi. Main pancreatic ductal decompression was achieved in 70.0% (175/250) of patients. Complications occurred in 5.6% (14/250) during ESWL and in 1.2% (3/250) during ERCP. A mean of 1.3 sessions, with mean+/-SD 5.5+/-0.7 intensity setting, 85.8+/-13.5 pulses per minute and 3862+/-1426 shocks per session were required. CONCLUSION: Clearance of multiple main pancreatic duct stones in patients with tropical pancreatitis is safely performed via ESWL followed by ERCP ductal drainage.     

Pathophysiology of graft-versus-host disease

Complications of allogeneic hematopoietic stem cell transplantation (HSCT) remain barriers to its wider application for a variety of diseases. Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality following allogeneic HSCT. GVHD can be considered an exaggerated, undesirable manifestation of a normal inflammatory mechanism, in which donor lymphocytes encounter foreign antigens in a milieu that fosters inflammation. Recent advances in the study of cytokine networks, chemokine gradients, and the direct mediators of cellular cytotoxicity have led to improved understanding of this complex syndrome. The pathophysiology of acute GVHD can be considered as a three-step process in which the innate and adaptive immune systems interact: (1) tissue damage to the recipient by the radiation/chemotherapy pretransplant conditioning regimen; (2) donor T-cell activation and clonal expansion; and (3) cellular and inflammatory factors. Here we review the immunologic interactions that cause clinical GVHD and discuss the risk factors and prophylactic strategies for acute GVHD according to this model.     

Pathogen inactivation of Leishmania donovani infantum in plasma and platelet concentrates using riboflavin and ultraviolet light

BACKGROUND AND OBJECTIVES: Leishmania is transmitted by the bite of the phlebotomine sandfly or by transfusion of infected blood products. Leishmaniasis currently poses a significant problem in several parts of the world, and is an emerging problem in others. The Mirasol PRT technology is based on the use of riboflavin and ultraviolet light to generate chemical reactions in the nucleic acids of pathogens, which prevents replication and leads to inactivation. The intent of this study was to examine the ability of the Mirasol PRT System to kill the Leishmania parasite in human plasma and platelet concentrates. MATERIALS AND METHODS: In visceral Leishmaniasis, amastigotes are present in the blood and in the reticuloendothelial system within monocytes. For each unit of plasma or platelets treated, isolated mononuclear cells obtained from 100 ml of normal donor whole blood were incubated with 1.0 x 10(8) Leishmania donovani infantum promastigotes to produce amastigote-laden macrophages. The infected macrophages were added to 250 ml of human plasma or to 250 ml of platelet concentrates. Infected units were cultured pretreatment in 10-fold serial dilutions to determine the limits of detection. Thirty millilitres of 500 microM riboflavin was added to each unit, which was then illuminated with 5.9 J/cm2 of ultraviolet light (6.24 J/ml). After treatment and after 2 months of frozen storage, plasma units were cultured in 10-fold serial dilutions. Platelets were cultured on the day of treatment and on day 5 of storage post-illumination. RESULTS: A 5 log reduction of Leishmania was demonstrated in five of six units of plasma, and a 7 log reduction of Leishmania was demonstrated in one plasma unit. A 5 log reduction of Leishmania was demonstrated in five of six units of platelets, and a 6 log reduction of Leishmania was demonstrated in one unit. CONCLUSIONS: There is no donor screen for Leishmania and other pathogens constantly emerging in our blood supply. The Mirasol PRT System for Platelets and Plasma is an effective means of killing Leishmania and other emerging pathogens in these blood products.     

The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth

The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play a crucial role in vascular development during embryogenesis. The soluble monomeric derivative of the extracellular domain of EphB4 (sEphB4) was designed as an antagonist of EphB4/EphrinB2 signaling. sEphB4 blocks activation of EphB4 and EphrinB2; suppresses endothelial cell migration, adhesion, and tube formation in vitro; and inhibits the angiogenic effects of various growth factors (VEGF and bFGF) in vivo. sEphB4 also inhibits tumor growth in murine tumor xenograft models. sEphB4 is thus a therapeutic candidate for vascular proliferative diseases and cancer.     

Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus

OBJECTIVES: The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci. METHODS: This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis. RESULTS: We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease. CONCLUSIONS: Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD.     

Interleukin-18: recent advances

PURPOSE OF REVIEW: Interleukin-18 (IL-18) has potent immunomodulatory effects. It is the only cytokine with a unique capacity to induce T helper 1 or T helper 2 polarization, depending on the immunologic context. Serum levels of IL-18 are increased in many human diseases and it has been implicated in the pathogenesis of several immune-mediated processes. Some of the recent key advances in the immunobiology of IL-18 are discussed in this review. RECENT FINDINGS: Recent data from several laboratories have shed light on the structure of IL-18; the signaling cascades that are initiated; and its role on modulating T cells, dendritic cells, and natural killer cell function. Several new reports have expanded and delineated the role of IL-18 in a multitude of diseases, but only recent advances in the role of IL-18 in three disease processes (acute graft-versus-host disease, insulin-dependent diabetes, and sepsis), where it appears to play paradoxic roles are discussed. SUMMARY: Although emerging data shed more light on the complex role of IL-18 in immune reactions, they also pose more questions. Given the pleiotropic, complex, and at times paradoxic effects of IL-18 in various disease processes, better understanding of its immunobiology might lead to the development of IL-18 and/or its antagonists as therapeutic agents against immune-mediated diseases.     

Profound thrombocytopenia associated with tirofiban: case report and review of literature

Platelet glycoprotein (GP)IIb/IIIa inhibitors prevent fibrinogen binding and platelet aggregation. Inhibition of platelet activity at the injured coronary plaque is a target for novel therapeutic strategies. They decrease ischemic complications associated with non-ST-segment elevation acute coronary syndromes and percutaneous coronary intervention. Thrombocytopenia is a serious complication well described with the use of the prototype GP IIb/IIIa inhibitor abciximab. Its association with other agents of this class has been underemphasized. It is important to monitor platelet counts closely after initiation of GP IIb/IIIa inhibitor therapy, not only for abciximab, but also for small molecule inhibitors such as eptifibatide and tirofiban. Monitoring of platelet counts at 2 to 6 hours and 24 hours will detect most cases of acute thrombocytopenia. Adverse events may be prevented by prompt discontinuation of GP IIb/IIIa inhibitor therapy. The authors present a case of profound thrombocytopenia after the administration of tirofiban in the treatment of a patient with an acute coronary syndrome.