An Alternative Hemostatic Dressing: Comparison of CELOX, HemCon, and QuikClot

Objectives:  Uncontrolled hemorrhage remains a leading cause of traumatic death. Several topical adjunct agents have been shown to be effective in controlling hemorrhage, and two, chitosan wafer dressing (HemCon [HC]) and zeolite powder dressing (QuikClot [QC]), are being utilized regularly on the battlefield. However, recent literature reviews have concluded that no ideal topical agent exists. The authors compared a new chitosan granule dressing (CELOX [CX]) to HC, QC and standard dressing in a lethal hemorrhagic groin injury.
Methods:  A complex groin injury with transection of the femoral vessels and 3 minutes of uncontrolled hemorrhage was created in 48 swine. The animals were then randomized to four treatment groups (12 animals each). Group 1 included standard gauze dressing (SD); Group 2, CX; Group 3, HC; and Group 4, QC. Each agent was applied with 5 minutes of manual pressure followed by a standard field compression dressing. Hetastarch (500 mL) was infused over 30 minutes. Hemodynamic parameters were recorded over 180 minutes. Primary endpoints included rebleed and death.
Results:  CX reduced rebleeding to 0% (p < 0.001), HC to 33% (95% CI = 19.7% to 46.3%, p = 0.038), and QC to 8% (95% CI = 3.3% to 15.7%, p = 0.001), compared to 83% (95% CI = 72.4% to 93.6%) for SD. CX improved survival to 100% compared to SD at 50% (95% CI = 35.9% to 64.2%, p = 0.018). Survival for HC (67%) (95% CI = 53.7% to 80.3%) and QC (92%; 95% CI = 84.3% to 99.7%) did not differ from SD.
Conclusions:  In this porcine model of uncontrolled hemorrhage, CX improved hemorrhage control and survival. CELOX is a viable alternative for the treatment of severe hemorrhage.     

Gastrointestinal bleeding during an ultramarathon

Digestive symptoms and gastrointestinal bleeding occur in endurance runners and may contribute to runner's anemia. The cause is unknown, but the frequency of fecal blood loss has been reported to be 8–23% of marathon runners (1–7). Races of longer distances have not been investigated. An ultramarathon is a race that is longer than the 26.2 miles of a marathon and commonly involves distances of 30–100 or more miles and can last 24 hr or more. It differs from the marathon in duration, pace, and intrarace diet. The Old Dominion One Hundred Mile Endurance Run is held in the mountains of Virginia each June. It is open only to experienced ultrarunners who have completed a 50-mile race in less than 9 hr. This race offers a unique opportunity to study highly trained individuals undergoing a tremendous stress to not only their cardiovascular and musculoskeletal systems but also to their gastrointestinal system. The purpose of this prospective study is to determine the incidence of Hemoccult positivity occurring in association with an ultramarathon and evaluating, by means of a questionnaire, cofactors contributing to the gastrointestinal bleeding.The opinions and assertions contained herein are those of the authors and are not to be construed as reflecting the views of Walter Reed Army Medical Center, the Department of the Army or the Department of Defense.     

Molecular characterization of quinine/quinidine drug-dependent antibody platelet interaction using monoclonal antibodies

Two murine monoclonal antibodies, FMC 25 and AN 51, directed against distinct epitopes on the glycoprotein Ib complex, have been used to further define the mechanism of quinine/quinidine drug-dependent antibody interaction with platelets. FMC 25, directed against an epitope on glycoprotein IX, had no effect on platelet aggregation induced by collagen or adenosine diphosphate and little, if any, effect on ristocetin-induced platelet agglutination. FMC 25 and its (Fab)2 fragment, however, were potent inhibitors of drug-dependent antibody- induced platelet aggregation and blocked binding of drug-dependent antibody to platelets as assessed by indirect platelet immunofluorescence. In contrast, AN 51, directed against an epitope on the alpha-subunit of glycoprotein Ib, blocked ristocetin-induced, factor VIII/von Willebrand factor (FVIII/vWF)-dependent platelet agglutination but not drug-dependent antibody-induced platelet aggregation or binding of drug-dependent antibody to platelets. Selective proteolytic removal of the majority of the alpha-subunit of glycoprotein Ib (glycocalicin) from platelets by treatment with calcium- dependent protease did not affect binding of drug-dependent antibody. In addition, a quinidine-dependent antiplatelet antibody immunoprecipitated glycoprotein Ib complex from normal platelets and the membrane-associated proteolytic remnant of the glycoprotein Ib complex from calcium-dependent protease-treated platelets. Preincubation of drug-dependent antibody with purified glycoprotein Ib complex inhibited subsequent binding of antibody to platelets, but the separated components, glycoprotein Ib and glycoprotein IX, were both ineffective, suggesting that the normal interaction between glycoprotein Ib and glycoprotein IX in the intact complex was necessary for drug-dependent antibody recognition. The functional response of platelets to drug-dependent antibody was not mediated by way of platelet Fc receptor, since aggregation of washed platelets by acetone- aggregated IgG was not inhibited by FMC 25 (Fab)2. FVIII/vWF was not required for drug-dependent antibody-induced platelet aggregation. The combined evidence is consistent with quinine/quinidine-dependent antibody-platelet interaction occurring by way of a FVIII/vWF- independent, Fc receptor-independent mechanism that probably involves binding of antibody to glycoprotein IX or the beta-subunit of glycoprotein Ib or both.     

CD44 mediates hyaluronan binding by human myeloid KG1A and KG1 cells

Hyaluronan-binding function of the CD44 molecule has not been so far detected in myeloid cells. To study pure populations of primitive myeloid cells, we investigated the hyaluronan-binding function of the CD44 molecule from three myeloid cell lines: KG1a, KG1, and HL60. Both KG1a and KG1 cells express the CD34 antigen characteristic of the hematopoietic stem cells and HL60 cells do not; accordingly, KG1a and KG1 cells are generally considered as the most primitive and HL60 cells as the most mature of these cell lines. Measurement of cell adhesion to hyaluronan-coated surfaces (using 51Cr-labeled cells) and of aggregate formation in hyaluronan-containing solutions, showed that 45% of KG1 cells and 22% to 24% of KG1a spontaneously bind to hyaluronan, whereas HL60 cells do not either spontaneously or after treatment with a phorbol ester. Hyaluronan binding by KG1a and KG1 cells is mediated by CD44, because it is specifically abolished by monoclonal antibodies (MoAbs) to this molecule. The binding might require phosphorylation by protein kinase C and perhaps also by protein kinase A, because it is prevented by staurosporine, which inhibits these enzymes. 12-O- tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C, rises to 80% the proportion of KG1 and KG1a cells that bind hyaluronan; this activation is dependent on protein synthesis, for it is abrogated by cyclophosphamide, a protein synthesis inhibitor. Binding of TPA- treated cells to hyaluronan is only partly inhibited by MoAb to CD44: this suggests that TPA may induce synthesis of a hyaluronan-binding protein distinct from CD44. Considering the abundance of hyaluronan in human bone marrow, these results suggest that CD44 may be involved in mediating precursor-stroma interaction.     

Relationship between urinary excretion of modified nucleosides and rheumatoid arthritis process

The levels of the five methylated nucleosides pseudouridine (psi-Urd), 1-methyladenosine (1-MeAdo), 4 acetylcytidine (4-AcCyd), 1 methylinosine (1-Melno) and 7 methylguanosine (7-MeGuo) resulting from RNA degradation were examined in the urine of rheumatoid arthritis (RA) patients. Of these five, 1-MeAdo and psi-Urd were correlated with the active phase of the disease, while two others (4-AcCyd and 1-Melno), which require further evaluation, appeared to be linked to the prognosis of the disease. As RNA turnover is closely associated with cell proliferation, including that of lymphocytes in RA, there may be a hitherto unsuspected benefit in measuring 1-MeAdo and psi-Urd as biochemical markers of RA disease activity.