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M W Flye

Publications and source records attributed to M W Flye.

262 records · Page 15Linked to original sources

Gadolinium chloride inhibits lipopolysaccharide-induced mortality and in vivo prostaglandin E2 release By splenic macrophages.

The monocytic phagocytic system, consisting primarily of tissue macrophages of the liver and spleen, produces prostaglandin E(2) (PGE(2)), a modulator of the septic response. Macrophages are known to internalize gadolinium chloride (GD), a lanthanide metal, which inhibits phagocytic function. Thus we studied the effect of in vivo GD on lipopolysacchride (LPS)-induced mortality and on LPS-stimulated PGE(2) release by cultured splenic macrophages. GD (7 mg/kg intravenously) given on the two days prior to LPS challenge (30 mg/kg intravenously) completely prevented the uniform mortality in rats. This protective effect was transient since rechallenge with LPS 10 days later was uniformly lethal. Previous work in this laboratory has established a critical role of arginine concentration on macrophage behavior in vitro. Therefore, to establish culture conditions reflective of the milieu within the portal venous system, alanine and arginine levels were measured in the portal and hepatic veins of normal and endotoxemic (LPS, 10 mg/kg intraperitoneally) rats. In contrast to alanine levels, which were not altered by endotoxemia, there was a reduction of arginine concentrations from a range of 50 to 250 micromol/L in normal rats to a range of 10 to 50 micromol/L after LPS challenge. Consequently subsequent in vitro assays of splenic macrophage secretory behavior were performed in concentrations of 1200 micromol/L arginine (in standard RPMI-1640), as well as in concentrations reflective of physiologic arginine levels (10 and 100 micromol/L in modified RPMI-1640). Rat splenic macrophages harvested after two consecutive days of either in vivo saline or GD injection (7 mg/kg intravenously) were stimulated with LPS (0.025 to 2.5 microg/ml). At 72 hours of culture, the release of PGE(2) by splenic macrophages from GD-treated rats was significantly (P <0.0001) reduced at all LPS concentrations. Increased PGE(2) production was not present when the splenic macrophages were cultured in the supraphysiologic arginine (1200 micromol/L) concentration. The results demonstrate the relevance of physiologic arginine concentrations in cell culture studies and suggest that the protection conferred by GD against septic mortality may be related to downregulation of the release of immunosuppressive PGE(2) by the monocytic phagocytic system.

Alanine↗

Delayed hemolytic transfusion reaction caused by anti-P1 antibody.

A 67-year-old white woman received transfusions of a total of 87 units of whole blood and red blood cells during and within 48 hours following a pneumonectomy. Although she had previously received blood transfusions, unexpected antibodies were not detectable by routine screening. On the second postoperative day, she developed fever, hemoglobinemia, hemoglobinuria, and oliguria. However, the direct antiglobulin test and the antibody screen were negative. On the eighth postoperative day, an IgM anti-P1 antibody was detected for the first time. This anti-P1 antibody increased in thermal amplitude from 22 to 37 C, but remained IgM. The circulating transfused P1-positive cells decreased progressively without evidence of bleeding. Testing of the patient's preoperative blood at 15 C found her serum to be weakly reactive with P1 cells, while her own cells were P2. Thus, an anamnestic response to the P1 antigen is the most likely cause of her delayed hemolytic transfusion reaction.

Aged↗

Blood component use in orthotopic liver transplantation.

Blood component use during orthotopic liver transplantation (OLT) was evaluated after an initial 23-month experience with 37 consecutive transplant procedures. Blood component support of OLTs in 24 adult and 13 pediatric patients was reviewed. Adult procedures required intraoperatively a mean of 24.5 units of red cells (RBCs), 38.7 units of fresh-frozen plasma (FFP), 26.1 random-donor platelets (RDP), and 12.2 units of cryoprecipitate (Cryo); pediatric procedures required 4.8 units of RBCs, 5.8 of FFP, 3.9 of RDP, and 1.2 of Cryo. RBC salvage constituted 17 percent of the RBCs transfused intraoperatively. Intraoperative support in adult and pediatric OLT patients accounted for the majority of the total components required for the entire hospital stay. OLT blood component use constituted 1.3, 7.0, 3.6, and 8.1 percent of hospital-wide use of RBC, FFP, RDP, and Cryo, respectively, during the period of the study.

Adolescent↗