Angiostrongylus cantonensis meningitis presenting with facial nerve palsy.
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Adult↗
Biomedical subjects
J Sevigny
Publications and source records attributed to J Sevigny.
Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants.
Mouse-to-rat cardiac transplants survive long term after transient complement depletion by cobra venom factor and T cell immunosuppression by cyclosporin A. Expression of heme oxygenase-1 (HO-1) by the graft vasculature is critical to achieve graft survival. In the present study, we asked whether this protective effect was attributable to the generation of one of the catabolic products of HO-1, carbon monoxide (CO). Our present data suggests that this is the case. Under the same immunosuppressive regimen that allows mouse-to-rat cardiac transplants to survive long term (i.e., cobra venom factor plus cyclosporin A), inhibition of HO-1 activity by tin protoporphyrin, caused graft rejection in 3--7 days. Rejection was associated with widespread platelet sequestration, thrombosis of coronary arterioles, myocardial infarction, and apoptosis of endothelial cells as well as cardiac myocytes. Under inhibition of HO-1 activity by tin protoporphyrin, exogenous CO suppressed graft rejection and restored long-term graft survival. This effect of CO was associated with inhibition of platelet aggregation, thrombosis, myocardial infarction, and apoptosis. We also found that expression of HO-1 by endothelial cells in vitro inhibits platelet aggregation and protects endothelial cells from apoptosis. Both these actions of HO-1 are mediated through the generation of CO. These data suggests that HO-1 suppresses the rejection of mouse-to-rat cardiac transplants through a mechanism that involves the generation of CO. Presumably CO suppresses graft rejection by inhibiting platelet aggregation that facilitates vascular thrombosis and myocardial infarction. Additional mechanisms by which CO overcomes graft rejection may involve its ability to suppress endothelial cell apoptosis.
Acute Disease↗
Impact of therapeutic plasma exchange on cyclosporine kinetics during membrane-based lipid apheresis.
Cyclosporine is used widely as an immunosuppressant in transplant recipients and for various autoimmune diseases. In some cases, these patients require therapeutic plasma exchange (TPE). Cyclosporine is known to be highly bound to lipoproteins, and their removal by TPE would be expected to have an impact on drug dosing. We studied cyclosporine kinetics in a 54-year-old woman who is status post-cardiac transplant and has been receiving weekly TPE for familial hypercholesterolemia. We obtained serial measurements of cyclosporine, low-density lipoproteins, and high-density lipoproteins at scheduled times related to the dosing of the medication on days that she received TPE versus a day she did not. We also measured cyclosporine, low-density lipoprotein, and high-density lipoprotein levels in the fixed volume (3.5 L) of the discarded plasma. Our results show a similar rate of decline of serum cyclosporine levels on TPE days as compared with a day without TPE. Net cyclosporine in the discarded plasma was found to be approximately 1 mg per treatment or less, a relatively insignificant amount when compared with the ingested daily dose of 150 to 250 mg twice a day. Despite substantial removal of lipoproteins, there is minimal impact of TPE on serum levels of cyclosporine, and dosage adjustment is not needed for patients undergoing this procedure.
Blood Component Removal↗
CD39/vascular ATP diphosphohydrolase modulates xenograft survival.
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Adenosine Triphosphatases↗
CD39 as a caveolar-associated ectonucleotidase.
CD39 is a human lymphoid cell activation antigen, (also referred to E-ATPDase or apyrase) that hydrolyzes extracellular ATP and ADP. Although it has been widely studied, its physiological role, however, still remains unclear. This ectonucleotidase generally is said to be evenly distributed in the membrane of the cells. However, we observed that in cell types which possess caveolae, specialised membrane invaginations involved in signalling, CD39 is preferentially targeted to these membrane microdomains. Since all molecules involved in signalling (eNOS, G-proteins, receptors) which are targeted to the caveolae undergo posttranslational modifications (e.g., palmitoylation) we hypothesize the same to be the case for CD39. Furthermore, its presence in the caveolae supports its participation in signalling events.
Adenosine Triphosphatases↗
Extracorporeal treatment of thrombotic microangiopathy: a ten year experience.
We reviewed 24 episodes of thrombotic microangiopathy (TMA) representing 22 patients from July 1989 to July 1998. Nine cases presented with a community acquired (CA group) thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (TTP/HUS), 3 cases were related to pregnancy (P group), 10 cases were compatible with TMA after bone marrow transplantation or chemotherapy (BMT/C group), and 2 cases had a background of scleroderma (SC group). Twenty episodes were treated exclusively with therapeutic plasma exchange (TPE) using fresh frozen plasma (FFP) replacement. In the BMT/C group, 4 patients underwent immunoadsorption with the Prosorba protein A column in addition to TPE. The CA, P, and SC groups had favorable outcomes with 78% (7 of 9), 100% (3 of 3), and 100% (2 of 2) survival, respectively. Despite intensive therapy, there was only 1 survivor in the BMT/C group (1 of 10). Successful outcome required up to 57 TPE treatments. We could not document any benefit to immunoadsorption with the Prosorba protein A column.
Adolescent↗
Dietary intake data: usefulness and limitations.
In past decades, the main objectives of nutrition surveys were to define nutritional status at the time of the study, to cross-sectionally describe dietary patterns of consumption and food preparation practices, and to identify areas for improvement. Nowadays, the need for ongoing evaluation of nutritional status of individuals and of population is gaining recognition. The present paper, in discussing usefulness and limitations of dietary intake data, will focus on the importance of considering nutrition as a component of overall quality of life as well as a discipline that gains to be integrated to other disciplinary fields such as medicine, biochemistry, immunology, anthropometry and agribusiness. In this respect, the present paper will discuss the methodology of dietary data collection, the various uses of dietary data collected at the individual, community and general population levels and finally will try to define new vistas in regard to emphasis and tools for future dietary intake studies.
Agriculture↗
One year's experience using a rotating filter for therapeutic plasma exchange.
The authors previously demonstrated the feasibility of using a rotating filter system for therapeutic plasma exchange. They now report on the technical details of a 1 year clinical experience. Seventeen patients underwent 188 treatments. Hemoaccess was provided by antecubital veins (147 Rx), femoral catheters (37 Rx), or an a-v fistula (3 Rx). Blood flows ranged from 75 to 100 ml/min. Net plasma removed per treatment was 3,231 +/- 53 ml (mean +/- SE, n = 188). Mean plasma removal rate per treatment was 40.2 +/- 0.6 ml/min; mean treatment time was 83 +/- 2 min. Platelet counts before and after treatment revealed a 15 +/- 4% decline (n = 46 Rx). Despite filtration fractions up to 86% there was no evidence of significant membrane plugging or hemolysis. For semiselective removal of cholesterol, the rotating filter was used in a cascade system with a secondary filter. Eighty percent of processed plasma was returned to the patient, but the treatment time was prolonged by 37% and the total cholesterol removed was 26% less when compared with the single pass system. The authors conclude that an inexpensive rotating filter can provide a highly efficient plasma exchange. The inherent efficiency of this system must be considered when evaluating its use with secondary filtration techniques.
Cholesterol↗
High flux plasma exchange using a modified rotating membrane system.
The results of increasing blood flow capability in a modified system for plasma exchange with a rotating filter are reported. There were 742 treatments performed with the authors' original system (OS), limited to blood flows of 100 ml/ min, and 327 treatments performed with the updated system (US), allowing for blood flows of 150 ml/min. Blood flows for OS were 98 +/- 5 ml/min (mean +/- SD) vs 145 +/- 12 ml/min for US (p < 0.001). Plasma flows were 65 +/- 7 ml/min for OS vs 98 +/- 12 ml/min for US (p < 0.001). Plasma removal rate was 42 +/- 8 ml/min for OS vs 61 +/- 14 ml/min for US (p < 0.001). Mean treatment time was reduced from 76 +/- 23 min for OS to 52 +/- 17 min for US (p < 0.001) in spite of providing a similar amount of plasma removed per treatment (3,113 +/- 577 ml/Rx for OS vs 3078 +/- 797 ml/Rx for US; p = 0.48). Despite statistical significance, there were only small differences in filtration fractions (65 +/- 12% for OS vs 62 +/- 11% for US; p < 0.001) and patient hematocrits (34 +/- 6% for OS vs 33 +/- 6% for US; p < 0.001). In conclusion, modification of the OS to allow for increased blood flow has resulted in a substantial improvement in procedure efficiency and a clinically useful decrease in treatment time.
Biocompatible Materials↗