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Pharmacokinetics of intravenous immunoglobulin (GAMMAGARDR) in bone marrow transplant patients
Abstracts
813
206. IMMUNOTHERAPY OF FLORENCE NIGHTINGALE SYNDROME (FNS) WITH DIALYZABLE LYMPHOCYTE EXTRACT (DLyE) H. Hugh Fudenberg, Medical University of South Carolina, Charleston, SC 29403 During the last five years, we have seen an increasing number of patients who complain of cognitive disorder, hyperfatigability, sleep disorder, muscle pain and depression. In Great Britain, the predominant virus is one of the entero viruses, and in the U.S., one of the herpes group. The disorder has been termed myalgic encephalitis in Great Britain and Chronic Fatigue Immune Dysregulation Syndrome (SFIDS) in the U.S. (It has also been called Chronic Epstein-Barr Virus and the Yuppie Syndrome in the U.S.). Our evidence suggests that this syndrome is due to the continual stimulation of immune cells by a dead or incomplete virus. To eliminate the confusion caused by the many conflicting terminologies, we propose to call it Florence Nightingale-Syndrome, because her diary showed that she had all symptoms of this synd=ome. All previous studies have lumped together all patients with this syndrome, despite their varying degrees of severity and different durations of symptoms. We've studies 50 patients with severe FNS unable to function for at least 2 years and without any unusual febrile episodes for those 2 years. Before we saw them, many had been given intravenous magnesium and IgG,both of which produced clinical benefits only as long as injections were continued. We used Dialyzable LYMPHOCYTE Extract (DLyE) prepared from carefully selected donors. Of the 39 who received DLyE prepared from close household or intimate social contacts, 34 are working full-time after 18 months of therapy. Of the ii who received DLE) preared from random normal donors, only 1 is back at work after 18 months of therapy. In addition. clinical response to preparations made from leukocvtes containg less than 20% granulocytes. This may explain why DLyE gave good results in some patients who completely failed to resona to DLE.
207
PHARMACOKINETICS OF INTRAVENOUS IMMUNOGLOBULIN (GAMMAGARD R) IN BONE MARROW TRANSPLANT PATIENTS Kenneth H. Rand, Katherine Gibbs, Hartmut Derendorf, and John Graham-Pole Departments of Pathology, Medicine, Pediatrics, and Pharmaceutics, University of Florida and the Department of Veteran's Affairs Medical Center, Gainesville. FL 32610 The pharmacokinetics of an intravenous immunoglobulin (IVIG), Gammagard a, were measured in 31 Cytomegalovirus (CMV) antibody negative Bone Marrow transplant (BMT) patients as pan of a multicenter efficacy trial of 2 weekly dose regimens. Since all patients lacked antibody to CMV and received only screened CMV negative blood products, the half-life of the passively administered CMV antibody could be measured with an ELISA assay. The CMV antibody titer was related to the immunoglobulin concentration using a standard curve. Compared with the 22 day half life in normal subjects, the half life in 8MT patients was exceedingly short, approximately 6 days for either the 250 mg/kg or 500 mg/kg dose regimen. The half life did not change over the subsequent 3 weekly doses. Peak titers of CMV antibody were (Iog~0) 2.39_+0.10 and 2.30_+0.12 following the first dose of 500 mg/kg and 250 mg/kg respectively and were significantly greater for the 500 mg/kg compared with the 250 mg/kg dose at all time points (p<0.02).
2(18
Protection Against Aerosol Influenza Infection, Phagocytic Cell Activity and Cellular Immunity by Influenza V~ccines Adjuv~ntized wi~h Immunomodulator AdDP A.M.Palache , K.N.Masihi , K.Masek ~ I. Duphar B.V.P.O.B. 900, 1380 AA Weesp, the Netherlands. 2. Robert Koch Institute, Federal Health Office, Berlin, FRG. 3. Institute of pharmacology, Academy of Sciences, Prague, CSSR We investigated the dose-dependent humoral and cellular immune responses and protective capacity in mice against influenza infections by vaccines adjuvantised with 50-,100 or 200 ~g adamantylamidedipeptide (AdDP). One month after the primary immunisation with 2.5 ~gHA A/Sichuan/2/87 (H3N2) subunlt vaccine, a booster injection with vaccine alone was given. Two weeks after the booster immunisation, the animals were given an aerosol of mouse-pathogenic influenza A/PR/8/34 (BIN1) virus infection. Eighty percent of animals treated with either 100 or 200 ~g AdDP survived the challenge infection. DTH reactions were elicited by footpad injections of I000 HAU of either infectious A/PR/8/34 (HINI) or A/Sichuan/2/87 (H3N2). AdDP had a marked effect on the DTH reaction in response to BIN1 but not to H3N2 virus, suggesting that CMI is, at least partly, responsible for the heterologous protection by AdDP. One month after immunisation with the subunit vaccine adjuvantized with 1,25,50 Or 200 ~g AdDP, splenic cells were isolated and assayed for chemoluminescence (CL) response to zymosan particles. Doses over 50 ~g AdDP showed a marked doserelated increase in phagocytic cell activity. This study shows that AdDP is an immunomodulator which triggers a variety of host immune defence mechanisms which may be relevant to broaden the protective capacity of currently available inactivated influenza vaccines.
813
206. IMMUNOTHERAPY OF FLORENCE NIGHTINGALE SYNDROME (FNS) WITH DIALYZABLE LYMPHOCYTE EXTRACT (DLyE) H. Hugh Fudenberg, Medical University of South Carolina, Charleston, SC 29403 During the last five years, we have seen an increasing number of patients who complain of cognitive disorder, hyperfatigability, sleep disorder, muscle pain and depression. In Great Britain, the predominant virus is one of the entero viruses, and in the U.S., one of the herpes group. The disorder has been termed myalgic encephalitis in Great Britain and Chronic Fatigue Immune Dysregulation Syndrome (SFIDS) in the U.S. (It has also been called Chronic Epstein-Barr Virus and the Yuppie Syndrome in the U.S.). Our evidence suggests that this syndrome is due to the continual stimulation of immune cells by a dead or incomplete virus. To eliminate the confusion caused by the many conflicting terminologies, we propose to call it Florence Nightingale-Syndrome, because her diary showed that she had all symptoms of this synd=ome. All previous studies have lumped together all patients with this syndrome, despite their varying degrees of severity and different durations of symptoms. We've studies 50 patients with severe FNS unable to function for at least 2 years and without any unusual febrile episodes for those 2 years. Before we saw them, many had been given intravenous magnesium and IgG,both of which produced clinical benefits only as long as injections were continued. We used Dialyzable LYMPHOCYTE Extract (DLyE) prepared from carefully selected donors. Of the 39 who received DLyE prepared from close household or intimate social contacts, 34 are working full-time after 18 months of therapy. Of the ii who received DLE) preared from random normal donors, only 1 is back at work after 18 months of therapy. In addition. clinical response to preparations made from leukocvtes containg less than 20% granulocytes. This may explain why DLyE gave good results in some patients who completely failed to resona to DLE.
207
PHARMACOKINETICS OF INTRAVENOUS IMMUNOGLOBULIN (GAMMAGARD R) IN BONE MARROW TRANSPLANT PATIENTS Kenneth H. Rand, Katherine Gibbs, Hartmut Derendorf, and John Graham-Pole Departments of Pathology, Medicine, Pediatrics, and Pharmaceutics, University of Florida and the Department of Veteran's Affairs Medical Center, Gainesville. FL 32610 The pharmacokinetics of an intravenous immunoglobulin (IVIG), Gammagard a, were measured in 31 Cytomegalovirus (CMV) antibody negative Bone Marrow transplant (BMT) patients as pan of a multicenter efficacy trial of 2 weekly dose regimens. Since all patients lacked antibody to CMV and received only screened CMV negative blood products, the half-life of the passively administered CMV antibody could be measured with an ELISA assay. The CMV antibody titer was related to the immunoglobulin concentration using a standard curve. Compared with the 22 day half life in normal subjects, the half life in 8MT patients was exceedingly short, approximately 6 days for either the 250 mg/kg or 500 mg/kg dose regimen. The half life did not change over the subsequent 3 weekly doses. Peak titers of CMV antibody were (Iog~0) 2.39_+0.10 and 2.30_+0.12 following the first dose of 500 mg/kg and 250 mg/kg respectively and were significantly greater for the 500 mg/kg compared with the 250 mg/kg dose at all time points (p<0.02).
2(18
Protection Against Aerosol Influenza Infection, Phagocytic Cell Activity and Cellular Immunity by Influenza V~ccines Adjuv~ntized wi~h Immunomodulator AdDP A.M.Palache , K.N.Masihi , K.Masek ~ I. Duphar B.V.P.O.B. 900, 1380 AA Weesp, the Netherlands. 2. Robert Koch Institute, Federal Health Office, Berlin, FRG. 3. Institute of pharmacology, Academy of Sciences, Prague, CSSR We investigated the dose-dependent humoral and cellular immune responses and protective capacity in mice against influenza infections by vaccines adjuvantised with 50-,100 or 200 ~g adamantylamidedipeptide (AdDP). One month after the primary immunisation with 2.5 ~gHA A/Sichuan/2/87 (H3N2) subunlt vaccine, a booster injection with vaccine alone was given. Two weeks after the booster immunisation, the animals were given an aerosol of mouse-pathogenic influenza A/PR/8/34 (BIN1) virus infection. Eighty percent of animals treated with either 100 or 200 ~g AdDP survived the challenge infection. DTH reactions were elicited by footpad injections of I000 HAU of either infectious A/PR/8/34 (HINI) or A/Sichuan/2/87 (H3N2). AdDP had a marked effect on the DTH reaction in response to BIN1 but not to H3N2 virus, suggesting that CMI is, at least partly, responsible for the heterologous protection by AdDP. One month after immunisation with the subunit vaccine adjuvantized with 1,25,50 Or 200 ~g AdDP, splenic cells were isolated and assayed for chemoluminescence (CL) response to zymosan particles. Doses over 50 ~g AdDP showed a marked doserelated increase in phagocytic cell activity. This study shows that AdDP is an immunomodulator which triggers a variety of host immune defence mechanisms which may be relevant to broaden the protective capacity of currently available inactivated influenza vaccines.