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Biomedical subjects

M Mullaney

Publications and source records attributed to M Mullaney.

6 recordsLinked to original sources
PubMed1999

Investigation of plasma protein adsorption on functionalized nanoparticles for application in apheresis.

Particles with specific ligands for the adsorption of plasma proteins can be used in therapeutic or preparative apheresis. The development of these particles may benefit from an improved knowledge of the relationship between protein adsorption and the structure of ligands. Nanoparticles were functionalized with aliphatic diamines of increasing chain length; with the amino acids lysine, tryptophan, histidine, and their corresponding amines; and with tryptophan and histidine spaced with diamines of different length. Suitable protocols were developed for the washing of particles and the subsequent desorption of proteins adsorbed from human plasma. The adsorption pattern, as well as the quantification of the overall adsorption of proteins on these modified particles, was investigated with gel electrophoresis. This was followed by immunoblotting which yielded specific assessments of bound human serum albumin and fibrinogen. The comparison of protein adsorption with surface charge density and measured hydrophobicities yielded no simple correlations although in general more hydrophobic ligands bound higher quantities of protein. The detection of human serum albumin yielded similar results because it was observed for overall protein adsorption while the adsorption of fibrinogen expressed a different pattern. In this case, particular nanoparticles functionalized with aliphatic diamines bound significantly higher amounts of fibrinogen than all other ligands.

Adsorption↗
PubMed1994

Pure red cell aplasia after chemotherapy for Hodgkin's lymphoma: in vitro evidence for T cell mediated suppression of erythropoiesis and response to sequential cyclosporin and erythropoietin.

Acquired pure red cell aplasia (PRCA) has been associated with various lymphoproliferative conditions but its occurrence with Hodgkin's disease is rare. We report a case of PRCA occurring immediately following the completion of induction chemotherapy in a patient with Stage IIIB nodular sclerosing Hodgkin's disease. In vitro erythroid colony studies documented evidence for T cell mediated suppression of erythropoiesis and lack of a serum inhibitor. Addition of cyclosporin to the in vitro cultures stimulated erythroid colony growth. Following in vivo treatment with cyclosporin peripheral blood CD4/CD8 ratios returned to normal. However, serum erythropoietin levels were inappropriately low. Subsequent treatment with erythropoietin induced a reticulocytosis and transfusion independence. Since discontinuing the erythropoietin, the patient has been able to maintain a hemoglobin of 100 g/L. This case illustrates that red cell aplasia occurring in the setting of Hodgkin's disease may be due to T cell mediated suppression of erythropoiesis. A response to cyclosporin may be masked by inappropriately low erythropoietin levels.

Adult↗
PubMed1993

Mobilization of peripheral blood stem cells by subcutaneous injections of yeast-derived granulocyte macrophage colony stimulating factor: a phase I-II study.

A phase I-II study was conducted in 15 patients to determine the tolerability, efficacy and optimal dose of s.c. yeast-derived granulocyte-macrophage colony stimulating factor (GM-CSF) for mobilization of peripheral blood stem cells (PBSC). PBSC were measured by the colony forming unit granulocyte-macrophage (CFU-GM) and burst forming unit erythroid (BFU-E) in vitro colony assays and CD34 flow cytometric analysis. GM-CSF was administered for 12 days as a single daily s.c. injection at 125 micrograms/M2 (n = 3), 250 micrograms/M2 (n = 3), 375 micrograms/M2 (n = 6) and 500 micrograms/M2 (n = 3). At these doses, sustained serum GM-CSF levels of approximately 100-400 pg/ml were observed for at least six hours. Most (97.2% or 175/180) of the planned GM-CSF doses were administered with no serious adverse effects at any of the dose levels. Three leukapheresis procedures were performed before and then after 8, 10 and 12 doses of s.c. GM-CSF. Compared with basal leukapheresis collections, s.c. GM-CSF mobilized leukapheresis collections yielded greater numbers of total white blood cells ([WBC] 15/15 patients or 100%, p < 0.001) mononuclear cells ([MNC] 8/15 patients or 53%, p = 0.55), CFU-GM (11/15 patients or 73%, p = 0.037), BFU-E (9/15 patients or 60%, p = 0.13) and CD34+ cells (6/15 patients or 40%, p = 0.15). The in vitro CFU-GM were augmented approximately two to tenfold in GM-CSF mobilized collections with no clear dose effects from 125-500/micrograms/M2. However, in vivo engraftment time to absolute neutrophil count (ANC) 500/mm3 correlated strongly with GM-CSF PBSC mobilizing dose (r2 = 0.99). We conclude that s.c. yeast-derived GM-CSF is a simple, effective and tolerable method for mobilization of PBSC.

Adult↗
PubMed1993

Phase I/II study of high-dose cyclophosphamide, etoposide and cisplatin followed by autologous bone marrow or peripheral blood stem cell transplantation in patients with poor prognosis Hodgkin's disease or non-Hodgkin's lymphoma.

We conducted a phase I/II study to determine the efficacy, toxicity and maximum tolerable doses of CY, etoposide and cisplatin (CEP) in the management of patients with relapsed or refractory malignant lymphoma. Thirty patients with relapsed or refractory Hodgkin's disease (n = 10) or non-Hodgkin's lymphoma (n = 20) received CY 6000 mg/m2, etoposide 900-2700 mg/m2 and cisplatin 150 mg/m2 followed by autologous BM or autologous peripheral blood stem cell rescue. The dose of etoposide was escalated after each 3 to 4 patients. The maximum tolerated dose of etoposide, when administered with the indicated doses of CY and cisplatin, was 2400 mg/m2. Three of the 30 patients (10%) died of treatment-related toxicity. Although 14 of the 30 patients had residual bulky and/or chemotherapy-resistant disease at the time of the transplant, 26 patients (87%) responded to this regimen, including 18 patients (60%) who achieved CR and 8 patients (27%) who achieved partial remission. Seven patients (23%) remain alive and free of progression at a median of 21 months post-transplant. Three additional patients relapsed after transplant but are enjoying prolonged disease-free survival at a median of 31 months post-transplant following additional post-transplant therapy. We conclude that high-dose CY, etoposide and cisplatin followed by autologous BM or peripheral blood stem cell rescue is an active and acceptably tolerated regimen in the treatment of relapsed or refractory malignant lymphoma.

Adolescent↗
PubMed1992

Autoimmune neutropenia following peripheral blood stem cell transplantation.

The differential diagnosis of unexpected neutropenia following bone marrow transplantation includes several potentially life-threatening complications including graft rejection, overwhelming infection, relapse of the underlying neoplasm, and intrinsic graft failure. However, a number of recent reports document that the differential diagnosis also includes autoimmune neutropenia, which, although potentially life-threatening, often responds well to corticosteroids or splenectomy. Autoimmune neutropenia has been reported following both autologous and allogeneic bone marrow transplantation. Herein we report a 31-year-old woman who developed a rapidly falling neutrophil count 11 days following peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. A laboratory evaluation supported a diagnosis of autoimmune neutropenia, and the neutropenia resolved following treatment with steroids and granulocyte-colony stimulating factor.

Adult↗