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Biomedical subjects

M C Poon

Publications and source records attributed to M C Poon.

At least 73 records · Page 4Linked to original sources
PubMed1989

Double autologous bone marrow transplantation for acute myelogenous leukemia in a patient treated for Hodgkin's disease.

A 30-year-old man developed acute myelogenous leukemia nearly 3 years after treatment of Hodgkin's disease with radiation and three chemotherapy combinations. Remission was induced with one cycle of high-dose Ara-C therapy. Three cycles of consolidation chemotherapy were given. The patient then had two autologous bone marrow transplants, the first after conditioning with 5 Gy total body irradiation, the second after Melphalan 140 mg/m2. The procedures were well tolerated, although hematological reconstitution was very slow after the second autotransplant. The patient has been disease-free for over 4 years. Such patients may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation, which may damage several organs including the bone marrow. This report demonstrates that patients with secondary acute myelogenous leukemia may tolerate a double autotransplant procedure and achieve durable remissions.

Adult↗
PubMed1989

Primer-mediated enzymatic amplification of cytomegalovirus (CMV) DNA. Application to the early diagnosis of CMV infection in marrow transplant recipients.

A nucleic acid amplification procedure, the polymerase chain reaction (PCR), has been used to establish a diagnostic assay for the identification of cytomegalovirus (CMV) immediate-early sequences in clinical specimens. Preliminary testing against virus-infected cell cultures indicated that the PCR assay was highly CMV-specific, recognizing both wild-type and laboratory strains of CMV. There was no cross-reactivity with human DNA or with DNA from other herpes viruses. The sensitivity of the assay, using cloned CMV AD169 Eco RI fragment-J as template, was 1 viral genome per 40,000 cells. In a prospective study of CMV infection in bone marrow transplant recipients, the PCR assay correctly identified four patients with confirmed CMV infection. In three of these patients who were followed longitudinally, correlation of DNA reactivity with CMV culture and CMV antibody status over time indicated that DNA was the most sensitive marker for the diagnosis of CMV infection.

Adolescent↗
PubMed1989

Hemopoietic origin of factor XIII A subunits in platelets, monocytes, and plasma. Evidence from bone marrow transplantation studies.

Factor XIII A subunit (FXIIIA) is found in plasma, platelets, and monocytes. The hemopoietic contributions to FXIIIA in these components were studied in patients transplanted with marrows from donors with different FXIIIA phenotypes. In three patients with successful engraftment (by DNA genotyping, red cell phenotyping, and cytogenetic studies) platelet and monocyte FXIIIA changed to donor phenotypes with hematologic recovery. Thus, FXIIIA in platelets and monocytes is synthesized de novo and/or from their progenitor cells. Plasma FXIIIA phenotype change after transplantation was more complex. Patient I changed from phenotype 1-1 (one electrophoretically fast band) to 1-2 (three bands) in 115 d; patients 2 and 3 did not change completely from phenotype 1-2 to 1-1 in up to 458 d, but did show enrichment of the fastest band. Thus, while there is a definite contribution of donor hemopoiesis to plasma FXIIIA, another source of recipient FXIIIA appears to be present to delay or prevent the phenotype change.

Adult↗
PubMed1989

Treatment of advanced Hodgkin's disease with high dose melphalan and autologous bone marrow transplantation.

Twenty patients with Hodgkin's disease which had relapsed at least once after chemotherapy, were treated with melphalan 140-220 mg/m2 i.v. followed by reinfusion of non-cryopreserved autologous bone marrow. Four patients (20%) remain alive and disease-free 28, 45, 52, and 96 months after treatment respectively. There were no treatment-related deaths. This appears to be the only reported series of patients treated with a single agent in this situation. The results are comparable to those achieved by multi-agent regimens with autologous or allogeneic bone marrow transplantation.

Adult↗
PubMed1988

G6PD Viangchan: a new glucose 6-phosphate dehydrogenase variant from Laos.

We describe a previously unreported glucose-6-phosphate dehydrogenase-(G6PD) variant. G6PD Viangchan was found in a Laotian immigrant to Calgary, Canada, and was characterized by severe enzyme deficiency, normal electrophoretic mobility, increased pH optimum, and abnormal kinetics for the natural substrates G6PD and NADP, as well as the artificial substrates 2-deoxy G6PD and deamino NADP. The inhibition constant for NADPH was decreased. The subject has no evidence suggesting chronic or episodic hemolysis.

Child↗
PubMed1988

Mesenteric venous thrombosis due to antithrombin III deficiency.

A 19-year-old woman developed gradually worsening abdominal pain, signs of peritonitis, and hematemesis. Laparotomy revealed peritonitis due to segmental small-bowel infarction, and the underlying pathologic condition was mesenteric vein thrombosis. A primary thrombotic disorder was suggested and antithrombin III deficiency was found. Before anticoagulant therapy could be initiated, she developed hemorrhagic cerebral infarction and died. Her history included three episodes of deep vein thrombosis while taking oral contraceptives. Her father died of spontaneous mesenteric and portal vein thrombosis at age 29 years. This report underlines the importance of careful interpretation of the vascular pathology in cases of intestinal ischemia.

Adult↗
PubMed1987

Humoral immune response in patients with hemophilia.

Hemophiliacs require frequent infusions of allogeneic proteins to control bleeding. Previous reports have demonstrated that thymus-derived lymphocytes (T cells) from hemophiliacs are antigenically primed to the lyophilized antihemophilic factor and that natural killer cells from hemophiliacs demonstrate impaired response to interferon-beta and -gamma Some aspects of the humoral immune response were investigated in eight patients who require large amounts of Factor VIII. Polyclonal hypergammaglobulinemia was detected in six patients and seven had elevated titers of autoantibodies of various specificities. There was no evidence of impaired concanavalin A-inducible T-suppressor cell activity. Polyclonal immunoglobulin secretion secondary to pokeweed mitogen in vitro was elevated in three of eight patients and depressed in five. Spontaneous production of both B-cell growth and differentiation factors (BCGF and BCDF) was elevated but mitogen-induced production was impaired. These data demonstrate that the humoral immune response of hemophiliacs may be chronically stimulated, thus impairing their ability to respond to new antigens such as viruses.

AIDS-Related Complex↗
PubMed1987

Hemophilia B (Christmas disease) variants and carrier detection analyzed by DNA probes.

We have used two strategies to study 14 hemophilia B families from 11 kindreds for possible carrier detection and prenatal diagnosis. First, we sequentially used the Factor IX probes (sequentially with restriction enzymes Taq I, Xmn I, and Dde I), and the linked probes p45h (Taq I), p45d (Pst I), and 52a (Taq I) for restriction fragment length polymorphism (RFLP) analysis. Second, we searched for useful variant Taq I digestion fragments using the Factor IX complementary DNA. Two separate new Taq I variants in exon VIII were identified. Using both strategies, 11 of 14 families (from 9 of 11 kindreds) were informative for further studies. In five kindreds studied in detail, the carrier status of all 11 at risk females was determined and prenatal diagnosis could be offered to the offsprings of each of the six carriers identified. Thus, in this study, we have identified a higher proportion of informative families than has previously been reported.

DNA↗
PubMed1986

Embryonic zeta-globin chains in adults: a marker for alpha-thalassemia-1 haplotype due to a greater than 17.5-kb deletion.

Hemolysates from adults with the alpha-thalassemia-1 haplotype due to the greater than 17.5-kb deletion of both alpha-globin genes from the same chromosome were found to contain embryonic zeta (zeta)-globin chains (alpha-globin-like chains), as determined by a specific and sensitive radioimmunoassay and an electrophoretic technique. zeta-Globin chains were not present in hemolysates from adults with deletion of a single alpha-globin gene from one or both chromosomes. These results indicate that zeta-globin chains, which can be assayed by immunologic techniques, can serve as markers for the alpha-thalassemia-1 haplotype due to the greater than 17.5-kb deletion. The ability to detect zeta-globin chains may be useful in populations in which the gene frequency of the greater than 17.5-kb deletion is high, for screening couples at risk of having offspring with homozygous alpha-thalassemia.

Adult↗
PubMed1986

Bone marrow transplantation for acute monocytic leukemia following the treatment of Hodgkin's disease.

A 32-year-old woman developed acute monocytic leukemia within a year of treatment for Hodgkin's disease with chemotherapy and radiation. Residual leukemia was present in the bone marrow after two induction courses of high-dose Ara-C. She received a bone marrow transplant from an HLA- and DR-identical sister and remains in complete remission more than 2 years after transplantation. Only one other instance of a remission greater than 2 years after transplantation for secondary acute leukemia could be found in the literature. Although bone marrow transplantation may be carried out successfully in these patients, it is possible that they may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation. Only further study can clarify this matter and determine the best time for the procedure and which regimen should be used.

Adult↗
PubMed1986

Sideroblastic anemia associated with thrombocytosis and a chromosome 3 abnormality.

A unique patient with sideroblastic anemia and thrombocytosis with a recurrent and ultimately fatal thromboembolic phenomenon is described. Cytogenetic analysis of bone marrow metaphases revealed a pseudodiploid chromosome complement, 46,XY,ins(3;3)(q26;q21q26). The association of thrombocytosis and ins(3;3) in patients with preleukemia or myelogenous leukemia has been reported previously. The association of ins(3;3) and thrombocytosis in our patient with sideroblastic anemia suggests that the disorder may involve a hematopoietic progenitor cell capable of giving rise to all three cell lineages. Our findings also support the suggestion that a gene on the long arm of chromosome #3 may encode a protein that, at least in part, regulates megakaryopoiesis.

Adult↗
PubMed1986

T lymphocytes from hemophiliacs proliferate after exposure to factor VIII product.

Chronic exposure of hemophiliacs to allogeneic proteins via factor VIII concentrate for control of bleeding could lead to a state of chronic antigen stimulation. Immune function from eight hemophiliacs requiring large amounts of factor VIII concentrate was assessed. It was found that 5 of 8 had a positive blastogenic response to low concentrations of factor VIII in a 7-day thymidine uptake assay. Separation of lymphocyte subpopulations indicated that the reactivity was contained in the T cell-enriched fraction. There was no blast transformation noted secondary to the factor VIII product in 20 controls tested in a 7-day assay nor was there any mitogenic effect of the factor VIII in a 3-day assay. In fact, high concentrations of factor VIII impaired that T lymphocytes from hemophiliacs are antigenically primed to some constituent in the lyophilized factor VIII concentrate.

Adult↗
PubMed1986

Natural killer cell activity from hemophiliacs exhibits differential responses to various forms of interferon.

Patients with hemophilia are at risk for the development of acquired immunodeficiency syndrome (AIDS). Patients with AIDS have recurrent infections and/or malignancy and altered immune response, including decreased T lymphocyte counts, decreased T helper lymphocytes, defective T cell blastogenesis, hypergammaglobulinemia, defective natural killer (NK) activity and impaired response of NK to interferon-beta (IFN-beta). It is feasible that chronic antigen stimulation with subsequent release of interferon could be related to the impaired NK reactivity to IFN-beta of patients with AIDS. Because hemophiliacs are subjected to chronic antigen stimulation secondary to the administration of foreign protein, the reactivity of NK cells from patients with hemophilia to IFN-alpha, IFN-beta and IFN-gamma was studied. Eight patients with hemophilia requiring high levels of clotting factor replacement were assessed. Three patients were antibody positive to HTLV-III. All had normal baseline NK cell function. In the first set of experiments, all patients responded normally to in vitro IFN-alpha by increasing NK activity, but four patients had significant failure and two had mild impairment in NK response to IFN-beta. This latter observation was particularly evident at very low concentrations of IFN. In repeated experiments, seven of eight had impaired NK response to IFN-beta and IFN-gamma but normal response to IFN-alpha. Only one patient's NK cells responded better to IFN-gamma. There was no obvious correlation of these findings to antibody status to HTLV-III. Chronic antigen stimulation and the modulation of interferon receptors are discussed as possible mechanisms that could produce these findings.

Adult↗