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Biomedical subjects

A Zuiable

Publications and source records attributed to A Zuiable.

18 recordsLinked to original sources

In vitro effects of ethanol on the phagocytic and microbial killing activities of normal human monocytes and monocyte-derived macrophages.

Human blood monocytes were cultured within the wells of chamber slides in growth medium to which 0, 1, 2, or 3 mg ethanol per ml was added at the start of the culture. After incubation for 1 h, 1 day and 7 days, their ability to phagocytoze IgG-sensitized red cells and to phagocytoze and kill non-opsonized Candida albicans was assessed. In all alcohol-containing wells, the concentration of alcohol in the growth medium fell progressively, reaching negligible values after 3 days. When compared with control cells, monocytes incubated with 1, 2 or 3 mg ethanol/mg for 1 h showed impaired phagocytosis of IgG-sensitized RBC and non-opsonized C. albicans and those incubated with 1 or 2 mg ethanol/ml for 1 h showed impaired killing of Candida. After incubation for 7 days, the monocyte-derived macrophages in wells initially containing 1, 2 or 3 mg ethanol/ml showed increased phagocytic activity towards C. albicans but not towards sensitized RBC. In addition, in 4 of 5 experiments, the percentage of phagocytozed organisms killed was increased in wells initially containing 1 mg ethanol/ml. The results support the view that the susceptibility of chronic alcoholics to certain infections may be partly dependent on an ethanol-induced depression of the phagocytic and killing functions of macrophages. They also suggest that a few days after a brief period of exposure to ethanol there may be stimulation of certain but not all effector functions of macrophages.

Candida albicans↗

Thrombocytopenia after bone marrow transplantation for leukaemia: changes in megakaryocyte growth and growth-promoting activity.

Megakaryocyte growth-promoting activity (MK-GPA) was scored on a scale of 0-3 in the serum of 23 patients up to 120 d following bone marrow transplantation (BMT) for leukaemia. Nine of 19 allografts and two of four autografts had thrombocytopenia requiring platelet transfusion more than 30 d after BMT. There was a close correlation between MK-GPA and platelet count. MK-GPA reached a maximum before day 30 after BMT but remained elevated in patients with persisting thrombocytopenia secondary to poor engraftment, graft-versus-host disease (GVHD) or relapse. Recent platelet transfusion did not suppress serum MK-GPA. Two of four patients undergoing autologous BMT for acute myeloid leukaemia (AML) showed delayed platelet recovery and persistence of MK-GPA in the serum. Seven further AML remission marrows were tested for megakaryocyte production before or after autologous BMT, using pooled sera with known MK-GPA activity. Megakaryocyte generation was reduced before BMT and absent in post transplant samples. This failure of MK production was not corrected by T-cell depletion or by the presence of adherent cells from normal marrow. We conclude that thrombocytopenia after BMT is associated with an appropriate increase in MK-GPA levels in response to a reduction in the megakaryocyte pool rather than the platelet pool, and that persisting thrombocytopenia after autologous BMT is due to decreased numbers of available megakaryocyte precursors.

Adolescent↗

In vitro studies of ways to overcome resistance to VAMP--high dose melphalan in the treatment of multiple myeloma.

Myeloma colonies (MY-CFUc) from 7/24 patients undergoing treatment with VAMP (vincristine, adriamycin and methyl prednisolone) and high dose melphalan (HDM) were melphalan-resistant. It was not possible to conclude that VAMP induced melphalan resistance in MY-CFUc, but that resistance is endogenous in some myeloma cell populations. In 12/13 of the same patients of whom four had MY-CFUc which were melphalan resistant, the sensitivity of MY-CFUc and GM-CFUc to busulphan was similar. Thus resistance of MY-CFUc to melphalan did not confer resistance to busulphan. MY-CFUc from 1/7 of a second group of patients were adriamycin-resistant. This resistance was removed when the cells were treated with a combination of verapamil (3 micrograms/ml) and adriamycin. Verapamil also enhanced the toxicity of adriamycin to MY-CFUc from two patients where there was no evidence for adriamycin resistance. In these three patients the sensitivity of both MY-CFUc and GM-CFUc was similar after treatment with verapamil. Verapamil did not affect the uptake or efflux of 3H-daunorubicin in sensitive and resistant RPMI-8226 cells (myeloma) and peripheral blood mononuclear cells from a normal donor; neither did it affect the binding of 3H-daunorubicin to nucleic acid. It is concluded that verapamil may be a useful adjuvant to VAMP chemotherapy and that busulphan may provide an alternative to melphalan in patients whose myeloma cells are melphalan resistant.

Antineoplastic Combined Chemotherapy Protocols↗

Melphalan and total body irradiation (TBI) versus cyclophosphamide and TBI as conditioning for allogeneic matched sibling bone marrow transplants for acute myeloblastic leukaemia in first remission.

Between June 1981 and April 1986 63 patients with acute myeloid leukaemia (AML) in first remission and HLA-identical sibling donors were entered into a prospective study comparing cyclophosphamide (CY) + total body irradiation (TBI) with melphalan + TBI as conditioning therapy prior to transplantation. Thirty-six patients received CY/TBI and 27 received melphalan/TBI. The actuarial probability of remaining in remission for patients receiving melphalan/TBI was 94% compared with 66% following CY/TBI (p greater than 0.01). By including a comparable group of 41 patients with AML in first remission, conditioned with CY/TBI prior to the onset of the study, the greater anti-leukaemic effect of melphalan/TBI compared to CY/TBI was unchanged and statistically the chance of this being wrong is 1 in 10 (p less than 0.1). The overall survival in remission of both arms of the study was the same with 15/27 patients (55%) surviving in remission following melphalan/TBI compared with 19/36 patients (53%) following CY/TBI. The benefit obtained in reduced relapse was offset by the combined nephrotoxic effect of melphalan and cyclosporin which was not identified until the programme had been underway for a period of time. This shows that misinterpretation of 'no survival advantage' for the new treatment may occur due to unforeseen and preventable toxicities.

Actuarial Analysis↗

Hodgkin's disease in an adult with acute lymphoblastic leukaemia.

A 53 year old woman with common acute lymphoblastic leukaemia (ALL) developed Hodgkin's disease 20 months after the initial diagnosis of ALL. This is by far the oldest case of Hodgkin's disease complicating ALL. The unusual presentation and the aetiology of Hodgkin's disease in ALL are discussed.

Female↗

Platelet associated immunoglobulins (PAIgG and PAIgM) in autoimmune thrombocytopenia.

An enzyme linked assay system was used to quantitate platelet associated IgM (PAIgM) in addition to platelet associated IgG (PAIgG) in normal subjects and in 145 patients with autoimmune thrombocytopenia (AITP). The mean PAIgM level in normals was 1.17 ng/10(6) platelets with a range of 0.01-2.45 ng (mean +/- 2 SD). The corresponding PAIgG values as follows: mean 6.0 ng, range 2.0-10 ng/10(6) platelets. Elevated PAIgG was seen in 67.6% and abnormally raised PAIgM in 79.3% of patients. Both values were raised together in 57.2% and either elevated PAIgG or PAIgM in 89.7%. All patients with PAIgG values greater than 4 times upper limit of normality were found to have abnormal PAIgM. The relevance of elevated PAIgM, the possible interaction between PAIgG and PAIgM and the implication of our results in patients with autoimmune thrombocytopenia are discussed.

Autoantibodies↗

The kinetics of unmatched and HLA-matched 111in-labelled homologous platelets in recipients with chronic marrow hypoplasia and anti-platelet immunity.

The kinetics of homologous platelets, labelled in plasma with 111In-tropolonate, have been studied in five recipients with chronic marrow hypoplasia and severe thrombocytopenia, who were refractory to platelet transfusions as a result of alloimmunization. Mean platelet life span (MPLS), recovery, plasma 111In level and splenic and hepatic uptake kinetics were studied on two occasions, one using HLA-matched platelets and the other unmatched platelets. In each case, recovery of labelled platelets at 1 h post-injection and MPLS improved with HLA matching, although this improvement was highly variable. Only two of the five subjects would have derived any significant benefit from HLA-matched as compared with unmatched platelet transfusions. It was concluded that the need exists for additional cross-matching procedures, possibly related to platelet specific antigens, in patients who remain refractory to platelet transfusion.

Adolescent↗

The relative incidence of idiopathic and secondary autoimmune thrombocytopenia: a clinical and serological evaluation in 508 patients.

Abnormally elevated levels of platelet-associated immunoglobulins were detected in 508 patients with the clinical and haematological criteria of autoimmune thrombocytopenia (AITP). In 246 patients (48.4%), thrombocytopenia was accompanied by a variety of disease entities, the most commonly associated being autoimmune disorders (21.0%) and lymphoproliferative diseases (14.8%). This group was classified as 'secondary' AITP. There was a female preponderance in both the idiopathic and secondary AITP's and peak age incidences were identified in the 3rd-4th decades and in the 7th-8th decades of life. In 253 patients, only platelet-associated IgG (PAIgG) was quantitated; there being insufficient material for further study. Both platelet associated immunoglobulins (PAIgG and PAIgM) were measured in the remaining 255 patients. When both parameters were quantitated, elevated PAIgM was seen slightly more frequently in the idiopathic group, in contrast to the secondary AITP's when PAIgG was seen more frequently abnormal. Both parameters were found most commonly elevated together in patients with systemic lupus erythematosus (SLE) and in those in whom thrombocytopenia was induced by drug intake or preceding viral illness. PAIgG and PAIgM were quantitated by modification of a previously described enzyme-linked immunoassay (Hegde et al. 1981).

Adolescent↗