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Biomedical subjects

R Or

Publications and source records attributed to R Or.

229 records · Page 13Linked to original sources

Prediction of haemorrhagic diathesis in thrombocytopenia by mean platelet volume.

The Coulter counter, model S Plus, Provides a platelet count and a mean platelet volume in all routine specimens of blood for cell count. The value of mean platelet volume in the prediction of the haemostatic potential of thrombocytopenic patients was investigated in 175 patients with haematological disorders who underwent 1473 blood counts over five months. Eighty-four haemorrhagic episodes were detected, most in thrombocytopenic patients. The mean platelet volume of patients with haemorrhagic tendency was significantly lower (5.52 +/- SD 0.7 fl) than that of patients without these tendencies (7.87 +/- SD 1.75 fl) (p less than 0.001). In cases of severe thrombocytopenia (less than 20 x 10(9)/1 platelets) haemorrhagic episodes were frequent; however, the frequency of bleeding was considerably lower in cases in which the mean platelet volume was higher than a suggested cut-off point of 6.4 fl. Discriminant analysis selected mean platelet volume as more important than platelet count for prediction of haemorrhagic state in severe thrombocytopenia. In view of the useful discrimination that mean platelet volume provides between thrombocytopenic patients who bleed and those who do not bleed, it may serve as a guide to predict the danger of haemorrhage and the need for prophylactic platelet transfusion.

Adolescent↗

Use of multiparameter studies and scanning electron microscopy in the interpretation and attempted correlation of surface morphology with cell type in 135 cases of human leukemias.

Multiparameter studies and scanning electron microscopy (SEM) were performed on cells obtained from 135 cases of leukemia in an attempt to clarify whether there was a reliable correlation between surface morphology and cell type as defined by cytochemistry, membrane markers, and transmission electron microscopy. These studies also attempted to determine whether SEM could be used to distinguish lymphoid and nonlymphoid leukemias, to recognize different types of lymphoid leukemia, and to define the cell type involved in cases of unclassified leukemia. The results of this study suggest that there is a good correlation between surface morphology as seen by SEM and cell type identified by multiparameter techniques. In most cases, nonlymphoid leukemic cells could be distinguished from lymphoid leukemic cells on the basis of their surface morphology. SEM did not appear to contribute to the diagnosis of unclassified leukemia, but more cases of this nature must be studied. Despite the fact that acute lymphoblastic leukemia cells frequently showed fewer microvilli than did other lymphoid leukemias, overlap of surface features in about one-third of the cases did not enable SEM to be used as a reliable means of distinction. The above conclusions appear to be supported by preliminary scanning immunoelectron microscopic observations on leukemic cells. It is concluded that SEM is a useful aid to other modes of microscopy in leukemia but should not be used on its own to establish diagnosis.

Cell Membrane↗

Analysis of the peanut agglutinin-binding site as a differentiation marker of normal and malignant human lymphoid cells.

The lectin peanut agglutinin (PNA), which interacts specifically with D-galactosyl residues, was studied for its binding to human normal and malignant lymphoid cells at various stages of differentiation. As previously reported, PNA binds to thymocytes; however, it does not interact with the prothymocytes which precede the cortical thymocyte differentiation stage. No mature peripheral cells in any of the lymphoid organs bind PNA. In contrast to the normal T differentiation pathway, the expression of the PNA-binding site does not seem to coincide with that of T cell characteristics in the various malignant lymphoid cells studied. We therefore conclude that more information is needed about the nature of the PNA-binding site before it can be used as a differentiation marker in malignant lymphoid cells.

Binding Sites, Antibody↗

Spinal meningeal uptake of technetium-99m methylene diphosphonate in meningeal seeding by malignant lymphoma.

Definite diagnosis of meningeal seeding by systemic cancer relies on the presence of malignant cells in the cerebrospinal fluid (CSF). In the absence of such cells in the CSF, only two other tests strongly suggest the diagnosis--a CT scan and a myelogram. We report a case in which the diagnosis was strongly suggested by an unusual uptake of Tc-99m methylene diphosphonate by the leptomeninges during a skeletal scan and later established by the presence of malignant cells in the CSF. We believe that radionuclide scan may be an additional diagnostic test in some cases with meningeal seeding by systemic cancer. We therefore are extending our studies to validate this possibility.

Aged↗

Impaired liver function tests in patients treated with antithymocyte globulin: implication for liver transplantation.

Antithymocyte globulin (ATG) is traditionally used as a conventional immunosuppression agent in various pathological states including severe aplastic anaemia (SAA), graft versus host disease (GVHD), and for the prevention and treatment of graft rejection and GVHD post bone marrow and liver transplantation. We reviewed the liver functions of 16 haematological patients with no previous liver disorders who received ATG as part of their pre-bone marrow transplantation (BMT) conditioning regimen, and the liver function tests of five SAA patients who received ATG as part of their treatment. Liver functions were evaluated at day -1 pre-, and days +3 and +10 post-ATG treatment. All patients had normal liver functions before treatment. In the haematological patients, the mean serum lactic dehydrogenase (LDH) levels increased from 408.7 +/- 37.7 U/l pre-treatment to 1394.4 +/- 488.7 U/l 3 days post-treatment (n = 16; p < 0.029), and then declined to 561.4 +/- 61.3 U/l 10 days post-treatment (n = 16; p < 0.043). The mean alanine aminotransferase (ALT) levels increased from 51.9 +/- 11.3 U to 184.6 +/- 74.6 U (n = 16; p < 0.036), and then declined to 121.9 +/- 61.3 U (n = 16; NS). The mean aspartate amino transferase (AST) levels increased from 31.2 + 5.7 U to 152.0 +/- 67.0 U (n = 16; p < 0.44) and then declined to 46.0 +/- 14 (n = 16; p < 0.049). The mean tau-glutamyltransferase (GTP) levels increased from 93.0 +/- 34 to 188.0 +/- 36 (n = 16; p < 0.02), and were 168.0 +/- 37.0 at day +10 (n = 16; NS). The mean bilirubin levels increased from 18.0 +/- 1.9 microM l(-1) to 22.7 +/- 2.8 (n = 16); NS), at day +3 and to 31.9 +/- 6.9 at day +10 (n = 16; NS). In contrast, no significant changes in liver function tests were demonstrated in the SAA patients treated with ATG. The possible pathophysiologic mechanisms and the clinical implications for liver transplantation are discussed.

Adolescent↗

Lymphokines in bleomycin-induced lung injury in bleomycin-sensitive C57BL/6 and -resistant BALB/c mice.

To study the pattern of lymphokines in bleomycin-induced lung injury, T cells were isolated from lung interstitial tissue (LIL), peribronchial lymphatic tissue (PBLT), and bronchoalveolar lavage (BAL) fluid of bleomycin-"sensitive" C57Bl/6 and bleomycin-"resistant" BALB/c mice at 3, 6, and 14 days following intratracheal instillation of bleomycin or saline. After 48 hours in culture, conditioned media were collected and assayed with specific enzyme-linked immunosorbent assay (ELISA) for interferon (IFN)-gamma, interleukin (IL)-2, IL-4 and IL-5. In bleomycin-treated C57B1/6 mice, IFN-gamma production was increased up to 20-fold at 3 and 6 days in LIL, and at 3 days in PBLT lymphocytes. IL-4 production was slightly decreased in LIL and PBLT lymphocytes at 14 days. IL-2 and IL-5 were not changed by bleomycin. In BALB/c mice, IFN-gamma production was increased 5-fold at 14 days, and IL-2 production at 6 days, in LIL but not PBLT. IL-4 and IL-5 were not significantly changed. The increase in IFN-gamma may play a role in the pathogenesis of bleomycin-induced lung injury. Differences in the cytokine pattern between the strains of mice may contribute to the variable strain susceptibility in bleomycin-induced lung injury.

Animals↗

Donor lymphocyte infusions to displace residual host hematopoietic cells after allogeneic bone marrow transplantation for beta-thalassemia major.

PURPOSE: Donor lymphocyte infusion (DLI) was used to reverse relapse after allogeneic bone marrow transplantation (BMT) in a patient with beta-thalassemia major. PATIENTS AND METHODS: The patient with unstable mixed chimerism after BMT was treated with graded increments of donor lymphocytes (10(5) T cells/kg to 5 x 10(7) T cells/kg) to displace residual hematopoietic host cells. RESULTS: DLI resulted in complete donor-derived reconstitution of the hematopoietic compartment. The patient developed mild graft-versus-host disease (GVHD) that could be controlled by steroid treatment. CONCLUSIONS: This case report shows that DLI can effectively eradicate host stem cells in mixed chimeras after BMT in nonmalignant hematopoietic diseases.

Bone Marrow Transplantation↗

Amelioration of bleomycin-induced pulmonary injury by cyclosporin A.

This study evaluated the effect of cyclosporin-A (CyA), a potent immunosuppressive drug, on Bleomycin (Bleo)-induced pulmonary inflammation in hamsters. Pulmonary injury was induced by a single intratracheal (i.t.) instillation of Bleo. Four groups of 10 male Syrian hamsters each received one of four treatments: (1) i.t. Bleo and daily intraperitoneal (i.p.) injections of CyA starting 1 day before i.t. instillation of Bleo (Bleo-CyA); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. CyA (Sal-CyA); (4) i.t. saline and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated histologically, biochemically, and by analysis of bronchoalveolar lavage (BAL) fluid. Treatment of hamsters with CyA significantly ameliorated the Bleo-induced lung injury, as determined by a semiquantitative morphological index that assesses the severity and extent of the injury on a scale of 0-3. Lung hydroxyproline measurements were lower in Bleo-CyA compared to Bleo-Sal, comparable to Sal-Sal and Sal-CyA controls. The percentage of neutrophils, eosinophils, and lymphocytes in BAL fluid was higher in Bleo-Sal and Bleo-CyA animals when compared with control Sal-CyA or Sal-Sal animals. A further increase in percentage of eosinophils was observed in Bleo-CyA compared with Bleo-Sal animals (13.3 +/- 6.6% [mean +/- SE] and 3.7 +/- 2.1%, respectively, p = .0007). BAL fluid protein content was higher in Bleo-Sal compared to Sal-Sal animals, but BAL fluid protein content from Bleo-CyA was not significantly different from that of Bleo-Sal animals. These results indicate that CyA ameliorates the Bleo-induced inflammation but does not prevent leakage of plasma protein or cells into the airspaces. The increased eosinophil numbers in Bleo-CyA-treated hamsters suggests enhanced production of interleukin-4 and -5.

Animals↗

Effect of interleukin-2 and interleukin-4 on lymphocytes from peribronchial lymphatic tissue.

Lymphocyte activation in spleen and peribronchial lymphatic tissue (PBLT) following stimulation with T-cell mitogens and lymphokines was investigated in the hamster. Optimal mitogen-induced cell proliferation was achieved after culturing for 6 days in vitro. Interleukin-2 (IL-2) and interleukin-4 (IL-4) did not induce DNA synthesis in resting T-cells from either spleen or PBLT.IL-2 or IL-4 in combination with concanavalin A promoted splenic T-cell proliferation. In contrast, in PBLT, IL-2-but not IL-4-enhanced cell proliferation (p < .001). The findings indicate that PBLT represents an independent compartment of the immune system. Furthermore, in the hamster PBLT cells consist predominantly of IL-2-responsive cells, i.e., are of the Th1 type. Immunological pathogenesis of lung injury can therefore be studied by functional analysis of PBLT lymphocytes.

Animals↗

New approaches for the prevention of rejection and graft-vs.-host disease in clinical bone marrow transplantation.

The two major barriers to successful allogeneic bone marrow transplantation (BMT) in animals and man are graft-vs.-host disease (GVHD) and the risk of graft rejection. GVHD is the result of alloreactivity of mature donor T-lymphocytes present in the graft-vs.-host tissues and can be completely prevented by pregraft depletion of T-lymphocytes. Graft rejection results from residual host immunocompetent lymphocytes that survive heavy chemoradiotherapy prior to allogeneic BMT. Host resistance to allograft cannot be eradicated even by conventional conditioning with high-dose cyclophosphamide (120 mg/kg) and lethal whole body irradiation (1,200 rad). In the present report we have utilized two new techniques to overcome GVHD and graft rejection following allogeneic BMT. GVHD can be prevented by a new monoclonal rat antihuman lymphocyte antibody, CAMPATH-1, which binds human complement, enabling donor serum to serve as the source of complement. Prevention of rejection of T-lymphocyte-depleted marrow allografts can be achieved by the application of total lymphoid irradiation (TLI) in addition to conventional chemoradiotherapy, prior to allogeneic BMT. TLI causes potent immunosuppression with minimal side effects. A combination of TLI for overcoming host resistance to allograft, and CAMPATH-1 for overcoming GVHD, leads to a relatively smooth posttransplant outcome with no evidence of GVHD and with no need for posttransplant immunosuppression.

Antilymphocyte Serum↗

Cerebral toxoplasmosis complicating bone marrow transplantation.

Cerebral toxoplasmosis occurred in a 34-year-old patient with chronic myelogenous leukemia following bone marrow transplantation. The clinical picture included headaches, nuchal rigidity, and right-sided hemiparesis during a course of disseminated cutaneous herpes zoster. The diagnosis of toxoplasmosis was based on serologic evidence and typical computed tomography scan of the brain as well as clinical improvement following specific anti-Toxoplasma treatment. To the best of our knowledge, this is the first report of cerebral toxoplasmosis in Israel.

Adult↗