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Biomedical subjects

R Or

Publications and source records attributed to R Or.

At least 145 records · Page 8Linked to original sources
PubMed1994

The anti-emetic efficacy and tolerability of tropisetron in patients conditioned with high-dose chemotherapy (with and without total body irradiation) prior to bone marrow transplantation.

Nausea and vomiting are among the most distressing side-effects of chemoradiotherapy. Conditioning protocols for patients undergoing bone marrow transplantation consist of highly emetogenic high-dose chemotherapy with or without total body irradiation. Marked improvement in controlling emesis and nausea was achieved by the introduction of a new class of antiemetic drugs, the 5HT3 serotonin-receptor antagonists. Tropisetron is a highly potent, selective antagonist of 5HT3 receptors. Previous studies have used a single 5-mg dose i.v. of tropisetron to control nausea and vomiting in cancer patients. The present study was undertaken to evaluate the efficacy and safety of a single daily dose of tropisetron in controlling emesis in patients receiving high-dose chemotherapy (with or without total body irradiation) prior to bone marrow transplantation. The anti-emetic efficacy was investigated in a non-homogeneous cohort in a prospective and open study. Of 11 patients evaluated, 9 (81%) showed complete or major control, 1 (9%) minor control and 1 (9%) failed to respond. The most common adverse events reported during the study included diarrhea (46%) and headache (18%), no patients being withdrawn because of side-effects. Our data suggest that a single 5-mg i.v. dose of tropisetron is safe and effective in preventing chemotherapy-induced emesis in patients receiving bone marrow transplantation conditioning. A larger randomized study is warranted to confirm our preliminary results.

Adolescent↗
PubMed1994

Intracranial haematomas following bone marrow transplantation.

Intracranial haemorrhage (ICH) is a known grave complication of leukaemia and has been described post mortem following bone marrow transplantation (BMT). Ante mortem following BMT, the incidence and significance of ICH is not well defined. The records of 471 bone marrow transplantation recipients over 11 years at the Hadassah University Hospital Bone Marrow Transplantation Department were reviewed. The relevant data of all patients with ICH were analysed. A resolute diagnostic and treatment protocol for subdural haematomas had been employed. The indication for transplantation in 273 of the patients was leukaemia. Thirteen of these patients developed subdural haematomas within 42 days of the transplant, and nine of these haematomas were bilateral. None of the 198 patients with other malignancies or nonmalignant indications for BMT (predominantly aplastic anaemia and beta thalassaemia major) had subdural haematomas. One thalassaemia patient and three leukaemia patients had intracerebral haematomas. There was no mortality or major morbidity from the subdural haematomas, which were all successfully resolved. In contrast, all of the patients with intracerebral haematomas consequently died. Subdural haematomas occur in approximately 5% of patients with leukaemia following BMT, but the clinical outcome is relatively benign. Intracerebral haematomas are a sporadic, lethal complication following BMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Cytomegalovirus pneumonia prior to engraftment following T-cell depleted bone marrow transplantation.

CMV pneumonia is a frequent complication of allogeneic bone marrow transplantation (BMT). It usually appears 23 months following transplantation and is associated with a high mortality rate. The incidence of CMV pneumonia in our T-lymphocyte depleted allogeneic BMT recipients, transplanted between 1987-1991, was 18 out of 197 (9.2%) patients. In 3 patients (1.5% of allogenic BMT recipients), pneumonia occurred prior to marrow engraftment, on days 12-16 post BMT. These patients did not develop acute GVHD in contrast to 9/11 patients who had acute GVHD in addition to developing CMV pneumonia between engraftment and day +100 (p < 0.03). Furthermore, these three patients did not receive steroid therapy as opposed to 14/15 patients who were treated with steroids and eventually contracted CMV pneumonia post-engraftment (p < 0.01). The three patients did not have two additional risk factors known for the development of CMV pneumonia: increasing age and a diagnosis of acute myeloblastic leukemia (AML) as the primary disease. Despite prompt diagnosis and therapy with ganciclovir and high doses of intravenous immunoglobulin (IVIG), two of the patients died. Tcell depleted BMT may be a risk factor for development of CMV pneumonia occurring prior to engraftment. In the era of post-BMT anti CMV prophylaxis, one should be aware that life-threatening CMV pneumonia may appear prior to engraftment and consider aggressive CMV prophylaxis.

Adolescent↗
PubMed1994

Detection of minimal residual disease state in chronic myelogenous leukemia patients using fluorescence in situ hybridization.

Detection of minimal residual disease and relapse remain major problems in chronic myelogenous leukemia (CML) patients following bone marrow transplantation (BMT). In order to disclose the 9;22 Philadelphia translocation, we used a fluorescence in situ hybridization (FISH) technique. BCR and ABL gene fragments were used as probes for the detection of the BCR/ABL fusion product in peripheral blood and bone marrow cells from 11 CML patients in which 5 were post-BMT. The sensitivity and specificity of this approach were compared to conventional cytogenetic and polymerase chain reaction (PCR) methods. FISH demonstrated a high degree of sensitivity (1%) for the detection of the BCR/ABL translocation in these patients. A linear correlation was found between FISH detection of the BCR/ABL fusion product and routine chromosomal analysis (r = 0.995; p < 0.001). Detection of the BCR/ABL signal by FISH was observed in all patients showing a positive PCR signal. A significant reduction in BCR/ABL signal was observed post-transplant (p < 0.001). However, the BCR/ABL translocation was detected in four of five transplanted patients immediately (0.75-2.5 months) following transplant and was found in patients with a low expression of the translocation.

Adult↗
PubMed1994

Loss of Y chromosome. An age-related event or a cytogenetic marker of a malignant clone?

Cytogenetic analysis of bone marrow cells performed at the time of diagnosis of ALL in an 80-year-old male patient revealed two unrelated abnormal clones. One included the 9;22 translocation (Philadelphia chromosome) as the sole aberration and the second was missing the Y chromosome. The significance of this finding in the light of the role of -Y clone in malignancy is discussed.

Aged↗
PubMed1994

Development of antibodies to hepatitis B virus surface antigen in bone marrow transplant recipient following treatment with peripheral blood lymphocytes from immunized donors.

Bone marrow transplantation (BMT) recipients are immunosuppressed and are at risk for contracting severe infections. Recently, adoptive transfer of immunity against hepatitis B virus (HBV) was documented in BMT recipients receiving bone marrow from 'naturally' HBV-infected individuals who recovered spontaneously, or those transplanted with bone marrow cells obtained from actively immunized donors. Furthermore, reconstitution of the immune system in a BMT recipient who was a hepatitis surface antigen (HBsAg)+/HBV DNA+ carrier with HBV immune bone marrow cells led to clearance of the replicating virus, presumably through adoptive cell-mediated immunotherapy. We report three cases of induction of immunity to HBV by selective adoptive transfer by i.v. injection of peripheral blood lymphocytes (PBL) obtained from BMT donors who were actively immunized against HBV after harvesting of bone marrow. All three BMT recipients developed anti-HBs antibodies. In one BMT case in whom antibodies to HBsAg developed following adoptive transfer of immune PBL, a mild booster effect was documented in the BMT recipient upon immunization with a recombinant hepatitis B vaccine. The two remaining patients lost their antibodies to HBsAg in association with relapse of leukaemia. This immune manipulation may open the door to evaluation of adoptive transfer of immunity to HBV through selective transplantation of HBV immune lymphocytes in selected patients such as those with persistent HBV infection, as well as liver transplant recipients who require protection of the graft against HBV re-infection.

Adolescent↗
PubMed1994

Rhinocerebral aspergillosis in patients undergoing bone marrow transplantation.

Rhinocerebral aspergillosis (RA) is becoming increasingly common in patients undergoing bone marrow transplantation (BMT). The disease can involve nearly all major head and neck structures, including the nose, paranasal sinuses, and orbits. Intracranial extension of the infection is of major concern, since this is usually a fatal complication. Our study population comprised 423 consecutive BMT patients at Hadassah University Hospital from January 1986 to August 1992. Eight patients (1.9%) developed RA, 5 of whom had underlying hematologic malignancies, and 3 of whom had severe aplastic anemia. Only 2 of the 8 patients responded completely to therapy, with a follow-up of 15 months. It appears that RA is a fatal complication in immunocompromised patients post-BMT. Early diagnosis followed by extensive surgical debridement of necrotic tissue and systemic, as well as topical, antifungal therapy with amphotericin B or its new formulations and the patient's recovery of bone marrow function may improve the outcome of this life-threatening complication.

Adolescent↗
PubMed1994

Lymphoma-associated pancreatitis as a presenting manifestation of immunoblastic lymphoma.

A 55 year old man presented with clinical signs and symptoms of subacute pancreatitis of unknown aetiology. Two weeks later, inguinal lymphadenopathy developed and a lymph node biopsy revealed a B cell immunoblastic lymphoma. Computerized tomography showed enlargement of the pancreas and imaging features consistent with pancreatitis. Administration of VACOP-B combination chemotherapy achieved complete resolution of the pancreatic mass and the enlarged lymph nodes. We consider this patient to have had lymphoma associated pancreatitis. This case represents a rare clinical presentation of lymphoma suggesting an alternative aetiology of subacute pancreatitis in some cases.

Acute Disease↗
PubMed1994

Salivary immunoglobulins in recipients of bone marrow grafts. I. A longitudinal follow-up.

Patients receiving bone marrow transplantation (BMT) are prone to a variety of bacterial, viral and fungal infections in their oral cavity. We have therefore followed alterations in salivary Ig levels associated with BMT. Most of the patients were transplanted with allogeneic, MHC-matched BM after T cells were depleted by ex vivo treatment with an anti-lymphocytic monoclonal antibody (Campath-1) and autologous complement. Parotid saliva was collected at various time intervals before and after BMT, and IgM, IgG and IgA concentrations were determined by an enzyme linked immunosorbent assay (ELISA). A gradual fall in Ig levels was detected following patient's conditioning with a combination of chemo- and radiation therapy beginning 10 days prior to BMT. A rise in the titer of salivary Ig could be detected as early as 4 days post-BMT, which increased continuously and reached plateau levels within 2-3 weeks. However, about 3 weeks later the Ig titers decreased again and persisted at low levels for variable periods of time. A second increase in salivary Ig was detected approximately 2 months post-BMT, which persisted for prolonged periods of time. These results suggest that Ig secreted by donor B-lymphocytes and plasma cells passively transferred with the BM can rapidly reconstitute the salivary IgM, IgG and IgA of the immunocompromised recipient. However, when these cells cease to produce Ig the patients are still immunoincompetent and therefore enter a second phase of salivary Ig deficiency which may render them highly susceptible to opportunistic oral infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Salivary immunoglobulins in recipients of bone marrow grafts. II. Transient secretion of donor-derived salivary IgA following transplantation of T cell-depleted bone marrow.

Patients undergoing bone marrow transplantation (BMT) have decreased levels of salivary Ig over long periods of time. However, shortly after transplantation, a transient rise of Ig concentration in their saliva gland is detected. In order to trace the origin of this Ig, seven BM donors were immunized with tetanus toxoid (TT) 4-7 days prior to BMT harvesting. Four patients received BM from non-immunized donors. All but one of the patients had no detectable anti-TT IgA in their parotid saliva prior to BMT. Recipients of T cell-depleted BM from pre-immunized donors transiently displayed high titers of salivary anti-TT IgA 7-28 days after transplantation. No significant anti-TT IgA titers were detected in saliva of patients grafted with non-immunized BM. We conclude that antibody-producing cells activated in the donor are passively transferred with the BM to the recipient. IgA committed cells home to the mucosa-associated lymphoid tissues (MALT) and continue to secrete antibodies until senescence.

Adolescent↗
PubMed1994

Total lymphoid irradiation, anti-lymphocyte globulin and Campath 1-G for immunosuppression prior to bone marrow transplantation for aplastic anemia after repeated graft rejection.

Allogeneic BMT for severe aplastic anemia is associated with a significant rate of graft rejection, especially in patients who have been previously transfused. We report a child with aplastic anemia who rejected donor marrow twice despite adequate immunosuppression as part of the conditioning therapy but engrafted successfully following combined administration of three modalities of immunosuppression: antithymocyte globulin, total lymphoid irradiation and the monoclonal antibody Campath-1G. Restriction fragment length polymorphism studies > 1 year after BMT show full donor hematopoiesis with no evidence of autologous recovery.

Alemtuzumab↗
PubMed1993

Characterization of the progression signal for human T-cell proliferation provided by monoclonal antibodies to the CD3-TCR complex.

Following T-cell activation, two distinct stages in the proliferative response can be identified. The first stage or state of competence (G0 to G1 transition) is defined by the acquisition of the ability of activated T cells to proliferate in response to growth factors. The second or progression phase relates to the progression of cells to DNA synthesis in response to exogenous growth factors (e.g., IL-2) or inducers of growth factor synthesis (e.g., phorbol esters). In the present manuscript we provide evidence that soluble monoclonal antibodies (mAbs) to CD3 or the T-cell receptor (TCR), similar to the phorbol esters, can induce IL-2 production and cell proliferation in competent but not resting T cells. The data indicate the role of CD3-TCR complex triggering not only as an "activating or competence signal" but demonstrate its capacity to signal in the progression phase as well. However, there were distinct differences when competent T cells were stimulated by phorbol ester compared to soluble antibodies to CD3 or TCR. Antibodies to the CD3-TCR complex, when compared to phorbol ester, induced less proliferation in competent, memory T cells (CD45RO) than in competent, naive T cells (CD45RA). In contrast to phorbol ester, the induction of IL-2 transcription and cell proliferation in competent cells by soluble mAbs BMA 031 (anti-alpha/beta T-cell receptor) or OKT3 (anti-CD3) was inhibited by cyclosporin A (CsA). This implies that in activated T cells there is a step between activation of the CD3-TCR complex and the point(s) of action of phorbol ester that is susceptible to CsA in activated cells. Alternatively, the data may indicate involvement of different regulatory elements with different sensitivities to CsA for the induction of IL-2 transcription by phorbol ester or antibodies to the CD3-TCR complex.

Antibodies, Monoclonal↗
PubMed1993

Definition of the roles for iron and essential fatty acids in cell cycle progression of normal human T lymphocytes.

A serum-free cell culture system for human T lymphocytes was used to investigate the synthesis and metabolism of several important cell cycle-regulated proteins (p62c-fos, p110Rb, and p34cdc2 and its homologs) and the possible roles of iron and essential free fatty acids in regulating cell cycle progression. Following stimulation with phorbol dibutyrate (PDB) and ionomycin under serum-free conditions, resting T cells entered the cell cycle, as evidenced by a burst of synthesis of p62c-fos and an increase in the amount of the p33 homolog of the cdc2 kinase. However, in the absence of other additions, cells were arrested in the G1 phase of the cell cycle. Supplementation of the medium with two components, iron and linoleic acid (LA), permitted activated cells to progress through the G1 phase of the cycle and initiate DNA synthesis. Under these conditions p110Rb became phosphorylated and p34cdc2 was synthesized similar to T cells proliferating in normal serum-containing medium. The addition of iron, without LA, had little effect on activated cells; however, the addition of LA, in the absence of added iron, had profound effects. RNA accumulated to levels characteristic of cells at the G1/S interface, phosphorylation of p110Rb was almost complete, and p34cdc2 was synthesized, although at lower levels than in proliferating cells. However, no DNA synthesis was detected; under these conditions the cells appeared to be blocked at or near the G1/S border. Since there was a possibility that some component of the cell culture system could provide "trace" amounts of iron, and also to further delineate the role of iron in this system, cells were activated in medium containing LA and deferoxamine (10 microM), a chelator of iron. The accumulation of p34cdc2 was now reduced to nearly undetectable levels although phosphorylation of p110Rb was not substantially affected. It therefore appears that synthesis of p34cdc2 requires a low amount of iron, a finding which may define a possible regulatory point in the cell cycle for iron before its well-recognized role in regulating S phase entry by acting as a cofactor for the enzyme ribonucleotide reductase.

CDC2 Protein Kinase↗
PubMed1993

Normal hematopoietic reconstitution following ASTA-Z 7557-purged grafts in the absence of in vitro CFU-GM colony growth.

Hematopoietic reconstitution was assessed in 26 consecutive patients who underwent autologous bone marrow transplantation (ABMT) with ASTA-Z 7557 purged bone marrows. Of the 26, 17 had acute non-lymphoblastic leukemia (ANLL), 7 had acute lymphoblastic leukemia (ALL), 1 had non-Hodgkin's lymphoma (NHL) and 1 had multiple myeloma (MM). Twelve patients had practically no CFU-GM growth after ASTA-Z treatment. No statistical difference was observed in hematopoietic reconstitution between patients with or without in vitro CFU-GM colony growth. No significant linear correlation was observed between CFU-GM content in the treated graft and day of engraftment. In vitro CFU-GM growth has no predictive value in assessing hematopoietic recovery in vivo. Patients with no CFU-GM growth demonstrated normal engraftment.

Adolescent↗