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Biomedical subjects

R J Marder

Publications and source records attributed to R J Marder.

At least 19 recordsLinked to original sources
PubMed2000

Effect of Medicaid managed care on pregnancy complications.

OBJECTIVE: This study examined the impact of managed care on hospital obstetric outcomes in Medicaid-sponsored women. METHODS: The study sample consisted of a total of 525,517 maternal deliveries for singleton births from three payer groups, Medicaid managed care, Medicaid fee-for-service, and private managed care in 439 short-term-stay nonfederal hospitals in California and Florida. Quality of care comparisons were made using six indicators. Data were derived from linked computer files of birth certificates, hospital discharge abstracts, Medicaid eligibility records, Medicaid health care claims, and surveys of hospital characteristics. RESULTS: The overall multivariate likelihood of an adverse maternal outcome during hospitalization for a delivery was not significantly different between Medicaid managed care and Medicaid fee-for-service groups in California and Florida. However, mothers in the Medicaid managed care group compared with mothers in the private managed care group experienced a higher likelihood of eclampsia (California) (adjusted odds ratio = 1.26; 95% confidence interval 1.05, 1.57; P = .04). CONCLUSION: Overall, managed care has not adversely affected pregnancy outcomes in Medicaid-sponsored women. Yet, payer system changes may be insufficient to achieve complete parity of outcomes relative to private managed care patients.

California↗
PubMed1998

Enhancing clinical pathway placement.

Soaring health care costs have fueled the immense growth in managed care. To contain these costs, health care organizations have turned to clinical pathways. However, clinical pathways cannot do an effective job if health care personnel are not aware of their existence. The article presents a simple, effective, and efficient method to increase placement of clinical pathways in inpatient medical records.

Cost Control↗
PubMed1991

Measuring the quality of care for the cancer patient.

In recent years, the efforts to better define quality of patient care have focused on attempts to improve on the measurement of quality. These efforts raise three questions: (1) Why attempt to measure quality? (2) What is the best way to measure quality of care of the cancer patient? and (3) What must be done to achieve this? Three main reasons for measuring quality of patient care are to describe the current state, plan strategies for improvement, and implement and monitor improvements. To measure quality, both the definition of quality and the tools available for measurement must be addressed. The difficulty in developing a measurable definition of quality is achieving agreement on the measurable components of quality. The tools to measure quality have evolved to focus on monitoring of key indicators for comparative use. The utility of indicators lies in demonstrating that they have the capacity to identify opportunities for improving care. The Joint Commission is improving measurement tools through the development and testing of oncology indicators for reliability and the capacity to identify opportunities for improving care. The development and teaching of new quality improvement methods to health care professionals also is necessary.

Health Services Research↗
PubMed1989

The elimination of malignant B lymphocytes from human bone marrow using monoclonal antibodies DLC-48 and LN-1 and human serum: a preclinical study.

Monoclonal antibodies DLC-48 and LN-1 were evaluated for use in purging malignant lymphoma cells from human bone marrow. Using a 51Cr-release assay and sensitive clonogenic assay for the SU-DHL-2 and -4 cell lines, it was established that greater than four logs of malignant lymphoid cells can be eliminated from human bone marrow autografts with three treatments of antibody and autologous human serum at a final cell concentration of 1 X 10(7) cells/ml. A combination of DLC-48 and LN-1 was more effective than either antibody alone. Treatment with antibody and autologous serum had no effect on the growth of human hematopoietic progenitor cells. The clinical effects of marrow treatment with DLC-48 and LN-1 will be evaluated in upcoming clinical trials.

Animals↗
PubMed1988

Heterogeneity among the non-Hodgkin's lymphomas. Implications for autologous bone marrow transplantation with in vitro purging using monoclonal antibodies.

To investigate the possible implications of heterogeneity among the non-Hodgkin's lymphomas for bone marrow purging using complement-fixing monoclonal antibodies to lymphoma-associated antigens, a panel of large cell lymphoma cell lines of diverse phenotypes was treated with monoclonal antibodies DLC-48 and LN-1. An association was demonstrated between the percentage of suppression of colony formation by the cell line and both the percentage of cells staining with the antibody and the intensity of its binding. Flow cytometric analysis of cells surviving treatment with antibody and complement demonstrated that the population that escaped lysis showed weak immunofluorescent staining. Similarly, 40% of the clones derived from cells surviving treatment with antibody and complement stained weakly compared with the parent cell line. For a given fluorescence intensity, cells differed in their susceptibility to treatment. Some cells with moderate to strong staining survived incubation with antibody and complement. In five cases, treatment of bone marrow contaminated with malignant lymphoma cells resulted in complete eradication of even cells with weak staining. In two cases, a population of cells that stained dimly survived treatment with either antibody. DNA-content analysis showed that the cell cycle distribution of cells surviving treatment with DLC-48 or LN-1 and complement was similar to that of cells treated with control antibody 46-1G7 and complement. Phenotypic heterogeneity may hinder efforts to purge malignant lymphoma cells from human bone marrow with complement-fixing monoclonal antibody reagents. Relative resistance to complement-mediated lysis may underlie differences in the susceptibility of cells to treatment and also limit the effectiveness of this technique.

Antibodies, Monoclonal↗
PubMed1988

Complete resolution of pure red cell aplasia in a patient with chronic lymphocytic leukemia following antithymocyte globulin therapy.

Pure red cell aplasia has been reported to be associated with chronic lymphocytic leukemia. It has been proposed that this complication may be a result of T-cell populations that suppress erythropoiesis. It has been postulated that antithymocyte globulin might reverse this abnormality by eliminating the population of suppressor T cells responsible for this inhibition. We treated a 74-year-old man who had B-cell chronic lymphocytic leukemia and pure red cell aplasia that was refractory to cytotoxic and corticosteroid therapy with equine antithymocyte globulin and methylprednisolone sodium succinate. This therapy resulted in a durable complete remission of both the chronic lymphocytic leukemia and the pure red cell aplasia and was associated with normalization of helper/suppressor T-cell ratios in the bone marrow. Antithymocyte globulin should be investigated further as a therapeutic modality for patients with pure red cell aplasia associated with chronic lymphocytic leukemia.

Aged↗
PubMed1988

Heterogeneity of phenotypic expression in normal and neoplastic B-cell proliferations detected by monoclonal antibodies LN-1 and DLC-48.

Recently developed monoclonal antibodies DLC-48 and LN-1 have been shown to be effective reagents for complement-mediated cell lysis of human B-cells. The authors have initially found that these reagents are useful in elimination of malignant lymphomas cells from human bone marrow for autologous bone marrow transplantation. In the current study, the authors have further characterized the reactivity of these antibodies in B-cell neoplasia and have analyzed the heterogeneity of antigenic expression among benign and neoplastic lymphoid cells for B-cell monoclonal antibodies. With the use of quantitative flow cytometric techniques to assess heterogeneity of antigen expression, the findings indicate that phenotypic heterogeneity within neoplasms from individual patients exists for a number of B-cell-related monoclonal antibodies, including B1, common acute lymphocyte leukemia antigen (CALLA), Ia, Ba-1, DLC-48, and LN-1. Within a given histologic class of lymphoid neoplasia, phenotypic heterogeneity was found to be a property of some individual cases and not others for all B-cell monoclonal antibodies examined. This heterogeneity was not consistently expressed in patients with similar tumors, nor was it a consistent property of a given antigen. Using cell lines derived from large cell lymphomas, the authors were able to find phenotypic heterogeneity within neoplastic cell lines that can be used to develop models for dealing with phenotypic heterogeneity in the context of complement-mediated cell lysis. They also established that for DLC-48 and LN-1, the heterogeneity was not related to the phase of the cell cycle of the proliferating cells. The results suggest that single monoclonal antibody treatment for bone marrow depletion of neoplastic cell may be insufficient to overcome phenotypic heterogeneity of B-cell neoplasms.

Antibodies, Monoclonal↗
PubMed1988

Immunohistochemical characterization of two new monoclonal antibodies (LN-4, LN-5) reactive with human macrophage subsets and derived malignancies in B5-fixed, paraffin-embedded tissues.

Two monoclonal antibodies (LN-4, LN-5) reactive to human macrophages in B5 formalin-fixed, paraffin-embedded tissue sections have been produced by using deparaffinized cell extracts of peripheral blood mononuclear cells. Both monoclonal antibodies were initially identified on paraffin-embedded sections of hyperplastic lymph nodes by using the immunoperoxidase staining procedure. Specificity screens on normal human tissues show that LN-4 and LN-5 stain the cytoplasm of macrophages and histiocytes in hematopoietic organs including Kupffer's cells of the liver and Langerhans' cells of the skin. LN-4 also showed strong positivity with acini of the stomach, whereas LN-5 was positive with mantle zone B lymphocytes of the lymph node and spleen, spermatogonia, and chief cells of the stomach. Both antibodies were strongly reactive with cases of true histiocytic lymphoma but, except for infiltrating macrophages, were entirely negative in Hodgkin's disease and non-Hodgkin's lymphomas. In all cases of nodular sclerosis Hodgkin's disease, LN-4 was positive in macrophagelike cells present in the collagen bands surrounding the Hodgkin's lesions. Both monoclonal antibodies were also positive in macrophages and histiocytes present in a variety of benign lymphoid lesions including persistent generalized lymphadenopathy, Gaucher's disease, sinus histiocytosis, and dermatopathic lymphadenopathy. Because of their specificity for human macrophages, and their ability to stain B5-fixed, paraffin-embedded tissues, LN-4 and LN-5 are important new reagents for the diagnosis and classification of malignant and benign histiocytic lesions.

Animals↗
PubMed1987

Monoclonal antibody DLC-48: an effective reagent for use in the depletion of malignant lymphoma from human bone marrow.

A combination of large-cell lymphoma cell lines was used as immunogen in the production of DLC-48, a mouse monoclonal antibody (MAb) to a B-cell-associated antigen. This reagent identifies a protein found on a majority of peripheral blood B-cells, B-cell derived tumor cell lines, and lymphoma biopsy specimens. In reactive lymph-node sections, DLC-48 stains both germinal center and mantle zone B-lymphocytes when the immunoperoxidase technique is used. DLC-48 is an IgM, and is highly cytotoxic in the presence of human serum complement. The conditions for complement-mediated cytotoxicity were first optimized by utilizing the chromium-release assay with 2 large-cell lymphoma cell lines, and were then applied to the treatment of the cell lines prior to cloning in agar. A single treatment with antibody and human serum eliminated 4 orders of magnitude of target cells. The cytolytic activity of this antibody was not inhibited by the presence of a 20-fold excess of normal human bone marrow. Treatment with antibody and autologous serum did not affect the growth of human hematopoietic progenitor cells (CFU-GEMM and CFU-GM). These results suggest that DLC-48, either alone or in combination with other MAb reagents, should be effective in eliminating malignant cells of B-lineage from human bone marrow for purposes of autologous bone-marrow transplantation.

Antibodies, Monoclonal↗
PubMed1987

Two new monoclonal antibodies, Lym-1 and Lym-2, reactive with human B-lymphocytes and derived tumors, with immunodiagnostic and immunotherapeutic potential.

Two new monoclonal antibodies (Lym-1 and Lym-2), reactive with the cell surface of B-lymphocytes and derived tumors, have been produced using tumor cell nuclei preparations as immunogens. Specificity screens using live cell radioimmunoassay techniques with 52 well-characterized human lymphoma and leukemia cell lines showed that both Lym-1 and Lym-2 bound to cell lines of B-cell lineage but were unreactive with those of T-cell, myeloid, or erythroid derivation. The B-cell specificity of these reagents was confirmed on 36 lymphoma and 15 leukemia biopsy specimens by using immunoperoxidase or immunofluorescence techniques. Additionally, flow cytometric analysis of 22 lymphoma biopsies showed that the majority of B-cell tumors were Lym-1 and/or Lym-2 positive and that within a given biopsy, a high percentage of the malignant cell population was stained. In both the immunoperoxidase and flow cytometric studies, reactive T-cells or T-cell lymphomas were consistently negative with the exception of Hodgkin's disease tissues which, in some instances, showed a higher than expected positivity with Lym-1 and Lym-2. Approximately 40% of B-cell chronic lymphocytic leukemias were found to be positive with Lym-1 while 80% were positive with Lym-2. Immunoperoxidase staining of frozen sections of human lymphoid tissues showed that both Lym-1 and Lym-2 stained germinal center and mantle zone B-lymphocytes as well as interfollicular histiocytes. Flow cytometric analysis of normal peripheral blood demonstrated specific staining of B-cells which comprised approximately 8% of circulating lymphocytes. Immunoperoxidase staining of nonlymphoid human organs and tissues revealed weak reactivity of Lym-1 with surface colonic epithelium only. Consistent with these findings, 35 solid tumor cell lines of diverse nature were found unreactive with both Lym-1 and Lym-2. Although standard techniques have thus far failed to identify the antigen recognized by Lym-2, the membrane antigen which binds Lym-1 has been shown by immunoprecipitation and competitive radioimmunoassay studies to be a polymorphic variant of the HLA-Dr antigen. Solid-phase radioimmunoassay techniques have shown that the antigens recognized by Lym-1 and Lym-2 are not significantly modulated after antibody exposure nor shed into the circulation of lymphoma patients. Finally, using iodine-125 labeled preparations of purified Lym-1 and Lym-2, we have determined that both reagents have a relatively large number of antibody binding sites per tumor cell and increased avidity for lymphoma cells when compared to normal and reactive lymph node B-cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1987

Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study.

A radiolabeled murine monoclonal antibody (T101) was used for imaging and therapy of six patients with cutaneous T cell lymphoma (CTCL). Radioimmunodetection was performed with a 5.6 to 13.1 mCi 131I-T101 preparation (9.6 to 10.5 mg). A therapeutic dose of 100.5 to 150.1 mCi 131I on 9.9 to 16.9 mg of antibody was administered to five patients, with subsequent retreatment following plasmapheresis in three patients at the time of disease progression. All patients responded to their initial therapy and two patients responded to retreatment. Regression of skin lesions and peripheral adenopathy was witnessed. All patients reported resolution of their chronic pruritus. The duration of response ranged from 3 weeks to 3 months. Acute toxicity included fevers, pruritus, and mild dyspnea in two instances. Myelosuppression was seen in patients receiving the 144.7 mCi, 145.0 mCi, and 150.1 mCi 131I-T101 doses. Radioimmunodiagnostic and therapy studies included gamma scintigraphy, plasma, urinary, and wholebody antibody clearances, and biodistribution determined from skin, bone marrow, and liver biopsies. Immunologic studies included immunoperoxidase staining of target tissues, immunofluorescent flow cytometric analysis on peripheral blood and bone marrow, assays for serum blocking factors, determination of a human antimouse antibody (HAMA) response, and quantitation of circulating T101 levels. These preliminary data suggest that 131I-T101 has therapeutic potential in CTCL and that myelosuppression will be the limiting toxicity.

Aged↗
PubMed1987

Human T-cell lymphotropic virus type I-associated adult T-cell leukemia/lymphoma in an atypical host.

Human T-cell lymphotropic virus type I (HTLV-I) is a unique retrovirus associated with specific malignancies of T cells in humans. The virus is endemic to Japan, the Caribbean, Africa, and the southeastern United States. We report here the first case of HTLV-I-associated lymphoma in an atypical host. The incidence of antibodies in this individual with a T-cell malignancy strongly suggests HTLV-I virus as the causative agent. Direct identification of viral DNA using an HTLV-I-specific probe provides definitive evidence of infection.

Aged↗
PubMed1987

Immunohistochemical characterization of a 183 KD myeloid-specific-DNA-binding protein in B5 fixed, paraffin-embedded tissues, and bone marrow aspirates by monoclonal antibody BM-1.

A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.

Animals↗
PubMed1987

Establishment and characterization of a neuroendocrine skin carcinoma cell line.

A neuroendocrine skin carcinoma cell line MKL-1 has been established from a nodal metastasis in a 26-year-old patient. The line grows as irregularly outlined, loosely packed floating aggregates lacking central necrosis. MKL-1 is hyperdiploid and has a mean doubling time of 120 hours. Xenografts of 2 X 10(7) MKL-1 cells produce tumors in nude mice at 4 to 6 weeks after subcutaneous inoculation. The xenografts were morphologically indistinguishable from the original skin primary and the nodal metastasis. Electron microscopy revealed sparse membrane-bound neurosecretory granules, and conspicuous, paranuclear aggregates of intermediate filaments. Immunohistochemical study showed diffuse and consistent staining with neuron-specific enolase, while bombesin, adrenocorticotrophic hormone, Leu-enkephalin, substance P, and vasoactive intestinal polypeptide displayed heterogeneous and variable expression. Uniform staining of all cells appearing as cytoplasmic fibrils and paranuclear aggregates was noted with antibodies to cytokeratin. Appreciable amounts of cytokeratin polypeptides 8, 18, and 19 and IT protein were seen on two-dimensional gel electrophoresis of cytoskeletal preparations from MKL-1 cells and from tumor-rich frozen sections. Immunostaining also showed coexpression of neurofilaments arranged in paranuclear aggregates; gel electrophoresis and immunoblotting demonstrated the presence in MKL-1 cells of prominent amounts of the small neurofilament polypeptide. Focal expression of desmoplakin was noted in the xenografts. The cells reacted with monoclonal antibodies anti-Leu-7 and anti-Leu-M1 but did not react with antibodies to human lymphocyte antigens (HLA)-A, HLA-B, and HLA-C. Cytogenetic analysis revealed the presence of 3 chromosomally abnormal cell lines with the majority of metaphase cells demonstrating a gain of an isochromosome of the short arm of chromosome 5. Thus, MKL-1 cell line shares several characteristics with small cell neuroendocrine bronchopulmonary carcinoma cell lines but shows distinct cytogenetic abnormalities.

Adult↗