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Biomedical subjects

J F Desforges

Publications and source records attributed to J F Desforges.

At least 19 recordsLinked to original sources

Treatment of acute myeloid leukemia in the elderly with low-dose cytarabine, hydroxyurea, and calcitriol.

Twenty-nine patients aged 62-82 years with acute myeloid leukemia (AML) were treated with a 21-day course of continuous infusion cytarabine, oral hydroxyurea, and 1,25-dihydroxyvitamin D3 (calcitriol). Ten patients had an antecedent myelodysplastic syndrome. Calcitriol was continued as the only postremission therapy. Thirteen patients (45%) obtained a complete remission, and 10 patients (34%) had a partial response for an overall 79% response rate. There were three early deaths. The median remission duration was 9.8 months. Overall median survival was 12 months for all patients and 14 months for responding patients. All responding patients had marked bone marrow hypoplasia. Twenty patients received part or all of their chemotherapy as outpatients. This regimen has acceptable toxicity and can result in prolonged remissions in elderly, high-risk patients with AML. The favorable results may be related to the synergistic effect of hydroxyurea, cytarabine, and calcitriol.

Acute Disease

Engraftment with peripheral blood stem cells collected by large-volume leukapheresis for patients with lymphoma.

Seven patients with refractory lymphomas underwent marrow reconstitution with peripheral blood stem cells (PBSCs) harvested by large-volume leukapheresis (LVL). PBSCs were collected from all patients more than 1 month after the last cycle of chemotherapy, and no patient received growth factors. The median number of LVL procedures performed per patient was 4.5, with a mean volume of 24.5 L of blood processed per procedure to obtain 7 x 10(8) mononuclear cells per kg. Autologous PBSCs and platelets were frozen at a controlled rate in plasma and 10-percent dimethyl sulfoxide and stored in the vapor phase of liquid nitrogen. This group of patients was compared to a control group (n = 18) who received medullary marrow (MM) transplants for the same diagnoses under the same protocols during the same period. Posttransplant days to white cell engraftment (PBSC = 17, MM = 15.5) were no different. Days to platelet independence were significantly longer in the LVL PBSC group (PBSC = 33, MM = 16; p < 0.05). This pattern of engraftment is typical of patients treated in this manner. Although Day 0 platelet counts (PBSC = 75.5 x 10(9)/L, MM = 85 x 10(9)/L) and total single-donor unit platelet use (PBSC = 8, MM = 9) were no different, Day 1 platelet counts (PBSC = 128 x 10(9)/L, MM = 61.5 x 10(9)/L; p < 0.05) and Day 14 platelet use (PBSC = 5, MM = 8; p < 0.05) were significantly different, because of the transfusion of cryopreserved autologous platelets with PBSCs on Day 0.

Adolescent

Prompt engraftment using autologous peripheral blood stem cells for double autologous bone marrow rescue.

A patient with Hodgkin's Disease, stage IIIA, was treated for recurrent disease with autologous peripheral blood stem cells after ablative chemotherapy. Bone marrow rescue occurred promptly and his disease was significantly reduced. Ablative chemotherapy was administered again and a second bone marrow rescue with peripheral blood stem cells was successful. Sequential peripheral blood stem cell bone marrow rescue, following high dose chemotherapy, may provide an alternative approach in selected patients.

Adult

Trisomy 13q in a case of acute leukemia with lineage inconsistency.

A case of acute leukemia has two distinct immature blast lines, lineage inconsistency with CD 4 positivity, and trisomy 13q as the effective cytogenetic abnormality. This case represents another instance of trisomy 13 with acute leukemia developing in a more primitive pluripotent stem cell.

Antigens, CD

Antiproliferative effects of lipoxygenase inhibitors on malignant human hematopoietic cell lines.

Eicosanoids regulate a wide spectrum of cellular processes including cell proliferation. We have shown previously that lipoxygenase metabolites of arachidonic acid modulate normal human hematopoiesis by in vitro colony assays. In this study we investigated the role of lipoxygenase metabolites in regulating the proliferation of several malignant hematopoietic cell lines, including K562 and EM-2 (chronic myelogenous leukemia blasts), HL-60 (promyelocytic leukemia cells), and U937 (malignant histiocytes). Piriprost, a specific inhibitor of 5-lipoxygenase, inhibits proliferation of these cell lines up to 95% with 50% cell inhibition at approximately 3 x 10(-5) M. Other less specific lipoxygenase inhibitors such as caffeic acid, nordihydroguaiaretic acid, and BW755C have similar activity in a [3H]-thymidine incorporation assay. In contrast, indomethacin, which is a cyclooxygenase inhibitor, has no suppressive effect in these assays. Inhibition by these drugs is completely reversible. Several nonhematopoietic malignant cell lines do not appear to be affected by these drugs. Two specific lipoxygenase metabolites, leukotriene B4 and leukotriene D4, stimulate leukemia cell line proliferation to 150% of control levels when added directly to cell cultures. These data suggest that certain lipoxygenase products, perhaps leukotrienes, are critical for the proliferation of malignant hematopoietic cells in vitro.

Arachidonate 5-Lipoxygenase

Paraproteinemic crystalline keratopathy.

Paraproteinemic crystalline keratopathy is an uncommon complication of multiple myeloma and other plasma cell dyscrasias. A case of 16 years' duration was associated with an IgG kappa monoclonal gammopathy and recurrent uveitis. The corneal changes were unusually extensive and distributed throughout all corneal layers. The deposits consisted of diffuse, small, polymorphic aggregates, which were iridescent in the superficial cornea, mat elsewhere, and associated with a diffuse stromal haze; specular microscopy showed additional features. Both corneas were thickened. The deposits failed to stain histochemically, except patchily with Masson Trichrome. There was extensive immunohistochemical labeling for IgG, kappa, and surprisingly, lambda. Ultrastructurally, pleomorphic deposits were found in every corneal cell; paracrystalline deposits with internal banding were seen only in the basal epithelium. Keratocytes and endothelial cells were damaged and reduced in number. Disease recurred in a corneal graft. Three main types of paraproteinemic keratopathy can be distinguished. The deposits probably represent various metabolic products of the monoclonal protein. This is not necessarily a benign condition; hematologic control may be necessary on purely ophthalmological criteria.

Corneal Opacity

Lipoxygenase metabolites of arachidonic acid modulate hematopoiesis.

Lipoxygenase (LPO) metabolites of arachidonic acid participate in the activation and/or proliferation of a variety of cell types. In this study, we examined the role of LPO metabolites in controlling myelopoiesis and erythropoiesis in vitro. Monocyte depleted cells (MDC) prepared from human whole blood or whole mononuclear cells from human bone marrow were cultured in methylcellulose in the presence of various growth factors. Conditioned media containing human colony stimulating factors (CSF) or the tumor-promoting phorbol ester, phorbol myristate acetate (PMA), were added to induce myelopoiesis. Semipurified human erythropoietin (EPO) was added along with an endogenous source of burst-promoting activity (BPA) to induce erythropoiesis. The LPO inhibitor BW755C blocked all types of colony formation in a dose-dependent manner, with ID50 of 20 and 5 micrograms/mL for myeloid and erythroid colonies, respectively. MDC depleted of T cells were similarly inhibited by BW755C. Similar results were seen with two other LPO inhibitors, 1-phenyl-3-pyrazolidone and butylated hydroxyanisole. A fourth LPO inhibitor, nordihydroguaiaretic acid, inhibited at higher concentrations. Indomethacin, at concentrations that inhibit cyclooxygenase, had no significant effect, either alone or in combination with the LPO inhibitors. These results suggest that certain LPO products may be important mediators of both CSF- and PMA-induced myelopoiesis, and of BPA/EPO-induced erythropoiesis.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz

Hodgkin's disease.

During the past two decades, new approaches to the diagnosis and treatment of Hodgkin's disease have contributed to improved rates of survival and probable cure. Currently, patients with Hodgkin's disease are treated according to the stage and symptoms of their disease. The degree of certainty necessary for determining stage depends on the potential effectiveness of the therapeutic options available in a given case. Certain cases have been identified where treatment with a single modality has been disappointing, and the use of both radiotherapy and chemotherapy may be considered for these. Such decisions can be made only by evaluating the effectiveness of salvage after relapse following single-modality treatment and assessing the added hazards of initial treatment with both modalities.

Adolescent

Cells on stems.

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Adult

Decision analysis to evaluate lymphangiography in the management of patients with Hodgkin's disease.

We used decision analysis to explore the role of lymphangiography for staging Hodgkin's disease. Factors included were status of the patient before the test, accuracy and mortality of lymphangiography, mortality of laparotomy and effectiveness of selected treatment. We analyzed hypothetical cases with varying probabilities being in Stages I+II, III and IV to determine the population in which indication for laparotomy would depend upon results of lymphangiography. Calculations made for asymptomatic patients revealed that the diagnostic usefulness of lymphangiography is restricted to patients either with a relatively low probability of Stage IV or with a very high probability of Stage IV disease. This population is further restricted as false-positive and false-negative results of lymphangiography increase.

Antineoplastic Agents

Diagnostic planning using computer assisted decision-making for patients with Hodgkin's disease.

A family of computer programs has been developed to help physicians effectively utilize available clinical information as in indicator of tumor extent for the staging of Hodgkin's disease patients. Decision analysis techniques were employed to suggest chronologic sequencing of selected, risk-associated tests, tailored to the individual patient, that minimize the risk of iatrogenic mortality. These quantitative techniques provide an objective measure of expected survival for a given plan of action. By using this information a physician and patient can balance expected survival vs morbidity of proposed staging procedures. Physicians can then focus on the interrelation between the inherent diagnostic uncertainty, therapy-induced expected survival, and morbid consequences of staging procedures. The use of these decision-making tools enables the physician to identify patient-specific presentations where the formation of an individual diagnostic plan could lead both to reduction in testing and to an increased survival rate.

Computers

Intraerythrocyte pH, pCO2 and the hexose monophosphate shunt.

We have documented a rise in pCO2 when erythrocytes are haemolysed by freeze-thaw using solid CO2 and methanol. This is partially corrected by preventing leakage of CO2 into the system. The remaining increment is partially explained by stimulation of the hexose monophosphate shunt when erythrocytes are haemolysed by this technique.

Carbon Dioxide