Prevention of high dose L-PAM-induced mucositis by cryotherapy.
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Biomedical subjects
Publications and source records attributed to C Dumontet.
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A 7 1/2-year-old patient with glycogenosis type lb had chronic neutropenia, recurrent bacterial infections, and severe hypoglycemia in spite of continuous nasogastric feeding. She was treated with lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) and orthotopic liver transplantation. Absolute neutrophil counts and platelet counts rapidly reached normal values, and infectious episodes were reduced. She resumed oral feeding after transplantation and had no subsequent hypoglycemic episodes.
Peripheral blood stem cells (PBSC) from 15 patients with advanced non-Hodgkin's lymphoma (NHL), two patients with chronic lymphocytic leukemia, and two patients with myeloma were collected by continuous-flow leukapheresis after chemotherapy with MIV (mitoxantrone, ifosfamide, and etoposide, five patients) or high-dose cyclophosphamide (14 patients), followed by administration of GM-CSF. Sixteen patients (84%) had persistent marrow involvement at time of inclusion. Results were compared to those obtained in a control group of similar age and disease status in whom collection had been performed after MIV chemotherapy alone. The number of mononuclear cells, granulocyte-macrophage colony-forming units (CFU-GM), CD34+ cells were higher in GM-CSF treated patients with a lower mean number of leukapheresis (3.5 versus 6.4). Among the 19 patients harvested after chemotherapy plus GM-CSF, more progenitor cells were obtained in the cyclophosphamide group than in the MIV group. In all these patients except one, the number of mononuclear cells was sufficient to realize a transplantation. Seventeen patients received intensification with BEAM regimen (8 patients) or cyclophosphamide plus etoposide and total body irradiation (9 patients). Two patients failed to reconstitute correct hematopoiesis and three early toxic deaths occurred for a total of five procedure-related deaths. Nine of these 17 patients are in persistent complete remission with a median post-transplant follow-up of 18 months. Time to reach granulocyte and platelet recovery was not correlated with the number of mononuclear cells, CFU-GM, granulocyte-erythroid-macrophage-megakaryocyte colony-forming units (CFU-GEMM), CD34+ cells, and CD34+ CD33- cells but with the number of previous chemotherapy regimens. PBSC harvesting is achievable after chemotherapy plus GM-CSF in heavily pretreated patients with persistent marrow involvement. Moreover, these cells are able to reconstitute correct hematopoiesis after intensive treatment in these patients.
Serum kinetics and organ distribution of [14C]-sialic acid-GM3 and [3H]-sphingosine-GM1, administered as an intravenous bolus, were analysed in Wistar rats. [3H]-GM1 and [14C]-GM3 had serum half-lives of 1.4 hours and 1.8 hours, respectively. Three hours after injection 75% of the GM1- and 38% of the GM3-associated label were present in the liver. Smaller yet significant amounts of label were present in the central nervous system, kidneys and lung. In vitro studies showed that [14C]-GM3 and [3H]-GM1 incubated with serum were predominantly bound to the High Density Lipoprotein and the Low Density Lipoprotein fractions. These results suggest a rapid serum clearance of exogenous gangliosides by the liver in rats.
We report two observations of intrahepatic cholestasis with normal serum levels of gamma-glutamyl-transpeptidase. These cases fit the diagnostic criteria of benign recurrent cholestasis and show that it, like Byler disease, is another form of pediatric intrahepatic cholestasis with a normal gamma-glutamyl-transpeptidase level in the infant.
One hundred patients with aggressive malignant lymphoma treated with the LNH-80 regimen were evaluated for long-term survival, late relapse and long-term sequelae. The LNH-80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. The fifty-two long-term responders were evaluated for their ability to resume work, sexual function, fertility and presence of long-term sequelae. Of the 41 patients who worked before diagnosis of their disease, 66% had resumed their normal jobs and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) were considered to have mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had second neoplasias. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity.
The 100 patients with aggressive malignant non Hodgkin lymphoma treated with the LNH-80 regimen were evaluated for long-term survival and quality of life. The LNH-80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two patients are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. Factors adversely correlated with response in multivariate analysis were poor performance status, bone marrow involvement and the presence of more than one extranodal site. Factors adversely correlated with survival were age, high grade subtypes, and bone marrow involvement. The fifty-two long-term responders were evaluated for quality of life parameters such as working ability, sexual function, fertility and absence of long-term sequelae. Of the 41 patients who worked before disease, 66% had resumed their normal job and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) considered having mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had a second neoplasia. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity.
The role of drugs inhibiting viral replication in patients infected with HIV has been confirmed. Until now only dideoxynucleosides, which are reverse transcriptase inhibitors, have demonstrated antiviral activity in humans. A number of compounds acting on other steps of the viral cycle are currently being evaluated and clinical trials are being performed. Some investigators are attempting to inhibit the binding of viral particles to target cells and their penetration into these by acting on the interaction between HIV ant the CD4 molecule. Another approach consists in the characterization of enzymatic activities which are specific of HIV, other than reverse transcriptase, such as ribonuclease H, integrase or protease, in order to prepare specific inhibitors. Attempts are made to inhibit retroviral gene expression and production of viral particles in infected cells. The development of new nucleoside analogues and drugs with mechanisms of action and toxicities different from those of zidovudine should allow in the near future combination chemotherapy of HIV infection.
Twenty-two patients with locally advanced or metastatic soft tissue sarcomas received high dose chemotherapy with autologous bone marrow graft. Eleven patients receiving melphalan also received fractionated total body irradiation. Six patients (four in CR and two in PR) were intensified after first line therapy. Thirteen patients were grafted after chemosensitive relapse: seven in second CR, one in third CR, one in first PR, three in second PR and one in fourth PR. Three patients with primary refractory disease were intensified. The overall response rate in 66% in nine evaluable patients. The overall median survival and disease-free survival were 19 and 15 months, respectively. The actuarial survival rates at 2 and 5 years were 40% and 32% respectively. There was one treatment-related death due to infection. We conclude that high dose chemotherapy is feasible and provides reasonable response rates in patients with advanced soft tissue sarcomas.
Two patients with previously treated CLL received autologous PBSC transplantation after total body irradiation and high-dose chemotherapy. Before intensification, a partial marrow response had been obtained in both patients, with disappearance of peripheral blood involvement as shown by immunophenotypic assessment using fludarabine. PBSC collection was performed after a single course of high-dose cyclophosphamide followed by GM-CSF administration. One patient failed to reconstitute normal hematopoiesis and died 3 months post-transplant. The other is in continuous complete remission 12 months after intensification. This strategy in young patients with poor prognosis CLL warrants further investigation.
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A 20-yr-old woman with no history of pulmonary disease presented with acute dyspnea and fever. After various investigations and treatments the symptoms persisted and a lung biopsy was performed. Pathologic analysis disclosed the presence of silicotic crystals within lung tissue and mediastinal lymph nodes. The patient admitted having repeatedly inhaled a domestic scouring powder rich in silica during the preceding 6 months. This is the first report of acute pulmonary silicosis developing after exposure to a common household product.
Gangliosides are glycosphingolipids which contain neuraminic acid. Although they are present in the plasma membranes of all cells, gangliosides are expressed differently, both quantitatively and qualitatively, in certain types of cancer. Modifications in ganglioside composition may account for some of the abnormal interactions between these tumor cells and their environment. Furthermore, some of the gangliosides are shed by tumor cells and may modify host immunity, thus contributing to the development of tumors. In cases of melanoma and neuroblastoma, the modifications in ganglioside expression are such that gangliosides may be used both as tumor markers and as targets for immunotherapy.
Distal metastases are classically situated below the knee or elbow. However, metastases of the extremities: wrist and hand, or ankle and foot, have etiological and histological characteristics. We report one case of bone metastasis and one case of soft tissue metastasis. The distal bone metastases are often solitary. Bronchial cancers represent the most frequent cause of distal metastases (20% of all cases). They are responsible for 50% of distal metastases of the upper limb and more often occurs as a squamous cancer. Their localization may sometimes reveal a bronchial cancer, and so allow curative surgery. The metastases of soft tissue are exceptional. In the literature, only 2 cases of soft tissue metastasis of bronchopulmonary cancer are described. Clinically, it is a painful swelling preserving the under lying bone. The prognosis is always one of bronchial metastasis cancer with an average survival of 3-6 months.
Monoclonal antibodies, produced in vitro from hybridoma supernatants, may be administered to cancer patients either directly or after coupling to an anticancer agent (immunoconjugates). Monoclonal antibodies concentrate in tumor site, where they initiate an anti-tumor effect, either by activation of the patient's immune system or by the cytotoxic agent which is present at high concentration within the tumor, while systemic concentrations of this agent remain low. Monoclonal antibodies which are radiolabelled also allow the immunoscintigraphic study of the immunoconjugates' diffusion within the body. Given certain precautions of administration, the clinical and biological tolerance of this type of treatment is satisfactory, most of the side effects correspond to an allergic response to the murine antibodies used. Clinical studies performed in patients with leukemias have demonstrated a significant antitumor effect although this effect is transitory. Studies performed on small series of patients with solid tumors (gastrointestinal neoplasms, melanoma, leptomeningeal localizations, ovarian peritoneal carcinosis) have shown a few cases of major responses and/or complete remissions having lasted up to periods of many months. These studies as well as the perspectives for the development of this type of therapy are presented and discussed.
HTLV-I has recently been shown to be a direct activator of resting human peripheral T cells. In order to determine the susceptibility of T-cell precursors to HTLV-I mitogenic activity we have exposed human thymic T cells to uv-inactivated HTLV-I. Unlike mature T cells, thymocytes were not directly susceptible to HTLV-I-induced activation although agglutination of cells did occur after exposure to HTLV-I alone. However, in the presence of another stimulus, phyto-hemagglutinin or anti-CD3 monoclonal antibodies and accessory cells, thymocytes proliferated when exposed to HTLV-I. Concanavalin A did not induce HTLV-I comitogenic activity. HTLV-I-induced thymocyte proliferation was enhanced by autologous or heterologous accessory cells. This proliferation was shown to be mediated by the interleukin-2/interleukin-2 receptor pathway. Simultaneous stimulation by HTLV-I and nonmitogenic doses of phytohemagglutinin were required both for the production of interleukin-2 and for the expression of the interleukin-2 receptor. These data demonstrated functional differences between peripheral T cells and thymocytes.
Monoclonal antibodies directed against antigens borne by tumors have already been the object of clinical trials in patients with leukemia or solid tumors. These antibodies, generally obtained from murine hybridomask, are used alone or as immunoconjugates, i.e. coupled to a non-specific antimitotic agent. Under the proper conditions they may be administered with a satisfactory clinical and biological tolerance. The antimitotic action of these antibodies, which is specifically directed against neoplastic cells, has been demonstrated in vitro and in animal models and is found inconstantly in leukemias. Studies have been performed in patients bearing solid tumors, with large initial tumoral mass, showing partial regression in a few cases. A number of parameters, including modalities of administration, types of immunoconjugates and mechanisms of action in vivo, must be explored to increase the antineoplastic potential of monoclonal antibodies.