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Biomedical subjects

J M Delage

Publications and source records attributed to J M Delage.

At least 19 recordsLinked to original sources

Erythrocyte mean corpuscular volume during cytotoxic therapy and the risk of secondary leukemia.

Erythrocyte mean corpuscular volume (MCV) evolution during cytotoxic therapy of Hodgkin's disease, lymphoma, multiple myeloma, ovarian cancer, and breast cancer was studied. The fastest and the highest MCV increases were observed in the diseases and with the therapies the most frequently involved in secondary leukemia: Hodgkin's disease treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone), and multiple myeloma and ovarian cancer treated with melphalan. On the contrary, with cytotoxic regimens not linked to a high frequency of secondary leukemia such as CMF (cyclophosphamide, methotrexate, 5-fluorouracil) used in ovarian or breast cancer, MCV increase was moderate. As the MCV increase reflects the bone marrow reaction to cytotoxic therapy, an unusually high increase could indicate bone marrow damages which could lead to secondary leukemia.

Antineoplastic Combined Chemotherapy Protocols

[Changes in the mean corpuscular volume during the cytotoxic treatment of cancer and risk of secondary leukemia. Preliminary results].

Changes in mean corpuscular volume (MCV) were studied in cancer patients. Vitamin B12 or erythrocyte folate deficiencies were observed in only 9% of macrocytic patients (MCV greater than or equal to 100 fl). Bone marrow study in seven macrocytic patients with normal hemograms and normal levels of vitamin B12 and folic acid, on per os daily cyclophosphamide single agent therapy, showed myelodysplastic features. The highest MCV and MCV increases during therapy among 203 patients were observed in those cancers and cytotoxic therapies most commonly followed by secondary leukemia: Hodgkin's disease treated with MOPP and radiotherapy, and multiple myeloma and ovarian cancer treated with Melphalan. 21 patients who developed secondary leukemia had a higher MCV and a greater MCV increment than the control patients. Differences were significant in Hodgkin's disease. This preliminary report strongly supports monitoring MCV changes during cytotoxic therapy to attempt identification of patients at high risk of secondary leukemia.

Adult

An enzyme-linked immunosorbent assay for the detection of complement components on red blood cells.

A new technic using the principle of enzyme-linked immunoassay (ELISA) has been developed for the detection of complement components on red blood cells sensitized in vivo or in vitro. Using a double-antibody technic, anticomplement antisera (anti-C3c or anti-C3c/C3d) produced in rabbits was incubated with the red blood cells, followed by incubation with antirabbit alkaline phosphatase conjugated antiglobulin. The amount of the enzyme fixed was measured spectrophotometrically by the enzymatic hydrolysis of the substrate PNPP. A calibration curve was made from red blood cells on which complement was deposited by the method of Fruitstone . The technic showed a greater sensitivity than the standard antiglobulin tests and allowed simultaneous qualitative and semiquantitative estimates. The technic can be performed in any laboratory equipped with the standard equipment found in a blood bank, including a spectrophotometer. The authors made a modification of Alsever 's solution, which allowed the safe and stable preservation of complement coated red blood cells for 15 days. Significant positive results were obtained clinically using this technic, while negative or weakly positive reactions were obtained by the conventional antiglobulin tests.

Animals

Study of erythrocyte mean corpuscular volume during cytotoxic therapy as a predictive parameter of the risk of secondary leukemia in Hodgkin's disease.

Erythrocyte mean corpuscular volume (MCV) evolution was studied during cytotoxic therapy in 12 patients with Hodgkin's disease who developed secondary acute leukemia and in 83 patients with Hodgkin's disease without secondary leukemia as control group. Significant differences were observed in the maximum MCV and in the MCV maximum increase during therapy between the two groups of patients. These differences remained significant between the patients treated with chemotherapy alone and those treated with chemotherapy and radiotherapy. MCV maximum increase greater than 23.9 fl was observed in all patients with secondary leukemia and in only 20% of those without secondary leukemia; it was reached 46.3 months before the first sign of preleukemia. Its value in predicting the leukemic risk in Hodgkin's disease is discussed.

Antineoplastic Agents

Erythrocyte populations in pyruvate kinase deficiency anaemia following splenectomy. I. Cell morphology.

Light and scanning electron microscopic examination of fresh erythrocytes from the blood of four patients splenectomized for severe pyruvate kinase (PK) deficiency haemolytic anaemia has revealed three morphologically different cell populations. Most striking in these patients was the presence of crenated red cells (30-50% of total) which fit current criteria for definition as echinocytes, but also with unusual surface retraction compatible with the existence of intracellular shrinkage, a phenomenon known to occur after incubation of PK deficient red cells in vitro. Additional cell types include immature reticulocytes (7-8% of total) and thin macrocytic discocytes (45-65% of total) none of which are considered specific for the disease. These morphological findings are in sharp contrast with the paucity of red cell shape abnormalities usually described in PK deficient patients before splenectomy and may provide insight into the mechanisms leading to accelerated erythrocyte destruction in this disease.

Adolescent

[Fibrinogen Quebec I and Quebec II: two new families of dysfibrinogenemia (author's transl)].

Two new families of congenital dysfibrinogenemia originating from French Canada are reported. The dysfibrinogenemia in the first family is characterized by an abnormal aggregation of the fibrin monomers; the defect in the second family is due to a faulty release of fibrinopeptides during the proteolytic phase of the thrombin-fibrinogen reaction.

Blood Coagulation Disorders

P-aminosalicylate metabolism in cancer patients sensitive and resistant to chemotherapy.

A reduced response of a tumour to chemotherapy may be due to the host's drug metabolism. To test this hypothesis, we measured the metabolism of a model drug, para-aminosalicylate (PAS). Volunteers and cancer patients ingested a single oral dose (2 g) of PAS and we measured the plasma disappearance curve of the drug and its metabolite. In 7 patients suffering from lymphosarcoma, acute or chronic leukaemia and resistant to cancer chemotherapy, we observed low plasma PAS concentrations, an increase in PAS acetylation and an increased number (and a higher frequency) of abnormal liver-function tests. In 14 patients with malignant blood disease, yet responding well to chemotherapy, the metabolism of PAS is similar to that of healthy controls of the same age and sex. The plasma half-life of PAS is similar in sensitive and resistant patients, but slightly longer than in volunteers. Finally, in urine collected 120 min after drug administration, we observed the same results as in plasma. In conclusion, cancer patients resistant to chemotherapy do not metabolize the model drug PAS as volunteers or sensitive patients do, and this might be relevant to the terminal stage of the disease.

Acute Disease

The enhancement of the haemolytic activity of the first component of complement by trasylol.

Trasylol, a basic polypeptide extracted from bovine lung considerably enhances the complement activity of whole serum. The complement component influenced by Trasylol is C1, either in its activated form (C1) or in its precursor form (C1). An effect on the binding of C1 to the immunoglobulin molecule has been excluded and on becoming part of a cellular intermediate C1 has been shown to be insensitive to Trasylol. It seems that Trasylol modulates C1 in such a way as to render it more efficient haemolytically. An attempt has been made to explain these results by consideration of the relationship existing between complement and other biological systems, such as the fibrinolytic and kallikrein-kinin systems.

Aprotinin