Biomedical subjects
Publications and source records attributed to B Pignon.
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In November 1987, the French group GOELAM initiated a randomized study comparing allogeneic bone marrow transplantation (BMT), autologous bone marrow transplantation (ABMT) and intensive consolidation chemotherapy (ICC). The induction treatment was randomized between Idarubicin plus Cytarabine and Zorubicine plus Cytarabine: 223 patients with de novo AML and aged 15-50 years are currently evaluable and 178 of them (80%) have achieved complete remission (CR) with no significant difference between both arms. Forty four patients under 40 years of age and having a HLA identical sibling were assigned to BMT and 38 were actually transplanted. Thirty of the 134 other patients did not receive the planned first course of ICC, 4 patients died during this course, and 21 were excluded before randomisation. Thus, only 64 patients have currently been randomized between the 2nd course of ICC (34 patients) and ABMT (30 patients). ABMT was prepared by the Baltimore regimen and the marrow was unpurged. With a median follow-up time of 29 months, the actuarial risk of relapse at 3 years is 29% for BMT, 38% for ABMT and 53% for ICC. The 3 year disease free survival (DFS) is 51% for BMT, 62% for ABMT and 47% for ICC. These differences are not statistically significant. When intention to treat is considered, there is no difference in the actuarial DFS between the BMT and the non BMT groups. Longer follow-up time and larger number of patients are warranted to demonstrate any significant advantage of one of these approaches.
Several groups have evaluated detection of antibodies against Candida, with somewhat conflicting results. In this study, co-counterimmunoelectrodiffusion was used to detect antimannan antibodies specific of components of the Candida membrane. Study patients were divided into two groups according to whether their history for Candida infection was negative (population A, n = 102) or positive (population B). Different antigen levels were used in order to differentiate low and high antimannan antibody levels. Among the 102 sera in population A, 42 were positive for antimannan antibodies; the antimannan antibody titer was low in 40 cases and high in 2 cases. In population B (53 patients), antimannan antibodies were found in 97 of the 98 sera studied; titers were high in 95 cases. Use of an antigen level that detects only high titers of antimannan antibodies thus provides a sensitive and specific tool for the diagnosis of deep candidiasis. The simplicity and rapidity of this test are particularly valuable in situations where emergency treatment is needed.
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired, intrinsic haemolytic anaemia believed to occur with an incidence of 1.5 per million in France. The disease is characterised by acute and chronic intravenous haemolysis and pancytopenia, without leukocytopenia. Pregnancy is rare and a high incidence of spontaneous abortion has been reported. The case reported here describes the successful outcome of a pregnancy where PNH was diagnosed. A 25 year old primigravida was admitted for evaluation of pancytopenia discovered in the 32nd week of an hypertensive pregnancy. On admittance R.B.C. were 1.67 x 10(12)/1, W.B.C. 3.4 x 10(9)/1 and platelets 12 x 10(9)/1; Hb was 6.8 g/dl and MGV 126 mu 3. Initial arterial pressure was 160/90 mm/Hg, with oedema and proteinuria 0.7 g per day. Obstetrical parameters were good and physical examination revealed to spontaneous haemorrhage, no jaundice, no dark urine, no organomegaly, no consumptive coagulopathy (C.C.) and no biological liver abnormalities. The patient received saline-washed packed red cells and fresh platelets. R.B.C. increased to 2.5 x 10(12)/1 and remained stable and platelets decreased to 5 x 10(9)/1 with increased arterial pressure and proteinuria, and appearance of C.C. A Caesarean section was performed, under general anaesthesia, and a male healthy baby weighing 2750 g was delivered. The post operative course was uneventful, except for a parietal haematoma which needed surgical evacuation. Because of the low platelet count, no heparin was given and the patient had no thrombosis and no infection.(ABSTRACT TRUNCATED AT 250 WORDS)
A prospective study was carried out in 44 patients treated by intensive chemotherapy inducing a prolonged neutropenia (granulocytes less than 0.5.10(9)/l). All the patients were isolated in protected rooms, received a pathogen-free diet and nonabsorbable oral antibiotics. After double-blind randomization, 22 patients received 2 g of Ceftriaxone (Cef) in a daily infusion beginning on the first day of chemotherapy; and 22 patients received 2 g of placebo (P) under the same conditions. Prophylaxis was continued until the neutropenia resolved (granulocytes greater than 0.5.10(9)/l) or until the onset of infectious symptoms. 19 patients in each group developed febrile episodes, occurring significantly later in the Cef group (16.6 days versus 10.6 days in the P group). No Cef-resistant organism was isolated. Finally, the time at which apyrexia was obtained after the beginning of curative antibiotherapy was the same in both groups. The routine intravenous administration of Cef in combination with nonabsorbable antibiotics is a useful approach in reducing the risk of infection in the neutropenic host.
Four cytogenetic studies were performed in the course of a paroxysmal nocturnal hemoglobinuria evolving into acute megakaryoblastic leukemia. The clonal evolution was characterized by a unique structural change (9p) at the time of diagnosis, heralding an accelerated and complex karyotypic alteration including 5q-, 12p-, +21, -5, -7. At the terminal phase, the initial population was replaced within 1 week by a new overgrowing clone with -5, +8, +17. This suggests that the paroxysmal nocturnal hemoglobinuria-associated preleukemia and leukemic states share with acute nonlymphocytic leukemia the same nonrandom chromosomal changes.
A case of malignant histiocytosis was studied by cytology, cytochemistry, electron microscopy, and cytogenetics. It was shown that the malignant cells expressed a fully differentiated histiocytic pattern with high macrophagic activity. This correlated with the presence of polyploid metaphases. The significance of polyploid cells in the definition of malignant histiocytosis is discussed.
Thirty-three leukaemic patients in CR were treated by high-dose therapy followed by ABMT: 18 of them had acute non-lymphoblastic leukaemia (ANLL) in first remission (CR1) with a mean age of 23.7 years (3-44). All but one of them were conditioned with a polychemotherapy regimen including 6-thioguanine, Ara-C, CCNU, and cyclophosphamide. The marrow cells were purged by chemical means in 16 cases. Five transplant-related deaths were observed: three cardiac failures, one interstitial pneumonitis and one aspergillus pneumonia. At the time of analysis (October 1984), four patients had relapsed and eight were still in unmaintained CR1 (44+, 46+, 30+, and five between 2.5+ and 8+ months post transplant). Fifteen patients had acute lymphoblastic leukaemia: four were autografted in CR1 and 11 children were grafted in CR2; the conditioning regimen was fractionated total body irradiation followed by cyclophosphamide for all but one patient who was conditioned with BACT (Burkitt leukaemia); the marrow was purged by a chemical agent in 11 patients and by monoclonal antibodies and C' in four: four out of 15 patients relapsed (two grafted in CR1 and two grafted in CR2); 10 patients are still in unmaintained CR: two adults grafted in CR1 (26+; 12+ months) and eight children with a mean follow-up of 13.4 months post graft (2 + -45+ months). The clinical study leads to the following conclusions: in adult patients the marrow should be harvested during CR1 and at the time of minimal residual disease. The quality of previous chemotherapy and conditioning regimen prior to ABMT play a prominent role in the in vivo eradication of the leukaemic cells. The real impact of marrow purging is still unknown and a larger series of homogeneous patients, conditioned with the same protocols and the same transplant timing, is required before any conclusions can be drawn.
The anti-leukaemic effect of low-dose cytosine arabinoside was assessed in 36 patients; 15 patients presented with an acute myeloblastic leukaemia and were treated in first induction because of age or preexisting disease and clinical and biological stabilization was obtained in 7 cases, with a mean duration of 8.7 months. In 4 relapsed patients 2 complete remissions were obtained, 1 of which after several courses of cytosine arabinoside. In all cases an important haematopoietic and extra-haematopoietic toxicity was noticed. In 15 patients treated for a myelodysplastic syndrome terminating in acute myeloblastic leukaemia stabilization was obtained in 8 cases, but final conclusions were difficult. The cytotoxic effect of cytosine arabinoside even at low dosage remains important. The optimal modalities in the administration, and the actual advantages of this treatment compared with conventional chemotherapy have still to be defined.
The recognition of the postoperative thrombopenia is important because thrombopenia give an hemorrhage risk and modify the tolerance to preventive anticoagulant treatments. Some thrombopenias can be iatrogenic: thrombopenias by transfusion of a large volume of preserved blood, or by hemodilution, but require a substitution, therapy are easily diagnosed. Post-transfusional thrombopenias require an antibody analysis (especially for antiPLA1). The search for drugs interactions is often complex; heparin induced thrombopenia constitutes a severe but fortunately a rare complication of the heparin therapy. Other thrombopenias are related to operative complications this is the case of consumption-coagulopathies due to infections, the release of thromboplastin from tissues, hepatic cirrhosis, pancreatitis, etc. The evaluation of hemostasis verifies clinical hypotheses and guides the treatment. Thrombopenias can be due to various disorders revealed or occurring during an operation. Although the concurrences are rare, they do not always preclude the possibility of finding a collagen disease (connectivitis), a thrombocytogenetic thrombotic purpura, and especially an idiopathic thrombopenic purpura. In any case, diagnosis is easier if the preoperative platelet levels are known. Thus, platelet counts should be included in pre and postoperative evaluations.
We have studied some rheological parameters in different clinical status by using two coaxial viscometers. The Contraves Low Shear sinus 30 allows available shear rates range from gamma (128s-1 to 0,0175 s-1), and the parameters studied were viscoelastiticy, thixotropy and blood viscosity. The Ecktacytometer+ is another method for measuring cell deformation in couette flow. The aim of our study was to compare these two technics, to consider their clinical interest and finally to visualize an eventual correlation.
We report ten cases of acute myeloid leukemia treated by intensive therapy followed by autologous bone marrow transplantation. Seven patients were in first relapse, and three were in complete remission. The conditioning regimen consisted of either chemotherapy alone (6-thioguanine, cytarabine, lomustine, and cyclophosphamide [TACC; eight patients]) or cyclophosphamide and total-body irradiation (two patients). All the patients in first relapse achieved complete remission (CR). The median remission duration was 9.9 months (range, 5-14), and the median survival was 14.4 months (range, 9-23.8). Of the three patients autografted during CR, one relapsed at Month 5 and two others remain in CR and are well at 18+ and 18.3+ months. High-dose chemotherapy followed by autologous bone marrow transplantation seems to be a valuable treatment for acute myeloid leukemia, if it is used immediately after the CR to consolidate the remission.
This study was designed to investigate the rheological and plasmatic parameters from multiple transfused patients and patients undergoing surgery non transfused. Blood filtrability compared with the erythrocyte electrophoretic mobility shows the perturbance resulting from the delay of conservation and the importance of the transfused blood. The 2-3 DPG, ATP and oxygen-hemoglobin affinity suggest the excellent recuperation of the erythrocyte metabolic function in vitro. The rheological parameters seems to be a good mean in the supervision of red massive transfusion blood cell.
The accumulation of doxorubicin (DOX) in white blood cells of treated patients has been studied by quantitative microspectrofluorometry. From blood samples of treated patients, leucocyte subpopulations were separated by the gradient method. Emission fluorescence spectra from a microvolume of a single living cell nucleus were analysed in terms of spectral shape and fluorescence yield between free and DNA-bound doxorubicin. With this non-destructive analysis technique, intranuclear doxorubicin concentrations were determined within +/- 10%. Doxorubicin concentrations were measured in patients treated with bolus injection. After an accumulation of DOX in leucocytes during the first 30 min, intranuclear doxorubicin concentration did not vary significantly for 24 h, whereas its concentration in plasma decreased. Despite large differences between patients, monocytes accumulated significantly more doxorubicin than granulocytes or lymphocytes did.
An improved knowledge of the initial prognostic factors of multiple myeloma and regular monitoring of the disease should result in the choice of the most effective treatment. The conventional prognostic factors have been divided into three stages by Durie and Salmon. These stages are based on the proportion and type of the monoclonal component, on haemoglobin, calcium and creatinine blood levels and on the extent of bone lesions. However, this widely used classification has certain disadvantages: the size of the tumoral mass is evaluated mainly from the proportion of monoclonal gammopathy, the bone lesions are difficult to determine and the kinetics of cell proliferation are not taken into account. Parameters with high prognostic value have recently been demonstrated; they include beta 2-microglobulin, LDH, interleukin-6, C-reactive protein, serum albumin and kinetic of cell proliferation. When associated, these data allow to establish prognostic staying that are at least as relevant as those of the Durie-Salmon's classification. Monitoring of patients with multiple myeloma by means of a time-related curve of either the tumoral mass or the amount of monoclonal gammopathy leads to the best possible treatment.
The proposed serological diagnosis of systemic Candida infections is based on a microplate immunocapture technique detecting IgM, IgA and IgE anti-Candida antibodies. Activity is revealed with a suspension of human erythrocytes sensitized with somatic antigen of Candida albicans, and is quantified on an automated plate reader. The sera were obtained from patients with deep-seated (n = 56) and superficial (n = 193) candidosis. We compared this immunological method with a combination of indirect immunofluorescence and co-immunoelectrodiffusion. The immunocapture method was more sensitive (80.4% vs. 48.2% with indirect immunofluorescence and 58.9% with co-immunoelectrodiffusion), and often provided the diagnosis at an earlier stage, with clear therapeutic advantages. The IgA isotype was a particularly valuable marker of deep-seated Candida infections.
Enzyme-linked immunofiltration assay technique (Elisa) has been applied to the characterization of G, M, A and E anti-Candida antibodies isotypes specific to cell wall mannans in 201 sera from 126 patients. These sera were studied at the same time using Co-immunoelectrodiffusion and indirect immunofluorescence. In 18 of 21 patients with systemic candidiasis, Elisa demonstrated the presence of antimannan IgG antibodies in sera contemporary of Candida positive blood culture. These IgG were associated with antimannan IgM, A and E in 15 patients. In 37 patients colonized with Candida, used as negative controls, antimannan IgG were detected in 3 cases, and in 2 were associated with specific IgMs. The sensitivity and specificity of Elisa IgM and IgA in the diagnosis of systemic Candidiasis were 85.7% and 81%, respectively. The kinetic study shows that the different isotypes appeared most of the time simultaneously. The evolution of the 4 isotypes beyond the acute episode was variable and without correlation with the clinical status. The decrease of IgG was slower than the one of IgM, IgA or IgE. The systematic research, in at risk patients, of antimannan antibodies using Elisa required simple technology. A simple method should allow to aim at other functional antigens which could be used in a quantitative manner to determine the efficacy of the medical treatment.