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Biomedical subjects

P Dufour

Publications and source records attributed to P Dufour.

At least 19 recordsLinked to original sources

[Role of interferon in the treatment of renal cancer in adults].

Alpha interferon is effective in the treatment of metastatic renal cell cancer. To obtain a maximal efficacy, alpha interferon should be used at a dose of 10 MU/m2, or 18 MU total dose, given daily or three times a week. At such doses interferon produces flu-like symptoms and severe asthenia and thus should be proposed only to patients who have a good performance status. The response rate is low, in the order of 15-20%, and the median remission duration is short (6-10 months). However a few patients experience very durable remissions, sometimes for more than 5 years. The response rate may possibly be improved to 20% to 35% by combining interferon alpha with antineoplastic agents or to other cytokines, namely interleukin 2. Finally because of its supposed mechanisms of action-direct tumor growth inhibition and enhancement of the host's immune defenses--interferon may be of benefit in the adjuvant setting.

Adult

[Rare opportunistic fungal diseases in patients with organ or bone marrow transplantation].

Candidiasis, aspergillosis and cryptococcosis are the most common fungal infections in transplant recipients. However other fungal infections have been reported. Mucormycosis, Scedosporium infections, fusariosis and trichosporonosis represent the largest part of these rare mycosis. The clinical and mycological features are described here. In addition, cases of very uncommon mycosis, most of them only once reported, have been reviewed. Overall the diagnosis is difficult as mycological examinations are often negative till the disease is disseminated. Amphotericin B remains the reference treatment except in Scedosporium infections which respond more likely to azole antifungal agents. Despite the treatment the outcome is usually fatal.

Bone Marrow Transplantation

[Invasive aspergillosis in immunocompromised patients. An analysis of 57 patients].

Fifty seven cases of invasive aspergillosis have been analyzed. Most patients were severely neutropenic. The main underlying diseases were acute leukemia, malignant lymphoma and bone marrow transplantation. The clinical and radiological manifestations and the mycological data rare presented. A dramatic increase of the annual incidence has been observed since 1986. The main causes appear to be the increase in intensity of chemotherapy regimen for acute leukemia and the progressive colonisation of a part the department. Overall mortality is especially high (74%) but the mortality rate appears to decrease since 1989.

Adult

[Trichosporon capitatum septicemia. Apropos of 5 cases].

Invasive Trichosporon capitatum infections are seldom reported. We present here five cases of septicemia. All patients had an acute myeloblastic leukemia and were severely neutropenic. They have also been treated before the onset of the fungal infection with broad-spectrum antibiotherapy and also with an oral azole antifungal agent. The role of this antifungal therapy in the development of T. capitatum infection is discussed. The prognosis of T. capitatum infections is severe. Eight of the 10 published cases had a fatal outcome and one of our patients died of the fungal infection in spite of the treatment.

Adult

[Cytokines and pregnancy: physiology].

Several biological systems originating in the fetus and in the mother are involved in embryo implantation, maintenance of the pregnancy, protection of the fetus against outside influences and the start of labour (these are the immune system, endocrine system, and the endothelial system). In order to work efficiently there has to be some co-ordination. Cytokines which were first described by immunologists make it possible for information between the systems to be exchanged. The authors, referring to recent publications, show that there are several cytokines with specific receptors at the feto-placental interface. The place and the physiological role of these molecules in co-ordinating the links are discussed. These cytokines can be involved in many pathological situations.

Colony-Stimulating Factors

Etoposide, ifosfamide, and methotrexate combination chemotherapy for aggressive non-Hodgkin's lymphomas after failure of the LNH 84 regimen.

We assessed the efficacy and tolerability of VIM (etoposide/ifosfamide/methotrexate) combination therapy in 24 patients who were failing the treatment protocol of the Lymphomes Non Hodgkiniens (LNH) 84 study. Eight patients were refractory to the LNH 84 induction cycles, but ten achieved a partial response (PR). The six remaining patients attained complete response (CR) after LNH 84 induction, but relapsed either during consolidation therapy or after completing the whole program. Twenty-three patients are evaluable for response. The VIM regimen provided a CR rate of 43% and a PR rate of 17%. Treatment failed in nine cases (39%). The CR rate was particularly high (67%) in the group of patients who had PR with LNH 84 induction treatment. Of the ten who had attained CR, five relapsed after 4 to 42 months and five are still alive with no evidence of disease after 29 to 62 months. VIM therapy was well tolerated. A total of 101 VIM courses were given. Myelotoxicity was the most common side effect. Grade 3 or 4 cytopenia was recorded after 11% of the cycles. Among eight infectious episodes recorded, one was fatal. This study demonstrates that CR and long disease-free survival are obtainable with the VIM regimen in a small number of patients failing a high-dose doxorubicin-containing first-line treatment.

Adult

Hairy cell leukemia and factor VIII inhibitor: a case report.

Acquired factor VIII inhibitors are usually described in hemophilia A, although some cases have been documented in chronic inflammatory diseases and malignant tumors. We report here the first case of a factor VIII inhibitor appearing in the course of hairy cell leukemia. Interferon therapy over a 5 month period led to complete remission of leukemia with parallel disappearance of the acquired factor VIII inhibitor.

Factor VIII

[Turner's syndrome and pregnancy in donor oocytes and in vitro fertilization. Three case reports].

It is extremely rare for pregnancy to occur spontaneously in a woman with a mosaic or non-mosaic karyotype 45 x 0. (Till now only 13 patients with a homogeneous x 0 karyotype have been reported out of 62 patients who between them have had 138 pregnancies). Furthermore these pregnancies have been plagued by a number of important complications or fetal malformations (21% have had chromosome anomalies). It is therefore clear that in vitro fertilization with donor oocytes is a tempting solution for these women. The authors having three personal cases try and point out the conditions under which this technique can be used. It is important to realise that from the age of 10 or 12 years these patients have to have hormone treatment in order to avoid hypoplasia and hypovascularization of the uterus. Those conditions explain why so many these women had premature labours and also suffer from pre-eclampsia. Caesarean section was often found to be necessary because of feto-pelvic disproportion.

Adult

[Immunologic aspects of endometriosis].

Endometriosis is thought to result from implantation of endometrial tissue swept back into the pelvic cavity during menstruation, or from coelomic metaplasia of the peritoneum. Yet not all women with menstrual reflux develop endometriosis. The authors present and analyse the arguments in favour of immune system involvement in the physiopathology of this frequent disease. A knowledge of the antigens that have been recognized and of the operative mechanisms will probably make it possible to understand better the repercussions of endometriosis on fertility, to develop diagnostic methods less traumatic than those available at present and to modulate treatments and improve their effectiveness.

Antibody Formation

Autologous bone marrow transplantation vs intensive chemotherapy in first complete remission: interim results of GOELAM study in AML.

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.

Acute Disease

Phase I study of liposomal MTP-PE-activated autologous monocytes administered intraperitoneally to patients with peritoneal carcinomatosis.

We have conducted a phase I study with autologous monocytes activated ex vivo and administered intraperitoneally in nine patients with peritoneal carcinomatosis. Blood monocytes were collected by leukapheresis and then purified by counterflow elutriation (up to 10(9) cells, with a purity of greater than 90%). Ex vivo activation was obtained by incubating these cells with 1 micrograms liposomal MTP-PE/10(6) monocytes for 18 hours in hydrophobic culture bags at 37 degrees C in 5% carbon dioxide humidified air. The activated monocytes were then infused in the peritoneal cavity once a week for 5 consecutive weeks through an implanted peritoneal infusion system, Port-A-Cath (Pharmacia Deltec, St Paul, MN), on an intrapatient dose-escalating schedule (10(7) to 10(9) monocytes). No severe adverse reactions occurred. Toxicity was mild, the chief acute reactions being fever (27%), chills (13%), and abdominal pain (25%). None of the side effects led to dose reduction. No consistent change in hemostatic function, liver function, or renal function was observed. Significant increases in granulocyte counts, neopterine, and acute phase reactants (fibrinogen, C-reactive protein) occurred in the peripheral blood. In vitro monocyte activation was demonstrated by the relapse of procoagulant activity and monokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-alpha [TNF alpha]) in the supernatants of cultured monocytes. Evidence for in vivo monocyte activation was provided by the increase of these monokines in the peritoneal fluids. Kinetic studies with indium-111 (111In)-labeled activated autologous monocytes in five patients suggest that these infused monocytes may remain in the peritoneal cavity for up to 7 days. This locoregional immunotherapeutic approach seems to be encouraging in view of adjuvant therapeutic modality in ovarian cancer patients with minimal residual intraabdominal disease following second-look laparotomy.

Aged

Cunninghamella bertholletiae: an uncommon agent of opportunistic fungal infection. Case report and review.

Cunninghamella bertholletiae is a fungus of the Zygomycetes class, Mucorales order. Only very few cases of disseminated infection have been reported. We observed a new case in a 19 years old man with severe aplastic anemia, due to pulmonary primoinfection and hematologic dissemination. This aplastic anemia failed to respond first to an antithymocyte globulin and steroid treatment and then to cyclosporine A. Deferoxamine was infused weekly to prevent iron overload. During a second antithymocyte globulin and steroid treatment, the patient developed bilateral pneumonia. Culture of the broncho-alveolar washing fluid established the diagnosis by isolation of C. bertholletiae. Despite amphotericin B and 5-fluorocytosine intravenous therapy, the patient died of disseminated infection six days after diagnosis, which was confirmed by necropsy. Underlying conditions, diagnosis and treatment are discussed, together with a review of the literature.

Adult

High dose melphalan and ABMT with or without abdominal radiotherapy as consolidation treatment for ovarian carcinoma in complete remission or with microscopic residual disease.

We initiated in February 1982 a pilot study of high dose melphalan (HDM) and ABMT as consolidation treatment for ovarian carcinoma. Eleven patients entered into this study; 6 patients received HDM and ABMT (group 1), 5 patients received HDM in combination with flash abdominal radiotherapy followed by ABMT (group 2). Two of 6 group 1 patients and 3 of 5 group 2 patients are still alive with NED more than 3 years after ABMT (58+, 72+, 37+, 39+, 43+) and are hopefully cured. Main toxicity was haematological, we have not observed any death related to therapy. HDM and ABMT compared favorably with other consolidation treatments (abdominopelvic radiotherapy or IP chemotherapy) and merits a larger evaluation.

Abdominal Neoplasms

[Severe fetomaternal anti-Duffy allo-immunization].

The authors report a case of severe post-transfusion anti-Duffy (Fya) allo-immunization which required a treatment of four intrauterine exchange transfusions. The child was born at 32 weeks of amenorrhoea and he benefited from an exchange perfusion at birth. The outcome was fully satisfactory. On the basis of this case, the authors present a review of immuno-haematology concerning the Duffy system. This system holds fourth rank, after the ABO, rhesus and Kell systems, on the clinical importance scale of group systems. It concerns two alleles, Fya and Fyb, located on the first chromosome. The anti-Duffy antibodies are IgG immune antibodies; they may be responsible for haemolytic accidents, sometimes lethal, during transfusions, and they are an occasional cause of haemolytic disease of the newborn. A review of the literature yielded only 25 cases of haemolytic disease of the newborn, thereby showing that this allo-immunization is very rare, and it demonstrated its potential danger. Finally, the authors present the therapeutic methods used to treat the haemolytic disease of the newborn caused by anti-Duffy antibodies. Plasmapheresis and intrauterine exchange perfusion have dramatically improved the prognosis of this disease.

Adult

[Gaucher's disease and pregnancy].

Gaucher's disease is rare in association with pregnancy (we have only found 53 cases of women with this disease who had at least one pregnancy since 1945). A review of literature on this subject and this one case confirms that it is unlikely that the disease will progress as far as the symptomatology is concerned and that there are unlikely to be obstetric or fetal complications. All the same there are certain complications that can occur as the haematological state is concerned (thrombocytopenia, coagulation defects such as bleeding, particularly post-partum from the genital organs). Mechanical difficulties may occur because of the greatly enlarged spleen. Pregnancy is not contra-indicated but it is a high risk pregnancy that has to watched very carefully with ultrasound and great attention to the obstetric and biological condition.

Adult

[Embolization of the foramen ovale in metastatic course of abdominal liposarcoma].

The authors report a case of embolization of the foramen ovale by a liposarcoma metastasis in a young woman of 28 years of age. Cardiac impact due to the progress of this rare tumor type remains unusual. The various clinical situations resulting from secondary cardiac locations are recalled. The diagnostic role of ultrasonography and the information which can be provided by nuclear magnetic resonance imaging in this context are also recalled.

Abdominal Neoplasms

Intraperitoneal mitoxantrone as consolidation treatment for stage III ovarian carcinoma: a pilot study.

In June 1986 we initiated an intra-peritoneal (IP) mitoxantrone chemotherapy trial as consolidation treatment for ovarian carcinoma in CR or PR after induction therapy (surgery + CHAP combination chemotherapy). Thirty-two patients received 25 mg IP mitoxantrone every 3 wk for 6 months. The most frequent side-effects were abdominal pains; haematological toxicity was minimal. The response was assessed by third-look surgery. In group I patients (patients in histological complete remission at second-look surgery) 12 of 14 evaluable patients remained in CR at the time of third look. Ten of the 12 patients are still alive with no evidence of disease (NED) with a median follow-up of 9.7 months after completion of treatment. In group II patients (microscopic residual disease at second-look surgery), 7 of 9 evaluable patients entered in CR at the time of third look; 6 of the 7 are still alive with NED and with a median follow-up of 14.3 months. In 7 group III patients (macroscopic residual disease at the time of second look) no response to IP therapy was observed and all patients progressed. We conclude that IP mitoxantrone is a valuable consolidation treatment for patients in CR or with minimal residual disease; further follow-up is necessary to assess the impact on duration of remission and survival.

Adult