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Biomedical subjects

Y Najean

Publications and source records attributed to Y Najean.

At least 19 recordsLinked to original sources

[Treatment of polycythemia vera with hydroxyurea or pipobroman. Efficacy and toxicity analysed from a protocol of 96 patients under 65 years of age. Le Groupe d'Etude des Polyglobulies].

Between 1980 and 1991, 96 patients with documented polycythemia vera were treated by hydroxyurea or pipobroman, according to a protocol including randomization, and maintenance therapy. Complete remission was induced in all cases. Two cases treated with hydroxy-urea had a very severe granulothrombocytopenia during the initial phase. Maintenance was generally satisfactory on pipobroman, but the platelet count often remained high (400 to 900.10(9)/l) on low-dosage hydroxy-urea, with a risk of vascular events. Progressive resistance to these drugs was observed in 5 cases. Digestive and cutaneous troubles were more frequent on pipobroman maintenance, sometimes enough to legitimate a therapeutic change. It may be concluded that such a treatment is less easy to use and to follow than is currently accepted. In the present series (397/years/patients follow-up, median 5-3 years), only one leukemia and one cancer were observed, which however only demonstrates the absence of any carcinogenic risk at short- but not at long-term.

Digestive System Diseases

[Current data on GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) in acute myeloid leukemia].

GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) activates neutrophil, eosinophil, granular, and macrophage precursors through binding to specific receptors. GM-CSF receptor is a member of the "cytokine receptor superfamily", which displays a particular transmembrane structure. It is expressed in small amounts on normal mature blood or medullary cells, with a high affinity. On acute myeloid leukemia blasts (18 patients), our results agree with the review of the literature: GM-CSF receptors are in small amounts, of two types (high and low affinity), with no relation to the FAB classification of leukemias.

Colony-Stimulating Factors

Histological and urinary reactivity of monoclonal antibody 1BE12 in bladder carcinoma. Purification of the antigen from urine.

We have previously reported the production of monoclonal antibody (MAb) 1BE12, which recognizes a glycoprotein in breast-cancer cells. In the present work, 1BE12 reactivity was tested by immunohistochemistry in bladder carcinoma (92 cases) and in non-tumoral bladder samples (15 cases). In 71% of bladder tumors, more than 30% of cells were intensely stained by 1BE12. The percentage of reactive cells was higher in cancers invading the muscle than in more superficial tumors (p = 0.039). In non-tumoral bladder, immuno-staining, when present, was usually confined to the superficial layers with a low number of cells stained (less than 30%) in 13/15 cases. Slot blots, performed on urine samples from 43 bladder-cancer patients and 21 healthy controls, were quantified by densitometry scanning. We found higher optical density (OD) values in urine from muscle-invasive-cancer patients than in urine from more superficial tumors and healthy controls, with a significantly different distribution (p = 0.005). The urinary antigen was detected by immunoblotting with 1BE12 as high-molecular-weight species (greater than 150 kDa). The reactive glycoprotein could thus be purified by immunoaffinity and FPLC filtration from the perchloric-acid-soluble fraction of urine from patients with invasive bladder carcinoma. The availability of purified antigen will allow us to quantitate our assay, in order to evaluate its potential use as a prognostic indicator in bladder-cancer patients.

Antibodies, Monoclonal

The site of platelet destruction in thrombocytopenic purpura as a predictive index of the efficacy of splenectomy.

The significance of the site of platelet sequestration in determining the indication for splenectomy in idiopathic thrombocytopenic purpura (ITP) is a controversial subject. However, most of the negative conclusions are based on 51chromium labelling of homologous platelets. We report here the results of an analysis of 222 cases in which the kinetic study of 111indium-oxinate-labelled autologous platelets was performed under homogeneous technical conditions. 103 of these patients subsequently underwent splenectomy. This study demonstrates that the site of platelet sequestration in active ITP constitutes a variable independent of the patient's age, history of the disease and its severity (platelet count, lifespan). The sequestration site is a good predictive element of the short-term efficacy of splenectomy (71/76 cases with splenic sequestration obtained a platelet count exceeding 100 x 10(9)/l versus 7/13 cases with mixed sequestration and 1/14 cases with hepatic sequestration), and the long-term results (6 months to 5 years after splenectomy) do confirm the clinical value of this study.

Adolescent

[Splenectomy for chronic thrombocytopenic purpura].

During the period 1985-1989, 49 patients underwent splenectomy for chronic idiopathic thrombocytopenic purpura in our department. A correct follow-up was available for 39 patients. All patients had been previously treated with corticosteroids. We evaluated the platelet count one year after the operation and the relation between this count and several preoperative and postoperative factors. We observed a favourable prognosis when the preoperative study of platelet sequestration showed splenic destruction, when the duration of symptoms was less than one year and when there was a rapid increase in the platelet count during the first week after the operation.

Adrenal Cortex Hormones

The sequestration of 111-In-labelled autologous platelets and the efficiency of splenectomy.

The main information is the excellent correlation between the site of sequestration of autologous platelets (the use of 111-indium allows autologous labelling even in case of severe thrombocytopenia) and the efficiency of splenectomy. From 76 cases with splenic sequestration studied 2 to 10 weeks after splenectomy, an excellent increase of the platelet count (higher than 300 10(9)/l) was observed in 65 cases, a moderate increase (100-300) in 6, a failure in 5. In contrast, in the 16 cases with hepatic sequestration, only one success did occur, and failure (platelet count lower than 100) occurred 15 times. Beyond the 6th month, in spite of some relapses, the prediction remains excellent. From the 67 evaluated cases with initial splenic sequestration, 58 have a platelet count higher than 100 10(9)/l. From the 14 cases with hepatic sequestration, 13 have, at long term, less than 100 10(9)/l platelets.

Blood Platelets

Stimulatory effect of thyroid hormone on RA-induced granulocytic differentiation in leukemic cells.

Retinoic acid, vitamin D3, and dexamethasone are known inducers of myeloid leukemic cell differentiation. Recent evidence indicates that these drugs mediate their biological effects through binding to a nuclear receptor which belongs to the steroid/thyroid hormone receptor superfamily. This paper shows that the ligands of the other receptors of this family, estrogens, progesterone, androgens and thyroid hormone, do not induce leukemic cell differentiation. However, thyroid hormone potentiates, by one order of magnitude, the dose-response effect of retinoic acid in HL-60 cells.

Cell Differentiation

Association of renal carcinoma and polycythemia vera: 5 cases in which nephrectomy preceded and did not influence the clinical course of the polycythemia.

In a series of 300 cases of PV evaluated and treated over the last 12 years, 5 cases had a kidney carcinoma, either previously treated (2 cases) or discovered at the same time as the PV (3 cases). In all these cases, the blood disease had the criteria of a myeloproliferative syndrome (abnormality of three cell-lines), was not influenced by nephrectomy and evolved in the long term like a primary PV. No kidney cancer was observed during follow-up of the other 32P treated PV patients. There appears to be an abnormal association between PV and kidney cancer which needs confirmation in larger series and would justify a prospective evaluation.

Adenocarcinoma

Chronic myelocytic leukaemia with unusual (27 years) complete remission terminating in acute undifferentiated leukaemia: a clinical and karyotypic study.

A case of clinically typical CML (300 x 10(6)/l leukocytes, 400 x 10(6)/l platelets, splenomegaly) is presented. After complete remission induced by busulphan, no clinical or haematological abnormalities were observed for 27 years until the development of acute leukaemia (type M1), which was rapidly fatal after a brief chemotherapy-induced remission. The cytogenetic findings were also original: no chromosome Ph1 (during remission 3 years after the onset of the disease), no translocation (banding study 5 years later), and no bcr/abl rearrangement (during the terminal phase).

Busulfan

Long-term (5 to 20 years) Evolution of nongrafted aplastic anemias. The Cooperative Group for the Study of Aplastic and Refractory Anemias.

In the presence of aplastic anemia (AA), therapeutic choices should be determined while taking into account not only changes for immediate improvement, but also both the risks for late-occurring complications and the following quality of life. We report here data concerning a long-term clinical survey (5 to 18 years with a median of 12 years) including 156 nongrafted patients receiving androgen therapy; all patients were alive more than 5 years after diagnosis (40% of patients included at time of diagnosis in our multicentric analysis). Between the 5th and the 13th year follow-up, 21 patients died of various causes either related to AA or to its treatment: 12 of infection or hemorrhage secondary to pancytopenia (6 relapses and 6 that had never been improved; 2 with paroxysmal nocturnal hemoglobinuria [PNH]); 5 of leukemia; 1 of a non-Hodgkin's lymphoma; 2 of late side effects following transfusion (1 acquired immunodeficiency syndrome and 1 chronic B hepatitis); and a single case of myocardial infarction (the latter could possibly result of androgen therapy). Thirteen patients in total developed PNH (among which 10 had clinical symptoms including 2 deaths, and 3 exhibited only biologic abnormalities). Few long-term side effects of androgens could be noticed. Adult height was normal in patients treated during childhood and so was young women's fertility. No malignant hepatoma occurred. This survey allows the recording of late spontaneous hematologic improvement (between 5 and 10 years of evolution). This occurred in 50% of patients that had remained cytopenic 5 years after diagnosis. Although bone marrow stem cell concentration remained abnormal after 10 years of evolution. 85% of patients had a normal red blood cell count, 80% a normal polymorphonuclear count, and 66% a normal platelet count. All patients who did not show late complications had an excellent quality of life.

Adolescent

[Screening for cancer of the prostate using prostate-specific antigen].

Systematic screening for prostate cancer was carried out in 600 men over 50 years of age by the industrial medicine departments of four big companies in the Paris region. The exploratory methods included prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) assays, rectal palpation and two-dimensional transrectal ultrasonography. Biopsy of the prostate was performed either when the PSA level was above 5 ng/ml or when rectal palpation gave suspicious results, or when ultrasonography showed abnormal images. A total of 93 biopsies were performed, and 18 cases of cancer were detected. Eleven of these 18 patients underwent radical prostatectomy. The PSA assay, with an accepted limit of 5 ng/ml, detected 17 out of 18 cancers but was not very specific. The PAP assay had low sensitivity (only 5 positive results). Combined PAP assay and rectal palpation provided high sensitivity and good specificity. Transrectal ultrasonography was helpful only to determine the site of biopsy and the distribution of the lesions.

Acid Phosphatase

Genetic thrombocytopenia with autosomal dominant transmission: a review of 54 cases.

On the basis of a retrospective study of 3600 platelet kinetic studies, we have isolated 54 cases with chronic thrombocytopenia, a normal autologous and homologous platelet lifespan, and increased mean platelet volume without Döhle bodies, the absence of any functional platelet abnormalities, and a normal megakaryocyte count. These cases were either discovered during the first few years of life (i.e. constitutional) and/or were proven to be familial (autosomal dominant transmission). Previous treatments (corticosteroids, immunoglobulins, androgens, immunosuppressor agents, splenectomy) were not effective in any of these cases or in their relatives. A new syndrome can therefore be proposed which can easily be suspected on the basis of platelet kinetic studies performed in cases of early onset, increased platelet volume, failure of corticosteroids or evidence of a familial blood disorder. It can be proved when the autologous platelet life span is demonstrated to be normal in spite of a chronic thrombocytopenia and a normal megakaryocytic count. The recognition of this syndrome will avoid neonatal complications (cephal-haematomas), surgical complications, and the use of expensive and possibly harmful ineffective treatments, both in the propositus and in other abnormal family members. The syndrome is certainly frequent (54 cases are presented here), but the diagnosis is often missed or delayed due to the low risk of haemorrhage. However, it is associated with a certain risk of leukaemia (four cases in three families).

Adolescent

Clinical significance of serum pro-collagen III in chronic myeloproliferative disorders.

Pro-collagen III (PC III) has been proposed as a useful value for diagnosis and follow-up of myeloproliferative disorders. A significant difference is observed between polycythaemia vera (PV) and essential thrombocythaemias (ET) on one hand, and the pure erythrocytoses (PE) on the other hand, but a large overlap makes this test of low diagnostic value. High values are observed in primary and post-PV myelofibrosis, but excessive PC III levels in active PV are not predictive of evolution toward myelofibrosis. PC III level is lower in myelo-suppressed patients (32P, or hydroxy-urea) than in active cases or in patients treated by phlebotomies. We conclude that PC III measurement is of low diagnostic value for discriminating PV and PE, does not appear to allow short-term prediction of evolution to myelofibrosis, but may be useful to evaluate the role of treatment in delaying progression of PV toward myelofibrosis.

Aged

Partial splenectomy in homozygous beta thalassaemia.

Partial splenectomy was performed on 30 patients with homozygous beta thalassaemia to reduce blood requirements and to avoid the risk of overwhelming postsplenectomy infections; 24 patients had thalassaemia major and six thalassaemia intermedia. Five patients received a high transfusion regimen before and after surgery and 25 a lower one. Follow up after surgery ranged from one to four years. Partial splenectomy improved the long term haematological state in the six patients with thalassaemia intermedia. Recurrence of hypersplenism occurred in nine of the 24 patients with thalassaemia major, however, and complete splenectomy was required. Serum IgM concentrations were not significantly modified by surgery. The mean (SD) residual spleen after surgery was 4.45 (2.36) cm measured by scintigraphy. No severe infections occurred after surgery; however, most patients were routinely treated with phenoxymethylpenicillin and the protective effect of the remaining spleen could not be exactly determined. Because of the possibility of recurrence of hypersplenism, routine partial splenectomy when splenectomy is needed in thalassaemia major is not advised, except in children under 5 years whose risk of overwhelming postsplenectomy infection is greatest.

Adolescent

Radioimmunoassay of erythropoietin: analytical performance and clinical use in hematology.

We report here the performance of a recently commercialized radioimmunoassay kit for determining erythropoietin (EPO) in serum or plasma. The lower detection limit of the method was 3 U/L. Precision, analyzed by the variation coefficients between different assay runs and in the same experiment, was always less than 10%; accuracy was assessed by recovery and dilution tests. In anemic patients (hematocrit 18-39%), the concentration of EPO was logarithmically related to hematocrit. A relatively large dispersion of the results was noted, as reported by others with various RIAs. Patients with severe renal failure demonstrated a very low EPO value, whatever the degree of their anemia. In some chronic anemias resulting from malignancy, EPO concentrations were also relatively low. In the polycythemia vera group, the EPO mean was below normal for greater than 95% of the patients, whatever their clinical stage (first evaluation, relapse, or remission). In contrast, 91% of the patients with pure erythrocytosis had a normal or increased EPO value, even when the etiology was unknown. Measurement of EPO concentration may be useful for the clinical differentiation of myeloproliferative disorders and, subsequently, for their prognosis and choice of treatment.

Erythropoietin