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Biomedical subjects

Y Najean

Publications and source records attributed to Y Najean.

At least 37 records · Page 2Linked to original sources
PubMed1995

Hereditary thrombocytopenias in childhood.

Thrombocytopenia is generally known in its most severe form as acquired immunologic disease. However, in some cases thrombocytopenia is constitutional and may or may not be associated with thrombocytopathy. This review focuses on the clinical and biologic diagnostic criteria of genetic thrombocytopenia, with specific emphasis on the clinical value of the platelet life span and wishes to reiterate the necessity of their identification, as an excessively rapid diagnosis of ITP may be a source of treatment failure. As an example of constitutional thrombocytopenia, we report here 83 familial cases with pure genetic macrothrombocytopenia. They are characterized by the absence of significant bleeding disorders, stable thrombocyte counts higher than 50 x 10(9)/l, platelet macrocytosis, normal platelet function, normal or never increased presence of megakaryocytes, and rarely positive immunological abnormalities. In all cases, platelet life span clearly indicated a defect of production with destruction linked to the ageing population (more than 7 days) and no abnormal sequestration in the spleen or liver. Thus, apart from thrombocytopenia with thrombocytopathy, kinetic studies are necessary in thrombocytopenias whenever clinical parameters do not suggest the presence of excessive platelet destruction.

Blood Platelets↗
PubMed1995

Interpretation of measured red cell mass and plasma volume in adults: Expert Panel on Radionuclides of the International Council for Standardization in Haematology.

Four European centres provided height and weight data on 202 males and 204 females undergoing red cell mass (RCM) and plasma volume (PV) measurements. For these populations, the RCM and PV predictions by the various published methods were compared. It was shown clearly that predictions based solely on body weight were inappropriate, particularly because approximately half of the male and female populations could be regarded as overweight or obese. Although there was reasonable agreement in the prediction values given by the formulae based on both height and weight, it was not possible to establish which formulae could be recommended. For that reason, the published literature containing normal RCM and PV measurements were re-examined. RCM data for 283 males and 171 females and PV data for 100 males and 67 females were included. Measurements were standardized for variables such as trapped plasma in the PCV, exclusion of buffy coat in the PCV and calculation of PV at zero time. As a result of this analysis, prediction formulae based on surface area for RCM and PV with 98/99% reference ranges have been established.

Adult↗
PubMed1994

Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells.

Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AMLs) characterized by the presence of the t(15,17) translocation and the resulting promyelocytic myeloid leukemia/retinoic acid receptor alpha (PML/RAR alpha) fusion proteins. To date APL is the only AML that is sufficiently sensitive to all-trans retinoic acid's (ATRA) differentiating effect. In vivo ATRA alone achieves complete remission in most APL patients. However, failure or partial responses are observed and the molecular basis of the absence of ATRA response in these patients has not been determined. To gain insights in the cell growth and differentiation of APL cells, expression of hematopoietic growth factors (HGF) shown to be produced by leukemic cells (interleukin-1 beta [IL-1 beta], IL-6, tumor necrosis factor alpha (TNF alpha), granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and IL-3) was studied in 16 APL samples. Twelve APL cases expressed IL-1 beta, IL-6, and TNF alpha, but not G-CSF, GM-CSF, and IL-3. These cases achieved complete remission with ATRA therapy. The four remaining patients (either TNF alpha negative or G-CSF, GM-CSF or IL-3 positive) did not achieve complete remission with ATRA. In all cases, in vivo response to ATRA therapy was correlated to the in vitro differentiation effect of all-trans retinoic acid 10(-6) mol/L. Thus, ATRA differentiation induction was strongly correlated to the HGF expression (P < .0001). These results suggest that the presence or absence of HGF's expression by APL cells may contribute to the therapeutic effect of ATRA in this disease.

Cell Differentiation↗
PubMed1994

The very-long-term course of polycythaemia: a complement to the previously published data of the Polycythaemia Vera Study Group.

The very-long-term follow-up of patients initially included in the PVSG protocols provides useful information. The excess risk of cancer after chlorambucil appears to persist for 5 years after stopping this treatment. The risk of leukaemia induced by marrow suppression (32P or chemotherapy) was marked before the 10th year, but low thereafter. Phlebotomy is unacceptable as permanent treatment because of the poor clinical tolerance and the frequency of vascular complications. This treatment is also associated with a risk of early progression towards myelofibrosis with myeloid splenomegaly. In the very long term, 15 years or more after the diagnosis, this complication is the major clinical risk, affecting almost 50% of our patients surviving at this time. The prevention of this type of complication could constitute one of the objectives of future protocols dealing with this disease.

Aged↗
PubMed1994

Modulation of IL-8, IL-1 beta, and G-CSF secretion by all-trans retinoic acid in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AML) characterized by the presence of the t(15;17) translocation and the resulting PML/RAR alpha fusion proteins. To date APL is the only AML which is sufficiently sensitive to all-trans retinoic acid (ATRA) differentiating effect. We have recently reported that APL express and secrete hematopoietic growth factors (HGF) such as IL-1 beta, TNF alpha, and IL-6. In vivo ATRA alone allows achievement of complete remission in APL patients. One of ATRA therapy's drawbacks is the increase of peripheral blast cells often associated with the ATRA leukocyte activation syndrome. To determine if this specific side-effect was linked to an increase of HGF release by APL cells, we studied the modulation of cytokine production by APL cells, we studied the modulation of cytokine production by APL samples (n = 12) before and after incubation with ATRA. ATRA failed to modulate TNF alpha, IL-6 or GM-CSF secretion levels; however, IL-8 levels decreased in 11 cases, and in four cases up-regulation of IL-1 beta and G-CSF protein expression was observed. These modulations were found to be linked to ATRA sensitivity as ATRA failed to modulate cytokine production in non-APL cells (n = 8). Interestingly, the increase of IL-1 beta and G-CSF production in the presence of ATRA was highly correlated to an increase in APL cell count in vitro and in vivo hyperleukocytosis, resulting in fatal outcome. IL-1 beta, TNF alpha, IL-6, and IL-8 are known to be implicated in leukocyte activation. The results of this study suggest that ATRA-induced hyperleukocytosis and ATRA leukocyte activation syndrome in APL may be inherent to the secretion of specific hematopoietic growth factors by the APL cells.

Blotting, Northern↗
PubMed1994

Risks and benefits of splenectomy in myelofibrosis: an analysis of 39 cases.

From 1980 to 1993, 39 splenectomies were performed in the Department of Visceral Surgery of Saint-Louis Hospital, in patients referred for myelofibrosis associated with myeloid splenomegaly. The short term morbidity was considerable: 33 serious haemorrhagic, infectious or thrombotic complications including 5 fatal accidents were observed in 18 patients. Severe thrombotic or infectious complications leading to 6 further deaths occurred in 8 patients over the two years following splenectomy, while six cases of acute leukaemia appeared between 6 months and 3 years after splenectomy. In 40% of cases with regular follow-up, the operation did not provide any haematological improvement and all these patients died. Only patients with minimally progressive or stable myelofibrosis and residual marrow activity in isotope studies showed an amelioration of general status with relief of pain and reduction of transfusional requirements. The indication for splenectomy should therefore probably be limited to such cases.

Adult↗
PubMed1994

Identifying abnormal parathyroid glands in the thyroid uptake area using technetium-99m-sestamibi and factor analysis of dynamic structures.

UNLABELLED: A rapid (25 min) single tracer scintigraphic method to localize parathyroid gland abnormalities was evaluated in 24 patients with hyperparathyroidism. METHODS: Scintigraphy was performed with 99mTc-sestamibi prior to surgery. A 25-min dynamic series centered on the neck was acquired immediately after injection of 99mTc-MIBI. Two planar static views were obtained after 1 and 2 hr. To identify abnormal parathyroid tissue in the thyroid uptake area, a factor analysis of dynamic structure (FADS) was applied to the dynamic acquisition. The results were compared to the analysis of the two planar static views. RESULTS: FADS demonstrated abnormal uptake of the tracer in the thyroid area for 26 of the 31 parathyroid glands found to be abnormal at surgery (5/6 adenomas, 21/25 hyperplastic glands). In three cases, FADS demonstrated parathyroid uptake despite the absence of parathyroid tissue at surgery. FADS revealed as specific and more sensitive than the visual analysis of the two static views, since only 13/30 glands were still visible after 1 hr, and 5/26 after 2 hr. Furthermore, a study with two static views was found to be less sensitive for the detection of hyperplastic glands. CONCLUSION: FADS99mTc-MIBI is performed in less time than existing scintigraphic protocols. It is a promising method to detect abnormal parathyroid glands in the cervical area with a single tracer.

Adenoma↗
PubMed1994

Induction of high-affinity GM-CSF receptors during all-trans retinoic acid treatment of acute promyelocytic leukemia.

Differentiation of normal myeloid cells is accompanied by the increase of high-affinity GM-CSF receptors necessary for progenitor proliferation/differentiation and mature neutrophil function. All-trans retinoic acid (ATRA) induces terminal differentiation of acute promyelocytic leukemia cells (AML3 subtype). We report in this study that AML3 cells, like other AML subtypes, harbor high-affinity GM-CSF R (n = 138.3 +/- 69.3 sites/cell, Kd = 76.9 +/- 68.8 pM). In all cases, incubation with ATRA induces either an increase in the number of affinity of GM-CSF R (n = 212.7 +/- 116.2 sites/cell, Kd = 43.2 +/- 22.5 pM). The data presented show that modulation of GM-CSF receptors cells is correlated to the degree of ATRA-induced granulocytic differentiation but not to increased cell growth.

Cell Differentiation↗
PubMed1994

Is a clinical consensus possible for the polycythaemic patients?

No conference of consensus was previously held in France, in the field of hematology. We decided to study the polycythemias, since it is a disease of relatively large frequency (about 1-2/100,000/year) relatively well defined, but in which initial evaluation, choice of treatment, quality or survey need really a consensus. Since the definition given in 1975 by the Polycythemia Vera Study Group (PVSG), some examinations became obsolete, and new ones (erythropoietin, stem cell culture) did appear, so that it seems useful to re-define the criteria of the disease. On another hand, the financial problems of our health systems make necessary do define what biological tests are really useful. As the vascular complications are the main risk of these patients, it would be useful to define what type of study is necessary for predicting the risk and also what preventive treatment could be advised. Such a study has presently never been done. Many questions still remain un-solved concerning the treatment. Beyond which age are the advantages of 32 P higher than the risk of leukemia? Is the chemotherapy by hydroxyurea or vercyte as easy to use than it is perhaps too often said? What is the best treatment, able to delay the development of myelofibrosis? The problem of survey is also, often, badly solved. What is the part of the specialist and that of the private physician?

Chronic Disease↗
PubMed1994

The mechanism of thrombocytopenia in patients with HIV infection.

From a retrospective analysis of 85 patients with thrombocytopenia and HIV infection, in whom platelet production and destruction were studied by isotopic methods, the following conclusions are drawn. In most recently infected patients thrombocytopenia is due to accelerated platelet destruction; in these patients the platelet sequestration is predominantly splenic, and splenectomy is usually effective. The same pattern is seen in approximately one third of patients with more advanced disease (i.e., those with AIDS-related complex or frank AIDS). In most patients with AIDS-related complex or AIDS, the thrombocytopenia is due chiefly to a platelet production defect; splenectomy is less likely to help and is thus generally inadvisable. When the patients who were receiving zidovudine were examined separately, they were found to have a lesser rate of platelet destruction but also to have a more prominent defect in platelet production defect. This suggests that the drug may help blunt platelet destruction but may do so at a price in marrow response to the thrombocytolysis.

Adolescent↗
PubMed1993

[Treatment of polycythemia with 32P with or without hydroxyurea maintenance therapy. Preliminary results in 237 elderly and high vascular risk subjects studied since 1980].

Between 1980 and 1992, 237 polycythaemic patients aged 65 or more, or with high vascular risk factors were treated with 32P according to a protocol using, or not, maintenance therapy with low-dose hydroxy-urea (500 mg/day). The present follow-up covers 1448 years/patient. Maintenance therapy was seldom discontinued because of blood toxicity or gastrointestinal intolerance, but it was stopped in 20 percent of the cases because monitoring was difficult in very old patients. Maintenance therapy reduced the mean annual 32P dose by at least 50 percent. However, the actual risk of malignant blood diseases (myelodysplasia, acute leukaemia, lymphoma) was similar in the two arms of the protocol: 14 percent at the 10th year. Compared with the French population of the same age-groups, there was no excess of epithelial cancers in both arms. Maintenance therapy did not control platelet counts perfectly. The risk of severe vascular events was identical in both arms; probably no higher than expected at that age and significantly lower than in previously published data. The actuarial survival curves in both groups showed a 50 percent survival of about 11 years, i.e. very near to that of the reference French population (12.5 years) of similar sex and age.

Age Factors↗
PubMed1993

[Bone marrow scintigraphy. Contribution to the diagnosis and the prognosis of myelofibrosis].

During the last three years 77 patients with myelofibrosis were studied by scintigraphy, using 99m Tc colloids and 111 In transferrin as tracers. Low axial uptake of the colloids, extension of the indium uptake beyond the axis towards the knees and sometimes the ankles and elbows, and splenic indium uptake are valuable diagnostic criteria, particularly useful to exclude myelofibrosis associated with a malignant disorder. The clinical severity of the disease, and in particular the disappearance of a physiologically active bone marrow (indium uptake) can be predicted from isotopic studies. Bone marrow scintigraphy could contribute to the difficult decision of splenectomy.

Adult↗
PubMed1993

[Gallium-67 scintigraphy in malignant lymphoma].

The presence of a residual mass is a frequent and difficult problem in the treatment of Hodgkin's or non-Hodgkin's lymphoma: since it is of major importance to determine whether the lesion is a fibrous mass or a still progressing tumour requiring additional therapy. Gallium-67 scanning, performed in a series of 52 patients, provides an answer to this question since there is an excellent correlation between gallium uptake by the tumoral masses and their progressiveness. Magnetic resonance imaging was carried out in half of our patients: the finding of a low-intensity signal on T2-weighted sequences proved that the residual mass was fibrous, whereas a high-intensity signal on T2-weighted sequences did not distinguish between fibrous and tumour masses. The priceless information provided by the simple and non invasive method that is gallium scanning is extremely useful to evaluate the extension of lymphomas and to determine whether residual masses are tumoral or fibrous.

Adult↗
PubMed1993

Platelet production in idiopathic thrombocytopenic purpura.

522 patients with chronic thrombocytopenia were studied over a period of three years. 252 of them suffered from idiopathic, acquired, thrombocytopenic purpura with excessive platelet destruction (platelet count less than 50,000 and mean survival less than 3 days). All of these cases were studied by using Indium oxinate labelled autologous platelets. The essential finding in these cases was the absent or only slight reactive hyperproduction, regardless of age and regardless of the severity of platelet destruction. No significant modification in platelet production was observed in the presence or in the absence of anti-platelet antibodies. No significant difference in the haematopoietic response, which was only exceptionally greater than twice the normal value, was observed whether thrombocytopenia was or not very long-standing, very severe, or affected a child or an adult. Megakaryocytosis, assessed on smears or biopsy sections, and the mean platelet volume do not constitute parameters for measuring platelet production. These findings confirm previous findings reported in the 1970s using radioactive chromium as the tracer. They demonstrate that the regulation of megakaryocyte production differs from that of erythropoietic production. They also show that determination of platelet production based on the survival of autologous platelets is able to distinguish between excessive destruction, even in the absence of a haematopoietic response, and defective production, demonstrated when the haematopoietic response is less than 50% of the normal value.

Adult↗
PubMed1993

Bone marrow scintigraphy in myelofibrosis.

Seventy-seven patients with myelo-fibrosis have been studied during the last three years, by using as tracers 99m Tc- colloids and 111 In-transferrin. A low axial uptake of the colloids, an extension of the indium uptake beyond the axis towards the knees and sometimes ankles and elbows, the splenic indium uptake, are valuable diagnostic criteria, particularly useful for excluding a myelo-fibrosis associated to a malignant disorder. The clinical severity of the disease may be predicted from isotopic studies, particularly the disappearance of a physiologically active bone marrow (indium uptake). The bone marrow scintigraphy could contribute to the difficult decision of splenectomy.

Bone Marrow↗
PubMed1992

[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↗