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Biomedical subjects

Y Najean

Publications and source records attributed to Y Najean.

At least 109 records · Page 6Linked to original sources

Diagnostic and prognostic value of bone marrow biopsy in aplastic anemia. A study of 119 cases.

A retrospective analysis of 119 bone marrow biopsies, performed at the time of aplastic anemia (AA) diagnosis, emphasized the prognostic value of several pathological features. Cellularity was evaluated with a better accuracy from biopsies as compared to aspirates and iron kinetics. Only bone marrow biopsies assessed myeloid "hot spots", which featured as favorable prognostic parameters in addition to the usual prognostic indices. The presence of megakaryocytes provided another positive prognostic influence. In contrast, lymphocytosis, plasmocytosis, and stroma injuries were negative in terms of prognosis. Such histological data should be systematically studied in AA at the time of initial evaluation and taken into account prior to choice of therapy.

Anemia, Aplastic↗

Diagnostic value of bone marrow imaging with 111indium-transferrin and 99m technetium-colloids in myelofibrosis.

111Indium--transferrin (111In) and 99mTechnetium-colloids (99mTc) bone marrow imaging of 55 myelofibrosis (MF) cases has been compared with clinical, histological, and iron-kinetics data. The best correlations are seen between the splenic uptake of 111In with the spleen/sacrum ratio of 59Fe at the first hour (r = 0.69, P less than 0.001) and also with the splenic erythropoiesis histologically assessed in ten splenectomized patients (r = 0.75, P less than 0.01). Moreover, sacrum uptake of 111In, when compared with sacrum uptake of 59Fe (r = 0.51, P less than 0.001) and with hematopoietic cellularity of the bone marrow (r = 0.57, P less than 0.001) reflects faithfully the hematopoietic cell content of the marrow. Thus, 111In bone marrow imaging provides a noninvasive and useful tool for the diagnosis of myeloid metaplasia in MF. Ferrokinetic studies still appreciate with better insight the amount of ineffective erythropoiesis or hemolysis and remains therefore of great value when splenectomy is discussed.

Adult↗

Red cell kinetics in thalassaemia intermedia: its use for a prospective prognosis.

A kinetic study of erythroid cell production and destruction (radioactive iron incorporation, red blood cell survival time, bone marrow scintigraphy) was performed in 12 cases of thalassaemia intermedia (six adults and six children), classified retrospectively, and compared to that performed in 17 cases of Cooley's anaemia. Our results confirm the genetic heterogeneity of these cases, the level of Hb F varies from 30% to 100% and the non alpha/alpha chain synthesis is only statistically superior to that seen in Cooley's disease. On the other hand, the kinetic study clearly separates the cases who are, or will be, clinically intermediate, showing a higher radioactive iron medullary uptake, a less ineffective erythropoiesis than that seen in Cooley's disease, and a greater peripheral haemolysis. In our study, no overlap was seen between the two groups. Iron kinetic study is then of prognostic interest and may help in therapy decisions, transfusion regimen and iron chelation, and splenectomy.

Adolescent↗

Measurement of gastric emptying in dyspeptic patients: effect of a new gastrokinetic agent (cisapride).

Symptoms suggesting gastroparesis in patients without gastric outlet obstruction are very common but their relation to an objective delay of gastric emptying has been poorly investigated. A dual isotopic technique was used to evaluate patients with non-obstructive dyspepsia (idiopathic and secondary) (part 1) and to assess the effects of a new gastrokinetic agent: cisapride, on gastric emptying in such patients (part 2). Sixty patients with postprandial dyspeptic symptoms (vomiting, nausea, gastric bloating or full feeling) and without lesions at upper endoscopy were studied. They were distributed into three groups: idiopathic dyspepsia (n = 31), postvagotomy dyspepsia (n = 16) and dyspepsia secondary to medical disorders (n = 13). All patients ingested the same ordinary meal; 99mTc sulphur colloid tagged egg white was the solid phase marker and 111In chloride was the liquid phase marker. In part 1, evaluation of gastric emptying in the first 50 patients shows a delay of gastric emptying rate of solids and liquids as compared with controls. Striking differences separate the three groups of patients, however, percentages of delayed gastric emptying rate of solids and or liquids averaged 90% in postvagotomy or secondary dyspepsia groups whereas it was 44% in idiopathic dyspepsia group. Moreover, liquid emptying rate was often the only one impaired in idiopathic dyspepsia, and in 12 of the 27 patients of this group the faster emptying rate of liquids as compared with that of solids (always found in normal subjects), could not be evidenced. In part 2, 10 patients entered a double blind cross over study of cisapride (8 mg intravenously). A significant increase of solid (p<0.01) and liquid (p<0.05) emptying rates was found in patients with initial gastric emptying delay. This study emphasises the importance of an objective evaluation of gastric emptying in the presence of symptoms of gastric stasis and suggests that specific local acting therapy may be useful in patients with identified abnormal gastric emptying.

Adult↗

[Development of polycythemia to myelofibrosis. Monitoring by the assay of the procollagen III amino-propeptide].

The conventional methods used in the follow-up of myelofibrosis being both invasive and expensive, we propose an easy and sensitive immunoassay of the procollagen III aminoterminal peptide (propeptide) which is separated and released in serum during synthesis of collagen III by bone marrow fibroblasts. This propeptide was assayed in the sera of 25 healthy adults (controls), 48 patients with polycythaemia vera and 20 patients with myelofibrosis (secondary to polycythaemia in 14). Significant differences in mean values were found between controls (7.6 +/- 2.1 ng/ml), patients with polycythaemia (9.9 +/- 4.3 ng/ml) and patients with myelofibrosis (38.1 ng/ml). There was some overlapping between values in controls and in patients with polycythaemia, partly due to the fact that 12 of these 48 patients without reticulin bone marrow fibrosis had normal serum propeptide levels. Propeptide values in patients with myelofibrosis were much scattered (range: 13-103 ng/ml). Moreover, values above 25 ng/ml were associated with myelofibrosis of recent onset (less than or equal to 2 years) and values below 25 ng/ml with myelofibrosis of more than 4 years' duration. The procollagen III aminoterminal peptide immunoassay therefore is a non-invasive and sensitive method for accurate assessment of bone marrow progressive involvement in myeloproliferative diseases associated with myelofibrosis. It could also be used to evaluate the effectiveness of antifibrosing agents.

Adult↗

[Gougerot-Sjögren syndrome. Functional study of the salivary glands by scintigraphy].

One-hundred and twenty patients with sicca syndrome, connective tissue disease or chronic graft-versus-host disease were investigated in the Saint-Louis Hospital Department of Nuclear Medicine. Technetium scanning of the salivary glands was performed in all patients. The results of the scintigraphic study were closely correlated with clinical and histological data in patients with Sjögren's syndrome. This method, which accurately quantifies the salivary function without danger nor discomfort to the patients, has a number of advantages: (a) it is sensitive enough to detect minimal salivary gland dysfunction; (b) it differentiates between parotid gland and submandibular gland involvement and demonstrates asymmetry in pathological processes; (c) it helps in following up patients with Sjögren's disease and in assessing the results of immunosuppressive or anti-inflammatory treatment.

Adolescent↗

An analysis of prognostic factors in preleukemia: interest of bone marrow scintigraphy.

Simultaneous bone marrow scintigraphy with 99m Technetium colloids and 111 Indium transferrin was performed on 34 cases of preleukemic anemias and was shown to be of good prognostic value. Groups of different outcome were defined: for a normal and parallel uptake of the two markers, 90% of the patients died of acute leukemia; for a low Indium and high Technetium uptake, only 1 patient out of 15 died of leukemia (P less than 0.001). Standard clinical and hematological data were of no predictive value. Iron kinetic data and CFU/GM colony growth were correlated to the scintigraphic results. Taken together, these three kinetic parameters have a good sensitivity and specificity for the prognosis of preleukemic states.

Aged↗

Treatment of polycythemia vera with hydroxyurea.

Conventional treatment of polycythemia vera (PV) with radioactive phosphorus or alkylating agents is associated with a significant excess of acute leukemia and cancer of the gastrointestinal tract and skin. There is thus a need for a nonmutagenic agent in the treatment of this disorder. Hydroxyurea (HU) was administered to 118 patients with a loading dose of 30 mg/kg/day for 1 week, which was then reduced to 15 mg/kg/day. Initial control of the elevated hematocrit and platelet count was achieved within 12 weeks in over 80% of patients. Long-term disease control was defined and the accumulative 1-year failure-free survival was 73% in the previously untreated patients and 59% in those patients previously treated with other myelosuppressive modalities. The HU was well tolerated and cytopenia, which generally occurred within the first 8 weeks of therapy, was transient and of little clinical significance. However, it is recommended because of this toxicity that HU be administered initially at a dose of 15-20 mg/kg/day. Three patients developed acute leukemia; two were untreated and one had had myelosuppressive therapy. Hydroxyurea is an effective agent in the treatment of PV, but continued assessment of its mutagenic potential is necessary.

Acute Disease↗

The body/venous haematocrit ratio and its use for calculating total blood volume from fractional volumes.

The measurement of body/venous haematocrit ratio has been assessed in 329 cases, in order to study the degree of error if the total blood volume were calculated from the red cell or plasma volume, using a pre-established correction factor. Three facts are clear from this study: (1) the ratio (correction factor f) is slightly lower than in the previous published data; (2) in polycythaemic and normal subjects, a low dispersion of the results around the mean value makes the potential error very low in all the cases; (3) in patients with an enlarged spleen, with anaemia and with dysproteinaemia, the large variation from case to case of the body/venous haematocrit ratio could cause large errors in determining total blood volume when using such a simplified method.

Anemia↗

Cytogenetic studies on acute nonlymphocytic leukemias following polycythemia vera.

Chromosome studies were performed on 15 patients suffering from acute nonlymphocytic leukemia (ANLL) and in one patient in a preleukemic state following polycythemia vera (PV). Clonal chromosome abnormalities that were present in all cases were clearly nonrandom and involved chromosomes #1, #5, #7, #8, #9, #11, and #21. A subdivision of ANLL into two categories occurring in the course of PV is proposed from the clinical, hematologic, and cytogenetic data: one resembling de novo ANLL with rapid initial evolution, easy classification into one group of the FAB nomenclature, and simple chromosome abnormalities; the other resembling induced leukemia, often with more progressive initial evolution, difficulty or impossibility of classification into one group of the FAB nomenclature, and complex chromosome abnormalities. The consequences for the commitment level of progenitor cell from which the leukemic clones originate are discussed.

Acute Disease↗

Chromosome studies in polycythemia vera patients.

One hundred thirty-five polycythemia vera (PV) patients (30 untreated by chemotherapy and 105 treated) were studied cytogenetically . The incidence of clonal chromosomal abnormalities was 20.7% (28 patients in nonleukemic phase). The incidence of 20q - was 3.7% (5 patients). The presence of cytogenetically abnormal clones did not allow prediction of the evolution of the disease. In a few cases, abnormal clones disappeared at the time of later studies. Although nonrandom, the majority of clonal chromosomal abnormalities are believed to be secondary events in PV patients.

Aged↗

The 'spent' phase of polycythaemia vera: hypersplenism in the absence of myelofibrosis.

A clinical phase (spent phase) in the course of polycythaemia vera (PV) cases is described as enlargement of the spleen in spite of treatment, frequent cytopenia of one or several lines, persistent red cell hypervolaemia with considerable increase of plasma volume, persistence of myeloid hyperplasia with no collagen myelofibrosis or osteomyelosclerosis, absence of hepatosplenic erythroblastic metaplasia, as shown by radio-iron kinetics and/or 111In-transferrin scintigraphy. The frequency of this phase was 5% in a study where it was not systematically sought, but it could in fact be greater. Its occurrence is not related to the clinical and biological parameters of PV. On the other hand, it is significantly more frequent and earlier in patients treated by phlebotomies than in those treated by myelosuppression (32P). In four of the 12 cases, this phase was rapidly followed by an acute leukaemia. In eight cases there was a 1-5 year interval before a myelofibrosis with splenic myeloid metaplasia. This evolution could at this stage be delayed by chemotherapy. The efficacy of splenectomy should be studied.

Aged↗

Measurement of intestinal progression of a meal and its residues in normal subjects and patients with functional diarrhoea by a dual isotope technique.

A new double isotopic method was used to measure the gastrointestinal progression of a meal in nine healthy subjects and seven patients with functional diarrhoea. 51 Chromium chloride (colonic marker) was ingested eight hours before the beginning of the scintigraphic study so that it was by then located in the colon at that time. A second marker, 99m Technetium sulphur colloid labelled the meal. Scintigraphic images were taken before and after the meal for two hours, detecting simultaneously the two isotopes. In the 51 Cr window right colon was localised and intracolonic propulsion was studied; and in the 99m Tc window gastric emptying and colon filling of the meal marker was quantified. A propulsive gastrocolic reflex was evidenced in five of the seven patients with functional diarrhoea but in none of the normal subjects. Unabsorbed residues of the meal are propelled rapidly in the ileocaecal region. Small intestinal transit of the meal marker was twice as rapid in patients with functional diarrhoea as in normal subjects.

Adult↗

Beta-thromboglobulin and platelet factor 4 in polycythemia patients treated by ticlopidine.

34 polycythemic patients, in complete or partial stable remission, were studied for beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) before, during and after treatment by an antiaggregating agent, ticlopidine, in comparison with 30 untreated patients. The cases with initial high value have an obvious drop, which is still maintained at the 2nd month after treatment, independent of variations of red cell and platelet counts. Any long-term protocol for clinical evaluation of antiaggregating therapy in myelo-proliferative diseases should be founded on evaluation of the markers of platelet function.

Anticoagulants↗

[Diphosphoglyceromutase deficiency: new cases associated with erythrocytosis].

New cases of diphosphoglyceromutase (DPGM) have been detected, associated with erythrocytosis in two unrelated families. The deficiency appears to be inherited as an autosomal dominant trait. Diphosphoglycerate phosphatase activity paralleled DPGM activity in all the subjects. Three of the latter displayed complete DPGM deficiency with about 0.4% of the normal 2,3-diphosphoglycerate (2,3 DPG) level. The other four showed partial deficiency (about 50% normal mean) with a similar decrease in 2,3-DPG level. The P50 values are in agreement with the red cell 2,3-DPG concentrations. Il all the deficient subjects the ATP level was elevated and the pattern of glycolytic intermediates was disturbed, with an increase in fructose 1,6-diphosphate, triose-phosphates, 3-phosphoglycerate, glucose 1,6-diphosphate, and reduced or normal levels of glucose-6-phosphate and fructose-6-phosphate.

Adult↗

A study of the efficacy of 5 alpha- and 5 beta-androstanes in chronic experimental aplastic anemia in mice.

The efficacy of in vivo administration of a 5 alpha-androstane and two 5 beta-androstanes (3 alpha and 3 beta) on CFU/GM and CFU/E mouse bone marrow stem cells was compared. The subjects were two groups of Swiss Webster mice: one normal group and one group in whom chronic aplastic anemia was induced by irradiation followed by mesenteric node lymphocyte grafting from C57/Bl donor mice. In normal animals, the two types of androgens (5 alpha and 5 beta) had the same efficacy, and the injection of 5 beta-androstane, before that of 5 alpha, significantly increased its efficacy. In aplastic mice, 5 alpha and 5 beta-androstanes had the same efficacy on CFU/E but 5 beta-androstanes were more efficient on the granulopoietic committed stem cells. The efficacy of the association of the two compounds in aplastic mice was not superior to that of each drug alone, which can be explained by the depletion of the stem cell compartment induced by the stimulating effect of the first androgen.

Androsterone↗

[Anemia of kidney failure treated by periodical hemodialysis. III. The effect of splenectomy. A retrospective study of 25 cases].

Twenty-five patients with severe renal impairment treated by periodical haemodialysis underwent splenectomy (for spleen injury or tuberculosis in 2). All have been on long-term follow-up. At present, 7 patients have not improved; 7 are no longer transfused but remain anaemic with a less than 20% haematocrit; 11 have a more than 20% haematocrit without transfusion. Statistical analysis of the data shows that splenectomy, when effective, acts by reducing excess plasma volume and excessive haemolysis. Red cell production is not increased. The beneficial effect of splenectomy cannot be predicted from age, sex, cause of renal impairment or severity of anaemia. However, in this series there was a positive correlation between the degree of haemolysis, the site of red cell sequestration, the size of the spleen and the effectiveness of splenectomy. Infection, notably septicaemia in grafted (and immunodepressed) patients is a major risk of splenectomy and requires preventive measures.

Anemia↗

[Anemia of chronic renal insufficiency. II. Effect of androgen therapy in 17 subjects treated with periodic hemodialysis].

Seventeen patients with severe anaemia due to renal insufficiency treated by periodical haemodialysis received high parenteral doses (7 mg/kg/week) of androgens for a period of 10 months. Kinetic studies of erythroid stemcells (plasma clot method), erythropoiesis (radio-iron kinetics, bone marrow scintigraphy) and haemolysis (autologous and homologous red cell life span) were performed before and after treatment. Complete failure was observed in 6 patients, slight improvement in 4 and distinctly satisfactory results in 7. In three cases relapse was noted after treatment was discontinued. Clinical effectiveness was due to correction of the erythropoietic defect, without changes in the degree of haemolysis. Virilization was the only side-effect recorded. All subjects whose anaemia improved, even to a slight degree, felt much better. The following parameters were found to be predictive of androgen effectiveness: absence of bilateral nephrectomy, young age, and relatively slight erythropoietic deficiency. The clinical results were unrelated to the initial number of erythroid stem cells and to their increase under androgen therapy.

Adolescent↗