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Biomedical subjects

Y Najean

Publications and source records attributed to Y Najean.

At least 73 records · Page 4Linked to original sources

[Pure genetic thrombocytopenia. A new clinical entity].

From a retrospective study of 3,500 platelet kinetic studies, we isolated 51 cases with chronic thrombocytopenia, excessive platelet volume without Döhle bodies and no functional platelet anomalies, normal megakaryocyte count and normal autologous and homologous platelet life-span. These cases were either discovered during the first year of life (i.e. constitutional) or proved as familial (with autosomal dominant transmission). Previous therapies (corticosteroids, immune globulins, androgens, immuno-suppressive agents, splenectomy) were unefficient in all cases as in their relatives.

Adolescent↗

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

On the basis of a retrospective study of 3,600 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 be easily suspected in cases of early onset in life, 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-hematomas), surgical complications, and the use of expensive and possibility harmful ineffective treatments, both in the propositus and in other abnormal family members. The syndrome is certainly frequent (54 families are presented here), but the diagnosis is often missed or delayed due to the low risk of hemorrhage. However, it is associated with a certain risk of leukemia (4 cases in 3 families).

Blood Platelets↗

Chronic pure thrombocytopenia in elderly patients. An aspect of the myelodysplastic syndrome.

From a group of 276 elderly patients studied in the last 12 years in a department of nuclear medicine for investigating a chronic thrombocytopenia, 36 patients have an acquired disorder, with normal platelet life span, a normal megakaryocytic bone marrow count, and absence of any evident cause at the time of clinical evaluation. During the 2 to 10 subsequent years, 16 patients developed symptoms of the myelodysplastic syndrome, i.e., chronic aregenerative anemia, granulocytopenia, dysmyelopoiesis, and appearance of circulating blast cells; three of them died from acute myeloblastic leukemia. So a pure thrombocytopenia due to a platelet production defect, without any demonstrated functional platelet defect or morphologic dysmegakaryocytosis, may be a preleukemic syndrome. In the other 20 patients, with the same pure chronic thrombocytopenia, no malignant evolution has been seen with long follow-up delays, which is often also the case in pure refractory anemias. In the absence of objective criteria of a possible premalignant disorder, the classification of these cases is difficult, which it is also the case for the so-called refractory anemias. We suggest to individualize, in the classification of the myelodysplastic syndromes, a group of pure refractory thrombocytopenias. From a practical point of view such a diagnosis may be useful, at least to avoid inefficient and possibly harmful treatments.

Aged↗

Radioimmunodetection of lymph node invasion in prostatic cancer. The use of iodine 123 (123I)-labeled monoclonal anti-prostatic acid phosphatase (PAP) 227 A F(ab')2 antibody fragments in vivo.

The therapeutic indications in prostatic cancer depend on the regional and distant extension of the cancer and are difficult to assess before lymphadenectomy. Radioimmunodetection of lymph node involvement with monoclonal anti-prostatic acid phosphatase (PAP) antibodies can be proposed as a noninvasive alternative to lymphadenectomy. Fifteen patients with various stages of histologically proven prostatic cancer were examined by immunolymphoscintigraphy (ILS) before treatment to detect lymph node metastases. These patients had Stage A (n = 7), Stage B (n = 3), Stage C (n = 2), and Stage D (n = 3) tumors. They received between 100 and 400 micrograms of monoclonal antibody 227 A in the form of F(ab')2 fragments labeled with iodine 123 (123I). The antibody was injected directly into the periprostatic area. ILS images were obtained after 1, 3, 6, and 24 hours. Three days later, each patient underwent a lymphadenectomy for histologic examination. The results of the histologic examination and ILS were compared. In ten patients, the examination did not show any images capable of being interpreted as lymphadenopathy and histologic examination confirmed the integrity of the nodes examined. In five cases, scintigraphy suggested the presence of lymph node invasion by prostatic cancer and this was confirmed by histologic examination in three of the five cases. Overall, in terms of lymphadenopathy, this examination had a sensitivity of 100% and a specificity of 83%. Therefore, ILS appears to be capable of detecting lymph node metastases in prostatic cancer.

Acid Phosphatase↗

[Refractory anemia with partial blastosis. A new therapeutic approach].

Refractory anaemia with partial myeloblastosis is classified among myelodysplasia syndromes which are characterized by abnormalities in the differentiation of haematopoietic cells, but it differs from these syndromes in that blast cells are in excess and the prognosis is darker. So far, this type of anaemia has resisted all treatment. The possibility of differentiating leukaemic cells in vitro has opened new therapeutic prospects.

Aclarubicin↗

[Critical analysis of 1000 systematic assays of serum levels of vitamin B12 and folates].

Between January 15 and April 30, 1988, one thousand assays of serum vitamin B12 and folates were performed, and the reasons why they were requested as well as their clinical usefulness are discussed. In 50 cases these assays were requested for a suspected myeloproliferative syndrome; in some of the patients with polycythaemia vera an excess of B12 was observed without hyperleukocytosis, an argument for keeping the B12 assay as an element of initial evaluation. In numerous cases the assays were performed for aetiological evaluation of a macrocytosis of suspected alcoholic origin in most patients; more than 50 per cent of the patient had folate deficiency and only a few had low B12 values. Folate levels were frequently low and B12 levels generally normal in patients with gastrointestinal disease, but many of them had been supplemented with folate and/or B12 prior to the assay. More than 20 per cent of the 1,000 assays were performed in patients aged 80 years or more, and more than 50 per cent of them had a low folate level; this has no consequences for individual subjects, but it may be of epidemiological or sociological interest. It must be mentioned that too many blood samples (more than 40 per cent) were sent to the laboratory without adequate information and after supplementation in 20 per cent of the cases. Very few patients with very low B12 levels were subjected to Schilling's test, so that the clinical usefulness of this assay, as currently utilized, is questionable in a large number of cases.

Adolescent↗

Kinetics of erythropoiesis in dialysis patients receiving recombinant erythropoietin treatment.

In eleven patients with uraemia on intermittent haemodialysis treatment, recombinant human erythropoietin (rHuEpo) was used at a dosage schedule of 100 IU/kg bodyweight thrice weekly. Erythrokinetic studies (blood volume, RBC survival and iron kinetics) were performed in nine cases before and after 6 months of treatment. The remaining two patients had only RBC and plasma volume determinations before and after treatment. Although total blood volume remained unchanged, RBC volume was increased in all cases. Red cell loss was not modified, and quantitative improvement of RBC production was noted in all cases. No qualitative defect of erythroid maturation or release was observed in the treated patients. In conclusion, rHuEpo treatment improves the anaemia of haemodialysis patients by normalising circulating RBC volume only through an increase in red cell production.

Adolescent↗

Kinetics of adriamycin injected proximal to a tumor: a comparative study between venous and arterial injections.

A kinetic study of plasma concentration of Doxorubicin (Adriamycin) was performed in 25 cases of malignant melanoma of the extremity with malignant adenopathy, treated with the same dose (20 mg per m2). Drug concentration was measured using a radioimmunoassay, with good intra-assay and inter-assay reproducibility. The kinetic analysis used the multiple compartmental method and a simulation of the plasma curves. Adriamycin injected intravenously quickly leaves the plasma into an exchangeable compartment with a slow plasma return and subsequent prolonged mean duration of the plasma half life at a low concentration. Thus, the intravenous perfusion results in a high plasma concentration only during the time of infusion. After intra arterial injection proximal to the tumor, a fraction variable (average 35%) is not released back into the circulation, or released very slowly. This local sequestration (important in terms of local concentration) explains the efficiency and the potential local toxicity of this method of administration. The rapid release of about 70% of the drug into the plasma, with kinetics similar to that observed after intravenous infusion, allows for no significant reduction of systemic toxicity.

Adult↗

[Initial results in man of immunolymphoscintigraphy of cancer of the prostate].

The loco-regional investigation of carcinoma of the prostate usually comprises ilio-obturator lymphadenectomy. This procedure carries a significant morbidity. Immunolymphoscintigraphy may provide a non-invasive alternative to this operation. Monoclonal (MAB) 227 A anti-prostatic acid phosphatase antibodies have been produced and selected for their affinity and specificity. This MAB was fragmented to its F (ab')2 form and marked with Iodine 123. Fifteen patients with prostate cancer were given 100 to 400 micrograms of the MAB by periprostatic perineal injection. The region was scanned 1 hr, 3 hrs, 6 hrs and 24 hrs after the injection. The results of the immunolymphoscintigraphy were compared with the histology of the ganglia removed at surgery or needle biopsy guided by CT scanning. In 13 cases the results were concordant for the two techniques (10 negatives and 3 positives). Two patients showed extra-prostatic fixation whilst the histology remained negative. Immunolymphoscintigraphy may therefore provide a simple method of detecting local metastases of carcinoma of the prostate if these initial results are confirmed.

Aged↗

Acute leukemia and myelodysplasia in polycythemia vera. A clinical study with long-term follow-up.

The analysis of 288 cases of polycythemia vera (PV) with a minimal follow-up of 10 years enabled us to study the characteristics of acute leukemia as observed in 33 patients (11.4%). In 50% of the patients (16 of 33), the malignant transformation is of the refractory anemia with excess of blasts (RAEB) type. Half of these further transform to acute nonlymphocytic leukemia (ANLL). Their life expectancy is not better than patients who abruptly develop ANLL. Leukemic transformation shows a frequency peak in the eighth year after initial evaluation in PV treated with chemotherapy and in the 11th year in patients treated with radiotherapy. In 30% of the patients myelofibrosis, or the spent phase of PV, is present before the transformation to acute leukemia (AL). This complication is, however, part of the natural history of PV and is observed in 20% of PV patients at 10 years when leukemic transformation is absent. Marrow fibrosis can therefore not be considered as a preleukemic phase. It was also noted that the occurrence of myeloid metaplasia/myelofibrosis is more frequent and begins earlier in patients treated by phlebotomy alone, and who do not transform to leukemia. The clinical characteristics of these AL, including high frequency of partial marrow invasion, difficulties in cytologic classification, a peak incidence similar to that in patients treated by chemotherapy or radiotherapy for a prior malignancy, multiple chromosome abnormalities, and poor response to therapy are all highly suggestive of secondary leukemias.

Acute Disease↗

Pregnancy and paroxysmal nocturnal hemoglobinuria.

Our study concerns eight pregnancies, six of which were successful, in four patients with paroxysmal nocturnal hemoglobinuria (PNH). Several complications of PNH during pregnancy were prevented: chronic anemia, folate and iron deficiency, and deep-vein thrombosis. During puerperium, acute hemolytic crises, most probably triggered by delivery, were observed in two patients. Thrombotic complications could be prevented by early initiation of an anticoagulant therapy after delivery. The only neonatal complication, observed in two cases, was isoimmune hemolytic anemia related to the multiple blood transfusions received before and during pregnancy. These results show that successful pregnancies are possible in women with PNH provided that both the obstetricians and physicians in charge monitor the pregnancies closely.

Adult↗

Prostate-specific antigen in prostatic cancer.

In an attempt to establish the value of prostate-specific antigen (PSA) in prostatic cancer, serum PSA measurements were performed in 600 patients, including 75 previously untreated prostatic cancer patients. The mean PSA levels in the benign prostatic hypertrophy (BPH) and cancer groups were highly significantly different, but less difference was found between BPH and localized prostatic cancer. A PSA level above 50 ng/ml was never recorded for BPH, but lower levels can be due to either prostatic cancer or to BPH. Our data suggest that PSA is not a specific marker of prostatic cancer but increased serum PSA levels must draw the physician's attention to the possible presence of prostatic cancer.

Antigens, Neoplasm↗

[Prostate-specific antigen in prostatic pathology].

UNLABELLED: Prostate-specific antigen (PSA), like prostate acid phosphatase (PAP), are prostate tissue markers that are useful in prostate disorders. Increased PSA levels are often seen in carcinomas of the prostate, but have also been reported in benign inflammatory disorders of the prostate. We therefore studied PSA levels in 600 patients aged 22 to 89 years to evaluate the usefulness of this marker in prostate disorders. The 600 patients were divided into four groups: 120 normal subjects, 180 patients with carcinoma of organs other than the prostate, 75 patients with carcinoma of the prostate, and 225 patients with benign hypertrophy of the prostate. RESULTS: a significant difference in PSA levels was found between carcinomas and adenomas of the prostate, as well as between stage A carcinomas and adenomas of the prostate. Conversely, non significant difference was evidenced between stage A carcinomas and benign prostatic hypertrophy with inflammation. Rather than a specific marker for cancer, PSA indicates the presence of active prostatic disease, other investigations being necessary to determine whether this disease is malignant. PSA remains extremely useful for monitoring prostate carcinoma patients, especially following radical prostatectomy.

Adult↗

[Kinetic study of thrombocytopenia associated with HIV infection].

In the last 2 years, 46 cases of HIV-induced pure thrombocytopenias have been studied, using either autologous 111 In-labeled platelets and/or homologous 51Cr-labeled platelets. The most interesting data seem to be: more than 50% of the cases were observed in young, drug addicts, a population statistically different from the general epidemiological survey of AIDS; in most the cases, thrombocytopenia was an isolated symptom with no other symptoms due to the HIV infection, or any other hematological abnormality; cortico steroids and immunoglobulins were either inefficient or only temporarily useful. In contrast splenectomy was efficient, at short or middle-term, in 12 cases of the present series; this last fact correlated with the splenic sequestration observed in almost all the cases; the platelet life-span was short in all these patients, except those with AIDS disease and pan myelopathy.

Acquired Immunodeficiency Syndrome↗

Radio-iron kinetic studies in anaemia and the measurement of dyserythropoiesis.

Analysis of radioactive iron kinetics was performed using a multi-compartment model on a series of 300 patients having either a quantitative (aplasia, haemolysis, iron deficiency) or qualitative (dyserythropoiesis, agnogenic myeloid metaplasia) anomaly of iron metabolism. Calculations were performed using a mammillary model of iron metabolism. The study demonstrated that the flux of iron from the plasma to the exchangeable compartment was a constant fraction of the global iron flux, equal to 15%, in those cases without dyserythropoiesis. This suggested that a constant correction for calculations of iron flux from the slope of the initial portion of the radioactive iron elimination curve may be applied to calculations of haemoglobin production and to the movements of iron to its exchangeable pools. Contrary to previously published information, the exchange of iron between the plasma and the exchangeable pools was not related to circulating iron levels when the other parameters were held constant. In the patients with aplastic anaemia the iron flux was diminished, but never eliminated, demonstrating that the exchangeable compartment was not solely erythroblastic, but included non-erythroid transferrin receptors. In dyserythropoietic states and myelofibrosis, the iron flux from the plasma was elevated, indicating that an important fraction of radio-iron leaves the plasma and then returns, without participating in effective erythropoiesis as determined by the appearance in the circulation of labelled viable red blood cells. The determination of this movement permitted the measurement of ineffective erythropoiesis.

Anemia↗

[Polyglobulia vera. Difficulties and complications of treatment by phlebotomy].

The authors report the results of phlebotomy for polyglobulia vera in a series of 73 patients eligible for inclusion in an international co-operative study. Previous studies usually gave actuarial survival curves but failed to mention the complications and discomfort associated with phlebotomy, although these are of importance in clinical practice. Most of the 73 patients were excluded on account of discomfort (20%), vascular thrombosis (almost 50%) or transformation into myelofibrosis within a mean period of 4 years (20%). Only 10% were treated with long-term phlebotomy. Although phlebotomies avoid the long-term risk of leukaemia attached to radiophosphorus or chemotherapy (20% on average after a mean delay of 12 years), they have practical limitations and their own, important risks. In patients over 65 and in those at high vascular risk, the best treatment is myelosuppression. However, younger subjects with polyglobulia vera but no vascular risk and/or thrombocytosis may benefit, at least temporarily, from phlebotomy.

Adult↗