Biomedical subjects
Publications and source records attributed to Y Najean.
Four cases of bone marrow aplasia, with temporary agranulocytosis (one of them fatal) are described in patients treated with Ticlopidine, an anti-aggregating drug prescribed for prevention of thromboembolic disease. These data suggest that a systematic hematological assessment would be required in the first three months after initiation of Ticlopidine therapy.
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A retrospective study of 544 patients with autoimmune thrombocytopenic purpura showed that 81 had immunological abnormalities (antinuclear factors and/or positive direct Coombs; test and/or anti-smooth muscle antibodies). After one year, 58-8% of all patients were still in complete remission, irrespective of treatment. The outcome of the disease was studied in relation to therapeutic regimens. Prognosis was worst in patients with immunological abnormalities, since 11% died as compared with 4% of the whole patient population. Most relapses occurred during the first two years following remission.
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No single radioisotopic exploration is capable of detecting metastases of malignant melanomas, but the successive use of three different scintigraphic techniques (liver, bone and 67Ga citrate) has increased the detection rate from 55 to 68%. Since these metastases are small and may develop anywhere in the body, several methods must systematically be combined, particularly when one of them gives normal results. Experience has shown that 13% of metastases would have passed unnoticed if the three scintigraphic techniques had not been used.
In studies to determine the optimal treatment for polycythemia vera, 431 previously untreated patients whose disease met established diagnostic criteria were entered into a prospective, randomized controlled trial between 1967 and 1974. Three treatment regimens were used: phlebotomy alone, chlorambucil supplemented by phlebotomy, or radioactive phosphorus supplemented by phlebotomy. Despite minor differences in age and sex, the three groups were comparable in initial hematocrit, white-cell and platelet counts, and disease-related symptoms. The median duration of follow-up is now more than 6 1/2 years. As of February 15, 1980, there were no statistically significant differences in survival among the groups. However, the risk of acute leukemia in patients given chlorambucil was 2.3 times that in patients given radioactive phosphorus and 13 times that in patients treated with phlebotomy alone. The increased incidence of leukemia during chlorambucil treatment is statistically significant (P less than or equal to 0.002); accordingly, the Polycythemia Vera Study Group has discontinued the use of chlorambucil in the treatment of polycythemia vera.
Fifty-one cases of pure, primary erythrocytosis were identified and followed at Hôpital Saint-Louis, Paris, and compared with 350 cases of polycythemia vera (PV) observed during the same period. At the initial evaluation, these cases did not differ from PV cases with respect to age, sex ratio, degree of red cell volume increase, and clinical symptoms. They did differ by the absence of splenomegaly, granulocytosis and thrombocytosis. At a late stage of evolution only a few cases developed classical criteria of PV. From this group of apparently homogeneous cases, two subgroups evolved. Sixty percent of the cases were highly responsive to myelosuppression with 32P. The median duration of the first remission was greater than five years, the mean yearly dose of 32P was very low, and there was a low incidence of complications. The other group (40% of cases) was relatively resistant to myelosuppressive agents. The development of better methods of investigate this disorder might help in discriminating these two groups from both an etiological and pathophysiological viewpoint. The thromboembolic risk of these diseases suggests that myelosuppressive therapy should be utilized in older patients with higher risk of vascular accidents, reserving phlebotomy for younger patients and those who are shown to be resistant to 32P therapy.
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beta-Thromboglobulin (beta-TG) and the anti-heparin activity platelet factor 4 (PF4) were simultaneously assayed by a radioimmune method in 108 subjects, most of whom had already be studied for platelet kinetics. The following data were obtained : while there was no technical cross-reaction, the two assays correlated closely, which indicates that they explore the same physiological phenomena : when controls were chosen at random in a population of wide age range, considerable differences were observed in the results, the values that could be considered excessive in a large percentage of cases, particularly among old, "normal" individuals ; there was no correlation between beta-TG and PF4 values on the one hand platelet destruction rate on the other ; plasma levels of beta-TG and PF4 were significantly higher in patients with vascular diseases and polycythaemia vera than in control but clearly overlapped with the values observed in controls of the same age group. The clinical significance of these data requires, to be assessed, a long-term prospective study aimed at determining whether patients with high beta-TG and PF4 levels present a high risk of thromboembolic complications and whether this risk can be reduced by correcting the biological abnormality with agents altering platelet function.
In cases of thrombopenia of obscure origin, labelling human platelets in plasma medium with both radio-active indium and chromium makes it possible to study simultaneously the life span of infused autologous (111In) and homologous (51Cr) platelets. Examples are given where this method revealed a corpuscular abnormality of platelet kinetics.
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In a prospective group study, 254 cases of aplastic anemia treated with a high dose of androgens were followed a minimum of 4 months and up to 8 years. Damage to the liver was evaluated by the appearance of jaundice or abnormal liver function tests; these parameters were evaluated at least every 3 months. Of these patients, 17.3% had overt jaundice and 18.2% abnormal hepatic function tets (total 35.5%). The anomalies appeared rapidly, before month 4 for 50% of the patients and before month 10 for 80%. They were more frequent in men than in women or children, but not linked with previous biological abnormalities. Nor did frequency depend on whether C17 methyl androgen or C17 ethyl androgen was used. Associated corticosteroids offered no protection. None of the patients showed severe jaundice or cirrhosis. If the treatment was stopped, readministration led to relapse of the jaundice in only one-third of the cases. Only two patients in this series revealed a nonmalignant tumor of the liver. Therefore, this complication does not seem to suggest restriction in the use of androgens at high dosage and for long periods, considering the severity of aplastic anemia.
Tc-99m colloid and In-111 transferrin were used in a semiquantitative scintigraphic study of bone-marrow activity in 76 patients with aplastic anemia, the majority of which were severe cases. The results are compared with other known prognostic parameters and with a predictive index formulated from a prior multi-parametric analysis performed in 352 cases. In 47 cases parallel abnormality of Tc and In uptakes was noted and was well correlated with other prognostic factors. Indium uptake is apparently a good indicator of the severity of aplasia; extension of active erythroid tissue, demonstrated with this method, is correlated with prognosis. In nine cases, excessive In uptake is explained by dyserythropoiesis associated with granulo- and thrombocytopenia (Fanconi's anemia in most cases). In 20 of our patients, TcSC uptake was excessive compared with that of In and with other prognostic factors. Statistically, this phenomenon carries an unfavorable prognosis but its physiological meaning remains to be defined.