Oral idarubicin in elderly patients with acute myeloid leukemia.
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Biomedical subjects
Publications and source records attributed to H Karle.
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Twenty-seven patients with acute leukemia were examined at the time of diagnosis with MR imaging and in vivo T1 relaxation time measurements of the hemopoietic bone marrow. A 1.5 T whole body magnetic resonance scanner was used. Twenty of the patients had follow-up examinations in relation to chemotherapy. Bone marrow biopsies from the posterior iliac crest were obtained within a short time interval of all MR examinations. At the time of diagnosis, T1 relaxation times were increased significantly in all the leukemic patients, compared with 24 age-matched controls. A decrease in T1 relaxation time towards or into the normal range was observed in 10 patients who obtained remission. The T1 relaxation time remained prolonged in 6 patients who failed to obtain remission during chemotherapy. Four patients, who obtained remission with concomitant decrease of T1 values towards or into the normal range, also showed prolongation of T1 relaxation time in relation to leukemic relapse. The results indicate that changes observed in T1 relaxation times of the hemopoietic bone marrow in patients with acute leukemia reflect changes in disease activity, and, that serial measurements of T1 values may provide clinically useful information with the possibility for identification of residual disease in regions inaccessible for biopsy.
We used magnetic resonance imaging (MRI) to study vertebral bone marrow in hemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). We found changes in T1 relaxation times and image contrast within 14 days after starting treatment, before any response was seen in the hemoglobin concentration in peripheral blood. The increase in T1 relaxation times, together with earlier reported changes observed with localized magnetic resonance spectroscopy, indicate an alteration in cellular composition of the hemopoietic bone marrow with an increase in the amount of hemopoietic active tissue. MRI may be a useful, non-invasive way of evaluating bone marrow response to different modes of rHuEPO administration and dosage.
Eleven patients with chronic leukemia (7 with chronic lymphocytic leukemia and 4 with chronic myeloid leukemia) were evaluated with magnetic resonance (MR) imaging and T1 relaxation time measurements by use of a 1.5 tesla whole body MR scanner. Bone marrow biopsies were obtained from the posterior iliac crest (within 72 hours of the MR examination) in order to provide data on bone marrow cellularity and differential counts. The patients with chronic leukemia all showed a significant prolongation of the T1 relaxation times compared with the normal range for hemopoietic bone marrow.
The incidence of multiple myeloma in Denmark during the period 1943-82 was examined, based on the files of the Danish National Cancer Registry. A total of 5535 patients (3023 male and 2512 female) were registered. Over the period 1943-62 the incidence increased 2- to 3-fold for both men and women, but the increase in men was steeper and was seen several years before the increase in women in all 5-yr age groups from 50 to 75 yr of age. This pattern would be compatible with an impact of environmental factors. The increase, also percentagewise, rose with increasing age. Since 1963 the incidence has been virtually stable with a possibly decreasing trend during the latest 5- to 10-yr period.
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Interactions of 125I-59Fe-lactoferrin with human monocytes were studied. After 4 hours of incubation, the uptake of 59Fe exceeded that of 125I. In dissociation studies the cellular 59Fe-activity was only partly dissociable during 16 h, whereas the 125I-activity could be released nearly completely. Disruption of the cells and studies on the cytosolic phase were performed employing gel-filtration and affinity chromatography. An appreciable amount of lactoferrin was found in the cytosolic phase. About 50% of the cytosolic 59Fe-activity was bound to ferritin. The results suggest that lactoferrin is internalized into monocytes and that iron is transferred to ferritin. These cellular events may contribute to an understanding of the accumulation of iron in the monocyte/macrophage system observed during inflammatory conditions.
In vivo tissue characterization by measurement of T1- and T2-relaxation processes is one of the greatest potentials of magnetic resonance imaging (MRI). This may be especially useful in the evaluation of bone marrow disorders as the MRI-signal from bone marrow is not influenced by the overlying osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla. In the patients MRI was done at the time of diagnosis and during follow-up of chemotherapy and related to bone marrow biopsies taken within three days of the MRI. At the time of diagnosis T1-relaxation time was increased two to three times in the patients (range 0.7-3.0 sec.) compared to the controls (range 0.38-0.60 sec.). No significant difference was seen in the T2-relaxation process. In relation to chemotherapy T1 decreased towards the normal range in the patients who obtained complete remission, whereas T1 remained prolonged in the patients who did not respond successfully to the treatment. The results indicate that MRI may be a non-invasive clinically useful tool in the evaluation of acute leukaemia especially as a follow-up control of chemotherapy.
In the 1970s and beginning of the 1980s Denmark like other western countries has experienced a substantial growth in the number of medical doctors. Throughout the country, the doctor population ratio has improved considerably, a number of new specialised methods of examination and treatment have been started, and the need for doctors to work overtime has largely been abolished. At the same time, however, the growth in the number of doctors has also given rise to problems of postgraduate education, unemployment, the emigration. Furthermore, there has been political anxiety about the impact of an ever growing supply of new doctors on the continuous growth in health expenditure. This article briefly describes the development in the number of doctors through the last decades and the status of the current employment of doctors. Problems created by the growth in the number of doctors, and various initiatives to solve the problems and limit the growth in the supply of doctors are examined. A subsequent article will discuss and elucidate the future development in supply and demand on the employment market for doctors. The article begins with a short outline of the Danish health care system.
In keeping with efforts made during the 1970s to achieve a better balance between supply and demand on the employment marker for doctors, several detailed prognoses have been produced for the future development of supply with regard to sex and age structure, mortality, early retirement, frequency of emigration, specialist distribution etc. On the demand side, the prognoses are of a more evaluating character partly because there has not been sufficiently effective methods developed to predict the growth of the demand, partly because the future demand is dependent on a wide range of health, technological, economic and political factors which can hardly be predicted. This article is an account of the main tendencies anticipated in the expansion of the supply of medical doctors in the coming decades. Further, the possibilities for achieving equilibrium between supply and demand in the future employment market will be discussed.
The Danish Specialist Board--the advisory organ to the National Board of Health in all matters of medical education--was established 50 years ago. In 1979 a complete new scheme of organisation of postgraduate medical education was introduced, now involving political and administrative instances directly in the decisions. The Specialist Board was enlarged and extended with three permanent subcommitees dealing respectively, with evaluation of education and authorization, theoretical education, and clinical education. A description of the various organs and their functions is presented. New rules concerning training within the 20 basic specialties and 19 subspecialties and in general medicine was layed down in 1982. The frames of postgraduate medical education and the main lines in the clinical training course and theoretical programme is described. A series of problems have accumulated over the last 10-15 years, mainly due to developments in medical demography and new conditions for clinical education related to a new agreement between the hospital administrations and the Association of Junior Hospital Doctors. On basis of an analysis made by the Specialist Board a plan has been designed with the purpose to establish a staff reform in the hospital departments and to transform postgraduate clinical education of doctors to a formally planned and supervised programme.
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The binding of 125I-lactoferrin to a variety of peripheral blood cells was examined. In the concentration range from 10(-9) mol/l to 10(-6) mol/l a receptor-like binding of lactoferrin was observed in monocytes as well as in polymorphonuclear leucocytes. At the low concentrations of lactoferrin in plasma (about 10(-9) mol/l) the cellular binding to monocytes was about 10 times higher than the binding to polymorphonuclear leucocytes and lymphocytes. A major result from a kinetic analysis was a lower apparent binding affinity to polymorphonuclear leucocytes (KD about 2 X 10(-7) mol/l) than to lymphocytes and monocytes (KD about 2 X 10(-8) mol/l). Studies in leukaemic cells showed that lymphocytes from patients with chronic lymphocytic leukaemia bound lactoferrin to the same small extent as normal lymphocytes. In contrast, a larger component of binding with high affinity (KD about 2 X 10(-8) mol/l) could be demonstrated to lymphoblasts as well as to myeloblasts.
The binding of iron-saturated 125I-lactoferrin to human monocytes was studied at pH 7.4 and 37 degrees C. Monocytes in suspension bound 125I-lactoferrin by a reversible, saturable and specific binding indicating the presence of a receptor. The dissociation constant (KD) of the binding was estimated at about 4.5 x 10(-9) M and the number of receptors was about 1.6 x 10(6) per monocyte. The affinity of native lactoferrin (20% iron saturated) was only slightly below that of iron-saturated lactoferrin (KD about 7.9 x 10(-9) M). Human transferrin, horse cytochrome c and human immunoglobulin G were without inhibitory effect on the binding of 125I-lactoferrin. The majority of cell-bound 125I-lactoferrin was dissociable. The dissociation rate was not affected by addition of unlabelled lactoferrin to the dissociation medium. The binding of 125I-lactoferrin to adherent mononuclear blood cells showed an about 100-fold lower affinity (KD about 2.5 x 10(-7) M) than to cells in suspension, but the specificity of the binding was the same. These results are compatible with the idea that lactoferrin exerts a biological effect mediated by an interaction with cells of the monocyte/macrophage lineage.
An epidemiologic study of the total population of patients with leukemia in Denmark during 1943-77 was performed with special emphasis on time trends. The material stemmed from the national Danish Cancer Registry and was believed to be virtually complete. Of the 13,813 patients, 40% had acute leukemia; 40%, chronic lymphocytic leukemia; patients, 40% had acute leukemia; 40%, chronic lymphocytic leukemia; and 20%, chronic myeloid leukemia. Over the 35-year period, the incidence of acute leukemia increased threefold in the age groups 0-9 and 50-70+ years; whereas the increase in the age group 0-9 years climaxed in the 5-year period 1968-72, and the increase in the age group 50-70+ years was sustained. The incidence of chronic lymphocytic and chronic myeloid leukemia remained unchanged. No geographic pattern was discernible.
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