[Hairy cell leukemia treated with interferon].
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Biomedical subjects
Publications and source records attributed to I Talstad.
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The revised ratio method which is recommended for standardization of the one-stage prothrombin time, presumes that identical regression lines exist between clotting times of abnormal and normal plasma. A modification is proposed which corrects for possible deviation of the mean clotting time of normal plasma from the regression line between clotting times of abnormal plasma. The modified revised ration method is theoretically preferable and does not need the restrictions in calibration which are recommended for the revised ratio method.
The increase of T lymphocytes in infectious mononucleosis (IM) is shown to be due to an increase of 'active' (early erythrocyte rosette-forming) T cells: 67.2 +/- 18.3% of IM lymphocytes were 'active' versus 34.7 +/- 14.9% of control lymphocytes. IM was also associated with an increase of lymphocytes demonstrating E receptors at 20 degrees C (E20-R). This phenomenon was not related to the heterophile antibody titre and could not be demonstrated with ox or rabbit erythrocytes. Patients with other lymphoproliferative diseases did not show an increase of E20-R-positive cells or of 'active' erythrocyte rosette-forming cells (E-RFC). Re-rosetting experiments indicated that E20-R and 'active' E-RFC belong to overlapping populations of cells. A double-gradient separation technique was shown to be superior to the conventional Ficoll-Isopaque method for the demonstration of 'active' and total T cells. A high proportion of T lymphocytes were also recovered in the granulocyte layer by this technique, indicating a selective loss of these cells by the conventional technique.
A patient with acute lymphocytic leukemia (ALL) who was treated with high-dose cytosine arabinoside (Ara-C) 3 g/m2 twice daily, developed reversible acute aseptic meningitis and signs of cerebellar dysfunction after a total dose of 24 g Ara-C. To our knowledge this is the first case report of meningitis complicating intravenous high-dose Ara-C therapy.
Recombinant interferon-alpha 2 (E. coli) produced a clinically significant improvement in hemoglobin, granulocytes and platelets in 7 of 8 patients with hairy cell leukemia. Response to treatment was already noticeable in the fourth treatment week. In one case without improvement after 120 days, treatment was stopped. So far only one complete remission has been documented. Because of the remarkable improvement in the peripheral blood values, the induction of a complete remission may not be the ultimate goal of interferon treatment. The side effects of this subcutaneous low-dose treatment consisted mainly of mild flu-like symptoms of short duration. The results obtained with recombinant interferon-alpha 2 confirm the initial observation by Quesada et al. with partially purified leukocyte-interferon. In our experience, these results are superior to those obtained in similar conditions with chlorambucil.
A linear relation between heparin concentrations and the dosage of heparin/kg body weight (r = 0.91, N = 47) was found after bolus injections of 2,500, 5,000, or 10,000 U heparin; the heparin concentrations agreed with plasma distribution. The maintenance therapy showed linearity between heparin concentrations and the dosage of heparin/kg body weight and 24 hours; however, the sensitivity for maintenance therapy differed between patients. The mean dosage required for maintaining heparin at 0.5 U/mL was 400 but ranged between 250 and 600 U heparin/kg body weight and 24 hours. A bolus dose of 75 U heparin/kg body weight, followed by a maintenance dose of 400 U heparin/kg body weight and 24 hours, showed therapeutic heparin response in 78% of patients, however, heparin monitoring two times daily is necessary for adjustment of dosage.
The ideal method of heparinization should achieve therapeutic concentrations (0.2-0.5 IU/mL) in the artificial kidney and the least possible amount of heparin in the patient. Total heparinization using a bolus dose (8400 IU) followed by continuous infusion of heparin (20 IU/min), initially showed 1.4-2.4 IU/mL in the artificial kidney and the patient, but unpredictable slopes. High-dose regional heparinization (120-144 IU/min) and neutralization showed sustained heparin concentrations (0.4-0.6 IU/mL) in the artificial kidney, and less than 0.2 IU/mL in the patient. Low-dose regional heparinization (25 IU/min) initially showed 0.25-0.45 IU/mL in the artificial kidney, but unpredictable slopes in the patient. Low-dose regional heparinization (25 IU/min) and neutralization showed sustained heparin concentrations (0.15-0.35 IU/mL) in the artificial kidney and less than 0.15 IU/mL in the patient.
Thromboplastins which were highly (Thrombotest) and slightly (Normotest) sensitive to the Pivka (protein induced by vitamin K absence) inhibitor were selected in this study. The influence of the Pivka inhibitor increased with increasing sample size and decreasing packed cell volume; however, a satisfactory correction for the Pivka inhibitor was possible. The inhibitor explained the different coagulation activities in the various assays and also interfered with the ratio method of standardization.
An analysis of the one-stage prothrombin time using thromboplastins highly (Thrombotest) and slightly (Normotest) sensitive to the Pivka (protein induced by vitamin K absence) inhibitor is presented. A one-tenth dilution of blood with 0.1 mol/l Na3 citrate was satisfactory even at an extreme packed cell volume (PCV). Whole blood and plasma were equally satisfactory as test materials; however, their accuracy and precision were greatly improved when a small sample size at a high coagulation activity and a large sample size at a low coagulation activity were used. The PCV correction method which corrected for the different Pivka inhibitor sensitivities of thromboplastins was preferable.
When exposed to zymosan or latex particles or heat-inactivated staphylococci, freshly prepared human blood monocytes and granulocytes rapidly released a large fraction of their lysozyme content. Within 24 hours the total lysozyme activity in the monocyte suspensions tripled, while it doubled in the granulocyte suspensions, indicating synthesis of the enzyme following release. The monocytes in particular seemed to release and synthesize lysozyme without any other stimulus than contact with lymphocytes and the tube walls. Potassium caseinate in solution did not influence the lysozyme release. Myeloperoxidase and beta-glucuronidase, which in the granulocytes are kept in lysosomal fractions separate from most of the lysozyme, were neither released nor synthesized to a significant degree. Moreover, the minute amount of lactate dehydrogenase released indicated that the lysozyme release was not the result of cell lysis. Accordingly, the monocytes, which are not already stimulated by adherence to nonphagocytosable surfaces, are capable of selective enzyme release similar to that of the granulocytes.
An analysis of the electronic counting of leukocytes in cerebrospinal fluid (CSFLpc) was made theoretically in models and in patients. At spinal fluid dilutions of 1/500, 1/50, 1/25, and 1/2, linearity was obtained by electronic counting down to 1,000, 100, 20, and 2 Lpc (10(6)/L), respectively. The electronic particle counters produce satisfactory results at Lpc greater than 100 (10(6)/L) but need modifications to produce satisfactory results at Lpc less than 100 (10(6)/L). It is theoretically possible to reduce the variation nine times by electronic counting as compared with microscopic counting. A method for the correction of blood admixture at traumatic spinal puncture by electronic counting was shown to be satisfactory.
The influence of plasma proteins on erythrocytes was studied by interference microscopy, scanning electron microscopy (SEM), and by Westergren erythrocyte sedimentation rate (ESR). Albumin kept erythrocytes dispersed as discoid spheres. Fibrinogen seemed responsible for the rouleaux phenomenon, but needed the co-influence of an immunoglobulin to induce rouleaux type of aggregates and high ESR. IgG, IgA and IgM caused immunologic type of aggregates. Albumin acted synergistically with fibrinogen and immunoglobulins. Normal blood contained a network of rouleaux, which probably explained the low normal ESR. High ESR was either due to rouleaux type aggregates where fibrinogen was dominant, or immunologic type aggregates where IgG, IgA or IgM were dominant proteins. Cold agglutinin disease showed normal blood morphology and normal ESR at 37 degrees C and immunologic type aggregates and high ESR at 25 degrees C.
The degranulation and release of lysosomal (myeloperoxidase, beta-glucuronidase, lysozyme) and cytoplasmic (lactate dehydrogenase-LDH) enzymes from polymorphonuclear neutrophil granulocytes (PMG) during phagocytosis of inert latex particles or bacteria were studied. Degranulation was much faster and more pronounced by phagocytosis of bacteria than of inert particles. A high frequency of lysosome-lysosome as well as lysosome-phagosome fusions suggested that granular material was transported by lysosome- lysosome- phagosome fusions. During bacterial phagocytosis there was evidence of release of granular material into cytoplasm causing enzymatic disintegration. After 60 minutes cell lysis occurred in about 5 per cent of the cells during bacterial phagocytosis. There was non-specific release of LDH during phagocytosis of inert particles, probably due to erythro-phagocytosis. After 60 minutes the release during bacterial phagocytosis amounted to 20-30 per cent of the enzyme content of the cells. A nearly equal release of lysosomal and cytoplasmic enzymes gave support for the idea that cell lysis was the main mechanism of enzyme release.
A patient with greatly increased erythrocyte protoporphyrin, but normal porphyrins in urine and feces, is described. The patient later developed a malignant lymphoma, and the reason why she accumulated protoporphyrin in her erythrocytes is not known. The protoporphyrin in the erythrocytes consisted of two types of protoporphyrin, free protoporphyrin (30%) and zinc protoporphyrin (70%). Upon irradiation of erythrocytes in the absence of albumin, protoporphyrin and zinc protoporphyrin, which were both bound to hemoglobin, were released. In contrast, when the irradiation was carried out in the presence of albumin, the photohemolysis was negligible, and there was release of free protoporphyrin, but not of zinc protoporphyrin, from the erythrocytes. In vivo albumin is present in the plasma and the results may help to explain why patients with erythropoietic protoporphyria (erythrocytes containing free protoporphyrin) are photosensitive, whereas patients with lead intoxication and iron deficiency (erythrocytes containing zinc protoporphyrin) are not.
Problems by using whole blood (WB) of various packed cell volume (PCV) in heparin measurements were studied. WB had to be used within 1 hr, due to influence of platelet Factor 4. The increase of Ca++ by increasing PCV, had a moderate influence by the assays studied. The recalcification time (RT) of WG was time-consuming and had low accuracy and precision, due to different heparin response. The activated partial thromboplastin time (APTT) also had low accuracy and precision, due to different heparin response; the results were equal for WB and plasma. The thrombin clotting time (TCT) had high accuracy and precision in plasma. The TCT could also be used for WB since there was a good correlation between T20 (20 NIH U thrombin/ml) using WB, and T30 using plasma (r = 0.89, N = 61). The calcium thrombin clotting time (CaTCT) is not recommended for WB assaying.
A patient with idiopathic sideroblastic anemia and atypical clinical and biochemical findings is described. He had a greatly increased erythrocyte and plasma protoporphyrin, but normal urine and fecal porphyrins. The erythrocyte protoporphyrin had a fluorescence spectrum typical of free protoporphyrin, but caused no photosensitivity. Bone marrow metal chelatase activity was normal. There were no clinical signs of liver disease. The abnormal porphyrin metabolism in this patient is not known though a number of explanations are discussed.
Problems in microscopic and electronic differential cell-counting of blood and cell suspensions were studied. Smears made from peripheral blood by the spreading technique or by the spin-slide technique did not show skewed cell distribution. The automatic differential cell counter Hemalog D was better than microscopy for basophils and showed satisfactory results compared with microscopy for polymorphonuclear neutrophil granulocytes, lymphocytes and eosinophils, while there was some disagreement for monocytes. Hemalog D, which includes blasts in large unstained cells (LUC), showed LUC in 95% of our patients, while blasts were found only in 4% by microscopy. The commonly used methods for preparing smears from cell suspensions showed markedly skewed cell distribution, which was avoided by an improved technique for cytocentrifugation, by a spin-slide technique and by a spreading technique resembling that used for blood.