Recurrent episodes of non-A, non-B hepatitis reactivated by chemotherapy.
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Biomedical subjects
Publications and source records attributed to I Tatarsky.
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In 30 patients with myeloproliferative disorders, decreased platelet aggregation in response to both ADP and collagen was demonstrated. The hypoaggregability was more drastic in patients with large spleens. Patients who had had splenectomy in the past showed normal platelet aggregation. In order to understand the role of the spleen in platelet function, platelet aggregation was studied in three patients with myeloproliferative disorders during the week following splenectomy and was compared to platelet aggregation in three control patients undergoing orthopedic operations. After splenectomy, platelet aggregation significantly increased, reaching a maximum after 3 to 4 days, but returned to presplenectomy values after 1 week. This is in contrast to the control patients, in whom no significant changes in platelet aggregation were observed. Our results suggest that the spleen retains or catabolizes the most hemostatically effective platelets.
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Coagulation studies and clinical observations were carried out in 47 members belonging to three generations in one kindred. Classical Hemophilia A, Von Willebrand (VWD) variants, and normal individuals were revealed in this study. The coexistence of Hemophilia A and VWD in different siblings of the same progenitors indicates the difficulty to distinguish between these two major factor VIII abnormalities as two different traits. A hypothesis based on these findings is elaborated.
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.
Increased autohemolysis with a partial protecting effect of added glucose is a common finding in hereditary spherocytosis (HS). For unknown reasons, in some rare cases, glucose fails to prevent the increased autohemolysis (Type II autohemolysis). The authors investigated the autohemolysis of such a patient and found that glucose actually induced the hemolysis prior to energy depletion. Old erythrocytes proved to be more fragile in the presence of D-glucose than did young ones. Other D-hexoses reacted similarly to D-glucose, while L-glucose did not. After being splenectomized, the patient's red blood cells' specific sensitivity to D-hexoses disappeared unless a 24-hour preincubation of his whole blood was performed. Other HS blood samples also became fragile in the presence of D-glucose if a 24-hour preincubation at 37 degrees C was made. Normal blood samples preheated to 50 degrees C or normal washed red blood cells in hypotonic conditions also showed a glucose-induced hemolysis. The authors assume that during the routine autohemolysis test, the accumulation of the hexose is followed by volume expansion and results in hemolysis of those cells with extremely low surface area-to-volume ratio.
Plasma lipids and lipoproteins were studied in 21 patients with benign monoclonal gammopathy, 21 patients with multiple myeloma and seven patients with Waldenström's macroglobulinaemia. Results were compared with those of a control group, age and sex matched. Low plasma cholesterol levels in all three patient groups were associated with low HDL-cholesterol concentrations. Apo A-I, but not apo B, was significantly reduced. Sixty per cent of the patients exhibited an extra lipid band on plasma lipoprotein electrophoresis, which could be an immunoglobulin-lipid complex. In these patients plasma and LDL-cholesterol levels were significantly lower than in those patients in whom this band was absent. No correlation was found between the severity of the disease and plasma lipid pattern.
A 74-year-old patient developed IgG multiple myeloma. 7 months later a right Pancoast's syndrome was observed. Computerized tomography established the extrapleural origin of the tumor. Fine needle aspiration revealed pathological plasma cells. Partial reduction of plasmacytoma was noted following radiotherapy, but the patient succumbed to pneumonia. Autopsy confirmed that a plasmacytoma caused the Pancoast's syndrome. The importance of early diagnosis and accurate therapy of this rare manifestation of multiple myeloma is discussed.
14 patients developed acute nonlymphocytic leukemia and 1 patient developed Burkitt's leukemia following longterm chemotherapy and/or radiotherapy for other disorders. The main primary disorders included multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma and breast carcinoma. Acute leukemia developed earlier in patients treated by chemotherapy with or without radiotherapy than in patients treated by radiotherapy alone (63 months, range 24-132 months; 201 months, range 48 months to 30 years, respectively). 13 patients presented without organomegaly and 8 were pancytopenic. Abnormalities of myeloid and erythroid cell lines were observed in the majority of the patients. A high rate of acute erythroleukemia (5 out of 14) was found. Increased reticulin fibers were found in 3 patients. The leukemia was invariably refractory to treatment with a median survival of 4 months. The possible role of preexisting abnormal marrow structure in the development of therapy-related leukemia is discussed.
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Immunoelectrophoresis and immunodiffusion of some IgD myeloma proteins fail to demonstrate precipitin bands between the light chain and anti-light chain serum. Reduction and alkylation of purified IgD preparation was found to render the molecule reactive to anti-lambda serum. Iodinated IgD myeloma protein was successfully precipitated by both anti-delta and anti-lambda antibodies. Both antisera precipitated heavy and light chains of a MW of 70,000 and 24,000 daltons respectively. In addition, a band of 39,000 daltons was also evident. Reduction and alkylation of the iodinated molecule, followed by precipitation with anti-delta serum demonstrated only the 70,000 and 39,000 daltons bands. The present report indicates that by sensitive techniques, such as iodination and immunoprecipitation, non-reactive hidden light chains can be detected in IgD lambda molecules.
Acetylcholinesterase of human erythrocytes from healthy donors and from patients with hematological disorders was analysed in a search for differential membrane parameters. Two substrates were used to estimate the exposure of acetylcholinesterase active site in the membrane: phenylacetate, a hydrophobic substrate, to determine total enzyme activity, and acetylcholine, an ionic substrate, to measure the externally reactive enzyme. The sensitivity of acetylcholinesterase to added stearic acid was also analysed. Three categories of the disorders studied were discerned: (a) The erythrocyte acetylcholinesterase profile was indistinguishable from normal control in beta-thalassemia minor and groups of patients with autoimmune hemolytic anemia or congenital dyserythropoietic anemia type II. (b) A marked decline in acetylcholinesterase with both substrates and reduced sensitivity to stearic acid were exhibited by the erythrocytes of paroxysmal nocturnal hemoglobinuria, beta-thalassemia major and other autoimmune hemolytic anemia and congenital dyserythropoietic anemia type II patients. Normal erythrocytes, either aged or pretreated to 50 degrees C, also showed similar characteristics. (c) Hereditary spherocytosis was singly differentiated by an elevated acetylcholinesterase activity with acetylthiocholine and by a vastly diminished sensitivity to stearic acid, while activity with phenylacetate was equal to control. This distinct profile may reflect the unique organization of the erythrocyte membrane in hereditary spherocytosis.
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Red cells of polycythaemia vera (PV) patients have a significantly higher rate of electrophoresis than red cells of normal controls and stress polycythaemia patients. The highest increment in the electrophoretic velocity was noted for PV patients treated with phlebotomy or hydroxy urea. The red cells of PV patients treated with 32P and those that progressed to myeloid metaplasia showed a normal rate of electrophoresis. We assume that the increased negative charge found on the red cells of PV patients is typical of the abnormal clone proliferating in this disease. The normal electrophoretic velocity found for the red cells of the 32P treated patients or those that progressed to myeloid metaplasia might indicate that the circulating red cells of these patients are no longer descendants of the abnormal stem cell.
Peripheral blood samples from normal individuals and from patients with benign monoclonal gammopathy or multiple myeloma were separated and assayed by immunofluorescence and rosette formation for T, B, TG and TM subpopulations. When compared with normal individuals and multiple myeloma patients, the benign monoclonal gammopathy patients could be divided into 2 groups. The 1st group demonstrated a T/B ratio similar to normal individuals, whereas in the 2nd group the ratio resembled that of the myeloma patients, with a decrease in the fraction of T lymphocytes, accompanied by an increased number of B lymphocytes. An analysis of the monoclonal Ig fraction levels indicated that the 2 groups differ in this respect as well. In the 1st group, the level of the monoclonal immunoglobulin was stable, with small fluctuations. The 2nd group demonstrated a general increasing M-component, especially in the 4-6 months preceding the study. The 2 benign monoclonal gammopathy groups exhibited a trend to a lower TM/TG ratio compared to normals; this change is more prominent in the 2nd group. Analysis of the T lymphocyte subpopulations indicated an overall decrease in the fraction of TM multiple myeloma. The above-mentioned parameters might thus aid in discriminating among BMG patients with regard to their tendency towards a malignant transformation.
A 30-year-old female presenting with arterial occlusions of the lower limbs was discovered to have a markedly abnormal thrombin time and reptilase time. Further investigations revealed the presence of a qualitatively abnormal fibrinogen. Two other family members who were completely asymptomatic had similar defects. The abnormal fibrinogen has been characterized and found to be a new variant and as such designated fibrinogen 'Haifa'.
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In 114 patients with systemic malignant gammopathies followed during a 10-year period in the hematology clinic of the Rambam Medical Center, 23 episodes of CNS involvement were recorded. 19 cases with spinal cord compression and 4 cases of intracranial plasmacytomas. Early diagnosis followed by prompt laminectomy and subsequent radiotherapy resulted in complete recovery in 50% and partial improvement in 30% of the patients with spinal cord involvement. In good responders. overall survival was not affected by the neurological complication. In the 4 patients with intracranial involvement, external plasmacytomas of the skull preceded the neurological symptoms. 3 of them were diagnosed late, which led to delay and failure of accurate treatment. Only 1 patient was immediately operated and continued to be well for the past 2 years.