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PubMed1986

[Effect of acute anemia or polycythemia on blood flow and iron transport in bone marrow].

Iron has been shown to be the limiting factor for erythropoiesis. The anemia and polycythemia effect on iron supplied to the bone marrow has been studied in a group of rabbits, by modifying the hematocrit without altering of the blood volume. The cardiac output and the percentage of blood flow to the skeleton was measured using 57Co and 113Sn radiolabelled microspheres, before and after the exchange of blood by plasma or red blood cells concentrates. In addition, ferrokinetic measurements were performed with 55Fe and 59Fe. The production of an acute anemia induced an increase in the cardiac output from 156 +/- 35 to 239 +/- 89 ml/min/kg and a decrease in the percentage of the total blood flow to the skeleton from 7.58 +/- 2.51 to 4.63 +/- 1.8. The production of an acute polycythemia induced a decrease in the cardiac output (97 +/- 28 ml/min/kg) and an increase in the percentage of the total blood flow to the bone marrow (11.69 +/- 4.03). However, in both cases, the absolute amount of blood flow and iron flow to the bone marrow were similar to the controls. These studies demonstrate that anemia or polycythemia per se do not determine the iron supply to the bone marrow.

Acute Disease↗
PubMed1985

Autosomal dominant polycythemia.

Two families with polycythemia inherited as an autosomal dominant trait are described. Serial hemoglobin determinations in multiple family members and RBC volume measurements in selected affected subjects documented their polycythemia. Measurements of arterial p02s, p50s, and blood oxygen affinity were normal in all affected individuals from each family who were tested. Erythropoietin (EPO) levels were low in affected individuals from family 1 and normal in affected members of family 2. Stimulation of in vitro CFU-E colony growth by low levels of EPO was significantly increased in subjects from family 1, but normal in those affected from family 2. We conclude that although the inheritance pattern for the polycythemia in both of these families appeared to be the same, the biologic defect leading to the disorder in each of these unique families was different. The precise mechanism of the increased EPO sensitivity noted in affected subjects from family 1 awaits elucidation.

Adenosine Triphosphate↗
PubMed1979

[In vitro study of erythroblast precursors in Vasquez disease (polycythemia vera). Arguments in favor of a double population of erythroblastic stem cells in the bone marrow].

In vitro studies using the plasma clot culture system have been performed in order to compare the red cell pregenitors able to rise to erythrocytic colonies in 7 days (CFUE) in the bone marrow of polycythemia vera (PV), secondary polycythemias and normal subjects. In PV but never in normal individuals or secondary polycythemias, the bone marrow cells producing erythroid colonies without addition of erythropoietin were found. The erythropoietin dode response curves in PV is biphasic with a plateau up to a concentration of erythropoietin of 0.02-0.05 i.U./ml followed by a near normal response to erythropoietin at higher doses. Thus our results demonstrate that two populations of erythroid stem cells coexist in PV, one being abnormally sensitive to (or independant of) erythropoietin, the other normally responding to erythropoietin. After remission induced by P32 treatment, the abnormal population can disappear but the prognostic significance of this disappearance is uncertain. On the whole these results are in agreement with those of others laboratories using the plasma clot culture system. The reasons of the disagreement with the data published using the methylcellulose technic of culture are discussed.

Animals↗
PubMed1983

Studies in polycythemia after kidney transplantation.

Mononuclear cells from peripheral blood of six patients with polycythemia after kidney transplantation were studied in methyl cellulose cultures using fetal calf serum with and without adding erythropoietin. Parallel tests were run with "synthetic medium". The data obtained were compared to those of patients with polycythemia vera and normal subjects. The erythropoietin independent proliferation in synthetic medium typical for polycythemia vera could not be found in patients with renal grafts. However, in the preparations with fetal calf serum without erythropoietin, a formation of erythroid colonies could be detected suggesting an increased sensitivity or proliferation of erythropoietically determined stem cells in patients with transplanted kidneys.

Adult↗
PubMedDate not supplied

Presence of erythropoiesis inhibitor in the urine of normal sheep and those with transfused polycythemia.

Presence of erythropoiesis inhibitor in the urine of normal sheep and those with transfused polycythaemia. Acta Physiol. Pol., 1978, 29 (1): 37-46. Urine from 18 ewes, normal and with transfused polycythemia, was analysed. The consequences of polycythemia were estimated in the period between 96 and 192h. The 24 h urine portions were separated on Sephadex G 100 columns, and after dialysis, tested biologically on normal mice of the BALB/c and Swiss strains. Changes of the erythropoietic activity in normal mice receiving the particular plasma fractions demonstrated that in the urine fraction IV, a factor with activity characteristic for the erythropoiesis inhibitor, is present in most normal sheep and in all those with moderate polycythemia.

Animals↗
PubMed1984

[Chromosomal study of polycythemia during different stages of the disease].

A cytogenetic analysis of blood and bone marrow cells of 15 polycythemia vera patients was carried out at different stages of disease during the G-banding technique. Chromosome aberrations of single character were noted before treatment only in one case, i.e. with the patient at stage II of disease. Cell clones with marker chromosomes were revealed in 6 of 9 patients examined in the course of treatment at stages II and III. The cytogenetic analysis was applied to the terminal stage of polycythemia (blast crisis) in one case, when 3 aberrant clones with multiple quantitative and structural chromosome rearrangements were discovered in blood cell cultures with and without PHA. No preferential involvement of definite chromosomes in aberrations was noticed in all the cases examined, no deletion of the 20q --chromosome being discovered. The role of the treatment in the induction of chromosome aberrations is discussed in addition to its dependence on the stage of disease. It is possible that all the clones of pathological character may appear during the long-termed course of polycythemia in patients treated at more serious stages of the disease.

Bone Marrow↗
PubMed1984

Polycythemia vera among participants of a nuclear weapons test.

Two cases of polycythemia vera and two cases of suspected polycythemia vera were found among 3,217 nuclear test participants present during the detonation of the nuclear device, "Smoky," on Aug 31, 1957, and traced through December 1981. The observed occurrence of four cases of polycythemia vera in a group this size significantly exceeds that expected. However, the small individual whole-body doses of radiation reported for these four participants makes the association with ionizing radiation tenuous, although this was the only known unusual risk factor.

Adult↗
PubMed1980

[Polycythemia resulting from abnormal hemoglobin with increased affinity for oxygen. Two cases (author's transl)].

An abnormal hemoglobin with increased oxygen affinity has to be suspected in all the cases of polycythemia where no direct signs of "polycythemia vera", or any of the classical reasons for erythropoietic stimulation can be demonstrated. This fact is documented by two new observations, one concerning a 44 year-old man with Hb Kempsey, another concerning a 58 year-old woman with Hb Malmö. The diagnosis is based on a scrupulous electrophoretic study involving an isoelectric focusing on polyacrylamide gel, and, on the study of the oxygen binding properties of the red blood cells. This polycythemia being a compensatory mechanism allowing a normal oxygen delivery to the tissues has to be respected and a compromise must be found with the cardiovascular risk.

Adult↗
PubMed1978

Hyperlipemia and myocardial infarction in polycythemia vera.

Hyperlipemia was found in 46 of 118 polycythemia vera patients and in 20 of a control group of 115 healthy subjects. Myocardial infarction in the polycythemia vera group occurred in 14 of the 46 hyperlipemic and in 17 of the remaining 72 nonhyperlipemic patients. Repeated phlebotomies may induce hyperlipemia; therefore, this form of treatment may be potentially dangerous in polycythemia vera patients who are already hyperlipemic.

Female↗
PubMed1978

[In vitro study of erythroid precursors in Vaquez' disease (polycythemia vera). Evidence supporting 2 populations of erythroid stem cells in the bone marrow].

In vitro studies using the plasma clot culture system have been performed in order to compare the red cell pregenitors able to rise to erythrocytic colonies in 7 days (CFUE) in the bone marrow of polycythemia vera (PV), secondary polycythemias and normal subjects. In PV but never in normal individuals or secondary polycythemias, the bone marrow cells producing erythroid colonies without addition of erythropoietin were found. The erythropoietin dose response curves in PV is biphasic with a plateau up to a concentration of erythropoietin of 0.02--0.05 i.U./ml followed by a near normal response to erythropoietin at higher doses. Thus our results demonstrate that two populations of erythroid stem cells coexist in PV, one being abnormally sensitive to (or independent of) erythropoietin, the other normally responding to erythropoietin. After remission induced by P32 treatment, the abnormal population can disappear but the prognostic significance of this disappearance is uncertain. In the whole these results are in agreement with those of others laboratories using the plasma clot culture system. The reasons of the disagreement with the data published using the methylcellulose technic of culture are discussed.

Cell Differentiation↗
PubMedDate not supplied

In vitro sensitivity of human erythroid progenitors to hemopoietic growth factors: studies on primary and secondary polycythemia.

BACKGROUND: Primary proliferative polycythemia is a clonal disease characterized by excessive hemopoiesis and associated with a lower than normal erythropoietin plasma level; in vitro colony studies may reveal increased sensitivity of the abnormal clone to hemopoietic growth factors. MATERIALS AND METHODS: We studied the in vitro formation of erythroid colonies (BFU-E derived clone) in cultures set up with a serum-free medium and containing Epo, interleukin 3 (IL-3) and stem cell factor (SCF), in various combinations. The clonogenic test was performed by plating non adherent mononuclear cells from the peripheral blood of normal subjects and from patients with PPP and secondary polycythemia (SP). RESULTS: SCF is a major amplifier of erythroid colony growth, in the presence of Epo; in cultures from PPP patients, however, the presence of SCF, in addition to Epo, enhances colony formation at about the same rate as in cultures from normal subjects. When SCF is omitted, the presence of even modest amounts of Epo and IL-3 is sufficient to obtain a statistically significant difference between colony formation from PPP patients on the one side, and SP patients and normal subjects on the other. CONCLUSIONS: Our results show that in vitro culture studies may contribute an additional diagnostic criterion for distinguishing between PPP and SP in uncertain cases. It is also possible that hypersensitivity to erythropoietic factors may play a role in the pathogenetic mechanism of primary proliferative polycythemia.

Adult↗
PubMed1994

Polycythemia associated with uterine fibroid.

Polycythemia has been observed to occur infrequently in association with uterine fibromyomas. Study of this case revealed polycythemia prior to surgery and remission was noted after myomectomy. The mechanisms proposed to explain polycythemia in such a tumor were revised.

Adult↗
PubMed1994

The use of 32 phosphorus (32P) in the treatment of polycythemia vera.

The treatment of polycythemia vera with 32phosphorus (32P) raises two problems: 1) what is its therapeutic efficacity? 2) Does the use of 32P increase the risk of acute leukemia? The large series of treated patients have shown the remarkable efficacy of 32P. This is particularly evident when comparing the recent series of patients treated with 32P with those of Videbaek whose patients were treated by phlebotomies only. Patients are treated one time with 3.7 x 10(6) mBq (0.1 mCi) of 33P per kg of body weight. Granulocytes and platelets are rapidly affected, whereas red cells show a response 3 months later due to their longer survival. Remission lasts from a few months to three years. If the result is not satisfactory, another dose can be given 3 months after the first one. Resistance to 32P may arise but may be reversible after a course of chemotherapy. The clear therapeutic effect of 32P renders it especially valuable for patients with a high vascular risk. Some authors have claimed that polycythemia vera evolves towards acute leukemia, but Modan's study has demonstrated that 32P is indeed responsible for the occurrence of acute leukemia; this has been largely confirmed by others. The dose to the bone marrow is not negligible and the leukemic incidence following the treatment is a factor which limits its indication. Trials were conducted to search for therapies with alkylating agents, such as Chlorambucil or Busulphan, which would be less leukemogenic. The Polycythemia Vera Study Group found that Chlorambucil was at least 2.3 fold more leukemogenic than 32P. The EORTC compared the leukemogenic effect of 32P with that of Busulphan.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1977

Polycythemia vera: hormonal modulation of erythropoiesis in vitro.

We performed in vitro culture studies examining the interaction of erythropoietin with red cell progenitors in polycythemia vera. Bone marrow was obtained from five patients with typical disease and from five healthy volunteers, and assayed for erythroid colony formation (CFU-E) by the methylcellulose technique. In cultures without added erythropoietin, a mean eightfold greater cloning efficiency was noted with the polycythemia vera marrows, as compared to normal. There was prominent stimulation of colony formation by erythropoietin, and the shape of the erythropoietin dose-response cruves appeared to be similar in both patients and controls. Anti-erythropoietin antibody reduced the number of CFU-E in cultures not containing added erythropoietin, but did not eliminate them. Dexamethasone (10(-9) M) caused a consistent increase in CFU-E in the patients' cultures. These studies provide evidence for functional erythropoietin and glucocorticosteroid receptor mechanisms on erythroid precursors in polycythemia vera. The observations are consistent with a concept of this disease as a disorder of hematopoietic stem cells in which peripheral erythrocytosis is caused by an expanded erythroid progenitor compartment which maintains responsiveness to hormonal modulation.

Antibodies↗
PubMed1993

[Comparison of 2 methods of partial exchange transfusion in newborns with polycythemia: peripheral-peripheral and central-peripheral].

Oneself presents the result of the prospective study from evaluate the morbility of the partial exchange-transfusion (exchange-dilution) to effect in two forms in newborn with polycythemia. The A group was newborn in the which extraction of blood volume was on peripheric vein is oneself administration crystalloid solution for another periphery vein; the B group was utilized umbilical vein to remove blood volume for another periphery vein is administration the crystalloid. To have 20 newborn in each group; to predisponent prenatal factors global were toxemic (12%); the plethora was the more frequent sing (55%) and nausea in (37%). Were not encountered difference in both groups for: gestational age, weight, birth rate, trophism, polycythemia type (asymptomatic vs symptomatic); neither to have difference in the seric electrolytes, protein and vital signs before and after procedure. Were encountered more infections process in the B group (P < 0.05). Were concluded what the exchange-dilution for polycythemia in newborn of term must be for periphery vein exclusive with security of not production metabolic and hemodynamic changes and without risk for sepsis and/or enterocolitis for manipulation of umbilical vessels.

Exchange Transfusion, Whole Blood↗
PubMed1996

[Fibrinolysis studied by an in vitro clot lysis test in polycythemia vera].

Results obtained by a simple in vitro clot lysis test in polycythemia vera, polyglobulia, essential thrombocythemia and chronic immun thrombocytopenic purpura are reported. Increased lysis resistance of the platelet-rich clots was demonstrated in polycythemia and essential thrombocythemia, ostensibly caused by the high plasma level of plasminogen activator inhibitor-1. Following retraction of platelet-rich clots no further increase of lysis-resistance occurred in polycythemia and essential thrombocythemia. This phenomenon is most likely due to abnormal platelet function. The well known thromboembolic complications may at least partly result from the impaired fibrinolysis in diseases with high platelet counts.

Adult↗
PubMed1996

Interstitial deletion constitutes the major mechanism for loss of heterozygosity on chromosome 20q in polycythemia vera.

An acquired deletion of the long arm of chromosome 20 is a recurrent abnormality in myeloproliferative disorders, particularly polycythemia vera and myelodysplastic syndromes. The association of 20q deletions with myeloid "stem cell" disorders suggests that the deletions mark the site of one or more genes, loss or inactivation of which plays a role in the regulation of normal hematopoietic progenitors. We have recently performed a detailed molecular analysis of 20q deletions in peripheral blood (PB) granulocytes and defined a commonly deleted region of 16 to 21 centimorgan (cM). To further reduce the size of the common deleted region we have searched for small deletions or mitotic recombination events, neither of which would be detected by conventional cytogenetics. We have studied 48 patients with polycythemia vera and four patients with idiopathic myelofibrosis. In each case, cytogenetic analysis had either failed or had shown no abnormalities of chromosome 20. Seventeen microsatellite markers that span the common deleted region were used to search for loss of heterozygosity in granulocyte DNA. No instance of microsatellite instability was observed in a total of 880 comparisons of granulocyte and T-cell DNA. Granulocyte DNA from four patients exhibited allele loss on 20q. In each case the allele loss was caused by an interstitial deletion because heterozygosity at distal markers was retained and because quantitative Southern blotting demonstrated hemizygosity. Loss of heterozygosity in PB granulocytes would be masked by the presence of significant numbers of normal granulocytes not derived from the malignant clone. Therefore, the human androgen receptor assay (HUMARA) was used to determine granulocyte clonality. In 21 of 27 informative female patients the majority of the granulocytes were clonally derived. In 5 patients the granulocytes appeared polyclonal and in 1 patient unilateral X inactivation was observed in both granulocytes and T cells. These results show that, in the vast majority of patients presented here, the failure to detect loss of heterozygosity cannot be attributed to the presence of normal polyclonal granulocytes. Our results therefore show that allele loss on chromosome 20q in polycythemia vera does not commonly involve mitotic recombination or chromosome loss and that microsatellite instability is a rare event in this disorder.

Chromosome Deletion↗
PubMed1996

Peripheral neuropathy associated with polycythemia vera.

The aim of this study was to determine the frequency and characteristics of peripheral neuropathy associated to polycythemia vera. A prospective clinical and electrophysiological study was performed of 28 patients with polycythemia vera. Other causes of neuropathy were excluded. Eleven patients experienced paresthesiae, which were usually mild. In 13 (46%) patients, clinical examination revealed features suggesting polyneuropathy. Nerve conduction indexes were abnormal in 20 (71%) patients, suggesting the presence of a predominantly sensory axonal polyneuropathy. In the somatosensory evoked potentials a delay of the P40 wave was seen in 17 patients, while 11 exhibited a delay of the N20 wave. Three of these patients also showed bilateral increases in the I-III, I-V and III-V intervals of brain-stem evoked potentials. In most cases, the delay was moderate and symmetrical. No differences in sex, age, duration of disease, hematocrit values, or platelet counts were found between patients with or without clinical or electrophysiological polyneuropathy. A high percentage of patients with polycythemia vera present clinical or electrophysiological signs of predominantly sensory axonal polyneuropathy which is probably secondary to ischemia, due to increased blood viscosity and platelet dysfunction.

Adult↗