Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of primary proliferative polycythaemia (polycythaemia rubra vera) may include radioactive phosphorus (P32) in conjunction with venesection. Acute leukaemia or carcinoma can be associated with the use of P32. We present a case of primary proliferative polycythaemia treated by repeat venesection together with P32 whose follow-up was complicated by the development of malignant neuroblastoma.
 ...
PMID:Polycythaemia and neuroblastoma. 191 34

The clinical course of 141 unselected patients (64 m, 77 f, median age 59) with polycythemia vera (PV), treated during the period 1967 to 1986 was analyzed to study prognostic factors and the correlation between treatment strategies and complication rates. Therapy was performed according to a prospectively defined treatment protocol. Primary control of the disease was achieved by phlebotomy. Marrow suppression by radioactive phosphorus or low dose busulphan was used only as a second-line therapy or to lower high platelet counts. The clinical course of the patients was characterized by a low rate of acute leukemia (4%) and a high rate of thromboembolic complications (40%). Myelofibrosis developed in 17 patients (12%). Median survival of the patents was 9.4 years. The prognostic influence of several parameters at the time of diagnosis was tested: age, sex, spleen size, percentage of blood blasts + promyelocytes, leucocyte count, platelet count, hemoglobin, hematocrit, reticulocyte count and the values of the lactate-dehydrogenase (LDH) and the alkaline neutrophil phosphatase (ANP) all had no significant influence on the length of survival. The prognosis of PV patients with atypical disease presentation at diagnosis was not different from patients with typical disease.
 ...
PMID:Polycythemia vera. A clinical study of 141 patients. 259 74

Fifteen cytoplasmic erythrocyte enzyme activities were determined in patients with polycythemia vera (PV), iron deficiency anemia (IDA), and a group of healthy volunteers. Among the PV patients, the erythrocyte enzyme activities were compared between 2 groups: patients treated solely with phlebotomy and patients treated with phlebotomy, Myleran (busulfan) and/or radioactive phosphorus 32P. Significant reduction in glutathione reductase activity was found in the PV group of patients. This activity was normalized by the addition of flavin adenine dinucleotide. In contrast to previous reports, no other enzyme activity was found to be significantly reduced. The activities of the enzymes known to be age-dependent were significantly elevated in all the groups tested except for phosphofructokinase and 3-phosphoglycerate mutase. The former was not elevated in any of the groups studied, while the latter was elevated only in the group of patients treated with Myleran and/or 32P. It was concluded that glutathione reductase (GR) deficiency is the only acquired enzyme deficiency in our group of PV patients and that radiation and chemotherapy did not induce further reduction in the activities of any of the enzymes tested. The possible involvement of GR deficiency in the etiology of the red cell life span shortening was discussed.
 ...
PMID:Erythrocyte enzymes in polycythemia vera: a comparison to erythrocyte enzyme activities of patients with iron deficiency anemia. 309 25

Eight patients with myeloproliferative disorders, five with polycythaemia rubra vera (PRV) and three with essential thrombocythaemia (ET), have been treated with the anti-folate drug Pyrimethamine for periods ranging from 1 to 24 years. In PRV this treatment was comparable in efficacy to that achieved with Busulphan or radioactive phosphorus, but required more frequent supervision. One patient was controlled on Pyrimethamine, having failed on conventional treatment. The major side effect was thrombocytopenia which was rapidly reversible on stopping the drug. In ET, Pyrimethamine produced satisfactory control of the platelet count and thrombocytopenia did not arise. No neurological sequelae were encountered. One patient developed a non-Hodgkin's lymphoma of the gut, but there were no other cases of secondary malignancy. Pyrimethamine may still have a role in the treatment of selected cases of myeloproliferative disorders.
 ...
PMID:Pyrimethamine in the myeloproliferative disorders: a forgotten treatment? 362 57

From 1963 to 1983, I treated 100 patients with polycythemia vera, using phlebotomy and the adjunctive agent hydroxyurea. These 78 male and 22 female patients ranged in age from 24 to 88 years (mean 55.7). Duration of therapy ranged from three to 216 months (mean 64.9). The mean daily dose was 0.72 gm, and the median dose was 0.64 gm. Hydroxyurea gave adequate control of red cells, platelets, and spleen size. Cytopenia was not observed. Phlebotomy requirements were markedly reduced. Leukocyte alkaline phosphatase scores were generally lowered and several blood chemistry values returned to normal. Side effects were minimal, and there were no drug-related deaths. Infections were not a problem. Hydroxyurea, a metabolic inhibitor of desoxyribonucleic acid, does not interfere with the synthesis of ribonucleic acid or protein and is thus probably less leukemogenic than radioactive phosphorus and alkylating agents. Acute myelogenous leukemia was seen in one patient after five years of continuous hydroxyurea therapy. He had received no other myelosuppressant agent. Because hydroxyurea is safe and effective in the treatment of polycythemia vera, it should be considered as first-line therapy. It probably offers practical and theoretic advantages over present therapy particularly when the disease is not well controlled by phlebotomy alone.
 ...
PMID:Hydroxyurea in the treatment of polycythemia vera: a prospective study of 100 patients over a 20-year period. 382 16

One hundred four patients with a diagnosis of polycythemia vera and a variable period of follow-up had one or more cytogenetic investigations. Chromosome abnormalities were found in 13% of untreated patients, in 56% of cases treated with radioactive phosphorus (32P) or cytotoxic drugs, and in 85% of patients in which transformation of the disease had occurred. Nonrandom chromosome abnormalities found before treatment included +8, +9, 13q-, 20q-; their prognostic value is little, as they are often associated with longstanding, stable disease. In contrast, 5q- anomaly and the appearance of subclones in patients with an abnormal karyotype were found to be poor prognostic signs, as they are usually coincidental with evolution of the disease to myelofibrosis or leukemia. Chromosomally two patterns of acute leukemia were observed in polycythemia vera patients. The first type resembles de novo acute leukemia, in that the clinical and cytologic characteristics of the disorder are easily defined by FAB criteria and the chromosome changes compatible with the types usually found in those conditions. In the second type, assignment to a FAB morphologic subgroup was more difficult, myelodysplastic changes were often present, and the karyotype showed complex abnormalities frequently involving chromosomes #5 and #7. All these features suggest the occurrence of secondary leukemia.
 ...
PMID:A chromosomal profile of polycythemia vera. 382 70

To characterize the biological changes which result in increased granulocyte alkaline p-nitrophenyl phosphatase activity in patients with polycythemia vera, the enzyme was purified from granule fractions of sucrose homogenates made from dextran-sedimented leukocytes of normal subjects and patients with polycythemia vera. Polycythemic blood yielded 3-10 times as much granulocyte alkaline phosphatase per 10(9) leukocytes as did normal blood. Sodium dodecyl sulfate extracts of granules were purified by DEAE-cellulose chromatography and sucrose gradient centrifugation to apparent homogeneity as judged by polycarylamide disk gel electrophoresis. Granulocyte alkaline phosphatase from normal subjects was purified 6910-fold with a 60% yield and a specific activity of 47 U/mg. Granulocyte alkaline phosphatase from polycythemic patients was purified 1.166-fold with a 50% yield and a specific activity of 70 U/mg. The two enzymes did not differ in molecular weight; both appeared to be about 160,000 daltons by sucrose gradient centrifugation. Both appeared to be zinc metalloenzymes, in that they were specifically inhibited by o-phenanthroline. Their elution requirements when adsorbed to DEAE-cellulose suggested they were lipoproteins although the content of phosphorus was below the threshold of detection. The identity of the two enzymes was suggested by immunological studies in which antibody prepared against purified polycythemia vera enzyme gave a precipitation reaction of identity with another polycythemia vera enzyme and two pools of normal enzyme. It is possible to account for the difference in alkaline phosphatase activity between the granulocytes of patients with polycythemia vera and normal subjects by differences in the quantity of enzyme synthesized.
 ...
PMID:Granulocyte alkaline phosphatase. Studies of purified enzymes from normal subjects and patients with polycythemia vera. 473 97

Analysis of controlled studies performed by the Polycythemia Vera Study Group (P.V.S.G.) and the European Organization for Research in Treatment of Cancer (E.O.R.T.C.) indicate that busulphan (Myleran) (BU) is the treatment of choice for polycythemia vera (PV). BU is particularly effective as compared to aspirin and dipyridamole (Persantine) or radioactive phosphorus (32P) in preventing the thrombotic and atherosclerotic complications of PV. In contradistinction to chlorambucil (CM), BU is not associated with an unacceptable increase in the incidence of leukemia. The pharmacology of BU remains unclear, but certainly it cannot be considered a classic alkylating agent. BU suppresses the activity of the reverse transcriptase-like RNA dependent DNA polymerase in the platelets of these patients. A clearer understanding of the role of BU in the treatment of the myeloproliferative disorders will provide important insights into the etiology and pathogenesis not only of preneoplastic states, but also thrombosis and atherosclerosis.
 ...
PMID:Busulphan: effect on platelet RNA dependent DNA polymerase--implications in the treatment of polycythemia vera, thrombosis and atherosclerosis. 618 58

The 61 observations of primary thrombocythemia described in this report represent approximately 15% of the cases of polycythemia vera recorded by the authors over the same 18-year period. The group includes 35 females and 26 males, with a mean age of 62. The disease is usually discovered on routine blood tests (half of cases), and more rarely because of hemorrhagic or thrombotic manifestations. Splenomegaly is found in one-third of cases. Platelet count is permanently above 800 X 10(9)/l (mean : 1 500 X 10(9)/l); mild hyperleukocytosis (mean : 16 X 10(9)/l) with predominant neutrophil polynuclears is usual but myelemia is not constant (28% of cases) and always very moderate; red cell parameters are normal in three-fourths of cases, while the remaining patients have anemia, either due to iron depletion or not. Reticulinic myelofibrosis, usually minimal, is found in 40% of cases. Medullary karyotype is always normal, without chromosome Ph1. Platelet functional abnormalities are not constant and do not correlate with the magnitude of thrombocythemia. 51 patients (84%) received myelosuppressive therapy, mainly by busulfan or radioactive phosphorus. Most deaths were due to intercurrent causes and only one patient developed acute leukemia. 71% of patients are alive at five years and subsequent decrease in the actuarial survival curve is very gradual.
 ...
PMID:[Essential thrombocythemia. Clinical, biological study and developmental study of 61 cases]. 632 10

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.
 ...
PMID:Treatment of polycythemia vera with hydroxyurea. 649 58


<< Previous 1 2 3 4 Next >>