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C Dresch

Publications and source records attributed to C Dresch.

At least 19 recordsLinked to original sources
PubMed1991

Thiamine responsive anemia: report of a new case associated with a thiamine pyrophosphokinase deficiency.

We report a new case of thiamine responsive anemia in a three years old boy with the characteristic association of anemia, diabetes mellitus and deafness. Thiamine therapy corrected anemia as described. A thiamine pyrophosphokinase deficiency (TPK) was found which was not influenced by treatment. However normal levels of thiamine pyrophosphate (TPP) were obtained without correction of all symptoms particularly dyserythropoïesis. Thus, etiology of the syndrome is not only a thiamine pyrophosphokinase deficiency as previously suggested.

Abnormalities, Multiple↗
PubMed1988

Acute leukemia and myelodysplasia in polycythemia vera. A clinical study with long-term follow-up.

The analysis of 288 cases of polycythemia vera (PV) with a minimal follow-up of 10 years enabled us to study the characteristics of acute leukemia as observed in 33 patients (11.4%). In 50% of the patients (16 of 33), the malignant transformation is of the refractory anemia with excess of blasts (RAEB) type. Half of these further transform to acute nonlymphocytic leukemia (ANLL). Their life expectancy is not better than patients who abruptly develop ANLL. Leukemic transformation shows a frequency peak in the eighth year after initial evaluation in PV treated with chemotherapy and in the 11th year in patients treated with radiotherapy. In 30% of the patients myelofibrosis, or the spent phase of PV, is present before the transformation to acute leukemia (AL). This complication is, however, part of the natural history of PV and is observed in 20% of PV patients at 10 years when leukemic transformation is absent. Marrow fibrosis can therefore not be considered as a preleukemic phase. It was also noted that the occurrence of myeloid metaplasia/myelofibrosis is more frequent and begins earlier in patients treated by phlebotomy alone, and who do not transform to leukemia. The clinical characteristics of these AL, including high frequency of partial marrow invasion, difficulties in cytologic classification, a peak incidence similar to that in patients treated by chemotherapy or radiotherapy for a prior malignancy, multiple chromosome abnormalities, and poor response to therapy are all highly suggestive of secondary leukemias.

Acute Disease↗
PubMed1988

Use of liquid culture and cell cycle analysis to compare drug damage following in vitro treatment of normal human bone marrow cells with adriamycin, arabinosyl-cytosine, and etoposide.

The effects of adriamycin (ADM), arabinosyl-cytosine (ARA-C), and etoposide (VP16) were studied on human bone marrow mononucleated cells using colony formation in agar, a modified liquid culture system, and flow cytometry analysis of the cell cycle. Drug concentrations tested during a 1-h incubation ranged from 0.1 to 4 micrograms/ml for ADM, from 0.3 to 30 micrograms/ml for VP16, and from 10(-7) to 10(-3) M for ARA-C. Regression analysis of the dose-response curves was used to assess the drug concentration that inhibited 90% +/- 5% (LD90) of colony growth. LD90s were 0.4 microgram/ml for ADM, 20 micrograms/ml for VP16, and 10(-4) M for ARA-C. LD90-surviving cells were cultured in liquid medium for 3 weeks. Surviving cells over this time were 13% of the control for ADM, 22% for VP16, and 95.7% for ARA-C. Although cells decreased drastically in ADM- and VP16-treated samples, granulocyte-macrophage colony-forming units (CFU-GM) per 10(5) surviving cells rose to twice the control for ADM, to 60% for VP16, and to 150% for ARA-C. Flow cytometry analysis of the cell cycle was performed at day 0 and at day 4 after treatment with the LD90 dose. It showed a rapid and reversible effect of ARA-C on cells in the S-phase, whereas the action of VP16 concerned all cells, regardless of their cycle phase. We conclude that the direct effects of the three drugs on CFU-GM in agar are poorly predictive of hematopoietic reconstitution capacity, except for VP16. Liquid culture gives a much more accurate appraisal of the long-term damage and recovery due to anticancer drugs.

Bone Marrow Cells↗
PubMed1988

Radio-iron kinetic studies in anaemia and the measurement of dyserythropoiesis.

Analysis of radioactive iron kinetics was performed using a multi-compartment model on a series of 300 patients having either a quantitative (aplasia, haemolysis, iron deficiency) or qualitative (dyserythropoiesis, agnogenic myeloid metaplasia) anomaly of iron metabolism. Calculations were performed using a mammillary model of iron metabolism. The study demonstrated that the flux of iron from the plasma to the exchangeable compartment was a constant fraction of the global iron flux, equal to 15%, in those cases without dyserythropoiesis. This suggested that a constant correction for calculations of iron flux from the slope of the initial portion of the radioactive iron elimination curve may be applied to calculations of haemoglobin production and to the movements of iron to its exchangeable pools. Contrary to previously published information, the exchange of iron between the plasma and the exchangeable pools was not related to circulating iron levels when the other parameters were held constant. In the patients with aplastic anaemia the iron flux was diminished, but never eliminated, demonstrating that the exchangeable compartment was not solely erythroblastic, but included non-erythroid transferrin receptors. In dyserythropoietic states and myelofibrosis, the iron flux from the plasma was elevated, indicating that an important fraction of radio-iron leaves the plasma and then returns, without participating in effective erythropoiesis as determined by the appearance in the circulation of labelled viable red blood cells. The determination of this movement permitted the measurement of ineffective erythropoiesis.

Anemia↗
PubMed1987

[Polyglobulia vera. Difficulties and complications of treatment by phlebotomy].

The authors report the results of phlebotomy for polyglobulia vera in a series of 73 patients eligible for inclusion in an international co-operative study. Previous studies usually gave actuarial survival curves but failed to mention the complications and discomfort associated with phlebotomy, although these are of importance in clinical practice. Most of the 73 patients were excluded on account of discomfort (20%), vascular thrombosis (almost 50%) or transformation into myelofibrosis within a mean period of 4 years (20%). Only 10% were treated with long-term phlebotomy. Although phlebotomies avoid the long-term risk of leukaemia attached to radiophosphorus or chemotherapy (20% on average after a mean delay of 12 years), they have practical limitations and their own, important risks. In patients over 65 and in those at high vascular risk, the best treatment is myelosuppression. However, younger subjects with polyglobulia vera but no vascular risk and/or thrombocytosis may benefit, at least temporarily, from phlebotomy.

Adult↗
PubMed1987

Polycythaemia vera in young people: an analysis of 58 cases diagnosed before 40 years.

Over 20 years, 58 cases of PV in young people (46 meeting the full PVSG criteria, 12 with elevated red cell volume and leucocytosis or thrombocytosis, without splenomegaly) were studied and have been followed for periods of 3-24 years. These cases represent approximately 5% of the cases of PV referred to the Department of Nuclear Medicine of St Louis Hospital during this period. They differ from older patients in the initial clinical severity, the short interval between the first symptoms and the diagnosis, frequent presentation with a life-threatening complication (two cases of hepatic vein thrombosis, six thrombotic or haemorrhagic events, six splenectomies, two abortions) and a very enlarged spleen in half the cases. However, after the initial complications, the overall survival is very long (exceeding 70%, even when including the initial complications, at 15 years). The vascular accidents occur exclusively in the phlebotomized patients, the main risk factor being the poor stability of the haematocrit. Only one acute leukaemia was observed among the 14 cases treated by radioactive phosphorus and/or alkylating chemotherapy. The most frequent late complication was evolution towards myelofibrosis. This spent phase seemed to occur earlier in patients treated by phlebotomy. On the basis of this data, we would advise the following therapeutic strategy: phlebotomies, as soon as the diagnosis is established, and a systematic long-term treatment by hydroxyurea with the hope of reducing the number of vascular complications and of delaying the evolution towards the spent phase and the myelofibrosis.

Adult↗
PubMed1986

Growth fraction of myelocytes in normal human granulopoiesis.

The labelling index (LI) of myelocytes (M) after flash labelling of normal human bone marrow cells with [3H]-thymidine ([3H]TdR) is always lower that the LI obtained for myeloblasts (MB) and for promyelocytes (PM). This fact can be interpreted in two ways: it may mean that the duration of the G1 phase of the cell cycle is longer in M than in MB or PM, or it may mean that the proportion of cells in cycle, i.e., the growth fraction (GF), is lower in the M population than in MB or PM. The evolution of the LI and of the mean number of grains per cell was monitored in [3H]TdR-labelled normal bone marrow during in vitro incubation for 50 hr. The generation time, measured by the halving time of the mean number of grains per cell after flash labelling, was similar for M to that for MB and PM. During continuous labelling, the LI of MB and PM reached 1 and the LI value for M never rose to more than 50% of the values recorded for MB and PM after 30 hr. These findings give support to the second hypothesis, i.e., a lower GF in the M population. Good correlation was found between the LI of M and the proportion of mature polymorphonuclear cells in the bone marrow of normal subjects and of patients with chronic benign neutropenia or hyperleucocytosis. Variations in the M growth fraction could be a medium-term (2-3 days) regulatory factor in granulocyte production.

Bone Marrow↗
PubMed1986

The choice of treatment in polycythaemia vera.

The current results of prospective protocols initiated by the Polycythaemia Vera Study Group are presented. These results help to define the best choice of treatment in accordance with the risk factors.

Bloodletting↗
PubMed1985

Differentiation of mixed colony-forming cells in normal human bone marrow and blood.

In blood and marrow samples from ten normal adults, mixed colonies were found in agar cultures at concentrations of 4.1 +/- 3.4/10(5) mononuclear bone marrow cells, and of 4.7 +/- 4/5 X 10(5) mononuclear blood cells. Reseeding of five- to seven-day clusters of immature cells in fresh medium with 5% PHA leukocyte-conditioned medium (PHA-LCM) and 2 U erythropoietin (Epo) showed that 10(5) mononuclear cells contained as many as 42 +/- 12 CFU-mix in bone marrow and 12 +/- 7 CFU-mix in blood, i.e., ten times more than in the primary cultures. Attempts were made to discover why these potentially mixed colonies failed to develop in primary cultures. For this purpose five- to seven-day clusters of immature cells from cultures of 5 X 10(4) bone marrow cells grown with PHA-LCM, Epo, or both were reseeded in medium containing one or both stimulants. The presence of both in secondary culture gave the best CFU-mix growth, whatever the primary stimulation, i.e., more than one-third of the immature clusters gave rise to colonies of red cells and granulocyte lineages. The addition of one or both stimulants between days 7 and 14 of primary culture, however, did not increase the number of mixed colonies or give rise to late developing ones. Reseeding of colonies and clusters of 14-day primary cultures showed that at least one-third of erythroid bursts or of late-developing granulocyte colonies contained CFU-mix, but that less than 10% of 14-day clusters developed into mixed colonies. Cultures of nonadherent cells, mononuclear cells of less than 1.065/g density or with a velocity sedimentation rate of less than 6 mm/h gave the same results as the culture of total mononuclear cells; i.e., at least ten times more multipotent progenitors were found by reseeding after five to seven days than in primary cultures. We conclude that in human bone marrow and blood the physical and kinetic properties of pluripotent stem cells are similar to those of 14-day erythroid bursts and GM colonies. Under normal culture conditions, most of these cell types differentiate into one cell lineage only, and plurilineage differentiation is inhibited.

Blood Cell Count↗
PubMed1984

An analysis of prognostic factors in preleukemia: interest of bone marrow scintigraphy.

Simultaneous bone marrow scintigraphy with 99m Technetium colloids and 111 Indium transferrin was performed on 34 cases of preleukemic anemias and was shown to be of good prognostic value. Groups of different outcome were defined: for a normal and parallel uptake of the two markers, 90% of the patients died of acute leukemia; for a low Indium and high Technetium uptake, only 1 patient out of 15 died of leukemia (P less than 0.001). Standard clinical and hematological data were of no predictive value. Iron kinetic data and CFU/GM colony growth were correlated to the scintigraphic results. Taken together, these three kinetic parameters have a good sensitivity and specificity for the prognosis of preleukemic states.

Aged↗
PubMed1984

Cytogenetic studies on acute nonlymphocytic leukemias following polycythemia vera.

Chromosome studies were performed on 15 patients suffering from acute nonlymphocytic leukemia (ANLL) and in one patient in a preleukemic state following polycythemia vera (PV). Clonal chromosome abnormalities that were present in all cases were clearly nonrandom and involved chromosomes #1, #5, #7, #8, #9, #11, and #21. A subdivision of ANLL into two categories occurring in the course of PV is proposed from the clinical, hematologic, and cytogenetic data: one resembling de novo ANLL with rapid initial evolution, easy classification into one group of the FAB nomenclature, and simple chromosome abnormalities; the other resembling induced leukemia, often with more progressive initial evolution, difficulty or impossibility of classification into one group of the FAB nomenclature, and complex chromosome abnormalities. The consequences for the commitment level of progenitor cell from which the leukemic clones originate are discussed.

Acute Disease↗
PubMed1984

Chromosome studies in polycythemia vera patients.

One hundred thirty-five polycythemia vera (PV) patients (30 untreated by chemotherapy and 105 treated) were studied cytogenetically . The incidence of clonal chromosomal abnormalities was 20.7% (28 patients in nonleukemic phase). The incidence of 20q - was 3.7% (5 patients). The presence of cytogenetically abnormal clones did not allow prediction of the evolution of the disease. In a few cases, abnormal clones disappeared at the time of later studies. Although nonrandom, the majority of clonal chromosomal abnormalities are believed to be secondary events in PV patients.

Aged↗
PubMed1984

The 'spent' phase of polycythaemia vera: hypersplenism in the absence of myelofibrosis.

A clinical phase (spent phase) in the course of polycythaemia vera (PV) cases is described as enlargement of the spleen in spite of treatment, frequent cytopenia of one or several lines, persistent red cell hypervolaemia with considerable increase of plasma volume, persistence of myeloid hyperplasia with no collagen myelofibrosis or osteomyelosclerosis, absence of hepatosplenic erythroblastic metaplasia, as shown by radio-iron kinetics and/or 111In-transferrin scintigraphy. The frequency of this phase was 5% in a study where it was not systematically sought, but it could in fact be greater. Its occurrence is not related to the clinical and biological parameters of PV. On the other hand, it is significantly more frequent and earlier in patients treated by phlebotomies than in those treated by myelosuppression (32P). In four of the 12 cases, this phase was rapidly followed by an acute leukaemia. In eight cases there was a 1-5 year interval before a myelofibrosis with splenic myeloid metaplasia. This evolution could at this stage be delayed by chemotherapy. The efficacy of splenectomy should be studied.

Aged↗
PubMed1984

In vivo protection of normal mouse hematopoiesis by a beta 2 blocking agent during S-phase chemotherapy.

Butoxamine, a beta 2-adrenergic blocking agent, which temporarily blocks the G1-S transition of human bone marrow granulocyte precursors in vitro, was used in vivo together with 1-beta-D-arabinofuranosylcytosine (ara-C) in mice. Butoxamine alone depressed the granulocyte labeling index and granulocyte-monocyte colony-forming Cell (GM-CFC) suicide rate at a dose of 3 micrograms/g body weight. A maximum effect was produced 6 to 12 hr after injection. Butoxamine administered 8 hr before an injection of ara-C modified the proportion of GM-CFC in S phase as compared with the number found after ara-C alone. After a series of five ara-C injections, administered at intervals of 16 hr, 70% of the treated mice died within 2 weeks, whereas only 42% of mice pretreated with butoxamine 7 to 9 hr before each ara-C injection died. This difference was due to the more rapid return to normal of GM-CFC numbers and an increase in the proportion of GM-CFC and granulocyte precursors in S phase in the butoxamine-pretreated animals. These findings suggest that butoxamine may have a potential use in protecting hematopoiesis during intensive chemotherapy for cancer.

Adrenergic beta-Antagonists↗
PubMed1984

In vitro bone marrow GM-CFC growth in aplastic patients. Correlation between E rosette forming cells and immunotherapy results.

In vitro bone marrow GM-CFC (granulomonocyte colony forming cell) growth following E rosette (+) cell depletion was studied in 14 aplastic patients to determine whether an autoimmune factor could be involved in the pathophysiological process leading to the decrease in bone marrow colony formation. The increase in GM-CFC growth after E rosette (+) cell depletion was high in 8 cases, suggesting that in these cases an autoimmune mechanism may have been involved. All these patients responded within a month to treatment with antithymocyte globulin (ATG) or corticosteroids. Six patients did not respond to immunotherapy, none showed increased GM-CFC growth. The increase of in vitro GM-CFC growth after E rosette (+) cell depletion in aplastic anemia could therefore be a good indication for the trial of immunotherapy. However this study seems to be useful only in patients with at least a few months evolution after diagnosis.

Adolescent↗
PubMed1983

[Anemia in renal insufficiency. I--Mechanisms of anemia in patients treated with periodic hemodialysis].

Fifty-two patients with anaemia due to chronic renal insufficiency treated by haemodialysis were divided into three severity groups. Except for bi-nephrectomized patients, none of the usual criteria such as age, sex, cause of the renal disease and duration of dialysis correlated with clinical severity. Kinetic studies showed that the severity of anaemia was unrelated to the degree of haemolysis, haemoglobin function or haemodilution. Stem cells were increased in all cases, irrespective of clinical severity. However, the degree of anaemia closely correlated with the degree of erythropoietic deficiency, as measured by radio-iron kinetics. A qualitative defect (slow release of labelled cells from the bone marrow) was associated with severe quantitative erythroid defect. These data indicate that kinetic studies of erythropoiesis constitute objective methods for measuring clinical severity. They favour the theory which makes a hypothetical inhibitor of differentiation and/or proliferation of erythropoietic precursors the main cause of anaemia.

Anemia↗
PubMed1983

Prognostic value of the combined suicide level of granulocyte progenitors and the labelling index of precursors in preleukemic states and oligoblastic leukemias.

Although abnormalities in granulopoiesis detected by means of bone marrow cytology, culture and kinetic studies have provided prognostic data in preleukemic states and oligoblastic leukemias, this information cannot be applied to individual cases. In order to determine the indications for treatment and the form it should take in a given case, data would be required concerning the probability of impending transformation into acute leukemia. In 45 studies involving 34 patients who were followed for 10-42 months, a combination of a rise in the proportion of granulocyte precursors in S-phase, indicated by a colony-forming cell suicide rate of over 40%, and a low labelling index of myeloblasts and promyelocytes, was always followed by the onset of acute leukemia within 10 months. Sequential studies in 13 patients revealed an increase in cluster-forming cells and in the suicide level in the second study. The changed kinetics of granulopoietic proliferation may provide an indication for chemotherapy.

Cell Division↗