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Biomedical subjects

G Duhamel

Publications and source records attributed to G Duhamel.

At least 55 records · Page 3Linked to original sources
PubMed1984

ASTA Z 7557 (INN mafosfamide) for the in vitro treatment of human leukemic bone marrows.

The in vitro treatment of leukemic bone marrows, collected during complete remission, aims at eliminating residual blast cells prior to freezing and preservation, while sparing normal hematopoietic stem cells. We report our experience on the activity of ASTA Z 7557 on human leukemic (CFU-L) and normal hematopoietic stem cells. The sensitivity of human leukemic and normal progenitor cells (CFU-c), detected in semi-solid media cultures, is similar. However, pre-CFUc progenitors detected in long term marrow cultures are much less sensitive to ASTA Z 7557. Therefore autologous bone marrow transplantation can successfully be done with pretreated marrows containing 5 +/- 5% residual CFUc. The wide range of stem cells sensitivity to ASTA Z 7557 justify the predetermination of the optimal dose of drug for incubation prior to marrow collection for each individual patient. Our preliminary clinical experience is exposed.

Bone Marrow Transplantation↗
PubMed1984

Plasma lipids, lipoproteins and apolipoproteins AI, AII, and B in renal transplanted children: what risk for accelerated atherosclerosis?

The aim of the study was to investigate the atherosclerosis risk factors related to hyperlipidemia in renal transplanted children. Plasma cholesterol, triglycerides, apolipoproteins (Apo) AI, AII and B, and the major lipoprotein classes separated by gradient ultracentrifugation were compared in 30 renal transplanted patients and 14 healthy children. Hyperlipidemia was present in 66% of the transplanted children. 'Positive' risk factors for atherosclerosis (high plasma cholesterol and Apo B) were present in hypercholesterolemic and combined hyperlipidemic subgroups. All transplanted children, whether normo- or hyperlipidemic, presented essentially 'negative' risk factors for atherosclerosis, i.e. significantly higher levels of Apo AI and AII in plasma and in high-density lipoprotein HDL2 and higher Apo AI/Apo B and/or Apo AII/B ratios. Repeated evaluations (over a 12-month period) in transplanted children indicated relatively frequent individual changes in the lipid pattern, but not in Apo AI and AII content. These results suggest that the risks for accelerated atherosclerosis related to hyperlipidemia may be considered as moderate in transplanted children.

Adolescent↗
PubMed1983

Delayed kinetics of recovery of haemopoiesis following autologous bone marrow transplantation. The role of excessively rapid marrow freezing rates after the release of fusion heat.

Thirty-five patients were treated by intensive chemotherapy and/or whole-body irradiation followed by reinjection of cryopreserved autologous bone marrow. In 8 patients the kinetics of recovery of haemopoiesis was delayed (recovery to 10(9) leucocytes/litre beyond day 27 and recovery to 50 X 10(9) platelets/litre beyond day 25). This delay was directly responsible for the death of 3 patients and contributed to a fatal outcome in 2 others (mortality rate 9-14%). Retrospective analysis of these 8 cases revealed that failure of autologous transplantation was associated with poor recovery of CFUc, which was in turn related to an excessively rapid freezing rate after the release of fusion heat. Recovery of CFUc to 50% or more was achieved in 100% of cases when the freezing rate was less than 5 degrees C/min, 45% for freezing rates between 5 and 10 degrees C/min and 22% when the freezing rate exceeded 10 degrees C/min (n = 71, P less than 0.001). There was an inverse linear or logarithmic relationship between CFUc recovery and freezing rate after the transition phase (r = -0.46, r = -0.43, P less than 0.001). The quantity of nitrogen introduced into the freezing chamber to annul the fusion heat must therefore be calibrated with accuracy so that the desired shortening of the transition phase will not be accompanied by an overly marked increase in the freezing rate, which would result in the destruction of stem cells. To ensure an adequate freezing rate, it is crucial to monitor the temperature continuously in each sample of bone marrow during the freezing process. This study also suggested that other factors may have interfered with the kinetics of recovery after autologous bone-marrow transplantation. These factors include myelofibrosis, the presence of an Australia antigen and administration of compounds that are toxic for the bone marrow after reinjection of cryopreserved marrow. However, the responsibility of these factors cannot be stated with certainty.

Adult↗
PubMed1983

Spur cells in patients with alcoholic liver cirrhosis are associated with reduced plasma levels of apoA-II, HDL3, and LDL.

The precise nature and origin(s) of the abnormalities in lipoprotein and apolipoprotein profile associated with severe hepatic dysfunction and the presence of spur cells remain poorly defined. To shed light on this question, we have analyzed the plasma lipoprotein and apolipoprotein profiles in five patients with alcoholic cirrhosis and spur cells, and compared them with those of a group with similar hepatocellular dysfunction, but lacking spur cells, and with that of a control group. Lipoproteins were subfractionated by density gradient ultracentrifugation and their physicochemical properties were determined; apolipoprotein A-I, A-II, and B contents in plasma and the respective subfractions were quantitated by radial immunodiffusion, while the complement of low molecular weight apolipoproteins in each subfraction was analyzed by isoelectric focusing and electrophoresis in alkaline-urea polyacrylamide gels. Spur cell plasma was distinguished by reduced levels of apoA-II and elevated ratios of apoA-I/apoA-II (approximately 13:1 as compared to 3.3-3.9:1 in the other two groups), and by reduced concentrations of HDL3. Gradient fractionation showed the apoA-II content of HDL3 to be dramatically and significantly diminished in spur cell plasma; in addition, apoA-II content was reduced relative to apoA-I in this subclass (4.7:1 as compared to 1:1 in cirrhotics lacking spur cells and 1.9:1 in controls). Spur cell HDL2 was similarly deficient in apoA-II, with elevated ratios of apoA-I:apoA-II (9.8:1 in comparison with 1.9-2.5:1 in the two other groups). Nonetheless, high HDL2 concentrations were seen in both series of cirrhotic patients, irrespective of red cell morphology. Spur cell HDL2 thus appears to consist primarily of particles possessing only apoA-I, with a minor population containing both apoA-I and apoA-II. The free cholesterol content of all lipoprotein subfractions from spur cell plasma was increased, as indeed was the molar ratio of free cholesterol to phospholipid, in comparison with that of corresponding fractions from alcoholic cirrhotics lacking spur cells and of control subjects. LDL levels were reduced in spur cell plasma, thereby distinguishing this group from the cirrhotics without spur cells who displayed elevated LDL levels. Markedly reduced plasma levels of apoA-II, HDL3, and LDL appear characteristic of alcoholic cirrhotics presenting with spur cells. Our findings suggest that apoA-II may be essential to the normal function and metabolism of HDL, one aspect of which may be the transport of free cholesterol and thereby the direct or indirect maintenance of red cell morphology.

Apolipoprotein A-II↗
PubMed1983

The role of serum lipoproteins on the in vitro proliferative potential of human hematopoietic progenitors CFUC and CFUE.

The influence of various lipoprotein fractions on the proliferation of normal human hematopoietic progenitors, CFUC and CFUE, was studied in vitro. The lipoprotein fractions, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL), high density lipoproteins (HDL2 and HDL3), were isolated by sequential ultracentrifugation. The addition of each subfraction to lipoprotein deficient medium allowed us to distinguish two categories of lipoproteins: firstly, those with density d greater than 1.030, LDL, HDL2 and HDL3 which showed a marked inhibitory activity on CFUC and CFUE proliferation and, secondly, those with density d less than 1.030, VLDL and IDL which did not show any inhibitory activity. The regulatory role of lipoproteins on progenitor cell proliferation is discussed.

Cell Division↗
PubMed1982

[Management of polycythaemia with pipobroman].

From 1971 to 1980, 86 patients with polycythaemia (vera 69, undetermined 15 and respiratory 2) were treated with pipobroman (N,N' bis bromopropionyl piperazine). The initial treatment in doses of 75 mg/day resulted, within 45 days, in complete remission in 46/49 new patients (93.9%), and in 17/20 previously treated patients with polycythaemia vera (85%) and in 14/15 patients with apparently primary polycythaemia. The main duration of the first remission was 17.5 months. Relapses occurred in 30% of the cases but responded to pipobroman at the initial high dosage level. Low-dose maintenance treatment appears to be necessary. Adverse effects on the blood were rare; they included leucopenia (8%) and moderate thrombocytopenia (7%); macrocytosis was noted in 20% of the patients. Acute leukaemia (3 cases) and osteomyelofibrosis (3 cases) were only observed in patients previously treated with 32 P or busulfan. Pipobroman therefore appears to be much less toxic than other alkylating agents. Its is as effective as 32 P but acts more rapidly. It seems to have little oncogenic power, but a more prolonged study is required to ascertain this point.

Female↗
PubMed1982

Combination chemotherapy with cyclophosphamide, vincristine, prednisone and the contribution of adriamycin in the treatment of adult non-Hodgkin's lymphomas a report of 131 cases.

Between January 1973 and January 1979, 131 patients with malignant non-Hodgkin's lymphomas (107 lymphocytic lymphomas, 24 histiocytic lymphomas) were treated with cyclophosphamide-vincristin-prednisone (CVP) either alone or combined with Adriamycin (CVP-A). Stage I and II lymphocytic lymphomas were all treated by CVP combined with radiotherapy. The survival curve for this group of patients plateaued at 89% from the 12th to the 60th month, which was the endpoint of the study. For Stage III and IV nodular lymphocytic lymphomas, actuarial survival was 69% at five years in the CVP-treated group as compared to 54% at three years in the group treated with CVP-A. For Stage III and IV diffuse lymphocytic lymphomas, the complete response rate and median survival were respectively 25% and 24 months in patients treated with CVP, as compared to 67% (P less than 0.01) and 26 months in the group treated with CVP-A. For histiocytic lymphomas, the complete response rate was 50% in the CVP-treated group as compared to 83% in the group treated with CVP-A. Most remarkable was the fact that while in the CVP treated group median survival was only 17 months, the small group of patients treated with CVP-A exhibited considerably improved survival with a horizontal survival curve at 90% after 36 months (12 patients). These results show that the CVP protocol remains an excellent treatment for nodular lymphocytic lymphomas. The addition of Adriamycin (CVP-A) as well as its inclusion in other drugs combination, has raised hopes for remissions of long duration and even for cures in patients with histiocytic lymphomas. Finally, in diffuse lymphocytic lymphomas, efforts will have to be pursued to improve the prognosis which remains poor despite the increased complete response rate achieved by the addition of Adriamycin.

Adolescent↗
PubMed1982

Evidence that hepatitis B virus has a role in liver-cell carcinoma in alcoholic liver disease.

We compared the presence of serologic markers of hepatitis B virus (HBV) infection with the presence of the viral DNA in the livers of patients with alcoholic liver disease with or without hepatocellular carcinoma. Among 51 patients with various kinds of alcoholic liver disease but without hepatocellular cancer, 19 had one or more serologic markers of HBV, but only three had viral surface antigen in their serum. These three patients, as well as three others who had HBV antibodies but no viral antigen in their serum and two others who had no serologic markers of any kind, had HBV DNA in their liver cells. In at least five of the eight patients with viral DNA in the liver, the DNA was integrated into the genome. Among 20 patients with alcoholic cirrhosis and hepatocellular carcinoma, nine of the 16 tested had serologic markers of HBV infection, but all 20 had HBV DNA integrated into the genome of the neoplastic liver cells. These data suggest that HBV plays a part in the pathogenesis of primary liver-cell cancer in alcoholics.

Adult↗
PubMed1982

[Protective effect of isaxonine against vincristine-induced neuropathy (author's transl)].

A double-blind survey versus a placebo was carried out with C.P.V. protocole on 25 patients treated for lymphosarcoma or reticulosarcoma; its aim was to appraise the preventive action of isaxonine on the appearance of neuropathy induced by vincristine. The frequency of such neuropathy was clearly lower in the isaxonine group (3/10) than in the placebo group (8/10) in a statistically significant manner. The protective effect of isaxonine was particularly striking on tendon reflexes and on the number of motor units recorded at musculus extensor digitirum pedis brevis; on the contrary, the patients treated with the placebo showed real denervation.

Adult↗
PubMed1982

[Bone marrow repopulation after heavy chemotherapy and autologous bone marrow transplantation. Monitoring with biopsies and marrow culture on agar (author's transl)].

Repopulation of the bone marrow after heavy chemotherapy and autologous transplantation was monitored by means of biopsies and bone marrow cultures on agar carried out simultaneously from the 2nd to the 33rd days after transplantation. A parallelism was observed between the reappearance of cell clusters on biopsy material and the growth of colonies in cultures, both being the centres from which the corresponding series proliferated. The clusters were almost invariably formed of one series. Repopulation began 3 to 5 days after transplantation and was complete between the 10th and 20th days. Oedematous dissociation persisted long after the clusters reappeared. Bone marrow repair was virtually always accompanied by plasmocytosis.

Adolescent↗
PubMed1982

[Critical role of rate previous freezing on the liberation of heat of fusion the preservation of hematopoietic cell lines].

71 bags of bone marrow cryopreserved and stored for periods up to 2 years, were thawed and CFUc recoveries were studied in relation to the rate of freezing following the heat of fusion. Excellent CFUc recoveries (greater than 50%) were obtained in all cases (11/11) for freezing rates smaller than 5 dgC/mn, whereas freezing rates greater than 10 dgC/mn produced poor recoveries in 78% of the cases (4/18). Intermediate freezing rates (5 less than 0 less than 10) resulted in intermediate yields of CFUc, with good recoveries in only 45% of the cases (19/42). These results indicate that CFUc recoveries and subsequently the kinetics of autologous engraftment following the infusion of cryopreserved marrow, which are already known to be related both to the freezing rate before the heat of fusion and the duration of the phase transition period, are also related to this new parameter, which should be carefully monitored during the freezing procedure.

Bone Marrow↗
PubMed1982

Pipobroman therapy of polycythemia vera.

Between 1971 and 1981, 74 patients with polycythemia vera were treated with pipobroman using a high-dose induction, low-dose maintenance regimen. Complete remission was achieved in 51 of 54 previously untreated patients (94.4%) and in 17 of 20 patients (85%) previously treated wih radioactive phosphorus (32 p) and busulfan. The earliest modifications were noted on day 16, and on the average, blood counts were normal by day 45. Thirty percent of the patients relapsed, the mean duration of the remission being 17.5 mo. Following recurrence pipobroman was consistently effective in the same doses but the mean duration of the next remissions was 10 mo. Transient leukopenia and thrombocytopenia occurred in 8% and 7% of patients, respectively, during initial phase, and anemia was noted in 3 patients. Macrocytosis was noted in 20% of patients during maintenance phase. Three cases of acute leukemia and 3 cases of osteomyelosclerosis were recorded, all occurring in patients who had previously received 32 p and/or busulfan. No hematologic malignancies were seen among patients treated with pipobroman alone; follow-up exceeded 6 yr for 20 patients and the median follow-up period was 3.6 yr. Pipobroman appears safer than other alkylating agents; it is as effective as 32 p and works more quickly. Longer follow-up will be required to evaluate the drug's oncogenic potential, which is still not known.

Drug Evaluation↗
PubMed1982

Study of granulocyte-macrophage progenitor (CFUc) preservation after slow freezing of bone marrow in the gas phase of liquid nitrogen.

Storage of human hematopoietic stem cells has been made possible through effective preservation of viability by freezing technique. We have studied the quantitative and qualitative aspects of granulocyte-macrophage precursor (CFUc) recovery from 29 bags of frozen bone marrow stored at - 160 degree C in the gas phase of liquid nitrogen for several months or years. it has been shown that with the freezing and preservation technique used, over 75% of the proliferative capacity of the cryopreserved CFUc was recovered. The influence of various factors on the quality of bone marrow preservation was studied and showed that dimethylsulfoxide (DMSO) appeared to cause substantial loss of CFUc at 4 degree C. Evaluation of CFUc in vitro is essential for determining the quality and richness of cryopreserved bone marrow with a view to using such marrow for autologous grafting intensive chemotherapy or total body irradiation in patients with hematological malignancies or solid tumors. No correlation was found between the number of nucleated bone marrow cells and CFUc content.

Adolescent↗
PubMed1982

[Diffuse normolipemic xanthomatosis and IgG monoclonal dysglobulinemia].

A 56-year-old man with diffuse cutaneous xanthomatosis had neither mucosal lesions nor diabetes insipidus. Cutaneous lesions were characterised by dermal histiocytic infiltration, without X bodies, associated with Touton's cells and abundant iron deposits. Plasma lipid levels were normal. A lambda G monoclonal dysglobulinemia was present without Bence-Jones proteinuria or myeloma, except for a moderate increase in medullary plasmocytic cell elements. The diagnosis of disseminated xanthomatosis was established, the differential diagnosis from other histiocytic proliferations, particularly diffuse plane xanthoma, being sometimes difficult. The relation between normolipaemic xanthomatosis and dysglobulinemia certainly exists, but no satisfactory pathogenic explanation was possible in this case, in the absence of cryoglobulin, paraprotein antilipoprotein activity, and cutaneous deposits of lipoprotein-paraprotein complexes.

Dysgammaglobulinemia↗
PubMed1981

[Acute leukaemias with myelofibrosis. Clinical, cytohistological and evolutive aspects. Their place among malignant blood diseases with myelofibrosis (author's transl)].

In a series of 154 patients with acute leukaemia (AL), 31 had myelofibrosis. The authors report in detail on 9 of these and demonstrate the distinctive features of this form of AL: pancytopenia is severe, circulating blast cells are rare, myelograms are difficult to read, and bone-marrow biopsies are necessary to the diagnosis, severity assessment and prognosis of the disease. Owing to the small number of cells, it is uneasy to distinguish these AL from acute myelofibrosis (a nosological entity which needs to be more precisely defined) and from megakaryoblastic leukaemias, recently individualized.

Acute Disease↗