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Biomedical subjects

G Duhamel

Publications and source records attributed to G Duhamel.

At least 37 records · Page 2Linked to original sources

Prolonged cholestasis after ajmaline-induced acute hepatitis.

We report the cases of 3 patients in whom ajmaline-induced acute hepatitis was followed by anicteric cholestasis persisting for more than 1 year after cessation of administration of the drug. Ajmaline was given for 8-16 days before the onset of acute hepatitis. Jaundice was preceded by fever, chills and abdominal pain, and was associated with hypereosinophilia. The initial lesions included centrilobular cholestasis and portal inflammatory infiltration. Jaundice lasted for 3 weeks to 11 months. In these 3 patients liver tests were still abnormal 17-26 months after ajmaline withdrawal; histological examination, performed 9-26 months after the onset of jaundice, showed a decreased number of interlobular bile ducts, ductular proliferation, and mild portal fibrosis; circulating immune complexes were demonstrated. These observations demonstrate that prolonged cholestasis can follow ajmaline-induced acute hepatitis. Persistence of cholestasis long after the withdrawal of ajmaline suggests some form of autoimmunity.

Acute Disease↗

Hepatitis B vaccination in chronic alcoholics.

Given the possible role of hepatitis B virus in the occurrence of hepatocellular carcinoma and the high prevalence of HBV infection in alcoholics, we attempted to prevent HBV infection in alcoholic patients with or without cirrhosis. Among 32 cirrhosis, 20 received three injections of hepatitis B vaccine at monthly intervals and 12 had a 4th injection one month later. Effectiveness was evaluated on the anti-HBs titer at the 6th month; it did not differ between the 3- and 4-injection groups. Two patients were good responders (anti-HBs greater than 300 mU/ml), 14 had a low response (m-30 mU/ml at the peak) and 16 (50%) had no detectable anti-HBs. All alcoholics without cirrhosis were given 4 injections; all had detectable anti-HBs but their mean antibody response was 97.7 +/- 4 SD. No obvious statistical difference in the response to the vaccine was noted on the basis of sex or age, or on the discontinuation or not of alcohol intake. Deficient antibody response to vaccines has not previously been demonstrated in patients with cirrhosis or in alcoholics. It remains to be determined whether this response is specific of HBV and how it could be related to the role of HBV in the occurrence of liver alterations in alcoholics.

Adult↗

Evaluation of lymphocyte subsets after autologous bone marrow transplantation with marrow treated by ASTA Z 7557 in acute leukemia: incidence of the in vitro treatment.

The lymphocyte subset reconstitution after high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation (ABMT) has been studied in ten patients with acute leukemia (AL) (6 ALL and 4 ANLL) in complete remission (CR). Bone marrow was treated in vitro with high-dose ASTA Z 7557, individually determined according to CFU-GM sensitivity. The different peripheral blood lymphocyte subsets were characterized by means of monoclonal antibodies (indirect immunofluorescence assay) belonging to the following classes of differentiation: OKT11-T11 (CD2), OKT3-T3 (CD3), OKT4-T4 (CD4), OKT8-T8 (CD8), OKIal-I2 (HLA-DR), Leu7 (natural killer/killer) and by means of polyspecific antiimmunoglobulin sera (direct immunofluorescence assay). Data in these ten patients were compared with those of a control group of 21 normal donors and with a control group of 14 patients in CR without ABMT. Our results showed a marked depression of the T4:T8 ratio in patients with AL before ABMT, compared with normal donors who had respective values of 1.02 and 1.33 (p less than 0.01). This depression was increased and prolonged up to day 515 after ABMT, with a value of 0.32 (p less than 0.01 compared with the pregraft situation; p less than 0.001 compared with normal donors). This T4:T8 ratio imbalance was related to the depletion of the T4+ population and to the increase of the T8+ subset. This imbalance was emphasized after ABMT. The Leu 7+ population was also increased in grafted patients compared with normal donors (p less than 0.01). The B-cell population remained unchanged throughout the study. We conclude that patients autografted with marrow treated in vitro by high-dose ASTA Z 7557 may experience a long-term T-cell subset imbalance.

Acute Disease↗

[Autograft of bone marrow for the treatment of acute leukemia: in vitro efficacy of anti-leukemic purification].

Autologous bone marrow transplantation (ABMT) is a new technique which is currently being evaluated in the treatment of leukemias, lymphomas, and a few solid tumors. In patients with acute leukemia (AL), high dose therapy + ABMT is of little benefit if done at time of relapse. On the other hand, when used for consolidation of remission, either with cleansed or non cleansed marrow, it may improve disease-free survival. In patients with acute myelocytic leukemia (AML) autografted during their 1st remission, the probability of remaining in remission at 2 years is 70 p. 100. It is slightly lower for patients with acute lymphocytic leukemia (ALL): 55 p. 100. The different techniques of cleansing the marrow, monoclonal antibodies, immunotoxins, drugs, are reviewed in this paper. A comparison of these techniques in term of tumor log cell kill is provided. ABMT is the best second line therapy for non-Hodgkin lymphomas (NHL), either after relapse after conventional chemotherapy or partial failure (partial remission). In these patients, the probability of remaining in remission at 3 years is about 50 p. 100. ABMT is currently under trial in the treatment of solid tumors and some success has been obtained in carcinoma of the ovary, non-seminomatous tumor of the testis, neuroblastoma, and some selected breast cancers.

Acute Disease↗

A prospective study of the value of bone marrow erythroid progenitor cultures in polycythemia.

The diagnostic value in polycythemia of the presence of endogenous erythroid colonies derived from bone marrow cells (EECs) was assessed in a prospective study on 108 patients referred for polycythemia (Hb greater than g/dL in men, greater than 16 g/dL in women) with normal plasma volume by comparison with the standard criteria, the bone marrow grade, and the serum erythropoietin (Epo) level. Total red cell volume (TRCV) was high (greater than 36 mL/kg in men, 32 mL/kg in women) in 87 cases (group A) and slightly increased in 21 cases (group B). Standard criteria were applicable in 63 of 108 cases (57%); 46 were PV and 17 were secondary polycythemia (SP). Standard criteria were nonapplicable in 45 cases. EECs were present in 65 cases (60%) with a ratio of EEC/Epo-stimulated colonies of 39.5% +/- 18% (extremes 10% to 80%). EECs were noted in 43 of 46 polycythemia vera (PV) and 0 of 17 SP. Among the 45 unclassified cases, EECs were noted in 22: 18 of 29 cases from group A (10 with 2 major and 1 minor criteria; 8 with 2 major criteria) and 4 of 16 cases from group B (with variable standard criteria, 2 belonging to a PV family). In group A, there was a positive significant correlation between EECs and the presence of two major and 1 minor criteria (P less than .0001). In group B, there was a positive significant correlation between EECs and the presence of at least 1 major criterion and 2 minor criteria or a family background (P less than .0001). The unclassified polycythemias with EECs in the bone marrow are characterized by a bone marrow grade and a mean serum Epo level not different from that of patients with PV and an active course of the disease. The unclassified polycythemias without EECs in the bone marrow are a heterogeneous group corresponding in some cases to SPs of unknown origin (slightly increased bone marrow grade and/or high serum Epo level), and in others cases to spurious polycythemias (normal bone marrow grade and/or normal Epo level). In conclusion, EECs were of great value in differentiating PV from SP (P less than .001), and in allowing the diagnosis of PV in the absence of all the standard criteria even when TRCV was slightly increased. In our study, EEC improved the classification of polycythemia by 22%. The recommended diagnostic steps for the evaluation of polycythemia must be reconsidered.

Adult↗

An unusual case of Crigler-Najjar disease in the adult. Classification into types I and II revisited.

We present the case of a 25-year-old man with Crigler-Najjar disease who had since birth a marked unconjugated hyperbilirubinemia without bilirubin overproduction, without any neurological involvement and in whom phenobarbital administration failed to produce any effect. Analysis of his biliary bile pigments on two occasions showed (i) a decrease excretion of bilirubin, as indirectly suggested by a high ratio of biliary bile acids over total bilirubin; (ii) an increase in unconjugated bilirubin IX alpha quantitated by thin-layer chromatography (TLC) following alkaline methanolysis and by direct extraction and TLC of the tetrapyrroles; (iii) a high proportion of bilirubin monoconjugates whereas the excretion of diconjugates was very low. Classification of the present patient into Crigler-Najjar disease type I or II was not possible. The most striking and practical difference among the various cases of Crigler-Najjar disease remains the response to phenobarbital. Among cases of Crigler-Najjar disease which respond to enzyme induction and Gilbert's syndrome, the continuous spectrum suggests a common defect.

Adult↗

Hepatitis B virus multiplication in the absence of usual serological markers. A study of 146 chronic alcoholics.

The possible role of HBV infection in the progression of alcoholic liver disease remains debated. However, serum HBV markers in alcoholics, although present with a high frequency, mainly consist of anti-HBs and/or anti-HBc antibodies. In order to detect an HBV multiplication that could be missed by the usual markers, we looked for HBV-DNA in the serum of 146 chronic alcoholics; the results were compared with those of the usual serological HBV markers. Sixty-eight of the 146 patients could be studied for HBV-DNA both in the liver and the serum. The 146 alcoholics were divided in 48 with normal liver function (group I); 67 with non-cirrhotic alcoholic liver disease (group II); 31 with alcoholic cirrhosis (group III). Among the 146 patients, 17 had a viral multiplication reflected by serum positive HBV-DNA, as against none of 100 healthy controls (P less than 0.01). Six of the 17 had a normal liver function (6/48 = 12.5%), 7 were of group II (7/67 = 10.4%) and 4 had cirrhosis (4/31 = 12.9%). Serum HBV-DNA was associated with HBsAg in 3 occasions; in addition serum HBV-DNA was also present in 5 HBsAg-negative patients with anti-HBc and/or anti-HBs and even in 9 without any usual HBV marker. The overall prevalence of HBV markers in the 146 patients went from 30.8% to 37.0% when serum HBV-DNA was taken into account; it was similar in the 3 groups studied. Eight patients, of the 68 studied, were liver HBV-DNA-positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regulation of human peripheral blood BFU-E growth in vitro by leukaemic B-lymphocytes.

We report a stimulating effect of leukaemic B-lymphocytes from anaemic and non-anaemic patients with CLL on the proliferation of normal peripheral blood BFU-E. Coculture of leukaemic B-cells at various concentrations (2.5 X 10(3)-10(6)) with 2.5 X 10(5) mononuclear cells from normal peripheral blood increased the number of BFU-E derived erythroid colonies. The same effect was observed when the number of target cells was varied in the presence of a fixed number of B-lymphocytes, with a clear linear relationship. B-cell conditioned medium gave a similar increase when added to the culture instead of B-cells. At high concentration of B-cells from anaemic patients, the size of the colonies was increased and a large number of macroscopic colonies was seen. The place of the B-cells in the regulation of erythroid progenitors in relation to monocytes and T-lymphocytes has still to be established.

Anemia↗

Vindesine-prednisone in the treatment of blast crisis of chronic myeloid leukemia.

Eight patients with chronic myeloid leukemia in blast crisis were treated with a combination of vindesine and prednisone. Complete remission was achieved in three patients; partial remission was achieved in three. All six responders received maintenance treatment with hydroxyurea and 6-mercaptopurine. The median duration of survival was 9 months. Two patients had long-term survival: one survived 32 months and the other is alive after 30 months. These data suggest that vindesine-prednisone polychemotherapy might improve the prognosis of blast crisis in chronic myeloid leukemia.

Adult↗

Human granulocyte colony growth: differences between serum-free and serum-dependent cultures.

Human granulocyte colony formation has been observed in serum-free methylcellulose cultures with Iscove medium, delipidated bovine serum albumin, iron-saturated transferrin, alpha-thioglycerol, oleylpalmitoyl lecithin, cholesterol, and linoleic acid using serum-free human placental-conditioned medium (SF-HPCM) as the source of colony stimulating factor (CSF). Dose-response curves for SF-HPCM indicated a lower sensitivity to colony-stimulating activity in serum-free cultures than in serum-dependent cultures. Gel filtration of SF-HPCM revealed that CSF fractions with molecular weights in the range of 30 kD are inefficient in serum-free cultures, while fractions with molecular weights in the range of 40 kD stimulate granulocyte colony formation in both types of cultures. These results demonstrate that serum constituents modulate the effects of one of the stimulating factors for granulocyte colony formation, and that serum-free culture conditions are essential for establishing the growth factor requirements of the granulocyte lineage.

Cells, Cultured↗

[Experimental bases of the in vitro treatment of leukemic bone marrow by a derivative of cyclophosphamide: ASTA Z 7557].

The authors report their experience with the ASTA Z 7557, a derivative of cyclophosphamide, for the in vitro treatment of leukemic bone marrows. They determined the sensitivity of human leukemic progenitors (CFU-L, n = 9) and normal progenitors studied in semi-solid media cultures (CFU-GM, n = 37; BFU-e, n = 11) and in long term marrow culture (pré-CFU-GM n = 41). Data establish: The inhibition of the in vitro proliferation of CFU-L by ASTA Z 7557. The similar sensitivity of CFU-L and normal CFU-GM. The respect, at doses toxic on CFU-L and CFU-GM, of more primitive stem cells, capable of self-renewing and the existence of correlation between the intensiveness of treatment and the regeneration capacity of CFU-GM; therefore, they defined a maximum tolerable dose which spares 5 +/- 5% CFU-GM (DL 95) after treatment. The existence of a wide range susceptibility from patient to patient which requires the determination of the DL 95 for each individual patient.

Bone Marrow↗

[Association of autoimmune thrombopenic purpura and leiomyoma. Recovery after excision of the tumor].

A case of auto-immune thrombocytopenic purpura in a woman with benign cystic leiomyoma in Retzius' space is reported. The platelet Coombs' test was positive on platelets; the indirect Coombs' test was negative on serum but strongly positive on cyst fluid. Following excision of the leiomyoma thrombocytopenia rapidly subsided and the serological findings became negative, which strongly suggests that the antibody was produced by the tumour.

Abdominal Neoplasms↗