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Biomedical subjects

J P Aymard

Publications and source records attributed to J P Aymard.

At least 19 recordsLinked to original sources
PubMed1993

Biliary elimination and pharmacokinetics of vinorelbine in micropigs.

The biliary elimination and pharmacokinetics of vinorelbine (NVB) were investigated in five conscious micropigs provided with a double-terminal choledocal fistula allowing the collection and reinstillation of bile. After the i.v. administration of NVB (0.5 mg/kg), serum and bile samples were collected over a 48-h period. The concentrations of NVB were measured by high-performance liquid chromatography. The serum concentrations decreased rapidly from a maximal value of 208.6 ng/ml (SD, 111.7 ng/ml). The mean half-life was 10.9 h (SD, 8.6 h) and the mean AUC0-48 h was 292.8 ng ml-1 h (SD, 79.4 ng ml-1 h). The bile concentrations were high, amounting to 16.0 micrograms/ml (range, 5.4-27.7 micrograms/ml). The 0- to 48-h biliary excretion of unchanged NVB accounted for 25.8% (SD, 5.7%) of the injected dose, with 21.5% (SD, 4.0%) being eliminated during the 0- to 8-h period. Desacetyl-NVB was found in an inconstant manner and in very low amounts in bile samples. In addition, no glucuronide of NVB could be detected. Thus, in the micropig, biliary excretion represents an important route of elimination for NVB.

Animals↗
PubMed1993

[Seroprevalence of hepatitis C antibodies among blood donors. Study of second generation ELISA and RIBA tests and surrogate markers].

Between March and November 1991, prevalence of hepatitis C antibodies was evaluated in 60,960 blood donors from the North-East of France. Using a second generation ELISA, 424 donors (0.69%) were reactive, with no significant difference between males (0.69%) and females (0.70%). Among these 424 donors, respectively 137 (32.3%), 86 (20.3%) and 201 (47.4%) were reactive, indeterminate or nonreactive by a second generation RIBA (RIBA-2) (Recombinant Immunoblot Assay). Donors with a high ELISA ratio (> or = 4) were significantly more likely to have a reactive RIBA-2. Of the 1906 donors with anti-HBc positivity (3.12%), 44 had a reactive ELISA; of these, respectively 27, 12 and 5 had a reactive, indeterminate and nonreactive RIBA. Of the 1201 donors (1.97%) with increased serum ALAT (alanine-amino-transferase) levels (> or = 2N), 42 had a positive ELISA; of these, respectively 35, 2 and 5 had a reactive, indeterminate and nonreactive RIBA. Of the 54 donors with both indirect markers, nine had a reactive ELISA; the same nine donors had a reactive RIBA. These data show that donors with both surrogate markers and a reactive ELISA are very likely to have a positive RIBA. Seventy-seven (18.16%) of the 424 donors with a reactive ELISA had at least one surrogate marker; 67 of these donors (30.04%) were among the 223 donors with a reactive ELISA and a reactive or indeterminate RIBA.

Biomarkers↗
PubMed1992

The in vitro effect of amodiaquine on bone marrow granulocyte-macrophage progenitor cells from normal subjects.

Amodiaquine is used for antimalarial prophylaxis and treatment and has been associated with neutropenia and agranulocytosis in man. The effect of the drug on the in vitro growth of bone marrow human myeloid progenitor cells (GM-CFU) was tested using the soft agar culture technique: 42 haematologically normal subjects were studied and it was found that amodiaquine, at concentrations tested in vitro (0.005, 0.05 and 0.5 micrograms.ml-1), had no quantitative effect on the colony and cluster growth. Our results argue against direct toxicity of the drug on GM-CFU. Therefore, in cases of amodiaquine-associated neutropenia, alternative mechanisms should be considered: a abnormally sensitive GM-CFU; b) toxic effect of metabolites such as desethyl-amodiaquine; c) immune-mediated toxicity.

Adolescent↗
PubMed1990

[Serum antibodies against hepatitis C: study of 4,100 blood donors from the northeast of France].

Between June 1989 and February 1990 the prevalence of antibodies to hepatitis C virus (anti-HCV) was studied in blood donations from 4,100 donors tested in north east France. 37 samples were found reactive for anti-HCV (prevalence of anti-HCV: 0.90%) without any significant difference in sex (males: 0.94%; females: 0.87%) and age distributions. 178 (4.34%) of the 4,100 donors were found anti-HBc positive, 5 of these donors being anti-HCV positive (13.51% of all anti-HCV positive donors). 52 donors (1.27%) had raised alanine aminotransferase (ALT) levels (greater than or equal to 2 N: 2 times the M +/- 2 SD value): 3 were found anti-HCV positive (8.11% of all anti-HCV positive donors). Association of the 2 surrogate markers is poorly sensitive since it detects only 8 (21.62%; males: 4, females: 4) of all anti-HCV positive donors. Furthermore, it appears weekly specific since it discards 230 blood samples of which 222 (96.52%) were anti-HCV negative. The 2 surrogate markers are complementary to one another and none of the anti-HCV positive donors had both anti-HBc antibodies and raised ALT. The mean ALT level is significantly higher in anti-HCV positive donors as compared to seronegative (M +/- 1 SD: 51 +/- 82 U/l versus 24 +/- 17 U/l). In anti-HCV positive donors, a marginal (r = 0.34) though statistically significant (p less than 0.05) positive correlation was found between ALT level and anti-HCV ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1989

Toxicity of HPA-23 (ammonium-21-tungsto-9-antimoniate) for normal human myeloid progenitor cells (GM-CFU) in vitro.

HPA-23 is a competitive inhibitor of the RNA-dependent DNA polymerase (reverse transcriptase) of the human immunodeficiency virus (HIV). It may therefore potentially benefit patients with HIV infection. This study aimed at defining the haematopoietic toxicity of this drug and particularly its effects on the normal human granulocyte-macrophage progenitor cells (GM-CFU). Our in vitro studies, in semi-solid agar, have shown an inhibitory effect of increasing concentrations of HPA-23 on colony and cluster formation. This effect is probably dose-dependent. An almost complete inhibition of colony formation was observed at doses of more than 20 micrograms/ml. Regarding cluster formation, a similar although much more progressive inhibitory effect was found. Our experimental data should be extrapolated with caution to clinical situations. However, they must be kept in mind for optimal design of HPA-23 therapy in HIV infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Epidemiologic study of HIV serology in blood donors from 5 departments in northeastern France (1985-1989)].

Between July 1985 and June 1989, the prevalence of HIV antibody was studied in 503,019 blood donations tested in 5 administrative areas ("departments") of north east France: 91 seropositive donations (donors) were detected (prevalence: 0.18%). The prevalence was 0.41% in 1985, 0.22% in 1986, 0.14% in 1987, 0.10% in 1988 and 0.11% in 1989: in each year, it was found lower than the national prevalence. 14 (15.4%) of the 91 seropositive donors were females, and the prevalences of HIV antibody in blood donations from female and male donors were 0.07% and 0.26% respectively. All seropositive donors were younger than 50 and 83 (91.2%) younger than 40. The prevalence of HIV antibody was higher in blood units at first donation (occasional donors) as compared with blood units collected from regular donors (0.60% versus 0.09%). The prevalence of HIV antibody was higher in blood donations from military donors as compared with donations from civilian donors (0.49% versus 0.07% in 1987, 1988 and 1989). Most seropositive military donors were young male recruits of the national armed forces conscription system. We believe that these recruits are subjects with risk factors which must be taken into account for the determination of national blood supply policies.

Adult↗
PubMed1989

Amodiaquine-induced immune agranulocytosis.

This report describes two patients who developed agranulocytosis while receiving prophylactic amodiaquine treatment. The neutrophil counts returned to normal in one after stopping the drug while the other died of sepsis. Amodiaquine-dependent circulating neutrophil IgG antibodies were demonstrated in both patients using the indirect granulocyte immunofluorescence test. The antineutrophil antibody activity was enhanced with the use of the major amodiaquine metabolite, mono-desethyl amodiaquine. Additional studies showed the activity of the sera to be nondialysable, heat stable, active against autologous as well as allogenic cells, and absent from the convalescent sera. There was no growth inhibition of allogenic myeloid committed progenitor cells (CFU-GM) following incubation with the patients' sera, complement and amodiaquine. These results indicate that agranulocytosis can be mediated by a drug-dependent antibody which affects mature blood cells.

Agranulocytosis↗
PubMed1989

Amodiaquine-induced agranulocytosis: report of a case with in vitro studies of granulocyte-macrophage progenitor cells.

We report a case of amodiaquine-induced agranulocytosis in a 60-year-old woman. Four months after the agranulocytosis episode we investigated the effect of the drug using in vitro agar culture techniques. Amodiaquine at increasing concentrations (0.005, 0.05 and 0.5 microgram/ml) displayed an inhibitory effect, probably dose-dependent, on the growth of the patient's bone marrow GM-CFU colonies in the absence of autologous serum. In contrast, no effect was found on the colony and cluster growth of bone marrow samples from 13 healthy controls. Though it has been shown in several cases that amodiaquine-induced agranulocytosis occurs via immune-mediated mechanisms, our data are in support of a direct toxic effect of the drug on abnormally sensitive myeloid progenitor cells.

Agranulocytosis↗
PubMed1989

Analysis of blood CD4+ and CD8+ T-lymphocyte subsets with monoclonal antibodies. Comparison of the Genetic Systems CD4/CD antigen typing kit with conventional indirect immunofluorescence microscopy and the automated Technicon-H1 Enzyme Immunoassay (EIA).

The Genetic Systems Technique (GS: direct immunofluorescence microscopy with ethidium bromide counterstaining of nuclei) was tested for quantitative analysis of T-lymphocyte subsets in human peripheral blood. The monoclonal antibodies anti-CD4 and anti-CD8 were used for detection of T-helper and T-suppressor cells respectively and the results compared to those obtained by conventional indirect immunofluorescence microscopy and the Technicon Enzyme Immunoassay (EIA) with automated reading. The GS technique provided results correlating well with both indirect immunofluorescence and EIA techniques. Moreover, this method has two advantages: it is less time-consuming than the indirect immunofluorescence microscopy and necessitates less expensive and more commonly available equipment than the automated EIA technique.

Antibodies, Monoclonal↗
PubMed1988

Lymphocyte proliferative responses in haemophiliac patients: relations to clinical and immunological findings.

Blood lymphocyte proliferative responses to mitogens were studied in 65 patients with haemophilia (haemophilia A: 54 patients, haemophilia B: 11 patients) in parallel with 39 male control subjects. As a group, patients with haemophilia did not demonstrate abnormal proliferative responses to phytohaemagglutinin (PHA), Concanavalin A (ConA) and pokeweed mitogen (PWM) when compared with healthy controls. When the patients were analysed according to their seropositivity for antibody to human immunodeficiency virus (HIV), those who were positive had significantly decreased PHA, ConA and PWM responses. Haemophiliac patients with T4+/T8+ ratios less than 1 had reduced proliferative responses to PHA, ConA and PWM when compared to patients with ratios greater than 1. No significant difference in mitogen responses were found when the patients were analysed according to the presence or absence of palpable lymphadenopathy. Those patients with haemophilia A who had received more than 5 x 10(4) units of factor VIII during the two years preceding the study showed no significant difference in PHA, ConA and PWM responses when compared to patients receiving less.

Adolescent↗
PubMed1987

[Clinical and biological evaluation of the preventive role of anti-cytomegalovirus specific immunoglobulins in bone marrow grafts. Randomized study of 60 patients].

The effects of i.v. cytomegalovirus (CMV) immunoglobulin given for prophylaxis of CMV infections in recipients of allogeneic and autologous marrow transplants were evaluated in a randomized trial: 60 patients were randomly assigned to receive (30 patients) or not to receive (30 patients) CMV immunoglobulin for a period of 90 days after transplantation. As to the allografted patients, the cumulative incidence of asymptomatic and symptomatic CMV infections was significantly reduced in the CMV immunoglobulin-treated group as compared to the control group (56.5% versus 92.9%, P less than 0.05). No other statistically significant effect of CMV immunoglobulin could be found. In particular, the incidence of symptomatic CMV infections (including interstitial pneumonia), the mean delay of post-transplant viraemia and haematopoietic recovery were similar in the control and CMV immunoglobulin-treated groups. We conclude that prophylactic CMV immunoglobulin administration, as designed in our study, is no more than marginally effective and cannot be recommended without additional trials.

Antibodies, Viral↗
PubMed1987

[Legionnaires' disease in hairy cell leukemia. 2 new cases].

We report the cases of two patients who developed legionnaires' disease during the course of hairy cell leukaemia. The clinical features are described with special emphasis on the severity of illness in one patient and marked jaundice in both. These cases demonstrate the enhanced susceptibility to Legionella pneumophila infections in patients with hairy cell leukaemia. We therefore suggest a reevaluation of empiric antimicrobial treatment of pneumonia in such patients.

Aged↗
PubMed1986

[Occurrence of non-A, non-B post-transfusion hepatitis in heart surgery. Prospective study on the value of the determination of serum alanine aminotransferase and detection of anti-HBc antibodies in blood donors].

We studied a group of 64 patients undergoing cardiac surgery for the occurrence of post-transfusion hepatitis during a follow-up period of 5 months. They received blood units (packed red cells in saline-adenine-glucose medium and/or fresh frozen plasma exclusively) from 447 volunteer donors. Post-transfusion hepatitis was identified in 5 patients: 1 patient had cytomegalovirus hepatitis and the remaining 4 cases were defined, by exclusion, as non-A, non-B hepatitis (with prevalence and incidence rates of 80% and 6.25% respectively). We found no statistically significant differences between the numbers of transfused blood product units in patients who developed non-A, non-B hepatitis as compared to those who did not. Our analysis of the predictive effectiveness of alanine aminotransferase and anti-HBc antibodies screening in blood donors to prevent non-A, non-B post-transfusion hepatitis led to the following conclusions: we failed to confirm the association between anti-HBc in blood donors and enhanced risk of non-A, non-B hepatitis in recipients since no case developed among patients receiving blood products from anti-HBc positive donors. So, 20 donors (4.5%) would have been discarded without any reduction of the incidence of non-A, non-B hepatitis. we could not confirm nor exclude the possibility that screening donor blood for elevated alanine aminotransferase levels would have reduced the number of non-A, non-B hepatitis in recipients.

Adult↗
PubMed1986

Post-transfusion non-A, non-B hepatitis after cardiac surgery. Prospective analysis of donor blood anti-HBc antibody as a predictive indicator of the occurrence of non-A, non-B hepatitis in recipients.

We prospectively studied the incidence of post-transfusion non-A, non-B hepatitis in 64 cardiac surgery patients: 4 (6.25%) developed non-A, non-B hepatitis after an incubation period of 4-10 weeks. Units of blood products from donors seropositive for antibody to hepatitis B core antigen (anti-HBc) were not associated with a greater risk of non-A, non-B hepatitis in recipients than units from seronegative donors. Our data indicate that donor blood anti-HBc testing is of no value as a screening method to reduce the incidence of post-transfusion non-A, non-B hepatitis.

Adult↗