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Biomedical subjects

J M Andrieu

Publications and source records attributed to J M Andrieu.

At least 55 records · Page 3Linked to original sources
PubMed1993

Biologic response to anti-CD16 monoclonal antibody therapy in a human immunodeficiency virus-related immune thrombocytopenic purpura patient.

A patient with refractory human immunodeficiency virus (HIV)-related immune thrombocytopenic purpura (ITP) was treated with 3G8 (anti-CD16) monoclonal antibody on days 1, 3, and 8 (25, 25, and 50 mg were administered intravenously, respectively). Side effects were those expected after the administration of a xenogenic protein, but a severe bone pain occurred from the second injection. At the time of the initiation of the treatment the platelet count was 20,000/mm3 and the absolute CD4 number was 100/mm3. We obtained a long-term correction of thrombocytopenia and, to a lesser extent, there was a stabilization of CD4 lymphocytes for 18 months. We observed a significant stimulation of natural killer (NK) function and an elevation in the serum level of tumor necrosis factor alpha, interferon gamma, and granulocyte-macrophage colony-stimulating factor. This suggests that in HIV-related ITP the removal of platelets is mediated by low-affinity Fc gamma receptors (CD16). The stimulation of NK function and elevation in CD4+ lymphocytes may be related to the production of cytokines by activated human NK cells through the interaction of their CD16-bearing receptor with the 3G8 monoclonal antibody. This observation warrants confirmation and further clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Early identification of human immunodeficiency virus-infected asymptomatic subjects susceptible to zidovudine by quantitative viral coculture and reverse transcription-linked polymerase chain reaction.

The effect of zidovudine (500 mg/day) on 32 asymptomatic subjects seropositive for human immunodeficiency virus (HIV) was evaluated by monitoring the concentrations of infections HIV-carrying blood mononuclear cells and serum virus particles. After 3 months of treatment, a significant reduction in cellular virus load (P < .001) and a marginal decrease in serum viremia (P = .068) were noted. After 6 months, 14 patients (44%) maintained a > or = 50% reduction in virus load, 12 patients (37%) had a virus load that declined by > 50% at 3 months but returned to the initial level at 6 months, and 6 patients (19%) retained their initial virus load. Thus, virus load measurements permit reliable follow-up of antiviral therapy on an individual basis and may enable the identification of patients for whom zidovudine is efficacious.

Base Sequence↗
PubMed1993

High concentration of peripheral blood mononuclear cells harboring infectious virus correlates with rapid progression of human immunodeficiency virus type 1-related diseases.

In a cohort of 103 asymptomatic seropositive subjects (Centers for Disease Control and Prevention [CDC] stage II/III) followed for 2 years, the concentration of peripheral blood mononuclear cells harboring infectious human immunodeficiency virus (HIV) type 1 (viral burden) was correlated with the rate of decrease of CD4 cell count (RD-CD4; R = .857). Rapidly progressing patients (RD-CD4 > or = 60%; n = 18) had a high viral burden (mean +/- SE, 572 +/- 202 cells/mL) and an 89% progression to CDC IV-A-C, while stable patients (RD-CD4 < 30%; n = 55) had a low viral burden (mean +/- SE, 28 +/- 4 cells/mL) and remained asymptomatic. Slowly progressing patients (RD-CD4 > or = 30 and < 60%; n = 30) showed an intermediate viral burden (mean +/- SE, 131 +/- 9 cells/mL) and a 10% CDC IV-A-C progression. Quantitative determination of infectious virus in blood cells adds important information on the prognosis of HIV-1 infection.

Adult↗
PubMed1993

Hodgkin's disease during HIV1 infection: the French registry experience. French Registry of HIV-associated Tumors.

BACKGROUND: The first cases of Hodgkin's disease (HD) associated with HIV infection were reported in 1984. Since then, short series of seropositive patients suffering from HD have been published. In order to identify the characteristics, treatment response and outcome of HIV-associated Hodgkin's disease (HIV-HD), the data of HIV-HD patients recorded between 1987 and 1989 were analysed and compared with those of primary HD patient and with those of HIV-associated non-Hodgkin's lymphoma (HIV-NHL), registered during the same period. PATIENTS AND METHODS: The 45 cases of HD collected by the French registry of HIV-associated tumors between January 1987 and December 1989 were included in this study. All patients were clinically staged according to the Ann Arbor system. To compare HIV-HD characteristics with those of primary HD, we used a cohort of 407 patients with clinical stages (CS) IA to IVB, who were enrolled between September 1981 and August 1988 in a multicentric clinical trial. To identify the relationship between HIV-HD and the course of HIV infection we studied, when available, the routes of infection, initial CD4 cell count at the moment of HD diagnostic as well as the CDC class of HIV infection and compared these data with the same parameters observed in 142 HIV-NHL enrolled in the registry during the same period. RESULTS: HIV-HD is characterized by an increase in mixed-cellularity histology (49%), with a predominance of advanced stages (75%) and B symptoms (80%). A unique observation is made regarding mediastinal involvement, present in only 13% of HIV-HD (71% in primary HD). The HIV-HD/HIV-NHL ratio was significantly higher in intravenous drug abusers than in male homosexuals. Median CD4 cell count was 306/microliters at HIV-HD diagnosis, and only 11% of the cases were preceded by an AIDS manifestation. With standard therapy, 79% of the patients achieved complete remission, but hematological and infectious complications were very frequent. The progression to AIDS rate was 94% at two years and opportunistic infections were the most frequent cause of death. Overall two-year survival was 41% with 71% for patients with initial CD 4 cell counts higher than 300/microliter and 0% for those with CD4 cell counts lower than 300/microliter (P < 0.01). CONCLUSION: HIV-HD has a particular clinico-pathological profile when compared to primary HD, with a predominance of mixed-cellularity type, a high frequency of advanced stages and a high proportion of patients without mediastinal involvement. Moreover, HIV-HD seems to occur preferentially in the group of subjects infected by needle sharing. Standard HD therapy seems to be efficient but excessively toxic.

Adolescent↗
PubMed1993

Lack of isolate-specific neutralizing activity is correlated with an increased viral burden in rapidly progressing HIV-1-infected patients.

OBJECTIVE: To delineate the interaction between in vivo HIV replication and host antiviral immunity during disease progression in order to elucidate the pathogenesis of AIDS. DESIGN: In a cohort of HIV-seropositive patients, the serum concentration of viral particles, the blood concentration of mononuclear cells harbouring infectious virus and the serum titre of isolate-specific neutralizing antibodies were correlated with the rates of CD4+ T-cell depletion and disease progression. METHODS: Using a quantitative reverse-transcriptase linked polymerase chain reaction assay, the concentration of viral particles was measured in blood samples from 103 initially symptom-free subjects who were followed up for > or = 24 months. The concentration of infectious virus and the neutralizing antibodies to autologous HIV isolates were assessed in 37 out of the 103 subjects. The rate of decrease in CD4 cells over the 24 months was calculated for each subject. RESULTS: Rapidly progressing patients (rate of decrease in CD4 cells > or = 60%) had a high concentration of viral particles and a high concentration of infectious virus associated with an undetectable serum titre of isolate-specific neutralizing antibodies. Stable patients (rate of decrease in CD4 cells < 30%) had a low concentration of infectious virus and either a low concentration of viral particles with the absence of isolate-specific neutralizing antibodies or a high concentration of viral particles with the presence of isolate-specific neutralizing antibodies. Slowly progressing patients (rate of decrease in CD4 cells > or = 30 and < 60%) showed an intermediate profile. CONCLUSIONS: Progression to AIDS is associated with a shift in the balance between viral replication and host immunity that increases the concentration of infected cells and destroys the CD4+ T-lymphocyte population.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Hodgkin disease, clinical stages IA-IIB: evaluation of the value of cisplatin. Preliminary results].

Cisplatinum is highly effective in numerous solid tumors and was evaluated in Hodgkin's disease clinical stages (CS) I/II. Sixty-five patients (43 male, 22 female; median age 25, with 12 patients under 16: CS IA-IIA 41, IB 5, IIB 19) were randomly assigned to one of the following arms (PAF87 protocol): 3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine with methylprednisolone) cycles (ABVD arm) or 3 ABVD plus cisplatinum cycles (ABVD-Plt arm) followed by radiotherapy (RT); extended field (40 Gy) RT with a short paraaortic field including the spleen (30 Gy) was then administered in the ABVD arm; extended field (30 Gy) without lombosplenic port prophylaxis. RT was administered in ABVD-Plt arm when patients were in complete remission (CR) after chemotherapy (CT). Median follow-up was 35 months (6-62 months). During CT, 1 patient (ABVD-Plt) died from viral meningo-encephalitis; five patients (1 ABVD, 4 ABVD-Plt) stopped treatment because of emesis, of whom three receiving only 1.5-2.5 (ABVD-Plt) cycles, are still in CR after 13-60 months. Fifty-five patients (27 ABVD-Plt) were in CR after CT. Among the 27 ABVD-Plt patients, all in CR after RT, two died (one from myocardial infarction and one from immunoblastic lymphoma); one patient from the ABVD arm died from gastro-intestinal hemorrhage in 1st CR. No ABVD-Plt patient relapsed; 1 ABVD patient relapsed in non-irradiated area. At five years, actuarial survival/relapse-free survival was 96.1/90% and 88.2/100% for ABVD and ABVD-Plt patients, respectively.

Adolescent↗
PubMed1992

Elevation of IgE in HIV-infected subjects: a marker of poor prognosis.

The IgE synthesis is tightly controlled by a complex network of T and B cells. Because human immunodeficiency virus (HIV) disease associates T cell activation and depletion, polyclonal B cell activation, atopic symptoms, drug hypersensitivity, and autoimmune activity, we have evaluated IgE, as well as IgA, IgG, and IgM, in 315 HIV-seropositive individuals with or without acquired immunodeficiency syndrome (AIDS) and compared the results to those of 100 HIV-seronegative subjects. IgE levels were higher in HIV-infected subjects as a whole, compared to levels in seronegative control subjects (p less than 0.05). This difference was particularly marked between patients with AIDS and control subjects (p less than 0.005). A strong relationship appeared between IgE and the immune status as assessed by CD4 cell counts (p less than 0.001 between IgE values in patients with CD4 less than 300 or greater than 300/microliters). In addition, we assessed the predictive value of IgE elevation over disease progression: in subjects with a CD4 count less than 300/microliters, the survival analysis disclosed a 24-month occurrence rate of AIDS of 83% in individuals with IgE greater than 150 KIU/L versus 44% in individuals with IgE less than 150 (p = 0.016). In subjects with an AIDS-related complex, IgE greater than 150 indicated a 100% rate of AIDS versus 9% in individuals with IgE less than 150 (p = 0.003). Thus, IgE levels appear to be a very discriminative marker between patients in late stages of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Relationship between frequency of infectious human immunodeficiency virus type 1-harboring cells and kinetics of viral replication: a simple procedure for quantitation of infectious virus-carrying cells in blood samples.

Statistical analysis of a limiting dilution assay (LDA) showed that the occurrence of infectious human immunodeficiency virus type 1 (HIV-1)-harboring cells in serially diluted samples of peripheral blood mononuclear cells (PBMCs) of HIV-1-seropositive patients fits the model describing a single-hit Poisson distribution. This observation led to the discovery that there is a direct correlation (r = 0.957) between the number of HIV-1-positive cells and the time when viral culture produces 1 ng of the HIV-1 p24 gag protein per ml. Frequency estimates based on this relationship were highly accurate (P less than 0.01) within the first 15 days of viral culture, which consisted of coculture of 10(6) normal PBMCs with the equivalent number of test PBMCs. This approach was less cumbersome than LDA and was sensitive enough to detect a single infectious HIV-1-harboring cell among as many as 320,000 cells. The values obtained for 57 patients agreed well with the data in the literature and showed that the frequencies of infectious cells in PBMCs reflect the advancement in the clinical stage, being 1/38,000, 1/11,000, and 1/7,000 for asymptomatic patients (Centers for Disease Control [CDC] group II/III), patients with AIDS-related complex (CDC group IVa), and patients with AIDS (CDC group IVb/c), respectively. A nearly 10-fold disparity in mean frequencies was observed when these values were correlated with the numbers of CD4-positive cells (1/9,000, 1/1,500, and 1/300, respectively, for asymptomatic patients, patients with AIDS-related complex, and patients with AIDS). The described method provides a simple means of determining infectious HIV-1-positive cells in blood samples.

HIV Infections↗
PubMed1992

Similar replication capacities of primary human immunodeficiency virus type 1 isolates derived from a wide range of clinical sources.

Numerous studies have suggested that there are significant differences in replication capacities and cytopathicities among human immunodeficiency virus type 1 (HIV-1) isolates and that these differences correlate with the clinical status and geographical origin of infected individuals. However, it has been difficult to assess whether reported distinctions could be attributed to the methods used or whether they imply a true disparity between viral isolates. We thus attempted to characterize the replication properties of HIV-1 isolates directly recovered from infected patients (primary isolates) by using a standardized infection assay. Viruses were isolated from patients' peripheral blood mononuclear cells (PBMC) by a single coculture with normal donor PBMC stimulated with phytohemagglutinin. Replication curves and cytopathic effect of a standard inoculum (1 ng of p24) of 66 primary HIV-1 isolates were similar regardless of clinical stage of the patient (asymptomatic, AIDS-related complex, or AIDS) and evolutive feature (rate of progression to AIDS). There was no difference between viruses derived from patients sensitive to zidovudine and those derived from patients resistant to zidovudine. Moreover, no difference was found among viral isolates of different geographical origins (Central Africa, Zaire, Brazil, or France). Similarly, the replication patterns and cytopathicities of isolates from bronchoalveolar lymphocytes did not differ from those of isolates derived from PBMC. In contrast, the same amount of viral inoculum of five laboratory HIV-1 strains (HIV-1, EL1, SF, MN, and RF) produced different replication curves and were much less cytopathic. In contrast to laboratory viral strains, it appears that the primary HIV-1 isolates tested, whatever their clinical status and source, exhibited similar replication capacities and cytopathicities in allogeneic donor PBMC.

AIDS-Related Complex↗
PubMed1992

[Biology of small-cell bronchogenic carcinoma: recent advances].

In the last ten years considerable progress has been made in small-cell lung carcinoma (SCLC) biology, along with the technical progress made in molecular biology. This progress now allows us to propose a model for the genesis and the development of this type of tumor. Tobacco, the principal causal factor plays a dual role. In bringing about secretion of growth factors by the bronchial epithelia, usually involved in the normal development of lungs, and by functioning autocrinally and paracrinally, it facilitates the occurrence of mitotic mutations. Without directly contributing to cellular transformation, this autocrine functioning also gives a selective advantage to cells going through transformation or immortalization. The procarcinogenic or carcinogenic agents contained in tobacco smoke, whose level of production could be genetically determined, would also contribute to the accumulation of mutations affecting both suppressor genes and oncogenes. Two tumour suppressor genes have been identified: RB1 and P53. At least one other putative tumour suppressor gene has constantly been implied. It lies on the short arm of chromosome 3. There could also be the possibility of detecting subjects susceptible to developing an SCLC, a functional hemizygote still needing evaluation. The activated oncogenes principally belongs to the myc family. Their activation could correspond with the appearance of cellular clones having aggressive behavior independent of growth factors, chemoresistant and more metastatic. SCLC may be distinguished from other malignant lung tumors by a fairly characteristic pattern consisting of the loss of suppressor genes and the activation of oncogenes. The links between the neuroendocrine properties of this type of tumor and its characteristic description are being clarified and will contribute to a better understanding of the relationship between the different types of lung tumors. From this biologic knowledge follow several therapeutic applications under investigation (blocking autocrine loop through anti-GRP antibodies), as well as potential applications (concerning the products of suppressor genes) and possible applications such as prevention oriented towards detection of high-risk subjects.

Carcinoma, Bronchogenic↗
PubMed1992

[Hodgkin's disease associated with HIV infection: clinical characteristics and development. French registry of tumors associated with HIV infection].

From May 1987 to July 1990, 45 cases of Hodgkin's disease (HD) were recorded by the French Registry of HIV-associated tumors. Thirty-nine patients were male and median age was 30 years. Twenty-two cases had mixed cellularity type (MC), 18 nodular sclerosis, two lymphocyte depletion and three were not classified. Thirty-four patients had advanced HD clinical stages (CS III and IV). Thirty-six patients (80%) presented with B symptoms. Bone marrow involvement was diagnosed in 12 patients. Mediastinal involvement was present in only 4/30 patients (12%). Risk groups for AIDS were homosexuality in 18 cases, intravenous drug abuse in 17, both in one, and other in nine cases. In 40 cases (89%), HD occurred before any AIDS-related episode. Median CD4 cell count at HD diagnosis was 304 cells/microliters. Seventy-nine percent of the patients achieved complete remission with standard therapy, but hematological and infectious complications were very frequent. The rate of progression to AIDS was 71% at three years and opportunistic infections (mainly pneumocystis carinii pneumonia) were the most frequent cause of death. Overall two-year survival was 41% (78% for patients with initial CD4 cell count higher than 300 cell/microliters and 0% for those with CD4 cell count lower than 300/microliters). HD-HIV has a specific clinical profile as compared to primary HD, with a predominance of MC type and advanced clinical stage, without mediastinal involvement (88%). This study provides a basis for future clinical trials on HD-HIV: intensity of chemotherapy should be adapted to CD4 cell count; pneumocystis carinii prophylaxis is mandatory in all cases. Zidovudine should be included during and after HD treatment; the potential role of hematological growth factors has still to be evaluated.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Small cell lung cancers: intensive and short chemotherapy followed by irradiation. Results of a pilot study].

Twenty-six patients with localized small cell lung cancer received 3 monthly courses of intensive chemotherapy consisting of cisplatin (40 mg/m2/day on days 1, 2, 3), cyclophosphamide (750 mg/m2/day on days 4 and 5), adriamycin (50 mg/m2/day on day 5), vindesine (2 mg/m2/day on days 1 and 5), etoposide (100 mg/m2/day on days 1, 2, 3) and methylprednisolone (120 mg/m2/day on days 1 to 5). The first 10 patients received radiotherapy of the chest (3 Gy/day on days 7 and 8) and brain (2 Gy/day on days 7 and 8) after each course of chemotherapy, followed by complementary chest (27 Gy) and brain (22 Gy) radiotherapy after the end of the aplasia induced by the 3rd course of chemo-radiotherapy (alternate protocol: AP). In view of the toxicity of this protocol (4 deaths) and of the occurrence of 2 epidural relapses, the remaining 16 patients received the same 3 courses of chemotherapy followed by radiotherapy of the chest (55 Gy), brain (34 Gy) and spinal cord (34 Gy) (sequential protocol: SP). Haematological toxicity was controlled without problem in a medical oncology intensive care unit. The complete response rate (AP + SP) was 100 percent. The median survival rate was 26 months. Survival at 2 years was 20 percent with AP and 78 percent with SP (P = 0.002), this difference being due to the absence of iatrogenic deaths and epidural relapses. Intensive chemotherapy combined with radiotherapy deserves to be developed in the management of localized small cell lung cancer.

Actuarial Analysis↗