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Biomedical subjects

D Sicard

Publications and source records attributed to D Sicard.

At least 37 records · Page 2Linked to original sources

DNA damage and repair in cells of lead exposed people.

BACKGROUND: One of the main sources of occupational exposure to lead in Colombia is in workers of battery industries and lead smelters. Genotoxic studies in human populations exposed to this metal have had conflicting results; this type of study has not been reported in Colombia. METHODS: Genotoxic effects of lead were studied in blood cell samples from workers of electric battery factories exposed to lead compounds. Single strand breaks and interference with DNA repair processes after an in vitro exposure of x-rays (300 cGy) were analyzed using the Comet Assay. The battery workers (n = 43) and 13 people not occupationally exposed to lead compounds who were selected as a control group, were classified into four categories according to their blood lead level. RESULTS: A significant difference was observed in DNA damage before the x-rays exposure (basal) between the lowest and highest categories of lead (mean DNA migration 55.6 micro and 85.9 micro, respectively). Additionally, a significant difference in DNA migration was also found immediately after irradiation between the lowest and highest lead categories (mean DNA migration: 199.8 micro and 317.8 micro respectively). The DNA migrations at different times after irradiation did not show a significant difference among the different lead levels. CONCLUSIONS: We concluded that although the single strand breaks following irradiation were not affected by blood lead concentration, the metal seems to sensitize the cells to damage induced by other genotoxicants.

Adolescent↗

[The precaution principle and blood transfusion].

Because of the HIV and HCV virus transmission by transfusion during the eighties, there has been a retrospective reflection about the non-application of the precautionary principle, which has appeared only recently in the medical world. Since it was difficult to identify the real cause of the above-cited transmission in France, mainly because of the bad selection of blood donors, we feel we are justified in applying this precautionary principle more and more, in a monopolistic way, for biological security reasons. As a result, the biological research is not limited to looking for a 'degree zero' risk. Whether it concerns the 'PCR', the research of a new potential virus, the excessive fear regarding the transfusion of the new ESB agent, the worry caused by the blood donors who lived in the British Isles, the need for security based upon the precautionary principle is increasing endlessly. It is, however, more reasonable to consider that the precautionary principle should be essence incite a multi-disciplinary reflection involving biological sciences as well as social sciences. The precautionary principle would not make sense if it were not questioned for bad estimations, its harmful influences or its opportunistic use. Transfusion security, which is so important as a goal and as a principle, cannot appeal to the precautionary principle all the time, since the excessive use of this principle would lead to the paradox of not being able to identify the issues anymore.

AIDS Serodiagnosis↗

Neurological complications of varicella-zoster virus infection in adults with human immunodeficiency virus infection.

This multicentre retrospective study describes the clinical features and prognostic significance of Varicella-zoster virus (VZV)-associated neurological complications. The study was performed in patients with human immunodeficiency virus (HIV) infection, hospitalized for VZV neurological complications, confirmed in every case by positive VZV polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). Between 1990 and 1995, 34 HIV-infected patients were included in the study. At diagnosis, 59% had AIDS, with a median CD4 count of 11 x 10(9)/l. A past history of zoster was noted in 35% of cases. A concomitant herpes zoster rash and/or acute retinal necrosis were noted in 71% and 12% of patients, respectively. The predominant neurological manifestations were encephalitis (13), myelitis (8), radiculitis (7) and meningitis (6). The mean CSF white blood cell count was 126/mm3 and the mean CSF protein concentration was 2.3 g/l. Interferon-alpha level was increased in 36% of patients. VZV was isolated from CSF cultures in 2/6 cases. Magnetic resonance imaging was abnormal, demonstrating encephalitis lesions. After intravenous antiviral therapy, complete recovery was obtained in 18 cases (53%), serious sequelae were observed in 10 cases (29%) and 6 patients died (18%). Severe symptoms and a low CD4 cell count appeared to be associated with death or sequelae. In conclusion, VZV should be considered as a possible cause of encephalitis, myelitis, radiculitis or meningitis in HIV-infected patients, especially in patients with a history of or concomitant herpes zoster or acute retinal necrosis. VZV-PCR in the CSF may allow rapid diagnosis and early specific antiviral treatment.

Adult↗

Pneumonia due to Scedosporium apiospermum in a patient with HIV infection.

A 29-y-old woman from Congo Democratic Republic was admitted to hospital with dyspnoea of 5-months duration. Chest X-ray showed left white lung and infiltrates of the right superior lobe. The patient underwent left pneumonectomy. Histopathological examination showed pulmonary cavitary lesions and bronchectasis full of branching septated fungi. Cultures yielded Scedosperium apiospermum.

Adult↗

Sarcoidosis in a patient with acquired immunodeficiency syndrome treated with interleukin-2.

Concomitant human immunodeficiency virus (HIV) infection and sarcoidosis is rare. Sarcoidlike reactions could belong to the "highly active antiretroviral therapy (HAART)-induced immune restitution syndrome." We report a case of sarcoidosis beginning after 2 months of interleukin-2 (IL-2) therapy in a patient with HIV who had undetectable plasmatic viral load under HAART and we discuss possible mechanisms.

Acquired Immunodeficiency Syndrome↗

[Adherence to antiretroviral treatments with a protease inhibitor in HIV-infected patients].

OBJECTIVE: Long-term therapeutic success of powerful antiretroviral treatments dependent on patient adherence. This study was conducted to assess the difficulties HIV-infected patients with advanced-stage disease encounter in adhering to antiretroviral treatments with a protease inhibitor. PATIENTS AND METHODS: A prospective self-administered questionnaire survey was conducted at our outpatient clinic for 2 months. CD4 counts and HIV viral loads were also determined. RESULTS: Seventy-one percent of the study population which included 262 responded to the questionnaire. The survey was made a median 215 days after initiating the antiprotease treatment with indinavir (71% of the cases), ritonavir (13%), saquinavir (6%), or a combination of protease inhibitors (10%). At onset of antiprotease treatment, mean CD4 count was 171+/-150/mm(3) and mean HIV viral load was 75,000 copies/ml. The treatment was considered to be difficult to take by 43% of the patients; 66% stated they had forgotten to take their drugs at least once a month. It was most difficult to take the drugs prescribed for the afternoon. Shifts of 1 hour were observed in 58% of patients. Non-adherence was frequent (1 failure to take drugs per week), observed in 13% of patients. Most often, the patients stated they had forgotten to take their drugs because of occupational or relational difficulties (52%). Non-adherence increased with duration of treatment. The drug most often associated with non-adherence was indinavir (73%). Age and sex did not influence adherence. Mean RNA HIV serum level was lower than at onset of the antiprotease treatment in the most non-adherent patients. At the time of the questionnaire, there was no difference in serum RNA HIV level or in the percentage of patients with an undetectable level between non-adherent and adherent patients. CONCLUSION: This survey confirmed difficulties in adherence are frequent and worsen with time. No relationship was found between non-adherence and reduction in viral load, suggesting that a short-term effect of these very active drugs despite lack of perfect adherence. Other factors (pharmacology, sensitivity to antiretroviral drugs.) also play a major role in therapeutic success.

Adult↗

Comparison of the distribution of IgG and IgA antibodies in serum and various mucosal fluids of HIV type 1-infected subjects.

We compared IgG and IgA distribution in serum, three different salivary samples, two different rectal secretion samples, cervicovaginal secretions, and seminal secretions from asymptomatic CDC stage II/III HIV-1-infected subjects (n = 44) and from HIV-1-seronegative volunteers (n = 52). In-house ELISAs were used to measure total IgG and total IgA levels, as well as HIV-specific anti-gp120 MN and anti-p24 LAI IgG and IgA. Human serum albumin was titrated in parallel to calculate the relative coefficient of excretion (RCE). In spite of substantial interindividual variability, total IgG concentrations in all fluids were found to be significantly greater in the HIV-1-infected group than in the seronegative subjects. Calculation of RCE values revealed three different types of mucosal secretion: secretions with no local Ig production, such as sperm; secretions with local production of IgA and transudative origin of IgG, such as salivary and rectal samples; and secretions with local production of both IgG and IgA, such as in cervicovaginal secretions. For all mucosal specimens from HIV-1-infected subjects, the response to HIV-1 was predominantly IgG, with highest titers observed in cervicovaginal secretions (although these were lower than serum levels). In contrast, the specific IgA response appeared weaker in the mucosa than in serum.

Adult↗

[Bone marrow transplantation in the treatment of autoimmune diseases. ISAMAIR Group].

EXPERIMENTAL BASIS AND CLINICAL OBSERVATIONS: Remission of an autoimmune disease has been observed in certain patients after bone marrow allograft from a healthy donor. Autoimmune disease in the donor can also be transmitted to an unaffected recipient. These phenomena would be hematopoietic-dependent. BONE MARROW ALLOGRAFTS: Indications for the treatment of refractory autoimmune diseases are exceptional due to the related mortality even in patients without malignant hematologic disease. A NEW THERAPEUTIC CONCEPT: Therapeutic intensification, followed with autologous peripheral stem cell grafts, a procedure with a mortality below 3% in 1997, constitutes a therapeutic alternative in these difficult indication concerning severe refractory autoimmune diseases including: sclerodermia, vasculitis, lupus, inflammatory myositis, autoimmune cyopenia.

Autoimmune Diseases↗

Detection and quantification of HIV-1 in semen: identification of a subpopulation of men at high potential risk of viral sexual transmission.

BACKGROUND: To assess HIV burden in both acellular and cellular fractions of semen in men with different levels of blood plasma HIV RNA by a cross-sectional study. PATIENTS: Fifty-two HIV-1-seropositive men (21 receiving antiretroviral therapy) with CD4 cell counts ranging from 1 to 1170 x 10(6)/l. METHODS: Semen was separated into seminal plasma and fractions enriched in motile spermatozoa or non-spermatozoal cells. HIV RNA was quantified by the HIV-Monitor technique (Roche) in blood plasma, seminal plasma and spermatozoa fractions. HIV DNA or infectious virions in cellular fractions were detected by either PCR or qualitative viral culture. RESULTS: HIV RNA was detected in 86.5% of seminal plasma specimens and in 14.6% of spermatozoa fractions; HIV DNA was detected in 57.1% of non-spermatozoal cell fractions. HIV RNA levels in blood plasma and seminal plasma were correlated (r5 = 0.56, P < 0.0001, Spearman's rank test). A majority of men had lower levels in seminal plasma than in blood plasma: one-third had HIV-positive seminal cell fractions. However, 20 men (38.5%) with HIV RNA levels in seminal plasma (median: 4.65 log10 copies/ml) comparable to or higher than those in blood plasma had all HIV-positive non-spermatozoal cells or spermatozoa fractions with a high frequency of positive cultures. CONCLUSION: A high frequency of men had detectable HIV in semen. We identified a subpopulation demonstrating high levels of HIV RNA in seminal plasma, comparable to or higher than those in blood plasma, frequently associated with a substantial viral shedding in seminal cells, raising the possibility of viral production within the genital tract and suggesting heterogeneity in the potential of HIV sexual transmission among infected men.

Adult↗

Safety and immunogenicity of a live recombinant canarypox virus expressing HIV type 1 gp120 MN MN tm/gag/protease LAI (ALVAC-HIV, vCP205) followed by a p24E-V3 MN synthetic peptide (CLTB-36) administered in healthy volunteers at low risk for HIV infection. AGIS Group and L'Agence Nationale de Recherches sur Le Sida.

A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.

AIDS Vaccines↗

Development and standardization of methods to evaluate the antibody response to an HIV-1 candidate vaccine in secretions and sera of seronegative vaccine recipients.

Enzyme-linked immunosorbent assays (ELISA) were developed to test, in serum and mucosal samples, total IgG, total IgA, serum albumin, and anti-gp120 MN and anti-p24 LAI IgG and IgA levels. These ELISAs were optimized according to reagents and experimental conditions. Inter- and intra-assay coefficients of variation ranged from 3.3% to 18.6%. The ELISA results were linear and precise, and for anti-HIV-1 IgG and IgA, the analytical recovery was close to 100%. For IgG and IgA titration against gp120 MN and p24 LAI, standards were made using pooled sera or gammaglobulins with assigned titres in ELISA units per ml (EU/ml). These standards were used to obtain a linear regression curve that could then be used to obtain the titres of experimental samples. The cut-offs for positivity were determined for sera and mucosal fluid using healthy controls. Validation conditions were defined for ELISAs, and samples that did not satisfy these conditions were retested. Measurement of total IgG and IgA allowed normalization and comparison of the results of specific immunoglobulin levels between different samples. Serum albumin was tested as a marker of transudation from serum to mucosal fluid, allowing calculation of the relative coefficient of excretion, which is one element required to determine the origin of the immunoglobulin detected in mucosal samples. These ELISAs were developed with samples from HIV-1-infected and healthy subjects. We now have the tools to study and understand mucosal immunity in seronegative subjects vaccinated with an HIV-1 candidate vaccine.

AIDS Vaccines↗

Identification of an ancestral resistance gene cluster involved in the coevolution process between Phaseolus vulgaris and its fungal pathogen Colletotrichum lindemuthianum.

The recent cloning of plant resistance (R) genes and the sequencing of resistance gene clusters have shed light on the molecular evolution of R genes. However, up to now, no attempt has been made to correlate this molecular evolution with the host-pathogen coevolution process at the population level. Cross-inoculations were carried out between 26 strains of the fungal pathogen Colletotrichum lindemuthianum and 48 Phaseolus vulgaris plants collected in the three centers of diversity of the host species. A high level of diversity for resistance against the pathogen was revealed. Most of the resistance specificities were overcome in sympatric situations, indicating an adaptation of the pathogen to the local host. In contrast, plants were generally resistant to allopatric strains, suggesting that R genes that were efficient against exotic strains but had been overcome locally were maintained in the plant genome. These results indicated that coevolution processes between the two protagonists led to a differentiation for resistance in the three centers of diversity of the host. To improve our understanding of the molecular evolution of these different specificities, a recombinant inbred (RI) population derived from two representative genotypes of the Andean (JaloEEP558) and Mesoamerican (BAT93) gene pools was used to map anthracnose specificities. A gene cluster comprising both Andean (Co-y; Co-z) and Mesoamerican (Co-9) host resistance specificities was identified, suggesting that this locus existed prior to the separation of the two major gene pools of P. vulgaris. Molecular analysis revealed a high level of complexity at this locus. It harbors 11 restriction fragment length polymorphisms when R gene analog (RGA) clones are used. The relationship between the coevolution process and diversification of resistance specificities at resistance gene clusters is discussed.

Amino Acid Sequence↗