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Biomedical subjects

D Sicard

Publications and source records attributed to D Sicard.

At least 19 recordsLinked to original sources

HIV type 1-specific IgG2 antibodies: markers of helper T cell type 1 response and prognostic marker of long-term nonprogression.

The helper T type 1 (Th1) function of CD4(+) T lymphocytes is presumed to be of key importance in host defense against HIV-1. As the production of different antibody isotypes is dependent on this helper T function, we investigated whether HIV-1-specific responses of a particular IgG isotype could be a reliable marker of long-term HIV-1 control. Assessment of the IgG subclass distribution in the plasma of HIV-1-infected patients enrolled in the French prospective Asymptomatic Long-Term (ALT) cohort showed that IgG2 directed against HIV-1 Env gp41 and Gag proteins was associated with low viral load, high CD4(+) lymphocyte count, and weak neutralizing activity. By contrast, levels of anti-Env and anti-Pol IgG1 as well as the magnitude of neutralizing activity were correlated with the viral load and thus merely reflect the level of HIV replication. Furthermore, IgG2 directed against Gag proteins was significantly associated with HIV-1 p24-specific Th1 cell production of interferon gamma and interleukin 2. In multivariate analysis, only two variables, anti-gp41 IgG2 and plasma HIV-1 RNA, were found to be independent prognostic factors of remaining long-term nonprogressive over time. By providing new insight into the nature of an HIV-specific antibody response associated with the control of virus replication, these findings have implications for the design of HIV vaccines.

Biomarkers↗

A terminal care support team in a Paris university hospital: care providers' views.

OBJECTIVES: Following three years of a terminal care support team (TCST) activity: (a) to describe current management of terminally ill patients from the care providers' viewpoint, (b) to compare the views of head nurses and physicians about this management, and (c) to identify ways of further improving palliative care. METHODS: A questionnaire was sent to all head nurses and physicians of the hospital. RESULTS: Care-providers consider that the TCST provides therapeutic counselling, training, and psychological help to patients, staff, and families. Few care providers were reluctant to request advice in the management of their patients. Most were satisfied with the partnership with the TCST and deemed it effective. Further improvements suggested for terminally ill patient care included greater assistance from the TCST, especially for nurses, and expanding TCST activities to outpatient management and home care programs. CONCLUSION: Health care providers consider the implementation of the TCST to have been successful.

Attitude of Health Personnel↗

IgG subclass distribution in serum and various mucosal fluids of HIV type 1-infected subjects.

We measured total IgG1, IgG2, IgG3, and IgG4 concentrations by ELISA in serum (S), total saliva (TS), cervicovaginal secretions (CVS), seminal secretions (SPE), and rectal secretions (RS) from either CDC II/III HIV-1-infected subjects or healthy volunteers. Human serum albumin was measured in parallel to calculate the relative coefficient of excretion (RCE). Levels of IgG1 and IgG3 directed against gp120 MN also were measured by ELISA in all samples, and the specific activity (SA) calculated. HIV-1-specific IgG2 and IgG4 were not compared, as total IgG2 and total IgG4 levels in HIV-1-infected subjects were found to be lower than in the healthy controls. Despite substantial interindividual variability, total IgG1 and IgG3 concentrations in all fluids were greater in the HIV-1-infected subjects than in the healthy controls. Calculations of RCE indicated predominantly a transudative origin for IgG subclasses in the different mucosal fluids, except for CVS, in which IgG1, IgG2, and IgG4 was produced locally. The transduction behavior of IgG3 in secretions appears to be different from that of other IgG subclasses. HIV-1-infected subjects were considered positive for IgG1 and IgG3 antibodies against gp120 MN if their antibody levels exceeded the maximum titer measured in the control group. Positive levels of anti-gp120 MN IgG1 were detected for 100% of HIV-1-infected individuals in S, CVS, and SPE, 97% in TS, and 75% in RS. Fewer subjects had positive levels of IgG3 to gp120 MN in their secretions (maximum 67% in CVS). Despite the low concentrations of total IgG3, mean SA values for IgG3 to gp120 MN were greater in secretions than in serum. No significant difference in the SA values for IgG1 to gp120 MN was observed between the different fluids. Only CVS had a local production of HIV-specific IgG1 Our results highlight the importance of an HIV-specific IgG1 and IgG3 immune response in mucosal fluids from HIV-1-infected subjects.

Adult↗

HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma.

Castleman disease (CD) is a lymphoproliferative disorder of unknown etiology that is associated with the development of secondary tumors, including B-cell lymphoma. Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus) sequences have been described in some cases of multicentric Castleman disease (MCD). Using a monoclonal antibody against an HHV-8-latent nuclear antigen, we show that HHV-8 is specifically associated with a variant of MCD in which HHV-8-positive plasmablasts that show lambda light-chain restriction localize in the mantle zone of B-cell follicles and coalesce to form microscopic lymphomas in some cases. Furthermore, we show that the frank plasmablastic lymphoma that develops in patients with this plasmablastic variant of MCD is also positive for HHV-8 and lambda light chain. Plasmablastic lymphoma associated with MCD is a new disease entity associated with HHV-8 infection. (Blood. 2000;95:1406-1412)

Adolescent↗

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↗