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Biomedical subjects

C Liesnard

Publications and source records attributed to C Liesnard.

At least 19 recordsLinked to original sources

High HIV prevalence among patients choosing anonymous and free testing in Belgium, 1990-2002.

From 1990 through 2002, 25,250 anonymous and free HIV tests were performed at a testing site, which carried out the majority (85%) of anonymous testing in Belgium. During the same period, approximately 7.3 million confidential tests were registered nationwide. The rate of new HIV infections diagnosed at the anonymous testing site was 11.1/1000 tests; it was significantly higher than the rate observed among confidential tests (relative risk = 7.41; P < 0.0001). New HIV cases diagnosed through anonymous testing include a higher proportion of young adults (42.0% versus 32.5% in confidential testing; P < 0.001) and a higher proportion of men who have sex with men (32.7% vs. 25.9% in confidential testing; P < 0.02). Anonymous and free HIV testing was particularly sought by persons with higher infection risk, and efficiently contributed to HIV diagnosis in this population. Anonymous and free testing should be and remain an accessible alternative integrated in HIV testing policies.

Belgium↗

High-dose chemotherapy and autologous CD34-positive blood stem cell transplantation for multiple myeloma in an HIV carrier.

The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-positive patients is poorly documented. There are uncertainties concerning the optimal management of this rare disorder. We report on the use of myeloablative chemotherapy with autologous stem cell transplantation in an HIV-positive patient with multiple myeloma.

Acquired Immunodeficiency Syndrome↗

[Medically assisted reproduction in couples carrying the human immunodeficiency virus].

Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication, and a growing number of them want to have children. The benefit of resorting to assisted procreation and the contamination prevention strategies, throughout pregnancy, are summarized as well as the changes in ethical considerations. The balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child, has evolved towards a growing interest for medical intervention in order to avoid the risks of spontaneous conception outside health care structures. We are presenting the medical structure adapted at Erasme hospital and the 38 first requests taken into account by our pluridisciplinary team. This approach, which is coherent from a scientific point of view, respects both the autonomy of people, carrying HIV as well as the essential interest of the child, in being born uninfected, and also has the enormous advantage of allowing access to parenthood without destroying the consistency and coherence of the message of prevention of sexual contamination.

Carrier State↗

[The microbiology department].

From the outset, the Department of Microbiology of Erasme Hospital has striven to offer to clinical teams a full range of high performance tests for diagnosis and therapeutic monitoring of bacterial, viral, fungal and parasitic infections, including opportunistic infections. Furthermore, the laboratory has developed and made available cutting edge tools for the epidemiologic surveillance and outbreak investigation in support to the hospital infection control and antibiotic resistance control programmes. Research and development programmes have led to technological innovation in the fields of molecular virologic diagnosis, notably for HIV and herpes viruses, rapid bacterial identification, detection of resistance genes and epidemiological typing. Research in collaboration with clinical teams has focused on congenital infections, HIV infection, opportunistic infections and prevention of nosocomial infection. The Department acts as national reference laboratory for a number of infectious diseases and co-ordinates or actively participates to several European multicentre studies and epidemiologic surveillance networks.

Belgium↗

Cultured Kaposi's sarcoma tumor cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1.

BACKGROUND: HIV-1 is known to play a critical role in the pathogenesis of AIDS-associated Kaposi's sarcoma (KS). However, it remains controversial whether KS cells are target cells for HIV infection. The aim of this study was to investigate the expression of chemokine receptors in KS cell cultures and to determine whether these cells can be infected by HIV-1. MATERIAL AND METHODS: KS-derived cells and KS-Y1 cells were investigated using RT-PCR for the expression of CD4, CCR3, CCR5, CCR8 and CXCR4 mRNA. HIV infectivity of these cells was determined by p24 antigen and HIV-1 RNA production, as well as by HIV-1 DNA integration. RESULTS AND DISCUSSION: With the exception of CCR8 which is expressed by KS-derived spindle cell cultures but not by KS-Y1 cells, unstimulated KS cells express no significant levels of CD4, CCR3, CCR5 or CXCR4 mRNA. HIV infectivity assays showed that KS cells were unpermissive to HTLVIIIB and JRFL strains. Although the expression of CXCR4 mRNA could be upregulated by interleukin-1beta, stimulation of KS cells by this cytokine did not allow infection by HIV-1. CONCLUSIONS: This shows that KS cells exhibit a chemokine receptor repertoire that does not allow infection by HIV-1. Other cell types making up KS lesions, such as inflammatory cells, are likely to represent the source of HIV-1 products cooperating to promote KS development and progression.

Actins↗

Fatal primary infection due to human herpesvirus 6 variant A in a renal transplant recipient.

We describe a fatal primary human herpesvirus 6 (HHV-6) variant A infection in a kidney transplanted adult woman. On day 20 post transplantation (TX), after rejection therapy, the patient presented an acute hemophagocytic syndrome with hepatitis and central nervous system involvement. HHV-6 IgG and IgM antibodies seroconversion was demonstrated. HHV-6 variant A was the sole pathogen detected by nested PCR and/or culture in blood, bone marrow aspiration, liver biopsy, cerebrospinal fluid and bronchoalveolar lavage. The graft was HHV-6 seropositive and the patient was not transfused before day 28 post TX, suggesting that the virus was transmitted by the graft. Despite immunoglobulins, ganciclovir and foscarnet therapy, the HHV-6 infection progressed and led to severe aplasia. The patient developed Aspergillus fumigatus pneumonia and died from fulminant candidemia. This case demonstrated for the first time that HHV-6 variant A primary infection can cause life-threatening disseminated infection in immunosuppressed patients.

Adult↗

[Medically assisted reproduction and the desire for a child by HIV infected couples: has the time for a change in attitude come?]].

Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication. A growing number of them want to have children. Medical possibilities for preventing contamination of the partners of seropositive men through assisted reproduction and of children thanks to antiviral medicines during pregnancy are summarized. These changes result in ethical considerations which lead the authors to question the conventional systematic medical advise against pregnancy and has encouraged them to assist reproduction for a number of these couples. Today, the balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child has tilted towards medical intervention. It would seem legitimate today to intervene in the most favourable situations rather than see these couples take the risk of spontaneous conception outside health care structures. This implies to adapt medical structure (separate laboratory, appropriate procedure, precise protocols). This approach, which is coherent from the scientific point of view, respects both the autonomy of people carrying HIV as well as the essential interest for the child, in "being" born uninfected and also has the enormous advantage of allowing access to parenthood without destroying the consistency of the message of prevention of sexual contamination.

Anti-HIV Agents↗

ART in HIV-infected couples: has the time come for a change of attitude?

Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication. A growing number of them want to have children. Medical possibilities for preventing contamination of the partners of seropositive men, through assisted reproduction, and of children thanks to antiviral medicines during pregnancy, are summarized. These changes result in ethical considerations which lead the authors to question the conventional systematic medical advice against pregnancy and has encouraged them to assist reproduction for a number of these couples. Today, the balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child has tilted towards medical intervention. It would seem legitimate today to intervene in the most favourable situations rather than see these couples take the risk of spontaneous conception outside health care structures. This implies the need to adapt medical structures (separate laboratory, appropriate procedure, precise protocols). This approach, which is coherent from the scientific point of view, respects both the autonomy of people carrying HIV as well as the essential interests of the child, in being born uninfected, and also has the enormous advantage of allowing access to parenthood without destroying the consistency of the message of prevention of sexual contamination.

Attitude of Health Personnel↗

Screening standards in assisted reproductive technologies. Is the British Andrology Society recommendation to recruit cytomegalovirus negative semen donors only, a reasonable one?

The British Andrology Society recently recommended the exclusion of all cytomegalovirus (CMV) seropositive semen donors to prevent the risk of congenital CMV infection. The recommendation is based on the results of recent studies that identified a high percentage of symptomatic congenital CMV infections in newborns of women with CMV seropositivity pre-existing to pregnancy and on the fact that CMV can be detected in semen of CMV seropositive men. These are not new data. CMV seropositive women can infect their fetuses with their own latent CMV strain that can reactivate, or with an exogenous strain that can be transmitted to them by a sexual partner, but also by contacts, for example with an excreting child. The efficiency of these various ways of transmission to the fetus and the factors that could influence this transmission are for the moment completely unknown. An infectious virus is recovered by culture in the semen of <5% of CMV seropositive men. Exclusion of a large population of donors on the sole criteria of a positive CMV serology introduces the general message that this part of the male population is also not suitable as possible partners in couples who have no fertility problems. The problem of congenital infection in neonates of CMV seropositive women is a complex one that has just begun to be investigated. No data exists concerning this risk in the setting of assisted reproduction. We think that alternatives to the drastic BAS recommendation exist and should be more deeply discussed.

Cytomegalovirus Infections↗

Prenatal diagnosis of congenital cytomegalovirus infection: prospective study of 237 pregnancies at risk.

OBJECTIVE: To develop recommendations for prenatal diagnosis of congenital cytomegalovirus (CMV) infection and evaluate possible prognostic markers. METHODS: We studied 237 pregnant women who had suspected or confirmed primary CMV infections by amniocenteses with or without funipuncture. Diagnosis of CMV was based on culture and polymerase chain reaction (PCR) done on amniotic fluid (AF) samples; fetal blood tests for CMV immunoglobulin M antibodies, PCR, and nonspecific biologic markers; and repeated ultrasound examinations. In cases of pregnancy termination, viral and pathologic examinations of fetuses were done. At birth, CMV infections were sought in newborns. Pediatric follow-up was scheduled for at least 2 years. RESULTS: Of 210 fetuses and newborns correctly evaluated, 55 had CMV infections. Ten of 38 fetuses infected before 20 weeks' pregnancy had severe congenital disease. The global sensitivity of prenatal diagnosis was 80%. Best sensitivity and 100% specificity were achieved by PCR done on AF sampled after 21 weeks' gestation, respecting a mean interval of 7 weeks between diagnosis of maternal infection and prenatal diagnosis. Fetal thrombocytopenia was associated with severe fetal disease. Ultrasound follow-up missed two fetuses who presented with neurologic impairment due to CMV after birth. CONCLUSION: A reliable prenatal diagnosis of congenital CMV infection based on PCR on amniocentesis samples can be made after 21 weeks' pregnancy, after a 7-week interval between diagnosis of maternal infection and antenatal procedure. Ultrasound and nonspecific biologic parameters are not sufficient to identify all fetuses at risk of severe sequelae.

Biomarkers↗

Spontaneous apoptosis and highly active antiretroviral therapy (HAART).

Increased programmed cell death (PCD) or apoptosis has been detected in the T cells of HIV-infected subjects; it is held partially responsible for the continuous loss of CD4+ T cells during the natural course of HIV infection. Highly active antiretroviral therapy (HAART) decreases the viral load and leads to an increase of CD4+ count in vivo. In this study we evaluated PCD in total peripheral blood mononuclear cells, CD8+ and CD4+ lymphocytes before and four weeks after initiation of HAART. Seven HIV-1-infected patients were investigated. Viral load was assessed by RT-polymerase chain reaction and PCD by flow cytometry using apoptosis by 7 amino actinomycin D (7AAD) and propidium iodide (PI). After four weeks of HAART, CD4+ T and CD8+ T cell levels were stable, and plasma HIV-RNA copies were significantly decreased. In four of the patients (4/7), HIV-RNA levels were reduced to undetectable levels (fewer than 400 copies per milliliter). A statistically significant reduction of apoptosis among CD4+ cells was observed (P < 0.03), though neither in the CD8+ T cell population nor in peripheral blood mononuclear cells (PBMCS). These results demonstrate the beneficial effect of HAART on apoptosis of CD4+ cells in the early treatment stage.

Adult↗

A human milk factor susceptible to cathepsin D inhibitors enhances human immunodeficiency virus type 1 infectivity and allows virus entry into a mammary epithelial cell line.

Human immunodeficiency virus type 1 (HIV-1) growth in lymphocyte cultures was increased when the virus inoculum was incubated in breast milk. The enhancing effect of milk was abolished by anti-cathepsin D antibody or by pepstatin A, a cathepsin D inhibitor. The cathepsin D-producing CD4-negative MCF7 mammary cells supported the growth of some HIV-1 isolates. An MCF7 line chronically producing HIV-1 IIIb was obtained. Cathepsin D may induce conformational modification of viral gp120, allowing direct interaction with a coreceptor. We demonstrated the presence of CXCR4 mRNA in MCF7 cells.

Animals↗

HIV-1 infectivity and host range modification by cathepsin D present in human vaginal secretions.

OBJECTIVE: To investigate HIV-1 infectivity in the natural environment of vaginal secretions. DESIGN: Vaginal wash samples collected from 14 healthy women were incubated in vitro with various HIV-1 strains for 10 min at 37 degrees C and then assayed for infectivity on primary lymphocyte cultures, or on CEM cells, or on CD4- ME180 cells derived from vaginal epithelium. METHODS: HIV-1 infectivity was measured by early virus growth in the various host cells tested using a quantitative p24 assay and by the Karber procedure. RESULTS: Preincubation of HIV-1(IIIB) with vaginal wash samples or 2 microg/ml cathepsin D increased the ability of the virus to grow in lymphocyte cultures. The vaginal wash effect was abolished by 5 microg/ml pepstatin A, an inhibitor of aspartyl proteases. Presence of precursor and mature forms of cathepsin D in vaginal wash was demonstrated after passage through a pepstatin A-agarose column. Median tissue culture infective doses of HIV-1(IIIB) and HIV-1(JRFL) strains were increased 14.4-fold and 18-fold, respectively, after preincubation in vaginal wash sample, and were increased by pretreatment with 2 microg/ml cathepsin D. When CD4 receptors of CEMss cells were blocked by OKT4a monoclonal antibody, the cells lost susceptibility to HIV-1 (IIIB), but supported the growth of virus pretreated with vaginal wash sample or cathepsin D. These treated viruses were able to initiate infection of CD4-ME180 epithelial cells, which were not receptive to untreated virus. ME180 cells were shown to possess the messenger of CXC-chemokine receptor-4. CONCLUSIONS: Vaginal secretions may help HIV-1 transmission to women by increasing infectivity for CD4+ cells and allowing entrance into some CD4-epithelial cells.

CD4-Positive T-Lymphocytes↗

A PCR based DNA hybridisation capture system for the detection of human cytomegalovirus. A comparative study with other identification methods.

A simple, sensitive and specific colourimetric hybridisation method for the detection of HCMV DNA in clinical specimens is described. This method combines a PCR assay with a sensitive sandwich hybridisation assay. It relies on the use of a specific capture probe linked covalently to polystyrene microplates and a specific polybiotinylated detection probe. Amplified DNA fragments, sandwiched between these two probes, are detected by an enzymatic colour reaction. This PCR-based colourimetric hybridisation method was compared with other known HCMV detection methods. Clinical specimens (n = 145, corresponding to 106 patients) were tested by both a nested PCR assay and this colourimetric hybridisation method; and by either the culture method or the pp65 antigenaemia test depending on the type of sample used. The results showed that the PCR-based hybridisation method has a specificity similar to tissue culture, known as the conventional gold standard method, and could be used for the examination of the clinical specimens.

Adolescent↗

Natural killer-like T-cell lymphoma of the stomach.

We report the case of a 69-year-old white woman who developed a natural killer (NK)-like T-cell lymphoma involving primarily the stomach. The tumour consisted of large and pleomorphic lymphocytes infiltrating the gastric mucosa. Immunohistochemistry performed on paraffin sections showed the neoplastic cells to be CD3+, CD5-, CD8-, CD43+, CD45RO+, and CD57+. In addition, these cells also expressed HLA-DR, granzyme B, and, to a lesser extent, the CD30 activation marker. No pathologic features suggesting Helicobacter pylori, Epstein-Barr virus infection, or lymphocytic gastritis were found within adjacent normal mucosa. The patient had no previous history of coeliac disease, and her serology for H. pylori was negative. Since lymphomas are usually considered the neoplastic counterpart of normal lymphocytic subsets, it is possible that in this case the tumour cells originate from a distinct cytotoxic T-cell population normally present within the gastric mucosa. The pathogenesis of this highly unusual neoplasm, however, remains a mystery.

Aged↗

Iron as a potential co-factor in the pathogenesis of Kaposi's sarcoma?

The role of iron in the pathogenesis of several tumours is being increasingly investigated. In particular, its involvement in the pathogenesis of Kaposi's sarcoma (KS) is suggested by the distribution of the endemic form of KS corresponding to continental rifts and associated iron-oxide-rich volcanic clays. We investigated in vitro to what extent iron supplementation or withdrawal could affect the growth of KS-derived cells, by analysing the effects of adding iron salts (iron chloride and ferric nitrilotriacetate) and/or reducing iron by iron chelators (desferrioxamine) on KS-derived cell cultures. The addition of iron salts strongly stimulated the growth of KS cells, as reflected by increase in thymidine incorporation and cell number. Conversely, desferrioxamine and deferiprone inhibited cell growth. The inhibitory effect of iron chelation was more pronounced on rapidly dividing basic fibroblast-growth-factor-stimulated cells. These results may point to a novel therapeutic approach to KS.

Carcinogens↗