Biomedical subjects
P Hermans
Publications and source records attributed to P Hermans.
[Histoplasmosis of the oral cavity].
Histoplasmosis is an endemic mycosis. Histoplasma capsulatum, and duboisiï are the pathogenic agents in humans. The disease is reported as endemic in more than 30 countries. Three clinical forms are distinguished; acute, chronic and disseminated. Oral lesions may take on different clinical aspects which are often associated with disseminated histoplasmosis. Disseminated histoplasmosis is frequently diagnosed in immunocompromised hosts. High risk of mortality dictates rapid diagnosis and treatment.
[Angiographic-histological correlation of late exudative age-related macular degeneration].
AIMS: To correlate the fluorescein angiographic (FAG) classification in age-related macular degeneration (AMD) with the histology of surgically excised choroidal neovascularization (CNV) membrane specimens. METHODS: 36 subretinal lesions surgically excised during macular translocation were investigated by light microscopy. Histologic results were correlated with fluorescein angiographic findings. RESULTS: Classic CNV lesions showed a subretinal fibrovascular membrane on histological examination. About 50% of the investigated classic CNV lesions had additional subpigment epithelial components, too. Occult CNV lesions showed a subpigment epithelial fibrovascular membrane on histological examination. A common histological component in lesions of exudative age-related macula degeneration was the appearance of diffuse deposits at the choroidal side of the retinal pigment epithelium. CONCLUSION: Different FAG characteristics in exudative AMD lesions were comparable with the histological results. In correspondence with FAG classification the CNV membranes were localized in different positions in relation to the RPE.
Stimulation of Kaposi's sarcoma cell growth by urine from women in early pregnancy, the current source for clinical-grade human chorionic gonadotropin preparations.
Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the results of clinical studies using commercial hCG preparations KS remain highly contradictory. More particularly, some hCG preparations could have a paradoxical growth effect on KS. Such discrepant results may be explained by the fact that the anti-KS activity is not associated with hCG itself but with one or more factors that are co-purified with the hormone. We found here that crude urine from first trimester pregnant women, the current source for commercial hCG, had a growth stimulatory effect on KS cells. By contrast, urine from last trimester pregnant women, from non-pregnant young women, from menopausal women and from men exhibited neither a growth stimulatory nor a growth inhibitory effect on KS cells. The amplitude of this pregnancy urine-associated pro-KS activity/hCG unit was higher than that achieved with clinical-grade hCG preparations. Partial co-purification of pregnancy-associated factors during the extraction procedure of commercial hCG from urine may explain the pro-KS activity achieved with some hCG preparations. We, therefore, suggest a cautious use of hCG purified from pregnancy urine for the treatment of KS.
Human herpesvirus 8 investigations: a role in the clinical management of Kaposi's sarcoma?
Kaposi's sarcoma (KS) is a vascular tumour associated with infection by human herpesvirus 8 (HHV-8). Most of the recent studies on KS have focused on the epidemiology and molecular biology of HHV-8. However, the contribution of virological investigations into HHV-8 to the clinical management of KS has been poorly evaluated so far. From a diagnostic point of view, HHV-8 currently appears as a useful tool for distinguishing KS from its mimics. Seroconversion to antibodies against HHV-8 may predict the development of KS in susceptible individuals, and reduction of HHV-8 viraemia is associated with therapies effective against KS. Further prospective studies are still required to determine the role of serological or genotypic investigations into HHV-8 in the prevention of KS and in KS response to therapy.
Viral load outcome of non-nucleoside reverse transcriptase inhibitor regimens for 2203 mainly antiretroviral-experienced patients.
OBJECTIVE: To assess the factors associated with virologic response to non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens in a large clinic cohort. DESIGN: Inception cohort. SETTING: HIV clinics in Europe PATIENTS: We identified all patients in EuroSIDA who began a regimen including either nevirapine or efavirenz (not both) after July 1997 and for whom pre-therapy viral load and CD4 cell count were known. MAIN OUTCOME MEASURES: Virological failure. RESULTS: A total of 1325 patients initiated nevirapine and 878 efavirenz. Respectively, median start dates were October 1998 and May 1999. Other factors at baseline, including CD4 cell count, viral load, previous AIDS, previous antiretroviral drug use and make-up of the NNRTI-containing regimen were all approximately similar between the nevirapine and efavirenz groups. A total of 669 patients experienced virological failure during follow-up. In a Cox model, less protease inhibitors and nucleoside reverse transcriptase inhibitors (NRTIs) previously used, higher CD4 nadir, lower viral load at baseline, a previous AIDS diagnosis and less NRTIs in the regimen were associated with lower risk of virological failure. The relative hazard of virological failure comparing those on efavirenz with those on nevirapine was 0.57 (95% confidence interval, 0.47-0.69; P < 0.0001). CONCLUSIONS: The difference in virologic outcome between those using nevirapine and efavirenz in this almost entirely drug-experienced population could reflect differences in effectiveness of the drugs in this setting but, despite the similarity between groups at baseline, bias cannot be excluded as an explanation. Replication of these findings in randomized trials and other cohort studies is required.
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.
Current review and clinical management of patients with primary HIV-1 infection: limits and perspectives.
Acute primary HIV-1 infection (PHI) remains underestimated or misdiagnosed in clinical practice. Meanwhile, it has been demonstrated that early therapeutic interventions with highly active antiretroviral therapy (HAART) may delay disease progression and possibly preserve and expand the most effective immune effector T-cells against HIV together with the humoral immune responses. Since long-life HAART is an unachievable goal due to long-term toxicity and risk of occurrence of resistant strains due to a decreased compliance or other still undefined host factors, preliminary data of programmed treatment interruption in patients treated for PHI suggest that a significant number (30-50%) could benefit from long periods off therapy. However, in more than half of them, the viral load will rebound, justifying that treatment be reinitiated. In order to reduce this proportion, new options are currently being investigated, including adjunctive immune therapy to HAART such as cytokines or vaccines, which could tackle the viral rebounds by increasing HIV-specific cellular responses. An update on the management of patients with PHI is reviewed and the limits of the current standard of care are discussed.
Acute pulmonary hypertension following paclitaxel in a patient with AIDS-related primary effusion lymphoma.
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Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis.
Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.
[Polymyositis associated with HIV immunodeficiency: clinical case and literature review].
A 33 year old female, suffering from HIV infection, presents with diffuse myalgia, generalized muscle weakness and painless dysphagia. An extensive work-up allows to diagnose an HIV-related polymyositis; while well-known, this entity is however rarely observed. Technetium-99m MDP skeletal scintigraphy shows multiple extra-osseous accumulations of the tracer: these observations, as well as the differential diagnoses of muscular involvement during HIV infection, are discussed.
Development of short and long-term management options for bergelenput to avoid fish kills caused by algal blooms.
Numerous stagnant waters in Flanders are characterized by high nutrient concentrations, leading to severe algal blooms and under critical conditions to fish mortality. In this context, a eutrophicated pond was analysed hydrobiologically during one month in order to develop a management plan for the coming years to restore its ecological stability. Bergelenput (Wevelgem), a former sand pit, is now a nature reserve, currently also used for recreational fishing. During the last decade, incidental fish kills have occurred. The main cause is thought to be nutrient enrichment, enhancing algal blooms. The most probable source of these nutrients is fertiliser runoff from the surrounding fields characterised by intensive agricultural activities. Two possible causes of these fish kills, both associated with algal blooms, were considered during this preliminary study. The first was oxygen depletion of the water caused by algal respiration during the night. The second was related to the presence of Microcystis aeruginosa, a cyanobacterium known to be toxic sometimes and hence responsible for fish kills. Short-term and long-term management options are being developed within the context of this research to rehabilitate the ecosystem.
Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients.
HIV-1 samples from six patients undergoing diverse anti-HIV therapies possessed the E138A mutation in their reverse transcriptase (RT) genome. Patients were receiving the following therapies: TIBO monotherapy (one patient); zidovudine plus didanosine combination therapy (one); zidovudine monotherapy (one); sequential therapy with zidovudine, then stavudine and finally zalcitabine plus didanosine (one); and two were drug naive. E138K, not E138A, is a known TSAO-specific resistance mutation, emerging under selective pressure in vitro. Our phenotypic data on the patient isolates, confirmed by data on an E138A mutant acquired through in vitro mutagenesis, indicated that an alanine substitution for glutamate at codon 138 of the HIV-1 RT renders the virus TSAO resistant, confirming the importance of this amino acid residue in the activity of TSAO derivatives. In addition, we have demonstrated through phenotypic analysis of the E138A and A98S mutants (after in vitro mutagenesis) that the mutation A98S, found in one of these patients, could be partially responsible for the phenotypic reversal of TSAO resistance. This reversal could be explained by the restoration of a hydrogen bond between 98S and the main-chain residue L349, which compensates for the loss of the E138-G99 main-chain hydrogen bond. As TSAO derivatives have not been used in the clinical setting, the presence of the E138A mutation at a frequency of 6.7% in our study of 90 TSAO-inexperienced HIV-seropositive individuals implies that 138A of the RT must be a natural variant and that the mutant virus is replication competent. Our observations suggest that the E138A mutation may likely arise in patients under the selective pressure of TSAO or related compounds that show a decreased antiviral potency toward the E138A variant.
Baseline HIV type 1 genotypic resistance to a newly added nucleoside analog is predictive of virologic failure of the new therapy.
We evaluated the predictive value of baseline HIV-1 genotypic resistance mutations for failure of a nucleoside reverse transcriptase inhibitor (NRTI) containing therapy. The change in therapy of 88 HIV-1-infected patients was analyzed retrospectively, relating the genotypic resistance profile at baseline to the evolution of viral load and CD4+ T cell counts. Genotypic resistance at baseline and at 6 months was evaluated with the LiPA HIV-1 RT, which detects mutations at codons 41, 69, 70, 74, 184, and 215. At 1 to 3 months after change in therapy, patients without preexisting resistance mutations to the new drug (group S) had a significantly better evolution in viral load (reduction of 0.37 log(10)) compared with patients with known preexisting resistance mutation(s) (group R) (increase of 0.08 log(10)). This difference was particularly striking for patients with the baseline M184V mutation and whose treatment was modified by the addition of lamivudine. After 6 months the median difference in viral load evolution between the two groups increased to 0.61 log(10): the viral load of patients of group S was still 0.18 log(10) below baseline while patients of group R had an increase of 0.43 log(10) in viral load above baseline. Changes in CD4+ T cell counts were not significantly different. The evolution in viral load in HIV-1-infected patients with and without baseline resistance mutation(s) toward a newly added NRTI is significantly different at 1-3 months and at 6 months after changing or adding one NRTI.
Patient HIV-1 strains carrying the multiple nucleoside resistance mutations are cross-resistant to abacavir.
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Camelid heavy-chain variable domains provide efficient combining sites to haptens.
Camelids can produce antibodies devoid of light chains and CH1 domains (Hamers-Casterman, C. et al. (1993) Nature 363, 446-448). Camelid heavy-chain variable domains (VHH) have high affinities for protein antigens and the structures of two of these complexes have been determined (Desmyter, A. et al. (1996) Nature Struc. Biol. 3, 803-811; Decanniere, K. et al. (1999) Structure 7, 361-370). However, the small size of these VHHs and their monomeric nature bring into question their capacity to bind haptens. Here, we have successfully raised llama antibodies against the hapten azo-dye Reactive Red (RR6) and determined the crystal structure of the complex between a dimer of this hapten and a VHH fragment. The surface of interaction between the VHH and the dimeric hapten is large, with an area of ca. 300 A(2); this correlates well with the low-dissociation constant of 22 nM measured for the monomer. The VHH fragment provides an efficient combining site to the RR6, using its three CDR loops. In particular, CDR1 provides a strong interaction to the hapten through two histidine residues bound to its copper atoms. VHH fragments might, therefore, prove to be valuable tools for selecting, removing, or capturing haptens. They are likely to play a role in biotechnology extending beyond protein recognition alone.
Linear CT-scan measurements in alcohol-dependent patients with and without delirium tremens.
The aims of the present study were to examine whether chronic alcohol dependence and the development of delirium tremens are characterized by changes in linear CT measurements of brain liquor spaces and intracranial distances indicative of prefrontal atrophy, and frontal (sub)cortical or temporal (sub)cortical atrophy. Toward this end linear measurements were performed in 47 alcohol dependent patients with and without a history of delirium tremens and in 10 healthy volunteers using CT-scanning. The following linear measurements were calculated: (1) the Evans ratio; (2) the cella media index (CMI); (3) the maximum width of the third ventricle; (4) the maximum width of the fourth ventricle; (5) the maximum frontal subarachnoid space (MFSS); (6) the maximum width of the anterior interhemispheric fissure (MIF), and (7) the maximum width of the Sylvian fissure (MSF). The alcoholics were divided into subgroups according to the Münchner Alkoholismus Test (MALT) and the presence of delirium tremens. The MFSS of the alcohol-dependent patients was significantly larger than that of the controls. The MIF and MSF of high MALT scorers were significantly larger than those of low scorers and controls. Alcohol-dependent patients with a known history of delirium tremens had significantly larger MIF and MSF than did patients without delirium tremens and controls. The results suggest that alcohol dependence is characterized by prefrontal atrophy, and that frontal cortical and temporal (sub)cortical atrophy may be related to the development of delirium tremens.
Opportunistic AIDS-associated malignancies in HIV-infected patients.
Three major neoplasms are associated with AIDS definition in the course of HIV infection due to their increased incidence. The relationship between the immune system and the epidemiology of these virus-induced tumors is of importance in order to identify new therapeutic approaches for treating or preventing these neoplasms. Major improvements in the understanding of the pathogenesis have already been performed. The impact of highly active antiretroviral therapy (HAART) on their incidence likely confirms the concept of 'opportunistic malignancies'. Other neoplasms are likely more prevalent in HIV-infected individuals, but their relative importance requires further prospective case-control cohort studies.