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Biomedical subjects

L Perrin

Publications and source records attributed to L Perrin.

At least 19 recordsLinked to original sources
PubMed2006

Multicenter performance evaluation of a new TaqMan PCR assay for monitoring human immunodeficiency virus RNA load.

A TaqMan real-time PCR assay, the COBAS TaqMan human immunodeficiency virus (HIV) (HPS-CTMHIV) PCR assay, recently developed for the quantification of HIV type 1 RNA in plasma, was evaluated in comparison with the licensed COBAS AMPLICOR HIV-1 MONITOR (CAHIM) assay. In this study, we have analyzed the tests' sensitivities, precisions, and linearities using multiple replicates of a standard panel of HIV RNA covering a 7-logarithm range of concentrations, as well as serial threefold dilutions of high-titer clinical samples. The subtype inclusivity was also investigated, using a panel of subtypes A to H, while a collection of 160 clinical samples was analyzed to assess the tests' specificities and the systems' similarities. The results of these experiments showed that the HPS-CTMHIV assay has a sensitivity of 53 copies/ml (95% hit rate), 100% specificity, and good intra- and interassay precision. The results of the HPS-CTMHIV assay were linear in the 50- to 10(7)-copies/ml range, with a correlation coefficient (R) for expected versus observed results of 0.98. Compared to the CAHIM assay, the HPS-CTMHIV assay showed a high correlation (R=0.99) across the dynamic range of RNA concentrations that, for the CAHIM assay, requires two different sample preparations. Equivalent performances were also observed for the two systems in the detection and quantification of HIV subtypes A to H. These data indicate that the HPS-CTMHIV assay may be one of the tests of choice for monitoring viral load throughout the course of HIV infection and during highly active antiretroviral therapy.

Analysis of Variance↗
PubMed2006

[Anti-tumor immunotherapy against multidrug resistance].

Overexpression of a membrane glycoprotein (P170) represents the most common multidrug resistance (MDR) mechanism in cancer therapy. Specific autoantibodies to extracellular loops 1, 2 and 4 of murine P170 are elicited in mice using palmitoylated synthetic peptides reconstituted in liposomes with or without Lipid A and resuspended in alum. IgM antibodies are detected 14 days following the first injection and IgG1 become predominant after the third challenge. Animals do not show any autoimmunity symptoms or induced toxicity up to 18 months after the immunization. Previous immunizations of mice using liposomes with mdr1 peptides efficiently improve chemotherapy with doxorubicin and vinblastine against P388 R cells with a 77% increase of survival half time in the immunized group. Sera from immunized mice are also effective in reducing cellular resistance to vinblastine and doxorubicin in vitro. Taken together these data suggest that this immunization approach might have potential clinical applications.

Animals↗
PubMed2006

Dietetic guidelines on food and nutrition in the secondary prevention of cardiovascular disease - evidence from systematic reviews of randomized controlled trials (second update, January 2006).

AIM: To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD. Each review was critically appraised by at least two members of the UK Heart Health and Thoracic Dietitians Group. The quality and results of each review were discussed and summarized at a group meeting. RESULTS: Evidence-based strategies that reduce cardiovascular events in those with CVD include reduction in saturated fat and substitution with unsaturated fats. Individuals who have suffered a myocardial infarction may also benefit from adopting a Mediterranean type diet and increasing intake of omega 3 fats, but it is not clear whether they are beneficial for all patients with CVD. There is no systematic review evidence to support the use of antioxidant vitamins supplements, low glycaemic index diets, or homocysteine lowering therapies in this group. CONCLUSION: There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.

Antioxidants↗
PubMed2004

Cytochrome P450-mediated oxidation of glucuronide derivatives: example of estradiol-17beta-glucuronide oxidation to 2-hydroxy-estradiol-17beta-glucuronide by CYP 2C8.

In the classical metabolic oxidation scheme, hydrophobic endogenous or xenobiotic compounds undergo phase I oxidation, generally catalyzed in the liver by cytochromes P450, followed by phase II conjugation reactions, in a way that allows much more polar metabolites to be expelled from the cell through active transport mechanisms. Cytochrome P450-mediated oxidation of steroid sulfate has been described, suggesting that oxidation of polar metabolites such as glucuronide derivatives of endogenous compounds can occur. As an example, we report here that hydroxyestradiol-17beta-glucuronide can be directly formed through oxidation of estradiol-17beta-glucuronide on the aromatic C2 position. This reaction is specifically catalyzed by CYP 2C8, which is more active in female than in male human liver microsomes. A thorough docking of the molecule within the CYP 2C8 crystal structure shows that the active site is large enough to handle a glucuronide conjugate. Moreover, the most energetically favored position of the bound ligand is fully consistent with the recently published structural determinants of substrate specificity of the CYP 2C8 active site. This is the first demonstration of cytochrome P450-mediated oxidation of a steroid glucuro-conjugate. Such oxidation of a glucuronide should be a general process since, in addition to estradiol and testosterone glucuronide, it has been observed for xenobiotic compounds, e.g., diclofenac or naproxen glucuronide.

Animals↗
PubMed2004

Molecular genetics of the Alhambra (Drosophila AF10) complex locus of Drosophila.

The Alhambra (Alh) gene is the Drosophila homologue of the human AF10 gene. AF10 has been identified as a fusion partner of MLL, a human homologue of the fly gene trithorax, in infant leukemias. The endogenous function of human AF10 is not known, but may be vital to its role in acute leukemia. This prompted us to analyse Alh function. We describe here the genetic organisation of the Alh locus in D. melanogaster. We show that an independent lethal complementation group encoding a muscle protein (Mlp84B) is located within an Alh intron. We have already shown that the leucine zipper (LZ) domain of ALH activates several Polycomb group-responsive elements. We further demonstrate that the LZ domain on its own bears the Alh vital function, since it is necessary and sufficient for rescue of Alh mutant lethality. Finally, we demonstrate that, in contrast to a previous report, Alh does not affect position-effect variegation.

Animals↗
PubMed2004

Inhibition of multidrug resistance by immunisation with synthetic P-glycoprotein-derived peptides.

Overexpression of the membrane glycoprotein (P170) represents the most common multidrug resistance (MDR) mechanism in cancer therapy. Specific auto-antibodies to extracellular loops 1, 2 and 4 of murine P170 were elicited in mice using palmitoylated synthetic peptides reconstituted in liposomes, with or without Lipid A, and resuspended in alum. IgM antibodies were detected 14 days following the first injection and IgG1 became predominant after the third challenge. Animals did not show any auto-immune symptoms or induced toxicity up to 18 months after the immunisation. Previous immunisations of mice using liposomes with MDR1 peptides increases the efficacy of chemotherapy treatments with doxorubicin and vinblastine against P388 R cells with increase of 77% in the survival half time in the immunised group. Sera from the immunised mice were also effective in reducing cellular resistance to vinblastine and doxorubicin in vitro. Taken together, these data suggest that this immunisation approach might have potential clinical applications.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2004

Updated European recommendations for the clinical use of HIV drug resistance testing.

In most European countries, HIV drug resistance testing has become a routine clinical tool. However, its practical implementation in a clinical context is demanding. The European HIV Drug Resistance Panel was established to make recommendations to clinicians and virologists on this topic and to propose quality control measures. The panel recommends resistance testing for the following indications: i) drug-naive patients with acute or recent infection; ii) therapy failure, including suboptimal treatment response, when treatment change is considered; iii) pregnant HIV-1-infected women and paediatric patients with detectable viral load when treatment initiation or change is considered; and iv) genotype source patient when post-exposure prophylaxis is considered. In addition, for drug-naive patients with chronic infection in whom treatment is to be started, the panel suggests that resistance testing should be strongly considered and recommends testing the earliest sample for drug resistance if suspicion of resistance is high or prevalence of resistance in this population exceeds 10%. The panel does not favour genotyping over phenotype, however it is anticipated that genotyping will be used more often because of its greater accessibility, lower cost and faster turnaround time. For the interpretation of resistance data, clinically validated systems should be used to the greatest extent possible. It is mandatory that laboratories performing HIV resistance tests take regular part in quality assurance programs. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and meet regularly to discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response. The panel also encourages the timely collection of epidemiological information to estimate the impact of transmission of resistant HIV and the prevalence of HIV-1 non-B subtypes in the different European countries.

Anti-HIV Agents↗
PubMed2003

Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial.

BACKGROUND: Scheduled treatment interruptions are being evaluated in an effort to decrease costs and side effects of highly active antiretroviral therapy (HAART). A schedule of 1 week on and 1 week off therapy offers the promise of 50% less drug exposure with continuously undetectable HIV RNA concentration. METHODS: In the Staccato study 600 patients on successful HAART were to be randomized to either continued therapy, CD4-guided therapy, or one week on, one week off therapy. A scheduled preliminary analysis evaluated effectiveness in the 1-week-on-1-week-off arm. RESULTS: Of 36 evaluable patients, 19 (53%) had two successive HIV RNA concentrations > 500 copies/ml at the end of the week off therapy, and were classified as virological failure. Most of those who failed took didanosine, stavudine, saquinavir, and ritonavir (11 patients). In these patients, there was no evidence of mutations suggestive of drug resistance, and plasma saquinavir levels were within the expected range. Two of three patients failing on triple nucleotides had drug resistance mutations, but nonetheless responded to reintroduction of triple nucleotide therapy. One of two patients taking nevirapine, and one of eight taking efavirenz, also failed. Both had resistance mutations at the time of failure, but not at baseline. CONCLUSIONS: The 1-week-on-1-week-off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated.

Anti-HIV Agents↗
PubMed2003

VOCs isotherms on day zeolite by static and dynamic methods: experiments and modelling.

A dynamic method and a static gravimetric method are respectively used to measure the adsorption equilibria of m-xylene and n-butyl acetate on Wessalith DAY zeolite F20. The equilibrium experiments are performed at different temperatures for both volatile organic compounds (VOCs). The m-xylene isotherms obtained in this study by the dynamic method are compared to our recently published data in which the static gravimetric method was used in order to test the influence of the experimental technique. Because the adsorption isotherms of m-xylene were correlated in our previous paper, in this study only the n-butyl acetate experimental data are correlated with various adsorption isotherm models: Langmuir, Toth and Dubinin equations.

Adsorption↗
PubMed2003

[Chylothorax: an unexpected complication of artificial ventilation in severe acute asthma].

INTRODUCTION: Complications of mechanical ventilation for severe acute asthma are common and are related essentially to barotrauma. However, the incidence has declined in recent years thanks to different techniques of ventilation. CASE REPORT: We report a case of spontaneous chylothorax occurring during the course of ventilation in a patient with severe acute asthma where the ventilatory parameters were in accordance with current recommendations. Recovery was straightforward with resolution of the chylothorax and no recurrence either immediately or later. Exhaustive clinical, biological and morphological investigations failed to find any cause other than the mechanical ventilation. CONCLUSION: This case of chylothorax may be considered as a rare barotraumatic complication of severe acute asthma.

Acute Disease↗
PubMed2002

Are the carbon monoxide complexes of Cp(2)M (M = Ca, Eu, or Yb) carbon or oxygen bonded? An answer from DFT calculations.

DFT calculations have been performed on the CO adducts of the bivalent lanthanides, Cp(2)M(CO)(x), where M is Eu or Yb and x is 1 or 2, the alkaline earth metallocene Cp(2)Ca(CO), and the methylisocyanide adducts of Yb. The calculated nu(CO) values are in agreement with experiment for Cp(2)M(CO) when M is Ca or Eu, but in striking disagreement when the CO is bound to the metal by way of the carbon atom in CO in the case of Yb. The calculated nu(CO) values for M = Yb are brought into agreement with experiment when the CO is allowed to bond to Cp(2)Yb by way of the oxygen atom.

Journal Article↗
PubMed2001

Acute HIV infection: impact on the spread of HIV and transmission of drug resistance.

OBJECTIVE: To assess the impact of primary HIV infection (PHI) on the spread of HIV and the temporal trends in transmission of HIV drug resistance between 1996 and 1999 in Switzerland. METHODS: Sequencing of the genes for reverse transcriptase (RT) and protease was performed for 197 individuals with documented PHI. Phylogenetic analyses were confronted with epidemiological data. RESULTS: Significant clustering was demonstrated for 29% of the RT sequences. All these cases occurred closely together in place and time; contact tracing demonstrated transmission at the time of PHI in 30% of them. Genotypic drug resistance was detected in 8.6% of PHI individuals in 1996, 14.6% in 1997, 8.8% in 1998 and 5.0% in 1999. Drug-resistant variants were identified in 11.3% of individuals infected by homosexual contacts, 6.1% by heterosexual contacts, 13% of intravenous drug users and more frequently in men (10.4%) than women (2.6%). Potential factors involved in the recent decrease of transmission of drug-resistant variants include increase of HIV non-B subtypes from 23% in 1996 to 35% in 1999 (only one non-B subtype had resistance mutations) and a steady increase of patients with undetectable viraemia as documented in Swiss HIV Cohort Study (10% in 1996 vs 53% in 1999). CONCLUSIONS: Phylogenetic and epidemiological analyses underline the impact of PHI in the spread of HIV. Moreover, this study indicates that drug resistance transmission may have decreased recently in Switzerland through the increased frequency of infection with HIV non-B subtypes and the steady increase of patients with undetectable viraemia.

Acute Disease↗
PubMed2001

Computed ligand electronic parameters from quantum chemistry and their relation to Tolman parameters, Lever parameters, and Hammett constants.

The calculated (DFT, B3PW91) A(1) nu(CO) frequency in LNi(CO)(3) defines an electronic parameter that reliably predicts the relative donor powers of a wide variety of cationic, neutral, and negatively charged ligands. These calculated parameters correlate very well with the available Tolman and Lever parameters, and also with Hammett's sigma(m), where available. The method avoids any experimental limitations and, in particular, can be used for proposed ligands not yet experimentally available.

Journal Article↗
PubMed2001

Distribution of functional HIV-specific CD8 T lymphocytes between blood and secondary lymphoid organs after 8-18 months of antiretroviral therapy in acutely infected patients.

OBJECTIVES: To assess whether drug-induced suppression of the plasma viral load is associated with selective differential distribution of virus-specific CD8 T cells between the blood and secondary lymphoid organs. METHODS: HIV-specific CD8 T lymphocyte responses were quantified in matched peripheral blood and lymph node samples from seven patients starting treatment shortly after infection, who received antiretroviral therapy (ART) for a median of 14 months. Cells recovered from samples were subjected to IFN-gamma ELISPOT analysis. A series of synthetic peptides corresponding to previously characterized cytotoxic T lymphocyte epitopes restricted by HLA I molecules present in each patient were used as antigens, together with appropriate positive and negative controls. RESULTS: HIV-specific CD8 T lymphocyte responses were found in six of the seven patients. The observed frequencies of HIV-specific CD8 T lymphocytes and the pattern of epitope recognition was identical within the two compartments. These results also confirm the observation that functional HIV-specific CD8 T cells are preserved on ART in most patients initiating treatment at the time of primary HIV-1 infection. CONCLUSION: This investigation demonstrated that patterns of antigenic immunodominance as well as frequencies of HIV-specific CD8 T lymphocytes are similar in blood and lymphoid tissue compartments in HIV-infected individuals. These findings support current approaches to the identification of HIV-specific CD8 T lymphocyte reactivity based on leukocytes isolated from blood even in patients with ART-induced suppression of viral load.

Anti-HIV Agents↗
PubMed2001

Nosocomial outbreak of multiple bloodborne viral infections.

In resource-limited countries, nosocomial transmission of bloodborne pathogens is a major public health concern. After a major outbreak of human immunodeficiency virus (HIV) infection in approximately 400 children in 1998 in Libya, we tested HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) markers in 148 children and collected epidemiological data in a subgroup of 37 children and 46 parents. HIV infection was detected in all children but one, with HCV or HBV coinfection in 47% and 33%, respectively. Vertical transmission was ruled out by analysis of parents' serology. The children visited the same hospital 1-6 times; at each visit, invasive procedures with potential blood transmission of virus were performed. HIV and HCV genotypic analyses identified a HIV monophyletic group, whereas 4 clusters of HCV sequences were identified. To our knowledge, this is the largest documented outbreak of nosocomial HIV transmission.

Adult↗
PubMed2001

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus.

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system. While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation. Patients with negative washings had a DFS of 96% at 36 months compared with 67% for patients with positive washings (log-rank P<0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor.

Adenocarcinoma↗