Biomedical subjects

Patrice Massip

Publications and source records attributed to Patrice Massip.

At least 19 recordsLinked to original sources

PubMed2007

Decreased semen volume and spermatozoa motility in HIV-1-infected patients under antiretroviral treatment.

Inconsistent results have been reported for the semen quality in HIV-infected men, due to the biases inherent in some studies. The objective of the present study was to investigate the semen parameters in HIV-1-infected patients and to compare their sperm characteristics with those of a control group of fertile, noninfected men. Factors implicated in semen alterations in HIV-1 patients were also analyzed. HIV-infected men (n=190), of whom 91% were undergoing antiretroviral therapy, and 218 fertile men were studied. Infertility risk factors were recorded and clinical examinations were performed for both groups. Records of history of HIV infection, antiretroviral treatment, and HIV-1 RNA detection in the blood as well as HIV-1 genome detection in the semen were obtained for the infected patients. Semen volumes, percentages of progressive motile spermatozoa, total sperm counts, and polymorphonuclear cell counts were decreased, while the pH values and spermatozoa multiple anomaly indices were increased in HIV-infected patients. Even after adjustment for possible sources of bias, the decreases in semen volume and progressive motility and the increase in pH remained significant. The present study demonstrates sperm motility and ejaculate volume alterations in HIV-1-infected patients, most of whom were receiving antiretroviral therapy. In HIV-1 patients, further longitudinal studies are required to analyze the impact of treatment regimen on sperm parameter alterations.

Adult↗

PubMed2006

Analysis of CCR5, CCR2, CX3CR1, and SDF1 polymorphisms in HIV-positive treated patients: impact on response to HAART and on peripheral T lymphocyte counts.

Although polymorphisms of chemokine genes (SDF1, stromal cell-derived factor-1 and RANTES, regulated on activation, normal T cell expressed and secreted) and chemokine-receptor genes (CCR5, CCR2, CX(3)CR1) were shown to be associated with sensitivity to HIV infection and untreated HIV disease progression, their association with the response to highly active antiretroviral therapy (HAART) remains unclear. To explore the possible influence of such polymorphisms on the evolution of AIDS in treated patients, we have studied SDF1-3'A, CCR5Delta32, CCR2-64I, CX(3)CR1-249I, and CX(3)CR1-280M polymorphisms in HIV-infected patients under HAART (n = 169). We studied the evolution of plasma virus load and peripheral T lymphocyte counts in these patients up to 3 years after the initiation of HAART. We observed that some of the genetic polymorphisms studied had an impact on the evolution of these two parameters. After 1 year of HAART, patients with a virological response (undetectable plasma HIV-1 RNA) have a higher frequency of the homozygous SDF1-3'A genotype than other patients (p = 0.005). Similarly, patients with a CD4 increase of over 200/mm(3) from baseline after 1 year of HAART display higher frequencies of homozygous SDF1-3'A (p = 0.035) and homozygous CX(3)CR1-280M genotypes (p = 0.04) than other patients. Moreover, we showed that the CX(3)CR1- 280M allele was associated with higher peripheral CD4+ T cell counts not only in HIV+ patients but also in healthy controls (p = 0.003).

Adult↗

PubMed2006

Naive T-cell depletion related to infection by X4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy.

The reasons for poor CD4+ T-cell recovery in some human immunodeficiency virus (HIV)-infected subjects despite effective highly active antiretroviral therapy (HAART) remain unclear. We recently reported that CXCR4-using (X4) HIV-1 could be gradually selected in cellular reservoirs during sustained HAART. Because of the differential expression of HIV-1 coreceptors CCR5 and CXCR4 on distinct T-cell subsets, the residual replication of R5 and X4 viruses could have different impacts on T-cell homeostasis during immune reconstitution on HAART. We examined this hypothesis and the mechanisms of CD4+ T-cell restoration by comparing the virological and immunological features of 15 poor and 15 good immunological responders to HAART. We found a high frequency of X4 viruses in the poor immunological responders. But the levels of intrathymic proliferation of the two groups were similar regardless of whether they were infected by R5 or X4 virus. The frequency of recent thymic emigrants in the poor immunological responders was also similar to that found in the good immunological responders, despite their reduced numbers of naïve CD4+ T cells. Our data, rather, suggest that the naïve T-cell compartment is drained by a high rate of mature naïve cell loss in the periphery due to bystander apoptosis or activation-induced differentiation. X4 viruses could play a role in the depletion of naïve T cells in poor immunological responders to HAART by triggering persistent T-cell activation and bystander apoptosis via gp120-CXCR4 interactions.

Adult↗

PubMed2006

Effects of discontinuing stavudine or protease inhibitor therapy on human immunodeficiency virus-related fat redistribution evaluated by dual-energy x-ray absorptiometry.

STUDY OBJECTIVE: To determine whether discontinuation of stavudine or protease inhibitor therapy improves human immunodeficiency virus (HIV)-related fat distribution in men. DESIGN: Observational, retrospective study consisting of a cross-sectional (part 1) and a longitudinal (part 2) study. DATA SOURCE: Medical records from Purpan University Hospital and La Grave University Hospital, Toulouse, France. Subjects. Eighty men with HIV infection treated with antiretrovirals and 151 healthy male controls matched for age. MEASUREMENTS AND MAIN RESULTS: In part 1, body composition and fat distribution of the HIV-infected men were compared by dual energy x-ray absorptiometry (DEXA) with those of the controls to determine whether body fat distribution is altered in HIV-infected men. In part 2, we analyzed modifications of body composition and fat distribution in 45 of the 80 patients. These 45 had been exposed to antiretroviral drugs, including stavudine and a protease inhibitor, for at least 5 months before the first of two DEXA assessments. They received three different treatment strategies for several months. In group 1, stavudine was withdrawn; in group 2, protease inhibitor was discontinued, and in group 3, stavudine plus protease inhibitor were continued. Group 1 showed a significant fat gain in the lower extremities 31.7 +/- 5.9 months after stavudine discontinuation (p<0.0001). Group 2 did not show any significant modification of total body, lower limb, or trunk fat despite protease inhibitor discontinuation for 35.2 +/- 6.6 months. Findings were similar for group 3, who continued receiving stavudine-protease inhibitor therapy for 21.2 +/- 12.8 months. CONCLUSION: These data suggest that long-term withdrawal of stavudine from the antiretroviral therapy regimen may be associated with significant improvement in lipoatrophy in the lower extremities, whereas long-term protease inhibitor withdrawal did not modify fat distribution.

Absorptiometry, Photon↗

PubMed2006

Giant cell arteritis and spinal cord compression: an overlap syndrome?

We describe 2 patients with spinal cord compression that occurred in the course of biopsy-proven giant cell arteritis (GCA). One case was due to an epidural tumorlike inflammatory lesion, the other to a concentric inflammatory thickening of the meninges. Both patients were highly corticodependent; they had low-titer anti-neutrophil cytoplasmic antibodies but no antimyeloperoxidase or antiproteinase 3 autoantibodies. The diagnosis was established by surgical biopsy. The histological pattern was reminiscent of Wegener granulomatosis. Both patients experienced relapse, despite high doses of corticosteroids, and experienced remission after the introduction of cyclophosphamide. Intravenous immunoglobulin perfusions were added for 1 patient. To our knowledge, spinal cord compression by a spinal pseudotumor or inflammatory meningitis has not been reported in the course of GCA. An overlap syndrome between GCA and Wegener granulomatosis is discussed.

Aged↗

PubMed2005

Persistence of distinct HIV-1 populations in blood monocytes and naive and memory CD4 T cells during prolonged suppressive HAART.

OBJECTIVE: Reservoirs of HIV-1 are a major obstacle to virus eradication. There is therefore a need to clearly understand the molecular nature of the virus populations that persist in patients with sustained suppression of plasma viraemia on highly active antiretroviral therapy (HAART). DESIGN: We performed a detailed analysis of the genotypes of HIV-1 quasispecies isolated from highly purified blood cell types taken from three selected patients with sustained undetectable viral loads on HAART for 7 years. METHODS: We used polychromatic flow cytometry to sort naive and memory CD4 T cells, CD14 monocytes, and CD56+CD3- natural killer (NK) cells from the total peripheral blood mononuclear cells after 7 years of HAART. Clonal analysis was used to determine coreceptor use and drug-resistance genotypes of HIV-1 quasispecies in the sorted blood cell types. RESULTS: We detected HIV-1 DNA in memory and naive CD4 T cells and in CD14 monocytes, but not in the CD56+CD3- NK cells. Phylogenetic analysis demonstrated that the various blood cells types of two of the three patients harboured genetically distinct HIV-1 quasispecies. Drug-resistance mutations were also distributed differently from one cell type to another. This compartmentalization suggests a minimal virus trafficking between blood cell types during suppressive HAART. CONCLUSIONS: We observed a cell-specific compartmentalization of the residual virus populations during prolonged suppressive HAART. The coexistence of numerous HIV-1 quasispecies with different resistance genotypes and coreceptor use in cellular reservoirs may be relevant for future antiretroviral treatment strategies.

Antiretroviral Therapy, Highly Active↗

PubMed2005

FOXP3 mRNA levels are decreased in peripheral blood CD4+ lymphocytes from HIV-positive patients.

The impact of HIV infection on regulatory CD4(+)CD25(high) (Treg) lymphocyte subpopulations was evaluated by FOXP3 quantitative reverse transcriptase polymerase chain reaction and by flow cytometry. FOXP3 mRNA was quantified in peripheral blood mononuclear cells or purified CD4(+) lymphocytes from HIV(+) lymphopenic patients. Patients were distributed among clinical stages A, B, and C and received highly active antiretroviral therapy. The frequency of CD4(+)CD25(high) lymphocytes, measured by flow cytometry, was decreased in HIV patients (n = 38) compared with the group of uninfected subjects (n = 39). FOXP3 mRNA levels were found decreased in HIV patients (n = 25) compared with controls (n = 17) when expression of CD3gamma or beta-actin but not that of TATA box binding protein 1 was used for data normalization. Our results are compatible with a decrease of the Treg lymphocytes during HIV infection. The consequences of a Treg decrease are discussed in the context of immunologic anomalies observed during HIV infection.

Adult↗

PubMed2005

R5 to X4 switch of the predominant HIV-1 population in cellular reservoirs during effective highly active antiretroviral therapy.

HIV-1 coreceptor usage plays a critical role for virus tropism and pathogenesis. A switch from CCR5 to CXCR4-using viruses can occur in the natural course of infection and correlates with subsequent disease progression. To investigate whether HIV-1 genetic evolution might lead to changes in virus coreceptor usage during highly active antiretroviral therapy (HAART), a longitudinal genotypic analysis of the virus found in cellular reservoirs was conducted in 32 patients with undetectable viral loads on HAART for 5 years. The genotype of the 3rd variable region of the env gene predicting coreceptor usage was retrospectively determined in the plasma or in peripheral blood mononuclear cells (PBMC) at baseline and then in PBMCs at months 30 and 60 of HAART. There was a switch from R5 to X4 variants in 11 of the 23 patients who harbored a majority virus population of R5 variants at baseline. X4 variants remained predominant in the 9 patients who harbored mainly X4 variants at baseline. The patients harboring predominantly X4 variants during HAART, either from baseline or after an R5 to X4 switch, tended to have lower CD4+ T-cell counts on HAART than did patients harboring continuously a majority population of R5 variants. These results suggest that potent antiretroviral therapy produces the conditions necessary for the gradual emergence of X4 variants in cellular reservoirs.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Decrease of Lewis frequency in HIV-infected patients: possible competition of fucosylated antigens with HIV for binding to DC-SIGN.

We explored the impact of human ABO glycosyltransferase and Lewis and secretor fucosyltransferase polymorphisms in HIV infection. We found that, compared with healthy blood donors, HIV-infected patients display a significant decrease in Le(a-b+) phenotype frequencies. We showed that HIV binding on DC-SIGN-transduced Jurkat cells was inhibited by fucosyl bovine serum albumin. Our results suggest a slight protective effect of Lewis b antigen on HIV infection, possibly by the competition of Lewis antigens with HIV for binding to DC-SIGN.

Cell Adhesion Molecules↗

PubMed2005

[Epidural abscess after prostatic biopsies].

Prostatic biopsy is a routine clinical procedure often wrongly considered to be perfectly harmless. The authors report the first case of epidural abscess after prostatic biopsy, despite properly conducted antibiotic prophylaxis. Although the epidural space is a known site of infection, the relationship with prostatic biopsies has never been previously reported. This clinical case emphasizes the need for complete patient information and the importance of anti-infective prophylaxis guidelines.

Biopsy↗

PubMed2004

Factors of intermittent HIV-1 excretion in semen and efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes.

OBJECTIVE: To study the risk factors for HIV-1 in semen according to the localization of HIV-1 in sperm cell fractions and to assess the efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes. METHODS: Ninety-four HIV-infected patients provided 281 paired blood and semen samples. Sperm cell separation was performed using two successive methods. HIV-1 RNA was quantified in blood and seminal plasma. HIV-1 RNA and DNA were detected in cell fractions. RESULTS: HIV-1 RNA was found in 14% of seminal plasma samples and up to 8.7% of native semen cells were positive for HIV-1 RNA and DNA. Ten seminal plasma samples had detectable RNA although blood viral load was undetectable. Antiretroviral treatment reduced the likelihood of RNA detection in seminal plasma. For semen with polynuclear cells and HIV-1 RNA in seminal plasma, the likelihood of detecting HIV-1 genomes in semen cells was increased fourfold and sixfold, respectively. In 25% of patients, HIV-1 excretion was intermittent. In the group of patients with systematic negative seminal plasma, HIV-1 genomes were detected in up to 10% of sperm cell samples. Our method of sperm processing always enabled us to obtain spermatozoa without detectable HIV-1 genomes. CONCLUSIONS: Polynuclear cells in semen are a risk factor for seminal HIV-1 excretion. Blood viral load was the only predictive factor for the intermittence of HIV-1 excretion in semen over time. Sperm processing using two successive methods was effective in obtaining spermatozoa without detectable HIV-1 genomes regardless of the viral load level in native semen.

Adult↗

PubMed2004

HIV therapy after treatment interruption in patients with multiple failure and more than 200 CD4+ T lymphocyte count.

The aim of the study was to investigate the safety and efficacy of a salvage therapy initiated after interrupting treatment in patients with virological failure and more than 200 CD4(+) T lymphocyte count. In this prospective study, 77 patients who received failing regimens had stopped completely all medication for 3 months before starting an optimised regimen consisting of 3-5 drugs. Patients were tested for HIV resistance before and after treatment interruption. Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 1.1 log(10), a median decrease in CD4(+) T cell count of 136 x 10(6)/L and five clinical events related to HIV, but no AIDS-defining event. Eighty-seven percent of patients showed a shift from a drug resistant genotype to a wild-type genotype based on the major resistance mutations. Forty-seven percent of patients with a genotype shift reached fewer than 200 HIV RNA copies/ml of plasma 6 and 12 months after treatment resumption whereas none of those without a genotype shift did so (P = 0.03). However, the genotypic shift was not associated with a sustained virological response by multivariate analysis. The use of a new therapeutic class of compound in the salvage regimen was the only predictor of the sustained virological response. Salvage therapy with 3-5 drugs after interrupting treatment for 3 months can be a safe and effective strategy provided the HIV disease is not too advanced. Randomised trials in this population are needed to assess the clinical benefit of this strategy.

AIDS-Related Opportunistic Infections↗

PubMed2004

Severe herpes virus (HSV-2) infection in two patients with myelodysplasia and undetectable NK cells and plasmacytoid dendritic cells in the blood.

BACKGROUND: How the immune system contains herpes simplex virus (HSV) infections is partly understood. T cells from infected persons proliferate in response to HSV antigens in vitro and may control local relapse rather than primary infection. NK cells have been involved in the control of experimental infections. A potentially important, as yet unexplored, population of interest might be the plasmacytoid dendritic cells (PDC), which contrary to monocytes, produce very high amounts of the major antiviral molecules, type-I interferon (IFN) following interaction with HSV. OBJECTIVES: Measure type-I IFN production, PDC, and NK cells in patients with unusually severe HSV infections. STUDY DESIGN: Two female patients of 33- and 50-year-old, respectively were referred because of severe disseminated HSV2 infection and myelodysplastic marrow. One patient had leukaemia and a primary HSV2 infection whereas the other had systemic lupus erythematosus (SLE) and a chronic HSV2 infection. The following studies were performed at various time points over 18 months: analysis of the lymphocytes and PDC subsets phenotype, lymphocyte proliferation assays to recall antigens; generation of NK cells in cultures, and production of type-I IFN in serum and by HSV-infected and by sendai virus (SV)-infected blood cells. RESULTS AND CONCLUSIONS: PDC and NK cells were undetectable in the blood of both patients and NK cells could not be generated in culture at the time of ongoing infection. PBMC failed to produce IFN after infection with HSV contrasting with a normal T cell proliferation to HSV antigens in patient 1. Our observation suggests that innate immunity, through NK cells and PDC may control HSV infections, and together with IFN-producing capacity, should be investigated in patients with unusually severe HSV infections.

Adult↗

PubMed2004

Pfcrt K76T mutation and its associations in imported Plasmodium falciparum malaria cases.

Over 3 years (1999-2002), 305 cases of falciparum malaria were diagnosed in Toulouse, France. After retrospective analysis, only 131 patients entered the study. The diagnosis of malaria was ensured by optical methods (QBC then thin smear examination), the results of which were checked from 1999 to mid-2001 by a conventional PCR method, replaced at that time by a real-time PCR using LightCycler. To detect Pfcrt K(lysine)76T(threonine) mutation, a real-time PCR assay was developed, the sensitivity of which was one mutated parasite per microliter, or 2% mutant asexual forms in a mixed population. Eighty-one patients harbored only mutant parasites, and 11 had a K76K/T76-mixed infection. The distribution of K76T mutation was significantly affected by the use of a chloroquine + proguanil (CQ + P) prophylaxis (P = 0.00037). Among 96 subjects who had no exposure to chloroquine or any history of CQ + P prophylaxis, the mean parasitemia was higher in K76-infected patients (P = 0.038), which suggested a lack of virulence in the falciparum mutant population.

Adult↗

PubMed2004

A systematic review of computer-based patient record systems and quality of care: more randomized clinical trials or a broader approach?

PURPOSE: To analyse the impact of computer-based patient record systems (CBPRS) on medical practice, quality of care, and user and patient satisfaction. DATA SOURCES: Manual and electronic search of the Medline, Cochrane, and Embase databases. STUDY SELECTION: Selected articles were published from 2000 to March 2003. CBPRS was defined as computer software designed to be used by clinicians as a direct aid in clinical decision making. To be included, the systems should have recorded patient characteristics and offered online advice, or information or reminders specific to clinicians during the consultation. DATA EXTRACTION: Keywords used for the search were: electronic record, informatic record, electronic medical record, electronic patient record, patient order entry, computer-based patient system, clinical decision support systems, and evaluation. RESULTS: Twenty-six articles were selected. Use of a CBPRS was perceived favourably by physicians, with studies of satisfaction being mainly positive. A positive impact of CBPRS on preventive care was observed in all three studies where this criterion was examined. The 12 studies evaluating the impact on medical practice and guidelines compliance showed that positive experiences were as frequent as experiences showing no benefit. None of the six studies analysing the impact of CBPRS on patient outcomes reported any benefit. CONCLUSIONS: CBPRS increased user and patient satisfaction, which might lead to significant improvements in medical care practices. However, the studies on the impact of CBPRS on patient outcomes and quality of care were not conclusive. Alternative approaches considering social, cultural, and organizational factors may be needed to evaluate the usefulness of CBPRS.

Consumer Behavior↗

PubMed2003

Intermittent detection of hepatitis C virus (HCV) in semen from men with human immunodeficiency virus type 1 (HIV-1) and HCV.

HCV is usually transmitted via the blood, but HCV RNA has been detected recently in seminal fluid. This study was done to study HCV seminal shedding and factors that could influence the presence of HCV in the seminal fluid of men coinfected with HCV and HIV-1. HCV and HIV-1 genomes were assayed in multiple paired blood and semen samples obtained from 35 men enrolled in an assisted medical procreation protocol. HCV RNA was found intermittently in semen samples from 9 patients (25.7%). Samples from 9 men with HCV RNA in their semen and 26 men without were compared to further analyze these parameters. No correlation was found between HCV RNA in the seminal fluid and age, HCV virus load, the duration of HIV-1 infection, HIV treatment, the CD4(+) cell count, HIV-1 virus load or HIV-1 detection in the semen. The intermittent detection of HCV RNA in semen samples support the systematic search for HCV RNA in semen and the use of processed spermatozoa in assisted medical procreation of infertile HCV serodiscordant couples.

Adult↗

PubMed2003

Utilisation and safety of low molecular weight heparins: prospective observational study in medical inpatients.

AIMS: Low molecular weight heparins (LMWHs) are widely used as curative or preventive treatments of thromboembolic diseases. The aim of our study was to: investigate the pattern of prescription of LMWHs in different departments of French teaching hospitals; andestimate the incidence of adverse drug reactions (ADRs) induced by LMWHs and associated risk factors for the occurrence of bleeding events. METHODS: This prospective study was performed in two teaching hospitals in Toulouse (south-western France) in March 1999 in different medical wards. All patients receiving a prescription for a LMWH were included in the survey. All data were prospectively recorded in each ward. RESULTS: A total of 334 patients were included. Sex ratio (male/female) was 1.25 and mean age was 72.5 +/- 16.3 years (extremes:18-101). 450 prescriptions for LMWHs were collected (1.34 prescription per patient) and involved mainly enoxaparin (61%), which was more frequently used than tinzaparin in patients over 75 years old (71.7 vs 28.3%; p < 0.0001). Ninety-nine patients received a LMWH for curative treatment (corresponding to 127 prescriptions of which 99 were for enoxaparin and 28 were for tinzaparin [p < 0.0001]). Indications included therapy for deep venous thrombosis, pulmonary embolism, acute coronary syndrome, unstable angina pectoris, non-Q-wave myocardial infarction. Serious renal insufficiency was significantly more frequent in patients from the geriatrics department (p < 0.00001). Enoxaparin was prescribed more frequently in patients with serious or moderate renal insufficiency than tinzaparin (72 vs 61%, p < 0.05). The incidence of LMWHs-induced ADRs was 10.5% occurring in 22 cases during preventive treatment of deep venous thrombosis and in 13 cases during curative therapy. ADRs were classified as 'serious' in 11 cases (31.4%). Reported ADRs were bleeding events (n = 15), thrombocytosis (n = 13), thrombopenia (n = 4) and hepatic cytolysis (n = 1). The mean delay for the occurrence of bleeding effects was 8.0 +/- 9.1 days (range 1-40). Multivariate analysis of the influence of several criteria on the occurrence of haemorrhagic effects showed that the decrease of creatinine clearance (10 ml/min) was associated with an increased haemorrhagic risk (relative risk [RR] = 1.34, 95% CI 1.12-1.65; p < 0.05). Moreover, the risk of adverse bleeding effects increased for patients with a creatinine clearance <20 ml/min (RR = 2.8; 95% CI 1.00-7.8). CONCLUSION: Our data firstly show a different pattern of LMWHs prescription in different clinical wards. Secondly, the risk of bleeding ADRs in patients treated by LMWHs increases significantly with renal function impairment for the two LMWH preparations studied. More pharmacoepidemiological studies are necessary in patients with several risk factors, particularly in elderly people who often have renal impairment, in order to determine the optimal pattern use of each LMWH.

Adolescent↗

PubMed2002

Evolution of total and integrated HIV-1 DNA and change in DNA sequences in patients with sustained plasma virus suppression.

Blood samples from patients with plasma HIV-1 RNA <20 copies/ml for more than 2 years were studied. Significant decreases in total and integrated HIV-1 DNA were observed during the first 15 months of suppressive therapy before the concentrations became stable. Clonal analysis of HIV-1 pol demonstrated that the proportions of resistance mutations in DNA sequences after 2 years were lower than those in baseline DNA and RNA sequences. The changes in the clonal composition of HIV-1 env populations in three patients with evidence of changes in HIV-1 pol populations indicated a shift from predominantly R5-like viruses to predominantly X4-like viruses in two patients and the persistence of predominantly X4-like viruses in the third. Our analyses indicate the reemergence of ancestral sequences from long-lived cells or the residual production of wild-type virus from anatomic sites with limited access to antiretroviral drugs and the preferential infection of cells expressing CXCR4.

Amino Acid Sequence↗