PubMed Health⌕ Search

Biomedical subjects

P Meylan

Publications and source records attributed to P Meylan.

17 recordsLinked to original sources
PubMed2006

[Evidence of new foci of tick-borne encephalitis in the French speaking part of Switzerland].

The incidence of tick-borne encephalitis (TBE) has more than doubled in Switzerland in recent years. In the French part of Switzerland several patients seem to have acquired the infection outside of known endemic foci. Thirty patients with TBE living or having acquired the infection in the French speaking part of Switzerland between 2000 and 2005 were identified. For one patient it wasn't possible to obtain precise information about the place of acquisition of the infection and 16 patients were infected in known endemic foci. Among the 13 remaining patients, 6 were infected on the southern shores of the lake of Neuchâtel and 7 in the plaine of Orbe. We conclude that there are new foci of TBE in the northern regions of the canton of Vaud. Vaccination should be proposed to the population at risk of these regions. In addition it is important that persons with outdoor activities in this regions respect the preventive

Adolescent↗
PubMed2005

[Swiss recommendations for the management of gential herpers and herpes simplex virus infection of the neonate].

Genital herpes is being recognised as a medical problem of increasing importance. Diagnosis and management are complex. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by all Swiss medical societies involved in the medical care of such patients. The aim is to improve the care of affected patients, to reduce horizontal and vertical transmission and to diminish the psychosocial burden.

Adult↗
PubMed2001

Resistance to nucleoside analog reverse transcriptase inhibitors mediated by human immunodeficiency virus type 1 p6 protein.

Resistance of human immunodeficiency virus type 1 (HIV-1) to antiretroviral agents results from target gene mutation within the pol gene, which encodes the viral protease, reverse transcriptase (RT), and integrase. We speculated that mutations in genes other that the drug target could lead to drug resistance. For this purpose, the p1-p6(gag)-p6(pol) region of HIV-1, placed immediately upstream of pol, was analyzed. This region has the potential to alter Pol through frameshift regulation (p1), through improved packaging of viral enzymes (p6(Gag)), or by changes in activation of the viral protease (p6(Pol)). Duplication of the proline-rich p6(Gag) PTAP motif, necessary for late viral cycle activities, was identified in plasma virus from 47 of 222 (21.2%) patients treated with nucleoside analog RT inhibitor (NRTI) antiretroviral therapy but was identified very rarely from drug-naïve individuals. Molecular clones carrying a 3-amino-acid duplication, APPAPP (transframe duplication SPTSPT in p6(Pol)), displayed a delay in protein maturation; however, they packaged a 34% excess of RT and exhibited a marked competitive growth advantage in the presence of NRTIs. This phenotype is reminiscent of the inoculum effect described in bacteriology, where a larger input, or a greater infectivity of an organism with a wild-type antimicrobial target, leads to escape from drug pressure and a higher MIC in vitro. Though the mechanism by which the PTAP region participates in viral maturation is not known, duplication of this proline-rich motif could improve assembly and packaging at membrane locations, resulting in the observed phenotype of increased infectivity and drug resistance.

Amino Acid Sequence↗
PubMed2001

Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease (PR) and reverse transcriptase (RT) inhibitors may display impaired infectivity and replication capacity. The individual contributions of mutated HIV-1 PR and RT to infectivity, replication, RT activity, and protein maturation (herein referred to as "fitness") in recombinant viruses were investigated by separately cloning PR, RT, and PR-RT cassettes from drug-resistant mutant viral isolates into the wild-type NL4-3 background. Both mutant PR and RT contributed to measurable deficits in fitness of viral constructs. In peripheral blood mononuclear cells, replication rates (means +/- standard deviations) of RT recombinants were 72.5% +/- 27.3% and replication rates of PR recombinants were 60.5% +/- 33.6% of the rates of NL4-3. PR mutant deficits were enhanced in CEM T cells, with relative replication rates of PR recombinants decreasing to 15.8% +/- 23.5% of NL4-3 replication rates. Cloning of the cognate RT improved fitness of some PR mutant clones. For a multidrug-resistant virus transmitted through sexual contact, RT constructs displayed a marked infectivity and replication deficit and diminished packaging of Pol proteins (RT content in virions diminished by 56.3% +/- 10.7%, and integrase content diminished by 23.3% +/- 18.4%), a novel mechanism for a decreased-fitness phenotype. Despite the identified impairment of recombinant clones, fitness of two of the three drug-resistant isolates was comparable to that of wild-type, susceptible viruses, suggestive of extensive compensation by genomic regions away from PR and RT. Only limited reversion of mutated positions to wild-type amino acids was observed for the native isolates over 100 viral replication cycles in the absence of drug selective pressure. These data underscore the complex relationship between PR and RT adaptive changes and viral evolution in antiretroviral drug-resistant HIV-1.

Animals↗
PubMed2000

Immunological and virological responses in HIV-1-infected adults at early stage of established infection treated with highly active antiretroviral therapy.

OBJECTIVE: To evaluate the immunological and virological responses to highly active antiretroviral therapy (HAART) in blood and lymphoid compartments of HIV-1-infected patients at an early stage of infection. DESIGN: An open-label, observational, non-randomized, prospective trial of outpatients attending the Centre of Clinical Investigation in Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. SUBJECTS: Forty-one antiretroviral-naive HIV-1-infected adults with 400 CD4 T cells/microl or greater and 5000 plasma HIV-1-RNA copies/ml or greater were enrolled, and 32 finished the study. Forty-nine HIV-negative individuals were included as controls. All subjects gave written informed consent. INTERVENTIONS: All patients received abacavir 300 mg by mouth every 12 h and amprenavir 1200 mg by mouth every 12 h for 72 weeks. MAIN OUTCOME MEASURES: The extent of immune reconstitution in blood and lymph nodes after 72 weeks of HAART was evaluated, and compared with immunological measures of 49 HIV-negative subjects. RESULTS: Virus replication was effectively suppressed (-3.5 log10 at week 72). Substantial increments of CD4 T cell count in blood and percentage in lymph nodes were observed over time, and these measures were comparable to HIV-negative subjects by week 24 in blood and by week 48 in lymph nodes. The increase was equally distributed between naive and memory CD4 T cells. Recovery of HIV-specific CD4 responses occurred in 40% of patients. CONCLUSION: The initiation of HAART at an early stage of established HIV infection induces systemic quantitative normalization of CD4 T cells, a partial recovery of HIV-specific CD4 cell responses, and effective and durable suppression of virus replication.

Adolescent↗
PubMed2000

Virological and immunological characteristics of HIV treatment failure.

BACKGROUND: Resistance to antiretroviral treatment is prevalent. There is limited knowledge of the determinants of disease evolution in subjects infected with multidrug-resistant HIV (MDR-HIV). METHODS: Infectivity, replication, chemokine receptor usage, and env, gag, protease and reverse transcriptase sequence analysis was performed for MDR-HIV isolates from 14 HIV-infected individuals and compared to wild-type HIV isolates from individuals naive to antiretroviral treatment. Expression of CD45RO/RA, Ki67 and interferon-gamma and CD4 proliferative response to various antigens was determined for individuals infected with MDR-HIV and compared to that in individuals with optimal suppression of viral replication. RESULTS: Infectivity and replication are diminished for various MDR-HIV isolates, usually in the context of an increase in CD4 and CD4+CD45RA+ T-cell counts. However, a number of MDR-HIV isolates are associated with high in vivo viraemia and pronounced immunosuppression, and display in vitro levels of infectivity and replication comparable to those of wild-type strains. No specific genetic sequence or chemokine receptor usage predicted the fitness of an MDR isolate. CONCLUSIONS: Despite the biological diversity of resistant viruses and the range of host responses observed, our descriptive analysis indicates that viral factors play a role in determining the degree of immune damage observed in the context of MDR-HIV infection.

Adult↗
PubMed1999

Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo.

The nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo remain unclear. We investigated the contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by studying infection with parental HIV-1 strain NL4-3 and with a nef mutant (DeltanefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than DeltanefNL4-3 did. Increased virus production with NL4-3 infection was associated with increased numbers of productively infected cells and greater loss of CD4(+) T cells over time. While the numbers of productively infected T cells were increased in the presence of nef, the levels of viral expression and production per infected T cell were similar whether the nef gene was present or not. Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL4-3-infected tissue in a dose-dependent manner. In contrast, DeltanefNL4-3 production was enhanced only marginally by IL-2. Thus, Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation.

Animals↗
PubMed1998

Limited CD4+ T-cell renewal in early HIV-1 infection: effect of highly active antiretroviral therapy.

We show that the fraction of proliferating CD4+ lymphocytes is similar in HIV-infected subjects in the early stage of disease and in HIV-negative subjects, whereas the fraction of proliferating CD8+ lymphocytes is increased 6.8-fold in HIV-infected subjects. After initiation of antiviral therapy, there is a late increase in proliferating CD4+ T cells associated with the restoration of CD4+ T-cell counts. These results provide strong support for the idea of limited CD4+ T-cell renewal in the early stage of HIV infection and indicate that after effective suppression of virus replication, the mechanisms of CD4+ T-cell production are still functional in early HIV infection.

Adult↗
PubMed1997

Tests of turtle phylogeny: molecular, morphological, and paleontological approaches.

We present phylogenetic analyses of both molecular and morphological data for the 23 major lineages of living turtles and seven key fossil taxa. Nearly 1 kilobase of cytochrome b sequence, 325 base pairs of 12S ribosomal DNA, and 115 morphological characters contained similar phylogenetic information, although each provided unique information on different nodes of chelonian history. A character-based combinability test (implemented in PAUP*) and a non-parametric test of taxonomic congruence indicated no strong evidence for heterogeneity among data sets, and we used a combined approach to estimate a final phylogeny of the major lineages of living turtles. This approach resulted in a very well-resolved tree, with only a few of the deep branches within the Cryptodira left as an unresolved polytomy. The addition of six relatively complete fossils chosen to help resolve this basal polytomy provided little added resolution to the tree and resulted in a sharp decline in bootstrap proportions for nodes near the fossils. Branch-length analysis and independent dates from the fossil record suggest that these unresolved nodes may represent a rapid radiation of the major cryptodiran lineages 90-120 million years ago.

Animals↗
PubMed1987

The inflammatory response and tissue damage. The example of renal scars following acute renal infection.

Most clinical and experimental evidence suggests that renal scarring occurs following urinary tract infections in those patients with an abnormality of the urinary tract or kidney function. Experimentally, bacterial multiplication within the kidney occurs only in the presence of obstruction, leading rapidly to acute exudative pyelonephritis and invariably to kidney scars within weeks. Various manipulations of the bacterial load and/or of the inflammatory response during acute pyelonephritis have demonstrated that the inflammatory processes, not the bacterial component of pyelonephritis, are responsible for permanent renal tissue damage. Polymorphonuclear leucocytes (PMNLs) infiltrating the kidney tissue during acute pyelonephritis appear to release metabolites that are toxic to the parenchyma. Indeed, both the prevention of PMNL influx into renal tissue, by means of colchicine or cyclophosphamide, and the inactivation of some of their toxic metabolites, by means of dapsone, have led to the prevention of tissue damage and kidney scars. However, the most potent protective activity was observed with early antibiotic treatment, which stopped bacterial multiplication and prevented the early influx of PMNLs, thus preventing tissue damage and scar formation. Similar observations have been made in children with acute pyelonephritic episodes, in whom early and aggressive antibiotic treatment prevented subsequent kidney scars, while delayed treatment did not.

Cicatrix↗
PubMed1986

Mechanisms of successful amoxicillin prophylaxis of experimental endocarditis due to Streptococcus intermedius.

Prophylaxis with amoxicillin (40 mg/kg) was studied in rats with aortic valve vegetations. Bacteria on the valves were quantitated early (10 min to 6 hr) and late (three days) after intravenous challenge with tolerant Streptococcus intermedius. Amoxicillin reduced by 40% the number of bacteria per valve 10 min after intravenous challenge with 10(5) S. intermedius (P less than .05) and by 74% the incidence of endocarditis three days thereafter (P less than .0001). Bacterial multiplication started 2 hr after challenge in control rats, whereas bacteria disappeared in 6 hr in amoxicillin-treated rats. Intravenous penicillinase 30 min after challenge abolished successful amoxicillin prophylaxis, a result demonstrating the necessity of prolonged growth inhibition for protection. Growth inhibition for 18 hr (two subsequent amoxicillin doses) was necessary for protection after intravenous challenge with 10(5) S. intermedius. Thus, in the absence of bacterial killing, inhibition of valvular colonization by amoxicillin was not as important a mechanism of endocarditis prophylaxis as was prolonged inhibition of bacterial growth, which allowed adherent bacteria to be cleared from the valves.

Amoxicillin↗
PubMed1983

Effect of indomethacin on the incidence of experimental Escherichia coli pyelonephritis.

In the presence of temporary obstruction (20 h), ascending Escherichia coli urinary infection leads to irreversible acute exudative pyelonephritis (AEP) in rats. The purpose of the present study was to investigate the early inflammatory events which take place in response to the presence of bacteria in the kidney parenchyma and lead to the development of AEP. Rats were given indomethacin before and during the obstructive phase of kidney infection and were sacrificed at different times thereafter. Although renal infection (as defined by bacterial counts) was equally frequent (76%) and severe in indomethacin-treated and control rats sacrificed at the end of the obstructive period, it was found that the incidence of AEP (as defined by the inflammatory response of the kidney elicited by bacteria) 2 days after removal of the obstruction was significantly reduced from 74% in controls given water to 48% in indomethacin-treated animals (P = 0.02). Rat kidneys without AEP had bacterial counts of 10(2)/g. Since indomethacin apparently had no direct antibacterial activity against E. coli and no effect on urine osmolalities, it is likely that the reduction in the incidence of AEP and the concomitant eradication of bacteria after removal of the obstruction was due to an effect of indomethacin that is related to the renal response to infection. This was possibly due to decreased inflammation, as indicated by the fact that when pyelonephritis developed in indomethacin-treated rats it was less severe than in controls. These results suggest that if inflammation can be mitigated when bacteria are present in the kidney during obstruction, the bacteria may be cleared spontaneously once the normal urinary flow is restored.

Animals↗