Comparison of 3 methods for estimating enteric methane and carbon dioxide emission in nonlactating cows.

Among techniques for estimating enteric methane (CH4) emission by ruminants, open-circuit respiration chambers (OC), the use of a gas tracer (SF6), and the GreenFeed (GF) device are the most commonly used. In this study, we compared these techniques in 8 dry cows receiving a diet made of 70% hay and 30% concentrates given in limited and constant amounts, in a 15-wk experiment. Two periods in free stalls for SF6 and GF and in chambers for OC were used; in addition, SF6 was determined in chambers for 1 period. Methane emission (g/d) and CH4 yield (g/kg DMI) were higher (P < 0.0001) for OC than for SF6 and GF (367, 310, and 319 g/d for OC, SF6, and GF, respectively). The difference between OC and GF was related to a difference in post-prandial rate of gas emission. The between-animal coefficient of variation of CH4 emission was higher for SF6 than for OC and GF (20.8, 13.5, and 12.0% on average, respectively). Correlation coefficients between OC and SF6 were high and significant for CH4 emission and CH4 yield (r = 0.782 and r = 0.717, respectively; P < 0.05), but not significant between OC and GF, or between SF6 and GF. Correlation coefficients were highly significant for SF6 determined either in free stalls or in chambers (r = 0.908 and 0.903 for CH4 in g/d and g/kg DMI, respectively; P < 0.01). Carbon dioxide (CO2) emission and CO2 yield were similar for GF and OC (10,003 and 9,887 g/d, 752 and 746 g/kg DMI, respectively); CO2 data obtained with SF6 were lower (7,718 g/d and 606 g/kg DMI; P < 0.0001), but this technique is not relevant for CO2 emission determination. Correlation coefficients between OC and GF were not significant for CO2 emission and CO2 yield. This set of results shows that differences between methods are minor for average values, but that individual correlations may limit their interchangeability for determining gas emissions of individual animals. This study also shows the reliability of GF on-farm determination of CH4 and CO2 emissions for groups of animals.

[From retroperitoneal fibrosis to gastric linitis]. / De la fibrose rétropéritonéale à la linite gastrique.

Retroperitoneal fibrosis may reveal many diseases, including neoplasias. An 83-year-old man presented with an acute renal failure due to compressive retroperitoneal fibrosis. Clinically the only abnormal feature was a cutaneous subclavicular infiltrated lesion and laboratory features included hypereosinophilia, anemia and elevated acute phase reactants. A thoracic CT-scan showed pleuritis and para-esophageal lymph node and the 18FDG-PET-scan an hypermetabolism lesion of the oesophagus. Gastroscopy and colonoscopy found a gastric linitis, already multi-metastatic at diagnosis. The gastric linitis can present with many decepting clinical forms, increasing the risk of delayed diagnosis.

Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort study.

OBJECTIVES: To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. METHODS: A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. RESULTS: The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/microL. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). CONCLUSIONS: A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome.

Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy.

The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The main outcome measures were as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-associated herpesviral load in peripheral blood mononuclear cells using real-time quantitative polymerase chain reaction (non-detectable if less than 100 copies per microg); human immunodeficiency viral charge in plasma (non-detectable if less than 200 copies per ml); and CD4 lymphocyte count. Time to undetectable Kaposi's-sarcoma-associated herpesviral load, time to undetectable human immunodeficiency viral charge, and time to CD4 >or= 150 per microl were also recorded over time, from 2 mo measurements. Patients were staged according to the AIDS Clinical Trials Group-based tumor, immune, systemic staging system criteria. At baseline, Kaposi's sarcoma was progressive for 25 (96%) of the 26 enrolled patients. Complete or partial response to highly active antiretroviral therapy alone or combined with chemotherapy was achieved in 22 patients (85%). Median time to clinical response was estimated at 251 d. Clinical response was faster in patients without chemotherapy at baseline (p = 0.003) as well as in patients not previously treated with reverse transcriptase inhibitors (p = 0.0012). Using univariable analyses, predictive factors of clinical response were undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immunodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005) were independently selected as having a predictive value for clinical response. Occurrence of nondetection of either Kaposi's-sarcoma-associated herpesvirus or human immunodeficiency virus was not associated with baseline CD4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antiretroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reconstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.

Highly active antiretroviral treatment initiated early in the course of symptomatic primary HIV-1 infection: results of the ANRS 053 trial.

Highly active antiretroviral treatment (HAART) was given early to 64 patients with symptomatic primary human immunodeficiency virus (HIV)-1 infection. At the time of analysis, patients had been followed up for 9-21 months. No patient had died or developed an AIDS-defining event. Survival analysis showed that by month 21 the proportion of patients with plasma HIV-1 RNA <50 copies/mL was 72% (95% confidence interval, 58%-95%) in intention-to-treat analysis. After 18 months of treatment, 50% of the patients with undetectable plasma HIV-1 RNA also had undetectable HIV-1 RNA in peripheral blood mononuclear cells (PBMC). Only 1 of 3 patients had undetectable HIV-1 RNA in lymphoid tissue, while all patients had quantifiable HIV-1 DNA both in PBMC and lymphoid tissue. The median CD4 lymphocyte increase from baseline was 230 cells/microL. These preliminary results support the use of HAART in patients with primary HIV-1 infection.

Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects.

Trecovirsen, a 25-mer antisense phosphorothioate oligonucleotide targeted at the gag site of the HIV gene, was administered to HIV-positive volunteers as an i.v. infusion. Single doses ranged from 0.1 to 2.5 mg/kg in an ascending escalation in cohorts of 6 to 12 subjects. Plasma trecovirsen concentrations and pharmacokinetic parameters could be assessed at doses > or = 0.3 mg/kg. Peak plasma concentrations and AUC values increased disproportionately with increasing dose while elimination half-life increased and plasma clearance decreased, indicating a saturable process over this dose range. The only significant adverse event observed was an isolated, transitory increase in activated partial thromboplastin time at doses > or = 2.0 mg/kg that was related to plasma trecovirsen concentrations and is attributed to the polyanionic character of the molecule. Thus, trecovirsen administration was well tolerated in single i.v. doses up to 2.5 mg/kg.

[Non-nucleoside antiretroviral agents]. / Les antirétroviraux non nucléosidiques.

Antiviral agents, other than nucleoside reverse transcriptase inhibitors, are currently being developed. Some have been marketed. Most of these new drugs are protease inhibitors which inhibit the formation and release of new infecting virions at the end of the intracellular cycle of the human immunodeficiency virus. Saquivanir, ritonavir, and indinavir are among the most widely studied. Non-nucleoside reverse transcriptase inhibitors (nevirapine is the leading product) include several components called TIBO or TIBO-like. These drugs have the advantage of good tolerance but resistance may develop early when they are given alone. Clinical trials aimed at preventing virus-cell fusion have not been successful in vivo. Other therapeutic approaches, including antisense oligonucleotids, ribozymes, and TAT or REV gene inhibitors are being explored. Several trials focusing on therapeutic strategy are being conducted using combinations of drugs. The objective is to use both non-nucleoside and nucleoside reverse transcriptase inhibitors together with antiproteases. Certain combination protocols using 3 or more antiviral agents have shown a synergetic effect and reduced or delayed resistance. Finally, the role of immunomodulation and immunotherapy is under investigation.