Association of apolipoproteins C3 and E with metabolic changes in HIV-infected adults treated with a protease-inhibitor-containing antiretroviral therapy.

OBJECTIVE: To examine the relationship between plasma levels of apolipoproteins C3 (APOC3) and E (APOE) and the presence of lipid and carbohydrate metabolism abnormalities or clinical signs of lipodystrophy in HIV-1-infected patients started with a protease-inhibitor-containing antiretroviral therapy. METHODS: The Aproco (Antiproteases Cohort) Study enrolled 1,181 HIV-1-infected adults in 47 French healthcare centres from May 1997 to June 1998. From December 1998 through July 1999, the APROCO-Metabolic Complications (APROCO-MC) cross-sectional study was performed at the month 20 visit for those patients enrolled in 1997 and at the month 12 visit for those enrolled in 1998. The current analysis presents results from a subset of patients who had undergone additional tests to measure APOC3 and APOE in order to study their relationship with metabolic syndrome (n=157) and abnormal results in an oral glucose tolerance test (n=135). RESULTS: Increases in triglycerides and non-high-density lipoprotein (HDL) cholesterol were associated with significantly higher levels of APOC3, in both Lp B (lipoproteins containing apolipoprotein B) and Lp non-B (lipoproteins free of apolipoprotein B), and a significant higher level of APOE Lp B. APOC3 and APOC3 Lp non-B were increased when glucose metabolism abnormalities were more severe. The presence of a metabolic syndrome was associated with increased plasma APOC3, APOC3 Lp B and APOC3 Lp non-B levels. In a multiple regression analysis, high levels of APOC3 in Lp B and APOC3 Lp non-B were associated with the presence of clinical signs of lipodystrophy, even after adjustment for triglycerides and HDL-cholesterol levels. CONCLUSIONS: Lipid and/or glucose metabolism abnormalities in treated HIV-1-infected patients are associated with increased levels of APOC3 and, to a lesser extent, APOE plasma concentrations. Increased values are also related to clinical signs of insulin resistance and lipodystrophy.

[Tuberculosis during treatment by TNFalpha-inhibitors]. / Tuberculose lors d'un traitement par agents inhibiteurs du TNF alpha.

The clinical forms of tuberculosis that occur during anti-TNFalpha treatment are frequently extrapulmonary or even disseminated and life-threatening. The paradoxical reactions that can occur under appropriate treatment after stopping TNFalpha inhibitors raise the question of an immune restoration phenomenon. Adverse drug reaction reporting and epidemiologic studies, despite their methodological limitations, appear to show an excess risk of tuberculosis. Experimental studies reinforce these data. The French drug agency (Afssaps) has issued guidelines for the prevention and management of tuberculosis occurring under anti-TNFalpha treatment. Analogous guidelines in Spain led to a reduction in the incidence of these cases.

[Cutaneous and bone metastases revealing hepatocarcinoma]. / Métastases mixtes cutanéo-osseuses révélatrices d'un carcinome hépatocellulaire.

We report the case of a 55-year-old patient who was admitted to our hospital for a frontal tumor. He had a left forehead nodule that had appeared several weeks before, measuring 6 cm in diameter. On palpation, it was painless and there was a pulse, and the skin above was non ulcerated. Radiography and computed tomographic scan of the skull suggested a subcutaneous metastasis. Computed tomographic scans of the lung and the abdomen showed a heterogeneous liver with irregular outlines and secondary adrenal infiltrations. A biopsy of the frontal tumor confirmed a metastatic hepatocellular carcinoma.

New reverse transcription-PCR assay for rapid and sensitive detection of enterovirus genomes in cerebrospinal fluid specimens of patients with aseptic meningitis.

Enterovirus (EV) detection by a new commercially available reverse transcription (RT)-PCR assay (Penter RT-PCR test) was compared with EV isolation from cell cultures and with EV detection by an in-house RT-PCR assay. Of the 54 cerebrospinal fluid specimens collected during a summer outbreak of aseptic meningitis, 52% were positive by cell culture versus 76% by in-house RT-PCR assay and 80% by the new RT-PCR test (52 versus 76 versus 80%; P = 0.003). This new reliable EV RNA detection test is suitable for clinical diagnosis of EV-related meningitis and may improve the management of EV-related neurological syndromes.

[Diagnostic value of clinical signs in giant cell arteritis: analysis of 415 temporal artery biopsy findings]. / Valeur diagnostique des signes de la maladie de Horton.

AIM OF THE STUDY: The American College of Rheumatology (ACR) has proposed a list of criteria for diagnosis of giant cell arteritis in order to guide clinical research by differentiating it from other vasculitis. The aim of this retrospective investigation, based on the findings of 415 temporal artery biopsies was to assess the diagnostic value of these criteria in the daily clinical setting. METHODS: The demographic, clinical and biological characteristics of patients with positive (confirmed cases of giant cell arteritis) or negative (controls) histopathological temporal artery biopsy findings were analyzed using downward step-by-step logistic regression analysis. This analysis enabled investigators to list signs with inherent diagnostic value. Based their odds-ratio, these factors were used to determine a clinical score for giant cell arteritis. RESULTS: A score of over 7 - out of a maximum score of 32 - enables the diagnosis for giant cell arteritis with the best possible compromise between a sensitivity of 75.7% and a specificity of 72.2%. ACR criteria had a sensitivity of 97.5% and a specificity of 78.9% when used in our patient group. CONCLUSION: Our study results are original in that the control group was composed of patients in whom the diagnosis of giant cell arteritis had been suggested but refuted by the absence of histopathological findings on the temporal artery biopsy. This pragmatic attitude in selecting the control group may explain the difference observed with the ACR criteria in terms of sensitivity and specificity. Further research is needed to develop a diagnostic method for giant cell arteritis without resorting to temporal artery biopsy.

Efficacy of zidovudine compared to stavudine, both in combination with lamivudine and indinavir, in human immunodeficiency virus-infected nucleoside-experienced patients with no prior exposure to lamivudine, stavudine, or protease inhibitors (novavir trial).

We compared the efficacy and the toxicity of zidovudine (AZT) versus stavudine (d4T), in combination with lamivudine (3TC) and indinavir, in AZT-, dideoxyinosine (ddI)-, and/or dideoxycytosine (ddC)-experienced patients in a randomized comparative multicenter trial. One hundred seventy human immunodeficiency virus type 1 (HIV-1)-infected patients, who had received AZT, ddI, and/or ddC for at least 6 months but were naive for d4T, 3TC, and protease inhibitors, were randomized to AZT at 250 to 300 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h or to d4T at 40 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h. The primary endpoint was time to virological failure, defined as plasma HIV-1 RNA levels of >5,000 copies/ml after at least 8 weeks of antiretroviral therapy. Additional endpoints were change from baseline in CD4 cell counts, AIDS-defining events and adverse events, and proportion of patients with HIV-1 RNA levels of <500 copies/ml and HIV-1 RNA levels of <50 copies/ml. At week 80, 15 patients in the AZT arm and 14 patients in the d4T arm had reached the primary endpoint, and time to virological failure did not differ between the two arms (P = 0.98). In the d4T and in the AZT arms, 67 and 73% of patients, respectively, had HIV-1 RNA levels of <500 copies/ml (P = 0.50). The median change from baseline in CD4 cell count was 195 x 10(6) and 175 x 10(6)/liter for the d4T- and AZT-containing arms, respectively. The proportions of patients with HIV-1 RNA levels of <50 copies/ml at weeks 8, 16, and 24 were similar in the two arms. The occurrence of serious adverse events was not significantly different between arms. In conclusion, in these patients heavily pretreated with AZT, switching from AZT to d4T when initiating indinavir and 3TC did not bring any additional benefit compared to maintaining AZT.