Bayesian phylogeographic inferences reveal contrasting colonization dynamics among European groundwater isopods.

The potentially important role of northern microrefugia during postglacial dispersal is challenging the view of southern Europe as a refuge and source area of European biota. In groundwaters, large geographic ranges of presumably good dispersers are increasingly suspected to consist of assemblages of cryptic species with narrow ranges. Moreover, a large species range, even when confirmed by molecular evidence, tells us little about the spatiotemporal dynamics of dispersal. Here, we used phylogenetic inferences, species delineation methods and Bayesian phylogeographic diffusion models to test for the likelihood of postglacial colonization from distant refugia among five morphospecies of Proasellus (Isopoda, Asellidae). All morphospecies except one were monophyletic, but they comprised a total of 15-17 cryptic species. Three cryptic species retained ranges that spanned a distance >650 km, similar to that of the nominal morphospecies. Bayesian diffusion models based on mitochondrial markers revealed considerable spatiotemporal heterogeneity in dispersal rates, suggesting that short-time dispersal windows were instrumental in shaping species ranges. Only one species was found to experience a recent, presumably postglacial, range expansion. The Jura and Alpine foothills probably played a major role in maintaining diversity within Proasellus in northern regions by acting both as diversification hotspots and Pleistocene refugia. Gaining insight into the spatiotemporal heterogeneity of dispersal rates revealed contrasting colonization dynamics among species that were not consistent with a global postglacial colonization of Europe from distant refugia.

Lack of isolate-specific neutralizing activity is correlated with an increased viral burden in rapidly progressing HIV-1-infected patients.

OBJECTIVE: To delineate the interaction between in vivo HIV replication and host antiviral immunity during disease progression in order to elucidate the pathogenesis of AIDS. DESIGN: In a cohort of HIV-seropositive patients, the serum concentration of viral particles, the blood concentration of mononuclear cells harbouring infectious virus and the serum titre of isolate-specific neutralizing antibodies were correlated with the rates of CD4+ T-cell depletion and disease progression. METHODS: Using a quantitative reverse-transcriptase linked polymerase chain reaction assay, the concentration of viral particles was measured in blood samples from 103 initially symptom-free subjects who were followed up for > or = 24 months. The concentration of infectious virus and the neutralizing antibodies to autologous HIV isolates were assessed in 37 out of the 103 subjects. The rate of decrease in CD4 cells over the 24 months was calculated for each subject. RESULTS: Rapidly progressing patients (rate of decrease in CD4 cells > or = 60%) had a high concentration of viral particles and a high concentration of infectious virus associated with an undetectable serum titre of isolate-specific neutralizing antibodies. Stable patients (rate of decrease in CD4 cells < 30%) had a low concentration of infectious virus and either a low concentration of viral particles with the absence of isolate-specific neutralizing antibodies or a high concentration of viral particles with the presence of isolate-specific neutralizing antibodies. Slowly progressing patients (rate of decrease in CD4 cells > or = 30 and < 60%) showed an intermediate profile. CONCLUSIONS: Progression to AIDS is associated with a shift in the balance between viral replication and host immunity that increases the concentration of infected cells and destroys the CD4+ T-lymphocyte population.

[Significance of isolated anti-HBs antibodies in subjects not vaccinated against hepatitis B viruses]. / Signification des anticorps anti-HBs isolés chez des sujets non vaccinés contre le virus de l'hépatite B.

The significance of isolated anti-HBs antibodies in subjects not vaccinated against the hepatitis B virus (HBV) was investigated in 13 healthy blood donors. All were European and none had any risk factor for hepatitis B infection. Serological assays included HBV-DNA and anti-preS 2 antibody determinations which were all negative. After injection with hepatitis B vaccine (Hevac B), only one out of the 13 subjects exhibited an anamnestic response in favor of secondary immunization. Neutralization tests for serum anti-HBs antibody were positive in only 6 subjects. Our data suggest that in most cases isolated anti-HBs positivity does not correspond to true antibody; booster injection of HBV vaccine seems to be the best way of verifying that antibodies are really protective.

[A survey of self medication. Comparison of results obtained at two centers]. / Enquête sur l'automédication. Comparaison des résultats obtenus dans deux centres.

Authors report results of an investigation led in 2 separate departments concerning 200 subjects: --blood donors: they are by definition healthy subjects who regularly are in touch with a medical structure; --patients with acute traumatic pathology leading to bone surgery consultation. The aim of this investigation was to analyse the different parameters involved in self-medication and to compare their distribution. Self-medication has an overall incidence of 87.5% in these studied groups and has generally been lasting from 2 to 9 years. The main reason for it is the lack of gravity to go and see a physician; although 52% of the patients tested take the advise of another person. The clinical signs leading to self-medication are looked for; 468 different drugs are listed essentially antalogics and drugs for ear, nose and throat as well as respiratory tract diseases. Self prescribed drugs usually come from the familial stock. Blood donors have some specific characteristics. In this population self-medication is more frequent and has been lasting longer. They more often feel able to take themselves in charge, but in contrast ask for the chemist's or the doctor's advise more frequently.

Actuarial rate of clinical and biological progression in a cohort of 250 HIV-1-seropositive subjects. Laennec HIV Study Group.

This study was undertaken to define the risk of AIDS in a cohort of 250 HIV-seropositive patients identified by their clinical and biological status. All patients were enrolled between October 1985 and March 1988. They were classified according to clinical classes A, asymptomatic (n = 97); B, lymphadenopathic (n = 123); and C, AIDS-related complex, (n = 30). Also as CD4 cell stages 1 (CD4 greater than or equal to 600/microliters; n = 126); 2 (CD4 less than 600 and greater than or equal to 300/microliters; n = 83); and 3 (CD4 less than 300/microliters; n = 41); and serum p24 antigen positive (n = 48) or negative (n = 202). All patients were evaluated every 3-6 months, until AIDS development or April 1989: 29 cases of AIDS occurred during the follow-up period. The risk of AIDS in class C is very high (64% at 2 years) compared with the 3-year risk of classes A (13%) and B (25%). On the other hand the three CD4 stages have significantly different prognosis (stage 1 6%; stage 2 22%; and stage 3 89%; P less than 10(-2]. Antigen p24 negative and positive patients have also different prognosis (18% and 53%; P less than 10(-4]. Interestingly, p24 antigen conserved its prognostic value in stage 2 (positive 37%, negative 16%) while stages 1 are at low risk of AIDS and stages 3 at high risk whatever their p24 antigen status. We have also identified the risk of becoming stage 3 and/or p24 antigen positive in p24 antigen negative patients at stages 1 and 2 (respectively, 18% and 47%). This classification should serve to design randomized trials better with experimental drugs with earlier end-points than AIDS onset.

High concentration of peripheral blood mononuclear cells harboring infectious virus correlates with rapid progression of human immunodeficiency virus type 1-related diseases.

In a cohort of 103 asymptomatic seropositive subjects (Centers for Disease Control and Prevention [CDC] stage II/III) followed for 2 years, the concentration of peripheral blood mononuclear cells harboring infectious human immunodeficiency virus (HIV) type 1 (viral burden) was correlated with the rate of decrease of CD4 cell count (RD-CD4; R = .857). Rapidly progressing patients (RD-CD4 > or = 60%; n = 18) had a high viral burden (mean +/- SE, 572 +/- 202 cells/mL) and an 89% progression to CDC IV-A-C, while stable patients (RD-CD4 < 30%; n = 55) had a low viral burden (mean +/- SE, 28 +/- 4 cells/mL) and remained asymptomatic. Slowly progressing patients (RD-CD4 > or = 30 and < 60%; n = 30) showed an intermediate viral burden (mean +/- SE, 131 +/- 9 cells/mL) and a 10% CDC IV-A-C progression. Quantitative determination of infectious virus in blood cells adds important information on the prognosis of HIV-1 infection.

A rational attitude toward serum alanine aminotransferase measurement by blood banks, based on a longitudinal study of a cohort of repeat blood donors.

A cohort of 879 blood donors was followed over a 3-year period. Of the 3858 units of blood collected, 112 (2.9%), obtained from 64 donors, had an alanine aminotransferase (ALT) activity over 45 IU per L; of these, 39 had a single ALT elevation. The incidence of ALT increase was 2.01 per 100 units, or 5.1 per 100 donors, per year. The pattern of elevated ALT was followed in 72 donors, 54 of whom were from the 64 cited above. At the second blood donation (BD2), about 5 months later, 62.5 percent had a normal ALT value, and most (91%) retained those values at blood donation 3 (BD3). However, 19 (70.3%) of the 27 whose ALT levels had not returned to normal at BD2 had an increased value at BD3. These results led to the formulation of the following algorithm to improve the management of blood donors; at the first donation, the ALT assay is done after the blood collection, but, at the next donation, the ALT level is measured before donation if the preceding ALT activity had been abnormal. If ALT is elevated, blood is not collected. Three consecutive ALT elevations are a criterion for permanent exclusion of the donor.

Serum HIV antigen and anti-P24-antibodies in 200 HIV seropositive patients: correlation with CD4 and CD8 lymphocyte subsets.

Serum HIV (P24) antigen (Ag) measured by an antigen capture ELISA (Abbott) and anti-P24-antibodies (Abs) measured by a competitive ELISA (Abbott) and by Western Blot (Dupont de Nemours) analysis were correlated with lymphocyte subsets (CD4 and CD8) in 174 HIV seropositive patients without AIDS (non-AIDS) and 26 with AIDS. In the non-AIDS group, 27% of the patients were anti-P24-Ab negative and 21% were Ag positive while in the AIDS group these figures were 62% and 54% respectively (P less than 0.001). Overall, a significant correlation exists between the Ab-Ag profile and the CD4 cell count: the percentage of patients with anti-P24-Ab positive and Ag negative decreases from 90% for patients with more than 900 CD4 cells/microliter to 21% for patients with 100 and less CD4 cells/microliter; on the contrary, the percentage of patients with anti-P24-Ab negative and Ag positive increases from 0% over 800 CD4 cells to 53% under 100 CD4 cells/microliter. A weak correlation may also exist with the CD8 cell count. The subgroup of patients with 1,000 or more CD8 cells/microliter have a higher (but not significant) percentage of subjects with Ag positive and anti-P24-Ab negative than the subgroup with less than 1,000 CD8 cells/microliter. A short-term longitudinal study (mean follow-up: 1 year) was performed on 80 non-AIDS subjects: 77% (10/13) of those who had a CD4 cell decrease (greater than 30%) were initially Ag positive, while only 21% (14/67) of those without a decrease were Ag positive at the beginning (P less than 0.1). Although the relative weight and individual predictive value of each of these parameters need to be classified, they are probably the best biological markers currently available for monitoring clinical trials with experimental drugs.

Effects of cyclosporin on T-cell subsets in human immunodeficiency virus disease.

Cyclosporin (7.5 mg/kg daily) was given to 8 AIDS patients for 17-66 days and to 25 HIV-seropositive non-AIDS patients, 15 with stage II (T4 cells/microliter greater than or equal to 300, less than 600) and 10 with stage III (T4/microliter less than 300), for 3-6 months with the hypothesis that the drug could inhibit both HIV replication and the potential autoimmune component of HIV disease. A sustained increase over 600 T4/microliter occurred in 7 patients with stage II and 1 with stage III. T8 cells significantly decreased in most patients and lymphadenopathy disappeared in 14/16. After cyclosporin withdrawal T4 and T8 cells as well as lymphadenopathy returned to pretreatment status. Cyclosporin side effects (hypertension, creatinine increase, and anemia) were moderate and reversible. These results might stimulate biological research as well as clinical trials with cyclosporin in selected groups of HIV-seropositive subjects with the aim of delaying or preventing AIDS occurrence.

Changes of soluble CD16 levels in serum of HIV-infected patients: correlation with clinical and biologic prognostic factors.

The modulation of soluble CD16 titers in human immunodeficiency virus (HIV)-infected patients' serum, with an initial increase in Centers for Disease Control (CDC) clinical stage II and III patients followed by a dramatic drop in patients with AIDS (CDC clinical stage IV), is reported. These changes are statistically correlated with the CDC staging system, the number of CD4+ cells, the amount of p24 antigen in serum, and the anti-p24 antibody titers, indicating the potential value of soluble CD16 titer as an easily available serum marker of disease progression. To evaluate a possible link between this observation and the expression of membrane-associated CD16/FcRIII, flow cytometry immunofluorescence analysis was performed on peripheral blood lymphocytes from patients in three CDC stages; no specific changes in the number of natural killer cells expressing CD16+ antigens or in the total number of Leu19+ cells were found. However, there was a statistical correlation between the absolute number of T cells expressing CD16 antigens (CD3+/CD16+) and the modulated titers of soluble CD16 in HIV-infected serum.

An epidemiological and clinical study of transaminase levels and hepatitis B antibodies in 1,100 blood donors.

In order to provide epidemiological and clinical information on surrogate testing of blood donations, the respective prevalences of serum hepatitis B virus (HBV) markers and elevated transaminase levels were studied in 1,100 blood donors according to their geographic origin and socioeconomic level. The frequency of serum HBV markers varied as a function of HBV endemicity in the country of origin; however, it was inversely correlated (p less than 0.05) to the socioeconomic level of the donors, even in those originating from countries of low HBV endemicity. There was no association between serum HBV markers and the increased transaminase level which was observed in 48 (4.3%) donors. Twenty-five of these accepted further clinical evaluation. A diagnosis appeared probable in 12 of the 25: alcohol in 5; drugs in 6; non-A, non-B hepatitis in 1. Seven of the remaining 13 subjects were more than 25% above ideal body weight. Transaminase activities determined at the time of clinical assessment were normal in 14. In addition, serum HBV DNA was found in 5 of 247 donors, even in the absence of any usual HBV marker and/or hypertransaminasemia. This could account for the few cases of B and B-like posttransfusion hepatitis which are known to still occur despite careful HBsAg screening of blood donors.