[The use of fluoroquinolone plasma levels by physicians]. / Utilisation des dosages plasmatiques des fluoroquinolones par les cliniciens.

OBJECTIVE: To assess how physicians use the results of fluoroquinolone plasma concentrations. METHODS: A retrospective study was carried out on all the patients of the Infectiology department of the University Hospital in Nice who had undergone measurement of ofloxacin, ciprofloxacin or pefloxacin plasma levels between the 1st of January 2001 and the 31st of May 2002. RESULTS: Seventy eight patients were included. Median duration of treatment was 90 days. In 43% of cases, the patients had also received an enzyme inducer (rifampin in 90% cases). The minimum inhibitory concentration was requested 12 times. In 26% of cases, a first inadequate concentration was not followed by a second control analysis. We noted that at the start of treatment, 56% of patients exhibited inadequate levels, and the dose of fluoroquinolone was hence increased by the physician in 40% of cases. We noted 4 bacteriological relapses, all within a context of insufficient dose, with selection of a resistant mutant three times. DISCUSSION: Physicians do not appear to use the fluoroquinolone plasma levels to their best advantage.

Relevance and complications of intravenous infusion at the emergency unit at Nice university hospital.

OBJECTIVE: Insertion of peripheral venous catheters (PVCs) is current practice within the hospital environment and particularly in the emergency department (ED). This simple yet invasive technique may result in venous thrombosis, infection or mechanical complications. We conducted a prospective study at the Nice University Hospital ED in order to determine the frequency, relevance and complications of peripheral venous cannulation. PATIENTS AND METHODS: Fourteen 24 h periods were surveyed over the months of May and June 2000, during which 2515 patients over 16 years of age attended the unit. Demographic and medical data were recorded for every patient who received a PVC. These patients were followed at 12 h intervals until the catheter was removed. Reasons for PVC, time left in place, and eventual complications were recorded. Justification for PVC was evaluated upon arrival at the ED, upon exiting the ED and in some cases within the hospital ward. RESULTS: Six hundred and thirty of 2515 patients (25%) received a PVC (290 women (46%) and 340 men (54%); meanage 58 years). Indication for the PVC was considered unjustified in 24.8% of cases upon arrival at the ED, and 33.8% upon leaving the ED. Upon admission in a hospital ward after passing through the ED, out of 318 patients, the PVC was left in place for no reason in 63 (20%). Overall, 390 PVCs were followed until the time of their removal. Mean duration of IV infusion was 28 h. Among these 390 patients, 62 (15.9%) developed complications, of which 54 (13.6%) had thrombophlebitis and 9 (2.3%) developed local infection. Mean duration of PVC left in place for patients with complications was 50 h vs 25 h for patients with no complications (P<0.001). CONCLUSION: Insertion of a PVC is common practice especially in EDs. The excessive use of this procedure leads to extra cost and iatrogenic complications. A renewed definition of its indication and raised awareness among hospital staff concerning the risks involved with this standard procedure should result in less use of PVC and fewer complications.

Differential divergence of three human pseudoautosomal genes and their mouse homologs: implications for sex chromosome evolution.

The human pseudoautosomal region 1 (PAR1) is essential for meiotic pairing and recombination, and its deletion causes male sterility. Comparative studies of human and mouse pseudoautosomal genes are valuable in charting the evolution of this interesting region, but have been limited by the paucity of genes conserved between the two species. We have cloned a novel human PAR1 gene, DHRSXY, encoding an oxidoreductase of the short-chain dehydrogenase/reductase family, and isolated a mouse ortholog Dhrsxy. We also searched for mouse homologs of recently reported PGPL and TRAMP genes that flank it within PAR1. We recovered a highly conserved mouse ortholog of PGPL by cross-hybridization, but found no mouse homolog of TRAMP. Like Csf2ra and Il3ra, both mouse homologs are autosomal; Pgpl on chromosome 5, and Dhrsxy subtelomeric on chromosome 4. TRAMP, like the human genes within or near PAR1, is probably very divergent or absent in the mouse genome. We interpret the rapid divergence and loss of pseudoautosomal genes in terms of a model of selection for the concentration of repetitive recombinogenic sequences that predispose to high recombination and translocation.

Prevalence and risk factors of cervicovaginal HIV shedding among HIV-1 and HIV-2 infected women in Dakar, Senegal.

OBJECTIVES: To assess the risk determinants and prevalence of cervicovaginal shedding of HIV-1 and HIV-2 among women in Dakar, Senegal. METHODS: We conducted a cross sectional study of 153 HIV seropositive female sex workers (FSW) and another 142 HIV seropositive women attending an infectious diseases unit, based on an interview, physical examination, and laboratory screening for major sexually transmitted infections (STI). Cervicovaginal lavage fluid was tested for HIV-RNA by means of nested PCR. Links between cervicovaginal shedding of HIV-1 and HIV-2 and sociodemographic, clinical, and laboratory variables were identified by using odd ratios and 95% confidence intervals. Logistic regression analysis was used to identify independent links with HIV shedding. RESULTS: The detection rate of HIV-RNA in cervicovaginal lavage fluid was low among FSW, with no difference between HIV-1 (7/90: 8%) and HIV-2 (3/48: 6%). The rate was far higher among the other women (41%, 48/117; 33%, 7/21 for HIV-1 and HIV-2, respectively). In multivariate analysis, high plasma viral load (>40 000 copies/ml) (AOR = 2.4 (1.0-5.6) p = 0.04) and basic vaginal pH (AOR = 2.2 (1.3-3.7) p = 0.002) were independently associated with HIV-1 shedding. For HIV-2 a CD4 count < 200 cells x 10(6)/l was the only factor associated with the shedding of HIV-2 (AOR = 9.0 (0.9-93)). The genital shedding rate was higher with HIV-1 than with HIV-2 (OR = 2.1 (0.9-4.8), but this difference disappeared after adjustment for the CD4+ cell count (AOR = 1.2 (0.5-2.9)). CONCLUSION: Advanced disease stage and immunosuppression are the major risk determinants for shedding of both HIV-1 and HIV-2. Basic vaginal pH is also a risk determinant for HIV-1 shedding.

Centromere repositioning.

Primate pericentromeric regions recently have been shown to exhibit extraordinary evolutionary plasticity. In this paper we report an additional peculiar feature of these regions that we discovered while analyzing, by FISH, the evolutionary conservation of primate phylogenetic chromosome IX. If the position of the centromere is not taken into account, a relatively small number of rearrangements must be invoked to account for interspecific differences. Conversely, if the centromere is included, a paradox emerges: The position of the centromere seems to have undergone, in some species, an evolutionary history independent from the surrounding markers. A significant number of additional rearrangements must be proposed to reconcile the order of the markers with centromere position. Alternatively, the evolutionary emergence of neocentromeres can be postulated.