Pelvic floor disorders: linking genetic risk factors to biochemical changes

Pelvic floor disorders (PFDs) such as stress urinary incontinence (SUI) and pelvic organ prolapse (POP) may share a common pathophysiological process related to pelvic floor tissue laxity and loss of support. We reviewed recent literature on observed biochemical changes in women with SUI and POP, linking them to genetic predisposition. We found that studies of pelvic tissues showed differences between control subjects and women with POP and SUI in collagen and elastin structure at a molecular and fibrillar level. Studies were heterogeneous but showed a trend towards decreased collagen and elastin content. The contribution of matrix metalloproteinases to increased collagenolysis can be related to genetic polymorphisms present in higher frequency in women with PFD. Extracellular matrix (ECM) protein turnover plays a role in the development of POP and SUI, but much remains to be understood of this complex dynamic interplay of enzymes, proteins and molecules. Genotyping of candidate genes participating in ECM formation will elucidate the missing link between the manifestation of the disease and the biochemical changes observed systematically, in addition to those in the pelvic floor.     

Surveillance of antimicrobial resistance and antimicrobial use in a university-affiliated hospital: implementation of a computerized system

After half a century of antibiotic use, the increasing problem of the emergence and spread of antimicrobial-resistant pathogens has created a problem of public health. The causes of this problem are multifactorial, but the excessive and inappropriate use of antimicrobials is the principal cause. The current guidelines for the control of antimicrobial resistance in hospitals recommend the implementation of a surveillance system of antimicrobial use and antimicrobial resistance data. AIM OF THE STUDY: The objective of our project was to develop a computerised tool to survey the antibiotic consumption data and the antimicrobial resistance. MATERIALS ET METHODS: We have collected antimicrobial resistance data from the software of the bacteriology laboratory, antibiotic use data from the pharmacy and demographical data from the hospital's admission department. These data were integrated in a database server and available with a web application. Antimicrobial resistance data of 15 major microorganisms were extracted and expressed as a frequency with elimination of repeats by using time criteria (7, 14 or 28 days). Antibiotic use data were converted into defined daily doses (DDD) and expressed per 1000 patient-days. RESULTS: Data are available for consultation in the form of tables or graphs per unit, type of units (medicine, surgery, pediatrics, intensive care units) or in the whole hospital. The system allows the confrontation on the same graph of antimicrobial resistance and antibiotic use data. CONCLUSION: Our surveillance system constitutes a needed prerequisite to the implementation of a global strategy of antibiotic use improvement in our hospital.     

Prone position and recruitment manoeuvre: the combined effect improves oxygenation

Introduction  

Among the various methods for improving oxygenation while decreasing the risk of ventilation-induced lung injury in patients with acute respiratory distress syndrome (ARDS), a ventilation strategy combining prone position (PP) and recruitment manoeuvres (RMs) can be practiced. We studied the effects on oxygenation of both RM and PP applied in early ARDS patients.     

Low-level resistance to fluoroquinolones conferred by efflux overproduction in Pseudomonas aeruginosa: clinical significance and routine detection

The aim of this study was (i) to assess the impact of stable overproduction of efflux systems MexAB-OprM and MexXY-OprM on the bacteriostatic activities of fluoroquinolones in clinical Pseudomonas aeruginosa strains and (ii) to find a convenient test for screening isolates with a low level resistance to fluoroquinolones. The minimal inhibitory concentrations (MICs) of ciprofloxacin and levofloxacin were determined for clinical isolates of P. aeruginosa overexpressing MexAB-OprM or MexXY-OprM. Efflux pumps derepression was associated with a modest two- to fourfold increase in resistance to the tested fluoroquinolones. Clinical significance of low level resistance conferred by the efflux mechanism was evaluated with a Monte Carlo simulation with various fluoroquinolone regimens. With this model, low levels of resistance to ciprofloxacin (MIC > or =0.25 mg/L) or levofloxacin (MIC > or =1 mg/L) such as those due to overproduced MexAB-OprM or MexXY-OprM were predicted to result in poor clinical outcomes. Altogether these data strongly suggest that when derepressed MexAB-OprM or MexXY-OprM provides P. aeruginosa with a resistance that may be sufficient to impair the efficacy of single therapy with highly potent fluoroquinolones such as ciprofloxacin and levofloxacin. Routine detection of clinical strains that displayed low-level resistance to fluoroquinolones with a Mueller Hinton agar containing 0.20 mg/L of ciprofloxacin will help clinician in his therapeutical choice.     

On the use of R1 and R2* for measurement of contrast agent concentration in isolated perfused rat liver

We present experimental MRI protocols at 4.7 T for quantitative determination of the Dotarem distribution volume in isolated perfused rat liver. The procedures involved either constant contrast agent (CA) concentration or bolus administration conditions. R1 and R2* effects of the CA in liver and perfusate were measured using gradient echo fast imaging (GEFI) experiments by varying either the excitation angle or the echo time. CA concentrations in liver and perfusate were also measured after MRI by inductively coupled plasma atomic emission spectroscopy, in order to determine in situ relaxivities in the perfusate (r1=4.2 +/- 0.1 s(-1) mm(-1), r2*=17 +/- 2 s(-1) mm(-1)) and in the liver (r1=7.2 +/- 0.2 s(-1) mm(-1), r2*=99 +/- 5 s(-1) mm(-1)). When CA concentrations were estimated from R1 measurements and r1, the CA distribution volume estimations in liver resulting from bolus (0.31 +/- 0.01) and stationary (0.32 +/- 0.05) experiments were not significantly different. In contrast, after a bolus, CA concentrations derived from R2* and r2* were overestimated in liver and even more in perfusate. However, with R1 and R2* being measured before CA bolus administration, zero echo time signal intensities computed from multiple TE measurements during multiple boli yielded good estimations of R1 and thus correct CA concentrations in liver and in perfusate. Under these conditions, a single multi-echo GEFI acquisition should be sufficient to determine the concentration-time curves. Consequently, this protocol should be appropriate to rapidly estimate the distribution volume in vivo when multiple boli have to be avoided.