Levofloxacin versus ciprofloxacin, flucloxacillin, or vancomycin for treatment of experimental endocarditis due to methicillin-susceptible or -resistant Staphylococcus aureus.

Levofloxacin is the L isomer of ofloxacin, a racemic mixture in which the L stereochemical form carries the antimicrobial activity. Levofloxacin is more active than former quinolones against gram-positive bacteria, making it potentially useful against such pathogens. In this study, levofloxacin was compared to ciprofloxacin, flucloxacillin, and vancomycin for the treatment of experimental endocarditis due to two methicillin-susceptible Staphylococcus aureus (MSSA) and two methicillin-resistant S. aureus (MRSA) isolates. The four test organisms were susceptible to ciprofloxacin, the levofloxacin MICs for the organisms were low (0.12 to 0.25 mg/liter), and the organisms were killed in vitro by drug concentrations simulating both the peak and trough levels achieved in human serum (5 and 0.5 mg/liter, respectively) during levofloxacin therapy. Rats with aortic endocarditis were treated for 3 days. Antibiotics were injected with a programmable pump to simulate the kinetics of either levofloxacin (350 mg orally once a day), ciprofloxacin (750 mg orally twice a day), flucloxacillin (2 g intravenously four times a day), or vancomycin (1 g intravenously twice a day). Levofloxacin tended to be superior to ciprofloxacin in therapeutic experiments (P = 0.08). More importantly, levofloxacin did not select for resistance in the animals, in contrast to ciprofloxacin. The lower propensity of levofloxacin than ciprofloxacin to select for quinolone resistance was also clearly demonstrated in vitro. Finally, the effectiveness of this simulation of oral levofloxacin therapy was at least equivalent to that of standard treatment for MSSA or MRSA endocarditis with either flucloxacillin or vancomycin. This is noteworthy, because oral antibiotics are not expected to succeed in the treatment of severe staphylococcal infections. These good results obtained with animals suggest that levofloxacin might deserve consideration for further study in the treatment of infections due to ciprofloxacin-susceptible staphylococci in humans.

False phylogenies on wood mice due to cryptic cytochrome-b pseudogene.

The phylogeny and phylogeography of the Old World wood mice (subgenus Sylvaemus, genus Apodemus, Muridae) are well-documented. Nevertheless, the distributions of species, such as A. fulvipectus and A. ponticus remain dubious, as well as their phylogenetic relationships with A. sylvaticus. We analysed samples of Apodemus spp. across Europe using the mitochondrial cytochrome-b gene (cyt-b) and compared the DNA and amino-acid compositions of previously published sequences. The main result stemming from this study is the presence of a well-differentiated lineage of Sylvaemus including samples of various species (A. sylvaticus, A. fulvipectus, A. ponticus) from distant locations, which were revealed to be nuclear copies of the mitochondrial cyt-b. The presence of this cryptic pseudogene in published sequences is supported by different pathways. This has led to important errors in previous molecular trees and hence to partial misinterpretations in the phylogeny of Apodemus.

Peritoneal carcinomatosis due to ovarian cancer: comparison between MDCT, MRI and positron emission tomography-computed tomography with F18-fluorodeoxyglucose

Purpose: To compare MDCT, MRI and 18F-FDG PET/CT for the detection of peritoneal carcinomatosis due to ovarian cancerMethods and Materials: Fifteen women (mean age 65±) with clinical suspicion of ovarian cancer and peritoneal carcinomatosis underwent MDCT, MRI and 18F-FDG PET/CT, simultaneously and shortly performed before surgery (delay 8.1± days). According to the peritoneal cancer index nine abdominopelvic regions were defined. We applied four scores of lesion size on MDCT and MR images, while the maximal standard uptake value (SUVmax) was measured on 18F-FDG PET/CT. Three sites of lymphadenopathy and posterobasal pleural carcinomatosis were also analyzed. First, one radiologist blindly and separately read MDCT and MR images, while one nuclear physician blindly read PET/CT images grading each lesion according to four diagnostic certitudes. Secondly, all the images were reviewed jointly and compared with histopathology. Receiver operating characteristics (ROC) analysis was performed.Results: Peritoneal implants were proven in ten women (75%). Altogether, 228 abdominopelvic sites were compared. Sensitivity and specificity for MDCT was 90.2% and 90.6%, for MRI 93.5% and 86.3%, and for 18F-FDG PET/CT 92.7% and 95.7%, respectively. ROC area under the curve were 0.93 for MDCT and MRI, and 0.96 for 18F-FDG PET/CT respectively. No significant differences (p=0.11) were found between the three modalities.Conclusion: Although MRI revealed to be the most sensitive and 18F-FDG PET/CT the most specific modality, no significant differences were shown between the three techniques.

Hypertension portale et prise en charge de l'ascite [Management of ascites due to portal hypertension].

Portal hypertension is regularly encountered by the general practitioner. It is defined by an elevation of the porto-systemic pressure gradient, with complications such as ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, hypersplenism, hepatopulmonary syndrome or hepatic encephalopathy occuring when a significant elevation of this gradient is reached. Cirrhosis is the primary cause of portal hypertension in industrialized countries. Symptomatic portal hypertension carries a poor prognosis. Management should be initiated rapidly, including the identification and correction of any reversible underlying condition. Liver transplantation should be considered in advanced cases.

RP 59500 prophylaxis of experimental endocarditis due to erythromycin-susceptible and -resistant isogenic pairs of viridans group streptococci.

RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against a number of erythromycin-susceptible and -resistant gram-positive bacteria. The following experiments investigate the ability of RP 59500 to prevent experimental endocarditis due to either of two erythromycin-susceptible streptococcal isolates or their constitutively erythromycin-resistant Tn916 delta E transconjugants. RP 59500 had low MICs (0.125 to 0.5 mg/liter) for all four test organisms and was substantially bactericidal in vitro. Rats with catheter-induced aortic vegetations were given single-dose antibiotic prophylaxis 30 to 60 min before bacterial inoculation through a computerized pump system which permitted the simulation of drug kinetics for humans produced by either 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Single-dose RP 59500 prophylaxis successfully prevented endocarditis due to both the erythromycin-susceptible parent strains and their erythromycin-resistant derivatives in rats challenged with the minimal inoculum infecting 90% of controls. In addition, RP 59500 also prevented infection in animals challenged with fivefold-larger inocula of the erythromycin-susceptible parent strains. Vancomycin successfully prevented endocarditis due to any of the four test organisms. These results underline the in vivo efficacy of RP 59500 against both erythromycin-susceptible and -resistant streptococci. Such good results against the resistant strains would not be expected with erythromycin or clindamycin, which are the standard macrolidelincosamide-streptogramin antibiotics used for endocarditis prophylaxis in humans. An oral form of RP 59500 which might advantageously replace some of the older prophylactic regimens is currently being developed.

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study.

INTRODUCTION Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients' well-being, assessed by several validated measures. METHODS Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. RESULTS Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001. CONCLUSIONS Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.

Nasal trauma due to continuous positive airway pressure in neonates.

PATIENTS: All neonates admitted between January 2002 and December 2007 treated by nCPAP were eligible. METHODS: Patients' noses were monitored during nCPAP. Nasal trauma was reported into three stages: (I) persistent erythema; (II) superficial ulceration; and (III) necrosis. RESULTS: 989 neonates were enrolled. Mean gestational age was 34 weeks (SD 4), mean birth weight 2142 g (SD 840). Nasal trauma was reported in 420 (42.5%) patients and it was of stage I, II and III in 371 (88.3%), 46 (11%) and 3 (0.7%) patients, respectively. Incidence and severity of trauma were inversely correlated with gestational age and birth weight. The risk of nasal trauma was greater in neonates <32 weeks of gestational age (OR 2.48, 95% CI 1.59 to 3.86), weighing <1500 g at birth (OR 2.28, 95% CI 1.43 to 3.64), treated >5 days by nCPAP (OR 5.36, 95% CI 3.82 to 7.52), or staying >14 days in the NICU (OR 1.67, 95% CI 1.22 to 2.28). Most cases of nasal trauma (90%) appeared during the first 6 days of nCPAP. Persistent visible scars were present in two cases. CONCLUSIONS: Nasal trauma is a frequent complication of nCPAP, especially in preterm neonates, but long-term cosmetic sequelae are very rare. This study provides a description of nasal trauma and proposes a simple staging system. This could serve as a basis to develop strategies of prevention and treatment of this iatrogenic event.

The Öresund region: A dynamic region in Europe due to inter-regional collaboration?

El cluster Medicon Valley es troba a la regió d'Oresund binacional que s'estén per Dinamarca i Suècia, inclosa la Universitat de Lund, ciutat i tercera ciutat més gran de Suècia, Malmö (veure figura 1). El 2000, aquestes dues parts nacionals estaven connectades físicament per l'establiment dels 18 quilòmetres de longitud, enllaç fix del Øresund (ponts i túnels).

Effect of statin therapy in the outcome of bloodstream infections due to Staphylococcus aureus: a prospective cohort study.

INTRODUCTION Statins have pleiotropic effects that could influence the prevention and outcome of some infectious diseases. There is no information about their specific effect on Staphylococcus aureus bacteremia (SAB). METHODS A prospective cohort study including all SAB diagnosed in patients aged ≥18 years admitted to a 950-bed tertiary hospital from March 2008 to January 2011 was performed. The main outcome variable was 14-day mortality, and the secondary outcome variables were 30-day mortality, persistent bacteremia (PB) and presence of severe sepsis or septic shock at diagnosis of SAB. The effect of statin therapy at the onset of SAB was studied by multivariate logistic regression and Cox regression analysis, including a propensity score for statin therapy. RESULTS We included 160 episodes. Thirty-three patients (21.3%) were receiving statins at the onset of SAB. 14-day mortality was 21.3%. After adjustment for age, Charlson index, Pitt score, adequate management, and high risk source, statin therapy had a protective effect on 14-day mortality (adjusted OR = 0.08; 95% CI: 0.01-0.66; p = 0.02), and PB (OR = 0.89; 95% CI: 0.27-1.00; p = 0.05) although the effect was not significant on 30-day mortality (OR = 0.35; 95% CI: 0.10-1.23; p = 0.10) or presentation with severe sepsis or septic shock (adjusted OR = 0.89; CI 95%: 0.27-2.94; p = 0.8). An effect on 30-day mortality could neither be demonstrated on Cox analysis (adjusted HR = 0.5; 95% CI: 0.19-1.29; p = 0.15). CONCLUSIONS Statin treatment in patients with SAB was associated with lower early mortality and PB. Randomized studies are necessary to identify the role of statins in the treatment of patients with SAB.

Impact of the MIC of piperacillin-tazobactam on the outcome of patients with bacteremia due to extended-spectrum-β-lactamase-producing Escherichia coli.

We investigated the impact of the piperacillin-tazobactam MIC in the outcome of 39 bloodstream infections due to extended-spectrum-β-lactamase-producing Escherichia coli. All 11 patients with urinary tract infections survived, irrespective of the MIC. For other sources, 30-day mortality was lower for isolates with a MIC of ≤ 2 mg/liter than for isolates with a higher MIC (0% versus 41.1%; P = 0.02).

Effective stiffening of DNA due to nematic ordering causes DNA molecules packed in phage capsids to preferentially form torus knots.

Observation that DNA molecules in bacteriophage capsids preferentially form torus type of knots provided a sensitive gauge to evaluate various models of DNA arrangement in phage heads. Only models resulting in a preponderance of torus knots could be considered as close to reality. Recent studies revealed that experimentally observed enrichment of torus knots can be qualitatively reproduced in numerical simulations that include a potential inducing nematic arrangement of tightly packed DNA molecules within phage capsids. Here, we investigate what aspects of the nematic arrangement are crucial for inducing formation of torus knots. Our results indicate that the effective stiffening of DNA by the nematic arrangement not only promotes knotting in general but is also the decisive factor in promoting formation of DNA torus knots in phage capsids.

Dental Phenotype in Jalili Syndrome Due to a c.1312 dupC Homozygous Mutation in the CNNM4 Gene.

Jalili syndrome denotes a recessively inherited combination of an eye disease (cone-rod dystrophy) and a dental disorder (amelogenesis imperfecta), which is caused by mutations in the CNNM4 gene. Whereas the ophthalmic consequences of these mutations have been studied comprehensively, the dental phenotype has obtained less attention. A defective transport of magnesium ions by the photoreceptors of the retina is assumed to account for the progressive visual impairment. Since magnesium is also incorporated in the mineral of dental hard tissues, we hypothesized that magnesium concentrations in defective enamel resulting from mutations in CNNM4 would be abnormal, if a similar deficiency of magnesium transport also accounted for the amelogenesis imperfecta. Thus, a detailed analysis of the dental hard tissues was performed in two boys of Kosovan origin affected by Jalili syndrome. Retinal dystrophy of the patients was diagnosed by a comprehensive eye examination and full-field electroretinography. A mutational analysis revealed a c.1312 dupC homozygous mutation in CNNM4, a genetic defect which had already been identified in other Kosovan families and putatively results in loss-of-function of the protein. The evaluation of six primary teeth using light and scanning electron microscopy as well as energy-dispersive X-ray spectroscopy showed that dental enamel was thin and deficient in mineral, suggesting a hypoplastic/hypomineralized type of amelogenesis imperfecta. The reduced mineral density of enamel was accompanied by decreased amounts of calcium, but significantly elevated levels of magnesium. In dentin, however, a similar mineral deficiency was associated with reduced magnesium and normal calcium levels. It is concluded that the c.1312 dupC mutation of CNNM4 results in mineralization defects of both enamel and dentin, which are associated with significantly abnormal magnesium concentrations. Thus, we could not disprove the hypothesis that a disrupted magnesium transport is involved in the development of the dental abnormalities observed in Jalili syndrome.

Painful total hip replacement due to sciatic nerve entrapment in scar tissue and lipoma.

Painful total hip replacement remains a challenging problem because of the large amount of possible diagnoses. We report about a 64-year-old female patient who was misdiagnosed during 4 years as psychiatric. She suffered of excruciating left retrotrochanteric pain after the implantation of a cementless total hip replacement and revision because of recurrent hip dislocations. Walking was limited to short distances using two crutches. The work-up at this time included the usual diagnoses and remained unsuccessful. No loosening, infection or malposition of the prosthesis could be found, and she had no neurologic deficits in her operated leg. An MRI was obtained to visualize the retrotrochanteric soft tissues and showed a tight scar surrounding the sciatic nerve, which was also compressed by an adjacent lipoma. Therefore, she was reoperated on to remove the lipoma and the scar tissue around the sciatic nerve. To decrease the risk of recurrent scarring around the sciatic nerve, an adhesion barrier was applied before closure. One year after the operation, the patient has no neurologic deficit, no more pain and is able to walk unlimited distances without crutches. Scar tissue around the sciatic nerve is frequently observed during revision surgery. However, we feel that sciatic nerve entrapment by scar tissue should be a part of the differential diagnosis of painful THR. MRI may be a useful tool to achieve this diagnosis.

Safety and efficacy in gamma knife radiosurgery for trigeminal neuralgia due to megadolichbasilar artery compression: a prospective series of 29 consecutive patients

Purpose: To analyse prospectively the long-term results of Gamma Knife surgery (GKS) in patients with trigeminal neuralgia secondary to megadolichobasilar artery (MBA). Methods: Between December 1992 and November 2010, 33 consecutive patients presenting with ITN secondary to MBA were operated by GKS and followed prospectively in Timone University Hospital. The follow up is at least of 1 year in 29 patients. The median age was 74.90 years (range 51 to 90). The GKS typically was performed using MR and CT imaging guidance and a single 4 mm isocenter. The median of the prescription dose (at the 100%) was 90 Gy (range 80 to 90). The target was placed on the cisternal portion of the Vth nerve. Clinical and dosimetric parameters were analyzed. GKS was the first surgical procedure in 23 patients (79.31%). Results: The median follow- up period was 46.12 months (range 12.95 to 157.93). All the 29 patients (100%) were initially pain free in a median time of 13.5 days (range 0 to 240). The probability of remaining pain free at 0.5, 1, 2 years was 93.1%, 79.3% and 75.7% respectively, reaching at this time the flat part of the curve. Seven patients (24.13%) experienced a recurrence with a median delay of 10.75 months (range 3.77 to 12.62). The actuarial rate of recurrence was not higher than in our population with essential TN although atypical pain was associated with a much higher risk of recurrence (HR= 6.92, p= 0.0117). The hypoesthesia actuarial rates at 0.5 years was 4.3% and at 1 year reach 13% and remains stable till 12 years with a median delay of onset of 7 (5, 12) months. Female patients had a statistically much lower probability of developing a facial numbness (p of 0.03). No patient reported a bothersome hypoesthesia. Conclusion: Retrogaserian, high dose GKS, turned out to be very safe with only 13.04% hypoesthesia, which was never disabling (0%), while achieving high quality pain control. The majority of the patients demonstrated a prolonged effect of radiosurgery in absence of any trigeminal nerve disturbance.