Evaluation of Reduced Susceptibility to Quaternary Ammonium Compounds and Bisbiguanides in Clinical Isolates and Laboratory-Generated Mutants of Staphylococcus aureus

The MICs and minimum bactericidal concentrations (MBCs) for the biocides benzalkonium chloride and chlorhexidine were determined against 1,602 clinical isolates of Staphylococcus aureus. Both compounds showed unimodal MIC and MBC distributions (2 and 4 or 8 mg/liter, respectively) with no apparent subpopulation with reduced susceptibility. To investigate further, all isolates were screened for qac genes, and 39 of these also had the promoter region of the NorA multidrug-resistant (MDR) efflux pump sequenced. The presence of qacA, qacB, qacC, and qacG genes increased the mode MIC, but not MBC, to benzalkonium chloride, while only qacA and qacB increased the chlorhexidine mode MIC. Isolates with a wild-type norA promoter or mutations in the norA promoter had similar biocide MIC distributions; notably, not all clinical isolates with norA mutations were resistant to fluoroquinolones. In vitro efflux mutants could be readily selected with ethidium bromide and acriflavine. Multiple passages were necessary to select mutants with biocides, but these mutants showed phenotypes comparable to those of mutants selected by dyes. All mutants showed changes in the promoter region of norA, but these were distinct from this region of the clinical isolates. Still, none of the in vitro mutants displayed fitness defects in a killing assay in Galleria mellonella larvae. In conclusion, our data provide an in-depth comparative overview on efflux in S. aureus mutants and clinical isolates, showing also that plasmid-encoded efflux pumps did not affect bactericidal activity of biocides. In addition, current in vitro tests appear not to be suitable for predicting levels of resistance that are clinically relevant.     

Acupotomy versus sodium hyaluronate for treatment of knee osteoarthritis in rabbits

Objective

To investigate the possible advantages of acupotomy over sodium hyaluronate injection for the treatment of knee osteoarthritis (KOA).

Role of non-polio enterovirus infection in pediatric hemolytic uremic syndrome

Verocytotoxin-producing Escherichia coli(VTEC) infections cause most cases of hemolytic uremic syndrome (HUS); 10-30% of patients, however, are negative for VTEC infection. The etiology of HUS in VTEC-negative cases remains poorly understood. Before the association between VTEC infection and HUS was recognized, sporadic cases of HUS with enterovirus infection were reported in the literature. Since May 1988, most cases of HUS in Italy have been reported to the Italian surveillance system, and in 73% of these, evidence of VTEC infection was demonstrated. The aim of this study was to determine whether the frequency of enteroviral infections was different in the acute phase of VTEC-positive and VTEC-negative HUS. Eighty-nine patients were investigated for enteroviral infection, of whom 58 were VTEC positive and 31 VTEC negative. Two serum samples from each patient were examined for seroconversion to enterovirus (coxsackie, echovirus, and picornavirus) by a complement fixation test. Serological evidence of acute infection with non-polio enterovirus was found in 33 patients (37%) [20/58 (34.5%) VTEC positive and 13/31 (41.9%) VTEC negative]. There was no statistically significant difference between the two groups. These results demonstrate that there are no significant differences for enteroviral infection in VTEC-positive and VTEC-negative patients and, therefore, enteroviral infections should not be considered a cause of HUS in VTEC-negative children.     

Biomechanical consideration regarding bone substitutes use in surgical treatment of chronic osteomyelitis

The main aim of this study is to present the use of bone substitutes in chronic ostheomielitis surgical treatment and its biomechanical influence. MATERIAL AND METHODS: First step is three-dimensional reconstruction to one femur using CT sections; the second is the reconstruction of infected bone volume, synthesis of material properties, synthesis of loading forces, synthesis of boundary condition and, finally, finite element analysis. RESULTS: The calculated Von Mises stress as a result of finite element analysis indicates that bone substitute implantation lead to a stress distribution in bone similar with a health femur.     

Fiber type-related changes in rat skeletal muscle calcium homeostasis during aging and restoration by growth hormone

The mechanisms by which aging induces muscle impairment are not well understood yet. We studied the impact of aging on Ca2+ homeostasis in the slow-twitch soleus and the fast-twitch extensor digitorum longus (EDL) muscles of aged rats by using the fura-2 fluorescent probe. In both muscles aging increases the resting cytosolic calcium concentration ([Ca2+]i). This effect was independent on calcium influx since a reduced resting permeability of sarcolemma to divalent cations was observed in aged muscles likely due to a reduced activity of leak channels. Importantly the effects of aging on resting [Ca2+]i, fiber diameter, mechanical threshold and sarcolemmal resting conductances were less pronounced in the soleus muscle, suggesting that muscle impairment may be less dependent on [Ca2+]i in the slow-twitch muscle. The treatment of aged rats with growth hormone restored the resting [Ca2+]i toward adult values in both muscles. Thus, an increase of resting [Ca2+]i may contribute to muscle weakness associated with aging and may be considered for developing new therapeutic strategies in the elderly.     

Increased levels of the CD40:CD40 ligand dyad in the cerebrospinal fluid of rats with vitamin B12(cobalamin)-deficient central neuropathy

The levels of the soluble (s) CD40:sCD40 ligand (L) dyad, which belongs to the tumor necrosis factor (TNF)-alpha:TNF-alpha-receptor superfamily, are significantly increased in the cerebrospinal fluid (CSF), but not the serum of cobalamin (Cbl)-deficient (Cbl-D) rats. They were normalized or significantly reduced after treatment with Cbl, transforming growth factor-beta1 or S-adenosyl-L-methionine, and the normal myelin ultrastructure of the spinal cord was concomitantly restored. The concomitance of the two beneficial effects of these treatments strongly suggests that the increases in CSF sCD40:sCD40L levels may participate in the pathogenesis of purely myelinolytic Cbl-D central neuropathy in the rat. In keeping with this, an anti-CD40 treatment prevented myelin lesions.     

Reoperation after selective amygdalohippocampectomy: an MRI analysis of the extent of temporomesial resection in ten cases

Background  

Selective amygdalohippocampectomy (SAHE) yields 60–80% of patients with medically refractory mesial temporal lobe epilepsy seizure-free and seems to be equally effective compared to the more extended temporal lobe resections. The resection of the entire entorhinal cortex (EC) is of crucial importance to warrant complete seizure control for those patients. Thus, evidence of residual EC could be a predictor of a potentially successful reoperation in patients with recurrent seizures after SAHE. We performed an analysis of preoperative and postoperative magnetic resonance imaging (MRI) in patients who underwent a reoperation after an unsuccessful transsylvian SAHE to assess the presence of residual EC before reoperation and to determine whether certain anatomical variants may dispose patients to incomplete resection of EC.     

Pregnancy under everolimus-based immunosuppression

The ability to give birth to a live child is one of the best success of kidney transplantation. While there are an increasing number of pregnancies reported in kidney transplant recipients treated with cyclosporine or tacrolimus, there is little evidence of pregnancy among kidney transplant recipients exposed to sirolimus or everolimus. We present the first successful delivery in an organ transplant recipient exposed to everolimus during the whole gestation. The absence of congenital anomalies in the child as well as the recipient's successful renal outcome are promising, although pregnancy in renal transplant recipients exposed to everolimus should be considered at higher risk.