Efficacy of cefcanel on staphylocci

The minimum inhibitory concentration (MIC) of cefcanel, a new oral cephalosporin, has been tested against 153 staphylococci subdivided into the species Staphylococcus aureus. S. epidermidis sensu lato and S. saprophyticus, with and without beta-lactamase production. The concentration inhibiting 50% of the strains was 0.5 mg/l for all three species while the corresponding values for 90% of the strains were 1, 2 and 1 mg/l, respectively. These values apply to all the strains. The MICs of the non-beta-lactamase-producing strains were identical to the MICs of the beta-lactamase-producing strains for S. aureus, three twofold steps lower for S. epidermidis and one step higher for S. saprophyticus. Consequently, beta-lactamase production had no consistent consequences for the activity of cefcanel against S. aureus and S. saprophyticus. In contrast, the beta-lactamase production of S. epidermidis did influence the activity of cefcanel. Among the tested cephalosporins, cefcanel had the highest antistaphylococcal activity, and no strain was resistant to this new cephalosporin.     

BJ-48, a novel thrombin-like enzyme from the Bothrops jararacussu venom with high selectivity for Arg over Lys in P1: Role of N-glycosylation in thermostability and active site accessibility.

BJ-48, a serine protease from the venom of Bothrops jararacussu, was purified to homogeneity using affinity chromatography on p-aminobenzamidine-agarose followed by HPLC gel filtration. BJ-48 presented 52kDa by SDS-PAGE analysis and 48,036Da by electron spray mass spectrometry. The enzyme was shown to be highly glycosylated with 42% of N-linked carbohydrates composed of Fuc(1):GalN(4):GlcN(5):Gal(1):Man(2) and a high content of sialic acid residues (8-12%). BJ-48 had optimal esterase activity at pH 7.5 and displayed maximum catalytic rate at 50 degrees C. Its hydrolytic activity was strongly inhibited by aprotinin and dithiothreitol while N-tosyl-l-phenylalanine chloromethyl ketone, 6-aminocaproic acid, E-64 and soybean trypsin inhibitor (SBTI) were ineffective. The kinetics of BJ-48 with chromogenic substrates revealed an unprecedented selectivity (10(4)-fold) for Arg over Lys in P1. BJ-48 proved to be a thrombin-like enzyme (TLE) with a specific fibrinogen-clotting activity of 73.4NIH units/mg. The TLE rapidly digested human fibrinogen Bbeta chain, but the Aalpha chain was cleaved specifically to release fibrinopeptide A with k(cat)/K(m)=2.1muM(-1)s(-1). The TLE showed no activity toward other thrombin substrates like protein C, protease-activated receptor-1 or inhibitors such as hirudin and antithrombin. A non-denaturing procedure using PNGase F and neuraminidase followed by hydrophobic interaction chromatography was employed to obtain active BJ-48 forms with variable carbohydrate content. Compared to the native enzyme, total or partially deglycosylated BJ-48 forms presented up to 2-fold reduction in their specific activities upon heating at 55/65 degrees C or treatment with SBTI. These results point out a role for BJ-48 glycosylation in thermostability and controlling the access of some canonical protein inhibitors to the active site.     

Clinicopathologic correlation of pigmented epiretinal membranes

We performed clinicopathologic correlation on ten surgically removed pigmented epiretinal membranes causing macular pucker. All cases occurred in eyes with existing retinal holes or tears, including eight cases of macular pucker after previous retinal detachment. These cases probably represented a limited form of proliferative vitreoretinopathy. All membranes contained pigment epithelial cells with polarity, basement membrane, and melanosomes. Cytoplasmic melanin granules accounted for the clinical feature of pigmentation in these eyes.     

Synaptic Plasticity in an In Vitro Slice Preparation of the Rat Nucleus Accumbens

Extra- and intracellular recordings in slices were used to examine what types of synaptic plasticity can be found in the core of the nucleus accumbens, and how these forms of plasticity may be modulated by dopamine. Stimulus electrodes were placed at the rostral border of the nucleus accumbens in order to excite primarily infralimbic and prelimbic afferents, as was confirmed by injections of the retrograde tracer fluoro-gold. In extracellular recordings, tetanization induced long-term potentiation (LTP) of the population spike in 20 out of 53 slices. The presynaptic compound action potential did not change following LTP induction. For the intracellularly recorded excitatory postsynaptic potential, three types of synaptic plasticity were noted: long-term potentiation (16 out of 54 cells), decremental potentiation (eight cells) and long-term depression (LTD; six cells). No correlation was found between the occurrence of potentiation or depression and various parameters of the tetanic depolarization (e.g. peak voltage, integral under the curve). The N -methyl- d -aspartate receptor antagonist d (–)-2-amino-5-phosphonopentanoic acid (50 μM; d -AP5) reduced, but did not completely prevent, the induction of LTP. The incidence of LTD was not markedly affected by d -AP5. No difference in LTP was found when comparing slices bathed in dopamine (10 μM) and controls. Likewise, slices treated with a mixture of the D1 receptor antagonist Sch 23390 (1 μM) and the D2 antagonist S (–)-sulpiride (1 μM) generated a similar amount of LTP as controls. In conclusion, both LTP and LTD can be induced in a key structure of the limbic-innervated basal ganglia. LTP in the nucleus accumbens strongly depends on N -methyl- d -aspartate receptor activity, but is not significantly affected by dopamine.     

The Use of Performance Improvement Methods to Enhance Emergency Department Patient Satisfaction in the United States: A Critical Review of the Literature and Suggestions for Future Research

Objectives: The authors reviewed the evidence on performance improvement methods for increasing emergency department (ED) patient satisfaction to provide evidence-based suggestions for clinical practice.
Methods: Data sources consisted of searches through MEDLINE, CINAHL, PSYCHINFO, Cochrane Library, and Emergency Medicine Abstracts and a manual search of references. Articles were included if they reported a performance improvement intervention targeting patient satisfaction in the ED setting. Articles on studies not conducted in the United States or that failed to provide enough details to allow critical evaluation of the study were excluded. Two authors used structured evaluation criteria to independently review each retained study.
Results: Nineteen articles met all selection criteria. Three studies found varying levels of support for multicomponent interventions, predominantly focused on implementation of clinical practice guidelines for specific presenting complaints and process redesign. Sixteen studies evaluated single-component interventions, with the following having at least one supportive study: using alternating patient assignment to provider teams rather than "zone"-based assignment, enhancing provider communication and customer service skills, incorporating information delivery interventions (e.g., pamphlets, video) that target patient expectations, using preformatted charts, and establishing ED-based observation units for specific conditions such as asthma and chest pain.
Conclusions: There is modest evidence supporting a range of performance improvement interventions for improving ED patient satisfaction. Further work is needed before specific, evidence-based recommendations can be made regarding which process changes are most effective. Recommendations are made for improving the quality of performance improvement efforts in the ED setting.     

Immature circulating lymphocytes in severely malnourished Guatemalan children

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes) was determined in 33 severely malnourished Guatemalan children, and in two groups of clinically well but mildly growth retarded children from the same environment. Mean E-rosettes in the acutely ill patients was lower than the value observed in the mildly malnourished children, although there was considerable overlap between groups. These data differ from previously published studies of severely malnourished children from other parts of the world in that not all patients had decreased values for E-rosettes, in contrast to the uniform depression reported by others. As all patients were clinically similar, the results suggest that there may be specific nutrient defects associated with protein-energy malnutrition that particularly affect immune function. In addition, in vitro incubation of lymphocytes from the acutely malnourished children with the thymic factor, thymosin fraction 5, increased the percentage of E-rosettes in a dose-dependent fashion. These data suggest that immature, thymosin-responsive T cells are present in circulation. It is possible that in vivo thymosin administration may be beneficial for malnourished individuals.