Bactericidal activities of LB20304, a new fluoroquinolone

The time-kill curves of LB20304, a novel fluoroquinolone that has potent antibacterial activity against gram-positve and gram-negative bacteria, were calculated at the concentration of 1/4-, 1/2-, 1-, 2- and 4-times the MIC againstStaphylococcus aureus 77, Escherichia coli, 3739E,Pseudomonas aeruginosa 1912E. The bactericidal activity of LB20304 for these strains was very rapid and comparable to that of ciprofloxacin. LB20304 produced a decrease in the log₁₀ CFU per milliliter of ≥3 within 2 h at 4-times the MIC for all strains and consitently prevented regrowth of bacteria after 24 h of incubation. The MBCs (Minimal Bactericidal Concentration) of LB20304 against test organisms were equal to or at most four-times higher than the MICs.     

Revisiting anaplastic astrocytomas I: An expansive growth pattern is associated with a better prognosis

Purpose

To study whether anaplastic astrocytomas that are nonenhancing and/or well‐circumscribed (expansive) are associated with a better prognosis.

Materials and Methods

We retrospectively identified 59 patients with pathologically confirmed World Health Organizaiton (WHO) grade III anaplastic astrocytoma who underwent craniotomy at our institution from 1995 through 2006. We assessed prognostic variables including age, enhancement (EAA—34 patients) vs. nonenhancement (NEAA—25 patients), MR growth patterns (expansive [28 patients] vs. mixed/infiltrative [31 patients]), recursive partitioning analysis (RPA) class, resection extent, and addition of chemotherapy. Primary outcome measure was survival.

Results

Kaplan‐Meier curves showed improved survival in NEAA, expansive tumors, and RPA 1 class patients. Within RPA class I patients, expansive growth pattern remained a significant advantage in survival time. Examining extent of resection also showed that patients with gross total resections (GTR) had a better prognosis. A multivariate (Cox proportional hazards) analysis showed that patient age and expansive tumor phenotype affected outcome, whereas RPA class, enhancement, and GTR did not.

Conclusion

Circumscribed growth in histologically proven anaplastic astrocytoma, which has not been emphasized in past studies, has a considerable survival advantage. J. Magn. Reson. Imaging 2008;28:1311–1321. © 2008 Wiley‐Liss, Inc.     

A New Lead for Transvenous Atrial Pacing and Sensing Clinical and Electrophysiological Experiences

The Medtronic 6961 lead has been used in 14 patients for transvenous atrial sensing and/or pacing. This lead is furnished with small tines of silicone rubber at the distal end. The conductor coil material is space wound for flexibility. Thus, the lead lacks intrinsic elasticity and can be fastened within the right atrial appendage without a preformed J-shape. The clinical experiences with the lead are encouraging. The lead is easier to introduce and position in the right atrial appendage than the previously used tined J-shaped leads (Medtronic 6991). The small size of the new lead makes the choice of vein less critical and a normally-sized external jugular or cephalic vein permits the use of the same vessel for a second ventricular lead. By means of a lead extension wire, consecutive determinations of the P-wave amplitude, stimulation threshold of the right atrium, electrode resistance, and P/QRS-ratio were made for four weeks following electrode insertion. The mean P-wave amplitude at insertion was 4.9 +/- 1.5 mV (mean +/- SD). There was a significant decrease to a lowest mean level of 309 +/- 1.1 mV after one week. From that time there were only small variations. In the supine position and with normal breathing there was a spontaneous variation of the P-wave amplitude of +/- 12%. The P-wave amplitude was influenced by body position and maximal breathing movements to a minor extent. The threshold of stimulation was 0.9 +/- 0.4 V after one week. Later there was a small decrease in the threshold which, however, still remained significantly higher than at the time of insertion. The total resistance of the electrode system was about 700 ohms and P/QRS-ratio about 4 +/- 3. During an observation time ranging from 4 to 11 months there were no electrode dislocations. The electrodes were connected to the intended pacemakers without complications. In conclusion, the transvenous endocardial atrial lead, Medtronic 6961, shows attractive and promising qualities. The electrophysiological data recorded are suitable for the pacemakers in use. The electrode definitely deserves further evaluation.     

Anti-IL17 therapies for psoriasis

Introduction: Interleukin-17 (IL-17) is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of plaque psoriasis. As a result, focus in clinical trials has undergone a shift towards disease specific targets, with the goals of more effective treatment and reduction in the incidence of serious adverse events.

Areas covered: Two monoclonal antibodies targeting IL-17A (secukinumab, ixekizumab) and one against the IL-17 receptor (brodalumab) are approved for the treatment of moderate-to-severe plaque psoriasis. Herein, the clinical efficacy, safety and tolerability of each is reviewed by summarizing the existing literature (found via PubMed database).

Expert commentary: The development and approval of the IL-17 inhibitor agents secukinumab, ixekizumab, and brodalumab has expanded psoriatic treatment with effective options, validating the importance of the pro-inflammatory role of IL-17 psoriatic pathophysiology. Biologic treatment options for psoriasis will continue to grow, especially IL-17 and IL-23 related agents, with an increasing specificity of agents to be available in the future.     

The lung-to-head ratio and fetoscopic temporary tracheal occlusion: prediction of survival in severe left congenital diaphragmatic hernia.

OBJECTIVES: To evaluate the reliability of sonographic lung-to-head ratio (LHR) measurement as a predictor of survival in fetuses with congenital diaphragmatic hernia (CDH) and to compare the probability of survival in those with temporary tracheal occlusion (TO) or standard care with respect to the LHR. METHODS: Fifty-six fetuses with left CDH with liver herniated into the thorax at complete prenatal evaluation were included in logistic regression analyses of antenatal predictors of survival to hospital discharge. Sixteen subjects underwent TO and 40 received standard care. RESULTS: LHR was a significant predictor of survival, with probability of survival increasing with increasing LHR (odds ratio (OR) 8.5, P = 0.04). When subjects with anomalies were excluded, the LHR effect was similar after adjustment for TO (OR 7.1, P = 0.11). Linear spline models suggested a plateau in survival at an LHR of 1.0 and all models suggested increased odds of survival with TO. Minimum LHR measurements had a high degree of inter- and intraobserver agreement (intraclass correlation coefficients of 0.70 and 0.80, respectively). CONCLUSIONS: Calculation of the LHR in fetuses with CDH is a reliable and powerful predictor of survival to hospital discharge, although improving odds of survival may plateau at an LHR of 1.0. TO may have an independent benefit on survival to hospital discharge.     

Beyond appendicitis; radiologic review of unusual and rare pathology of the appendix

Appendicitis is a very common cause of acute abdominal pathology, however, many other pathologic conditions of the appendix can be diagnosed utilizing CT. Examples of these conditions include primary appendiceal neoplasms, secondary inflammation of the appendix, stump appendicitis, endometriosis, appendicitis within a hernia, appendiceal diverticulosis and intussusception and intraluminal foreign bodies. The purpose of this article is to review appendiceal pathology outside of acute appendicitis, describe corresponding imaging findings on CT, and to illustrate various CT findings of appendiceal disease with representative cases.     

Development and implementation of a piperacillin-tazobactam extended infusion guideline

Administration of β-lactam antibiotics by extended infusion optimizes the pharmacodynamic properties and bactericidal activity of these agents resulting in a potential improvement in patient outcomes and reduction in drug expenditure. Consequently, a pharmacist-led piperacillin-tazobactam extended 4-hour infusion guideline was implemented hospital-wide at a 500-bed academic medical center. Each piperacillin-tazobactam infusion was prospectively monitored for 5 weeks to ensure accurate administration and identify barriers to guideline adherence. Overall, a total of 103 patients received 1215 doses of piperacillin-tazobactam by extended infusions. In all, 98% of the doses were administered at the correct extended infusion rate and 94% of the doses were given at the scheduled time. There were a total of 20 missed doses and 53 delayed doses, accounting for 2% and 4% of the total administered doses, respectively. The primary barrier to adherence was the patient not being on the unit at the time of the scheduled dose followed by the piperacillin-tazobactam dose not being available on the floor. While insufficient power prevented meaningful evaluation of clinical outcomes, we anticipate a conservative annual estimated cost savings of $108,529. Key elements contributing to our success included consistent pharmacy leadership, multidisciplinary involvement, thorough inservicing to health care professionals, hospital-wide implementation, and extensive quality assurance monitoring.     

Fusion of nearby inverted repeats by a replication-based mechanism leads to formation of dicentric and acentric chromosomes that cause genome instability in budding yeast

Large-scale changes (gross chromosomal rearrangements [GCRs]) are common in genomes, and are often associated with pathological disorders. We report here that a specific pair of nearby inverted repeats in budding yeast fuse to form a dicentric chromosome intermediate, which then rearranges to form a translocation and other GCRs. We next show that fusion of nearby inverted repeats is general; we found that many nearby inverted repeats that are present in the yeast genome also fuse, as does a pair of synthetically constructed inverted repeats. Fusion occurs between inverted repeats that are separated by several kilobases of DNA and share >20 base pairs of homology. Finally, we show that fusion of inverted repeats, surprisingly, does not require genes involved in double-strand break (DSB) repair or genes involved in other repeat recombination events. We therefore propose that fusion may occur by a DSB-independent, DNA replication-based mechanism (which we term “faulty template switching”). Fusion of nearby inverted repeats to form dicentrics may be a major cause of instability in yeast and in other organisms.     

Methylation status of the MGMT gene promoter fails to predict the clinical outcome of glioblastoma patients treated with ACNU plus cisplatin

We analyzed the methylation status of the O6‐methylguanine‐DNA methyltransferase (MGMT) promoter using a methylation‐specific polymerase chain reaction (MSP) in glioblastoma patients treated with 1‐(4‐amino‐2‐methyl‐5‐pyrimidinyl)methyl‐3‐(2‐chloroethyl)‐3‐nitrosourea (ACNU) plus cisplatin followed by radiation therapy. Forty‐eight patients with interpretable MSP results were included in this study. The MGMT promoter was methylated in 26 patients (54.2%, methylated group) and unmethylated in 22 patients (45.8%, unmethylated group). Comparison of clinical outcomes between the two groups revealed that the methylation status of the MGMT gene promoter was not a prognostic factor for overall survival (P = 0.516) or a predictive factor for radiological response to ACNU plus cisplatin treatment (P = 0.529). The most noteworthy explanation for the result is that the synergistic antitumor effects of ACNU and cisplatin resulting from inactivation of MGMT by cisplatin in MGMT active tumors offset the drug resistance.