New antibiotics for infections caused by resistant organisms

A continued increase in the expression of resistance among bacterial pathogens has prompted the development of a variety of new compounds directed against resistant strains of bacteria. Recently, the most dramatic increase in resistance has been among gram-positive organisms, and the predominant areas of development have been within a few classes of agents. Expanded spectrum fluoroquinolones offer advantages against many resistant gram-positive organisms, including S. pneumoniae and S. aureus. Newly developed classes of antimicrobials offer some unique activity against resistant staphylococci and enterococci. The first classes approved for use in the US are the streptogramins, specifically quinupristin/dalfopristin (Synercid), and the oxazolidinone linezolid (Zyvox). Other new classes of agents, including the ketolides, everninomycins, and newer glycopeptides, such as LY-333328, are in the early stages of development.     

Analysis of mitotic microtubule-associated proteins using mass spectrometry identifies astrin, a spindle-associated protein

We purified microtubules from a mammalian mitotic extract and obtained an amino acid sequence from each microtubule-associated protein by using mass spectrometry. Most of these proteins are known spindle-associated components with essential functional roles in spindle organization. We generated antibodies against a protein identified in this collection and refer to it as astrin because of its association with astral microtubule arrays assembled in vitro. Astrin is approximately 134 kDa, and except for a large predicted coiled-coil domain in its C-terminal region it lacks any known functional motifs. Astrin associates with spindle microtubules as early as prophase where it concentrates at spindle poles. It localizes throughout the spindle in metaphase and anaphase and associates with midzone microtubules in anaphase and telophase. Astrin also localizes to kinetochores but only on those chromosomes that have congressed. Deletion analysis indicates that astrin's primary spindle-targeting domain is at the C terminus, although a secondary domain in the N terminus can target some of the protein to spindle poles. Thus, we have generated a comprehensive list of major mitotic microtubule-associated proteins, among which is astrin, a nonmotor spindle protein.     

Atrial Fibrillation: A Risk Factor for Increased Mortality – An AVID Registry Analysis

Emerging evidence suggests that atrial fibrillation is not a benign arrhythmia. It is associated with increased risk of death. The magnitude of association is controversial and potential causes remain unknown. Patients in the registry of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial form the basis for this report. Baseline variables, in particular the presence or absence of a history of atrial fibrillation/flutter, were examined in relation to survival. Multivariate Cox regression was used to adjust for differences in important baseline co-variables using 27 pre-selected variables. There were 3762 subjects who were followed for an average of 773±420 days; 1459 (39%) qualified with ventricular fibrillation and 2303 (61%) with ventricular tachycardia. A history of atrial fibrillation/flutter was present in 24.4 percent. There were many differences in baseline variables between those with and those without a history of atrial fibrillation/flutter. After adjustment for baseline differences, a history of atrial fibrillation/flutter remained a significant independent predictor of mortality, (relative risk=1.20; 95% confidence intervals=1.03–1.40; p=0.020). Antiarrhythmic drug use, other than amiodarone or sotalol, was also a significant independent predictor of mortality (relative risk 1.34; 95% confidence intervals 1.07–1.69, p=0.011. Atrial fibrillation/flutter is a significant independent risk factor for increased mortality in patients presenting with ventricular tachyarrhythmias. This risk may have been overestimated in previous studies that could not adjust for the proarrhythmic effects of antiarrhythmic drugs other than amiodarone or sotalol.     

Demand–control–support among female and male managers in eight Swedish companies

This work is part of the Swedish project ‘Managers and Stress’. In the report the Swedish version of the Demand–Decision Latitude model was used, which made it possible to compare data with an earlier population study. A total of 179 male and 56 female managers were included. The demands and decision latitude scores were significantly higher than in the population study. Social support buffers high demands but surprisingly the managers did not report higher support than the participants in the population. Psychological demands and skill discretion differed significantly between companies. The hypotheses that psychological demands and decision latitude differ between female and male managers had to be rejected. The period of extensive changes which has taken place in working‐life, especially in the government sector, probably influenced the results. The results did not indicate higher stress in those managers working in the companies that were the most extensive ‘downsizers’. Copyright © 2001 John Wiley & Sons, Ltd.     

Literacy Education and Families: A Program and its Progress

Project Literacy Education and Families (LEAF) is a family literacy program that provides experiences for parents to develop their skills and confidence that will enable them to see possibilities instead of limitations. The purpose of Project LEAF is to provide intervention composed of four basic program components: adult literacy, early childhood education, parent education and parent-child literacy and play interaction time. The purpose of this article is to provide information related to the program's development, implementation, and evaluation.     

The mechanisms underlying MMR deficiency in immunodeficiency‐related non‐Hodgkin lymphomas are different from those in other sporadic microsatellite instable neoplasms

The spectrum of tumors showing microsatellite instability (MSI) has recently been enlarged to sporadic neoplasms whose incidence is favored in the context of chronic immunosuppression. We investigated the biological, therapeutic and clinical features associated with MSI in immunodeficiency‐related non‐Hodgkin lymphomas (ID‐RL). MSI screening was performed in 275 ID‐RL. MSI ID‐RL were further analyzed for MMR gene expression and for BRAF/KRAS mutations since these genes are frequently altered in MSI cancers. We also assessed the expression of O⁶‐methylguanine‐DNA methyltransferase (MGMT), an enzyme whose inactivation has been reported in lymphomas and may help in the selection of MMR deficient clones. Unlike other sporadic MSI neoplasms, MSI ID‐RL (N = 17) presented with heterogeneous MMR defects and no MLH1 promoter methylation. About one third of these tumors presented with normal expression of MLH1, MSH2, MSH6 and PMS2. They accumulated BRAF activating mutations (33%). Unlike other ID‐RL, MSI ID‐RL were primarily EBV‐negative NHL of T‐cell origin, and arose after long‐term immunosuppression in patients who received azathioprine as part of their immunosuppressive regimen (p = 0.05) and/or who exhibited methylation‐induced loss of expression of MGMT in tumor cells (p= 0.02). Overall, these results highlight that, in the context of deficient immune status, some MSI neoplasms arise through alternative mechanism when compared to other sporadic MSI neoplasms. They give the exact way how to make the diagnosis of MSI in these tumors and may help to define biological and clinicalrisk factors associated with their emergence in such a clinicalcontext. © 2009 UICC     

Tumor histology helps to identify Lynch syndrome among colorectal cancer patients

Objective To determine the value of histology in identifying Lynch syndrome among those patients with early onset of colorectal cancer (CRC). Methods Demographic, clinical and cancer history data from patients diagnosed with CRC before 60 years of age, and treated at our institution between 1997 and 2005, were collected from medical records and direct interview. Their tumors were assessed to identify histological features suggestive of high frequency microsatellite instability (MSI-H): tumor infiltrating lymphocytes, Crohn's like inflammatory reaction, mucinous, signet ring cells, medullary growth pattern and then, tested for microsatellite instability (MSI) and MLH1/ MSH2 protein expression. Results Sixty-five patients were included in the study. The mean age at diagnosis was 48 +/- 9.9 years. Overall, 28 (43%) patients, including 13 of 35 diagnosed between ages 50 and 60, had tumor demonstrating one or more histological features suggestive of MSI-H. These patients were younger (45 vs. 50 years, P = 0.02) and more commonly had family history of Lynch syndrome-related cancers (36 vs. 19%), though the latter feature did not reach statistical significance (P = 0.07). Eleven of 25 tumors with MSI-H histology, but only 1 of 29 tumors without special histological features were found to be MSI-H (P < 0.0001). Histology had a positive predictive value of 44% and a negative predictive value of 97% for identifying MSI-H tumors. Conclusions Limiting MSI analysis only to those tumors with suggestive histology would have reduced the need for testing by nearly 60% of all tumors from patients that met the revised Bethesda guidelines.     

Painless tonsillectomy

PURPOSE OF REVIEW: Even though pediatric tonsillectomy is a well accepted treatment for upper airway obstruction or recurrent tonsillar infection, the painful recovery of this operation is unwelcome. As more studies are published on the beneficial effects of tonsillectomy, the number of tonsillectomies performed is likely to increase. It would behoove any surgeon performing this operation to be aware of the available options for post/perioperative pain control. RECENT FINDINGS: New techniques used to perform tonsillectomy, innovative adjuvant medical therapy and other tools are reviewed. SUMMARY: The search for 'the painless tonsillectomy' continues. Finding a technique that works best for each surgeon is paramount to successful tonsillectomy. Patient comfort, surgical time, complications such as bleeding and regrowth of tonsillar tissue, or recurrence of symptoms that lead to the initial operation should all be considered in the surgeon's choice of a particular tonsillectomy technique. Medical therapies such as corticosteroids in the perioperative period are well accepted as a pain adjuvant. Newer adjuvants include the use of pretonsillectomy injection of mixtures that include local anesthetics with opioids and clonidine. The use of nonsteroidal antiinflammatory drugs appears to be helpful for pain, but controversial regarding bleeding. Another successful strategy used to decrease pain perception is distraction.     

Improved Pain Resolution in Hospitalized Patients through Targeting of Pain Mismanagement as Medical Error

Current strategies to reduce excess pain among hospitalized patients remain inadequate. New, effective approaches are urgently needed. In this prospective observational study of a performance-improvement intervention, we studied the effect of computer-generated, real-time alerts used by nurses on the rate of a medical error in pain management defined as lack of reassessment within 120 minutes from the last observation of severe pain. We also studied duration of severe pain events and frequency of treatment of opioid-related adverse effects. Analyses of 51,619 consecutive observations of severe pain were performed in monthly intervals. Significant decrease in error rate (delayed pain reassessment) was observed postintervention (mean ± standard error [SE]: 35.8% ± 0.7%) compared with preintervention rate (56.2% ± 1.4%, P < 0.0001). Among 6305 unique severe pain events examined during four months pre- and postintervention, time to resolution of severe pain decreased significantly (median time preintervention [January 2006] of 195 minutes compared with median time postintervention of 117, 106, and 101 minutes [January, April, and June 2007], P < 0.0001). Hospital-wide, unanticipated monthly naloxone administration decreased postintervention (mean ± SE: 1.48 ± 0.21 per month per 1000 inpatients) compared with preintervention (2.69 ± 0.35, P = 0.0130). Hospital-wide implementation of real-time, computer-generated alerts identifying instances of delayed pain reassessment resulted in sustained reduction of error rate and faster resolution of severe pain without oversedation.