Cumulative clinical experience from over a decade of use of levofloxacin in urinary tract infections: critical appraisal and role in therapy

The treatment of urinary tract infections (UTIs) continues to evolve as common uropathogens increasingly become resistant to previously active antimicrobial agents. In addition, bacterial isolates, which were once considered to be either colonizers or contaminants, have emerged as true pathogens, likely related to the more complex array of settings where health care is now delivered. Even though the reliability of many antimicrobial agents has become less predictable, the fluoroquinolone group of agents has remained a frequent, if not the most often prescribed, antimicrobial therapy for almost all types of UTIs. Levofloxacin has taken its position at the top of the list as one of the most regularly administered fluoroquinolone agents given to patients with a suspected or proven UTI. The authors review the clinical experience of the use of levofloxacin over the past decade and suggest that the use of levofloxacin for the treatment of UTIs, although still fairly dependable, is perhaps not the best use of this important antimicrobial agent

Pediatric pacemaker infections: Twenty years of experience

AbstractObjective: We sought to evaluate possible predictors of early and late pacemaker infections in children. Methods: A review was performed of all pacemakers implanted in children at The Children's Hospital of Philadelphia between 1982 and 2001. Infections were classified as superficial cellulitus, deep pacemaker pocket infection necessitating removal, or positive blood culture without an identifiable source. Results: A total of 385 pacemakers (224 epicardial and 161 endocardial) were implanted in 267 patients at 8.4 ± 6.2 years. All 2141 outpatient visits were reviewed (median follow-up, 29.4 months; range, 2-232 months). There were 30 (7.8%) pacemaker infections: 19 (4.9%) superficial infections; 9 (2.3%) pocket infections; and 2 (0.5%) isolated positive blood cultures. All superficial infections resolved with intravenous antibiotics. The median time from implantation to infection was 16 days (range, 2 days-5 years). Only 1 deep infection occurred after primary pacemaker implantation. Six patients with deep infections were pacemaker dependent and were successfully managed with intravenous antibiotics, followed by lead-generator removal and implantation of a new pacemaker in a remote location. In univariate analyses trisomy 21 (relative risk, 3.9; P <.01), pacemaker revisions (relative risk, 2.5; P <.01), and single-chamber devices (relative risk, 2.4; P <.05) were identified as predictors of infection. However, in multivariate analyses only trisomy 21 and pacemaker revisions were predictors. Conclusions: The incidences of superficial and deep pacemaker infections were 4.9% and 2.3%, respectively. Trisomy 21 and pacemaker revisions were significant risk factors in the development of infection after pacemaker implantation. For primary pacemaker implantation, the risk of infection requiring system removal is low (0.3%).J Thorac Cardiovasc Surg 2002;124:821-

The effect of diltiazem on coronary thrombosis in the conscious canine

The effect of diltiazem vs. saline was studied in a conscious canine model of coronary thrombosis. Diltiazem given as a 0.75 mg/kg loading dose intravenously followed by 0.4 mg/kg intravenously every 4 h for 24 h had no significant effect on thrombus wet weight, left ventricular infarct size, frequency of ventricular arrhythmias or ex vivo platelet aggregation. The search for antithrombotic agents using in vitro or ex vivo platelet aggregation studies should include concomitant in vivo thrombosis studies using therapeutic dosages of the drug in question.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24078/1/0000331.pd

Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries.

In the setting of type-2 diabetes, there are declines of structural stability and functionality of blood capillaries and red blood cells (RBCs), increasing the risk for microcirculatory disturbances. Correcting hyperglycemia is not entirely effective at reestablishing normal cellular metabolism and function. Therefore, identification of pathological changes occurring before the development of overt hyperglycemia may lead to novel therapeutic targets for reducing the risk of microvascular dysfunction. Here we determine whether RBC-capillary interactions are altered by prediabetic hypersecretion of amylin, an amyloid forming hormone co-synthesized with insulin, and is reversed by endothelial cell-secreted epoxyeicosatrienoic acids. In patients, we found amylin deposition in RBCs in association with type-2 diabetes, heart failure, cancer and stroke. Amylin-coated RBCs have altered shape and reduced functional (non-glycated) hemoglobin. Amylin-coated RBCs administered intravenously in control rats upregulated erythropoietin and renal arginase expression and activity. We also found that diabetic rats expressing amyloid-forming human amylin in the pancreas (the HIP rat model) have increased tissue levels of hypoxia-inducible transcription factors, compared to diabetic rats that express non-amyloid forming rat amylin (the UCD rat model). Upregulation of erythropoietin correlated with lower hematocrit in the HIP model indicating pathologic erythropoiesis. In the HIP model, pharmacological upregulation of endogenous epoxyeicosatrienoic acids protected the renal microvasculature against amylin deposition and also reduced renal accumulation of HIFs. Thus, prediabetes induces dysregulation of amylin homeostasis and promotes amylin deposition in RBCs and the microvasculature altering RBC-capillary interaction leading to activation of hypoxia signaling pathways and pathologic erythropoiesis. Hence, dysregulation of amylin homeostasis could be a therapeutic target for ameliorating diabetic vascular complications

2015-2016 Burley and Dark Tobacco Production Guide

Burley and dark tobacco growers in the U.S. make hundreds of decisions every growing season that impact the yield and quality of the crops that they produce. These decisions may include choosing appropriate varieties, planning effective pest control measures or perhaps deciding the best time to top or harvest a crop. Increasingly, tobacco growers are being required by the industry to record and justify their management decisions and actions. The most comprehensive example of this is the U.S. Tobacco Good Agricultural Practices (GAP) program that was initiated during the 2013 growing season and expanded in 2014. Under this program, all growers who sell tobacco to GAP Connections member organizations are required to attend training sessions on the principals of GAP and to keep detailed records of their production practices. Training requirements may change, but growers are currently required to attend training every season in which they plan to sell tobacco. Additional information about U.S. Tobacco GAP can be found by contacting GAP Connections. The written U.S. Tobacco GAP guidelines often refer growers to “University Tobacco Production Guides” for specific recommendations regarding management decisions. The information and recommendations provided in this guide have been developed and reviewed by tobacco production specialists and scientists at the University of Kentucky, University of Tennessee, Virginia Tech, and North Carolina State University. The purpose of this multi-state guide is to provide all burley and dark tobacco growers with the most current research-based recommendations for the production of high-yielding, high-quality tobacco. The guide provides advice on industry-accepted practices that may be applied across the burley and dark tobacco growing regions, although in some cases, growers may be referred to their local extension offices for additional information relevant to their specific situation

2013-2014 Kentucky & Tennessee Tobacco Production Guide

Tobacco growers in Kentucky and Tennessee have faced many challenges during the past two years, including weather, labor availability, and rising production costs. However, there have been opportunities as well. Some buying stations have closed or moved, but new buyers have come into the market and contract volumes have been stable overall. Good quality burley tobacco is in relatively short supply, and this has offered opportunities to those who have been able to overcome weather and labor challenges and produce good crops. These changes have had different impacts in different regions of both states, based largely on where buying stations closed and opened. Dark tobacco contract volumes have been more stable than burley, but dark tobacco growers have had challenges as well, including shortages of wood and quality sawdust needed to produce dark-fired tobacco. Labor costs have continued to rise as tobacco growers struggled to keep pace with changes in the H-2A labor program that allows them to legally employ migrant workers. Uncertainty about future regulatory action still hangs over the entire tobacco industry but does not seem as foreboding as two years ago. Overall, tobacco remains an important commodity in the agricultural economy of the region as growers prepare for future seasons

Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. RESULTS: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P CONCLUSIONS: AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.)

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Acute Sinusitis Resulting in a Craniotomy: An Uncommon Complication of a Common Infection

Acute bacterial sinusitis is a common infectious condition. Patients may initially present with an uncomplicated infection and later, despite appropriate initial antibiotic therapy, develop a potentially life-threatening complication. Interventions aimed at alleviating such unexpected events need be prompt and adequate. We describe a case of a patient who initially presented with signs and symptoms of acute sinusitis later to be diagnosed with a frontal epidural abscess