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

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