Once-Daily Oral Levofloxacin Monotherapy versus Piperacillin/Tazobactam Three Times a Day: A Randomized Controlled Multicenter Trial in Patients with Febrile Neutropenia

A prospective, randomized, controlled multicenter trial was performed to evaluate the efficacy and safety of once-daily oral monotherapy with 500 mg levofloxacin in comparison with 4.5 g piperacillin/tazobactam 3 times a day in patients with low-risk febrile neutropenia. Low risk was defined by oral temperature > or = 38.5 degrees C on one occasion or > or = 38.0 degrees C twice within 24 hours and granulocytopenia < or = 500/microL for less than 10 days. The primary end point was defined as defervescence after 72 hours followed by at least 7 afebrile days. Secondary end points were overall response, time to defervescence, survival on day 30, and toxicity. Thirty-four episodes were included. Fever of unknown origin accounted for 26 (76.5%) of the episodes, microbiologically defined infection for 5 (14.7%) of the episodes, and clinically defined infection for 3 (8.8%) of the episodes. On an intent-to-treat basis, all episodes were evaluable for the primary end point. Levofloxacin and piperacillin/tazobactam were successful after 72 hours of treatment in 76.5% and 88.3% of the episodes. Overall response was achieved in 94.1% and 100% of the episodes, respectively. One inpatient in the oral treatment group died of septic shock without identification of a causative pathogen. A larger phase III trial is warranted to further evaluate the lack of inferiority of the oral monotherapy regimen versus standard intravenous therapy.     

ECG signs mimicking acute inferior wall myocardial infarction are associated with elevated myocardial enzymes during isolation of pulmonary vein for focal atrial fibrillation.

In this study, we report an intraprocedural incident in patients undergoing ablation for atrial fibrillation. During left atrial manipulation our patients suffered from acute chest pain, showed ECG signs of an acute inferior wall myocardial infarction, and increased levels of cardiac Troponin I (cTnI). We strongly recommend being aware of unexpected reactions during isolating pulmonary veins for focal atrial fibrillation, especially when passing the dorsal part of the left atrium. If pericardial effusion is ruled out and ECG signs as well as symptoms disappear, the ablation procedure should proceed. We think patients undergoing pulmonary vein ablation for atrial fibrillation should be informed of this threatening complication.     

Comparative activities of ciprofloxacin, clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against epidemiologically defined Acinetobacter baumannii strains

In vitro activities of seven fluoroquinolones against 140 clinical Acinetobacter baumannii isolates representing 138 different strain types were determined. The rank order of activity was clinafloxacin > gatifloxacin > levofloxacin > trovafloxacin > gemifloxacin = moxifloxacin > ciprofloxacin. The 31 outbreak-related A. baumannii strains were significantly more resistant than were 109 sporadic strains.     

The systemic influence of recombinant interleukin 2 on the manifestations of lepromatous leprosy

14 patients with lepromatous leprosy received twice daily injections of 10 micrograms recombinant interleukin 2 (rIL-2), by the intradermal route, in the skin of the back for 8 d (total dose, 160 micrograms). Lymphokine administration was accomplished without drug toxicity, or the development of acute nerve damage. The majority of patients developed nontender axillary lymphadenopathy during the course of treatment. Local injection sites showed progressively larger zones of induration, peaking at 24 h and persisting for many days. Early 12-h reactions were of a macular, erythematous nature and exhibited an increasingly striking diurnal variation. The morning injection sites were three- to fourfold larger in diameter than those placed in the evening (9 am to 9 pm). Systemic manifestations of intradermal rIL-2 administration were noted. Peripheral blood T cells, including CD4+ and CD8+ phenotypes, increased 2-2.5-fold and NK cells increased sixfold. Elevations in [3H]TdR incorporation into peripheral blood mononuclear cells occurred to a variety of mycobacterial antigens, but not to those of Mycobacterium leprae. Within 2 wk, biopsies at sites far removed from the back showed increased infiltration of mononuclear cells in 12 of 14 patients. Immunocytochemistry revealed the presence of newly emigrated CD4+ T cells, monocytes, and dermal CD1+ Langerhans cells. Endothelial cells of small dermal vessels expressed major histocompatibility complex class II determinants on their surface. Transmission electron microscopy of these specimens revealed markedly enlarged endothelial cells with many surface projections extending into the lumen as well as extravasating lymphoid cells. The numbers of acid-fast M. leprae in the peripheral sites were examined by slit smear and in biopsies of matched leprosy lesions taken before and after IL-2 administration. Within 2 mo, slit smears showed a 0.5 log or greater reduction in 12 of 14 patients, with a mean for all patients tested of 0.5 log units. Biopsy specimens showed a 1 log unit or greater reduction in the bacterial index (B.I.) in 6 of 14 patients. Historical controls in this Nepalese population showed a 0.5 log unit reduction after multidrug therapy over a period of 12 mo. Thus, after 8 d of IL-2 injections, a fivefold reduction in B.I. was observed during the first 2 mo of the study. Antibody levels against M. leprae phenolic glycolipid 1 (PGL-1) and lipoarabinomanan B were markedly elevated after IL-2 injections, while PGL-1 antigen levels were reduced. We conclude that the administration of rIL-2 has had a significant effect in decreasing the total body burden of M. leprae.(ABSTRACT TRUNCATED AT 400 WORDS)     

Possible consequences of social drinking in the early stages of Alzheimer disease

Although research supports the idea that alcohol is not a risk factor for developing Alzheimer disease (AD), surprisingly little attention has been given to the role of social drinking in the early stages of the disorder. The current review highlights potential alcohol- and disease-related interactions on neurologic, cognitive, and behavioral functioning in individuals experiencing the early stages of AD. Understanding how alcohol interacts with AD can benefit both treatment providers (eg, interpreting clinical tests) and caregivers (eg, managing disruptive behaviors) by providing important clues to potentially reversible impairments that may negatively affect the everyday functioning of individuals with the disorder.     

Predictors of clinical response to intraarticular Hylan injections -- a prospective study using synovial fluid measures, clinical outcomes, and magnetic resonance imaging

OBJECTIVE: To evaluate synovial fluid (SF) and clinical and imaging predictors of clinical response in patients receiving intraarticular Hylan GF-20 injections. METHODS: Thirty-two patients with mild to moderate osteoarthritis (OA) of the knee [OsteoArthritis Research Society International (OARSI) grades I-II] were followed over 6 months. SF and clinical and radiographic measures were assessed. Patella and tibial cartilage volume and cartilage defect scores were measured at baseline and 6 months using magnetic resonance imaging (MRI). The primary outcome measure was the relationship between SF measures and clinical response as defined by the OARSI-Outcome Measures in Rheumatology Clinical Trials responder criteria for OA ("High improvement" >or= 50% improvement in pain or function; absolute change >or= 20 NU on Western Ontario and McMaster University Osteoarthritis Index questionnaire). Secondary outcomes included MRI outcomes (change in cartilage volume and cartilage defect scores). RESULTS: Fifteen patients achieved "High improvement." High baseline SF hyaluronic acid (HA) concentration was a statistically significant predictor of clinical response with odds ratio (OR) 6.04 (p < 0.02). HA concentration was divided into tertiles and fitted to a univariate regression model against clinical response. A baseline HA concentration value of > 2 mg/ml provided the greatest tradeoff between sensitivity and specificity with values of 60% and 77%, respectively, a likelihood ratio of 2.55, and OR of 4.88. Baseline clinical and radiological measures did not predict clinical response in this cohort with mild to moderate OA. Nineteen subjects had MRI at both timepoints. No change was noted in cartilage volumes or cartilage defect scores over 6 months. There was no association between baseline HA concentration and baseline cartilage volume. CONCLUSION: Baseline SF HA concentration predicts clinical response in patients receiving intraarticular Hylan. This has implications for the selection of patients who are likely to respond to this therapy.     

A comparative study of Butacote and Naprosyn in ankylosing spondylitis.

A double-blind, cross-over comparison of Naprosyn (naproxen) 750 mg daily and Butacote (enteric-coated phenylbutazone) 300 mg daily was carried out in a multi-centre trial. Twenty-five patients, mostly male and under 40 years of age, were entered. After a 2-week period in which any existing anti-inflammatory drugs were tailed off, patients were entered into the trial and treated for 1 month with each drug. Patients were assessed at 4-weekly intervals. Both drugs significantly reduced morning stiffness. Morning pain and discomfort and wall-tragus distance were also significantly reduced by both drugs during the trial. Results of the Schober test showed improvement during both treatment periods. There were no overall statistically significant differences between the effects of the 2 drugs on objective parameters. However, overall subjective assessment of symptoms showed a greater improvement on Butacote. Treatment preferences by physician and subjective assessment by the patient both favoured Butacote but the difference between the 2 drugs was not statistically significant. Side effects were mostly of a minor nature. One patient had to discontinue the trial, due to indigestion while taking Butacote.     

Intravenous and oral galactose loading of rats suffering from galactosamine hepatitis and ANIT-cholestasis; comparison of the kinetics in vivo and the galactose metabolism in the liver in vitro (author's transl)

Different groups of rats suffering from galactosamine hepatitis or ANIT-cholestasis received 200 mg galactose either by 5 minutes intravenous infusion or via a gastric tube. Blood galactose concentrations were measured for a time period of 1.5 hrs. after intravenous administration and the galactose elimination capacity (GEC) was calculated. After oral administration the galactose blood concentrations were determined for a period of 3.5 hrs. and the oral galactose clearance was estimated. After termination of both types of galactose loading the activity of the galactokinase (EC 2.7.1.6.) was determined in total liver homogenate and compared either to the GEC or to the oral galactose clearance in vivo. Galactokinase activity in the liver increased in the group of animals with experimental cholestasis and was significantly reduced in the galactosamine treated group. In vivo these changes could be estimated much better by the GEC than by determination of the oral galactose clearance.     

Vitamin D metabolites in synovial fluid.

This study has shown that it is possible to measure vitamin D metabolites and vitamin D binding protein (DBP) in synovial fluid as well as serum. Significant amounts of 25-OHD, 24,25-(OH)2D, and DBP are present in synovial fluid. The 25-OHD and DBP maintain a serum:synovial fluid ratio of approximately 2:1 irrespective of the type of joint disease, whereas no such relationship was detected for 24,25-(OH)2D. The possible reasons for these findings are diffusion of the metabolites into synovial fluid or local production from suitable precursors, or both.