Cefepime monotherapy for the empirical treatment of fever in granulocytopenic cancer patients

In a pilot study, we evaluated the efficacy and the safety of cefepime, a new cephalosporin with extended-spectrum activity against both Gram-positive and Gram-negative bacteria, as empirical monotherapy for 108 febrile episodes in 84 granulocytopenic cancer patients. Cefepime (2 g tds) was given for a minimum of 7 days or until resolution of infection. Of the 108 episodes, 91 were evaluable. Microbiologically documented infections occurred in 25 patients (27%) (18 Gram-positive, 7 Gram-negative), of whom 18 had bacteraemia. Infection was clinically documented in 47 patients (52%) and fever was unexplained in 19 (21%). Overall, 71% (65/91) of the infections resolved. Response rates were 86% (6/7) for Gram-negative infections, 44% (8/18) for Gram-positive infections (57%%for cefepime-susceptible Gram-positive bacteria), 77% (36/47) for clinically documented infections and 79% (15/19) for unexplained fevers. Of the 26 patients (29%) whose primary infections did not improve with cefepime monotherapy, 23 responded after the addition of other antibiotics. Sixteen patients (18%) developed secondary infections of which 13 were microbiologically documented; Gram-positive bacteria were isolated from seven patients, Gram-negative bacteria from two, fungi from three and a virus from one. Adverse effects were mild and did not require premature discontinuation of therapy except for one patient who developed an immediate allergic reaction after the first dose of cefepime from which he recovered fully. The survival rate after resolution of granulocytopenia was 96%; three patients died of primary bacterial infection and one from secondary disseminated candidiasis. In this pilot study, cefepime monotherapy appeared safe and effective as empirical therapy for fever in cancer patients with granulocytopenia. Whether cefepime is superior to other advanced-generation cephalosporins for the treatment of Gram-positive infections will require evaluation in a larger comparative stud

Clinical experience with Timentin in severe hospital infections

Sixty-four severe infections in hospitalized patients were treated with intravenous Timentin. Most patients (mean age: 50-5 years, range 18-85) had serious underlying conditions such as agranulocytosis, heart failure, cancer, diabetes mellitus, chronic alcoholism or other functional or anatomical abnormalities. Forty-three episodes were bacteriologically proved, and bacteraemia was diagnosed in 18. The sites of infection were: lower respiratory tract (10), upper respiratory tract (10), soft tissues(9), urinary tract (7), bones (6), peritoneal cavity (3), meninges (1) and pelvis (1). Inaddition, 13 episodes of fever and four of septicaemia in patients with agranulocytosis were treated with Timentin plus amilcacin. Overall, 59% of the episodes were cured, 14% improved and 17% failed to respond. In 9% of cases the efficacy of the Timentin was unassessable mainly because of concurrent administration of other antimicrobials. Failure appeared to be more frequent in soft tissue and intra-abdominal infections, in patients infected with bacteria susceptibleto Timentin but resistant to ticarcillin and in patients superinfected with Timentin-resistant strains. Major side effects were haemorrhagic diathesis with platelet dysfunction (1), severe water sodium overload (1), and possibly pancreatitis (1).Other side effects were mild: catheter-related phlebitis, and abnormal but clinically insignificant laboratory test results. Timentin appears to be an effective and safebroad-spectrum combination which compares favourably with third-generation cephalosporins in the treatment of severe hospital infections. More experience is needed to decide whether the some what lower response rate in patients infected with ticarcillin-resistant strains is significan

Antibodies to Lipopolysaccharides after Immunization of Humans with the Rough Mutant Escherichia coli J5

To investigate whether immunization with Escherichia coli J5 boiled cells induces antibodies directed at deep core structures, antibodies against JS lipopolysaccharide (LPS), Re LPSt and Iipid A were measured in the serum of 70 volunteers before and 2 weeks after immunization. To improve the sensitivity and the specificity ofELISAt complexes of core LPS with high-density lipoproteins were used instead of free core LPS as antigens. A median three-fold increase in antibodies directed against J5 LPS was observed, but no significant increase in the antibodies against Re LPS or lipid A was found. Since JS antiserum did not react with several smooth LPS or with Re LPS and lipid At cross-reactivity could not be demonstrated. Thus, immunization of volunteers with E. coli J5 produced a modest specific antibody response against J5 LPS. The mechanism of protection previously observed with J5 antiserum remains unclea

Demonstration of Cross-Reactive Antibodies to Smooth Gram-Negative Bacteria in Antiserum to Escherichia coli J5

We investigated the discrepancy between the broad cross-protection against gram-negative infections afforded by antiserum to Escherichia coli J5 and its apparently narrow cross-reactivity in vitro. Rabbits immunized with J5 bacteria produced antibodies to both the J5 lipopolysaccharide (LPS; titer by ELISA, 1:60,000) and LPS from the Re mutant of Salmonella minnesota (i.e., to the ketodeoxyoctonate [KDO] and lipid A determinants; titer, 1:3,200). In highly diluted antiserum, titers of antibody to J5 LPS were reduced by 28%-41% after adsorption with seven strains of smooth gram-negative bacteria and by only 4% after adsorption with the Re mutant. Smooth gram-negative bacteria adsorbed virtually all antibody to Re LPS. Therefore, rabbit antiserum to J5 contains type-specific antibodies to core determinants distal to KDO that can obscure highly cross-reactive antibodies to lipid A-KDO in vitro. Cross-reactive antibodies are demonstrable by adsorption with whole bacteria at limiting concentrations of antibod

Benchmark problems for continuum radiative transfer. High optical depths, anisotropic scattering, and polarisation

Solving the continuum radiative transfer equation in high opacity media requires sophisticated numerical tools. In order to test the reliability of such tools, we present a benchmark of radiative transfer codes in a 2D disc configuration. We test the accuracy of seven independently developed radiative transfer codes by comparing the temperature structures, spectral energy distributions, scattered light images, and linear polarisation maps that each model predicts for a variety of disc opacities and viewing angles. The test cases have been chosen to be numerically challenging, with midplane optical depths up 10^6, a sharp density transition at the inner edge and complex scattering matrices. We also review recent progress in the implementation of the Monte Carlo method that allow an efficient solution to these kinds of problems and discuss the advantages and limitations of Monte Carlo codes compared to those of discrete ordinate codes. For each of the test cases, the predicted results from the radiative transfer codes are within good agreement. The results indicate that these codes can be confidently used to interpret present and future observations of protoplanetary discs.Comment: 15 pages, 10 figures, accepted for publication in A&

The circumstellar disc in the Bok globule CB 26: Multi-wavelength observations and modelling of the dust disc and envelope

Circumstellar discs are expected to be the nursery of planets. Grain growth within such discs is the first step in the planet formation process. The Bok globule CB 26 harbours such a young disc. We present a detailed model of the edge-on circumstellar disc and its envelope in the Bok globule CB 26. The model is based on HST near-infrared maps in the I, J, H, and K bands, OVRO and SMA radio maps at 1.1mm, 1.3mm and 2.7mm, and the spectral energy distribution (SED) from 0.9 microns to 3mm. New photometric and spectroscopic data from the Spitzer Space Telescope and the Caltech Submilimeter Observatory have been obtained and are part of our analysis. Using the self-consistent radiative transfer code MC3D, the model we construct is able to discriminate parameter sets and dust properties of both its parts, namely envelope and disc. We find that the disc has an inner hole with a radius of 45 +/- 5 AU. Based on a dust model including silicate and graphite the maximum grain size needed to reproduce the spectral millimetre index is 2.5 microns. Features seen in the near-infrared images, dominated by scattered light, can be described as a result of a rotating envelope. Successful employment of ISM dust in both the disc and envelope hint that grain growth may not yet play a significant role for the appearance of this system. A larger inner hole gives rise to the assumption that CB 26 is a circumbinary disc.Comment: 18 pages, 15 figures, Accepted for publication in A&

Treatment options of invasive fungal infections in adults.

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

The Taurus Spitzer Survey: New Candidate Taurus Members Selected Using Sensitive Mid-Infrared Photometry

We report on the properties of pre-main-sequence objects in the Taurus molecular clouds as observed in 7 mid- and far-infrared bands with the Spitzer Space Telescope. There are 215 previously-identified members of the Taurus star-forming region in our ~44 square degree map; these members exhibit a range of Spitzer colors that we take to define young stars still surrounded by circumstellar dust (noting that ~20% of the bonafide Taurus members exhibit no detectable dust excesses). We looked for new objects in the survey field with similar Spitzer properties, aided by extensive optical, X-ray, and ultraviolet imaging, and found 148 candidate new members of Taurus. We have obtained follow-up spectroscopy for about half the candidate sample, thus far confirming 34 new members, 3 probable new members, and 10 possible new members, an increase of 15-20% in Taurus members. Of the objects for which we have spectroscopy, 7 are now confirmed extragalactic objects, and one is a background Be star. The remaining 93 candidate objects await additional analysis and/or data to be confirmed or rejected as Taurus members. Most of the new members are Class II M stars and are located along the same cloud filaments as the previously-identified Taurus members. Among non-members with Spitzer colors similar to young, dusty stars are evolved Be stars, planetary nebulae, carbon stars, galaxies, and AGN.Comment: Accepted to ApJS. Two large online-only figures available with the preprint here: http://web.ipac.caltech.edu/staff/rebull/research.htm

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered