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

Taxanes convert regions of perturbed microtubule growth into rescue sites

Microtubules are polymers of tubulin dimers, and conformational transitions in the microtubule lattice drive microtubule dynamic instability and affect various aspects of microtubule function. The exact nature of these transitions and their modulation by anti -cancer drugs such as Taxol and epothilone, which can stabilize microtubules but also perturb their growth, are poorly understood. Here, we directly visualize the action of fluorescent Taxol and epothilone derivatives and show that microtubules can transition to a state that triggers cooperative drug binding to form regions with altered lattice conformation. Such regions emerge at growing microtubule ends that are in a pre-catastrophe state and inhibit microtubule growth and shortening. Electron microscopy and in vitro dynamics data indicate that taxane accumulation zones represent incomplete tubes that can persist, incorporate tubulin dimers and repeatedly induce microtubule rescues. Thus, taxanes modulate the material properties of microtubules by converting destabilized growing microtubule ends into regions resistant to depolymerization

Dust amorphization in protoplanetary disks

High-energy irradiation of the circumstellar material might impact the structure and the composition of a protoplanetary disk and hence the process of planet formation. In this paper, we present a study on the possible influence of the stellar irradiation, indicated by X-ray emission, on the crystalline structure of the circumstellar dust. The dust crystallinity is measured for 42 class II T Tauri stars in the Taurus star-forming region using a decomposition fit of the 10 micron silicate feature, measured with the Spitzer IRS instrument. Since the sample includes objects with disks of various evolutionary stages, we further confine the target selection, using the age of the objects as a selection parameter. We correlate the X-ray luminosity and the X-ray hardness of the central object with the crystalline mass fraction of the circumstellar dust and find a significant anti-correlation for 20 objects within an age range of approx. 1 to 4.5 Myr. We postulate that X-rays represent the stellar activity and consequently the energetic ions of the stellar winds which interact with the circumstellar disk. We show that the fluxes around 1 AU and ion energies of the present solar wind are sufficient to amorphize the upper layer of dust grains very efficiently, leading to an observable reduction of the crystalline mass fraction of the circumstellar, sub-micron sized dust. This effect could also erase other relations between crystallinity and disk/star parameters such as age or spectral type.Comment: accepted for publication by A&

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&

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

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

Partial dearterialization of the liver allograft

The clinical course of five patients with partial dearterialization of their hepatic allografts is described. One patient died and three others suffered serious morbidity as a direct or indirect result of this complication. Partial dearterialization of the liver allograft is a serious and potentially life-threatening complication for which preservation of the complete hepatic arterial supply is important, even if this requires reconstruction of the aberrant vessels. © 1990 Springer-Verlag

Vancomycin versus Placebo for Treating Persistent Fever in Patients with Neutropenic Cancer Receiving Piperacillin-Tazobactam Monotherapy

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P = .52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P = .75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cance

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