Improving Diagnostic Accuracy of Anaphylaxis in the Acute Care Setting

The identification and appropriate management of those at highest risk for life-threatening anaphylaxis remains a clinical enigma. The most widely used criteria for such patients were developed in a symposium convened by National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network. In this paper we review the current literature on the diagnosis of acute allergic reactions as well as atypical presentations that clinicians should recognize. Review of case series reveals significant variability in definition and approach to this common and potentially life-threatening condition. Series on fatal cases of anaphylaxis indicate that mucocutaneous signs and symptoms occur less frequently than in milder cases. Of biomarkers studied to aid in the work-up of possible anaphylaxis, drawing blood during the initial six hours of an acute reaction for analysis of serum tryptase has been recommended in atypical cases. This can provide valuable information when a definitive diagnosis cannot be made by history and physical exam

Carbon Monoxide Binding to the Iron–Molybdenum Cofactor of Nitrogenase: a Detailed Quantum Mechanics/Molecular Mechanics Investigation

Carbon monoxide (CO) is a well-known inhibitor of nitrogenase activity. Under turnover conditions, CO binds to FeMoco, the active site of Mo nitrogenase. Time-resolved IR measurements suggest an initial terminal CO at 1904 cm–1 that converts to a bridging CO at 1715 cm–1, and an X-ray structure shows that CO can displace one of the bridging belt sulfides of FeMoco. However, the CO-binding redox state(s) of FeMoco (En) and the role of the protein environment in stabilizing specific CO-bound intermediates remain elusive. In this work, we carry out an in-depth analysis of the CO–FeMoco interaction based on quantum chemical calculations addressing different aspects of the electronic structure. (1) The local electronic structure of the Fe–CO bond is studied through diamagnetically substituted FeMoco. (2) A cluster model of FeMoco within a polarizable continuum illustrates how CO binding may affect the spin-coupling between the metal centers. (3) A QM/MM model incorporates the explicit influence of the amino acid residues surrounding FeMoco in the MoFe protein. The QM/MM model predicts both a terminal and a bridging CO in the E1 redox state. The scaled calculated CO frequencies (1922 and 1716 cm–1, respectively) are in good agreement with the experimentally observed IR bands supporting CO binding to the E1 state. Alternatively, an E2 state QM/MM model, which has the same atomic structure as the CO-bound X-ray structure, features a semi-bridging CO with a scaled calculated frequency (1718 cm–1) similar to the bridging CO in the E1 model

Boomerang returns unexpectedly

Experimental study of the anisotropy in the cosmic microwave background (CMB) is gathering momentum. The eagerly awaited Boomerang results have lived up to expectations. They provide convincing evidence in favor of the standard paradigm: the Universe is close to flat and with primordial fluctuations which are redolent of inflation. Further scrutiny reveals something even more exciting however -- two hints that there may be some unforeseen physical effects. Firstly the primary acoustic peak appears at slightly larger scales than expected. Although this may be explicable through a combination of mundane effects, we suggest it is also prudent to consider the possibility that the Universe might be marginally closed. The other hint is provided by a second peak which appears less prominent than expected. This may indicate one of a number of possibilities, including increased damping length or tilted initial conditions, but also breaking of coherence or features in the initial power spectrum. Further data should test whether the current concordance model needs only to be tweaked, or to be enhanced in some fundamental way.Comment: 11 pages, 3 figures, final version accepted by Ap

Inducers of Friend leukaemic cell differentiation in vitro--effects of in vivo administration.

Studies were conducted of the in vivo therapeutic potential of compounds which induce the differentiation of Friend leukaemia cells (FLC) in vitro. DBA2/J mice were inoculated with Friend leukaemia cells grown in tissue culture and at various times thereafter were treated with either N-methylacetamide, dimethylacetamide, or tetramethylurea. While survival was only occasionally prolonged, in every study these agents significantly inhibited leukaemia cell proliferation in the spleen and to a lesser extent in the marrow. These agents had no effect on the rate of proliferation of FLC growing subcutaneously nor on the proliferation of myeloid leukaemia in RFMS mice. These studies indicate that the administration of inducing agents to mice bearing Friend leukaemia can alter the proliferation characteristics of the leukaemia cells and hence suggest that these agents may have therapeutic potential

Energy Injection in GRB Afterglow Models

We extend the standard fireball model, widely used to interpret gamma-ray burst (GRB) afterglow light curves, to include energy injections, and apply the model to the afterglow light curves of GRB 990510, GRB 000301C and GRB 010222. We show that discrete energy injections can cause temporal variations in the optical light curves and present fits to the light curves of GRB 000301C as an example. A continuous injection may be required to interpret other bursts such as GRB 010222. The extended model accounts reasonably well for the observations in all bands ranging from X-rays to radio wavelengths. In some cases, the radio light curves indicate that additional model ingredients may be needed.Comment: Accepted for publication in the Astrophysical Journa

Problems Associated with Deprescribing of Proton Pump Inhibitors.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadProton pump inhibitors (PPIs) are recommended as a first-line treatment for gastroesophageal reflux disease (GERD) and other acid related disorders. In recent years, concerns have been raised about the increasing prevalence of patients on long-term PPI therapy and inappropriate PPI use. It is well known that short-term PPI therapy is generally well tolerated and safe; however, their extensive long-term use is a major global issue. One of these long-standing concerns is PPI-induced gastrin elevation secondary to hypoacidity. Hypergastrinemia is believed to play a role in rebound hyperacidity when PPIs are discontinued resulting in induced dyspeptic symptoms that might result in the reinstitution of therapy. Gastrin exerts tropic effects in the stomach, especially on enterochromaffin-like (ECL) cells, and concerns have also been raised regarding the potential progression to dysplasia or tumor formation following long-term therapy. It is well known that a substantial number of patients on long-term PPI therapy can discontinue PPIs without recurrence of symptoms in deprescribing trials. What is unknown is how sustainable deprescribing should be undertaken in practice and how effective it is in terms of reducing long-term outcomes like adverse drug events, morbidity and mortality. Moreover, there is no clear consensus on when and how deprescribing strategies should be attempted in practice. This review sought to summarize the harms and benefits of long-term PPI therapy with special focus on gastrin elevation and its relation to deprescribing studies and future interventions that may improve PPI use

A multi-feedzone wellbore simulator

A multi-feedzone wellbore simulator has been developed. This computer code is quite general as it enables one to compute downhole conditions in wells with an arbitrary number of feedzones during discharge or injection. The simulator is applied to flowing pressure and temperature surveys from various wells in Mexico, Iceland and Kenya. It is demonstrated that such a model can be used to estimate flow rates and enthalpies of individual feedzones