Epinephrine doses delivered from auto-injectors stored at excessively high temperatures

Context: Prompt injection of epinephrine (adrenaline) from epinephrine auto-injectors (EAIs) is the primary treatment for anaphylaxis in out-of-hospital settings. Storage of EAIs at room temperature (25?°C) is advised; however, storage at excessively high temperatures sometimes occurs. To our knowledge, there are no previous publications on the doses of epinephrine ejected from EAIs after storage at such temperatures.

Objective: We examined the epinephrine doses delivered from activated EAIs stored constantly or cyclically at 70?°C.

Methods: Twenty-five in-date EAIs were stored constantly or cyclically at 70?°C (excessive heat) or 25?°C (controls) for 5?d or 10?d. EAIs were activated and the epinephrine doses in the ejected solutions were measured using HPLC-UV. The enantiomeric purity of epinephrine was also measured by HPLC-UV.

Results: Control EAIs ejected a volume of 0.300?±?0.006?mL containing 103.7?±?3.3% of labeled dose (LD). After 5?d or 10?d of constant storage at 70?°C and activation at 70?°C, EAIs ejected a volume of 0.367?±?0.008?mL containing 96.8?±?3.8% LD and 0.373?±?0.007?mL containing 77.7?±?3.3% LD, respectively. After 5?d of cyclic storage at 70?°C and cooling to 25?°C before activation, EAIs ejected a volume of 0.311?±?0.008?mL containing 87.2?±?1.9% LD. Under the experimental conditions of this study, the resultant chromatographic peaks of epinephrine solutions from all EAIs represented only the pure l-enantiomer of epinephrine.

Conclusion: EAIs should be stored under recommended conditions of the manufacturer. EAIs stored at excessively high temperatures cannot be used to treat humans while still hot, and when cooled, cannot be relied on to deliver the labeled epinephrine dose in anaphylaxis.     

Effects of pH on rhodopsin photointermediates from lumirhodopsin to metarhodopsin II

Time-resolved absorption difference spectra of membrane suspensions of bovine rhodopsin at pH 5, 6, 7, 8, 9, and 10 were collected in the time range from 1 micro s to 200 ms after laser photolysis with 7-ns pulses of 477-nm light. The data were analyzed using singular value decomposition (SVD) and global exponential fitting. At pH 7 the data agree well with previously obtained data (Thorgeirsson et al. (1993) Biochemistry 32, 13861-13872) with fits improved at all pH's by inclusion of a small component due to an absorbance change caused by rotational diffusion which is detectable even at magic angle polarization. A "square scheme" suggested to best explain the previous data, which involves two branches following decay of the lumi intermediate with pathways (1) lumi --> MI480 right harpoon over left harpoon MII and (2) lumi right harpoon over left harpoon MI380 --> MII, could be confirmed throughout the entire pH range. However, to account for the increased rate of the MII --> MI480 reaction in path 1 for rising pH values, we propose that the MII in the square scheme consists of deprotonated MII and protonated MIIH+ forms in rapid equilibrium with each other, resulting in an extended square scheme and increasing the number of 380-nm products from two to three. In addition to the kinetic processes described by the extended square scheme, above pH 8 fast ( approximately 10 micro s) and slow ( approximately 50 ms) components were found. The fast component was assigned to the decay of a blue-shifted lumi intermediate, and the slow component, resolvable only at pH 10, was assigned to formation of a 450 nm absorbing photoproduct.     

Emission polarization of roughened glass and aluminum surfaces

Ellipsometer measurements of the effective complex refractive index at a wavelength of 10.6 μm are made on a series of glass and aluminum surfaces of increasing surface roughness. The measured values are then used to calculate the degree of emission polarization and are shown to be in agreement with the experimentally determined values when depolarization is small. Comparisons are also made with calculations based on the Kirchhoff scattering theory. Both the theory and the experimental results indicate that it is the local surface slope and not the roughness magnitude that is the prime factor in determining the degree of emission polarization from the samples studied.     

Integrated diffractive andrefractive elements for spectrum shaping

Diffractive elements can be designed for spectrum shaping in the Fourier or Fresnel plane by iterative methods. It is necessary to use a Fourier lens and the wavelength for which the diffractive elements were designed to get the required spectrum shaping at the Fourier plane. Using a different wavelength will cause chromatic aberration. We deal with the combination of refractive and diffractive elements and two or more different diffractive elements on the same element to get appropriate beam shaping of light sources with a multiple spectral output. Simulations are preformed that transform the profile of a He-Ne laser with a Nd:YAG laser source, and shape the trapezoidal beam profile of an excimer laser into a Gaussian beam is also considered.     

Chemotherapy with the "8 in 1" protocol for malignant brain tumors in children: a population-based study in Finland

We evaluated the outcome of 68 children with malignant brain tumors treated with the "8 in 1" chemotherapy protocol in Finland from 1986 to 1993, comparing 5-year survival rates with those for a historical control group (from 1975 to 1985). For all malignant brain tumors, overall survival was 43% (vs 28% in the control group; P <0.05), and progression-free survival (PFS) was 43% (vs 23%; P <0.05). For medulloblastoma and primitive neuroectodermal tumor, survival was 63% (vs 35%; P <0.05), and the corresponding PFS was 59% (vs 35%; P = 0.15). For high-grade glioma, both the survival rate and the PFS were 27% (vs 17%; P = NS). Thus the outcome was significantly better for our "8 in 1" -treated patients than for the historical controls, especially among the children with primitive neuroectodermal tumor and medulloblastoma. In contrast, those with high-grade gliomas and brain stem tumors seem to have received little benefit; different, more effective treatments are needed for these patients.     

Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin

G protein-coupled receptor kinases (GRKs) are implicated in the homologous desensitization of G protein-coupled receptors. Six GRK subtypes have so far been identified, named GRK1 to GRK6. The functional state of the GRKs can be actively regulated in different ways. In particular, it was found that retinal rhodopsin kinase (GRK1), but not the ubiquitous betaARK1 (GRK2), can be inhibited by the photoreceptor-specific Ca2+-binding protein recoverin through direct binding. The present study was aimed to investigate regulation of other GRKs by alternative Ca2+-binding proteins such as calmodulin (CaM). We found that Gbetagamma-activated GRK2 and GRK3 were inhibited by CaM to similar extents (IC50 approximately 2 microM), while a 50-fold more potent inhibitory effect was observed on GRK5 (IC50 = 40 nM). Inhibition by CaM was strictly dependent on Ca2+ and was prevented by the CaM inhibitor CaMBd. Since Gbetagamma, which is a binding target of Ca2+/CaM, is critical for the activation of GRK2 and GRK3, it provides a possible site of interaction between these proteins. However, since GRK5 is Gbetagamma-independent, an alternative mechanism is conceivable. A direct interaction between GRK5 and Ca2+/CaM was revealed using CaM-conjugated Sepharose 4B. This binding does not influence the catalytic activity as demonstrated using the soluble GRK substrate casein. Instead, Ca2+/CaM significantly reduced GRK5 binding to the membrane. The mechanism of GRK5 inhibition appeared to be through direct binding to Ca2+/CaM, resulting in inhibition of membrane association and hence receptor phosphorylation. The present study provides the first evidence for a regulatory effect of Ca2+/CaM on some GRK subtypes, thus expanding the range of different mechanisms regulating the functional states of these kinases.     

Editorial: Special issue on approximate dynamic programming and reinforcement learning

We are extremely pleased to present this special issue of the Journal of Control Theory and Applications.Approximate dynamic programming (ADP) is a general and effective approach for solving optimal control and estimation problems by adapting to uncertain environments over time.ADP optimizes the sensing objectives accrued over a future time interval with respect to an adaptive control law,conditioned on prior knowledge of the system,its state,and uncertainties.A numerical search over the present value of the control minimizes a Hamilton-Jacobi-Bellman (HJB) equation providing a basis for real-time,approximate optimal control.     

Cooperative adaptive control for synchronization of second‐order systems with unknown nonlinearities

This paper studies synchronization to a desired trajectory for multi‐agent systems with second‐order integrator dynamics and unknown nonlinearities and disturbances. The agents can have different dynamics and the treatment is for directed graphs with fixed communication topologies. The command generator or leader node dynamics is also nonlinear and unknown. Cooperative tracking adaptive controllers are designed based on each node maintaining a neural network parametric approximator and suitably tuning it to guarantee stability and performance. A Lyapunov‐based proof shows the ultimate boundedness of the tracking error. A simulation example with nodes having second‐order Lagrangian dynamics verifies the performance of the cooperative tracking adaptive controller. Copyright © 2010 John Wiley & Sons, Ltd.     

Scan-based volume animation driven by locally adaptive articulated registrations

This paper describes a complete system to create anatomically accurate example-based volume deformation and animation of articulated body regions, starting from multiple in vivo volume scans of a specific individual. In order to solve the correspondence problem across volume scans, a template volume is registered to each sample. The wide range of pose variations is first approximated by volume blend deformation (VBD), providing proper initialization of the articulated subject in different poses. A novel registration method is presented to efficiently reduce the computation cost while avoiding strong local minima inherent in complex articulated body volume registration. The algorithm highly constrains the degrees of freedom and search space involved in the nonlinear optimization, using hierarchical volume structures and locally constrained deformation based on the biharmonic clamped spline. Our registration step establishes a correspondence across scans, allowing a data-driven deformation approach in the volume domain. The results provide an occlusion-free person-specific 3D human body model, asymptotically accurate inner tissue deformations, and realistic volume animation of articulated movements driven by standard joint control estimated from the actual skeleton. Our approach also addresses the practical issues arising in using scans from living subjects. The robustness of our algorithms is tested by their applications on the hand, probably the most complex articulated region in the body, and the knee, a frequent subject area for medical imaging due to injuries.