Retrieval of Additional Doses of Epinephrine From the New Teva Epinephrine Autoinjector Pen.

Epinephrine autoinjectors are commonly used in urban environments for anaphylaxis. In remote environments, the effects of a single dose of epinephrine may diminish before one can access higher medical care. By retrieving additional epinephrine from common autoinjectors, a medical provider may be able to treat or delay decompensation of anaphylaxis in the field during evacuation. The new Teva epinephrine autoinjectors were obtained. The design of the mechanism was researched by studying patents and disassembling trainers and medication-containing autoinjectors. Multiple methods of access were tried to find the quickest, most reliable method that required minimal tools or equipment. A quick, reliable method of removing the injection syringe from the autoinjector using a knife was determined, as outlined in this article. The syringe plunger had a security design to prevent dispensing further doses from the syringe, so a long narrow object is also required to dispense additional doses. There are 4 additional doses of approximately 0.3-mg epinephrine in these Teva autoinjectors. Prior knowledge of epinephrine equipment and the devices that may be encountered in the field is important for providing life-saving medical care. The ability to retrieve additional doses of epinephrine from a used autoinjector can provide additional life-saving medication while evacuating to a higher level of medical care. This method does carry risks to rescuers and patients; however, it can potentially be life saving.

Point-of-Care Ultrasound Transmission for Remote Interpretation in Austere Environments.

INTRODUCTION: Point-of-care ultrasound (POCUS) is used in wilderness medicine and could potentially be the only imaging modality available. Cellular and data coverage is often lacking in remote areas, limiting image transmission. This study evaluates the viability of transmitting POCUS images from austere environments using slow-scan television (SSTV) image transmission methods over very-high-frequency (VHF) hand-held radio units for remote interpretation. METHODS: Fifteen deidentified POCUS images were selected and encoded into an SSTV audio stream by a smartphone and transmitted over a VHF radio. A second radio and smartphone 1 to 5 mi away received and decoded the signals back into images. The original images and transmitted images were randomized into a survey graded by emergency medicine physicians using a standardized ultrasound quality assurance scoring scale (1-5 points). RESULTS: The difference in mean scores between the original image and transmitted image showed a 3.9% decrease in transmitted image scores, with P <0.05 on a paired t test; however, this is not likely a clinically significant decrease. Comparing transmitted images using different SSTV encodings and distances ranging up to 5 mi, 100% of survey respondents determined the images to be clinically usable. This dropped to 75% when significant artifacts were introduced. CONCLUSIONS: Slow-scan television image transmission is a viable option for transmitting ultrasound images in remote areas where more modern forms of communication are unavailable or not practical. Slow-scan television may have potential as another data transmission option in the wilderness, such as electrocardiogram tracings.

Photoproduction of the f_{2}(1270) Meson Using the CLAS Detector.

The quark structure of the f_{2}(1270) meson has, for many years, been assumed to be a pure quark-antiquark (qq[over ¯]) resonance with quantum numbers J^{PC}=2^{++}. Recently, it was proposed that the f_{2}(1270) is a molecular state made from the attractive interaction of two ρ mesons. Such a state would be expected to decay strongly to final states with charged pions due to the dominant decay ρ→π^{+}π^{-}, whereas decay to two neutral pions would likely be suppressed. Here, we measure for the first time the reaction γp→π^{0}π^{0}p, using the CEBAF Large Acceptance Spectrometer detector at Jefferson Lab for incident beam energies between 3.6 and 5.4 GeV. Differential cross sections, dσ/dt, for f_{2}(1270) photoproduction are extracted with good precision due to low backgrounds and are compared to theoretical calculations.

Socializing the evidence for diabetes control to develop "mindlines": a qualitative pilot study.

BACKGROUND: Evidence on specific interventions to improve diabetes control in primary care is available, but this evidence is not always well-implemented. The concept of "mindlines" has been proposed to explain how clinicians integrate evidence using specifics of their practices and patients to produce knowledge-in-practice-in-context. The goal of this pilot study was to operationalize this concept by creating a venue for clinician-staff interaction concerning evidence. The research team attempted to hold "mindlines"-producing conversations in primary care practices about evidence to improve diabetes control. METHODS: Each of four primary care practices in a single health system held practice-wide conversations about a simple diabetes intervention model over a provided lunch. The conversations were relatively informal and encouraged participation from all. The research team recorded the conversations and took field notes. The team analyzed the data using a framework adapted from the "mindlines" research and noted additional emergent themes. RESULTS: While most of the conversation concerned barriers to implementation of the simple diabetes intervention model, there were examples of practices adopting and adapting the evidence to suit their own needs and context. Performance metrics regarding diabetes control for the four practices improved after the intervention. CONCLUSION: It appears that the type of conversations that "mindlines" research describes can be generated with facilitation around evidence, but further research is required to better understand the limitations and impact of this intervention.

Native aphids of New Zealand--diversity and host associations.

At least 15 species of aphids are now recognised as New Zealand natives and most of these are very likely to be endemic. Most native aphids belong in the subfamily Aphidinae (Aphidini), with a possible single species in Aphidinae-Macrosiphini, at least two in Neophyllaphidinae and one in Taiwanaphidinae. With one exception, native aphids are restricted to a single host plant genus, and these hosts are from 13 genera and 12 plant families in the Pinales and Angiospermae-Eudicotyledonae, suggesting that the aphids are a remnant fauna. No known native aphids have host plants from the Pteridophyta or Angiospermae-Monocotyledonae, with the possible exception of two possibly native species extracted from native tussock grassland turfs. Most host plant genera have some degree of Gondwanan distribution, but only two indigenous species are found on large forest trees and only one host is deciduous. Native aphids have been recorded from sea level to the subalpine zone, reflecting their host plant distributions. Sexual reproduction, followed by several parthenogenetic generations on the same host plant, appears to be the norm for most species. Eggs appear to be used for surviving winter conditions in some species and summer conditions in others. Native aphid distribution and abundance varies with five species considered to be scarce, one species localised, two species sparse and three relatively common based on current knowledge.

Chromosomal position mediates spinal cord expression of a dbx1a enhancer.

Dbx homeodomain proteins are important for the production of multiple spinal cord cell types. To examine the regulation of Dbx genes in more detail, we have generated transgenic zebrafish in which fluorescent protein expression is driven by predicted dbx1a enhancers. We identified three areas of sequence conservation upstream of the dbx1a coding sequence and generated fluorescent reporter constructs driven by these predicted enhancer elements and the endogenous dbx1a promoter. In multiple stable insertions of a 3.5-kb enhancer fragment, we observed that there was additional reporter expression in the dorsal spinal cord not normally observed by dbx1a in situ hybridization. In addition, these lines exhibited only transient reporter expression, unlike the endogenous gene. Surprisingly, a single insertion line expressed the reporter in the endogenous pattern, indicating that other local regulatory elements modulate gene expression through the 3.5-kb enhancer.

Protein metabolism in the developing brain: influence of birth and gestational age.

Incorporation of carbon-14-labeled phenylalanine into brain protein of newborn pigs falls sharply within 24 hours after birth. This decrease is related to the time of birth rather than the gestational age of the piglets, although the latter is also associated with a gradual decrease in brain protein synthesis.

Differential inhibition of F0F1-ATPase-catalysed reactions in bovine-heart submitochondrial particles by organotin compounds.

Preincubation of coupled submitochondrial particles with low concentrations of triorganotin compounds results in complete inhibition of the oligomycin-sensitive ATPase activity without any significant effect on the rate of succinate-driven ATP synthesis. The residual ATP synthetic activity is inhibited by oligomycin and uncouplers. The differential inhibition of ATP synthesis and hydrolysis by the triorganotin compounds examined suggests that the two processes are not 'mirror images' of each other, but that they occur through different routes and that the F1F0-ATPase is at least bifunctional.

The terminal respiratory chain of the methylotrophic bacterium Methylophilus methylotrophus.

Cytochrome oxidase o has been isolated from the obligately aerobic, methylotrophic bacterium Methylophilus methylotrophus in the form of a cytochrome cL-o complex. The latter is comprised of cytochrome cL (Mr 21 000) and cytochrome o (Mr 29 000) in a 1-2:1 ratio, possibly in association with one or more minor polypeptides; the complex exhibits a high ascorbate-TMPD oxidase activity which is inhibited non-competitively by cyanide (Ki approximately 2 microM). In contrast, the oxidation of methanol by whole cells is inhibited uncompetitively by cyanide (Ki approximately 4 microM), thus indicating the involvement in methanol oxidation of cytochrome oxidase aa3 rather than o.

Serum-free in vitro bioassay for the detection of tumor necrosis factor.

A sensitive, reproducible in vitro bioassay is described for quantitating the cytolytic activity of tumor necrosis factor (TNF). The assay target cells, murine connective tissue L-M, are propagated and the assay performed under serum-free conditions. The quantitation of cytolytic activity is based on the ability of TNF to lyse L-M cells in the presence of actinomycin D, as measured by crystal violet dye uptake of residual viable cells. The assay is sensitive to 88 pg/ml TNF-alpha. The simplicity of the culture medium combined with high sensitivity and low variability make this a particularly well-suited bioassay for routine detection of TNF cytolytic activity.

Effect of rabbit anti-human thymocyte globulin on lymphocyte subpopulations and functions following allotransplantation in the rhesus monkey.

The survival time of skin allografts from RhLA-nonidentical, unrelated donors was increased from a mean of 7.69 days in controls (n = 20) to a mean of 32.53 days in rhesus monkeys (n = 21) receiving a total dose of 250 mg of rabbit anti-human thymocyte globulin (RATG) per kg. Immunological monitoring studies were performed on the peripheral blood of mononuclear cells in control and treated monkeys. After administration of RATG, the percentage of E rosette-forming cells (E-RFC) was greater than 90% depressed, and the percentage of EAC rosette-forming cells was increased 5-fold in the circulation. Significant numbers of RATG-coated cells were detected only during the first week after RATG treatment. The percentage of E-RFC recovered to pretreatment levels within 3 to 4 weeks after RATG treatment, although the absolute E-RFC count remained depressed for 2 to 3 months. In addition, the in vitro proliferative responsiveness to polyclonal mitogens and to allogeneic lymphocytes remained greater than 80% depressed for 2 to 3 months after RATG treatment. The incidence of post-transplant-specific antidonor lymphocyte-mediated cytotoxicity (LMC) was similar in controls (85%) and RATG-treated monkeys (81%), and the appearance of LMC was correlated (r = 0.711) with partial recovery of absolute ERFC counts in the treated group. The appearance and peak of LMC were delayed (P less than 0.001) in RATG-treated monkeys, but preceded and correlated with rejection. Prior to rejection, the serum of RATG-treated monkeys inhibited LMC. Antibody-dependent cellular cytotoxicity appeared after rejection in the majority of recipients in both groups. The appearance and peak of antibody-dependent cell-mediated cytotoxicity (ADCC) were delayed (P less than than 0.001) in RATG-treated monkeys, but did not exhibit a significant correlation with the time of rejection.

Promotion of incompatible allograft acceptance in rhesus monkeys given posttransplant antithymocyte globulin and donor bone marrow. I. In vivo parameters and immunohistologic evidence suggesting microchimerism.

This report extends previous studies demonstrating that prolonged acceptance of incompatible kidney allografts in rhesus monkeys can be achieved by a short recipient rabbit antithymocyte globulin (RATG) treatment course followed by donor bone marrow infusion on day 12 without a requirement for chronic immunosuppression. Serial studies of antilymphocyte cyctotoxic antibody in recipients' sera following RATG injections showed pan-lymphocyte-reactive antibody present until day 10 posttransplant. On days 11 and 12, pan-lymphocyte-reactive antibody was no longer detectable, but cytotoxic antibody specific for mature T cells remained in recipients' sera. These findings might explain the critical time relationship between antithymocyte globulin treatment and donor bone marrow infusion, and further suggest that the tolerance-promoting cell in donor bone marrow is not a mature T cell, but rather a pre-T or a non-T cell. Finally, it was found that this treatment protocol resulted in development of lymphoid nodules in the transplanted kidney that express a CD8-positive, FcIgG-receptor-positive phenotype and appear to be of donor origin. The possibility of a veto cell type of mechanism is discussed as an explanation for the promotion of allograft acceptance in this model.

Promotion of incompatible allograft acceptance in rhesus monkeys given posttransplant antithymocyte globulin and donor bone marrow. II. Effects of adjuvant immunosuppressive drugs.

Previous studies from this laboratory demonstrated prolonged acceptance of MHC-mismatched kidney allografts in rhesus monkeys treated with posttransplant rabbit antithymocyte globulin (RATG)* and donor-specific bone marrow (DBM). Here we have investigated the effect of adjunctive immunosuppressive drugs on induction of allogeneic unresponsiveness in this primate model. Parameters examined included median kidney allograft survival time (MST), development of specific antidonor T lymphocyte-mediated cytotoxicity (LMC) and antidonor antibody-dependent cellular cytotoxicity (ADCC). Posttransplant infusion of DBM in RATG-treated kidney allograft recipients resulted in 70 days MST and a dramatic reduction in the incidence of antidonor LMC. However, development of antidonor ADCC was similar to that of RATG controls, suggesting an immune deviation or split tolerance in these animals. Adjunctive azathioprine did not have a beneficial effect in recipients given RATG & DBM, resulting in decreased MST and increased antidonor LMC responses. In contrast, adjunctive cyclosporine (CsA) and low-dose prednisone (P) exerted an additive immunosuppressive effect resulting in a 50% increase in MST and no detectable antidonor LMC. However, CsA & P appeared to enhance the humoral alloimmune response, increasing the incidence of recipients with antidonor ADCC. Long-term graft survival in this group was limited by chronic rejection and especially by CsA-associated toxicity. These studies point out deterrents and also directions for optimizing adjunctive immunosuppression in primates treated with posttransplant RATG & DBM. The results with CsA are relatively encouraging. However, the prevalence of alloantibody and of chronic rejection in these animals suggests that more homogeneous success with tolerance induction in this model may require adjunctive immunosuppressive strategies that reduce humoral immunity.

The development of a posttransplant TLI treatment strategy that promotes organ allograft acceptance without chronic immunosuppression.

The effectiveness of fractionated TLI in promoting allograft tolerance without chronic drug therapy is well established experimentally. TLI has not been widely applied in clinical transplantation, largely due to logistic and medical limitations of pretransplant TLI conditioning. Potential use of posttransplant TLI (PT-TLI) has not been critically evaluated. In this study we investigated PT-TLI in combination with rabbit antithymocyte globulin (RATG) in the absence of chronic immunosuppressive drugs as a strategy for inducing long-term kidney allograft acceptance. Recipients were studied with and without infusion of DR-CD3- donor bone marrow cells (DBMC). Normal rhesus monkeys, which received no pretransplant treatment, underwent bilateral intrinsic nephrectomy and splenectomy at the time of transplantation. RATG was administered daily for 3-5 consecutive days beginning on day 0. A total dose of 500-625 cGy of fractionated TLI was given in 4-5 treatments at 125 cGy per day beginning on day +1. Whereas neither PT-TLI nor RATG monotherapy induced long-term graft acceptance in splenectomized recipients, the combination of these modalities was remarkable in promoting long-term allograft acceptance without immunosuppressive drug therapy. Of 4 recipients given RATG x 5, splenectomy and PT-TLI, all were free of acute rejection. Of these, 3/4 had graft survivals greater than 100 days, 2/4 were greater than 150 days and 1/4 greater than 365 days. Of 5 recipients given this treatment plus an infusion of DR-CD3-DBMC, 4/5 grafts survived greater than 150 days and 3/5 still have normal functioning grafts at greater than 365 days. PT-TLI accentuated and prolonged changes in PBL subpopulations that were initially affected by RATG. Depressed levels of CD3+ cells were present for 4-5 months, with large numbers of circulating CD4+CD3- and especially CD8+ CD3- cells. In addition, antibody responses to RATG and alloantigens were suppressed in PT-TLI-treated recipients. Overall, the combination of PT-TLI, splenectomy, and RATG was found to be effective in promoting long-term allograft acceptance without chronic immunosuppressive drug therapy. The infusion of DR-CD3- DBMC in recipients treated with PT-TLI, RATG and splenectomy appeared to further increase the incidence of stable long-term survivors. If infectious complications can be improved, this approach may provide a clinically applicable posttransplant treatment strategy for inducing functional allograft tolerance.

Interpretation of serum total calcium: effects of adjustment for albumin concentration on frequency of abnormal values and on detection of change in the individual.

Serum total calcium was measured in 1693 patients during a four-month period. We examined the effects of adjustment for albumin concentration on the interpretation of single measurements of serum total calcium and on the variation of series of measurements in individual patients. Markedly abnormal total calcium concentrations--2.75 mmol/l (11.0 mg/100 ml) or more, or 2.00 mmol/l (8.0 mg/100 ml) or less--were found in 115 patients, but only 24 (21%) remained markedly abnormal after adjustment for albumin. Three patients, two with malignant disease and one with primary hyperparathyroidism, had significant hypercalcaemia which was masked by hypoalbuminaemia. The serum total calcium measured on a subsequent occasion had changed 0.15 mmol/l (0.6 mg/100 ml) or more in 60 patients, but after adjustment for albumin this number was reduced to 27 (45%). The within-person standard deviation for serum total calcium was calculated in 26 patients with normal mean adjusted calcium concentrations who had had six or more sequential measurements. The mean standard deviation was 0.148 mmol/1 (0.59 mg/100 ml) and, after adjustment for albumin, this was reduced to 0.100 mmol/1 (0.40 mg/100 ml). We conclude that adjustment of serum total calcium concentration for albumin is essential to detect abnormal values and to assess changes in a value.

Filicidal behavior: behavioral correlates and role of sensory systems.

The administration of para-chloro-D,L-phenylalanine (PCPA) produces a high incidence of filicidal (pup-killing) behavior in female rodents. The present series of experiments determined the major behavioral, sensory, and temporal correlates of filicidal behavior in nulliparous adult Sprague-Dawley female rats. In Experiment 1, behavioral episodes involving the interaction of test pups and PCPA-induced filicidal females were videotaped, and subsequent analyses of behaviors related to locating, carrying, mauling, attacking, gnawing, and consuming the prey object were performed. Analysis indicated that the primary behavioral correlates in the PCPA animals included location, initiation of the attack (mauling), and killing of the pup (filicide). Only location was observed in control animals. Experiment 2 evaluated the effects of sensory impairments on location, mauling, and filicide. Sensory impairment occurred at 24 days of age for enucleation and 62 days of age for olfactory bulbectomies and/or auditory destruction. Animals were injected either at 110 or 130 days of age with PCPA for three consecutive days and tested for filicide for five additional days. Locating of the test pup was not affected by sensory impairment. Mauling was reduced significantly in the enucleation/auditory destructed animals. Filicide was significantly lower in animals with visual/auditory destruction, and, compared to controls, was reduced in all sensory impaired groups.

Altered pharmacokinetics of antibiotics during vascular surgery.

Prophylactic antibiotics significantly decrease the incidence of infection in various surgical procedures. Although antibiotics must be administered preoperatively to be effective, it is unknown whether therapeutic concentrations are necessary throughout the operation to prevent infection. Furthermore, the pharmacokinetics of antibiotics during surgical procedures is not well understood. Several factors, including blood loss, fluid redistribution, and changes in renal blood flow may alter the pharmacokinetic disposition of the antibiotic. In a controlled investigation of intraoperative antibiotic pharmacokinetics, cefamandole was studied in eight patients undergoing elective surgery of the abdominal aorta and peripheral vasculature. Both elimination half-life (67 +/- 19 minutes versus 93 +/- 23 minutes) and the volume of distribution (16.8 +/- 5.3 liters versus 25.2 +/- 11.9 liters) increased when compared with the preoperative state. The increased volume may be due, in part, to redistribution of fluid. Plasma concentrations of antibiotic were low at the time of graft placement in those patients with normal renal function. Additional antibiotic dosing may be warranted prior to prosthesis insertion in these patients.

A physiologically relevant pharmacokinetic model of xenobiotic percutaneous absorption utilizing the isolated perfused porcine skin flap.

A physiologic pharmacokinetic model describing percutaneous absorption of topically applied compounds in the isolated perfused porcine skin flap (IPPSF) is presented. As an extension of a previously reported hybrid physiologically relevant compartmental model of uptake of intra-arterially administered drug in the IPPSF, this percutaneous model should allow experimental results obtained from an in vitro preparation to serve as quantitative input to an in vivo pharmacokinetic system. Model parameters estimated from 8-10-h IPPSF experiments were able to predict 6-day in vivo radiolabel absorptions in pigs for topically applied benzoic acid, caffeine, malathion, parathion, DFP, testosterone, and progesterone. These results compare favorably with those obtained previously using a classical compartmental modeling approach.

para-Chloro-D, L-phenylalanine induced filicidal behavior in the female rat.

The administration of para-chloro-D, L-phenylalanine (PCPA) produces a high incidence of aggressive (filicidal) behavior in pre-, postpartum, and nulliparious rodents. PCPA inhibits brain tryptophan 5-monooxygenase and can produce a reduction in whole brain serotonin. Apparently PCPA mediates the release of a natural latent aggressive tendency which is potentiated by the interference in, or reduction of, a suppressing system governed by serotonin. Latency of attack, intensity phases, and characteristics of the filicidal behavior were found to vary inversely with brain serotonin content, and be reversed or eliminated by replacement of serotonin i.e., via 5-hydroxytryptophan, serotonin's immediate precursor. Although aggressive tendencies were in evidence prior to filicide, filicide became evident once the apparently minimal whole brain level of serotonin reached ca 0.10 microgram/g. Neither the parturition process nor severe food deprivation are strong causative factors in the precipitation of filicidal behavior. Since not all animals become filicidal, other behavioral and/or biological variables must be involved in the mediation of this aggressive phenomenon.

Arachidonic acid release: an in vitro alternative for dermal irritancy testing.

Validated in vitro alternatives are being utilized extensively for mutagenicity and ocular irritancy testing. However, validation of alternative assays for dermal irritancy is progressing more slowly. As the irritant response in human skin is mediated, at least in part, by eicosanoids derived from arachidonic acid, the effect of relatively pure anionic surfactants (AS, n=8) and surfactant-containing finished products (FP, n=25) on the release of [3H]arachidonic acid from a prelabelled murine fibroblast cell line (C3H-10T1/2 cells) in vitro was examined. Test substances were administered at various non-lethal concentrations, in triplicate, to 12- and 24-well plates containing preconfluent monolayers (80-90% confluence) of C3H-10T1/2 cells. Because it is impossible to test all concentrations of each test substance in a single assay, statistical techniques were developed to 'standardize' in vitro assay results. In each assay, radiolabel release due to a positive control was also measured, using 0.04, 0.05 and 0.06 mM concentrations of sodium dodecyl sulfate (SDS). Test substance releases were then transformed into 'SDS equivalent' responses, significantly reducing both inter- and intra-assay variability. A straight line was fitted to the test substance responses and compared with that for SDS to calculate the relative potency in vitro for individual AS and FP. Relative potencies correlated with in vivo responses, that is primary dermal irritation indices obtained in rabbits, with Spearman p=0.408 (P<0.03) for 32 tested agents, and p=0.976 (P<0.001) for the eight AS. Exclusion of extremely alkaline or acidic FP (pH>11 or <2, n=4) and those which were insoluble in the aqueous cell culture media at the 1% stock dilution (n=5), improved the overall in vivo-in vitro correlation significantly (p=0.683, P<0.001, n=23) and produced a significant correlation for FP alone (p=0.539, P<0.05, n=15). These results suggest that release of [3H]arachidonic acid from cultured skin cells represents a novel, mechanistically based in vitro screen for dermal irritancy testing.