The aims of the study were to evaluate whether in situ (on-site) simulation training is associated with increased telemedicine use for patients presenting to rural emergency departments (EDs) with ...severe sepsis and septic shock and to evaluate the association between simulation training and telehealth with acute sepsis bundle (SEP-1) compliance and mortality.
This was a quasi-experimental study of patients presenting to 2 rural EDs with severe sepsis and/or septic shock before and after rollout of in situ simulation training that included education on sepsis management and the use of telehealth. Unadjusted and adjusted analyses were conducted to describe the association of simulation training with sepsis process of care markers and with mortality.
The study included 1753 patients, from 2 rural EDs, 629 presented before training and 1124 presented after training. There were no differences in patient characteristics between the 2 groups. Compliance with several SEP-1 bundle components improved after training: antibiotics within 3 hours, intravenous fluid administration, repeat lactic acid assessment, and vasopressor administration. The use of telemedicine increased from 2% to 5% after training. Use of telemedicine was associated with increases in repeat lactic acid assessment and reassessment for septic shock. We did not demonstrate an improvement in mortality across either of the 2 group comparisons.
We demonstrate an association between simulation and improved care delivery. Implementing an in situ simulation curriculum in rural EDs was associated with a small increase in the use of telemedicine and improvements in sepsis process of care markers but did not demonstrate improvement in mortality. The small increase in telemedicine limited conclusions on its impact.
New therapeutics designed as rescue treatments after toxic gas injury such as from chlorine (Cl2) are an emerging area of interest. We tested the effects of the metalloporphyrin catalytic antioxidant ...AEOL10150, a compound that scavenges peroxynitrite, inhibits lipid peroxidation, and has SOD and catalase-like activities, on Cl2-induced airway injury. Balb/C mice received 100ppm Cl2 gas for 5min. Four groups were studied: Cl2 only, Cl2 followed by AEOL10150 1 and 9h after exposure, AEOL10150 only, and control. Twenty-four hours after Cl2 gas exposure airway responsiveness to aerosolized methacholine (6.25–50mg/ml) was measured using a small-animal ventilator. Bronchoalveolar lavage (BAL) was performed to assess airway inflammation and protein. Whole lung tissue was assayed for 4-hydroxynonenal. In separate groups, lungs were collected at 72h after Cl2 injury to evaluate epithelial cell proliferation. Mice exposed to Cl2 showed a significantly higher airway resistance compared to control, Cl2/AEOL10150, or AEOL10150-only treated animals in response to methacholine challenge. Eosinophils, neutrophils, and macrophages were elevated in BAL of Cl2-exposed mice. AEOL10150 attenuated the increases in neutrophils and macrophages. AEOL10150 prevented Cl2-induced increase in BAL fluid protein. Chlorine induced an increase in the number of proliferating airway epithelial cells, an effect AEOL10150 attenuated. 4-Hydroxynonenal levels in the lung were increased after Cl2 and this effect was prevented with AEOL10150. AEOL10150 is an effective rescue treatment for Cl2-induced airway hyperresponsiveness, airway inflammation, injury-induced airway epithelial cell regeneration, and oxidative stress.
As more and more elderly people are being cared for in residential and nursing homes, how best can their psychiatric needs be met? We report on evaluation of a behavioural intervention by an old-age ...psychiatry hospital outreach team.
This randomised controlled trial of a training and education intervention over 6 months was done in south Manchester, UK. 12 matched nursing and residential homes were randomised to the control or intervention group and within each, the staff selected 10 residents whose behavioural problems made them difficult to care for. Care staff in the intervention homes attended seminars from the hospital outreach team and received weekly visits from a psychiatric nurse to assist in developing care planning skills. The main outcome measures were cognitive impairment and depression, behavioural disturbance, and functional ability, assessed by the geriatric mental state schedule, Crichton Royal behaviour rating scale, and Barthel index, respectively.
Residents in the intervention group had significantly improved scores for depression (before-and-after change difference −0·5 95% CI −0·8 to −0·1) and for cognitive impairment (−0·7 −1·1 to −0·2) but not for behaviour rating or Barthel index.
Elderly residents can benefit from improved quality of care achieved by training from a hospital outreach team.
Allelotype of gastric adenocarcinoma YUSTEIN, A. S; HARPER, J. C; PETRONI, G. R ...
Cancer research (Chicago, Ill.),
04/1999, Letnik:
59, Številka:
7
Journal Article
Recenzirano
Gastric adenocarcinoma is a leading cause of cancer mortality world-wide. Yet, the underlying molecular events important in the development of this cancer are largely undefined. Thus, we performed a ...comprehensive survey for allelic loss on our panel of xenografted human gastric carcinomas. Contaminating normal stromal cells of primary cancers often limit mutational analyses. Xenografted samples of our gastric carcinomas provided optimally enriched tumors for neoplasia that clearly and sensitively demonstrated genetic alterations. Additionally, total absence of allelic signals in these xenografted samples confirmed true loss of alleles rather than just allelic imbalance. Analysis of at least two highly polymorphic microsatellite markers per nonacrocentric chromosomal arm in our xenografted human gastric carcinomas demonstrated significant loss of heterozygosity well above background levels at 3p, 4p, 5q, 8p, 9p, 13q, 17p, and 18q. Several of these loci represent novel findings of significant loss in gastric cancers. On chromosome 17p, p53 is known to be inactivated either by mutation or deletion in a majority of gastric carcinomas. The critical target(s) of inactivation in gastric cancers at these other loci remain to be characterized.
A multigenic trait (biosynthesis of the secondary metabolite, dhurrin cyanogenic glucoside) was engineered de novo in grapevine (Vitis vinifera L.). This follows a recent report of transfer of the ...same trait to Arabidopsis (Arabidopsis thaliana) using three genetic sequences from sorghum (Sorghum bicolor): two cytochrome P450-encoding cDNAs (CYP79A1 and CYP71E1) and a UDPG-glucosyltransferase-encoding cDNA (sbHMNGT). Here we describe the two-step process involving whole plant transformation followed by hairy root transformation, which was used to transfer the same three sorghum sequences to grapevine. Transgenic grapevine hairy root lines that accumulated transcript from none, one (sbHMNGT), two (CYP79A1 and CYP71E1) or all three transgenes were recovered and characterisation of these lines provided information about the requirements for dhurrin biosynthesis in grapevine. Only lines that accumulated transcripts from all three transgenes had significantly elevated cyanide potential (up to the equivalent of about 100 mg HCN kg(-1) fresh weight), and levels were highly variable. One dhurrin-positive line was tested and found to release cyanide upon maceration and can therefore be considered 'cyanogenic'. In in vitro dual co-culture of this cyanogenic hairy root line or an acyanogenic line with the specialist root-sucking, gall-forming, aphid-like insect, grapevine phylloxera (Daktulosphaira vitifoliae, Fitch), there was no evidence for protection of the cyanogenic plant tissue from infestation by the insect. Consistently high levels of dhurrin accumulation may be required for this to occur. The possibility that endogenous grapevine gene expression is modulated in response to engineered dhurrin biosynthesis was investigated using microarray analysis of 1225 grapevine ESTs, but differences in patterns of gene expression associated with dhurrin-positive and dhurrin-negative phenotypes were not identified.
Eleven species of billbugs (Coleoptera: Dryophthoridae: Sphenophorus spp. Schönherr) infest managed turfgrass in North America. However, the regional variation in species composition remains ...unresolved and the seasonal phenology of several species has not been well documented.The latter gap is largely due to the inability to identify the larval stage to species—a confounding problem with several sympatric insect species. We used field trapping (adults) and soil sampling (larvae and pupae) surveys along with a DNA-based life-stage association to characterize the biology of billbugs associated with turfgrass in the Midwestern United States. Pitfall trapping at four locations in Indiana revealed four billbug species: S. venatus Say, S. parvulus Gyllenhaal, S. minimus Hart, and S. inaequalis Say. Sphenophorus venatus was the most abundant species on warm-season turfgrass while S. parvulus was most abundant on cool-season turfgrass. Investigation of S. venatus seasonal biology revealed two overwintered life stages—larva and adult—which resulted in two overlapping cohorts and two larval generations. Degree-day models describing S. venatus activity were more accurate for first-generation adults and larvae than for overwintering life stages. Maximum-likelihood analyses provided the first molecular species identification of billbug larvae and direct evidence that S. venatus larvae are capable of overwintering above 40°N latitude. Findings clarify the utility of molecular markers (CO1, 18S, and ITS2) for describing billbug larval population dynamics and seasonal phenology in regions where several sympatric billbug species occur. These results support the development of sustainable management strategies based on billbug seasonal phenology in different regions of North America.
Background
rVIII‐SingleChain, a novel recombinant factor VIII (rFVIII), has been designed as a B‐domain truncated construct with covalently bonded heavy and light chains, aiming to increase binding ...affinity to von Willebrand factor (VWF). Preclinical studies confirmed greater affinity for VWF, giving improved pharmacokinetic and pharmacodynamic properties compared with full‐length rFVIII.
Aim
To investigate the pharmacokinetics of rVIII‐SingleChain and compare them against those of full‐length rFVIII.
Methods
This study enrolled 27 patients with severe haemophilia A in the AFFINITY clinical trial programme. After a 4‐day washout period, all patients received a single infusion of 50 IU kg−1 octocog alfa (Advate®); after a ≥4‐day postinfusion washout period, they received a single infusion of 50 IU kg−1 rVIII‐SingleChain. Blood samples for pharmacokinetic assessments of each product were collected before infusion (predose) and at 0.5, 1, 4, 8, 10, 24, 32, 48 and 72 h postinfusion for both products.
Results
rVIII‐SingleChain had a longer mean half‐life (t1/2) (14.5 vs. 13.3 h), lower mean clearance (CL) (2.64 vs. 3.68 mL h−1 kg−1), higher mean residence time (20.4 vs. 17.1 h) and larger mean AUCinf (2090 vs. 1550 IU?h dL−1) than octocog alfa, respectively. The mean AUCinf after rVIII‐SingleChain infusion was ~35% larger than after octocog alfa. A similar pattern was observed for AUC0‐last. No serious adverse events or inhibitors were reported.
Conclusions
rVIII‐SingleChain has a favourable pharmacokinetic profile compared with octocog alfa and was well tolerated. The prolonged t1/2, larger AUC and reduced CL of rVIII‐SingleChain may permit longer dosing intervals, thereby improving patient adherence to prophylactic treatment.
There is increasing evidence that proinflammatory products of the 5-lipoxygenase pathway play an important role in cardiovascular disease. In the present study, we found that human endothelial cells ...rapidly oxidize the 5-lipoxygenase product 5
S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), a potent chemoattractant for myeloid cells. 5-Oxo-ETE synthesis is strongly stimulated by oxidative stress. This effect is enhanced following inhibition of the pentose phosphate pathway with dehydroepiandrosterone and is mimicked by diamide, which oxidizes intracellular GSH to GSSG. Conversely, it is blocked by depletion of intracellular GSH/GSSG. The kinetics of H
2O
2-induced 5-oxo-ETE synthesis by endothelial cells correlate well with changes in the intracellular levels of GSSG and NADP
+. These results suggest that exposure of the endothelium to oxidative stress and inflammation could result in the synthesis of 5-oxo-ETE, which could then induce the infiltration of inflammatory cells into the tissue.
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