Confronting system barriers for ST- elevation MI in low and middle income countries with a focus on India

© 2017 Our previous research found seven specific factors that cause system delays in ST-elevation Myocardial infarction management in developing countries. These delays, in conjunction with a lack of organized STEMI systems of care, result in inefficient processes to treat AMI in developing countries. In our present opinion paper, we have specifically explored the three most pertinent causes that afflict the seven specific factors responsible for system delays. In doing so, we incorporated a unique strategy of global STEMI expertise. With this methodology, the recommendations were provided by expert Indian cardiologist and final guidelines were drafted after comprehensive discussions by the entire group of submitting authors. We expect these recommendations to be utilitarian in improving STEMI care in developing countries

Regional Systems of Care Demonstration Project: American Heart Association Mission: Lifeline STEMI Systems Accelerator.

BACKGROUND: Up to 50% of patients fail to meet ST-segment-elevation myocardial infarction (STEMI) guideline goals recommending a first medical contact-to-device time of <90 minutes for patients directly presenting to percutaneous coronary intervention-capable hospitals and <120 minutes for transferred patients. We sought to increase the proportion of patients treated within guideline goals by organizing coordinated regional reperfusion plans. METHODS: We established leadership teams, coordinated protocols, and provided regular feedback for 484 hospitals and 1253 emergency medical services (EMS) agencies in 16 regions across the United States. RESULTS: Between July 2012 and December 2013, 23 809 patients presented with acute STEMI (direct to percutaneous coronary intervention hospital: 11 765 EMS transported and 6502 self-transported; 5542 transferred). EMS-transported patients differed from self-transported patients in symptom onset to first medical contact time (median, 47 versus 114 minutes), incidence of cardiac arrest (10% versus 3%), shock on admission (11% versus 3%), and in-hospital mortality (8% versus 3%; P<0.001 for all comparisons). There was a significant increase in the proportion of patients meeting guideline goals of first medical contact-to-device time, including those directly presenting via EMS (50% to 55%; P<0.001) and transferred patients (44%-48%; P=0.002). Despite regional variability, the greatest gains occurred among patients in the 5 most improved regions, increasing from 45% to 57% (direct EMS; P<0.001) and 38% to 50% (transfers; P<0.001). CONCLUSIONS: This Mission: Lifeline STEMI Systems Accelerator demonstration project represents the largest national effort to organize regional STEMI care. By focusing on first medical contact-to-device time, coordinated treatment protocols, and regional data collection and reporting, we were able to increase significantly the proportion of patients treated within guideline goals

Association of Rapid Care Process Implementation on Reperfusion Times Across Multiple ST-Segment–Elevation Myocardial Infarction Networks

BACKGROUND: The Mission: Lifeline STEMI Systems Accelerator program, implemented in 16 US metropolitan regions, resulted in more patients receiving timely reperfusion. We assessed whether implementing key care processes was associated with system performance improvement. METHODS AND RESULTS: Hospitals (n=167 with 23 498 ST-segment-elevation myocardial infarction patients) were surveyed before (March 2012) and after (July 2014) program intervention. Data were merged with patient-level clinical data over the same period. For reperfusion, hospitals were grouped by whether a specific process of care was implemented, preexisting, or never implemented. Uptake of 4 key care processes increased after intervention: prehospital catheterization laboratory activation (62%-91%; P<0.001), single call transfer protocol from an outside facility (45%-70%; P<0.001), and emergency department bypass for emergency medical services direct presenters (48%-59%; P=0.002) and transfers (56%-79%; P=0.001). There were significant differences in median first medical contact-to-device times among groups implementing prehospital activation (88 minutes implementers versus 89 minutes preexisting versus 98 minutes nonimplementers; P<0.001 for comparisons). Similarly, patients treated at hospitals implementing single call transfer protocols had shorter median first medical contact-to-device times (112 versus 128 versus 152 minutes; P<0.001). Emergency department bypass was also associated with shorter median first medical contact-to-device times for emergency medical services direct presenters (84 versus 88 versus 94 minutes; P<0.001) and transfers (123 versus 127 versus 167 minutes; P<0.001). CONCLUSIONS: The Accelerator program increased uptake of key care processes, which were associated with improved system performance. These findings support efforts to implement regional ST-segment-elevation myocardial infarction networks focused on prehospital catheterization laboratory activation, single call transfer protocols, and emergency department bypass

Structural requirements of iodothyronines for the rapid inactivation and internalization of type II iodothyronine 5\u27-deiodinase in glial cells

3,3\u275,5\u27-Tetraiodothyronine (T4), but not 3,3\u275-triiodothyronine (T3), acutely regulates the activity of the plasma membrane-bound enzyme, type II iodothyronine 5\u27-deiodinase (5\u27D-II), by inducing internalization of the enzyme through an extranuclear, energy-dependent mechanism that requires an intact actin cytoskeleton. The affinity label, N-bromoacetyl-L-T4, binds to 5\u27D-II and irreversibly inhibits the enzyme but does not initiate internalization. To determine the structural elements of T4 which are required for enzyme internalization, T4 analogs were modified in the alanine side chain and were then evaluated for their ability to induce enzyme internalization, to inhibit enzyme activity, and to promote actin polymerization in hypothyroid cells. The analogs studied showed marked variability in their ability to inactivate 5\u27D-II. The rank order of potency for enzyme inactivation was T4 \u3e COOH-blocked analogs \u3e NH3 and COOH blocked analogs \u3e\u3e NH3 blocked analogs (EC50 values range from 1 to \u3e 1000 nM). In contrast, all T4 analogs tested and T4 were excellent competitive inhibitors of 5\u27D-II with respect to substrate (Ki values ranged from 4 to 27 nM). The differential capability of iodothyronines to inactivate the enzyme was not related to their ability to enter the cell, since Ki values measured in intact glial cells were equivalent to those measured in cell sonicates. The power of the T4 analogs to inactivate 5\u27D-II was paralleled by their ability to polymerize actin in hypothyroid cells and to induce 5\u27D-II binding to F-actin. The data show that modification of the alanine side chain markedly alters the ability of T4 analogs to induce 5\u27D-II inactivation and actin polymerization. A net negative charge on the alanine side chain of T4 is detrimental for the hormone-dependent inactivation of 5\u27D-II and polymerization of actin, whereas uncharged or positively charged molecules retain significant activity

Intranasale Schutzimpfung gegen die Pasteurellose der Kaelber: Klinische Pruefung und Antikoerpernachweis im Nasenschleim mit dem ELISA

Available from: Zentralstelle fuer Agrardokumentation und -information (ZADI), Villichgasse 17, D-53177 Bonn / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Affinity labeling of rat liver and kidney type I 5\u27-deiodinase. Identification of the 27-kDa substrate binding subunit

Extrathyroidal production of 3,3\u27,5-triiodothyronine from the thyroid secretory product, thyroxine, is catalyzed by tissue-specific iodothyronine 5\u27-deiodinases. Type I 5\u27-deiodinase (5\u27D-I) produces greater than 75% of the T3 found in the circulation and in thyroid hormone-responsive tissues and is most abundant in rat liver and kidney. In this study, we used the bromoacetyl derivatives of T4 (N-bromoacetyl-[125I]L-thyroxine, BrAcT4) and T3 (N-bromoacetyl-[125I]3,3\u27,5-triiodothyronine, BrAcT3) as alkylating affinity labels to identify 5\u27D-I-related protein(s). BrAcT4 and BrAcT3 rapidly and irreversibly inactivated 5\u27D-I activity in liver and kidney microsomes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of affinity labeled 5\u27D-I preparations showed that approximately 80% of the affinity label was incorporated into a protein with a Mr of 27,000 (p27). 5\u27D-I substrates and inhibitors specifically blocked affinity labeling of p27 with a rank order of potency (BrAcT4 greater than BrAcT3 greater than 3,5,3\u27-triiodothyronine (rT3) approximately flavone EMD 21388 greater than iodoacetate greater than N-acetyl-T4 (NAcT4) greater than N-acetyl-T3 (NAcT3] identical to that determined for inhibition of 5\u27-deiodination. Hyper- and hypothyroidism-induced increases and decreases in 5\u27D-I activity, respectively, were matched by comparable changes in the quantity of affinity labeled p27. BrAcT3 was a less effective affinity label for p27 and minor labeling of a new band with 53 kDa was observed. Molecular sieve chromatography of detergent-solubilized 5\u27D-I showed coincident peaks of p27 and 5\u27-deiodinating activity with an apparent Mr approximately 51,000. Two-dimensional gel electrophoresis showed that p27 was a single polypeptide with a pI of 6.1. Approximately 2-5 pmol of p27 were present per mg of liver microsomal protein, equal to previous estimates for 5\u27D-I content. Our results suggest that p27 represents the substrate binding subunit of type I 5\u27-deiodinase, the enzyme catalyzing the key reaction in the activation of T4 to the thyromimetically active T3