ABSTRACT
BACKGROUND: Thrombolytic therapy improves mortality in acute myocardial infarction especially in those who receive treatment early. Pre-hospital therapy can reduce the time to treatment. METHODS: Open, randomized study of patients with acute myocardial infarction of less than six hours duration in a rural community. Pre-hospital thrombolysis was administered using a mobile coronary care unit (MCCU) and all patients received IV streptokinase. RESULTS: Two-hundred and forty-eight patients were studied, 82 in the MCCU and 166 in the hospital group. The mean delay time to treatment was 136 minutes (MCCU group) and 196 minutes (hospital group) (p < 0.001). Reperfusion time was 116 minutes for the MCCU group and 118 minutes for the hospital group. Mortality at 30 days was 4.9% for the MCCU group and 15.7% for the hospital group (p = 0.014). Mortality at one year was 9.8% for the MCCU group and 23.5% for the hospital group (p = 0.009). Mortality for patients followed up to five years was 17.7% for the MCCU group and 35.2% for the hospital group (p = 0.005). There were no significant adverse events in either treatment group. CONCLUSION: Pre-hospital thrombolysis by MCCU is feasible and allows significant reduction in the delay time to treatment initiation. There are encouraging improvements in short- and long-term survival with no apparent reduction in safety profile.
Subject(s)
Home Care Services , Hospitals, General , Mobile Health Units , Myocardial Infarction/drug therapy , Thrombolytic Therapy , Adult , Aged , Cardiac Care Facilities , Catchment Area, Health , Coronary Care Units , Feasibility Studies , Female , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Reperfusion , Rural Population , Streptokinase/therapeutic useABSTRACT
The extracellular globular domain of the mumps virus fusion (F) protein (amino-acids 28-481) has been overexpressed from GS115 his4 Pichia pastoris cells following the generation of a recombinant clone. The heterologous protein was directed for secreted expression by in-frame cloning with the S. cerevisiae alpha-factor secretion signal. The expressed protein was observed to secrete into the culture medium. An expressing clone was obtained initially by small-scale induction, metabolic labeling and immunoprecipitation. Expression analysis of the chosen clone was confirmed by western blotting with F protein specific polyclonal serum. The effects of culture volume, temperature and methanol concentration on the levels of expression, were studied. The results indicate that there is a balance required between the induction temperature and methanol concentration to achieve maximal expression. In addition, the presence of designated monomeric (47 K), dimeric (85-90 K) and trimeric (140 K) forms are dependent upon the induction conditions. Estimated secreted protein expression levels of > 1 mg/L were obtained in these studies. Further, the experiments demonstrate that the complete reconstruction of the KEX2 protease cleavage site is not necessary to facilitate secretion.
Subject(s)
Mumps virus/genetics , Pichia/genetics , Viral Fusion Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Blotting, Western , Chlorocebus aethiops , Cloning, Molecular , Methanol/pharmacology , Molecular Sequence Data , Pichia/metabolism , Precipitin Tests , Protein Structure, Tertiary , Temperature , Transformation, Genetic , Vero Cells , Viral Fusion Proteins/metabolismABSTRACT
In order to assess the feasibility and outcome of using prehospital thrombolysis in acute myocardial infarction in a rural community, we performed an open randomized study of patients with symptoms of acute myocardial infarction of less than 6 hours. One hundred and forty-five patients with acute myocardial infarction were allocated to receive IV streptokinase prehospital by means of a mobile coronary care unit (MCCU) (n = 43) or to receive IV streptokinase in hospital (n = 102). The mean delay time to treatment was 138 minutes (MCCU group) and 172 minutes (hospital group) (p less than 0.02). Reperfusion time was 88 minutes for the MCCU group and 92 minutes for the hospital group. Mortality at 14 days was 2.3% for the MCCU group and 11.7% for the hospital group (p less than 0.05). Six month mortality was 4.9% for the MCCU group and 17.3% for the hospital group (p = 0.03). Mortality at 1 year was 6.1% for the MCCU group and 20.0% for the hospital group (p = 0.04). There were no significant adverse events in either treatment group. Thus, prehospital thrombolysis by streptokinase is feasible and allows significant reduction in the delay time to treatment initiation. There are encouraging improvements in both short- and long-term survival with no apparent reduction in safety profile.
