Effect of intravenous streptokinase as compared with that of tissue plasminogen activator on left ventricular function after first myocardial infarction

In a double-blind trial comparing two thrombolytic agents as treatment for acute myocardial infarction, we randomized 270 consecutive patients an average (+/- SD) of 2.5 +/- 0.6 hours after the onset of chest pain from a first myocardial infarction--135 to receive intravenous streptokinase (1.5 million units over 30 minutes) and 135 to receive intravenous recombinant tissue plasminogen activator (rt-PA) (100 mg over three hours). The primary end point was left ventricular function as assessed by cineangiography performed three weeks after infarction. The effects of the two agents on left ventricular function were similar. The ejection fraction was identical (58 +/- 12 percent) in both groups. The end-systolic volume was 61 +/- 29 ml in the streptokinase group and 66 +/- 31 ml in the rt-PA group (P not significant). Patency rates at three weeks for the infarct-related artery were also similar (75 percent in the streptokinase group and 76 percent in the rt-PA group). Reinfarction rates at 30 days were the same (5 percent) in both groups. One patient had a fatal intracerebral hemorrhage 13 hours after receiving rt-PA, and another had a fatal cerebellar hemorrhage 21 hours after receiving rt-PA for reinfarction nine days after treatment with streptokinase. An intention-to-treat analysis revealed that mortality at 30 days was 3.7 percent in the rt-PA group as compared with 7.4 percent in the streptokinase group (P greater than 0.2). Follow-up for a mean of 9.0 months revealed no significant difference in survival; we observed 12 deaths (8.9 percent) in the streptokinase group and 8 deaths (5.9 percent) in the rt-PA group (P = 0.34). We conclude that rt-PA and streptokinase, in the doses given, have similar effects on left ventricular function after a first myocardial infarction. Because of the small number of deaths, it is not possible to determine whether their effects on mortality are similar.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.