Management and in-hospital outcome of patients with acute myocardial infarction admitted to intensive care units at the turn of the century: results from the French nationwide USIC 2000 registry.

OBJECTIVE: To assess actual practices and in-hospital outcome of patients with acute myocardial infarction on a nationwide scale. METHODS: Of 443 intensive care units in France, 369 (83%) prospectively collected data on all cases of infarction (within < 48 hours of symptom onset) in November 2000. RESULTS: 2320 patients (median age 68 years, 73% men) were included, of whom 83% had ST segment elevation infarction (STEMI). Patients without STEMI were older and had a more frequent history of cardiovascular disease. Median time to admission was 5.0 hours for patients with and 6.5 hours for those without STEMI. Reperfusion therapy was used for 53% of patients with STEMI (thrombolysis 28%, primary angioplasty 25%). In-hospital mortality was 8.7% (5.5% of patients without and 9.3% of those with STEMI). Multivariate analysis found that age, Killip class, lower blood pressure, higher heart rate on admission, anterior location of infarct, STEMI, diabetes mellitus, previous stroke, and no current smoking independently predicted in-hospital mortality. At hospital discharge, 95% received antiplatelet agents, 75% received beta blockers, and over 60% received statins. Angiotensin converting enzyme inhibitors were prescribed for 40% of the patients without and 52% of those with ST elevation. CONCLUSIONS: This nationwide registry, including all types of centres irrespective of their size and experience, shows continued improvement in patient care and outcomes. Time from symptom onset to admission, however, has not improved in recent years and reperfusion therapy is used for just over 50% of patients with STEMI, with an increasing use of primary angioplasty.

The molecular basis of the human serum paraoxonase activity polymorphism.

The organophosphate cholinesterase inhibitor paraoxon is hydrolysed by serum paraoxonase/arylesterase. A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning. We demonstrate that arginine at position 192 specifies high activity PON whereas a glutamine specifies the low activity variant. Allele-specific probes or restriction enzyme analysis of amplified DNA allow for the genotyping of individuals. PON maps to chromosome 7q21-22, proximal to the cystic fibrosis gene, in agreement with previous genetic linkage studies.

Defective gamma subunit of ATP synthase (F1F0) from Escherichia coli leads to resistance to aminoglycoside antibiotics.

A strain of Escherichia coli which was derived from a gentamicin-resistant clinical isolate was found to be cross-resistant to neomycin and streptomycin. The molecular nature of the genetic defect was found to be an insertion of two GC base pairs in the uncG gene of the mutant. The insertion led to the production of a truncated gamma subunit of 247 amino acids in length instead of the 286 amino acids that are present in the normal gamma subunit. A plasmid which carried the ATP synthase genes from the mutant produced resistance to aminoglycoside antibiotics when it was introduced into a strain with a chromosomal deletion of the ATP synthase genes. Removal of the genes coding for the beta and epsilon subunits abolished antibiotic resistance coded by the mutant plasmid. The relationship between antibiotic resistance and the gamma subunit was investigated by testing the antibiotic resistance of plasmids carrying various combinations of unc genes. The presence of genes for the F0 portion of the ATP synthase in the presence or absence of genes for the gamma subunit was not sufficient to cause antibiotic resistance. alpha, beta, and truncated gamma subunits were detected on washed membranes of the mutant by immunoblotting. The first 247 amino acid residues of the gamma subunit may be sufficient to allow its association with other F1 subunits in such a way that the proton gate of F0 is held open by the mutant F1.

Escherichia coli mutants defective in the uncH gene.

Plasmids carrying cloned segments of the unc operon of Escherichia coli have been used in genetic complementation analyses to identify three independent mutants defective in the uncH gene, which codes for the delta subunit of the ATP synthetase. Mutations in other unc genes have also been mapped by this technique. ATPase activity was present in extracts of the uncH mutants, but the enzyme was not as tightly bound to the membrane as it was in the parental strain. ATP-dependent membrane energization was absent in membranes isolated from the uncH mutants and could not be restored by adding normal F1 ATPase from the wild-type strain. F1 ATPase prepared from uncH mutants could not restore ATP-dependent membrane energization when added to wild-type membranes depleted of F1. Membranes of the uncH mutants were not rendered proton permeable as a result of washing with low-ionic-strength buffer.