Periods of differing mortality distribution during the first year after acute myocardial infarction

The mortality rate after acute myocardial infarction (AMI) has generally been modeled by a single exponential function. The present study was undertaken to determine, in 3 different populations, whether or not periods exist during the first year after AMI which have mortality distributions that differ from this pattern. The 3 patient populations included San Diego (346 patients, 71 deaths), Vancouver (704 patients, 146 deaths), and Copenhagen (1,140 patients, 262 deaths). Hospital admission was within 24 hours of the onset of symptoms, and patients dying within the first 24 hours after hospital admission or of noncardiac or unknown causes were not analyzed. The mortality between 2 and 21 days in the combined data base was 11.4% (range 10.9 to 11.7) and from 3 weeks to 1 year 10.5% (range 9.0 to 11.3). A high degree of similarity was noted among the shapes of the 3 survival curves. The hypothesis of an exponential mortality rate during the entire first year was rejected. Using a special statistic, changepoints at days 17,23, and 24 in the 3 populations (21 days for the combined data base) were identified and used thereafter to divide the year into 2 separate periods of mortality within which exponentiality for the mortality rate was not rejected. The point by which exactly 50% of deaths had occurred was day 19, with 75% of deaths occurring by day 100. These data further define the natural history after AMI and indicate optimal follow-up periods for short- and longer-term management strategies based on risk assessment or trials of risk reduction after AMI.     

Endoscopic evaluation of the effect of indomethacin capsules and suppositories on the gastric mucosa in rheumatic patients

Twelve patients with rheumatic diseases took part in a 6-week double-blind crossover trial comparing 14 days of oral with 14 days of rectal indomethacin treatment, 50 mg 3 X /day, with a 14-day placebo period. The patients had a gastroscopic and a proctoscopic examination after each of the 3 periods. The gastric acid production, serum concentrations and the 24-h urine excretion of indomethacin was measured. Both indomethacin capsules and suppositories caused an equal amount of gastric damage, indicating that the irritative effect of indomethacin on the gastric mucosa is not a local effect, but due to a systemic effect of indomethacin. Although the suppositories caused some mucus discharge no mucosal damage was found by proctoscopy.     

A novel suture method to place and adjust peripheral nerve catheters

We have developed a peripheral nerve catheter, attached to a needle, which works like an adjustable suture. We used in‐plane ultrasound guidance to place 45 catheters close to the femoral, saphenous, sciatic and distal tibial nerves in cadaver legs. We displaced catheters after their initial placement and then attempted to return them to their original positions. We used ultrasound to evaluate the initial and secondary catheter placements and the spread of injectate around the nerves. In 10 cases, we confirmed catheter position by magnetic resonance imaging. We judged 43/45 initial placements successful and 42/43 secondary placements successful by ultrasound, confirmed in 10/10 cases by magnetic resonance imaging.     

Induction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity to nonsteroid antiinflammatory drugs

The transformed monocyte/macrophage cell line J774.2 undergoes apoptosis when treated for 48 h with competitive inhibitors of cyclooxygenase (COX) isoenzymes 1 and 2. Many of these nonsteroid antiinflammatory drugs (NSAIDs), but in particular diclofenac, induce during this time period a COX activity that coincides with a robust induction of COX-2 protein. Induction of this activity requires high, apoptosis-inducing concentrations of diclofenac (>100 microM). Prolonged treatment of J774.2 cells with lower doses of diclofenac inhibits COX activity, indicating that diclofenac is a time-dependent, pseudoirreversible inhibitor of COX-2. It is difficult to wash out the inhibition. However, the activity evoked by high concentrations of diclofenac has a profoundly distinct COX active site that allows diclofenac, its inducer, to be washed readily from its active site. The diclofenac-induced activity also has the unusual property of being more sensitive to inhibition by acetaminophen (IC50 = 0.1-1.0 mM) than COX-2 induced with bacterial lipopolysaccharide. Moreover, relative to COX-1 or COX-2, diclofenac-induced enzyme activity shows significantly reduced sensitivity to inhibition by diclofenac or other competitively acting nonsteroid antiinflammatory drugs (NSAIDs) and the enzyme activity is insensitive to aspirin. If the robust induction of COX-2 observed is responsible for diclofenac-induced COX enzyme activity, it is clear that COX-2 can, therefore, exist in two catalytically active states. A luciferase reporter-construct that contains part of the COX-2 structure and binds into the membrane showed that chronic diclofenac treatment of fibroblasts results in marked mobilization of the fusion protein. Such a mobilization could result in enzymatically distinct COX-2 populations in response to chronic diclofenac treatment.