Impending Necrosis Research Articles

Using biomarkers to assess risk and consider treatment strategies in non-ST-segment elevation acute coronary syndromes

Since the first biomarker of myocardial necrosis was described in 1954, cardiac-specific biomarkers have been increasingly identified. This, coupled with dramatic evolution in assay technology and resultant highly sensitive assays, has rendered a remarkable transformation in the medical use of biomarkers. Initially used to aid in diagnosis of myocardial infarction, newer biomarkers of inflammation, plaque instability, and ischemia may complement biomarkers of necrosis by providing tools to diagnose impending myocardial necrosis before irreversible damage occurs, and offering additional information for risk stratification. Importantly, biomarkers of different processes may be combined to enhance risk stratification above that of any single marker.

Routine revascularization with resection of infected femoral pseudoaneurysms from substance abuse

Infected femoral artery pseudoaneurysms in narcotic addicts present challenging management options. Our policy of routine revascularization is based on the concern that a high rate of amputations must follow ligation and resection alone or with selective delayed revascularization. Fifteen of 16 patients with infected pseudoaneurysms of femoral arteries, treated with resection and bypass grafts, were observed from 1 to 44 months. Obturator bypass grafts were used in 10 patients, iliac-femoral grafts in three, axillopopliteal in one, and right external iliac crossover to left popliteal in one patient. One limb, unsalvageable at presentation, was amputated primarily, along with resection of pseudoaneurysm and femoral artery ligation, without bypass grafting. One iliac-femoral graft became infected and then thrombosed 4 months after operation. Unsuitable distal arteries and impending necrosis led to above-knee amputation. One late failure among 15 revascularization attempts (7%) is significantly lower than the 11% to 33% amputation rates reported in the literature with resection of pseudoaneurysm alone and delayed selective revascularization. The other 14 patients had functioning limbs without claudication or rest pain. Our experience indicates that revascularization at the time of resection of infected pseudoaneurysm offers better prospects for limb salvage.

Sequestration hypothesis of atherosclerosis.

Atherosclerosis of the human aorta has been studied by morphometric, chemical, and histochemical methods. Results of these separate approaches are converging upon a theory of pathogenesis. This theory begins with the standard view of a two stage process, intimal fibroplasia followed by atheronecrosis in the most thickened and aged places. The first stage, fibroplasia, can be described in terms of a stochastic process wherein smooth muscle cells, scattered in accordance with a Poison distribution, elaborate matrix materials over time, causing the realms of the cells to expand and to aggregate. The fusion of the expanded smooth muscle cell realms seems to mark the advent of necrosis. The second stage, atheronecrosis, can be described such that the probability of a necrotic core emerging at a site in a vessel is governed by the amount and the age of interstitial matrix materials at the site. Further evidence shows that the matrix materials tend to sequester lipids in greater than proportionate amounts as the intimal bulk increases. The sequestered perifibrous lipid is histochemically different from the lipids of the necrotic core, in that only the latter can be fixed with chromic acid. These results suggest that lipids undergo a qualitative change as well as a quantitative increase at the stage of impending necrosis. This qualitative change is governed by age, which raises the possibility that necrotizing toxicity accumulates in the sequestered lipid as it ages.

Interlaboratory evaluation of salicylate interference in colorimetric acetaminophen methods and its clinical significance.

Serum specimens with concentrations simulating an overdose of salicylate and acetaminophen were submitted to laboratories participating in an external quality-control program, to evaluate both the magnitude of salicylate interference in colorimetric acetaminophen methods and the clinical significance of the interference. The apparent acetaminophen concentration determined by nitration methods was increased by about 0.70 mg/L per milligram of salicylate per deciliter. Of those laboratories using nitration procedures, 25% do not routinely correct for salicylate and 66% use the (incorrect) correction factor provided by a kit manufacturer. Laboratory data, as they would have been reported to physicians, were used to estimate the acetaminophen half-life and were also applied to a nomogram used to assess the probability of hepatotoxicity. Interference by salicylate in the simulated overdose of 10 g (total dose) of each drug falsely indicated impending hepatic necrosis unless the appropriate correction factor was used. Laboratories using nitration procedures should screen samples submitted for acetaminophen assay for the presence of salicylate and, if present, either use a method specific for acetaminophen or utilize a correction factor determined in-house.