Citations

Pregnancy-associated plasma protein-A (PAPP-A) increases local IGF-I bioavailability through cleavage of inhibitory IGF binding protein (IGFBP)-4 in a variety of systems, including the cardiovascular system. To test the hypothesis that expression of PAPP-A promotes the development of atherosclerotic lesions, we generated transgenic mice that express human PAPP-A in arterial smooth muscle. Four founder lines were characterized for transgenic human PAPP-A mRNA and protein expression, IGFBP-4 protease activity, and tissue specificity. In study I, apolipoprotein E knockout (ApoE KO) mice, a well-characterized mouse model of atherosclerosis, and ApoE KO mice expressing the human PAPP-A transgene at relatively high levels (ApoE KO/Tg) were fed a high-fat diet. At harvest, aortas were dissected and opened longitudinally for en face staining of lipid-rich lesions. Lesion area was increased 3.5-fold in aortas from ApoE KO/Tg compared with ApoE KO mice ( P < 0.001), but no significant difference was seen in lesion number. In study II, replacement of PAPP-A expression in arterial smooth muscle of double ApoE KO/PAPP-A KO mice resulted in a 2.5-fold increase in lesion area ( P = 0.002), without an effect on lesion number. PAPP-A transgene expression was associated with a significant increase in an IGF-responsive gene ( P < 0.001), suggesting increased local IGF-I action. We therefore conclude that expression of human PAPP-A localized to arterial smooth muscle accelerates lesion progression in a mouse model of atherosclerosis. These data provide further evidence for the importance of PAPP-A in the cardiovascular system and suggest PAPP-A as a potential therapeutic target in the control of atherosclerosis.

Abstract A recent report indicated significant interference of naproxen with total bilirubin measurement when using the Jendrassik and Grof method. We explored the possibility of avoiding this interference by using a different method. We observed that naproxen has no effect on total bilirubin measurement by any method, but O-desmethylnaproxen (the naproxen metabolite) interfered significantly with total bilirubin assays using the Jendrassik and Grof method (Beckman Coulter [Brea, CA] and Siemens [Tarrytown, NY] bilirubin method). The Roche (Indianapolis, IN) bilirubin assay based on a different method was not affected. When serum samples of 9 patients receiving naproxen were analyzed for total bilirubin level, we observed good correlation in total bilirubin values measured by all 3 methods in 7 of 9 patients with therapeutic naproxen concentrations. In contrast, in 2 patients with elevated naproxen levels, the total bilirubin values observed by using the Beckman and Siemens methods were significantly higher than the value obtained by the Roche assay. The naproxen metabolite interferes with assays based on the Jendrassik and Grof method but not with the Roche bilirubin assay.

We retrospectively reviewed the first 14 patients who received preoperative paravertebral blockade prior to minimally invasive cardiac surgical procedures. The use of paravertebral blockade along with an anesthetic technique designed to facilitate rapid recovery allowed early extubation in the operating room or intensive care unit in all but one patient. Extubated patients leaving the operating room were comfortable. No postoperative respiratory complications occurred.