The response of myocardial lactate and hypoxanthine metabolism during percutaneous transluminal coronary angioplasty was studied in a series of 15 patients undergoing this procedure. A minimum of 4 balloon inflations was performed per patient with an average duration per occlusion of 49 ± 11 seconds (mean ± standard deviation) for a total occlusion time of 192 ± 40 seconds. Thermodilution coronary venous blood flow measured in the great cardiac vein decreased from control values of 72 ± 4 ml/min (mean ± standard error of the mean) to 47 ± 10 ml/min with the fourth coronary occlusion (p < 0.005). Arteriovenous lactate and hypoxanthine showed peak differences during the reactive hyperemia after the first 2 occlusions which did not increase after subsequent occlusions. Within minutes after the procedure, lactate and hypoxanthine efflux was no longer seen, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent alteration in lactate or hypoxanthine metabolism after percutaneous transluminal coronary angioplasty with 4 coronary occlusions of 40 to 60 seconds' duration, with a total occlusion time of 192 ± 40 seconds.
Inflammatory bowel disease (IBD) is characterized by periods of relapse and remission. Treatment is aimed at reducing symptoms during relapse and prolonging the duration of remissions. 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are commonly used to prolong clinical remissions. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are two widely used laboratory markers of inflammation. The authors observed an unexplained discordance between ESR and CRP in children with asymptomatic IBD who were being treated with AZA or 6-MP.To characterize children with IBD in remission treated with 6-MP or AZA who have persistently elevated ESR but normal CRP.All patients seen in Pediatric Gastroenterology Clinic between January 1, 1995, and December 31, 2002, with Crohn disease or ulcerative colitis who received AZA or 6-MP continuously for at least 6 months were identified and their medical records reviewed.One hundred twenty patients met the eligibility criteria. Twelve had an ESR >18 mm/hour on at least three occasions during at least 12 consecutive months with a simultaneous CRP <0.8 mg/dL. Eleven of these 12 had no signs or symptoms of active disease and had Pediatric Crohn Disease Activity Index scores <10 for at least 12 consecutive months while the ESR was elevated. Disease duration was similar in the 11 children with asymptomatic disease and with discordant ESR and CRP and in 108 children with concordant ESR and CRP (69.2 + 22.5 months v 54.3 +/- 40.1 months, P = 0.0709). Duration of AZA or 6-MP therapy was greater in the 11 children with asymptomatic disease and discordant ESR and CRP than in those with or without symptoms and with concordant ESR and CRP (58.1 +/- 16.4 months v 36.6 +/- 24.1 months, P = 0.0043). There were no differences between the groups with respect to diagnosis, location of disease, or age at onset of symptoms. The mean corpuscular volume (MCV) was somewhat larger in the children with discordant ESR and CRP than in the children with concordant ESR and CRP (91.4 +/- 6.97 fL v 87.0 +/-7.07 fL, respectively, P = 0.0373); however, in both groups, the MCV was in the normal range. There were no significant differences in hematocrit, white blood cell count, serum albumin, total serum protein, or estimated serum globulin between the groups.The results suggest that among children treated with AZA or 6-MP, CRP may be a more reliable indirect indicator of inflammation than ESR. This report alerts clinicians that some children taking AZA or 6-MP may have persistent elevation of the ESR with a normal CRP and have no clinical evidence of active disease.
Asthma is characterized by the expression of multiple genes for inflammatory proteins, such as cytokines, enzymes, receptors and adhesion molecules. This is orchestrated by transcription factors, which are proteins that bind to the promoter regions of these genes and may be activated by inflammatory stimuli, such as cytokines. Several transcription factors are involved in asthmatic inflammation, including nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), nuclear factor of activated T-cells (NF-AT), cyclic AMP response element binding protein (CREB) and signal transduction-activated transcription factors (STAT). These transcription factors lead to coordinated expression of multiple inflammatory genes. There is increasing evidence that synergistic interaction of these transcription factors (e.g. NF-kappaB and AP-1) results in the optimal expression of particular genes, resulting in the specific inflammatory pattern seen in asthmatic airways. Transcription factors are a target for antiasthma therapy. Corticosteroids activate glucocorticoid receptors, which themselves are transcription factors, and interact with other transcription factors to inhibit their actions. The interaction between transcription factors may be important in amplifying and inhibiting the inflammatory process. Many transcription factors interact with a large co-activator molecule CREB-binding protein (CBP) that coordinates the activation of several transcription factors and controls transcription through the regulation of deoxyribonucleic acid coiling around histone residues in the chromatin structure. Understanding transcription factors in asthma has given new insights into the complex chronic inflammatory process, the mechanism of action of corticosteroids, and may lead to new approaches to therapy in the future.
Procedures given in Eurocode 3 Part 1.1 (EN 1993-1-1) for design of the main types of structural member under given systems of loading are presented and described. Whereas some of these e.g. the procedure for axially loaded columns, are little changed from the early concept that appeared more than 25 years ago in the European Recommendations and have subsequently been adopted in many other steel codes of the world, others such as the interaction formulae for beam-columns are new, with aspects of the provisions still under development. For each type of member the basis of the procedure is described and some comparative comments made.
In September 1986, I had the privilege to implant the first endoluminal prosthesis (wall stent), as we called the stent at that time, in our first patient in Rotterdam just a few months after the pioneering cases of Jacques Puel in Toulouse and Ulrich Sigwart in Lausanne. In 1986, there was not yet an official Ethics Committee established at the Thoraxcenter, and it was only with the blessing of the chairman of cardiology and the permission of Paul Hugenholtz and with the support of the chief of surgery Egbert Bos that I was allowed to implant the first stent. Following the implantation, I performed an angioscopy, as it was available in Europe at that time. I was shocked by the vision of the shiny metal embedded in this delicate structure that is a human coronary artery. I felt guilty to have introduced in that very delicate biological structure such a rough device as a self-expanding stent. Honestly, I left the cath-lab with a tremendous feeling of guiltiness, having the impression that I had carried out something irreversible that would leave this human coronary artery caged forever. As ominously predicted by our chief surgeon… by the third case, I experienced my first stent thrombosis despite extensive platelet antiaggregation and anticoagulation with aspirin, heparin, warfarin, persantine and reomacrodex. On the same, day I started to reflect on the fact whether it could be possible to scaffold a vessel without using a permanent metallic implant to keep the vessel largely patent.
