Archive of Medical Research

Clinical Impact of Drug-eluting Stents in an Unselected Population of Diabetic Patients.

BACKGROUND: Drug-eluting stents (DES) have been shown in randomized trials to reduce clinical events in diabetic patients. Our aim was to determine whether these clinical results are applicable in an unselected population of patients with non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). METHODS: We studied 440 consecutive patients (271 NIDDM and 169 IDDM) who underwent percutaneous coronary intervention, divided into 2 cohorts: Group A (1998-2000): 220 patients with bare metal stents, and Group B (2002-2004): 220 patients with drug-eluting stents. We analyzed major coronary adverse events (death, nonfatal acute myocardial infarction, and target lesion revascularization) over a mean follow-up of 18 +/- 15 months. RESULTS: Group B had more patients who were insulin-dependent (44.5 versus 32.3% p<0.001) or had hypertension (64.5 versus 54.1%; p = 0.02), a lower left ventricular ejection fraction (53.89 versus 56.8%; p = 0.04), more complex lesions (B2/C) (82.7 versus 62.3%; p<0.001), more treated lesions (1.40 versus 1.26; p<0.001), more stents implanted (1.69 versus 1.15; p<0.0001), and more patients treated with abciximab (76.8 versus 42.7%; p<0.0001). During the follow-up, Group B had fewer major adverse coronary events (11.7 versus 27.9%; p<0.001) and a reduction in target lesion revascularization (3.9 versus 17.2%; p<0.001), with no differences in death or myocardial infarction. Both groups experienced a significant reduction in events (NIDDM: 8.1 versus 26.7%; p<0.001 and IDDM: 16 versus 31.9%; p = 0.016). Multivariate regression analysis showed the use of drug-eluting stents to be in direct relation with event-free survival (odds ratio [OR]: 3.37; 95% confidence interval [CI], 1.44-7.90; p = 0.005). CONCLUSION: Despite the worse angiographic characteristics, the use of DES reduced clinical events, particularly target lesion revascularization. Copyright (c) 2008 Wiley Periodicals, Inc.

Domínguez Franco AJ, Alonso Briales JH, Jiménez Navarro MF, Hernández García JM, García Pinilla JM, Pérez Caravante M, De Teresa Galván E.

Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Victoria de Malaga, Fundación IMABIS, Málaga, Spain.

Enhanced External Counterpulsation in the Treatment of Chronic Refractory Angina: A Long-term Follow-up Outcome from the International Enhanced External Counterpulsation Patient Registry.

BACKGROUND: The management of patients who suffer from medically refractory angina and are unsuitable for conventional revascularization therapy is often unsatisfactory. Enhanced external counterpulsation (EECP) is a noninvasive treatment that is safe and effective immediately after a course of treatment. However, the duration of benefit is less certain. HYPOTHESIS: To evaluate the 3-year outcome of EECP treatment. METHODS: One thousand four hundred and twenty seven patients from 36 centers registered in the International EECP Patient Registry (IEPR)-Phase 1 was prospectively followed for a median of 37 months. Two hundred and twenty patients (15.4%) died, while 1,061 patients (74.4%) completed their follow-up. RESULTS: The mean age was 66 +/- 11 years and 72% were men. Seventy-six percent had multivessel coronary disease for 11 +/- 8 years. Eighty-eight percent had a prior percutaneous or surgical revascularization and 82% were unsuitable for further coronary intervention.Immediately post-EECP, the proportion of patients with severe angina (Canadian Cardiovascular Angina Classification [CCS] III/IV) were reduced from 89% to 25%, p<0.001. The CCS class was improved by at least 1 class in 78% of the patients and by at least 2 classes in 38%. This was sustained in 74% of the patients during follow-up.Thirty-six percent of the patients had CCS II or less angina, which was better than pre-EECP state without a major adverse cardiovascular event during follow-up. More severe baseline angina and a history of heart failure or diabetes were independent predictors of unfavorable outcome. CONCLUSION: An EECP improves angina and quality of life immediately after a course of treatment. For most of the patients, these beneficial effects are sustained for 3 years. Copyright (c) 2008 Wiley Periodicals, Inc.

Loh PH, Cleland JG, Louis AA, Kennard ED, Cook JF, Caplin JL, Barsness GW, Lawson WE, Soran OZ, Michaels AD.

Department of Academic Cardiology, University of Hull, Hull Royal Infirmary;

Joint capsule mast cells and neuropeptides are increased within four weeks of injury and remain elevated in chronic stages of posttraumatic contractures.

The purpose of this article was to determine mast cell and neuropeptide nerve fiber numbers in joint capsules in posttraumatic contractures, as elevated numbers have been implicated in other fibrotic and contracture conditions. Twelve skeletally mature rabbits had intraarticular cortical windows removed from the medial and lateral femoral condyles and the knee joint immobilized. The contralateral unoperated limb served as a control. Equal numbers of rabbits were sacrificed 4 weeks after surgery or 40 weeks after the first surgery that included 32 weeks of remobilization. Six patients with chronic posttraumatic elbow joint contractures and six age-matched organ donor controls free of elbow contractures were also studied. Joint capsule myofibroblast, mast cell, and neuropeptide containing nerve fiber numbers were assessed with immunohistochemistry. The numbers of myofibroblasts, mast cells, and neuropeptide containing nerve fibers expressed as a percentage of total cells were significantly greater in the contracture capsules when compared to the control capsules at all time points (p < 0.0001). The range of percentages for the three components in the contracture capsules versus the controls were 41-48% versus 9-10%, 44-50% versus 11-13%, and 45-50% versus 10-12% for the acute and chronic stages of the rabbit model and the chronic stages in the human elbows, respectively. These data support the hypothesis that a myofibroblast-mast cell-neuropeptide fibrosis axis may underlie some of the pathologic changes in the joint capsule in posttraumatic contractures. Approaches designed to manipulate this axis, such as preventing degranulation of mast cells, warrant further investigation. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Hildebrand KA, Zhang M, Hart DA.

McCaig Centre, Bone and Joint Institute, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.

Changes in gene expression of individual matrix metalloproteinases differ in response to mechanical unloading of tendon fascicles in explant culture.

Immobilization of the tendon and ligament has been shown to result in a rapid and significant decrease in material properties. It has been proposed that tissue degradation leading to tendon rupture or pain in humans may also be linked to mechanical unloading following focal tendon injury. Hence, understanding the remodeling mechanism associated with mechanical unloading has relevance for the human conditions of immobilization (e.g., casting), delayed repair of tendon ruptures, and potentially overuse injuries as well. This is the first study to investigate the time course of gene expression changes associated with tissue harvest and mechanical unloading culture in an explant model. Rat tail tendon fascicles were harvested and placed in culture unloaded for up to 48 h and then evaluated using qRT-PCR for changes in two anabolic and four catabolic genes at 12 time points. Our data demonstrates that Type I Collagen, Decorin, Cathepsin K, and MMP2 gene expression are relatively insensitive to unloaded culture conditions. However, changes in both MMP3 and MMP13 gene expression are rapid, dramatic, sustained, and changing during at least the first 48 h of unloaded culture. This data will help to further elucidate the mechanism for the loss of mechanical properties associated with mechanical unloading in tendon. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Leigh DR, Abreu EL, Derwin KA.

Department of Biomedical Engineering and the Orthopaedic Research Center, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195.

Comparison of the healing of open tibial fractures covered with either muscle or fasciocutaneous tissue in a murine model.

The objective of this study was to compare the effects of soft tissue coverage by either muscle or fasciocutaneous tissue on the healing of open tibial fractures in a murine model. An open tibial fracture, stripped of periosteum with intramedullary fixation, was created in mice. Experimental groups were devised to allow exclusive comparison of either muscle alone or skin plus fascia in direct contact with healing bone. To exclusively assess the relative efficacy of muscle and fasciocutaneous tissue to promote healing of a fracture stripped of periosteum, a piece of sterile inert material (polytetrafluoroethylene) was positioned anteriorly, excluding skin and fascia (muscle group) or posteriorly, excluding muscle (fasciocutaneous group). Skeletal repair was assessed histologically and quantified by histomorphometry; quantitative peripheral computed tomography (pQCT) and mechanical testing using a four-point bending technique. This standardized, reproducible model allowed characterization of the morphology of open fracture healing. At 28 days postfracture, there was faster healing in the experimental muscle coverage group compared to skin and fascia alone. Furthermore, there was almost 50% more cortical bone content and a threefold stronger union beneath muscle compared to fasciocutaneous tissue (p < 0.05 by one-way ANOVA). Exclusive comparison of muscle and fasciocutaneous tissue in our novel murine model demonstrates that muscle is superior for the coverage of open tibial fractures for both the rate and quality of fracture healing. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Harry LE, Sandison A, Paleolog EM, Hansen U, Pearse MF, Nanchahal J.

Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, London, United Kingdom.

Complex, multidimensional thumb movements generated by individual extrinsic muscles.

The objective of this study was to investigate three-dimensional thumb joint movements produced by individual extrinsic thumb muscles. Ten cadaveric arms were dissected to expose the musculotendinous junctions of the flexor pollicis longus (FPL), abductor pollicis longus (APL), extensor pollicis brevis (EPB), and extensor pollicis longus (EPL). Each muscle/tendon was loaded to 10% of its maximal force capability whereas three-dimensional angular movements of the carpometacarpal (CMC), metacarpophalangeal (MCP), and interphalangeal (IP) joints were obtained simultaneously. We found that each extrinsic muscle produced unique joint angular trajectories in multiple directions. The FPL, APL, EBP, and EPL generated two, two, three, and six movements, respectively. The extrinsic muscles all together generated eight movements among the multiple thumb joints. High interjoint coordination was shown between the MCP joint flexion and IP joint flexion by FPL loading, as well as between the MCP joint extension and IP joint extension by EPL loading. High intrajoint coordination was observed between extension and supination at the CMC joint by the APL, EPL, and EPB. We concluded that each muscle produces movements in multiple joints and/or in multiple anatomical directions. The findings provide a novel insight into the biomechanical roles of the extrinsic muscles of the thumb. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Li ZM, Tang J, Chakan M, Kaz R.

Hand Research Laboratory, Departments of Orthopaedic Surgery and Bioengineering, University of Pittsburgh, 210 Lothrop Street, E1641 BST, Pittsburgh, Pennsylvania 15213.

Corrigendum.

The response of mineralizing culture systems to microtextured and polished titanium surfaces.

The surface texture of titanium has a predictable effect on peri-implant tissue formation in vivo. When implanted in an osseous environment, smooth surfaces (R(a) < 0.5 mm) are generally apposed by fibrous tissue and textured surfaces (R(a) > 1.0 mm) are generally apposed by osseous tissue. Thus in vitro study assessed the mineralization and proliferation response of TF274, MC3T3-E1, murine femoral stromal cells and canine stromal cells to tissue culture plastic (R(a) = 0.001 mm), polished (R(a) = 0.01 mm) and irregularly textured (R(a) = 3.26 mm) titanium surfaces. Amongst all culture systems, proliferation was significantly decreased on textured vs. smooth surfaces. Midway through the culture of the canine marrow cells, the cell layer detached from the tissue culture plastic and polished titanium surfaces. The TF274, MC3T3-E1, murine femoral stromal cell systems formed a mineralized matrix on the tissue culture plastic and polished titanium surfaces which was not observed with the canine stromal cell system. Compared to the tissue culture plastic and polished titanium surfaces, matrix mineralization was significantly reduced on the textured titanium surfaces for the TF274, MC3T3-E1, murine femoral stromal systems, a result which was differed significantly in comparison to the canine stromal system. These results were surprising given the large number of reports concerning the in vivo response to titanium in clinical and pre-clinical studies. Further work is required to determine if the TF274, MC3T3-E1 and murine femoral stromal systems are suitable for the in vitro investigation of the effects of titanium surface texture on osteoblast activity. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Hacking SA, Harvey E, Roughley P, Tanzer M, Bobyn J.

Jo Miller Orthopaedic Research Laboratory, McGill University, 740 Drive, Penfield, Montreal, Canada H3A 1A4.

Author\’s reply to correspondence from Drs Grant, Garland, and Boucher.

Marshall TG.

School of Biological Sciences and Biotechnology, c/o 3423 Hill Canyon Avenue, Murdoch University, Western Australia.

Physical vapor deposition of zirconium or titanium thin films on flexible polyurethane highly support adhesion and physiology of human endothelial cells.

The aim of this study was to develop and characterize novel metal-polymer constructs to improve the biocompatibility of flexible but hydrophobic polyurethane (PUR) implants. Using a physical vapor deposition (PVD) technique, thin films (</=100 nm) of zirconium (Zr) or titanium (Ti) were deposited on the polyurethane surface. Both coatings displayed good stability when subjected to cross-cutting test and especially Zr showed only minor and superficial cracks in the scanning electron microscopy analysis. PVD coating resulted in significantly lowered contact angles and the standard surface free energy of wetting (Delta(wet)G degrees ) turned to more favorable negative values (Ti: -40; Zr: -30; untreated PUR (uPUR): +10.1 mN/m). This may lead to the highly enhanced adhesion and proliferation properties observed with human umbilical vein endothelial cells (HUVECs). In addition, the novel coatings had no toxic effect and even drastically reduced apoptosis rates of HUVECs. Cell morphology, nitric oxide production, and mitochondrial membrane potential-both at static and flow conditions-were superior compared with uPUR, thus demonstrating intact physiological functions. Therefore, we suggest that combining PUR as a flexible material with a thin coating of Zr or Ti as the improved biocompatible surface may have advantages for use, for example, vascular graft material. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

Ozkucur N, Wetzel C, Hollstein F, Richter E, Funk RH, Monsees TK.

Institute of Anatomy, University of Technology, Dresden, Germany.