Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine.
J Am Coll Cardiol. 2009 Sep 8; 54(11): 1014-23Leor J, Tuvia S, Guetta V, Manczur F, Castel D, Willenz U, Petneházy O, Landa N, Feinberg MS, Konen E, Goitein O, Tsur-Gang O, Shaul M, Klapper L, Cohen SOBJECTIVES: This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). BACKGROUND: Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. METHODS: We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. RESULTS: Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 +/- 0.1 mm vs. 1.9 +/- 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. CONCLUSIONS: Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.
Single-port laparoscopic totally extraperitoneal inguinal hernia repair with the TriPort system: initial experience.
Surg Endosc. 2009 Sep 3; Agrawal S, Shaw A, Soon YBACKGROUND: Since the early 1990s, the laparoscopic approach to inguinal hernia repair using three ports has gained increased popularity worldwide. Recently, single-incision laparoscopic surgery to reduce the invasiveness of traditional laparoscopy further is under development. This study aimed to assess the safety and feasibility of the single-port approach for laparoscopic totally extraperitoneal (TEP) repair of inguinal hernia and to report the authors' initial experience using the TriPort system. METHODS: Between 18 October 2008 and 1 April 2009, 19 single-incision laparoscopic TEP repairs of inguinal hernia were performed for 16 patients at the Royal Surrey County Hospital, Guildford, United Kingdom. Data regarding patient demographics, type of hernia, operating time, complications, postoperative hospital stay, and recurrence were prospectively collected. The length of the incision at the time of the operation and at a clinic follow-up visit also was measured. RESULTS: All 16 patients were men, ranging in age from 21 to 87 years. Of the 16 men, 13 had a unilateral inguinal hernia. For 7 of the 13 men, the hernia was on the left side. The median operating time was 40 min for unilateral hernia and 70 min for bilateral hernia. There were no intraoperative complications and no deaths. Discharge was on the same day for 12 of the men, and within 24 h for the remaining 4 men. Minor wound complications developed for two men. One man reported transient pain in his testicle. There was no evidence of early recurrence during a median follow-up period of 72.5 days. The median incision length was 30 mm, and the median scar length at the clinic follow-up visit was 25 mm. CONCLUSION: The authors' experience has shown that single-port laparoscopic TEP inguinal hernia repair with the TriPort system is safe and feasible. Prospective randomized studies comparing single-access and conventional multiport laparoscopic TEP repairs with long-term follow-up evaluation are needed to confirm the authors' initial experience.
Probing vocal fold fibroblast response to hyaluronan in 3D contexts.
Biotechnol Bioeng. 2009 Jun 8; Munoz-Pinto DJ, Jimenez-Vergara AC, Gelves LM, McMahon RE, Guiza-Arguello V, Hahn MSA number of treatments are being investigated for vocal fold (VF) scar, including designer implants. The aim of the present study was to validate a 3D model system for probing the effects of various bioactive moieties on VF fibroblast (VFF) behavior toward rational implant design. We selected poly(ethylene glycol) diacrylate (PEGDA) hydrogels as our base-scaffold due to their broadly tunable material properties. However, since cells encapsulated in PEGDA hydrogels are generally forced to take on rounded/stellate morphologies, validation of PEGDA gels as a 3D VFF model system required that the present work directly parallel previous studies involving more permissive scaffolds. We therefore chose to focus on hyaluronan (HA), a polysaccharide that has been a particular focus of the VF community. Toward this end, porcine VFFs were encapsulated in PEGDA hydrogels containing consistent levels of high M (w) HA (${rm HA}_{{rm H}{M}_{rm W} } $), intermediate M(w) HA (${rm HA}_{{rm I}{M}_{rm W} } $), or the control polysaccharide, alginate, and cultured for 7 and 21 days. ${rm HA}_{{rm H}{M}_{rm W} } $ promoted sustained increases in active ERK1/2 relative to ${rm HA}_{{rm I}{M}_{rm W} } $ . Furthermore, VFFs in ${rm HA}_{{rm I}{M}_{rm W} } $ gels displayed a more myofibroblast-like phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in ${rm HA}_{{rm H}{M}_{rm W} } $ and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to ${rm HA}_{{rm I}{M}_{rm W} } $ relative to alginate in collagen-based scaffolds permissive of cell elongation, indicating that PEGDA hydrogels may serve as an effective 3D model system for probing at least certain aspects of VFF behavior. Biotechnol. Bioeng. (c) 2009 Wiley Periodicals, Inc.
Randomized Controlled Trial to Determine the Efficacy of Long-Term Growth Hormone Treatment in Severely Burned Children.
Ann Surg. 2009 Sep 2; Branski LK, Herndon DN, Barrow RE, Kulp GA, Klein GL, Suman OE, Przkora R, Meyer W, Huang T, Lee JO, Chinkes DL, Mlcak RP, Jeschke MGBACKGROUND:: Recovery from a massive burn is characterized by catabolic and hypermetabolic responses that persist up to 2 years and impair rehabilitation and reintegration. The objective of this study was to determine the effects of long-term treatment with recombinant human growth hormone (rhGH) on growth, hypermetabolism, body composition, bone metabolism, cardiac work, and scarring in a large prospective randomized single-center controlled clinical trial in pediatric patients with massive burns. PATIENTS AND METHODS:: A total of 205 pediatric patients with massive burns over 40% total body surface area were prospectively enrolled between 1998 and 2007 (clinicaltrials.gov ID NCT00675714). Patients were randomized to receive either placebo (n = 94) or long-term rhGH at 0.05, 0.1, or 0.2 mg/kg/d (n = 101). Changes in weight, body composition, bone metabolism, cardiac output, resting energy expenditure, hormones, and scar development were measured at patient discharge and at 6, 9, 12, 18, and 24 months postburn. Statistical analysis used Tukey t test or ANOVA followed by Bonferroni correction. Significance was accepted at P < 0.05. RESULTS:: RhGH administration markedly improved growth and lean body mass, whereas hypermetabolism was significantly attenuated. Serum growth hormone, insulin-like growth factor-I, and IGFBP-3 was significantly increased, whereas percent body fat content significantly decreased when compared with placebo, P < 0.05. A subset analysis revealed most lean body mass gain in the 0.2 mg/kg group, P < 0.05. Bone mineral content showed an unexpected decrease in the 0.2 mg/kg group, along with a decrease in PTH and increase in osteocalcin levels, P < 0.05. Resting energy expenditure improved with rhGH administration, most markedly in the 0.1 mg/kg/d rhGH group, P < 0.05. Cardiac output was decreased at 12 and 18 months postburn in the rhGH group. Long-term administration of 0.1 and 0.2 mg/kg/d rhGH significantly improved scarring at 12 months postburn, P < 0.05. CONCLUSION:: This large prospective clinical trial showed that long-term treatment with rhGH effectively enhances recovery of severely burned pediatric patients.