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Ann Plast Surg. 2009 Sep 4; Babuccu B, Babuccu O, Yurdakan G, Ankaral HIn this study, we developed a novel experimental model to evaluate muscular action on bone formation and remodeling by the help of Botulinum toxin-A (BTX).Forty-nine 15-day-old male Wistar rats were put into 4 groups randomly. Group 1 was the control group. BTX 0.4 IU (0.05 mL) was injected into the right masseter muscle in group 2 and into right temporalis muscle in group 3. The same volume of sterile saline was given into the both above-mentioned muscles in group 4. At the end of the fourth month, all animals were killed. Histology and weight of the masseter and temporalis muscles were studied. Thirty different osteometric measurements were also taken from skulls.Significant atrophy in BTX injected muscles was observed in groups 2 and 3. In group 4 (saline injection), only few osteometric measurements were significantly reduced, indicating the effect of the injection itself. Both groups 2 and 3 have apparent decrease in nasal bone, premaxilla, maxilla, and zygomatic dimensions on the injected side. When masseter group was compared with control and saline groups, no significant difference was found in skull base dimensions and mandibular length. In contrast, temporal group has also shown significant decrease in skull base dimensions.Our conclusions are as follows: (1) With this model, it is possible to study muscular action on bone formation and modeling without any surgical intervention, that is, by avoiding surgical artifacts, such as scar and contracture; (2) denervation of the skeletal muscles with BTX during the growing phase does effect bone development in a negative way; (3) pediatric use of the BTX deserves reevaluation under the light of these findings.

Anim Genet. 2009 Sep 10; Phillips RB, Dekoning JJ, Ventura AB, Nichols KM, Drew RE, Chaves LD, Reed KM, Felip A, Thorgaard GHSummary The previous genetic mapping data have suggested that most of the rainbow trout sex chromosome pair is pseudoautosomal, with very small X-specific and Y-specific regions. We have prepared an updated genetic and cytogenetic map of the male rainbow trout sex linkage group. Selected sex-linked markers spanning the X chromosome of the female genetic map have been mapped cytogenetically in normal males and genetically in crosses between the OSU female clonal line and four different male clonal lines as well as in outcrosses involving outbred OSU and hybrids between the OSU line and the male clonal lines. The cytogenetic maps of the X and Y chromosomes were very similar to the female genetic map for the X chromosome. Five markers on the male maps are genetically very close to the sex determination locus (SEX), but more widely spaced on the female genetic map and on the cytogenetic map, indicating a large region of suppressed recombination on the Y chromosome surrounding the SEX locus. The male map is greatly extended at the telomere. A BAC clone containing the SCAR (sequence characterized amplified region) Omy-163 marker, which maps close to SEX, was subjected to shotgun sequencing. Two carbonyl reductase genes and a gene homologous to the vertebrate skeletal ryanodine receptor were identified. Carbonyl reductase is a key enzyme involved in production of trout ovarian maturation hormone. This brings the number of type I genes mapped to the sex chromosome to six and has allowed us to identify a region on zebrafish chromosome 10 and medaka chromosome 13 which may be homologous to the distal portion of the long arm of the rainbow trout Y chromosome.

Curr Biol. 2009 Aug 27; Fricke R, Gohl C, Dharmalingam E, Grevelhörster A, Zahedi B, Harden N, Kessels M, Qualmann B, Bogdan SBACKGROUND: Developmental processes are intimately tied to signaling events that integrate the dynamic reorganization of the actin cytoskeleton and membrane dynamics. The F-BAR-domain-containing proteins are prime candidates to couple actin dynamics and membrane trafficking in different morphogenetic processes. RESULTS: Here, we present the functional analysis of the Drosophila F-BAR protein Cip4/Toca1 (Cdc42-interacting protein 4/transducer of Cdc42-dependent actin assembly 1). Cip4 is able to form a complex with WASP and SCAR/WAVE and recruits both actin-nucleation-promoting factors to invaginating membranes and endocytic vesicles. Actin-comet-tail-based movement of these vesicles depends not only on WASP but largely on WAVE function. In vivo, loss of cip4 function causes multiple wing hairs. A similar phenotype is observed when vesicle scission is affected after Dynamin suppression. Gene dosage experiments show that Cip4 and WAVE functionally interact to restrict wing hair formation. Further rescue experiments confirm that Cip4 is able to act through WAVE and WASP in vivo. Biochemical and functional data support a model in which Cdc42 acts upstream of Cip4 and recruits not only WASP but also SCAR/WAVE via Abi to control Dynamin-dependent cell polarization in the wing. CONCLUSION: Cip4 integrates membrane trafficking and actin dynamics through WASP and WAVE. First, Cip4 promotes membrane invaginations and triggers the vesicle scission by recruiting Dynamin to the neck of nascent vesicles. Second, Cip4 recruits WASP and WAVE proteins to induce actin polymerization, supporting vesicle scission and providing the force for vesicle movement.

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.

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.

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.

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.

Bull Acad Natl Med. 2009 Jan; 193(1): 107-26Anract PPatients with primary bone malignancies must be treated by specialized multidisciplinary teams composed of pathologists, surgeons, orthopedists, oncologists, radiologists and radiotherapists, all with experience in the diagnosis and treatment of these tumors. If a malignancy is suspected, the biopsy must also be performed in such a center. Biopsy is part of the treatment and must be done by a senior surgeon, before starting specific treatment. Indeed, inappropriate biopsy can compromise the patient's functional prognosis and sometimes the vital outcome. The biopsy can be done percutaneously under radiological control with a True-cut needle or a trocart to obtain cores of pathological tissue. The pathologist must be well-versed in bone disorders. Open surgical biopsy is preferable for primary bone tumors, especially when a cartilaginous tumor is suspected. A short incision is used, situated on the same approach as that which will be used for surgical resection of the tumor, so that the biopsy scar is excised along with the tumor, in a single block. Surgical treatment of primary bone malignancies requires extensive resection, i.e. excision of the affected bone segment and any invaded soft tissues, as a single block, without breaching the tumor, and preserving a peripheral margin of healthy tissue. In most cases, reconstruction is necessary to preserve the function of the resected region. It is based on standard orthopedic techniques, namely osteosynthesis, bone grafts (autografts and allografts), prostheses of variable size, or a combination of prostheses and allografts (composite reconstruction). Amputation is only indicated if conservative resection is impossible. It has been shown that conservative resection, now possible in about 80% of cases, does not reduce the survival chances of patients with osteosarcoma. The indications for amputation include massive tumors invading vessels and nerves, resection of which would leave the limb non functional, as sell as tumor infection (often secondary to biopsy), inappropriate biopsy (infection of vessels or periarticular muscles, etc.), and local relapse. Amputation must respect the same oncologic principles as conservative resection.

J Bone Joint Surg Am. 2009 Sep; 91(9): 2130-6Gong HS, Baek GH, Oh JH, Lee YH, Jeon SH, Chung MSBACKGROUND: Factors regarding patient willingness to undergo or avoid joint replacement have been studied; however, these factors have not been studied in patients with carpal tunnel syndrome. To further understand the aspects that are important for a patient with carpal tunnel syndrome in deciding whether to have surgery, we identified factors that affect this decision in women and that are not related to Workers' Compensation status. METHODS: We retrospectively reviewed 282 female patients with electrophysiologically confirmed carpal tunnel syndrome without a known cause who were recommended for carpal tunnel release by a single hand surgeon in a tertiary medical setting. Of those, thirty-six female patients who were not entitled to Workers' Compensation canceled the operation during the waiting period, which averaged four weeks. Thirty-three of them were surveyed with a questionnaire sent by mail, and eighteen completed surveys were reviewed at a mean follow-up of thirty-two months. Furthermore, seventy female patients who underwent carpal tunnel release were randomly sampled, and thirty-eight patients completed the survey. The operation and cancellation groups were compared with regard to the reasons for choosing or canceling surgery. RESULTS: The groups were similar with regard to age, sociodemographic variables, follow-up length, initial electrophysiological findings, and functional status. The highest-ranked reason for choosing surgery was symptom severity rather than fear of progression or a positive electrodiagnostic result. Those who canceled the operation rated symptom improvement during the waiting period as the leading reason for doing so, but they were also concerned about transient weakness, the financial burden, and a scar or pillar pain. Disease persistence or recurrence was the issue of most concern in both groups. At the time of the final review, the functional status was significantly improved in both groups and no significant difference between the groups was detected. CONCLUSIONS: Women with carpal tunnel syndrome report that subjective symptom severity is the most important reason for undergoing surgery. Understanding this and other patient concerns may help physicians during patient-oriented consultation and decision-making. In particular, recommendations for carpal tunnel release on the basis of symptoms are reasonable from the perspective of the patient who has carpal tunnel syndrome without a known cause.

Aesthet Surg J. 2009 Jul-Aug; 29(4): 272-83Kruavit ABACKGROUND: Reconstruction of the suprapalpebral fold (SPF) to create a double eyelid is a popular procedure in many East Asian countries. However, the traditional long-incision, double-eyelid blepharoplasty procedure can result in eyelid swelling that lasts for months, resulting in the temporary appearance of an excessively high SPF. OBJECTIVE: The author describes 18 years of experience using a short-incision technique for Asian blepharoplasty in 6215 patients. METHODS: A short incision to minimize eyelid trauma and surgical scarring was made on only the middle one-third of the upper eyelid. The dissection was extended far enough superiorly, medially, and laterally above the levator aponeurosis to obtain maximum upward movement of the globe. Three anchoring sutures were placed for the creation of the permanent SPF, with inverted stitches between either the levator aponeurosis or the lower border of the stripped orbital septum, to either the dermis or the dermomuscular junction of the lower margin of the incised skin. Intraoperative adjustment of the curvature and the lateral flare of the SPF was accomplished by changing or releasing the point of the anchoring suture in four different ways: to either the upper or lower dermal or dermomuscular junction of either the lower or upper margin of the incised wound or, on rare occasions, by a small elliptical excision of the upper skin flap. In 70% of patients, changing the medial anchoring suture to the proper position resulted in the creation of suprapalpebral outside fold, without any need to perform epicanthoplasty. RESULTS: The average operative time was 33 minutes. Most patients did not need to refrain from attending work or school. The postoperative complication rate was 3.8%. The most common temporary unfavorable results were minimal swelling, bruising, and eversion of the eyelid margin. Minor complications included asymmetrical fold, fading of the fold, depressed scar, and drooping of lateral eyelid skin. All of the minor complications were treated successfully. There were no severe complications. CONCLUSIONS: The short central incision is a semi-open blepharoplasty technique for creating the double eyelid that is suitable for all patients without loose upper eyelid skin.

Despite the availability of various new methods to treat vitiligo, surgical methods offer rapid, simple, and safe ways for treating small-sized vitiligo.

OBJECTIVE:
To evaluate the feasibility and efficacy in treating vitiligo using suction blister epidermal grafting (SBEG) combined with CO2 laser epidermal ablation.

METHODS:
Forty patients with small, stable vitiligo were treated using SBEG combined with CO2 laser epidermal ablation and followed up for at least 6 months and up to 10 years.

RESULTS:
Treatment outcomes were excellent for 32 patients (80%), good for four patients (10%), fair for three patients (7.5%), and poor for one patient (2.5%). No scar formation was observed in any patients. Location of the lesions was probably the most important factor in determining the outcomes of transplantation.

CONCLUSION:
This study suggests that SBEG combined with CO2 laser ablation is a rapid, simple, and safe method to treat vitiligo, especially for patients with small and stable vitiliginous lesions.


Suction blister epidermal grafts combined with CO2 laser superficial ablation as a good method for treating small-sized vitiligo.
Dermatol Surg. 2009 Apr; 35(4): 601-6Ko WC, Chen YF

Injury. 2009 Aug 17; Islam S, Ahmed M, Walton GM, Dinan TG, Hoffman GRAIM: Although the surgical care provided for patients who have sustained a maxillofacial injury has advanced in recent years, psychological disorders may develop. Anxiety and depression may be a cause of significant morbidity in these patients. Such problems are often unrecognised and untreated. PATIENTS & METHODS: We undertook a comparative cross-sectional study in a cohort of adult patients to assess the association between traumatic facial injury and the presence of anxiety and depressive disorders. Study subjects were recruited during the period of June 2008 through August 2008. Fifty consecutive adult patients attending the maxillofacial outpatient clinic following facial trauma were asked to complete the Hospital Anxiety and Depression Scale (HADS). Data gathered from this group of patients were compared to 50 adult control subjects who were under follow-up following elective oral and maxillofacial surgery. We also looked at several demographic and other variables to assess its association with poor mental health outcomes. RESULTS: Ten patients (20%) in the facial trauma group achieved high scores in both subscales suggesting a probable anxiety and depression state. The mean score for the depression subscale was significantly higher in the facial trauma group compared to the control group (p=0.006). The mean score for anxiety was also higher but did not reach statistical significance (p=0.07). Stratified analysis (Mantel-Haenszel) was used to control for possible confounding variables. The odds ratio for probable depression, for facial trauma patients compared with "control" patients, was 9.02, 95% CI=2.45, 33.1, p

J Plast Reconstr Aesthet Surg. 2009 Aug 20; Fattah A, Sebire NJ, Bulstrode NWBACKGROUND: Current techniques of autologous ear reconstruction involve the soft tissue coverage of a carved costal cartilage framework. However, assessment of the morbidity associated with this donor site has been little documented. This study describes a method to reconstruct the defect and analyses the outcomes with or without donor site reconstitution. METHODS: The donor site was reconstituted by wrapping morcelised cartilage in a vicryl mesh. Twenty-one patients with reconstitution and nine without were recruited to the study. Scar quality and length, dimensions of donor defect and visible deformity were recorded according to a modified Vancouver scar scale. Patients were also assessed by the SF36 questionnaire, a well-validated health survey. In a subset of our study group, we assessed the fate of the donor site reconstitution by direct visualisation in situ and histological analysis. RESULTS: Fifteen donor sites of patients without donor site reconstitution were compared to 23 reconstructed donor sites. In those without, all had a palpable defect with nearly half exhibiting visible chest deformity. In contrast, those that had rib reconstitution did not demonstrate significant chest wall deformity. Intraoperative examination demonstrated formation of a neo-rib, histologically proven to comprise hyaline cartilage admixed with fibrous tissue. Analysis of SF36 results showed a higher satisfaction in the reconstituted group, but in both groups, the donor site was of little overall morbidity. CONCLUSIONS: Although there is little difference between the groups in terms of subjectively perceived benefit, rib reconstitution is objectively associated with better costal margin contour and less chest wall deformity.

Radiology. 2009 Jul 31; Goldfarb JW, Roth M, Han JPurpose: To prospectively investigate the prevalence of fat deposition in chronic myocardial infarction (MI) by using magnetic resonance (MR) fat-water separation imaging with sampling of the entire left ventricular (LV) myocardium. A subsidiary aim was to determine the relationship between LV fat deposition and scar characteristics, as well as regional and global cardiac functional parameters. Materials and Methods: Twenty-five patients with LV MI were evaluated in this prospective institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study after they provided written informed consent. A 1.5-T MR system was used to perform volumetric cine, fat-sensitive, and late gadolinium-enhanced (LGE) infarct imaging. Water-fat separation was performed by using a three-point Dixon reconstruction from in- and opposed-phase black-blood gradient-echo images. Fat deposition location was compared with LGE infarct imaging by using a 17-segment model. Global and regional functional variables, LGE volumes, and fat deposition were compared by using the Pearson correlation, Student t test, and multiple regression. Results: A fat deposition prevalence of 68% was found in areas of chronic MI. The patients with fat deposition had larger infarctions (30.0 mL +/- 15.1 [standard deviation] vs 14.8 mL +/- 6.1; P = .002), decreased wall thickening (2.3% +/- 20.0 vs 37.8% +/- 34.4; P = .003), and impaired endocardial wall motion (2.9 mm +/- 2.0 vs 5.8 mm +/- 2.6; P = .007). The volume of fat deposition was correlated with infarct volume, LV ejection fraction, LV end-diastolic volume index, and LV end-systolic volume index. Conclusion: There is a high prevalence of fat deposition in healed MI. It is associated with post-infarction characteristics including infarct volume, LV mass, wall thickness, wall thickening, and wall motion. (c) RSNA, 2009.

J Refract Surg. 2009 Aug; 25(8): 739-46Esquenazi S, Esquenazi I, Grunstein L, He J, Bazan HPURPOSE: To evaluate the healing response at the flap interface in corneas with LASIK ectasia that required penetrating keratoplasty (PK). METHODS: Corneas of five patients who developed corneal ectasia after LASIK (range: 2.5 to 5 years postoperative) were collected after corneal transplant surgery. The corneas were bisected and processed for conventional histologic analysis and immunofluorescence. RESULTS: Light microscopy showed a hypocellular fibrotic scar at the wound margin compared with the adjacent corneal stroma in all eyes. All corneas had positive staining for alpha-smooth muscle actin (SMA), a myofibroblast marker. In one eye, alpha-SMA cells were located in the fibrotic scar region in the area of the semicircular ring of haze along the margin of the LASIK flap corresponding to an area of epithelial ingrowth. In all other eyes, alpha-SMA positive cells were fewer and mainly located in the superficial stroma under the epithelial wound margin surface. Type III collagen was minimal or absent in the central zone and wound margin of all corneas except for the cornea with epithelial ingrowth present in the hypercellular fibrotic scar region. Chondroitin sulfate was stronger in the periphery of the flap wound coinciding with a higher presence of alpha-SMA-positive cells in that region. Positive staining for matrix metalloproteinase 9 (MMP-9) in the paracentral wound margin scar was seen. CONCLUSIONS: A wound-healing process characterized by absence of significant fibrosis and myofibroblasts at the wound edge in the flap interface was noted in all keratectatic eyes. However, changes in the composition of collagen and the presence of MMP-9 at the wound edge several years after LASIK indicates active wound remodeling that may explain the ongoing loss of tissue and tendency of the cornea to bulge.

J Tissue Eng Regen Med. 2009 Aug 21; Wolbank S, Hildner F, Redl H, van Griensven M, Gabriel C, Hennerbichler SPreserved amniotic membrane (AM) has been used in the field of ophthalmology and wound care due to its bacteriostatic, antiphlogistic, protease-inhibiting, re-epithelialization, wound-protecting and scar formation-reducing properties. Typically, AM is applied after banking in a glycerol-preserved or freeze-dried state. Cell viabilities in different forms of preparation vary substantially, which in consequence may also be reflected in the amount and type of growth factors released from the preserved material. Therefore, we characterized the angiogenic factor (AF) profile released from different AM preparations. For this, medium was conditioned with non-preserved, glycerol- and cryo-preserved AM for 48 h, which was screened for AFs using a protein array system. In parallel, the preparations were tested for cell viability. Non-preserved as well as cryo-preserved AM maintained viabilities at 106.5 +/- 23.9% and 21.9 +/- 23.3%, respectively, whereas glycerol-preserved AM was found to be non-viable. Of the 20 investigated factors, high levels of angiogenin, GRO, IL-6/8, TIMP-1/2 and MCP-1 and low levels of EGF, IFNgamma, IGF-1, leptin, RANTES, TGFbeta1 and thrombopoietin were identified to be secreted from non-preserved AM. Cryo-preserved AM secreted high levels of IL-8, intermediate levels of GRO and TIMP-1/2 but only low levels of angiogenin, IFNgamma, IL-6 and MCP-1 and no detectable EGF, IGF-1, leptin, RANTES, TGFbeta1 and thrombopoietin. After banking in glycerol, AM releases only minute amounts of TIMP-1/2. Along with viability, the AF profile of amniotic membrane largely depends on the preparation method applied for banking. This should be considered for selection of an AM product for a specific clinical application. Copyright (c) 2009 John Wiley & Sons, Ltd.

J Neural Eng. 2009 Aug 21; 6(5): 56003McConnell GC, Rees HD, Levey AI, Gutekunst CA, Gross RE, Bellamkonda RVProsthetic devices that are controlled by intracortical electrodes recording one's 'thoughts' are a reality today, and no longer merely in the realm of science fiction. However, widespread clinical use of implanted electrodes is hampered by a lack of reliability in chronic recordings, independent of the type of electrodes used. One major hypothesis has been that astroglial scar electrically impedes the electrodes. However, there is a temporal discrepancy between stabilization of scar's electrical properties and recording failure with recording failure lagging by 1 month. In this study, we test a possible explanation for this discrepancy: the hypothesis that chronic inflammation, due to the persistent presence of the electrode, causes a local neurodegenerative state in the immediate vicinity of the electrode. Through modulation of chronic inflammation via stab wound, electrode geometry and age-matched control, we found that after 16 weeks, animals with an increased level of chronic inflammation were associated with increased neuronal and dendritic, but not axonal, loss. We observed increased neuronal and dendritic loss 16 weeks after implantation compared to 8 weeks after implantation, suggesting that the local neurodegenerative state is progressive. After 16 weeks, we observed axonal pathology in the form of hyperphosphorylation of the protein tau in the immediate vicinity of the microelectrodes (as observed in Alzheimer's disease and other tauopathies). The results of this study suggest that a local, late onset neurodegenerative disease-like state surrounds the chronic electrodes and is a potential cause for chronic recording failure. These results also inform strategies to enhance our capability to attain reliable long-term recordings from implantable electrodes in the CNS.

Basic Res Cardiol. 2009 Aug 23; Tiede K, Melchior-Becker A, Fischer JWBiglycan, a small leucine-rich proteoglycan, is essential for scar formation and preservation of hemodynamic function after myocardial infarction, as shown in biglycan-knockout mice. Because of this important role in cardiac pathophysiology, we aimed to identify regulators of biglycan expression and posttranslational modifications in cardiac fibroblasts. Cardiac fibroblasts were isolated from neonatal Wistar-Kyoto rats and used in the first passage. Expression of biglycan was analyzed after metabolic labeling with [(35)S]-sulfate by SDS-polyacrylamide gel electrophoresis and molecular sieve chromatography; mRNA expression was examined by Northern analysis and real-time RT-PCR. Serum, thrombin, transforming growth factor beta1 (TGFbeta 1) and platelet-derived growth factor BB (PDGF-BB) strongly increased [(35)S]-labeled proteoglycan levels. Tumor necrosis factor alpha further increased the stimulatory effect of PDGF-BB. PDGF-BB increased glycosaminoglycan (GAG) chain length as shown by molecular sieve chromatography after beta-elimination to release GAG chains. Nitric oxide was the only negative regulator of biglycan as evidenced by marked downregulation in response to DETA-NO ((Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate), a long acting nitric oxide donor and SNAP (S-nitroso-N-acetyl-l,l-penicillamine), which completely inhibited PDGF-BB-induced secretion of total [(35)S]-labeled proteoglycans and biglycan mRNA expression. Of note, the molecular weight of biglycan GAG chains was even further increased by NO donors compared to control and PDGF-BB stimulation. The current results suggest that in cardiac fibroblasts, biglycan is induced by a variety of stimuli including serum, thrombin and growth factors such as PDGF-BB and TGFbeta1. This response is counteracted by NO and enhanced by TNFalpha. Interestingly, both up- and downregulation were associated with posttranslational increase of GAG chain length.

J Orthop Trauma. 2009 Sep; 23(8): 570-4Renger RJ, Roukema GR, Reurings JC, Raams PM, Font J, Verleisdonk EJOBJECTIVE: To evaluate functional and radiologic outcome in patients with a Neer type II lateral clavicle fracture treated with the clavicle hook plate. DESIGN: Multicenter retrospective study. SETTING: Five level I and II trauma centers. PATIENTS: Forty-four patients, average age 38.4 years (18-66 years), with a Neer type II lateral clavicle fracture treated with the clavicle hook plate between January 1, 2003, and December 31, 2006. INTERVENTION: Open reduction and internal fixation with the clavicle hook plate. Removal of all 44 implants after consolidation at a mean of 8.4 months (2-33 months) postoperatively. MAIN OUTCOME MEASUREMENTS: At an average follow-up of 27.4 months (13-48 months), functional outcome was assessed with the Constant-Murley scoring system. Radiographs were taken to evaluate consolidation and to determine the distance between the coracoid process and the clavicle. RESULTS: The average Constant score was 92.4 (74-100). The average distance between the coracoid process and the clavicle was 9.8 mm (7.3-14.8 mm) compared with 9.4 mm (6.9-14.3 mm) on the contralateral nonoperative side. We observed 1 dislocation of an implant (2.2%), 2 cases of pseudarthrosis (4.5%), 2 superficial wound infections (4.5%), 2 patients with hypertrophic scar tissue (4.5%), and 3 times an acromial osteolysis (6.8%). Thirty patients (68%) reported discomfort due to the implant. These implant-related complaints and the acromial osteolysis disappeared after removal of the hook plate. With all the patients, direct functional aftercare was possible. CONCLUSIONS: The clavicle hook plate is a suitable implant for Neer type II clavicle fractures. The advantage of this osteosynthesis is the possibility of immediate functional aftercare. We observed a high percentage of discomfort due to the implant; therefore, we advise to remove the implant as soon as consolidation has taken place.

J Child Orthop. 2009 Aug 23; Teoh KH, Chee YH, Shortt N, Wilkinson G, Porter DEPURPOSE: Intramedullary (IM) nailing and plating are recognised fixation methods for both-bone midshaft forearm fractures. Although both methods are effective, IM nailing has recently been the accepted operative treatment for the paediatric population. The aim of the study was to compare the differences in the radiographic and functional outcomes of an age- and sex-matched cohort of children following treatment by IM fixation or plate fixation with screws for an unstable both-bone diaphyseal fracture. METHODS: A retrospective study was conducted and 17 age- and sex-matched pairs of patients returned for a research review clinic. The average age of our patients was 11.6 years at follow up, with 11 boys and six girls in each group. The mean follow up was similar in both groups (IM 31.5 months, plating 31.8 months). RESULTS: Plating and IM nailing result in good or excellent functional and radiological outcomes. Radiographs at the review clinic showed complete healing in the plating group, with reconstitution of the radial bow. Three patients in the IM group did not regain the natural radial bow radiographically. There were no significant differences between both groups for maximum radial bow and its location (P > 0.05). However, the maximum radial bow was significantly different from normative values in both groups (P = 0.003 plate, P = 0.005 IM). No non-union or malunion was observed. There were no significant differences in the loss of forearm motion and grip strength between both groups. There was no difference in the Pediatric Orthopaedic Society of North America (POSNA) scores between both groups. The plating group had a significantly worse Manchester scar score than the IM group (P = 0.012). One major complication was observed in each group: osteomyelitis for IM fixation and ulnar never palsy for plating. CONCLUSION: Our study suggests that functional outcome is likely to be equivalent, regardless of which method of internal fixation is used.