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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.

J Mol Cell Cardiol. 2009 Aug 13; Moreno-Gonzalez A, Korte FS, Dai J, Chen K, Ho B, Reinecke H, Murry CE, Regnier MCell transplantation improves cardiac function after myocardial infarction; however, the underlying mechanisms are not well-understood. Therefore, the goals of this study were to determine if neonatal rat cardiomyocytes transplanted into adult rat hearts one-week after infarction would, after 8-10 weeks: 1) improve global myocardial function, 2) contract in a Ca(2+) dependent manner, 3) influence mechanical properties of remote uninjured myocardium and 4) alter passive mechanical properties of infarct regions. The cardiomyocytes formed small grafts of ultrastructurally maturing myocardium that enhanced fractional shortening compared to non-treated infarcted hearts. Chemically demembranated tissue strips of cardiomyocyte grafts produced force when activated by Ca(2+), whereas scar tissue did not. Furthermore, the Ca(2+) sensitivity of force was greater in cardiomyocyte grafts compared to control myocardium. Surprisingly, cardiomyocytes grafts isolated in the infarct zone increased Ca(2+) sensitivity of remote uninjured myocardium to levels greater than either remote myocardium from non-treated infarcted hearts or sham-operated controls. Enhanced calcium sensitivity was associated with decreased phosphorylation of cTnT, tropomyosin and MLC2, but not changes in myosin or troponin isoforms. Passive compliance of grafts resembled normal myocardium, while infarct tissue distant from grafts had compliance typical of scar. Thus, cardiomyocyte grafts are contractile, improve local tissue compliance and enhance calcium sensitivity of remote myocardium. Because the volume of remote myocardium greatly exceeds that of the grafts, this enhanced calcium sensitivity may be a major contributor to global improvements in ventricular function after cell transplantation.

J Urol. 2009 Aug 17; Sugita Y, Ueoka K, Tagkagi S, Hisamatsu E, Yoshino K, Tanikaze SPURPOSE: Phimosis associated with concealed penis is not amenable to ordinary circumcision. To our knowledge we describe a new technique to repair concealed penis. MATERIALS AND METHODS: From September 2003 to January 2008, 57 consecutive patients with concealed penis were treated using our technique. Median age at surgery was 33 months (range 7 months to 34 years). The technique consists of 3 steps. Step 1 is a ventral incision to slit the narrow ring of the prepuce and expose the glans. Step 2 is a circumferential skin incision made between 2 edges of the ventral diamond-shaped skin defect, followed by midline incision of the dorsal inner prepuce to make 2 skin flaps connected to the glans. Step 3 is skin coverage. Two skin flaps are brought down and sutured together on the ventral side of the penis. The suture line between the penile shaft skin and the flap eventually becomes elliptical. Medical records were reviewed for voiding function, scar formation, and replies from older patients and the parents of younger children about impressions of the surgical results. RESULTS: Median followup was 26 months. No patient had voiding problems. Lymphedema persisted due to suture line constriction in 2 patients who underwent incision of the constriction. All older patients and the parents of younger children were satisfied with the surgical results. CONCLUSIONS: Our new method is easy to design and perform to correct concealed penis. It provides a good cosmetic appearance and seems to be applicable in all cases with deficient penile shaft skin.

J Urol. 2009 Aug 17; Ferro F, Vallasciani S, Borsellino A, Atzori P, Martini LPURPOSE: We report our retrospective, nonrandomized, single center experience with modified tubularized incised urethral plate repair, consisting of grafting the incised urethral plate before tubularization, as first introduced 10 years ago. Indications, technical points and results are described. MATERIALS AND METHODS: From 1997 to 2007 at our unit 1,095 cases of hypospadias were treated, including 75% primary and 25% repeat cases. Of primary cases 18 (8%) of those suitable for tubularized incised urethral plate were instead selected for a grafted tubularized incised urethral plate. All 18 patients were characterized anatomically by a small glans, a flat urethral groove and a long spongiosum defect. Of repeat cases 83 were suitable for a tubularized incised urethral plate, of which 44 (53%) were selected for the modified procedure. Grafted tubularized incised urethral plate surgery consisted of an extended longitudinal incision of the urethral plate distal beyond the neomeatal line associated with scar excision in repeat cases. The resulting urethral plate defect was then lined with a graft. RESULTS: Mean followup was 36 months (range 4 to 122). Complications were noted in 8 repeat cases (13% overall), representing 18% of this subgroup. CONCLUSIONS: Case selection is a crucial factor that influences the quality of tubularized incised urethral plate results. However, in most repeat cases scarring may lead to an increased complication rate after tubularized incised urethral plate surgery. The grafted modification has the advantage of extending indications for the tubularized incised urethral plate to cases in which another surgical procedure would be necessary. To our knowledge we present the first series of primary and repeat cases.

Circulation. 2009 Aug 17; Ding L, Dong L, Chen X, Zhang L, Xu X, Ferro A, Xu BBACKGROUND: -Left ventricular (LV) remodeling is associated with the development of heart failure after myocardial infarction. Here we investigated whether integrin-linked kinase (ILK) may regulate LV remodeling and function after myocardial infarction. Methods and Results-Adenoviral vector expressing ILK (n=25) or empty adeno-null (n=25) was injected into rat peri-infarct myocardium after left anterior descending coronary artery ligation. ILK expression was confirmed by Western blotting and immunofluorescence. Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in adeno-ILK animals. ILK treatment was associated with reduced infarct scar size, increased scar thinning ratio, and preserved LV diameter, wall thickness, cardiomyocyte size, and myofilament density. Enhanced angiogenesis and reduced fibrosis were observed in the adeno-ILK group, along with reduced apoptosis as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis. Moreover, increased cardiomyocyte proliferation was found in adeno-ILK animals, as measured by proliferating cell nuclear antigen, Ki-67, and phosphohistone-H3 staining. At long-term follow-up, most indices of cardiac function and hemodynamics showed no difference between adeno-ILK and control animals by 9 weeks, although LV end-systolic diameter and infarct scar size were reduced in the adeno-ILK group at this time point. Additionally, ILK overexpression was found to exert a rescue effect on remodeling when administered in a delayed fashion 1 week after coronary artery ligation. Conclusions-ILK gene therapy improves cardiac remodeling and function in rats after myocardial infarction and is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of postinfarct remodeling and subsequent heart failure.

Pharmacogenet Genomics. 2009 Aug 18; Tassaneeyakul W, Jantararoungtong T, Chen P, Lin PY, Tiamkao S, Khunarkornsiri U, Chucherd P, Konyoung P, Vannaprasaht S, Choonhakarn C, Pisuttimarn P, Sangviroon A, Tassaneeyakul WOBJECTIVES: Allopurinol, a uric acid lowering drug commonly used for hyperuricemia and gouty arthritis, has been reported as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between allopurinol-induced SCAR and HLA-B*5801 was observed in a Han Chinese population with high frequency of this allele, whereas only a moderate association was observed in populations with low frequency (i.e. European and Japanese). This study investigated the relationship between SJS/TEN and HLA-B*5801 in a Thai population that has a high allelic frequency of this allele. METHODS: Twenty-seven allopurinol-induced SJS/TEN and 54 allopurinol-tolerant patients were enrolled in the study. The presence of HLA-B*5801 and HLA-B genotypes in these patients were analyzed using a PG5801 DNA detection kit and sequence-based typing, respectively. RESULTS: All of the 27 (100%) allopurinol-induced SJS/TEN patients who were examined carried HLA-B*5801 whereas only seven (12.96%) of the control patients had this allele. The risk of allopurinol-induced SJS/TEN was significantly greater in patients with HLA-B*5801 when compared with those who did not carry this allele, with an odds ratio of 348.3 (95% confidence interval=19.2-6336.9, P = 1.6x10). The sensitivity and specificity of the HLA-B*5801 allele for prediction of allopurinol-induced SJS/TEN were 100 and 87%, respectively. By assuming a 0.2% prevalence rate, the positive predictive value and the negative predictive value of the HLA-B*5801 allele was 1.52 and 100%, respectively. CONCLUSION: A strong association of allopurinol-induced SJS/TEN with the HLA-B*5801 allele was observed in a Thai population. The results suggest that HLA-B*5801 is a valid genetic marker for screening Thai individuals who may be at risk for allopurinol-induced life-threatening SJS and TEN.

J Vasc Interv Radiol. 2009 Aug 19; Jahnke T, Schäfer JP, Charalambous N, Trentmann J, Siggelkow M, Hümme TH, Bolte H, Demirbas E, Heller M, Müller-Hülsbeck SPURPOSE: To determine the safety and efficacy of total percutaneous access closure for endovascular aortic aneurysm repair with a suture-mediated preclosing technique. MATERIALS AND METHODS: One hundred thirty-two femoral access sites in 70 patients who underwent endovascular aortic aneurysm repair were closed percutaneously with off-label use of two F-6 Perclose AT devices preapplied at a 90 degrees angle. Femoral access sizes ranged from 12 to 24 F. Technical success, complications, and procedure and access closure times were evaluated. Follow-up with computed tomography and/or magnetic resonance imaging was scheduled at 1-4 days and 3, 6, and 12 months and used to obtain groin hematoma and scar severity scores (grades 1-3). Data were compared with those from a cohort of 67 patients who underwent endovascular aortic aneurysm repair with surgical femoral cutdown. RESULTS: Technical success was achieved with the preclosing technique in 127 of the 132 arteries (96.2%). Two to four closure devices were used per groin. Five technical failures were managed intraoperatively with surgical suture. There was no access-related mortality and no late groin complications. The mean procedure duration was 91 minutes +/- 32, and the mean access closure time was 12 minutes +/- 9. For surgical management, the mean procedure time was 153 minutes +/- 112 (P < .05), and the mean closure time was 12 minutes +/- 13 (not statistically significant). Hematoma severity score at 1-4 days was 1.8 for total percutaneous endovascular aneurysm repair and 2.1 for surgical closure. Scar severity scores at 3, 6, and 12 months were 1.1, 1.0, and 1.0 for total percutaneous endovascular aneurysm repair and 2.4, 2.4, and 2.3 for surgical management, respectively. CONCLUSIONS: Total percutaneous endovascular aneurysm repair with a dual 6-F-Perclose preclosing technique is safe and effective. Compared with femoral cutdown, there are fewer late groin complications and scar tissue formation is less severe.

PLoS One. 2009; 4(8): e6688Scharstuhl A, Mutsaers HA, Pennings SW, Russel FG, Wagener FABACKGROUND: We previously identified curcumin as a potent inducer of fibroblast apoptosis, which could be used to treat hypertrophic scar formation. Here we investigated the underlying mechanism of this process. PRINCIPAL FINDINGS: Curcumin-induced apoptosis could not be blocked by caspase-inhibitors and we could not detect any caspase-3/7 activity. Curcumin predominantly induced mitochondria-mediated ROS formation and stimulated the expression of the redox-sensitive pro-apoptotic factor p53. Inhibition of the pro-apoptotic signaling enzyme glycogen synthase kinase-3beta (GSK-3beta) blocked curcumin-induced apoptosis. Apoptosis was associated with high molecular weight DNA damage, a possible indicator of apoptosis-inducing factor (AIF) activity. Indeed, curcumin caused nuclear translocation of AIF, which could be blocked by the antioxidant N-acetyl cysteine. We next investigated how AIF is effluxed from mitochondria in more detail. The permeability transition pore complex (PTPC), of which the voltage-dependent anion channel (VDAC) is a component, could be involved since the VDAC-inhibitor DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) efficiently blocked AIF translocation. However, PTPC is not involved in AIF release since cyclosporine A, a specific inhibitor of the complex did not block apoptosis. Alternatively, the pro-apoptotic protein Bax could have formed mitochondrial channels and interacted with VDAC. Curcumin caused mitochondrial translocation of Bax, which was blocked by DIDS, suggesting a Bax-VDAC interaction. Interestingly, ceramide channels can also release apoptogenic factors from mitochondria and we found that addition of ceramide induced caspase-independent apoptosis. Surprisingly, this process could also be blocked by DIDS, suggesting the concerted action of Bax, VDAC and ceramide in the efflux of AIF from the mitochondrion. CONCLUSIONS: Curcumin-induced fibroblast apoptosis is totally caspase-independent and relies on the mitochondrial formation of ROS and the subsequent nuclear translocation of AIF, which is released from a mitochondrial pore that involves VDAC, Bax and possibly ceramides. The composition of the AIF-releasing channel seems to be much more complex than previously thought.

J Hand Surg Am. 2009 Aug 14; Zhang X, He Y, Shao X, Li Y, Wen S, Zhu HPURPOSE: The second dorsal metacarpal artery flap from the middle finger is a reconstructive technique that can be used to repair extensive volar defects in a normal-length thumb. However, few reports advocate using it for coverage of volar thumb defects. In this article, an anatomic study of 9 flaps used for resurfacing thumb defects is presented along with the clinical experience of the authors. METHODS: From 2004 to 2006, 9 patients (6 men and 3 women; mean age, 33 years; range, 18-51 years) with extensive volar defects of their normal-length thumbs had reconstruction using the described technique. In all cases, the first dorsal metacarpal artery flap technique was unable to be used because of injury. Donor sites were covered using full-thickness skin grafts. After surgery, the thumb was immobilized with a splint, followed by rehabilitation. During the follow-up period, which lasted 24 to 30 months, flap-site skin quality, scar contractures, and finger mobility were assessed. The range of motion of the hand was measured by a goniometer. Sensibility was evaluated by the 2-point discrimination test and the Semmes-Weinstein monofilament test. Cold intolerance was also assessed. RESULTS: Patient postoperative courses were uneventful, and all flaps survived completely without complication. Good coverage was obtained in all cases. Full active range of motion was observed in all patients in both the donor finger and the thumb. The mean Semmes-Weinstein sensitivity and 2-point discrimination scores of the flap were 4.02 g and 8.4 mm, respectively. Mild cold intolerance was observed in all of the thumbs. CONCLUSIONS: The second dorsal metacarpal artery flap from the middle finger is a single-stage flap that produces good results. Although its pedicle length is limited, it is reliable and can be used as an alternative for reconstruction of extensive thumb-pulp defects, especially when the first dorsal metacarpal artery flap cannot be used. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Eur Spine J. 2009 Aug 19; Boriani S, Bandiera S, Donthineni R, Amendola L, Cappuccio M, De Iure F, Gasbarrini AThe morbidity of surgical procedures for spine tumors can be expected to be worse than for other conditions. This is particularly true of en bloc resections, the most technically demanding procedures. A retrospective review of prospective data from a large series of en bloc resections may help to identify risk factors, and therefore to reduce the rate of complications and to improve outcome. A retrospective study of 1,035 patients affected by spine tumors-treated from 1990 to 2007 by the same team-identified 134 patients (53.0% males, age 44 +/- 18 years) who had undergone en bloc resection for primary tumors (90) and bone metastases (44). All clinical, histological and radiological data were recorded from the beginning of the period in a specifically built database. The study was set up to correlate diagnosis, staging and treatment with the outcome. Oncological and functional results were recorded for all patients at periodic, diagnosis-related controls, until death or the latest follow-up examination (from 0 to 211 months, median 47 months, 25th-75th percentile 22-85 months). Forty-seven on the 134 patients (34.3%) suffered a total of 70 complications (0.86 events per 100 patient-years); 32 patients (68.1%) had one complication, while the rest had 2 or more. There were 41 major and 29 minor complications. Three patients (2.2%) died from complications. Of the 35 patients with a recurrent or contaminated tumor, 16 (45.7%) suffered at least one complication; by contrast, complications arose in 31 (31.3%) of the 99 patients who had had no previous treatment and who underwent the whole of their treatment in the same center (P = 0.125). The risk of major complications was seen to be more than twice as high in contaminated patients than in non-contaminated ones (OR = 2.52, 95%CI 1.01-6.30, P = 0.048). Factors significantly affecting the morbidity are multisegmental resections and operations including double contemporary approaches. A local recurrence was recorded in 21 cases (15.7%). The rate of deep infection was higher in patients who had previously undergone radiation therapy (RT), but the global incidence of complications was lower. Re-operations were mostly due to tumor recurrences, but also to hardware failures, wound dehiscence, hematomas and aortic dissection. En bloc resection is able to improve the prognosis of aggressive benign and low-grade malignant tumors in the spine; however, complications are not rare and possibly fatal. The rate of complication is higher in multisegmental resections and when double combined approach is performed, as it can be expected in more complex procedures. Re-operations display greater morbidity owing to dissection through scar/fibrosis from previous operations and possibly from RT. The treatment of recurrent cases and planned transgression to reduce surgical aggressiveness are associated with a higher rate of local recurrence, which can be considered the most severe complication. In terms of survival and quality of life, late results are worse in recurrent cases than in complicated cases. Careful treatment planning and, in the event of uncertainty, referral to a specialty center must be stressed.

Am J Sports Med. 2009 Aug 14; Ristanis S, Tsepis E, Giotis D, Stergiou N, Cerulli G, Georgoulis ADBACKGROUND: Changes in electromechanical delay during muscle activation are expected when there are substantial alterations in the structural properties of the musculotendinous tissue. In anterior cruciate ligament reconstruction, specific tendons are being harvested for grafts. Thus, there is an associated scar tissue development at the tendon that may affect the corresponding electromechanical delay. PURPOSE: This study was conducted to investigate whether harvesting of semitendinosus and gracilis tendons for anterior cruciate ligament reconstruction will affect the electromechanical delay of the knee flexors. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The authors evaluated 12 patients with anterior cruciate ligament reconstruction with a semitendinosus and gracilis autograft, 2 years after the reconstruction, and 12 healthy controls. Each participant performed 4 maximally explosive isometric contractions with a 1-minute break between contractions. The surface electromyographic activity of the biceps femoris and the semitendinosus was recorded from both legs during the contractions. RESULTS: The statistical comparisons revealed significant increases of the electromechanical delay of the anterior cruciate ligament-reconstructed knee for both investigated muscles. Specifically, the electromechanical delay values were increased for both the biceps femoris (P = .029) and the semitendinosus (P = .005) of the reconstructed knee when compared with the intact knee. Comparing the anterior cruciate ligament-reconstructed knee against healthy controls revealed similar significant differences for both muscles (semitendinosus, P = .011; biceps femoris, P = .024). CONCLUSION: The results showed that harvesting the semitendinosus and gracilis tendons for anterior cruciate ligament reconstruction significantly increased the electromechanical delay of the knee flexors. Increased hamstring electromechanical delay might impair knee safety and performance by modifying the transfer time of muscle tension to the tibia and therefore affecting muscle response during sudden movements in athletic activities. However, further investigation is required to identify whether the increased electromechanical delay of the hamstrings can actually influence optimal sports performance and increase the risk for knee injury in athletes with anterior cruciate ligament reconstructions.

Ann Chir Plast Esthet. 2009 Aug 12; Mojallal A, Saint-Cyr M, Wong C, Veber M, Braye F, Rohrich RBACKGROUND: The muscle-sparing latissimus dorsi flap pedicled on descending branch presents distinct advantages in breast reconstruction, specially when there is a transversely oriented skin paddle, including reduced donor site morbidity, sparing muscle function and greater freedom of orientation of the skin paddle. This study reports the anatomical basis, surgical technique, advantages and complications of this technique. Four clinical cases illustrate surgical indications in breast reconstructive surgery. METHODS: An anatomical cadaveric study underwent to University of Texas Southwestern Medical Center, Dallas. The goal was performed to determine the location of the bifurcation of the thoracodorsal artery and the course of its descending branch compare to the anterior side of latissimus dorsi muscle. Four clinical cases illustrated indications of muscle-sparing latissimus dorsi flap pedicled on descending branch in breast reconstruction. These cases showed advantages and complications of the technique, and impact on donor site. RESULTS: Fifteen descending branch muscle-sparing latissimus dorsi flaps were harvested. All flaps had a bifurcation of the thoracodorsal artery. The average was located at 5,1cm from posterior axillary side (from 2,1 to 7,5cm) and average of 2,2cm from the anterior side of latissimus dorsi muscle (from 1,3 to 3,1cm). To 5, 10 and 15cm from posterior axillary side, the descending branch was located at respectively an average of 2,0cm (from 1,4 to 2,5), 2,4cm (from 1,3 to 3,3), and 2,9cm (from 2,0 to 3,8) behind the anterior side of latissimus dorsi muscle. The average length of descending branch was measured at 15,2cm (from 13,2 to 19,0). None clinical cases paddle suffering was observed. Donor site morbidity was less than classical or extended adipomuscular technique. Latissimus dorsi muscle function is spared. CONCLUSIONS: The muscle-sparing latissimus dorsi flap, pedicled on descending branch, is versatile and reproducible. It results in minimal functional deficit of the donor site, absence of seroma, large freedom of orientation of the skin paddle, low rate of flap complications, and a cosmetically acceptable scar. There are a lot of indications in breast reconstruction.

Int Rev Neurobiol. 2009; 87: 445-64Rochkind S, Geuna S, Shainberg APosttraumatic nerve repair and prevention of muscle atrophy represent a major challenge of restorative medicine. Considerable interest exists in the potential therapeutic value of laser phototherapy for restoring or temporarily preventing denervated muscle atrophy as well as enhancing regeneration of severely injured peripheral nerves. Low-power laser irradiation (laser phototherapy) was applied for treatment of rat denervated muscle in order to estimate biochemical transformation on cellular and tissue levels, as well as on rat sciatic nerve model after crush injury, direct or side-to-end anastomosis, and neurotube reconstruction. Nerve cells' growth and axonal sprouting were investigated in embryonic rat brain cultures. The animal outcome allowed clinical double-blind, placebo-controlled randomized study that measured the effectiveness of 780-nm laser phototherapy on patients suffering from incomplete peripheral nerve injuries for 6 months up to several years. In denervated muscles, animal study suggests that the function of denervated muscles can be partially preserved by temporary prevention of denervation-induced biochemical changes. The function of denervated muscles can be restored, not completely but to a very substantial degree, by laser treatment initiated at the earliest possible stage post injury. In peripheral nerve injury, laser phototherapy has an immediate protective effect. It maintains functional activity of the injured nerve for a long period, decreases scar tissue formation at the injury site, decreases degeneration in corresponding motor neurons of the spinal cord, and significantly increases axonal growth and myelinization. In cell cultures, laser irradiation accelerates migration, nerve cell growth, and fiber sprouting. In a pilot, clinical, double-blind, placebo-controlled randomized study in patients with incomplete long-term peripheral nerve injury, 780-nm laser irradiation can progressively improve peripheral nerve function, which leads to significant functional recovery. A 780-nm laser phototherapy temporarily preserves the function of a denervated muscle, and accelerates and enhances axonal growth and regeneration after peripheral nerve injury or reconstructive procedures. Laser activation of nerve cells, their growth, and axonal sprouting can be considered as potential treatment for neural injury. Animal and clinical studies show the promoting action of phototherapy on peripheral nerve regeneration, which makes it possible to suggest that the time for broader clinical trials has come.

Oper Orthop Traumatol. 2009 Jun; 21(2): 141-56Berger A, Hierner ROBJECTIVE: Reconstruction of powerful active elbow flexion. Reconstruction of missing muscle unit by neurovascular pedicled functional muscle transplantation. INDICATIONS: Treatment of last choice for --secondary reconstruction of active elbow flexion in case of complete lesion of the brachial plexus or musculocutaneous nerve (M0 muscle function = replacement indication), partial but incomplete lesion of the brachial plexus or musculocutaneous nerve (M1-(3) muscle function = augmentation indication); --replacement of the elbow flexor muscles in case of primary muscle loss (tumor, trauma). CONTRAINDICATIONS: Concomitant lesions of the axillary artery. No adequate donor nerve. Relative: no sensibility at all at the forearm and hand. SURGICAL TECHNIQUE: Free functional biarticular myocutaneous transplantation of gracilis muscle. A myocutaneous gracilis flap is raised at the thigh. At the upper arm the flap is fixed proximally to the coracoid process or the lateral clavicle. The distal insertion is sutured to the distal biceps tendon. Vascular anastomoses are carried out in end-to-side fashion with the brachial artery and vein. Nerval coaptation is done in end-to-end technique using the muculocutaneous nerve. POSTOPERATIVE MANAGEMENT: Complete immobilization for 6 weeks. Dorsal upper arm splint until sufficient muscle power (M(4)). Progressive increase of active range of motion for another 6 weeks. Continuation of physiotherapy for 12-18 months. Postoperative standardized compression therapy, combined with scar therapy (silicone sheet). RESULTS: Functionally useful results can be expected in 60-75% of patients, especially if there is some residual function (M1 or M2) left ("augmentation indication"). Early free functional muscle transplantation shows best results in patients with direct muscle defect, because all vascular and neuronal structures are still available, and no secondary changes such as fibrosis or joint stiffness are present yet. There are inconsistent results for patients with neurologic insufficiency (i.e., total brachial plexus palsy) or mixed neuromuscular insufficiency, such as compartment syndrome. Especially in complete brachial plexus lesion, free functional muscle transfer is often the only treatment option. Provided there is a good patient selection, satisfactory results can be achieved for elbow flexion. Whether a higher number of axons, as provided by the contralateral C7 transfer, will lead to better results is the topic of an ongoing study.

Oper Orthop Traumatol. 2009 Jun; 21(2): 126-40Hierner R, Berger AOBJECTIVE: Active elbow flexion is necessary for bimanual tasks. Reconstruction of powerful active elbow flexion. Reconstruction of missing muscle unit by neurovascular pedicled functional muscle transposition. INDICATIONS: Treatment of second choice (first choice bipolar latissimus dorsi transfer according to Zancolli & Mitre, transfer of the flexor/pronator muscle onto the distal humerus, or transposition of the triceps onto the biceps): --(Secondary) reconstruction of active elbow flexion in case of lesion of the brachial plexus or musculocutaneous nerve. --Replacement of the elbow flexor muscles in case of primary muscle loss (tumor, trauma). CONTRAINDICATIONS: Ongoing spontaneous or postoperative nerve regeneration. Ankylosis of the elbow joint (in case of good shoulder and hand function, one should consider arthrolysis or even total joint replacement). Insufficient power of the pectoralis major muscle (< M(4)). Lesion of the axillary artery involving the thoracoacromial artery. Relative: concomitant lesion of the latissimus dorsi and teres major muscles (loss of glenohumeral adduction [thoracohumeral pinch]. SURGICAL TECHNIQUE: Distal muscle transposition: transposition of the origin--pars abdominalis, pars sternocostalis, pars clavicularis (unipolar or bipolar, partial or complete distal transfer): --Unipolar partial pectoralis major muscle transposition according to Clark. --Bipolar partial pectoralis major muscle transposition according to Schottstaedt et al. --Bipolar complete pectoralis major muscle transposition according to Dautry et al. and Carroll & Kleinmann, respectively, possibly in combination with transfer of the pectoralis minor muscle. --Myocutaneous flap in case of concomitant skin defect at the upper arm level. Proximal tendon transfer: transposition of the tendinous insertion at the humerus of the pectoralis major muscle. POSTOPERATIVE MANAGEMENT : Immobilization for 6 weeks in a dorsal upper arm splint, a Gilchrist bandage or a thorax-arm abduction orthesis with the elbow in 90 degrees flexion and supination. Early passive motion depending on pain within the sector 90-140 degrees. Progressive increase of active range of motion after 6 weeks. Protected exercise from "out of the splint" with increasing elbow extension of 10 degrees per week. It is important, that there is still an extension lag of 30-40 degrees at 3 months after transfer, in order to protect the reinnervated muscle and avoid overstretching. Although complete elbow extension should be the aim after 1 year, most patients will keep an extension lag of 20-30 degrees. Physiotherapy must continue for 12-18 months. Postoperative standardized compression therapy, combined with scar therapy (silicone sheet). RESULTS: Meta-analysis of the literature and personal results show functional (very good and good) results in 54-86% of patients. There are only few complications.

Heart Rhythm. 2009 Aug; 6(8 Suppl): S70-6Haqqani HM, Marchlinski FEThe electrophysiologic substrate underlying the development of ventricular tachycardia (VT) in patients with prior infarction has been studied in depth. An increased understanding of its composition and role in the maintenance of reentrant VT has led to the development of substrate modification approaches to ablation of unmappable VT. The area of low bipolar voltage that corresponds to the subendocardial projection of the scar as well as specific potential targets within it have been defined. These targets are selected because they may be involved in forming, or are in close proximity to, critical diastolic isthmuses during VT. The targets include sites of good pacemaps in the border zone, corridors of relatively preserved voltage within dense scar, regions between electrically unexcitable scar, isolated potentials, very late potentials, and regions with good pacemaps which display long stimulus to QRS delays. Ablation strategies have been designed based on these targets, mostly incorporating linear lesions to transect putative isthmus sites. This review examines the role that the electrophysiologic substrate plays in the mechanism of scar-related VT and how this substrate is mapped, defined, and ablated.

Eur J Radiol. 2009 Aug 7; Zaher S, Gedroyc W, Lyons D, Regan LThe purpose of this research was to identify a method for performing Magnetic Resonance Imaging Guided Focused Ultrasound Surgery (MRgFUS) of symptomatic uterine fibroids in patients with abdominal scars, by visualisation of these scars on MR images. 25 patients who presented with treatable symptomatic uterine fibroids and having transverse abdominal scars were treated with MRgFUS. A solution containing MRI contrast paramagnetic iron oxide particles was used to demark the skin surface scar tissue on the treatment planning MR images. During treatment, the focused ultrasound energy was steered around the scar based on its enhanced visual location. After the treatment, contrast enhanced MR images were acquired for immediate results evaluation. Adverse events and fibroid related symptoms were captured during the 6-months follow up period. All the women were treated with no complications. No episodes of skin burns, ulceration or skin redness were reported. The post-treatment contrast-enhanced MR images showed an average fibroid non-perfused volume ratio of 64%. At their 6-month follow-up, 92% of the patients reported a clinical improvement. Using paramagnetic iron oxide solution to highlight transverse abdominal scars helps in their identification on MR images, thereby enabling the operator to avoid scars and facilitating the treatment of women who were previously excluded.

Eur Radiol. 2009 Aug 14; Wybier M, Gaudart S, Petrover D, Houdart E, Laredo JDBACKGROUND: Selective steroid injections of the lumbar spine carry a risk of paraplegia of sudden onset. Seven cases have been reported in the English literature since 2002. MATERIALS AND METHODS: Five new cases have been analyzed, all coming from Paris area centers. Injections were performed between 2003 and 2008. The following items were searched for: location of a previous lumbar spine surgery if any, symptoms indicating the procedure, route of injection, imaging technique used for needle guidance, injection of a contrast medium, type of steroid, other drugs injected if any, paraplegia level, post-procedure MR findings. The current and reported cases were compared. RESULTS: MR findings were consistent with spinal cord ischemia of arterial origin. The high rate of patients who had been operated on in these cases does not correspond to that of patients undergoing injections. The presence of epidural scar might increase the risk. The foraminal route was the only one involved in nonoperated patients. Foraminal, interlaminar, or juxta-zygoapophyseal routes were used in operated-on patients. CONCLUSION: The high rate of French cases when compared to the literature might arise from the almost exclusive use of prednisolone acetate, a molecule with a high tendency to coalesce in macro-aggregates, putting the spinal cord at risk of arterial supply embolization.

Clin Ophthalmol. 2008 Sep; 2(3): 675-8Sonoyama H, Araki-Sasaki K, Kazama S, Kawasaki T, Ideta H, Sunada A, Asari S, Inoue Y, Hayashi KClinical findings and treatment of keratomycosis caused by Beauveria bassiana, an entomopathogenic filamentous fungus, are described for an 80-year-old woman, who was referred to the hospital for ocular pain and redness on the 9th day after an ocular injury caused by the frame of her glasses. She had a long history of recurrent diabetic iritis and continuously used topical antibiotics and corticosteroids. At her first visit, a slit-lamp examination indicated a corneal ulcer confined within the superficial stromal layer, along with a slight infiltration and edema. Only a very few inflammatory cells were seen in the anterior chamber. Direct microscopic examination of corneal scrapings revealed septate fungal hyphae with zig-zag rachis and budding that was subsequently identified as B. bassiana by slide culture. Topical voriconazole with miconazole, pimaricin and oral itraconazole were effective and the lesion disappeared leaving only a mild scar at 2 months. The sensitivity of B. bassiana to various antimycotic agents was confirmed by broth microdilution, agar dilution with the Clinical Laboratory Standard Institute standard, and a disk method using topically applied concentrations. B. bassiana, which exhibits a characteristic appearance in smears and causes superficial keratomycosis, is sensitive to voriconazole with miconazole, pimaricin, and itraconazole.

J Pharmacol Sci. 2009 Aug; 110(4): 483-92Seo TB, Baek K, Kwon KB, Lee SI, Lim JS, Seol IC, Kim YS, Seo YB, Namgung UShengmai-san (SMS) is a traditional Chinese medicine used to treat diverse symptoms including cardiovascular and neurological disorders. Here we investigated the effects of SMS on regenerative responses of spinal cord axons in rats that were given contusion injury at the lower thoracic level. The injury cavity was confined to a restricted area by SMS treatment, and the signals of glial scar protein chondroitin sulphate proteoglycan (CSPG) and inflammatory cell marker protein CD11beta were heavily observed within the injury cavity in SMS-treated animals. Anterograde tracing of DiI-labeled corticospinal tract (CST) axons revealed increases in collateral arborization around and within the injury cavity and caudal elongation by SMS treatment. Furthermore, SMS treatment facilitated neurite elongation of dorsal root ganglion (DRG) sensory neurons that were co-cultured with non-neuronal cells prepared from injured spinal cord. Phospho-Erk1/2 was strongly induced in both spinal cord and motor cortical areas after spinal cord injury (SCI), and it was further unregulated in the motor cortex by SMS treatment. In contrast, upregulation of cell division cycle 2 (Cdc2) production by SMS treatment was limited to a local, SCI area. These data suggest that SMS may play an active role in regenerative responses and facilitate axonal regrowth after SCI.

Clin Ophthalmol. 2008 Dec; 2(4): 773-80Ghazi NG, Conway BP, Tiedeman JS, Yoon SJPURPOSE: To emphasize the effect of photodynamic therapy (PDT) on the size and progression of the neovascular lesion (NL) and evolution of the disciform scar (DS) in predominantly classic subfoveal choroidal neovascularization (SFCNV). METHODS: A retrospective study of 62 eyes treated with PDT for SFCNV was performed. The greatest linear dimension (GLD) before and at last follow-up after treatment and the size of the DS post-PDT were analyzed. A subgroup of patients with DS in their fellow eye at presentation without prior PDT was also studied. The size of the scar in these eyes was compared to that following PDT. RESULTS: After an average follow-up at 9 months, the size of the NL was stabilized or reduced in 64% of the study eyes with absence of fluorescein leakage in 45%. Only 3 eyes (5%) developed DS. At presentation, 14 patients already had DS in their fellow eye, the size of which was significantly larger than that post-PDT (p = 0.044). It was also significantly larger than that of the potential scar in the study eyes of the same subgroup of patients (p = 0.002) and of the rest of the patients (p = 0.0001). CONCLUSION: This study demonstrates a beneficial effect for PDT on the size of the NL and DS in SFCNV, which might be of great significance, particularly when PDT fails to prevent severe vision loss.

Bone. 2009 Aug 5; Rozen N, Bick T, Bajayo A, Shamian B, Schrift-Tzadok M, Gabet Y, Yayon A, Bab I, Soudry M, Lewinson DThe angiogenic events that accompany bone regeneration function as a "limiting factor" and are the primary regulatory mechanisms that direct the healing process. The general aim of this study was to test whether blood-derived progenitor cells that have endothelial characteristics (EPC), when applied to a large segmental defect, would promote bone regeneration. We established a critical-sized gap platform in sheep tibiae. Our model system takes advantage of the physiological wound healing process that occurs during the first two weeks following injury, and results in the gap being filled with scar tissue. EPC were expanded ex-vivo and 2 x 10(7) cells/0.2 ml were implanted into a wedged-shaped canal excavated in the fibrotic scar tissue. Sham treated sheep served as controls. Bone regeneration was followed every two weeks for three months by x-rays radiography. At the end of the experimental period, the regenerating segments were subjected to microcomputed tomographic (muCT) analysis. While minimal bone formation was detected in sham-treated sheep, six out of seven autologous EPC-transplanted sheep showed initial mineralization already by 2 weeks and complete bridging by 8 - 12 weeks post EPC transplantation. Histology of gaps 12 weeks post sham treatment showed mostly fibrotic scar tissue. On the contrary, EPC transplantation led to formation of dense and massive woven bone all throughout the defect. The results of this pre-clinical study open new therapeutic opportunities for the treatment of large scale bone injuries.

J Neurosci. 2009 Aug 12; 29(32): 9967-76Busch SA, Horn KP, Silver DJ, Silver JTrauma to the adult CNS initiates multiple processes including primary and secondary axotomy, inflammation, and glial scar formation that have devastating effects on neuronal regeneration. After spinal cord injury, the infiltration of phagocytic macrophages coincides with long-distance axonal retraction from the initial site of injury, a deleterious phenomenon known as axonal dieback. We have previously shown that activated macrophages directly induce long-distance retraction of dystrophic axons in an in vitro model of the glial scar. We hypothesized that treatments that are primarily thought to increase neuronal regeneration following spinal cord injury may in fact derive a portion of their beneficial effects from inhibition of macrophage-mediated axonal retraction. We analyzed the effects of protease inhibition, substrate modification, and neuronal preconditioning on macrophage-axon interactions using our established in vitro model. General inhibition of matrix metalloproteinases and specific inhibition of MMP-9 prevented macrophage-induced axonal retraction despite significant physical interactions between the two cell types, whereas inhibition of MMP-2 had no effect. Chondroitinase ABC-mediated digestion of the aggrecan substrate also prevented macrophage-induced axonal retraction in the presence of extensive macrophage-axon interactions. The use of a conditioning lesion to stimulate intrinsic neuronal growth potential in the absence of substrate modification likewise prevented macrophage-induced axonal retraction in vitro and in vivo following spinal cord injury. These data provide valuable insight into the cellular and molecular mechanisms underlying macrophage-mediated axonal retraction and demonstrate modifications that can alleviate the detrimental effects of this unfavorable phenomenon on the postlesion CNS.