Astrocytes and oligodendrocytes can be generated from NG2(+) progenitors after acute brain injury: intracellular localization of oligodendrocyte transcription factor 2 is associated with their fate ch

Eur J Neurosci. 2009 May; 29(9): 1853-69Zhao JW, Raha-Chowdhury R, Fawcett JW, Watts CAbstract Brain injury induces gliosis and scar formation; its principal cell types are mainly astrocytes and some oligodendrocytes. The origin of the astrocytes and oligodendrocytes in the scar remains unclear together with the underlying mechanism of their fate choice. We examined the response of oligodendrocyte transcription factor (Olig)2(+) glial progenitors to acute brain injury. Both focal cortical (mechanical or excitotoxic) and systemic (kainic acid-induced seizure or lipopolysaccharide-induced inflammation) injury caused cytoplasmic translocation of Olig2 (Olig2(TL)) exclusively in affected brain regions as early as 2 h after injury in two-thirds of Olig2(+) cells. Many of the proliferating Olig2(+) cells reacting to injury co-expressed chondroitin sulphate proteoglycan neuron/glia antigen 2 (NG2). Using 5-bromodeoxyuridine (BrdU) tracing protocols, proliferating Olig2(TL)GFAP(+)BrdU(+) cells were observed from 2 days post-lesion (dpl). Immature oligodendrocytes were also seen from 2 dpl and all of them retained Olig2 in the nucleus (Olig2(Nuc)). From 5 dpl Olig2(TL)NG2(+)GFAP(+) cells were observed in the wound and some of them were proliferative. From 5 dpl NG2(+)RIP(+) cells were also seen, all of which were Olig2(Nuc) and some of which were also BrdU(+). Our results suggest that, in response to brain injury, NG2(+) progenitors may generate a subpopulation of astrocytes in addition to oligodendrocytes and their fate choice was associated with Olig2(TL) or Olig2(Nuc). However, the NG2(+)GFAP(+) phenotype was only seen within a limited time window (5-8 dpl) when up to 20% of glial fibrillary acidic protein (GFAP) cells co-expressed NG2. We also observed Olig2(TL)GFAP(+) cells that appeared after injury and before the NG2(+)GFAP(+) phenotype. This suggests that not all astrocytes are derived from an NG2(+) population.

Silver nanoparticles in therapeutics: development of an antimicrobial gel formulation for topical use.

Mol Pharm. 2009 May 27; Jain J, Arora S, Rajwade J, Khandelwal S, Paknikar KMSilver is an effective antimicrobial agent with low toxicity, which is important especially in the treatment of burn wounds where transient bacteremia is prevalent and its fast control is essential. Drugs releasing silver in ionic forms are known to get neutralized in biological fluids and upon long term use may cause cosmetic abnormality i.e. argyria and delayed wound healing. Given its broad spectrum activity, efficacy and lower costs, search for newer and superior silver based antimicrobial agents is necessary. Among the various options available, silver nanoparticles have been the focus of increasing interest and are being heralded as excellent candidate for therapeutic purposes. This report gives an account of our work on development of an antimicrobial gel formulation containing silver nanoparticles (SNP) in the size range of 7-20 nm synthesized by a proprietary biostabilization process. The typical minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against standard reference cultures as well as multi-drug resistant organisms were 0.78-6.25 mug/ml and 12.5 mug/ml, respectively. Gram-negative bacteria were killed more effectively (3 log10 decrease in 5-9 h) than Gram positive bacteria (3 log10 decrease in 12 h). SNP also exhibited good antifungal activity (50% inhibition at 75 mug/ml with antifungal index 55.5% against Aspergillus niger and MIC of 25 mug/ml against Candida albicans). When the interaction of SNP with commonly used antibiotics was investigated, the observed effects were synergistic (ceftazidime), additive (streptomycin, kanamycin, ampiclox, polymyxin B) and antagonistic (chloramphenicol). Interestingly, SNP exhibited good anti-inflammatory properties as indicated by concentration-dependent inhibition of marker enzymes (matrix metalloproteinase 2 and 9). The post agent effect (a parameter measuring the length of time for which bacterial growth remains suppressed following brief exposure to the antimicrobial agent) varied with the type of organism (e.g. 10.5 h for P. aeruginosa, 1.3 h for Staphylococcus sp and 1.6 h for Candida albicans) indicating that dose regimen of the SNP formulation should ensure sustained release of the drug. To meet this requirement, a gel formulation containing SNP (S-gel) was prepared. The antibacterial spectrum of S-gel was found to be comparable to a commercial formulation of silver sulfadiazine, albeit at a 30-fold less silver concentration. As part of toxicity studies, localization of SNP in Hep G2 cell line, cell viability, biochemical effects and apoptotic/necrotic potential was assessed. It was found that SNP get localized in the mitochondria and have IC50 value of 251 mug/ml. Even though they elicit an oxidative stress, cellular antioxidant systems (reduced glutathione content, superoxide dismutase, catalase) get triggered and prevent oxidative damage. Further, SNP induce apoptosis at concentrations up to 250 mug/ml, which could favor scar-less wound healing. Acute dermal toxicity studies on SNP gel formulation (S-gel) in Sprague Dawley rats showed complete safety for topical application. These results clearly indicate that silver nanoparticles could provide a safer alternative to conventional antimicrobial agents in the form of a topical antimicrobial formulation.

Desmoplastic cellular neurothekeoma: Clinicopathological analysis of twelve cases.

J Cutan Pathol. 2009 Mar 11; Zedek DC, White WL, McCalmont THBackground: Cellular neurothekeoma is a benign lesion most commonly found on the face and upper extremities in the first two decades of life. Methods: Retrospective clinicopathologic review of 12 examples of cellular neurothekeoma typified by prominent stromal sclerosis, a distinctive variant that we refer to as desmoplastic cellular neurothekeoma. Results: The mean age was 30 years (range, 3-55 years, 3 males, 9 females). The site was the head and neck in 3 cases, upper extremity in 4, lower extremity in 2, and trunk/abdomen in 3. All cases showed fascicles of slightly spindled and polygonal cells arrayed haphazardly in a prominent sclerotic background in the dermis and superficial subcutis. The cells displayed pale cytoplasm with indistinct membranes and vesicular nuclei with a single nucleolus. Lesional cells expressed NKI/C3, laminin, CD68, and CD10 and lacked expression of S-100 protein, EMA, and CD34. Clinical follow up was available on 10 cases with a mean duration of 24 months (range, 11-42 months) with no local recurrences or metastases. Conclusions: The immunohistochemical staining pattern, clinical findings, and benign nature are similar to "conventional" cellular neurothekeomas. The differential diagnosis includes desmoplastic melanocytic lesions, desmoplastic spindle cell carcinoma, dermatofibroma, "immature" scar, plexiform fibrohistiocytic tumor, perineurioma, and piloleiomyoma. Zedek DC, MD, White WL, MD, McCalmont TH, MD. Desmoplastic cellular neurothekeoma: Clinicopathological analysis of twelve cases.

[Cutaneous sarcoidosis through a hospital series of 28 cases]

Tunis Med. 2008 May; 86(5): 447-50Ben Jennet S, Benmously R, Chaâbane S, Fenniche S, Marrak H, Mohammed Z, Mokhtar IBACKGROUND: Sarcoidosis is a systemic disease, of unknown etiology, characterized by noncaseating epithelioid granulomas. It may affect many organs mainly lungs, lymph nodes and skin. AIM: The aim of our study is to evaluate retrospectively the epidemiological, clinical features and therapeutic particularities of cutaneous sarocidosis through a hospital series conducted in the dermatology department of Habib Thameur hospital. METHODS We have included 28 patients (23 females and 5 males) with a mean age of 45.5 years. RESULTS: The most frequent skin lesions were: papular sarcoidosis in 6 cases, nodular sarcoidosis in 8 cases and plaques in 6 cases. The other clinical types observed were: lupus pernio (2 cases), subcutaneous nodules (2 cases) and scar sarcoidosis (2 cases). Three patients presented erythema nodosum. Tuberculin skin test was negative in 77% of cases. Lymph nodes were palpable in 4 patients. Investigative exams revealed intrathoracic involvement in 8 cases and anterior uveitis sequels in 2 cases. Cutaneous manifestations were treated by chloroquin in 13 cases, allopurinol in 3 cases and intralesional betamethasone injections in 1 case. Five patients, with systemic involvement, underwent a therapy with oral corticosteroids. CONCLUSION: Sarcoidosis is a rare affection in Tunisia that affects mainly females. Cutaneous manifestations incite physicians to carry out complete investigations and to uphold a regular follow-up in order to detect systemic involvement.

Effects of antisense oligodeoxynucleotide to type I collagen gene on hypertrophic scars in the transplanted nude mouse model.

J Cutan Pathol. 2009 Mar 6; Xie J, Qi S, Yuan J, Xu Y, Li T, Li H, Liu X, Shu B, Liang HBackground: Antisense nucleic acids are effective in inhibiting harmful or uncontrolled gene expression. We had previously proved that the antisense DNA to type I collagen could effectively inhibit the synthesis of collagen type I in cultured hypertrophic scar fibroblasts, suggesting a potential role in anti-scarring, but there are no published reports of its effect on scar in the transplanted nude mouse model. Aims: To investigate the effects of antisense oligodeoxynucleotide (ASODN) to type I collagen gene on hypertrophic scars in the transplanted nude mouse model and clarify the potential of ASODN for the treatment of scars. Methods: The nude mouse model of hypertrophic scar was created and subjected to daily injections with ASODN and Lipofectamine for 2 ,4 or 6 weeks. We then examined the scars for changes in histopathological characteristics. The effects of ASODN on type I collagen gene expression were examined by reverse transcription-polymerase chain reaction and Western blots. Results: The ASODN could remarkably alleviate the scar in the nude mouse model and consistently inhibit type I collagen gene expression at both the mRNA and protein levels. Conclusion: ASODN was effective in downregulating type I collagen gene expression and could prove to be useful in the treatment of scars. Julin Xie, Shaohai Qi, Jishan Yuan, Yinbing Xu, Tianzeng Li, Houdong Li, Xusheng Liu, Bin Shu and Huizeng Liang.

Efficacy, Safety, and Biomarkers of Neoadjuvant Bevacizumab, Radiation Therapy, and Fluorouracil in Rectal Cancer: A Multidisciplinary Phase II Study.

J Clin Oncol. 2009 May 26; Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, Lahdenranta J, Chung DC, Fischman AJ, Lauwers GY, Shellito P, Czito BG, Wong TZ, Paulson E, Poleski M, Vujaskovic Z, Bentley R, Chen HX, Clark JW, Jain RKPURPOSE: To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response. PATIENTS AND METHODS: In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m(2)/24 hours) during cycles 2 to 4; external-beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks); and surgery 7 to 10 weeks after completion of all therapies. We measured molecular, cellular, and physiologic biomarkers before treatment, during bevacizumab monotherapy, and during and after combination therapy. RESULTS: Tumors regressed from a mass with mean size of 5 cm (range, 3 to 12 cm) to an ulcer/scar with mean size of 2.4 cm (range, 0.7 to 6.0 cm) in all 32 patients. Histologic examination revealed either no cancer or varying numbers of scattered cancer cells in a bed of fibrosis at the primary site. This treatment resulted in an actuarial 5-year local control and overall survival of 100%. Actuarial 5-year disease-free survival was 75% and five patients developed metastases postsurgery. Bevacizumab with chemoradiotherapy showed acceptable toxicity. Bevacizumab decreased tumor interstitial fluid pressure and blood flow. Baseline plasma soluble vascular endothelial growth factor receptor 1 (sVEGFR1), plasma vascular endothelial growth factor (VEGF), placental-derived growth factor (PlGF), and interleukin 6 (IL-6) during treatment, and circulating endothelial cells (CECs) after treatment showed significant correlations with outcome. CONCLUSION: Bevacizumab with chemoradiotherapy appears safe and active and yields promising survival results in locally advanced rectal cancer. Plasma VEGF, PlGF, sVEGFR1, and IL-6 and CECs should be further evaluated as candidate biomarkers of response for this regimen.

Usefulness of MRI to Differentiate Between Temporary and Long-Term Coronary Artery Occlusion in a Minimally Invasive Model of Experimental Myocardial Infarction.

Cardiovasc Intervent Radiol. 2009 May 27; Abegunewardene N, Vosseler M, Gori T, Hoffmann N, Schmidt KH, Becker D, Kreitner KF, Petersen SE, Schreiber LM, Horstick G, Münzel TThe surgical technique employed to determine an experimental ischemic damage is a major factor in the subsequent process of myocardial scar development. We set out to establish a minimally invasive porcine model of myocardial infarction using cardiac contrast-enhanced magnetic resonance imaging (ce-MRI) as the basic diagnostic tool. Twenty-seven domestic pigs were randomized to either temporary or permanent occlusion of the left anterior descending artery (LAD). Temporary occlusion was achieved by inflation of a percutaneous balloon in the left anterior descending artery directly beyond the second diagonal branch. Occlusion was maintained for 30 or 45 min, followed by reperfusion. Permanent occlusion was achieved via thrombin injection. Thirteen animals died peri- or postinterventionally due to arrhythmias. Fourteen animals survived the 30-min ischemia (four animals; group 1), the 45-min ischemia (six animals; group 2), or the permanent occlusion (4 animals; group 3). Coronary angiography and ce-MRI were performed 8 weeks after coronary occlusion to document the coronary flow grade and the size of myocardial scar tissue. The LAD was patent in all animals in groups 1 and 2, with normal TIMI flow; in group 3 animals, the LAD was totally occluded. Fibrosis of the left ventricle in group 1 (4.9 +/- 4.4%; p = 0.008) and group 2 (9.4 +/- 2.9%; p = 0.05) was significantly lower than in group 3 (14.5 +/- 3.9%). Wall thickness of the ischemic area was significantly lower in group 3 versus group 1 and group 2 (2.9 +/- 0.3, 5.9 +/- 0.7, and 6.1 +/- 0.7 mm; p = 0.005). The extent of late enhancement of the left ventricle was also significantly higher in group 3 (16.9 +/- 2.1%) compared to group 1 (5.3 +/- 5.4%; p = 0.003) and group 2 (9.7 +/- 3.4%, p = 0.013). In conclusion, the present model of minimally invasive infarction coupled with ce-MRI may represent a useful alternative to the open chest model for studies of myocardial infarction and scar development.

Efficacy of a polyurethane dressing versus a soft silicone sheet on hypertrophic scars.

J Wound Care. 2009 May; 18(5): 208-14Wigger-Albert W, Kuhlmann M, Wilhelm D, Mrowietz U, Eichhorn K, Ortega J, Bredehorst A, Wilhelm KPObjective: To compare the efficacy and safety of a polyurethane dressing with a silicone sheet in the treatment of hypertrophic scars. Method: Sixty patients participated in this intra-individual 12-week clinical trial. Each scar was divided into two areas, to which the polyurethane dressing and the silicone sheet were randomly allocated. The primary outcome measure was the percentage change in the overall scar index (SI) between baseline and week 12. Secondary outcome measures included changes in skin redness, objectively measured by chromametry, and patients views on the aesthetic outcome of treatment. Results: Both therapies achieved favourable results for all of the above outcome measures. Results were comparable for the primary outcome measure: 29.4% versus 33.7% for the silicone sheet and polyurethane product respectively. The decrease in the overall SI was significantly more pronounced for the polyurethane product after week 4 (5.6% versus 15.8% for the silicone sheet; p

Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury.

J Neurosci. 2009 May 20; 29(20): 6722-33Sellers DL, Maris DO, Horner PJProgenitors that express NG2-proteoglycan are the predominant self-renewing cells within the CNS. NG2 progenitors replenish oligodendrocyte populations within the intact stem cell niche, and cycling NG2 cells are among the first cells to react to CNS insults. We investigated the role of NG2 progenitors after spinal cord injury and how bone morphogen protein signals remodel the progressive postinjury (PI) niche. Progeny labeled by an NG2-specific reporter virus undergo a coordinated shift in differentiation profile. NG2 progeny born 24 h PI produce scar-forming astrocytes and transient populations of novel phagocytic astrocytes shown to contain denatured myelin within cathepsin-D-labeled endosomes, but NG2 progenitors born 7 d PI differentiate into oligodendrocytes and express myelin on processes that wrap axons. Analysis of spinal cord mRNA shows a temporal shift in the niche transcriptome of ligands that affect PI remodeling and direct progenitor differentiation. We conclude that NG2 progeny are diverse lineages that obey progressive cues after trauma to replenish the injured niche.

Differential and exclusive diagnosis of diseases that resemble keloids and hypertrophic scars.

Ann Plast Surg. 2009 Jun; 62(6): 660-4Ogawa R, Akaishi S, Hyakusoku HPrevious articles suggested the presence of various kinds of malignant tumors that resemble keloid or hypertrophic scar, including dermatofibrosarcoma protuberans, trichilemmal carcinoma, and keloidal basal cell carcinoma. Thus, we studied our cases that were diagnosed with diseases other than keloid or hypertrophic scar. From April 2003 to March 2007, we examined 378 patients self diagnosed with keloid or hypertrophic scar.We detected 4 other diseases (1.06%) in the group of patients. All tumors were benign: apocrine cystadenoma, adult-onset juvenile xanthogranuloma, mixed tumor, and chronic folliculitis. Our study led us to the conclusion that differential or exclusive diagnosis of diseases similar to keloid and hypertrophic scar is important. We found the following considerations important in the examination of keloid or hypertrophic scar: (1) biopsy should be conducted in anomalous cases because malignant disease may be the original or secondary problem, (2) steroid injection should be performed only after careful consideration because malignancy or infections may be present, (3) careful differential diagnosis is particularly challenging in African-Americans because skin and tumor color are often similar, and (4) the presence of bacterial or fungal infection should be investigated.

Echocardiography for cardiac resynchronization therapy selection: fatally flawed or misjudged?

J Am Coll Cardiol. 2009 May 26; 53(21): 1960-4Sanderson JEAfter the publication of the PROSPECT (Predictors of Response to CRT) trial, the use of echocardiography for the assessment of mechanical dyssynchrony and as a possible aid for selecting patients for cardiac resynchronization therapy has been heavily criticized. Calls have been made to observe the current guidelines and implant according to the entry criteria of recent major trials. However, although this approach is currently to be recommended, the attempt to identify patients who will not receive the benefits of cardiac resynchronization therapy and whose clinical condition may be worsened should continue. Devices are not analogous to drugs: initial costs are higher, complications are significant, and the device cannot readily be withdrawn. Professional resources and the costs to society are high and wasted if devices are implanted inappropriately. Rather that discarding the attempt to identify the most suitable patients pre-operatively, further work is needed to refine the techniques and new clinical trials performed. A combination of methods that include finding the site of latest mechanical activation, myocardial scar localization, and assessing venous anatomy pre-operatively may help to identify those who will not derive any benefit or be potentially worsened.

Endoscopic surgical treatment of posterior glottic stenosis.

J Laryngol Otol. 2009 May; 123(S31): 68-71Chitose S, Umeno H, Nakashima TA six-year-old girl developed posterior glottic stenosis following surgery for lateral curvature. She was post-operatively intubated for 17 days and had inspiratory stridor after extubation. Laryngoscopy revealed an adhesion at the posterior commissure which severely limited abduction of the bilateral vocal folds and arytenoids. Initially, tracheal fenestration was performed and the scar tissue of the posterior commissure was vaporised using a CO2 laser under endolaryngeal microsurgery. However, despite this procedure the stenosis reformed and an interarytenoid adhesion developed.Endolaryngeal microsurgery was performed again three months later. Using endoscopic microscissors, the posterior commissure and interarytenoid scar tissue were submucosally separated and the bilateral corniculate cartilages of the superior arytenoids were debulked using CO2 laser. A posteriorly based mucosal flap obtained from the postcricoid region was extended to approximate to the mucosa of the posterior commissure. The mucosal flap was sutured to the inferior subglottic mucosa by two 4-0 polyglactin absorbable sutures. Three months later, the patient's respiratory and phonatory function was satisfactory.Based on the successful results of the present case, the authors highly recommend the use of a posterior mucosal flap for the treatment of posterior glottic stenosis. This procedure does not require the use of either a laryngofissure or a laryngeal stent.

Microform cleft lip repair with intraoral muscle interdigitation.

Ann Plast Surg. 2009 Jun; 62(6): 640-4Desrosiers AE, Kawamoto HK, Katchikian HV, Jarrahy R, Bradley JPBACKGROUND: With a microform (forme fruste) cleft lip, obtaining an optimal functional and esthetic result is a challenge to a reconstructive surgeon. We describe modifications to existing techniques by Mulliken, Furlow, and Cutting that provides an optimal functional result with correction of the cleft furrow, vermillion notch, and cleft nose deformity. METHODS: Sequential unilateral microform cleft lip patients underwent our microform cleft lip repair modified from the following 3 techniques: the Mulliken microform cleft lip repair with no cutaneous scar, the Furlow complete cleft lip repair with interdigitating muscle, and the Cutting cleft nose repair (n = 12). From follow-up (1 year) examinations, photographs (and 3-dimensional images), and video, 3 reviewers scored esthetic and functional outcomes using a 0 to 4-point scale. In addition, parental surveys were obtained. RESULTS: For our microform cleft lip repair, there were no infections, bleeding, or other complications. Esthetic outcome score, evaluating the cutaneous scar, symmetry of philtral columns, alignment of lip line and vermillion border, and nasal tip symmetry was a mean of 3.7 (+/-0.3). Thus, the reviewers' scored the cleft lip and nose repair as "Very Good" (minor cleft lip/nose deformity but no need for revision) to "Excellent" (Imperceptible cleft lip or nose deformity). The functional outcome score, based on the ability to smile, pucker their lips, and whistle, was a mean of 3.8 (+/-0.2). The parental survey, including postoperative course, functional, and cosmetic outcome, demonstrated a high level of satisfaction with a score of 3.9 (+/-0.2). CONCLUSIONS: The modified microform cleft lip and nose technique provided very good to excellent esthetic and functional results in a series of patients with this rare deformity.

The Utility of Microscopic Findings and Immunohistochemistry in the Classification of Necrotic Testicular Tumors: A Study of 11 Cases.

Am J Surg Pathol. 2009 May 20; Miller JS, Lee TK, Epstein JI, Ulbright TMNecrotic testicular tumors are relatively frequent and can present a significant diagnostic challenge. Because of differing treatments for seminomas versus nonseminomas, accurate diagnosis is critical. Eleven totally (n=9) or almost totally (n=2) necrotic testicular tumors were retrieved from our consult files. The submitting pathologists favored benign processes in 4 cases, Leydig cell tumor in 1, and lymphoma in 1. The cases were evaluated for histologic features and, when material was available, by immunostaining with 7 antibodies: keratin (AE1/AE3), OCT4, placental alkaline phosphatase, alpha-fetoprotein (AFP), CD117, CD30, and S100. Only distinct reactivity in a cellular distribution in the necrotic zone was considered positive; nuclear reactivity alone was scored for OCT4 and membrane reactivity for CD117 and CD30. Mean patient age was 35 years (range 16-63). Mean tumor size was 19 mm (range 7-53). All patients presented with unilateral testicular masses (6 right, 5 left); 2 also had acute pain. The combination of histologic features, immunostains and, in 1 case, serum AFP permitted classification of 8 tumors (4 seminomas, 3 embryonal carcinomas, 1 yolk sac tumor). Three were not classifiable. The necrotic seminomas lacked associated coarse intratubular calcifications and were positive for OCT4 (4/4) and CD117 (3/3) but negative for keratin (0/4) and CD30 (0/4). The necrotic embryonal carcinomas had associated coarse intratubular calcifications and were positive for keratin (2/3), OCT4 (2/2), and CD30 (3/3). OCT4 stained 1 unclassifiable tumor, which lacked other specific markers. We did not find placental alkaline phosphatase, AFP, and S100 stains useful, although S100 did highlight tumor "ghost" cells in 1 case. Other features in most cases included intratubular germ cell neoplasia (6/11), tubular atrophy/hyalinization (10/11), tumor "ghost" cells (10/11), scar (9/11), and inflammation (10/11). Of the 5 patients with available follow-up, 3 were free of disease at 1, 5, and 8 years after orchiectomy (2 necrotic seminomas and 1 germ cell tumor, unclassified). One patient with yolk sac tumor (age 63 y) developed widespread metastases after 15 months and died of disease. The final case was initially misinterpreted as "testicular infarction, no malignancy" and 16 months later the patient developed a large retroperitoneal seminoma. Most totally necrotic testicular tumors can be placed into clinically important groups by assessment for coarse intratubular calcifications and staining reactions for keratin, OCT4, CD117, and CD30.

A new method for facial epidermoid cyst removal with minimal incision.

J Eur Acad Dermatol Venereol. 2009 May 3; Yang HJ, Yang KCAbstract Background Facial epidermoid cyst is a common benign epithelial tumour frequently seen in young or middle-aged people and may cause aesthetic disability. Surgical excision is the most frequently used method but may result in obvious scar. Objective To improve cosmetic result of removing facial epidermoid cyst through minimal incision surgery. Methods Twenty-two cases of facial epidermoid cysts ranging from 0.5 to 1.4 cm in diameter were treated. The skin above the epidermoid cysts was infiltrated with local 0.1-cc 1% xylocaine anaesthetic by using a 26-gauge needle first, then 3-mm incisions were made with a No.11 surgical blade. The cystic contents and its capsule were then squeezed out through the small incision and the underlying connective tissue was chemically cauterized by 20% trichloroacetic acid. The incision wounds were left unsutured. Result Minimal incision method successfully treated 16 out of the 22 epidermoid cyst cases that ranged from 0.5 to 1 cm in diameter. And only one out of six was successfully treated for diameters greater than 1.1 cm. Conclusion The proposed method can minimize the scar when treating facial epidermal inclusion cysts that are less than 1 cm and obtained better cosmetic results. Conflicts of interest None declared.

Cortactin Promotes Migration and PDGF-induced Actin Reorganization by Signaling to Rho-GTPases.

Mol Biol Cell. 2009 May 20; Lai FP, Szczodrak M, Oelkers JM, Ladwein M, Acconcia F, Benesch S, Auinger S, Faix J, Small JV, Polo S, Stradal TE, Rottner KMonitoring Editor: David G. Drubin Dynamic actin rearrangements are initiated and maintained by actin filament nucleators, including the Arp2/3-complex. This protein assembly is activated in vitro by distinct nucleation promoting factors such as WASP/Scar family proteins or cortactin, but the relative in vivo functions of each of them remain controversial. Here we report the conditional genetic disruption of murine cortactin, implicated previously in dynamic actin reorganizations driving lamellipodium protrusion and endocytosis. Unexpectedly, cortactin-deficient cells showed little changes in overall cell morphology and growth. Ultrastructural analyses and live-cell imaging studies revealed unimpaired lamellipodial architecture, Rac-induced protrusion and actin network turnover, although actin assembly rates in the lamellipodium were modestly increased. In contrast, PDGF-induced actin reorganization and Rac activation were impaired in cortactin null cells. In addition, cortactin deficiency caused reduction of Cdc42 activity, and defects in random and directed cell migration. Reduced migration of cortactin null cells could be restored, at least in part, by active Rac and Cdc42 variants. Finally, cortactin removal did not affect the efficiency of receptor-mediated endocytosis. Together, we conclude that cortactin is fully dispensible for Arp2/3-complex activation during lamellipodia protrusion or clathrin pit endocytosis. Furthermore, we propose that cortactin promotes cell migration indirectly, through contributing to activation of selected Rho-GTPases.

Cesarean scar ectopic pregnancy in a patient with multiple prior cesarean sections: a case report.

J Reprod Med. 2009 Apr; 54(4): 251-4Kiley J, Shulman LPBACKGROUND: Cesarean scar pregnancy, an abnormal gestation implanted in the hysterotomy site of a previous cesarean section, is a unique type of ectopic pregnancy. Once uncommon, these life-threatening gestations are increasing in frequency. Outcomes depend on a high index of suspicion and early diagnosis. CASE: A 39-year-old, gravida 9, para 5-0-3-5, with a history of 5 cesarean deliveries, presented with vaginal bleeding secondary to cesarean scar pregnancy at 8 weeks' gestation. The patient, who desired future fertillty, was successfully treated conservatively with methotrexate and uterine artery embolization. CONCLUSION: Reports of cesarean scar pregnancies are rising in the literature, and we describe a scar pregnancy in a woman with multiple prior cesareans. Although the relationship between cesarean scar pregnancy and the number of previous cesarean deliveries is unclear, rising cesarean section rates worldwide will further increase overall incidence. The optimal treatment modality remains uncertain, but conservative management is appropriate when desired by the patient and administered under close observation.

Signal Intensity of Myocardial Scars at Delayed-enhanced MRI.

Acta Radiol. 2009 May 15; 1-6Themudo RE, Johansson L, Ebeling-Barbier C, Lind L, Ahlstrom H, Bjerner TBackground: Traditionally, unrecognized myocardial infarction (UMI) is defined as the appearance, in a non-acute setting, of a new diagnostic Q wave. In the recent past, delayed-enhanced magnetic resonance imaging (DE-MRI) has provided a new imaging method for evaluating myocardial viability and to detect myocardial scars. Purpose: To investigate differences in tissue characteristics between UMI and recognized myocardial infarction (RMI) scars, by assessing the signal intensity (SI) detected by DE-MRI. Material and Methods: A randomized subgroup of 259 subjects from the Prospective Investigation of the Vasculature of Uppsala Seniors (PIVUS) study was submitted to cardiac magnetic resonance imaging (MRI). DE-MRI-detected myocardial scars were divided in two groups, UMI and RMI, according to the hospital medical records. The scars detected by DE-MRI were analyzed by measuring SI ratio of scar tissue to normal myocardium. Results: The mean SI ratio in the UMI group (4.5+/-3.0, mean+/-SD) was lower than in the RMI group 8.9+/-5.1 (P-value = 0.001). This difference was still significant (P

A randomised controlled trial of amniotic membrane in the treatment of a standardised burn injury in the merino lamb.

Burns. 2009 May 15; Fraser JF, Cuttle L, Kempf M, Phillips GE, Hayes MT, Kimble RMBurn injury is associated with disabling scar formation which impacts on many aspects of the patient's life. Previously we have shown that the fetus heals a deep dermal burn in a scarless fashion. Amniotic membrane (AM) is the outermost fetal tisue and has beeen used as a dressing in thermal injuries, though there is little data to support this use. To assess the efficacy of AM in scar minimisation after deep dermal burn wound, we conducted a randomised controlled study in the 1-month lamb. Lambs were delivered by caesarian section and the amniotic membranes stored after which lambs were returned to their mothers post-operatively. At 1 month, a standardised deep dermal burn was created under general anaesthesia on both flanks of the lamb. One flank was covered with unmatched AM, the other with paraffin gauze. Animals were sequentially euthanased from Day 3-60 after injury and tissue analysed for histopathology and immunohistochemically for alpha-smooth muscle actin (alphaSMA) content. AM resulted in reduced scar tissue as assessed histopathologically and reduced alphaSMA content. This study provides the first laboratory evidence that AM may reduce scar formation after burn injury.

CT and MR Imaging Findings in Patients with Acquired Heart Disease at Risk for Sudden Cardiac Death.

Radiographics. 2009 May-Jun; 29(3): 805-23Sparrow PJ, Merchant N, Provost YL, Doyle DJ, Nguyen ET, Paul NSNoninvasive imaging is an important screening and diagnostic tool in conditions associated with sudden cardiac death. The most common cause of sudden cardiac death is coronary artery disease, with myocarditis, cardiac sarcoidosis, and dilated and infiltrative cardiomyopathies being less common acquired causes. Common risk factors for sudden cardiac death, regardless of the disease process, include severe ventricular dysfunction and the presence of macroscopic scar seen at delayed contrast material-enhanced imaging. Recent advances in electrocardiographically (ECG) gated cardiac magnetic resonance (MR) imaging and multidetector computed tomography (CT) have led to increased referrals for cross-sectional imaging; thus, cardiac radiologists should be familiar with the disease entities associated with sudden cardiac death. Inflammatory processes and cardiomyopathies are best depicted with cardiac MR imaging. Steady-state free precession cine sequences coupled with inversion-recovery prepared gradient-echo T1-weighted sequences performed after the intravenous administration of gadolinium-based contrast material should form the basis of cardiac MR imaging protocols for cardiomyopathy. A clinical history that is suggestive of myocardial ischemia, specific requests to exclude coronary artery disease, or contraindications for MR imaging may imply that multidetector CT would be more appropriate. Nevertheless, both cardiac MR imaging and ECG-gated multidetector CT offer robust diagnosis and risk stratification for individual disease processes associated with sudden cardiac death. (c) RSNA, 2009.

Control protocol for robust in vitro glial scar formation around microwires: essential roles of bFGF and serum in gliosis.

J Neurosci Methods. 2009 May 14; Polikov VS, Su EC, Ball MA, Hong JS, Reichert WMPreviously, we reported an in vitro cell culture model that recreates many of the hallmarks of glial scarring around electrodes used for recording in the brain; however, the model lacked the reproducibility necessary to establish a useful characterization tool. This methods paper describes a protocol, modeled on protocols typically used to culture neural stem/precursor cells, that generates a predictable positive control of an intense scarring reaction. Six independent cell culture variables (growth media, seeding density, bFGF addition day, serum concentration in treatment media, treatment day, and duration of culture) were varied systematically and the resulting scars were quantified. The following conditions were found to give the highest level of scarring: Neurobasal medium supplemented with B27, 10% fetal bovine serum at treatment, 10ng/ml b-FGF addition at seeding and at treatment, treatment at least 6 days after seeding and scar growth of at least 5 days. Seeding density did not affect scarring as long as at least 500,000 cells were seeded per well, but appropriate media, bFGF, and serum were essential for significant scar formation - insights that help validate the in vitro-based approach to understanding glial scarring. With the control protocol developed in this study producing a strong, reproducible glial scarring positive control with every dissection, this culture model is suitable for the in vitro study of the mechanisms behind glial scarring and neuroelectrode failure.

Complete removal of load is detrimental to rotator cuff healing.

J Shoulder Elbow Surg. 2009 May 6; Galatz LM, Charlton N, Das R, Mike Kim H, Havlioglu N, Thomopoulos SHYPOTHESIS: This study evaluated the effect of the mechanical environment on the healing rotator cuff by paralyzing the supraspinatus muscle in the operative shoulder of a rat model of rotator cuff injury and repair. METHODS: Unilateral shoulders of rats underwent a supraspinatus injury and repair. Botulinum toxin A was used to paralyze the muscle after repair. Postoperatively, 1 group was immobilized and 1 group was allowed free range of motion. Saline-injected, casted rats were used as the control group. Repairs were evaluated histologically, geometrically, and biomechanically. RESULTS: Specimens from the saline-injected rats had greater scar volume and cross-sectional area of the repair compared with the paralyzed groups. Structural properties were increased in the saline group compared with the paralyzed groups. Free range of motion (ie, uncasted group) resulted in modest improvements in biomechanical properties but did not obviate the effect of paralysis. CONCLUSIONS: Complete removal of load was detrimental to rotator cuff healing, especially when combined with immobilization. LEVEL OF EVIDENCE: Basic science study.

Spontaneous recovery of myocardial function after ligation of Ameroid-stenosed coronary artery.

Scand Cardiovasc J. 2009 May 13; 1-9Patila T, Ikonen T, Kankuri E, Ahonen A, Krogerus L, Lauerma K, Harjula AObjectives. We aimed to assess the spontaneous healing of myocardial function after occlusion of a chronically stenosed coronary vessel in a porcine model. Design. Ischemia and infarction was produced by Ameroid constrictor placement and a subsequent ligation of the left circumflex artery. Cardiac MRI and 18FDG-PET were performed one and five weeks later. Ki67 staining was used to identify proliferating cells. Results. Restoration of perfusion defect was detected by MRI (p = 0.0065), reduced systolic function of the lateral segment spontaneously recovered (p = 0.03). There was also a suggestive raise in impaired ejection fraction (p = 0.06). Left ventricular early diastolic filling and peak filling rate were substantially improved (p = 0.039 and p = 0.0078). Scar size reduced (p = 0.03). On the 18FDG-PET, deranged metabolism was alleviated (p = 0.03). Cardiomyocytes with positive Ki-67 staining were located principally in the non-infarcted myocardium as compared to the infarction or border areas (p = 0.037). Conclusions. We demonstrated spontaneous functional healing of ischemic and infarcted left ventricle, suggesting border zone perfusion recovery. Scar reduction was detected. Different pattern of myocyte proliferation between infarction and non-ischemic myocardium was seen.

Differential Long-Term Stimulation of Type I versus Type III Collagen After Infrared Irradiation.

Dermatol Surg. 2009 Apr 27; Tanaka Y, Matsuo K, Yuzuriha S, Shinohara HBACKGROUND The dermis is composed primarily of type I (soft) and type III (rigid scar-like) collagen. Collagen degradation is considered the primary cause of skin aging. Studies have proved the efficacy of infrared irradiation on collagen stimulation but have not investigated the differential long-term effects of infrared irradiation on type I and type III collagen. OBJECTIVE To determine differential long-term stimulation of type I and type III collagen after infrared (1,100-1,800 nm) irradiation. METHODS AND MATERIALS In vivo rat tissue was irradiated using the infrared device. Histology samples were analyzed for type I and III collagen stimulation, visual changes from baseline, and treatment safety up to 90 days post-treatment. RESULTS Infrared irradiation provided long-term stimulation of type I collagen and temporary stimulation of type III collagen. Treatment also created long-term smoothing of the epidermis, with no observed complications. CONCLUSIONS Infrared irradiation provides safe, consistent, long-term stimulation of type I collagen but only short-term stimulation in the more rigid type III collagen. This is preferential for cosmetic patients looking for improvement in laxity and wrinkles while seeking smoother, more youthful skin. The authors have indicated no significant interest with commercial supporters.

Promoted activation of matrix metalloproteinase (MMP)-2 in keloid fibroblasts and increased expression of MMP-2 in collagen bundle regions: implications for mechanisms of keloid progression.

Histopathology. 2009 May; 54(6): 722-30Imaizumi R, Akasaka Y, Inomata N, Okada E, Ito K, Ishikawa Y, Maruyama YAIMS: Keloid is characterized by excessive deposition of collagen, resulting from aberrant extracellular matrix (ECM) production and degradation. The aim was to investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in pathological wound healing in keloids. METHODS AND RESULTS: Semiquantitative analysis of 60 keloid tissue samples and 25 mature scar tissue samples demonstrated significantly increased expression of MMP-2, TIMP-2 and TIMP-3 in keloids compared with mature scars. Within keloid regions, MMP-2 expression was significantly higher in collagen bundle regions than in non-collagen bundle regions. Double immunofluorescence revealed that keloid fibroblasts between collagen bundles exhibited MMP-2, TIMP-2 and membrane-type 1 MMP (MT1-MMP) co-expression, whereas only MMP-2 expression was evident on the edge of collagen bundles. Western blot analysis and gelatin zymography of 13 keloid-derived fibroblasts (KFbs) and six normal skin dermal-derived fibroblasts (NFbs) demonstrated that unstimulated KFbs exhibited significantly increased MMP-2 activity and expression compared with NFbs under the same conditions. CONCLUSIONS: These results together indicate that MMP-2 activity can be promoted in keloid fibroblasts between collagen bundles in cooperation with TIMP-2 and MT1-MMP. This could contribute to remodelling of collagen bundle regions and invasion of fibroblasts into peripheral normal regions through promoted degradation of ECM.

Open versus minimal invasive repair with achillon device.

Foot Ankle Int. 2009 May; 30(5): 391-7Aktas S, Kocaoglu BBACKGROUND: We prospectively analyzed and compared the functional and clinical results of patients with standard open and minimally invasive repair with the Achillon suture system at mid-term followup. MATERIALS AND METHODS: From February 2004 to May 2007, 40 consecutive patients were operated for the treatment of acute Achilles tendon rupture with two different methods. None of the cases required adjunctive procedures like plantaris, flexor hallucis longus or gastrocnemius augmentation (Lindholm, Bosworth) to allow for acceptable end to end apposition. The patients were divided equally into two groups. In Group 1, only Krakow end-to-end suturing technique and in Group 2, Minimal invasive repair with Achillon suture system (Integra Life Sciences Corporation, Plainsboro, NJ) was used respectively. The average age of the patients was 40 years. Patients in study groups were followed up at mean of 22.4 (range, 10 to 48) months after surgery. At the end of the followup time, functional outcome scores and complications were evaluated. RESULTS: The AOFAS hindfoot clinical outcome scores were 98.7 in Group 1, 96.8 in Group 2. Although there was a numerical increase in AOFAS Scores in Group 1, there was no significant difference. The surgical outcome concerning local tenderness, skin adhesions, scar and tendon thickness was better in Group 2 than in Group 1 with statistical significance. CONCLUSION: Although functional outcomes of both treatment groups were the same, minimally invasive repair with the Achillon suture system provided safe, reliable and practical treatment with low risk of complications in the treatment of acute Achilles tendon ruptures.

The use of 1540 nm fractional photothermolysis for the treatment of acne scars in Asian skin: a pilot study.

Photodermatol Photoimmunol Photomed. 2009 Jun; 25(3): 138-42Yoo KH, Ahn JY, Kim JY, Li K, Seo SJ, Hong CKBACKGROUND: Various modalities have been used to treat acne scars, but limited efficacy and considerable side effects have restricted their proper use. Recently, a new-generation fractional photothermolysis modality has been introduced that has deeper penetrating ability; however, a 1540 nm fractional photothermolysis study has not yet been performed. OBJECTIVES: To evaluate the efficacy and safety of 1540 nm fractional photothermolysis for the treatment of acne scars in Asian skin. METHODS: Sixteen volunteers (Fitzpatrick skin types III-IV) with mild to moderate acne scars were enrolled. Acne scar lesions were treated with 1540-nm fractional photothermolysis (Starlux 1540). Three treatment sessions were performed for each patient 4 weeks apart. Outcome assessments included the following four methods: (1) clinical evaluation of the photographs that were taken before and after the treatment; (2) comparison of the quality of life (QOL) of the patients before and after the treatment; (3) patients' satisfaction with the treatment; and (4) comparison of the quantity of collagen and elastic fibers in the skin biopsies before and 12 weeks after the last treatment. RESULTS: A mild to moderate clinical improvement was observed in most of the patients. Moreover, the QOL of all the patients improved, and all of them were satisfied with the results of the treatment. Significant collagen and elastic-fiber increases were also observed after the treatment, and side effects were limited to transient erythema and edema, which occurred in 50% of the patients. No severe side effect was observed. CONCLUSIONS: 1540 nm fractional photothermolysis is an effective and safe method for improving acne scar, even in Asian skin.

Effect of botulinum toxin type a on a rat surgical wound model.

Clin Exp Otorhinolaryngol. 2009 Mar; 2(1): 20-7Lee BJ, Jeong JH, Wang SG, Lee JC, Goh EK, Kim HWOBJECTIVES: The tension on a wound is one of the important factors that determine the degree of fibrosis and scar formation. We hypothesized that local botulinum toxin type A (Botox) induced paralysis of the musculature subjacent to a surgical wound with a skin defect would minimize the repetitive tensile forces on the surgical wound's edges, and this will result in a decreased fibroplastic response and fibrosis of the wound. METHODS: This is a prospective randomized experimental study. Two distinct surgical wounds were made to the dorsum of 15 adult rats, respectively. One of the 2 wounds was injected with Botox, and the other wound was used as a control, and this was done for all the rats' wounds. We evaluated the wound size, the degree of fibrosis and inflammation, the blood vessel proliferation, the thickness of the wound and the expression of transforming growth factor (TGF)-beta1 in the wounds. RESULTS: There were significant differences of wound size at the 3rd and 4th week between the Botox and control groups (P

Causes of severe visual impairment and blindness in children in schools for the blind in eastern Africa: changes in the last 14 years.

Ophthalmic Epidemiol. 2009 May-Jun; 16(3): 151-5Njuguna M, Msukwa G, Shilio B, Tumwesigye C, Courtright P, Lewallen SPURPOSE: To determine the causes of severe visual impairment and blindness in children attending schools for the blind in Kenya, Malawi, Uganda, and Tanzania and to compare the findings with those of a 1994 study. METHODS: Children attending schools for the blind or annexes in 4 eastern African countries were examined. The major anatomical site of and underlying etiology of severe visual impairment and blindness was recorded using the standardized World Health Organization (WHO) reporting form. RESULTS: A total of 1062 children aged below 16 years were examined of whom 701 (65.2%) had severe visual impairment or blindness. The major anatomical sites of visual loss overall (% and 95% CI) were cornea scar/phthisis bulbi (19%,16.1-21.9), whole globe lesions (15.7%,13.0-18.4), retina (15.4 %, 12.7-18.1), lens related disorders (13.1%, 10.7-15.5), and optic nerve disorders (12.3%, 9.9-14.7). Corneal scar/phthisis was not distributed equally among the countries and was highest in Malawi, similar to findings in 1995. The major etiology of visual loss was childhood factors (29.9%) and an estimated 40% of severe visual impairment and blindness was due to potentially avoidable causes. CONCLUSION: The major causes of severe visual impairment and blindness overall have not changed appreciably since 1995. There are important differences among countries, however, and using overall estimates for planning may be misleading.

SSR and SCAR mapping of a multiple-allele male-sterile gene in Chinese cabbage (Brassica rapa L.).

Theor Appl Genet. 2009 May 13; Feng H, Wei P, Piao ZY, Liu ZY, Li CY, Wang YG, Ji RQ, Ji SJ, Zou T, Choi SR, Lim YPThe genic multiple-allele inherited male-sterile gene Ms in Chinese cabbage (Brassica rapa L.) was identified as a spontaneous mutation. Applying this gene to hybrid seed production, several B. rapa cultivars have been successfully bred in China. A BC(1) population (244 plants) was constructed for mapping the Ms gene. Screening 268 simple sequence repeat (SSR) markers which cover the entire genome of Chinese cabbage was performed with bulked segregant analysis (BSA). On the basis of linkage analysis, the Ms gene was located on linkage group R07. In addition, through the amplified fragment length polymorphism (AFLP) and the sequence-characterized amplified region (SCAR) techniques combining BSA, two SCAR markers which were converted from corresponding AFLP markers flanked the Ms gene. Finally, a genetic map of the Ms gene was constructed covering a total interval of 9.0 cM. Two SCAR markers, syau_scr01 and syau_scr04, flanked the Ms gene at distances of 0.8 and 2.5 cM, respectively. All the SSR markers (cnu_m273, cnu_m030, cnu_m295, and syau_m13) were mapped on the same side of the gene as syau_scr04, the nearest one of which, syau_m13, was mapped at a distance of 3.3 cM. These SSR and SCAR markers may be useful in marker-assisted selection and map-based cloning.

Degradable PLGA scaffolds with basic fibroblast growth factor: experimental studies in myocardial revascularization.

Tex Heart Inst J. 2009; 36(2): 89-97Wang Y, Liu XC, Zhao J, Kong XR, Shi RF, Zhao XB, Song CX, Liu TJ, Lu FOur goal was to investigate the efficacy of degradable poly(D,L-lactic-coglycolic acid) (PLGA) scaffolds loaded with basic fibroblast growth factor (bFGF) in inducing cardiac neovascularization, increasing perfusion, and improving cardiac function.For ease of scaffold implantation into the ventricular wall, we developed a channel-producing device. Mini-swine, established as the animal model, were grouped as follows: channels-alone (control) group, channels and blank scaffolds (CBS) group, and channels and bFGF-incorporating scaffolds (CFS) group. Two scaffolds were implanted in each animal in the CBS and CFS groups. Six weeks postoperatively, endothelial cells were immunohistologically stained for von Willebrand factor, and proliferating cells for Ki-67 antigen. The density of new vessels was counted by image-analysis software. Left ventricular function and myocardial perfusion were documented by echocardiography and nuclear scanning, respectively, before implantation and 6 weeks postoperatively.The combined application of PLGA and bFGF ensured sustained release of growth factor in the target region. In the CFS group, Ki-67-positively stained cells, vascular density, and perfusion-defect percentage all showed significant improvement (P < 0.001), compared with the control and CBS groups, which did not. Moreover, the left ventricular fractional shortening percentage in the CFS group (28.98% +/- 1.24%) showed a significant increase, compared with the control group (26.57% +/- 1.92%, P = 0.009) and the CBS group (27.11% +/- 0.71%, P = 0.033), neither of which showed a difference (P = 0.508).The bFGF-incorporating PLGA scaffold can promote neovascular formation, enhance blood-flow perfusion, and improve myocardial function, although the original scaffold lumina were eventually occluded by inflammatory cells and scar tissue.

Traumatic brain injury results in disparate regions of chondroitin sulfate proteoglycan expression that are temporally limited.

J Neurosci Res. 2009 May 12; Harris NG, Carmichael ST, Hovda DA, Sutton RLAxonal injury is a major hallmark of traumatic brain injury (TBI), and it seems likely that therapies directed toward enhancing axon repair could potentially improve functional outcomes. One potential target is chondroitin sulfate proteoglycans (CSPGs), which are major axon growth inhibitory molecules that are generally, but not always, up-regulated after central nervous system injury. The current study was designed to determine temporal changes in cerebral cortical mRNA or protein expression levels of CSPGs and to determine their regional localization and cellular association by using immunohistochemistry in a controlled cortical impact model of TBI. The results showed significant increases in versican mRNA at 4 and 14 days after TBI but no change in neurocan, aggrecan, or phosphacan. Semiquantitative Western blot (WB) analysis of cortical CSPG protein expression revealed a significant ipsilateral decrease of all CSPGs at 1 day after TBI. Lower CSPG protein levels were sustained until at least 14 days, after which the levels began to normalize. Immunohistochemistry data confirm previous reports of regional increases in CSPG proteins after CNS injury, seen primarily within the developing glial scar after TBI, but also corroborate the WB data by revealing wide areas of pericontusional tissue that are deficient in both extracellular and perineuronal net-associated CSPGs. Given the evidence that CSPGs are largely inhibitory to axonal growth, we interpret these data to indicate a potential for regional spontaneous plasticity after TBI. If this were the case, the gradual normalization of CSPG proteins over time postinjury would suggest that this may be temporally as well as regionally limited. (c) 2009 Wiley-Liss, Inc.

Pure 'natural orifice transluminal endoscopic surgery' for transvaginal nephrectomy in the porcine model.

BJU Int. 2009 Apr 4; Haber GP, Brethauer S, Crouzet S, Berger A, Gatmaitan P, Kamoi K, Gill IOBJECTIVES To determine the technical feasibility and reproducibility of pure natural orifice transluminal endoscopic surgery (NOTES) transvaginal nephrectomy using NOTES-specific instrumentation, with no transabdominal assistance. MATERIALS AND METHODS Five female farm pigs (mean weight 45 kg) had a right NOTES nephrectomy, using a single-channel gastroscope in the first three pigs and a dual-channel gastroscope in the remaining two. The peritoneal cavity was accessed through the posterior fornix of the vagina. Dissection was started at the lower pole of the kidney, and the ureter was retracted laterally and followed towards the hilum. An XL articulated 60 cm endo-GIA stapler (US Surgical, Norwalk, CO, USA), inserted transvaginally via a separate vaginal incision, was used for tissue retraction and renal hilar transection. The kidney was freed, entrapped in an impermeable sac, and extracted intact transvaginally. RESULTS All five procedures were successful with no addition of a transabdominal laparoscopic port or open conversion. The total operative duration decreased from 200 min in the first pig to 60 min in the last (mean 113 min); the mean blood loss was

Health-related quality of life assessment after breast reconstruction.

Br J Surg. 2009 May 11; 96(6): 613-620Potter S, Thomson HJ, Greenwood RJ, Hopwood P, Winters ZEBACKGROUND:: Health-related quality of life (HRQL) is an important outcome following breast reconstruction. This study evaluated current methods of HRQL assessment in patients undergoing latissimus dorsi breast reconstruction, hypothesizing that early surgical morbidity would be reflected by poorer HRQL scores. METHODS:: Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and breast module (QLQ-BR23), the Functional Assessment of Cancer Therapy (FACT) general measure, and breast module and arm subscale (FACT-B + 4), and the Body Image Scale and Hospital Anxiety and Depression Scale (HADS) 3 months after surgery. They also reported additional HRQL problems not included in the questionnaires. HRQL scores were compared between patients with and without early surgical morbidity. RESULTS:: Sixty women completed the questionnaires, of whom 25 (42 per cent) experienced complications. All EORTC and FACT subscale and HADS scores were similar in patients with or without morbidity. Women with complications were twice as likely to report feeling less feminine and dissatisfied with the appearance of their scar than those without problems. Thirty-two women (53 per cent) complained of problems not covered by the questionnaires, most commonly donor-site morbidity. CONCLUSION:: Existing HRQL instruments are not sufficiently sensitive to detect clinically relevant problems following breast reconstruction. Copyright (c) 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Attenuation of alpha1 Collagen Production with Antisense Ribonucleic Acid in Cultured Hypertrophic Scar Fibroblasts.

J Cutan Med Surg. 2009 May-Jun; 13(3): 129-33Ju-Lin X, Shao-Hai Q, Tian-Zeng L, Chao-Quan L, Hou-Dong L, Ying-Bin X, Xu-Sheng L, Bin S, Hui-Zhen L, Yong HBACKGROUND:It has been demonstrated that hypertrophic scar fibroblasts (HSFs) overexpress collagen messenger ribonucleic acid (mRNA) and protein, especially alpha1 collagen. Antisense nucleic acids are effective in inhibiting harmful or uncontrolled gene expression, suggesting that antisense ribonucleic acid (RNA) can effectively downregulate the expression of alpha1 collagen gene and attenuate the scars.AIMS:This study was conducted to observe the effect of recombinant plasmid pREP9-COL1 on alpha1 collagen expression in HSFs and clarify the prospect of antisense RNA on scar treatment.METHODS:The alpha1 collagen gene fragment including the region of 5' UTR to exon (229 bp) was cloned in the eukaryotic expression plasmid pREP9 in the antisense orientation relative to the RSV-LTR promoter to reconstruct the pREP9- COL1 plasmid. Then it was transferred into HSFs through lipofectamine. The expression of alpha1 collagen was examined by immunostaining, reverse-transcriptase polymerase chain reaction, and Western blots.RESULTS:The recombinant plasmid pREP9-COL1 with a correct sequence was constructed successfully; pREP9-COL1 consistently inhibited human alpha1 collagen gene expression at both mRNA and protein levels.CONCLUSIONS:Antisense RNA was effective in downregulating alpha1 collagen expression of HSFs. Therefore, this approach offered a prospect of scar treatment by attenuation of alpha1 collagen production with antisense RNA.

[Application of labium minus flaps in vaginal plastic surgery]

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009 Apr; 23(4): 448-50Tang Y, Zhou C, Li Y, Li Q, Li F, Zhao M, Yang ZOBJECTIVE: To investigate the surgical procedures and outcomes of repairing the wound in the posterior wall of vaginal orifice by labium minus flap transfer, when vagina tightening plastic surgery is performed on the patient with scar in the posterior wall of vaginal orifice and labium minus hypertrophy. METHODS: From May 2007 to May 2008, 10 patients suffering from postpartum vaginal relaxation combined with scar in the posterior wall of vaginal orifice and labium minus hypertrophy were treated. The patients aged 28-40 years old and the width of their labium minus was 3-5 cm. Six of them had coitus pain. Vaginal tightening surgery was performed, meanwhile the hypertrophic labium minus was prepared into the anterior-pedicle labium minus flap (4 cm x 1 cm - 5 cm x 1 cm) and the posterior-pedicle labium minus flap (3 cm x 2 cm - 4 cm x 3 cm), respectively. The posterior-pedicle labium minus flap was transferred inwards by 90 degrees to repair the wound caused by the resection of the scar, and the anterior-pedicle labium minus flap was sutured in situ to form the new labium minus. RESULTS: All the posterior-pedicle labium minus flaps survived, except for 3 cases in which the epidermis 1 cm around the distal end of posterior-pedicle labium minus flap was exfoliated and recovered 2 weeks after hip bath with potassium permanganate solution (1:5000). All the anterior-pedicle labium minus flaps survived, and all the incisions healed by first intention. Over the follow-up period of 2-8 months, all the patients were satisfied with their vulva configuration, good elasticity of vaginal orifice and no tenderness pain of vaginal orifice. The sensitivities to feeling, such as touch and pain, of the transferred labium minus flap were similar to the normal labium minus. Postoperatively, the coitus pain disappeared, 7 cases had much better sex life and 3 cases had no significant improvement in sex life. CONCLUSION: Transferring labium minus flap to vaginal orifice is an effective way to improve the coital pain resulted from the scar of vaginal orifice.

Bone marrow stem cells implantation with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel improves cardiac function after myocardial infarction.

Acta Biomater. 2009 May 5; Wang T, Jiang XJ, Tang QZ, Li XY, Lin T, Wu DQ, Zhang XZ, Okello EBACKGROUND: Cellular transplantation represents a promising therapy for myocardial infarction (MI). However, it is limited by low transplanted cell retention and survival within the ischemic tissue. This study was designed to investigate whether injectable alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel could improve cell transplant retention and survival, reduce infarct expansion, and inhibit left ventricle (LV) remodeling. METHODS AND RESULTS: Bone marrow derived stem cells (BMSCs) were encapsulated in alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel and kept the morphologies during the cell culturing, MTT assays were used for in vitro cell viability studies of the hydrogel and showed non-cytotoxic. 7 days after MI, 100mul alpha-cyclodextrin solution containing 2o10(7) BMSCs and 100mul MPEG-PCL-MPEG solution were injected into the infarcted myocardium simultaneously, the solutions solidified immediately after injection. Injection of culture medium or cell alone served as controls. Four weeks after the treatments, histological analysis indicated that the hydrogel was absorbed, injection of BMSCs with hydrogel increased cell retention and vessel density around the infarct, and subsequently prevented scar expansion compared with BMSCs injection alone. Echocardiography studies showed that injection of BMSCs with hydrogel increased left ventricle ejection function, and attenuated left ventricular dilatation. CONCLUSION: This study indicated that injection of BMSCs with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel was an effective strategy which could enhance the effect of cellular transplantation therapy for myocardial infarction.

Negative pressure wound therapy for soft tissue injuries around the foot and ankle.

J Orthop Surg Res. 2009 May 9; 4(1): 14Lee HJ, Kim JW, Oh CW, Min WK, Shon OJ, Oh JK, Park BC, Ihn JCABSTRACT: BACKGROUND: This study was performed to evaluate the results of negative pressure wound therapy (NPWT) in patients with open wounds in the foot and ankle region. Materials and Methods: Using a NPWT device, 16 patients were prospectively treated for soft tissue injuries around the foot and ankle. Mean patient age was 32.8 years (range, 3-67 years). All patients had suffered an acute trauma, due to a traffic accident, a fall, or a crush injury, and all had wounds with underlying tendon or bone exposure. Necrotic tissues were debrided before applying NPWT. Dressings were changed every 3 or 4 days and treatment was continued for 18.4 days on average (range, 11-29 days). RESULTS: Exposed tendons and bone were successfully covered with healthy granulation tissue in all cases except one. The sizes of soft tissue defects reduced from 56.4cm2 to 42.9cm2 after NPWT (mean decrease of 24%). In 15 of the 16 cases, coverage with granulation tissue was achieved and followed by a skin graft. A free flap was needed to cover exposed bone and tendon in one case. No major complication occurred that was directly attributable to treatment. In terms of minor complications, two patients suffered scar contracture of grafted skin. CONCLUSION: NPWT was found to facilitate the rapid formation of healthy granulation tissue on open wounds in the foot and ankle region, and thus, to shorten healing time and minimize secondary soft tissue defect coverage procedures.

Ras inhibition attenuates myocardial ischemia-reperfusion injury.

Biochem Pharmacol. 2009 May 15; 77(10): 1593-601Pando R, Cheporko Y, Haklai R, Maysel-Auslender S, Keren G, George J, Porat E, Sagie A, Kloog Y, Hochhauser EMyocardial injury, developed after a period of ischemia/reperfusion (I/R) results in the destruction of functional heart tissue, this being replaced by scar tissue. Intracellular signaling pathways mediating cardiomyocyte death are partially understood and involve the activation of Ras. p38-MAPK, JNK and Mst-1 are downstream effectors of Ras protein. We hypothesized that S-farnesylthiosalicylic acid (FTS), a synthetic small molecule that detaches Ras from the inner cell membrane, consequently inhibiting Ras activity, reduces I/R myocardial injury in vitro and in vivo. Wistar rat hearts were isolated, mounted on the Langendorff apparatus and subjected to ischemia (30min, 37 degrees C) and reperfusion. During the reperfusion period, the hearts were perfused with FTS (1muM) solution or control buffer. Left anterior descending (LAD) ligation and subsequent reperfusion was performed in two groups of Wistar rats. Rats received 5mg/kg FTS or PBS according to two protocols: (A) FTS or PBS were administered daily 7 days prior, immediately before and 14 days (every other day) after LAD occlusion or (B) every other day for 14 days post-I/R. Hearts from FTS-treated rats (Langendorff) and FTS-treated rats (protocol A) showed a significant improvement in myocardial performance and smaller scar tissue compared with the PBS group. Infarct size in the FTS-treated group was 12.7+/-2% vs. 23.7+/-4% in the PBS-treated (in vitro) group and 17.3+/-2.5% vs. 36+/-7% compared with control I/R rats (in vivo) p

[Expression of Notch receptors, ligands and downstream target genes in epidermis of hypertrophic scar]

Zhonghua Zheng Xing Wai Ke Za Zhi. 2009 Jan; 25(1): 41-5Xia W, Pan BH, Liu B, Zhang X, Ma FC, Wang YM, Yang XT, Liu D, Guo SZOBJECTIVE: To study the expression of Notch receptors, ligands and downstream target genes in hypertrophic scar and normal skin, and to investigate its role in the development of hypertrophic scar. METHODS: By immunohistochemistry, the expression of epidermal differentiation markers- beta1 integrin, keratin 14 (K14) and keratin 19 (K19), as well as Notch 1-4 and Jagged1 were examined in hypertrophic scars and normal skins. The expression of Notch downstream genes- P21 and P63 was analyzed with real-time quantitative PCR and immunohistochemistry staining. RESULTS: Histological analysis revealed a significant epidermal thickening in the hypertrophic scars, with excessive cell layers above the basal layer. Compared to the normal epidermis, the expression of beta1 integrin, K19 and K14 decreased in hypertrophic scars (P

Wavy line closure for revision of abdominal scars with suture marks in children.

Scand J Plast Reconstr Surg Hand Surg. 2009 Apr 28; 1-5Tokioka K, Obana K, Ishida K, Nakatsuka TAlthough various methods are available to treat scars, it is difficult to manage those with suture marks that look like fish-bones, mainly because a large amount of tissue between the suture marks must be discarded with the scar. We report the wavy line closure for revision of abdominal scars with suture marks in three children who were operated on for congenital abdominal diseases. The entire scar, including all the suture marks, was excised using an incision consisting of a pair of smoothly waved lines. This incision makes it possible to reduce the tension on the wound by preserving the normal skin between the suture marks, which is followed by fine scars. The resulting wave-shaped scar is less noticeable and more resistant to postoperative contracture than a straight scar.

Advantages of open treatment for syndactyly of the foot: Defining its indications.

Scand J Plast Reconstr Surg Hand Surg. 2009 Apr 28; 1-5Hikosaka M, Ogata H, Nakajima T, Kobayashi H, Hattori N, Onishi F, Tamada IFor the repair of syndactyly of the foot, skin grafting is often used to close the skin defect, but open treatment is not common. However, with grafting, an additional scar at the donor site and patchwork-like scar at the recipient site are inevitable. Our aim was to describe the process of epithelialisation and define the indications for open treatment of syndactyly of the foot. The open treatment was used on 16 webs. The texture of epithelialised surface resembled volar skin; the visible scar was mainly at the dorsal edge; and web creep occurred predominantly on the volar side and resembled the natural slope of the commissure. Open treatment is better than skin grafting because of better match of texture without a patchwork-like scar, and it is indicated in cases of simple incomplete syndactyly of the foot that extends proximal to the distal interphalangeal joint.

[276 cases of horizontal infrahyoid myocutaneous flap.]

Rev Stomatol Chir Maxillofac. 2009 Apr 27; Ricard AS, Laurentjoye M, Faucher A, Zwetyenga N, Siberchicot F, Majoufre-Lefebvre CINTRODUCTION: The infrahyoid myocutaneous flap was described by Wang et al. in 1986. The horizontal design of the skin paddle is a modification of this technique allowing for a smaller scar. We have been systematically using this modified technique for 10 years. We had for aim to describe the interest of the horizontal infrahyoid myocutaneous flap for cervicofacial carcinology. PATIENTS AND METHODS: A horizontal infrahyoid myocutaneous flap procedure was performed in 276 cervicofacial carcinology patients for lesions of the mouth floor, the mandibular gum, the oropharynx and the tongue between March 1997 and March 2007. RESULTS: No complications were observed in 252 patients. No patient presented with total flap necrosis. DISCUSSION: Modifying the infrahyoid myocutaneous flap technique with a horizontal design of the skin paddle does not modify the reliability of the flap and prevents more extensive scars. The main indications of this technique are defects of the mouth floor, the tongue and the oropharynx.

Reversal of cardiac fibrosis and related dysfunction by relaxin.

Ann N Y Acad Sci. 2009 Apr; 1160: 278-84Du XJ, Xu Q, Lekgabe E, Gao XM, Kiriazis H, Moore XL, Dart AM, Tregear GW, Bathgate RA, Samuel CSAs a hallmark of heart disease, cardiac fibrosis contributes to the development of heart failure and arrhythmias and forms a key therapeutic target. There is a major unmet need for selective, potent, and safe antifibrotic drugs. Earlier studies revealed a cardiac fibrosis phenotype in relaxin-1-deficient mice. Recent studies in several rodent models of cardiac fibrosis have documented reversal of fibrosis by treatment with relaxin peptide or virally mediated relaxin gene delivery. In mice with surgically induced transmural myocardial infarction, relaxin therapy inhibited scar density. In these studies, however, functional benefits achieved by relaxin therapy were limited or less explored. Collectively, there is good experimental evidence that relaxin is able to reverse cardiac fibrosis due to distinct mechanisms. Future research needs to explore functional improvement following fibrosis reversal by relaxin and the usefulness of relaxin in antiarrhythmic or stem cell-based therapy.

Prominent role of relaxin in improving postinfarction heart remodeling.

Ann N Y Acad Sci. 2009 Apr; 1160: 269-77Bani D, Nistri S, Formigli L, Meacci E, Francini F, Zecchi-Orlandini SStem cell transplantation is a promising approach for treatment of the postinfarcted heart and prevention of deleterious cardiac remodeling and heart failure. We explored this issue by transplanting mouse C2C12 myoblasts, genetically engineered to express enhanced green fluorescent protein (eGFP) or eGFP and relaxin (eGFP/RLX), into swine with chronic myocardial infarction. One month later, C2C12 myoblasts selectively settled in the ischemic scar around blood vessels, showing an activated endothelium (ICAM-1 and VCAM positive). Although unable to differentiate to a muscle phenotype, these cells induced extracellular matrix (ECM) remodeling by matrix metalloprotease secretion and increased microvessel density by vascular endothelial growth factor expression. C2C12/RLX myoblasts gave better results than C2C12/GFP. By echocardiography, C2C12-engrafted swine, especially those that received C2C12/RLX, showed better heart contractility than the untreated controls. Hence, the advantage afforded by the grafted myoblasts on cardiac function is primarily dependent on their paracrine effects on ECM remodeling and vascularization.

[Essure((R)) implants for tubal sterilisation in France.]

Gynecol Obstet Fertil. 2009 Apr 30; Grosdemouge I, Engrand JB, Dhainault C, Marchand F, Martigny H, Thevenot J, Villefranque V, Lopes P, Panel POBJECTIVES: Law no. 2001-588 of 4 July 2001 liberalised the practice of tubal sterilisation in France, at the same time as a new hysteroscopic method of female sterilization appeared. The growth of this method has been spurred by the reduced need for analgesia, absence of incision and scar, reduced duration of hospitalization and diminution of costs. The aim of this study was to analyse the use of the Essure((R)) procedure in France. PATIENTS AND METHODS: This multicentre study covered seven French facilities from January 2004 through June 2006. This study included 1061 attempted placements of the Essure((R)) micro-insert, marketed by Conceptus SAS (France). RESULTS: The first placement attempt was successful in 992 cases (94.4%). The success rate for second attempts was 59% (n=23). Mean VAS was 3,23+/-0.19. Ninety-three percent of patients undergoing Essure((R)) placement were satisfied or very satisfied. DISCUSSION AND CONCLUSION: Tubal sterilisation with Essure((R)) micro-inserts is a reliable and reproducible method that requires a short period of training. In the future, the hysteroscopic pathway will replace the laparoscopic route.

Histology of periapical lesions obtained during apical surgery.

J Endod. 2009 May; 35(5): 634-42Schulz M, von Arx T, Altermatt HJ, Bosshardt DThe aim of this was to evaluate the histology of periapical lesions in teeth treated with periapical surgery. After root-end resection, the root tip was removed together with the periapical pathological tissue. Histologic sectioning was performed on calcified specimens embedded in methylmethacrylate (MMA) and on demineralized specimens embedded in LR White (Fluka, Buchs, Switzerland). The samples were evaluated with light and transmission electron microscopy (TEM). The histologic findings were classified into periapical abscesses, granulomas, or cystic lesions (true or pocket cysts). The final material comprised 70% granulomas, 23% cysts and 5% abscesses, 1% scar tissues, and 1% keratocysts. Six of 125 samples could not be used. The cystic lesions could not be subdivided into pocket or true cysts. All cysts had an epithelium-lined cavity, two of them with cilia-lined epithelium. These results show the high incidence of periapical granulomas among periapical lesions obtained during apical surgery. Periapical abscesses were a rare occasion. The histologic findings from samples obtained during apical surgery may differ from findings obtained by teeth extractions. A determination between pocket and true apical cysts is hardly possible when collecting samples by apical surgery.

Transforming growth factor-beta in allergic inflammatory disease of the upper airways: friend or foe?

Clin Exp Allergy. 2009 Apr 21; Salib RJ, Howarth PHTGF-beta is a multi-functional cytokine with a huge array of effects on a variety of cell types. It is rapidly emerging as a key major player in the way the airway epithelium behaves and its ability to repair itself. This is not only of relevance to allergic airway diseases such as asthma and allergic rhinitis, which are increasing in prevalence worldwide, but in many other diseases. The full impact any disruption of TGF-beta signalling may have in the development and persistence of allergic inflammatory airway diseases is yet to be fully realized and remains the subject of ongoing research. There has been a recent revival of interest in the role of regulatory T cells in controlling allergic inflammation. Evidence is emerging of a significant contribution by TGF-beta to this regulatory process. This review aims to summarize current knowledge relating to TGF-beta in relation to allergic inflammatory upper airways disease, and attempts to clarify some of the discrepancies and inconsistencies in this area. It also considers the therapeutic implications of novel TGF-beta therapy, including potential future applications in the treatment of nasal polyposis and reduction of post-operative scar tissue formation following endoscopic sinus surgery.

Actinic cheilitis: Evolution to squamous cell carcinoma after carbon dioxide laser vaporization. A study of 43 cases.

J Dermatolog Treat. 2009 Jan 1; 1-5Castineiras I, Del Pozo J, Mazaira M, Rodriguez-Lojo R, Fonseca EBackground: Actinic cheilitis (AC) is a precancerous lesion of the lip. Treatment of AC is indicated for prevention of squamous cell carcinoma (SCC), although the exact transition rate of AC to SCC is unknown. Carbon dioxide laser (CO(2)) vaporization seems to be an adequate therapy for AC, but there are no references about the evolution rate of AC to SCC after this treatment. Objective: To evaluate the results obtained after treatment of AC by CO(2) laser vaporization in comparison with other treatment modalities and the evolution rate of AC to SCC after CO(2) laser treatment. Methods: A retrospective review identified 43 patients with AC treated with CO(2) laser vaporization at our hospital from 2002 to 2006. Clinical and therapeutic information was evaluated. All patients were followed for more than 15 months after treatment. Results: After a mean follow-up period of 29.4 months, 3/43 treated AC showed local recurrence. Another two patients developed SCC in the treated field. A residual scar was clinically evident in two patients. Conclusions: CO(2) laser vaporization with an adequate postoperative follow-up is an effective treatment for chronic AC. Nevertheless, some patients (6%) went on to develop lip SCC. The follow-up of these patients is mandatory.

Donor Site Morbidity of the Posterior Conchal Region.

Dermatol Surg. 2009 Apr 8; Erba P, Wettstein R, D'Arpa S, Kalbermatten DFBACKGROUND The perichondral cutaneous graft (PCCG) from the posterior conchal region is an elegant solution for the coverage of facial defects with particular stability requirements. The donor defect can easily be covered with a transposition flap from the postauricular region. Although this region is a common donor site for skin grafts and has an important supporting function for glasses or hearing aids, little is known about long-term morbidity after graft harvest. OBJECTIVE To assess the morbidity of the posterior concha and the postauricular region in terms of pain, scar formation, and patient satisfaction. MATERIALS AND METHODS A retrospective study of 16 patients who had a PCCG harvested from the posterior concha. RESULTS Two patients presented with a postoperative wound dehiscence on the postauricular region and one with a keloid scar on the posterior concha. One case of transitory hyperesthesia and pain when sleeping on the operated site was observed. None had complaints related to wearing glasses or hearing aids. CONCLUSION Donor site morbidity of the postauricular and posterior conchal region is minimal and associated with high patient satisfaction, excellent aesthetic results, and emotional detachment from the hidden donor site. The authors have indicated no significant interest with commercial supporters.

Laparoscopic posthysterectomy vaginal vault excision for chronic pelvic pain and deep dyspareunia.

J Minim Invasive Gynecol. 2009 May-Jun; 16(3): 326-32Trehan AK, Sanaullah FSTUDY OBJECTIVE: To evaluate the outcome of posthysterectomy laparoscopic vaginal vault excision and its long-term effects on chronic pelvic pain, dyspareunia, quality of life, and patient satisfaction. MATERIALS AND METHODS: This is a retrospective cohort study (Canadian task force classification II-3) incorporating case note review and a postal questionnaire. It describes 22 consecutive patients who underwent laparoscopic vaginal vault excision for posthysterectomy dyspareunia and chronic pelvic pain. At laparoscopy, full thickness vaginal vault was excised along with scar tissue or any cyst. The vaginal cuff was closed laparoscopically. The patients were sent a validated questionnaire to assess their pain scores, general health, quality of life, and satisfaction with the surgery. The mean interval from vaginal vault excision and to questionnaire distribution was 1.8 years. The statistical analysis was performed with SPSS 15. RESULTS: The mean age of the women was 40 years. All women had vaginal vault tenderness on examination and underwent laparoscopic vaginal vault excision. The only intraoperative complication was 1 puncture injury of the bladder, which was produced by 10-Veres needle during manipulation. A single or a combination of additional procedures was performed at the same time. The patient satisfaction questionnaires were received from 16 (72.7%) women. Of the 16 (72.7%) respondents, 13 (81.25%) confirmed improvement in dyspareunia. The mean pain scores decreased, and quality of life and general health improved significantly after vaginal vault excision (p

Narrow angle light scatter in rabbit corneas after excimer laser surface ablation.

Ophthalmic Physiol Opt. 2009 May; 29(34th European Meeting in Visual and Physiological Optics (EMPO)): 357-362Ginis H, Pentari I, de Brouwere D, Bouzoukis D, Naoumidi I, Pallikaris ICorneal haze following excimer laser ablation is an adverse after-effect of photorefractive keratectomy (PRK) and is associated with the development of subepithelial opacities. The present work pertains to the measurement of light scattering in rabbit corneas following excimer laser treatment; to the microscopic analysis of the light-scattering corneal structures; and to the development of a mathematical model of light propagation through the post-laser treatment cornea. Photorefractive keratectomy (PRK-6D, 6 mm optical zone) followed by standard postoperative pharmaceutical treatment was performed on rabbit eyes. Animals were examined clinically on a weekly basis and sacrificed after the tenth postoperative week. Confocal microscope image sequences were acquired immediately before animal sacrifice. After the scatter measurement, the corneas were prepared for histopathological evaluation. The subepithelial structures observed using the confocal microscope correspond to refractive index (and therefore optical path difference (OPD) variation. This OPD distribution can be approximated with a fractal surface, band-pass filtered in the Fourier domain. The angular distribution of scattered light is characterised by a narrow forward peak of the order of 0.5 degrees full-width at half maximum (FWHM) in accordance with the sizes of the subepithelial structures (5-150 mum).The intensity of scattered light is correlated with the thickness of the subepithelial scar-tissue layer.

The surgical management of the sentinel lymph node in cutaneous melanoma might be different when the primary lesion was previously resected with 1 cm margin.

Nucl Med Commun. 2009 May 6; Junior ND, Anselmi CE, Riccardi F, Furian R, Fernandes DD, Brito R, Lima MD, Anselmi OEAIM: To simulate the effects of previous wide cutaneous melanoma excision in sentinel lymph node (SLN) biopsy feasibility through a change in the radiotracer injection site. MATERIALS AND METHODS: Thirty-three patients with cutaneous melanoma underwent two preoperatory lymphoscintigraphic studies. In the first, the radiopharmaceutical was injected intradermally 0.3 cm away from the lesion/scar. Dynamic images were acquired to find the SLN. On the following day, the procedure was repeated with the radiopharmaceutical injected 1 cm farther from the previous injection sites. The number of lymph nodes and sites of drainage were compared with the findings of the first study. All the patients underwent SLN biopsy using a gamma probe and patent blue. RESULTS: Seventy-five SLNs were identified with radiopharmaceutical injected at 0.3 cm from the lesion versus 82 SLNs when injected at 1.3 cm. All lymph nodes visualized with close injection were identified with the farther injection. Twenty-seven (81%) patients presented the same number and location of SLNs. Six (19%) patients presented more SLNs with the expanded technique, three patients in the same basin and three in a new lymph node station. All metastatic SLNs were harvested by the two injection techniques. CONCLUSION: The value of the SLN biopsy in patients with cutaneous melanoma is maintained even after the primary lesion has been removed with a margin of up to 1 cm. Some patients might show an increased number of SLNs and some might show drainage to additional lymph node stations.

Development of taxon-specific sequence characterized amplified region (SCAR) markers based on actin sequences and DNA amplification fingerprinting (DAF): a case study in the Phoma exigua species compl

Mol Plant Pathol. 2009 May; 10(3): 403-14Aveskamp MM, Woudenberg JH, de Gruyter J, Turco E, Groenewald JZ, Crous PWPhoma exigua is considered to be an assemblage of at least nine varieties that are mainly distinguished on the basis of host specificity and pathogenicity. However, these varieties are also reported to be weak pathogens and secondary invaders on non-host tissue. In practice, it is difficult to distinguish P. exigua from its close relatives and to correctly identify isolates up to the variety level, because of their low genetic variation and high morphological similarity. Because of quarantine issues and phytosanitary measures, a robust DNA-based tool is required for accurate and rapid identification of the separate taxa in this species complex. The present study therefore aims to develop such a tool based on unique nucleotide sequence identifiers. More than 60 strains of P. exigua and related species were compared in terms of partial actin gene sequences, or analysed using DNA amplification fingerprinting (DAF) with short, arbitrary, mini-hairpin primers. Fragments in the fingerprint unique to a single taxon were identified, purified and sequenced. Alignment of the sequence data and subsequent primer trials led to the identification of taxon-specific sequence characterized amplified regions (SCARs), and to a set of specific oligonucleotide combinations that can be used to identify these organisms in plant quarantine inspections.

Scar prevention and cosmetically enhanced wound healing using relaxin.

Ann N Y Acad Sci. 2009 Apr; 1160: 336-41Stewart DRRelaxin has previously been tested in rodent wound healing models and been shown to promote angiogenesis and to speed healing. However, pigs have been shown to be a better model for human skin in dermatology studies, so juvenile pigs were selected for a study of scar reduction and cosmetic appearance. Twelve 20- by 6-mm excisional wounds were created on the backs of all animals. Topical formulations of relaxin with 0, 0.5, or 2.5 mg/mL were applied twice daily for weeks 2-3 and then daily for weeks 3-6 in all animals. In addition, some animals received systemic relaxin, which was administered via infusion pumps at a rate of 125 microg/kg of body weight/day. Assessments of healing and cosmetic appearance were made by a dermatologist at weeks 2, 4, and 6. Wound sites were collected at 6 weeks and evaluated histologically for granulation tissue, inflammation, and collagen organization. Wounds in animals receiving systemic relaxin had an improved appearance with less redness, reduced granulation tissue, and lower amounts of inflammation. They showed a more-well-knit collagen structure compared to controls. Wounds treated with topical formulations did not show improvement over controls. The topical formulation used was found to have a short residence time, which likely limited penetration of relaxin. Reformulated relaxin preparations with improved penetration might be useful as a topical treatment for wounds to prevent or reduce scarring.

Adipose stem cell side population in the mouse.

J Tissue Eng Regen Med. 2009 May 5; Ramos TV, Wang T, Maki CB, Pascual M, Izadyar FAdipose tissue has become a reliable source of adult stem cells, which appear to possess a yet-undetermined degree of plasticity. With the difficulties associated with harvesting adult bone marrow stem cells, adipose tissue may represent a valuable and easily acquired source of stem cells. Stem cells have been identified using the DNA binding dye Hoechst 33342 and flow cytometry in various tissues known as the side population (SP). The present study shows, for the first time, the presence of side population stem cells in adult adipose tissues. Flow cytometric identification and isolation of this subpopulation of stem cells revealed that in the mouse there are 2.5% of adipose SP cells within the stromal vascular fraction of adipose tissue. In culture, mouse adipose SP cells showed the capacity to undergo in vitro differentiation into osteogenic, chondrogenic and adipogenic lineages. In NOD/SCID mice, freshly sorted mouse adipose SP cells were able to engraft and assist in wound healing. This animal model study showed that adipose SP cells were able to regenerate epithelial layers and connective tissue with minor scar formation. The ability of this novel cell population within adipose tissue to undergo directional differentiation in vitro and to regenerate skin in vivo has potential impact for uses in surgical dermal applications. Copyright (c) 2009 John Wiley & Sons, Ltd.

Neural reconnection in the transected spinal cord of the freshwater turtle Trachemys dorbignyi.

J Comp Neurol. 2009 Mar 20; 515(2): 197-214Rehermann MI, Marichal N, Russo RE, Trujillo-Cenóz OThis paper provides the first evidence that freshwater turtles are able to reconnect their completely transected spinal cords, leading to some degree of recovery of the motor functions lost after injury. Videographic analysis showed that some turtles (5 of 11) surviving more than 20 days after injury were able to initiate stepping locomotion. However, the stepping movements were slower than those of normal animals, and swimming patterns were not restored. Even though just 45% of the injured turtles recovered their stepping patterns, all showed axonal sprouting beyond the lesion site. Immunocytochemical and electron microscope images revealed the occurrence of regrowing axons crossing the severed region. A major contingent of the axons reconnecting the cord originated from sensory neurons lying in dorsal ganglia adjacent to the lesion site. The axons bridging the damaged region traveled on a cellular scaffold consisting of brain lipid-binding protein (BLBP)- and glial fibrillary acidic protein (GFAP)-positive cells and processes. Serotonergic varicose nerve fibers and endings were found at early stages of the healing process at the epicenter of the lesion. Interestingly, the glial scar commonly found in the damaged central nervous system of mammals was absent. In contrast, GFAP- and BLBP-positive processes were found running parallel to the main axis of the cord accompanying the crossing axons. J. Comp. Neurol. 515:197-214, 2009. (c) 2009 Wiley-Liss, Inc.

Implantation of amniotic membrane to reduce postlaminectomy epidural adhesions.

Eur Spine J. 2009 Apr 30; Tao H, Fan HPostlaminectomy epidural adhesion is implicated as a main cause of "failed back surgery syndrome" and associated with increased risk of complications during revision surgery. Various materials acting as mechanical barriers to reduce fibroblasts infiltration into epidural space have met with limited success. In present research, amniotic membrane (AM) was studied to investigate its effects on reducing epidural scar adhesion after laminectomy in a canine model. Laminectomy sites were created at L-1, L-3, L-5, and L-7 levels in 24 adult mongrel dogs. Freeze dried AM (FAM), cross-linked AM (CAM), and autologous free fat (AFF) were implanted, respectively, at a randomly assigned site in each dog with the remaining untreated site serving as internal control. The animals were sacrificed at 1, 6, and 12 weeks postoperatively. Then, gross pathologic observation including scar amount and adhesion tenacity, qualitative histology evaluation, and quantitative histology analysis were compared. Gross observation demonstrated that scar amount and adhesion tenacity of CAM group were significantly lower in comparison with those of FAM and non-treatment groups. A white, slightly vascularized CAM layer covered the dura mater without tenacious scar adhesion. The histology analysis also indicated reduced fibroblasts infiltration and consequent epidural fibrosis, which were similar to the results of AFF group. In conclusion, the CAM is effective in reducing epidural fibrosis and scar adhesion after laminectomy in canine model. It is a promising biomaterial for future clinical applications.

The connexin43 carboxyl-terminal peptide ACT1 modulates the biological response to silicone implants.

Plast Reconstr Surg. 2009 May; 123(5): 1440-51Soder BL, Propst JT, Brooks TM, Goodwin RL, Friedman HI, Yost MJ, Gourdie RGBACKGROUND: The implantation of a biomedical device elicits a wound-healing response that progresses through the three phases of wound healing: inflammation, cellular proliferation, and matrix remodeling. This response culminates in a fibrous collagen encapsulation of the implant. Subsequent contraction of this "scar-like" tissue can lead to physical disfigurement, implant extrusion, or impairment of implant function, necessitating surgical revision or removal. ACT1 is a synthetic peptide derived from the carboxyl-terminal sequence of the cellular gap junction protein connexin43. This novel peptide has recently been shown to modulate cutaneous wound healing, reduce scarring, and promote regenerative repair of the skin following injury. In this study, the authors investigated the ability of the ACT1 peptide to modulate the wound-healing response to biomedical device implantation. METHODS: Silicone disks coated with either vehicle control or ACT1 peptide were implanted submuscularly into male Sprague-Dawley rats. Capsulectomies were performed on days 1, 2, 3, 14, and 28. The implant capsules and surrounding tissue were analyzed histologically and biochemically. RESULTS: ACT1 modulated the wound-healing response to silicone implants by attenuating neutrophil infiltration, increasing vascularity of the capsule tissue, reducing type I collagen deposition around the implant, and reducing the continued presence of contractile myofibroblasts. CONCLUSION: ACT1 may provide an enabling technology for modulating the wound-healing response to implants, promoting integration of implanted materials and tissue-engineered devices in the human body.

Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair.

J Orthop Res. 2009 Apr 28; Chen H, Sun J, Hoemann CD, Lascau-Coman V, Ouyang W, McKee MD, Shive MS, Buschmann MDBone marrow stimulation is performed using several surgical techniques that have not been systematically compared or optimized for a desired cartilage repair outcome. In this study, we investigated acute osteochondral characteristics following microfracture and comparing to drilling in a mature rabbit model of cartilage repair. Microfracture holes were made to a depth of 2 mm and drill holes to either 2 mm or 6 mm under cooled irrigation. Animals were sacrificed 1 day postoperatively and subchondral bone assessed by histology and micro-CT. We confirmed one hypothesis that microfracture produces fractured and compacted bone around holes, essentially sealing them off from viable bone marrow and potentially impeding repair. In contrast, drilling cleanly removed bone from the holes to provide access channels to marrow stroma. Our second hypothesis that drilling would cause greater osteocyte death than microfracture due to heat necrosis was not substantiated, because more empty osteocyte lacunae were associated with microfracture than drilling, probably due to shearing and crushing of adjacent bone. Drilling deeper to 6 mm versus 2 mm penetrated the epiphyseal scar in this model and led to greater subchondral hematoma. Our study revealed distinct differences between microfracture and drilling for acute subchondral bone structure and osteocyte necrosis. Additional ongoing studies suggest these differences significantly affect long-term cartilage repair outcome. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

[Comparison of the mechanisms of intralesional steroid, interferon or verapamil injection in the treatment of proliferative scars]

Zhonghua Zheng Xing Wai Ke Za Zhi. 2009 Jan; 25(1): 37-40Xu SJ, Teng JY, Xie J, Shen MQ, Chen DMOBJECTIVE: To investigate the effects of intralesional steroid, interferon alpha-2b or verapamil injection on proliferation, apoptosis and TGF-beta1 expression in keloid and hypertrophic scar in vivo. METHODS: 6 patients with keloids and 6 patients with hypertrophic scar were treated with intralesional injection of triamcinolone acetonide (40 mg/ml) or IFN alpha-2b (15 x 10(5) U/ml) or verapamil (2.5 mg/ml). Samples were collected on the 7th day after intralesional injection. Samples of untreated keloid and hypertrophic scar and normal skin were used as control. Expression of PCNA and TGF-beta1 was detected in situ by immunohistochemical staining, and apoptosis was detected in situ by terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate-biotin nick end labeling (TUNEL). RESULTS: 1) Triamcinolone acetonide could prohibit proliferative scars through inhibiting cell proliferation and TGF-beta1 expression, as well as inducing apoptosis. 2) IFN alpha-2b could prohibit proliferative scars through inhibiting cell proliferation and TGF-beta1 expression, but not inducing apoptosis; 3) Verapamil could also prohibit proliferative scars through inhibiting proliferation and TGF-beta1 expression in fibroblasts, as well as inducing apoptosis. While the effect of inducing apoptosis was stronger than that of triamcinolone acetonide, the effect of inhibiting TGF-beta1 expression was weaker than those of triamcinolone acetonide and IFN alpha-2b. CONCLUSIONS: Although intraleional injection of steroid, interferon alpha-2b or verapamil were all effective in the treatment of keloid and hypertrophic scar, their mechanisms are not similar.

The Patient Scar Assessment Questionnaire: a reliable and valid patient-reported outcomes measure for linear scars.

Plast Reconstr Surg. 2009 May; 123(5): 1481-9Durani P, McGrouther DA, Ferguson MWBACKGROUND: There is a lack of rigorously validated patient-based outcomes measures of scarring. The aim of this study was to construct such a scale and demonstrate reliability and validity by applying the scale in a wide range of scarring samples. METHODS: The Patient Scar Assessment Questionnaire with five subscales (i.e., Appearance, Symptoms, Consciousness, Satisfaction with Appearance, and Satisfaction with Symptoms) was constructed using multiple categorical response items. The Patient Scar Assessment Questionnaire was applied to various surgical samples (total scar assessments n = 667) at months 3, 6, and 12 after surgery (and preoperatively in the scar revision group) and tested for internal consistency, test-retest reliability, convergent validity, known group differences, and sensitivity, against widely accepted criteria from psychometric measurement science. RESULTS: Subscales showed high internal consistency (Cronbach alpha, 0.73 to 0.93), except the Symptoms subscale. Test-retest reliability was high across all subscales (intraclass correlation coefficient, 0.74 to 0.87) across all groups except the scar revision group. Change in Patient Scar Assessment Questionnaire scores was significant between months 3 and 6 postoperatively (p < 0.001) and subscales demonstrated known group differences (p < 0.001). Convergent validity was demonstrated by significant moderate correlations with various measures of similar constructs (r = 0.26 to 0.61, p < 0.001). CONCLUSIONS: The Patient Scar Assessment Questionnaire is a reliable and valid measure of the patient's perception of scarring, although the Symptoms subscale requires further refinement. Subscales can be used independently of each other to allow assessment of scar change in specific domains.

Restoration of the shape, location and skin of the severe burn-damaged breast.

Burns. 2009 Apr 29; Grishkevich VMThermal injuries to the anterior chest in pre-pubescent girls result in breast contracture. During puberty, the breast parenchyma develops and grows underneath the scars, resulting in being flattened and disfigured. The breast mound, as well as the nipple-areolar complex, is partially or completely levelled out and displaced. The contours are unclear and the inframammary fold is effaced. This feature of the most severe breast contracture still poses a challenge for most surgeons. This type of breast contracture can be successfully eliminated with the author-suggested, improved free-skin grafting technique. The scars are excised and the shifted area of parenchyma is mobilised symmetrically to the border of the undamaged breast. Then, the shape and positioning of the breast as well as the nipple-areolar complex are reconstructed with the help of circular suturing through the fat layer on two to three breast levels. The suture ends are led beyond the wound area and are affixed with certain tension contralateral to the breast displacement. The suture ends, being in state of tension, are tied into untied knots around bolsters and are retained in place for about 3 months. During this time, the form and the positioning of the breast can be corrected using the traction of the untied sutures; the skin transplants are stabilised, under which the scar tissue is formed. Skin transplant and the scar tissue hold the shape and positioning of the breast and the sutures can be removed at this stage. In this series, 11 patients were operated upon and 13 breasts were reconstructed. Good results were achieved in all cases: the breast's shape and skin was restored and the positioning was corrected.

Reconstruction of postburn antebrachial contractures using pedicled thoracodorsal artery perforator flaps.

Plast Reconstr Surg. 2009 May; 123(5): 1544-52Uygur F, Sever C, Tuncer S, Alagöz SBACKGROUND: Full-thickness burns involving the antecubital area result in severe contractures. Functional impairment is inevitable if the affected areas are not managed properly. Proper treatment requires complete release and radical excision of the scar tissue, followed by reconstruction using durable tissue that will not contract during long-term follow-up. METHODS: Nine patients with flexion contractures were reconstructed with pedicled thoracodorsal artery perforator flaps between 2004 and 2008. All of the patients were male, and their ages ranged from 20 to 23 years (mean, 21.4 years). The size and orientation of the skin islands were planned according to the defect size and orientation. The size of the flaps varied from 6.5 to 9.0 cm in width (mean, 8.0 cm) and 16.0 to 21.0 cm in length (mean, 20.0 cm). All of the patients were followed up for 6 to 12 months (mean, 9.3 months). RESULTS: All of the flaps used on the postburn antecubital contractures survived completely. Minimal transient venous congestion occurred in two flaps during the early postoperative period. A complete range of motion at the elbow joint was achieved in all patients by the end of the reconstruction period. CONCLUSIONS: This study revealed that the pedicled thoracodorsal artery perforator flap is a suitable alternative for postburn elbow contractures. A very long pedicle can be obtained to transfer the flap to the antecubital area without tension. With its thin, pliable texture and large size, it adapts well to forearm skin and the donor-site scar is considered cosmetically acceptable.