Acne Scars

The Effect of the Botulinum Toxin-A on Craniofacial Development: An Experimental Study.

2009-09-13T17:36:00.001-07:00

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

Recombination is suppressed over a large region of the rainbow trout Y chromosome.

2009-09-12T15:58:00.001-07:00

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

Drosophila Cip4/Toca-1 Integrates Membrane Trafficking and Actin Dynamics through WASP and SCAR/WAVE.

2009-09-11T17:52:00.001-07:00

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

Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine.

2009-09-10T23:34:00.001-07:00

J Am Coll Cardiol. 2009 Sep 8; 54(11): 1014-23Leor J, Tuvia S, Guetta V, Manczur F, Castel D, Willenz U, PetnehÃ¡zy O, Landa N, Feinberg MS, Konen E, Goitein O, Tsur-Gang O, Shaul M, Klapper L, Cohen SOBJECTIVES: This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). BACKGROUND: Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. METHODS: We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. RESULTS: Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 +/- 0.1 mm vs. 1.9 +/- 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. CONCLUSIONS: Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.

Single-port laparoscopic totally extraperitoneal inguinal hernia repair with the TriPort system: initial experience.

2009-09-10T17:43:00.001-07:00

Surg Endosc. 2009 Sep 3; Agrawal S, Shaw A, Soon YBACKGROUND: Since the early 1990s, the laparoscopic approach to inguinal hernia repair using three ports has gained increased popularity worldwide. Recently, single-incision laparoscopic surgery to reduce the invasiveness of traditional laparoscopy further is under development. This study aimed to assess the safety and feasibility of the single-port approach for laparoscopic totally extraperitoneal (TEP) repair of inguinal hernia and to report the authors' initial experience using the TriPort system. METHODS: Between 18 October 2008 and 1 April 2009, 19 single-incision laparoscopic TEP repairs of inguinal hernia were performed for 16 patients at the Royal Surrey County Hospital, Guildford, United Kingdom. Data regarding patient demographics, type of hernia, operating time, complications, postoperative hospital stay, and recurrence were prospectively collected. The length of the incision at the time of the operation and at a clinic follow-up visit also was measured. RESULTS: All 16 patients were men, ranging in age from 21 to 87 years. Of the 16 men, 13 had a unilateral inguinal hernia. For 7 of the 13 men, the hernia was on the left side. The median operating time was 40 min for unilateral hernia and 70 min for bilateral hernia. There were no intraoperative complications and no deaths. Discharge was on the same day for 12 of the men, and within 24 h for the remaining 4 men. Minor wound complications developed for two men. One man reported transient pain in his testicle. There was no evidence of early recurrence during a median follow-up period of 72.5 days. The median incision length was 30 mm, and the median scar length at the clinic follow-up visit was 25 mm. CONCLUSION: The authors' experience has shown that single-port laparoscopic TEP inguinal hernia repair with the TriPort system is safe and feasible. Prospective randomized studies comparing single-access and conventional multiport laparoscopic TEP repairs with long-term follow-up evaluation are needed to confirm the authors' initial experience.

Probing vocal fold fibroblast response to hyaluronan in 3D contexts.

2009-09-09T23:26:00.001-07:00

Biotechnol Bioeng. 2009 Jun 8; Munoz-Pinto DJ, Jimenez-Vergara AC, Gelves LM, McMahon RE, Guiza-Arguello V, Hahn MSA number of treatments are being investigated for vocal fold (VF) scar, including designer implants. The aim of the present study was to validate a 3D model system for probing the effects of various bioactive moieties on VF fibroblast (VFF) behavior toward rational implant design. We selected poly(ethylene glycol) diacrylate (PEGDA) hydrogels as our base-scaffold due to their broadly tunable material properties. However, since cells encapsulated in PEGDA hydrogels are generally forced to take on rounded/stellate morphologies, validation of PEGDA gels as a 3D VFF model system required that the present work directly parallel previous studies involving more permissive scaffolds. We therefore chose to focus on hyaluronan (HA), a polysaccharide that has been a particular focus of the VF community. Toward this end, porcine VFFs were encapsulated in PEGDA hydrogels containing consistent levels of high M (w) HA (${rm HA}_{{rm H}{M}_{rm W} } $), intermediate M(w) HA (${rm HA}_{{rm I}{M}_{rm W} } $), or the control polysaccharide, alginate, and cultured for 7 and 21 days. ${rm HA}_{{rm H}{M}_{rm W} } $ promoted sustained increases in active ERK1/2 relative to ${rm HA}_{{rm I}{M}_{rm W} } $ . Furthermore, VFFs in ${rm HA}_{{rm I}{M}_{rm W} } $ gels displayed a more myofibroblast-like phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in ${rm HA}_{{rm H}{M}_{rm W} } $ and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to ${rm HA}_{{rm I}{M}_{rm W} } $ relative to alginate in collagen-based scaffolds permissive of cell elongation, indicating that PEGDA hydrogels may serve as an effective 3D model system for probing at least certain aspects of VFF behavior. Biotechnol. Bioeng. (c) 2009 Wiley Periodicals, Inc.

Randomized Controlled Trial to Determine the Efficacy of Long-Term Growth Hormone Treatment in Severely Burned Children.

2009-09-09T02:40:00.001-07:00

Ann Surg. 2009 Sep 2; Branski LK, Herndon DN, Barrow RE, Kulp GA, Klein GL, Suman OE, Przkora R, Meyer W, Huang T, Lee JO, Chinkes DL, Mlcak RP, Jeschke MGBACKGROUND:: Recovery from a massive burn is characterized by catabolic and hypermetabolic responses that persist up to 2 years and impair rehabilitation and reintegration. The objective of this study was to determine the effects of long-term treatment with recombinant human growth hormone (rhGH) on growth, hypermetabolism, body composition, bone metabolism, cardiac work, and scarring in a large prospective randomized single-center controlled clinical trial in pediatric patients with massive burns. PATIENTS AND METHODS:: A total of 205 pediatric patients with massive burns over 40% total body surface area were prospectively enrolled between 1998 and 2007 (clinicaltrials.gov ID NCT00675714). Patients were randomized to receive either placebo (n = 94) or long-term rhGH at 0.05, 0.1, or 0.2 mg/kg/d (n = 101). Changes in weight, body composition, bone metabolism, cardiac output, resting energy expenditure, hormones, and scar development were measured at patient discharge and at 6, 9, 12, 18, and 24 months postburn. Statistical analysis used Tukey t test or ANOVA followed by Bonferroni correction. Significance was accepted at P < 0.05. RESULTS:: RhGH administration markedly improved growth and lean body mass, whereas hypermetabolism was significantly attenuated. Serum growth hormone, insulin-like growth factor-I, and IGFBP-3 was significantly increased, whereas percent body fat content significantly decreased when compared with placebo, P < 0.05. A subset analysis revealed most lean body mass gain in the 0.2 mg/kg group, P < 0.05. Bone mineral content showed an unexpected decrease in the 0.2 mg/kg group, along with a decrease in PTH and increase in osteocalcin levels, P < 0.05. Resting energy expenditure improved with rhGH administration, most markedly in the 0.1 mg/kg/d rhGH group, P < 0.05. Cardiac output was decreased at 12 and 18 months postburn in the rhGH group. Long-term administration of 0.1 and 0.2 mg/kg/d rhGH significantly improved scarring at 12 months postburn, P < 0.05. CONCLUSION:: This large prospective clinical trial showed that long-term treatment with rhGH effectively enhances recovery of severely burned pediatric patients.

[Surgical management of primary bone cancer]

2009-09-08T17:27:00.001-07:00

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

Factors affecting willingness to undergo carpal tunnel release.

2009-09-05T16:27:00.001-07:00

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

Asian blepharoplasty: an 18-year experience in 6215 patients.

2009-09-02T08:07:00.001-07:00

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

Treating small-sized vitiligo

2009-09-02T08:00:00.000-07:00

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

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

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

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

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

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

The association between depression and anxiety disorders following facial trauma-A comparative study.

2009-08-31T18:42:00.001-07:00

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

Donor site reconstitution for ear reconstruction.

2009-08-30T15:51:00.000-07:00

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

Myocardial Fat Deposition after Left Ventricular Myocardial Infarction: Assessment by Using MR Water-Fat Separation Imaging.

2009-08-30T08:09:00.001-07:00

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

Immunohistological evaluation of the healing response at the flap interface in patients with LASIK ectasia requiring penetrating keratoplasty.

2009-08-30T03:52:00.001-07:00

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

Impact of human amniotic membrane preparation on release of angiogenic factors.

2009-08-28T22:17:00.001-07:00

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

Implanted neural electrodes cause chronic, local inflammation that is correlated with local neurodegeneration.

2009-08-28T16:19:00.001-07:00

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

Transcriptional and posttranscriptional regulators of biglycan in cardiac fibroblasts.

2009-08-27T16:00:00.001-07:00

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

The clavicle hook plate for Neer type II lateral clavicle fractures.

2009-08-27T02:35:00.001-07:00

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

An age- and sex-matched comparative study on both-bone diaphyseal paediatric forearm fracture.

2009-08-26T16:11:00.001-07:00

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

Cell Therapy Enhances Function of Remote Non-Infarcted Myocardium.

2009-08-25T15:50:00.001-07:00

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

A New Technique of Concealed Penis Repair.

2009-08-25T02:25:00.001-07:00

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

Snodgrass Urethroplasty: Grafting the Incised Plate-10 Years Later.

2009-08-24T23:01:00.001-07:00

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

Increased Expression of Integrin-Linked Kinase Attenuates Left Ventricular Remodeling and Improves Cardiac Function After Myocardial Infarction.

2009-08-24T16:14:00.001-07:00

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

Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population.

2009-08-24T08:20:00.001-07:00

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

Total Percutaneous Endovascular Aneurysm Repair with the Dual 6-F Perclose-AT Preclosing Technique: A Case-control Study.

2009-08-23T23:29:00.001-07:00

J Vasc Interv Radiol. 2009 Aug 19; Jahnke T, SchÃ¤fer JP, Charalambous N, Trentmann J, Siggelkow M, HÃ¼mme TH, Bolte H, Demirbas E, Heller M, MÃ¼ller-HÃ¼lsbeck SPURPOSE: To determine the safety and efficacy of total percutaneous access closure for endovascular aortic aneurysm repair with a suture-mediated preclosing technique. MATERIALS AND METHODS: One hundred thirty-two femoral access sites in 70 patients who underwent endovascular aortic aneurysm repair were closed percutaneously with off-label use of two F-6 Perclose AT devices preapplied at a 90 degrees angle. Femoral access sizes ranged from 12 to 24 F. Technical success, complications, and procedure and access closure times were evaluated. Follow-up with computed tomography and/or magnetic resonance imaging was scheduled at 1-4 days and 3, 6, and 12 months and used to obtain groin hematoma and scar severity scores (grades 1-3). Data were compared with those from a cohort of 67 patients who underwent endovascular aortic aneurysm repair with surgical femoral cutdown. RESULTS: Technical success was achieved with the preclosing technique in 127 of the 132 arteries (96.2%). Two to four closure devices were used per groin. Five technical failures were managed intraoperatively with surgical suture. There was no access-related mortality and no late groin complications. The mean procedure duration was 91 minutes +/- 32, and the mean access closure time was 12 minutes +/- 9. For surgical management, the mean procedure time was 153 minutes +/- 112 (P < .05), and the mean closure time was 12 minutes +/- 13 (not statistically significant). Hematoma severity score at 1-4 days was 1.8 for total percutaneous endovascular aneurysm repair and 2.1 for surgical closure. Scar severity scores at 3, 6, and 12 months were 1.1, 1.0, and 1.0 for total percutaneous endovascular aneurysm repair and 2.4, 2.4, and 2.3 for surgical management, respectively. CONCLUSIONS: Total percutaneous endovascular aneurysm repair with a dual 6-F-Perclose preclosing technique is safe and effective. Compared with femoral cutdown, there are fewer late groin complications and scar tissue formation is less severe.

Involvement of VDAC, Bax and ceramides in the efflux of AIF from mitochondria during curcumin-induced apoptosis.

2009-08-23T07:23:00.001-07:00

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

Second Dorsal Metacarpal Artery Flap From the Dorsum of the Middle Finger for Coverage of Volar Thumb Defect.

2009-08-23T00:17:00.001-07:00

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

Morbidity of en bloc resections in the spine.

2009-08-22T21:30:00.001-07:00

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

Electromechanical Delay of the Knee Flexor Muscles Is Impaired After Harvesting Hamstring Tendons for Anterior Cruciate Ligament Reconstruction.

2009-08-22T17:49:00.001-07:00

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

[Muscle indications in breast reconstruction and applications sparing latissimus dorsi flap. Vascular anatomy.]

2009-08-21T18:53:00.001-07:00

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

Chapter 25 phototherapy in peripheral nerve injury effects on muscle preservation and nerve regeneration.

2009-08-20T20:54:00.001-07:00

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

[Free functional gracilis muscle transplantation for reconstruction of active elbow flexion in posttraumatic brachial plexus lesions]

2009-08-20T17:47:00.001-07:00

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

[Pectoralis major muscle transfer for reconstruction of elbow flexion in posttraumatic brachial plexus lesions]

2009-08-20T07:42:00.001-07:00

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

Electrophysiologic substrate underlying postinfarction ventricular tachycardia: characterization and role in catheter ablation.

2009-08-20T00:05:00.001-07:00

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

A novel method to aid in the visualisation and treatment of uterine fibroids with MRgFUS in patients with abdominal scars.

2009-08-19T21:59:00.001-07:00

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

Paraplegia complicating selective steroid injections of the lumbar spine. Report of five cases and review of the literature.

2009-08-19T17:34:00.001-07:00

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

The characteristics of keratomycosis by Beauveria bassiana and its successful treatment with antimycotic agents.

2009-08-19T00:29:00.001-07:00

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

Shengmai-san-Mediated Enhancement of Regenerative Responses of Spinal Cord Axons After Injury in Rats.

2009-08-18T02:20:00.001-07:00

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

Management of severe pediatric subglottic stenosis with glottic involvement

2009-08-17T23:45:00.000-07:00

We sought to describe our experience in the management of complex glotto-subglottic stenosis in the pediatric age group.

METHODS:
Between 1978 and 2008, 33 children with glotto-subglottic stenosis underwent partial cricotracheal resection, and they form the focus of this study. They were compared with 67 children with isolated subglottic stenosis (no glottic involvement). The outcomes measured were need for revision open surgical intervention, delayed decannulation (>6 months), and operation-specific and overall decannulation rates. Fisher's exact test was used for comparison of outcomes.

RESULTS:
Results of preoperative evaluation showed Myer-Cotton grade III or IV stenosis in 32 (97%) patients and grade II stenosis in 1 patient. All patients with glotto-subglottic stenosis were treated with partial cricotracheal resection and simultaneous repair of the glottic pathology. Bilateral fixed vocal cords were seen in 19 (58%) of 33 patients, bilateral restricted abduction was seen in 7 (21%) of 33 patients, and unilateral fixed vocal cord was seen in 7 (21%) of 33 patients. Ten patients underwent single-stage partial cricotracheal resection with excision of interarytenoid scar tissue. The endotracheal tube was kept for a mean period of 7 days as a stent. Twenty-three patients underwent extended partial cricotracheal resection with LT-Mold (Bredam S.A., St. Sulpice, Switzerland) or T-tube stenting. The overall decannulation rate included 26 (79%) patients, and the operation-specific decannulation rate included 20 (61%) patients.

CONCLUSIONS:
Glotto-subglottic stenosis is a complex laryngeal injury associated with delayed decannulation and decreased overall and operation-specific decannulation rates when compared with those after subglottic stenosis without glottic involvement after partial cricotracheal resection.

Management of severe pediatric subglottic stenosis with glottic involvement.
J Thorac Cardiovasc Surg. 2009 Jun 30; George M, Jaquet Y, Ikonomidis C, Monnier P (Hubmed.org)

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Is reduction in the risk of vision loss the only benefit of photodynamic therapy in predominantly classic subfoveal choroidal neovascularization?

2009-08-17T23:25:00.001-07:00

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

New experimental delayed wound healing

2009-08-17T22:45:00.000-07:00

Chronic wounds pose important problems in clinical practice and their treatment is difficult and costly. Here we describe a new delayed wound healing animal model. Fifteen male New Zealand rabbits were used in this study.

A horizontal incision 4 cm in length was made on the dorsal part of the torso and pure skin flaps were raised in front of and behind this incision. This exposed the panniculus carnosus layer and it was resected. Skin flaps were returned to their places and sutured.

After a 3 week period of healing third degree burn injury was inflicted using hot metal plates both on the healed flaps and at the same location on the opposite side. Scar samples were sent for histopathological examination after healing.

The wounds on the panniculectomy side healed in an average of 43.20 days but on the control side they healed in an average of 32.80 days (p < 0.05). Wound healing was slower and scars were broader and more irregular on the panniculectomy side.

In our new model, addition of panniculectomy to full thickness burn injury significantly delayed wound healing with a decrease in scar quality. This is a simple, economic and effective animal model to study delayed wound healing.

"A new experimental delayed wound healing model in rabbits"
Eur J Dermatol. 2009 Aug 6; Aksoy B, Aksoy HM, CivaÅ E, UstÃ¼n H, Atakan N (Hubmed.org)

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Hydroa vacciniforme-like cutaneous T cell lymphoma

2009-08-17T19:45:00.000-07:00

To study the clinical features, diagnosis and therapy of hydroa vacciniforme-like cutaneous T cell lymphoma.

METHODS:
The clinical presentations and the findings of laboratory examinations and skin biopsy of affected tissue in a child with hydroa vacciniforme-like cutaneous T cell lymphoma were retrospectively reviewed.

RESULTS:
The child manifested as rash, fever and lymph node intumesce. Rash was pantomorphia, including edematous erythema, vesicles, crusts, necrosis and depressed scar, and it was mild in winter and severe in summer, mainly involving in the face and extremities. Epstein-Barre vivus (EBV)-IgM was positive. Histopathological findings revealed focal lymphocyte invasion in subcutaneous panniculus adiposus. The clinical symptoms were improved after glucocorticoid treatment in this child.

CONCLUSIONS:
Hydroa vacciniforme-like cutaneous T cell lymphoma has special clinical manifestations. This disorder may be definitely diagnosed by skin biopsy of affected tissue and immunohistochemistry assay. Glucocorticoid treatment is effective. EBV infection may be related to the development of this disorder.

Hydroa vacciniforme-like cutaneous T cell lymphoma: a case report and literature review
Zhongguo Dang Dai Er Ke Za Zhi. 2009 Jul; 11(7): 596-8Li HY, Wang HL, Gao TZ, Zhuo ZH, Li DM, Li H (Hubmed.org)

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Transplanted Blood-Derived Endothelial Progenitor Cells (EPC) Enhance Bridging of Sheep Tibia Critical Size Defects.

2009-08-17T05:50:00.001-07:00

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

Overcoming macrophage-mediated axonal dieback following CNS injury.

2009-08-16T22:57:00.000-07:00

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

The phenotype and potential origin of nestin cardiac myocyte-like cells following infarction.

2009-08-15T22:56:00.001-07:00

Nestin((+)) cardiac myocyte-like cells were detected in the peri-infarct/infarct region of the ischemically damaged heart. The present study was undertaken to elucidate the phenotype and potential origin of nestin((+)) cardiac myocyte-like cells and identify stimuli implicated in their appearance.

In the infarcted human and rat heart, nestin((+)) cardiac myocyte-like cells were morphologically and structurally immature, exhibited a desmin-immunoreactive striated phenotype, expressed the beta1-adrenergic receptor and associated with an aberrant pattern of connexin-43 expression and/or organization.

Nestin((+)) cardiac myocyte-like cells were detected 24 hrs post ischemic injury and persisted in the infarcted rat heart for 9 months. In the normal rat heart, cardiac progenitor transcriptional factors Nkx2.5/GATA4 were detected in a subpopulation of nestin((+)) neural stem cells.

Following an ischemic insult, nestin((+))/Nkx2.5((+)) neural stem cells migrated to the peri-infarct/infarct region and appeared to be in a primordial state of differentiation to a nestin((+)) cardiac myocyte-like cell. The exposure of adult male rats to normobaric hypoxia (12% O2) for ten days failed to promote the appearance of nestin((+)) cardiac myocyte-like cells. Following osmotic pump delivery of isoproterenol to normal adult rats, nestin((+)) cardiac myocyte-like cells were detected, albeit the response was modest and secondary to tissue loss.

Thus, ischemia-induced appearance of nestin((+)) cardiac myocyte-like cells apparently represents an adaptive response to heal the infarcted heart. Nkx2.5/GATA4 expression in a subpopulation of resident neural stem cells provides the appropriate phenotype for their potential differentiation to a nestin((+)) cardiac myocyte-like cell.

"The phenotype and potential origin of nestin(+) cardiac myocyte-like cells following infarction".
J Appl Physiol. 2009 Aug 13; Beguin PC, El-Helou V, Assimakopoulos J, Clement R, Gosselin H, Brugada R, Villeneuve L, Rohlicek CV, Del Duca D, Lapointe N, Rouleau JL, Calderone A (Hubmed.org)

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Protein kinase Cdelta activation induces close homolog of adhesion molecule L1 (CHL1) expression in cultured astrocytes.

2009-08-13T17:36:00.001-07:00

Regulation of expression of the close homolog of adhesion molecule L1 (CHL1) by reactive astrocytes in the glial scar reduces axonal regeneration and inhibits functional recovery after spinal cord injury (SCI).

Here, we investigate the molecular mechanisms underlying upregulation of CHL1 expression by analyzing the signal transduction pathways in vitro. We show that astrogliosis stimulated by bacterial lipopolysaccharide (LPS) upregulates CHL1 expression in primary cultures of mouse cerebral astrocytes, coinciding with elevated protein synthesis and translocation of protein kinase delta (PKCdelta) from cytosol to the membrane fraction.

Blocking PKCdelta activity pharmacologically and genetically attenuates LPS-induced elevation of CHL1 protein expression through a phosphatidylinositol 3-kinase (PI3K) dependent pathway. LPS induces extracellular signal-regulated kinases (ERK1/2) phosphorylation through PKCdelta and blockade of ERK1/2 activation abolishes upregulation of CHL1 expression.

LPS-triggered upregulation of CHL1 expression mediated through translocation of nuclear factor kappaB (NF-kappaB) to the nucleus is blocked by a specific NF-kappaB inhibitor and by inhibition of PI3K, PKCdelta, and ERK1/2 activities, implicating NF-kappaB as a downstream target for upregulation of CHL1 expression. Furthermore, the LPS-mediated upregulation of CHL1 expression by reactive astrocytes is inhibitory for hippocampal neurite outgrowth in cocultures.

Although the LPS-triggered NO-guanylate cyclase-cGMP pathway upregulates glial fibrillary acid protein expression in cultured astrocytes, we did not observe this pathway to mediate LPS-induced upregulation of CHL1 expression.

Our results indicate that elevated CHL1 expression by reactive astrocytes requires activation of PI3K/PKCdelta-dependent pathways and suggest that reduction of PI3K/PKCdelta activity represents a therapeutic target to downregulate CHL1 expression and thus benefit axonal regeneration after SCI. (c) 2009 Wiley-Liss, Inc.

"Phosphatidylinositol 3-kinase/protein kinase Cdelta activation induces close homolog of adhesion molecule L1 (CHL1) expression in cultured astrocytes"
Glia. 2009 Aug 11; Wu J, Wrathall JR, Schachner MUp

Severe cutaneous adverse reactions

2009-08-12T17:35:00.001-07:00

Severe cutaneous adverse reactions (SCARs) are associated with over 200 medicines including lamotrigine, an antiepileptic drug. Previous studies have suggested the involvement of immune mechanisms in the development of drug-induced SCARs.

High-resolution HLA genotyping was performed for 65 patients of European ancestry treated with lamotrigine (22 cases with lamotrigine-induced SCARs and 43 controls on lamotrigine without SCAR-related symptoms). Association of HLA genetic variants with SCARs in these patients were evaluated by contrasting allele frequencies between the cases and the controls for each of 112 HLA four-digit alleles.

RESULTS:
Five alleles were observed with higher frequencies in the cases compared with the treated controls with exact P values less than 0.05.

In contrast to the study of carbamazepine-induced Stevens-Johnson syndrome in Han Chinese patients, none of the cases carried B*1502. Accounting for the large number of hypothesis tests conducted, none of the associations identified were statistically significant.

CONCLUSION:
No single major HLA-related genetic risk factor was identified for lamotrigine-induced SCARs in patients of European origin. Only suggestive evidence was obtained for B*5801, A*6801, Cw*0718, DQB1*0609, and DRB1*1301.

Confirmation of these results in a larger, independent sample is needed to determine whether any of the HLA alleles identified are truly associated with the development of lamotrigine-induced SCARs.

"High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients."
Pharmacogenet Genomics. 2009 Aug 6; Kazeem GR, Cox C, Aponte J, Messenheimer J, Brazell C, Nelsen AC, Nelson MR, Foot E

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Submucosal tunneling using endoscopic submucosal dissection for peritoneal access and closure in natural orifice transluminal endoscopic surgery: a porcine survival study.

2009-08-12T06:37:00.001-07:00
Endoscopy. 2009 Aug; 41(8): 707-11Yoshizumi F, Yasuda K, Kawaguchi K, Suzuki K, Shiraishi N, Kitano SBACKGROUND AND STUDY AIMS: Safe peritoneal access and gastric closure are the most important concerns in the clinical application of natural orifice transluminal endoscopic surgery (NOTES). We aimed to clarify the feasibility of a submucosal tunnel technique using endoscopic submucosal dissection (ESD) for transgastric peritoneal access and subsequent closure for NOTES. METHODS: Seven female pigs, each weighing about 40 kg were included in the study. The following procedures were performed: (i) after injection of normal saline into the submucosa, the mucosa was cut with a flex knife; (ii) the submucosal layer was dissected using an insulation-tipped electrosurgical knife to make a narrow longitudinal 50-mm submucosal tunnel; (iii) a small incision was made at the end of the tunnel and enlarged with a dilation balloon. After transgastric peritoneoscopy, the mucosal incision site was closed with clips. The following outcome measures were used: (a) evaluation of the technical feasibility of making a submucosal tunnel; (b) clinical monitoring for 7 days; (c) follow-up endoscopy and necropsy; and (d) peritoneal fluid culture. RESULTS: Natural orifice transluminal endoscopic peritoneoscopy with a submucosal tunnel was successfully carried out in all pigs. The pigs recovered well, without signs of peritonitis. Follow-up endoscopy showed healing of mucosal incision sites without open defects. Necropsy revealed no findings of peritonitis, confirming completeness of gastric closure; there was a thin scar in one pig and adhesion of the omentum in six pigs. Peritoneal fluid culture demonstrated no bacterial growth. CONCLUSIONS: The submucosal tunnel technique is feasible and effective for transgastric peritoneal access and closure.

Administration of chondroitinase ABC rostral or caudal to a spinal cord injury site promotes anatomical but not functional plasticity.

2009-08-10T23:17:00.001-07:00
J Neurotrauma. 2009 Aug 6; Tom VJ, Kadakia R, Santi L, Houle JDGrowth inhibitory chondroitin sulfate proteoglycans (CSPG) are a primary target for therapeutic strategies after spinal cord injury because of their contribution to the inhibitory nature of glial scar tissue, a major barrier to successful axonal regeneration. Chondroitinase ABC (ChABC) digestion of CSPG promotes axonal regeneration beyond a lesion site with subsequent functional improvement. ChABC also has been shown to promote sprouting of spared fibers but it is not clear if functional recovery results from such plasticity. Here we sought to better understand the roles rostral or caudal sprouting may play in ChABC-mediated functional improvement. To achieve this, ChABC or vehicle was injected rostral or caudal to a unilateral C5 injury. When injected rostral to a hemisection, ChABC promoted significant sprouting of 5HT+ fibers into dorsal and ventral horns. When ChABC was injected into tissue caudal to a hemisection, no additional sprouting was observed. When injected caudal to a hemicontusion injury, ChABC promoted sprouting of 5HT+ fibers into the ventral horn but not the dorsal horn. None of this sprouting resulted in a change in the synaptic component synapsin nor did it impact performance in behavioral tests assessing motor function. These data suggest that ChABC-mediated sprouting of spared fibers does not necessarily translate into functional recovery.

Saline replacement after local resection of the breast: a simple technique with good control and improved patient satisfaction.

2009-08-09T23:19:00.001-07:00
Breast Cancer. 2009 Aug 4; Tanaka F, Mimori K, Tahara K, Inoue H, Mori MBACKGROUND: Here we report a study on the use of saline replacement after local resection of the breast. Local resection of breast tissue is widely used in the treatment of breast cancer due to the development of imaging analysis technology such as mammography, ultrasound sonography, computed tomography, and magnetic resonance. Preserving the size and shape of the breast after treatment is beneficial for the patient, and deformity of the residual breast can be a serious problem. METHODS: Following resection, the subcutaneous tissue was sutured with 4-0 polydioaxanone, and a 20-G syringe was inserted through the skin into the hole. After suturing the skin with 4-0 nylon, an adequate volume of saline was injected. A conservative treatment group did not receive saline injections and was used as controls. We sent self-administered questionnaires to 60 patients who had undergone local resection of the breast and received 55 responses (92%). RESULTS: Saline replacement was performed in 28 of the 55 patients, and conservative treatment (no saline replacement) was performed in 27 patients. The average volume of injected saline was 46 ml (range, 5-150 ml). There were no statistically significant differences in skin irritation, pain, fatigue, or daily activity between the two groups, but the saline replacement group was more satisfied with the surgical scar (p < 0.05) and shape of the breast (p = 0.05) after surgery. CONCLUSIONS: Saline replacement after local resection of the breast is a simple technique that provides benefits for patients undergoing conservative surgery of the breast.

Expression of Transforming Growth Factor-beta Receptors in Meningeal Fibroblasts of the Injured Mouse Brain.

2009-08-09T17:24:00.001-07:00
Cell Mol Neurobiol. 2009 Aug 4; Komuta Y, Teng X, Yanagisawa H, Sango K, Kawamura K, Kawano HThe fibrotic scar which is formed after traumatic damage of the central nervous system (CNS) is considered as a major impediment for axonal regeneration. In the process of the fibrotic scar formation, meningeal fibroblasts invade and proliferate in the lesion site to secrete extracellular matrix proteins, such as collagen and laminin. Thereafter, end feet of reactive astrocytes elaborate a glia limitans surrounding the fibrotic scar. Transforming growth factor-beta1 (TGF-beta1), a potent scar-inducing factor, which is upregulated after CNS injury, has been implicated in the formation of the fibrotic scar and glia limitans. In the present study, expression of receptors to TGF-beta1 was examined by in situ hybridization histochemistry in transcortical knife lesions of the striatum in the mouse brain in combination with immunofluorescent staining for fibroblasts and astrocytes. Type I and type II TGF-beta receptor mRNAs were barely detected in the intact brain and first found in meningeal cells near the lesion 1 day postinjury. Many cells expressing TGF-beta receptors were found around the lesion site 3 days postinjury, and some of them were immunoreactive for fibronectin. After 5 days postinjury, many fibroblasts migrated from the meninges to the lesion site formed the fibrotic scar, and most of them expressed TGF-beta receptors. In contrast, few of reactive astrocytes expressed the receptors throughout the postinjury period examined. These results indicate that meningeal fibroblasts not reactive astrocytes are a major target of TGF-beta1 that is upregulated after CNS injury.

Functional impact of targeted closed-chest transplantation of bone marrow cells in rats with acute myocardial ischemia/reperfusion injury.

2009-08-09T15:41:00.001-07:00
Cell Transplant. 2009 Aug 5; Ghanem A, Ziomka A, Krausgrill B, Schenk K, Troatz C, Michalszki-Jamka T, Nickenig G, Tiemann K, MÃ¼ller-Ehmsen JIntramyocardial transplantation of bone marrow derived stem cells is a potential therapeutic option after myocardial infarction (MI). Intramyocardial administration is invasive but allows efficient and targeted stem cell delivery. Aims of this study were validation of minimal-invasive, echo-guided closed-chest cell transplantation (CTx) of mononuclear (MNC) or mesenchymal stem cells (MSC) and quantification of systolic left-ventricular function and assessment of contractile reserve with high-resolution reconstructive 3D-echocardiography (r3D-echo) three weeks after CTx.Female Fischer344 rats received syngeneic male MNC, MSC or medium after myocardial ischemia and reperfusion via echo-guided percutaneous injection (open-chest for control). Left-ventricular systolic function was measured and dysfunctional myocardium was quantified with r3D-echo. For investigation of contractile reserve and myocardial viability r3D-echo was additionally conducted during low-dose dobutamine three weeks after CTx. Cell persistence after echo-guided CTx was quantified via real-time PCR, scar size was measured histologically.Echo-guided percutaneous CTx was feasible in all animals (n=30) without periprocedural complications. 1.4+/-1.1% of transplanted MNC and 1.9+/-1.2% of MSC were detected after three weeks. These numbers were comparable to those after open-chest intramyocardial injection of MNC (0.8+/-1.1%; n=8, p=0.3). In r3D-echo no functional benefit was associated with CTx after MI and reperfusion. All groups (MNC, MSC and controls) revealed a significant decrease of dysfunctional myocardium and similar contractile reserve during inotropic stimulation.In conclusion, percutaneous echo-guided closed-chest CTx promises to be an effective and safe approach for CTx in small animal research. However, intramyocardial CTx of MNC or MSC had no influence on systolic function and contractile reserve after reperfused MI.

From microsurgery to nanosurgery: how viral vectors may help repair the peripheral nerve.

2009-08-09T07:19:00.001-07:00
Prog Brain Res. 2009; 175: 173-86Tannemaat MR, Boer GJ, Eggers R, Malessy MJ, Verhaagen JReconstructive surgery of the peripheral nerve has undergone major technical improvements over the last decades, leading to a significant improvement in the clinical outcome of surgery. Nonetheless, functional recovery remains suboptimal in the majority of patients after nerve repair surgery. In this review, we first discuss the molecular mechanisms involved in peripheral nerve injury and regeneration, with a special emphasis on the role of neurotrophic factors. We then identify five major challenges that currently exist in the clinical practice of nerve repair and their molecular basis. The first challenge is the slow rate of axonal outgrowth after peripheral nerve repair. The second problem is that of scar formation at the site of nerve injury, which is detrimental to functional recovery. As a third issue, we discuss the difficulty in assessing the degree of injury in closed traction lesions without total loss of continuity of the involved nerve elements. The fourth challenge is the problem of misrouting of regenerating axons. As a fifth and final issue we discuss the potential drawbacks of using sensory nerve grafts to support the regeneration of motoneurons. For all these challenges, solutions are likely to emerge from (a) a better understanding of their molecular basis and (b) the ability to influence these processes at a molecular level, possibly with the aid of viral vectors. We discuss how lentiviral vectors have been applied in the peripheral nerve to express neurotrophic factors and summarize both the advantages and drawbacks of this approach. Finally, we discuss how lentiviral vectors can be used to provide new, molecular neurobiology-based, approaches to address the clinical challenges described above.

Comparison of the effects of short- and long-pulse durations when using a 585-nm pulsed dye laser in the treatment of new surgical scars.

2009-08-09T06:56:00.001-07:00
Lasers Med Sci. 2009 Aug 7; Nouri K, Elsaie ML, Vejjabhinanta V, Stevens M, Patel SS, Caperton C, Elgart GMore than 70 million surgical procedures are performed annually in the USA with the majority involving a skin lesion and almost all individuals in their lifetime will have one or more surgical procedures resulting in scars. Patients and physicians alike are thereby motivated to improve the cosmetic outcome of scars. Prior studies have shown that the pulsed dye laser (PDL) is effective in improving the quality and appearance of the scar when using the 585-nm PDL immediately after the removal of sutures. Most published studies used a pulse duration of 450 micros, which along with the other study parameters, has led to an overall improvement of the scars. However, a pulse duration of 1.5 ms is also available when using the pulsed dye laser and it should theoretically cause fewer side-effects. To our knowledge, there are no other studies comparing the effectiveness of different pulse durations in the treatment of surgical scars starting on the day of suture removal. The purpose of this study is to compare the effect of different pulse durations (450 micros vs. 1.5 ms) in the treatments of postsurgical linear scars immediately after suture removal when using the 585-nm pulsed dye laser (PDL). Twenty non-hospitalized male and female patients (older than 18 years of age) with skin types I-IV and with postoperative linear scars measuring at least 2.1 cm were enrolled in this prospective study. Scars were randomly divided into three equal sections. The different fields were randomly chosen to receive treatment (two out of three fields) or remain as control (one field). The two fields chosen to be treated received treatment with the 585-nm PDL using a 7-mm spot size at 4.0 J. One of the treated sections was randomly selected to receive a pulse duration of 450 micros, and the other section to receive a 1.5-ms pulse. The remaining scar section was designated as control (no treatment). The three sections were mapped and recorded. The patient received treatment immediately after the sutures were removed from the wound and then monthly for 3 months. Evaluations were performed before each treatment and 1 month after the last treatment. The short-pulse and long-pulse 585-nm PDL-treated sections demonstrated a statistically significant overall average improvement of the VSS of 92 and 89%, respectively, compared to 67% for the control site (Fig. 1). Further, for individual parameters of the Vancouver scar scale (VSS), there were significant (p < 0.05) differences between control and treatment groups for all parameters, but there were no differences between the short- and long-pulse treatment groups for any parameter. Both short-pulse and long-pulse PDL are safe and effective in improving the quality and cosmetic appearance of surgical scars in skin type's I-IV starting on the day of suture removal with no significant difference between the two pulse durations.

Catheter Ablation of Recurrent Scar-Related Ventricular Tachycardia Using Electroanatomical Mapping and Irrigated Ablation Technology: Results of the Prospective Multicenter Euro-VT-Study.

2009-08-08T01:04:00.001-07:00
J Cardiovasc Electrophysiol. 2009 Jul 28; Tanner H, Hindricks G, Volkmer M, Furniss S, KÃ¼hlkamp V, Lacroix D, DE Chillou C, Almendral J, Caponi D, Kuck KH, Kottkamp HCatheter Ablation of Ventricular Tachycardia. Introduction: Ventricular tachycardia (VT) late after myocardial infarction is an important contributor to morbidity and mortality. This prospective multicenter study assessed the efficacy and safety of electroanatomical mapping in combination with open-saline irrigated ablation technology for ablation of chronic recurrent mappable and unmappable VT in remote myocardial infarction. Methods and Results: In 8 European institutions, 63 patients (89% males) were enrolled in the study. All patients had remote myocardial infarction and presented with a median number of 17 (range 1-380) VTs in the preceding 6 months. Incessant VT was present in 14 patients (22%). Left ventricular ejection fraction measured 30 +/- 13%. A mean of 3 VTs were targeted per patient and 22% of all patients had only unmappable VT. The mean follow-up period was 12 +/- 3 months. A total of 164 VTs were targeted during catheter ablation. Ablation was acutely successful in 51 patients (81%). One patient (1.5%) experienced a major complication with degeneration of VT into ventricular fibrillation necessitating cardiopulmonary resuscitation maneuvers. However, no death occurred acutely or within the first 30 days after catheter ablation. During the follow-up, 19 of the initially successful ablated patients (37%) and 31 of all ablated patients (49%) developed some type of VT recurrence. Conclusions: The results of this multicenter study demonstrate the high acute success rate and a low complication rate of irrigated tip catheter ablation of all clinical relevant VTs in remote myocardial infarction. However, during the follow-up a relevant number of recurrences occurred.

Kinematic evaluation of cruciate-retaining total knee replacement patients during level walking: A comparison with the displacement-controlled ISO standard.

2009-08-07T16:13:00.001-07:00
J Biomech. 2009 Aug 1; Ngai V, Wimmer MADifferences between wear-scar features of simulator-tested and retrieved tibial total knee replacement (TKR) liners have been reported. This disagreement may result from differences between in vivo kinematic profiles and those defined by the International Organization for Standardization (ISO). The purpose of this study was to determine the knee kinematics of a TKR subject group during level walking and compare them with the motion profiles defined by the ISO standard for a displacement-controlled knee wear testing simulator. Twenty-nine patients with a posterior cruciate ligament-retaining TKR design were gait tested using the point cluster technique to obtain flexion-extension (FE) rotation, anterior-posterior (AP) translation and internal-external (IE) rotation knee motions during a complete cycle of level walking. Relative ranges of motion and timing of key points within the in vivo motion data were compared against the same ranges and same key points from the input profiles of the displacement-controlled wear testing standard ISO14243-3. The subjects exhibited a FE pattern similar to ISO, with an insignificant difference in range of FE rotation from midstance to terminal stance. However, the subjects had a significantly higher range of knee flexion from terminal stance into swing. The subjects also exhibited a phase delay for the entire gait cycle. For AP translation, the standard profile had statistically significant lower magnitudes than seen in vivo. Opposite pattern of AP motion was also apparent from midstance and swing. Similarly, ISO specified a smaller IE total range of rotation with a motion pattern in complete opposition to that seen in vivo. In conclusion, significant differences were found in both the magnitudes and pattern of in vivo motion compared with ISO.

[Augmentation of quality of wound healing of deep burn]

2009-08-06T02:32:00.001-07:00
Zhonghua Shao Shang Za Zhi. 2009 Feb; 25(1): 3-5Huang XYThis article summarizes methods of repair of massive and deep wounds, elucidates how to improve wound healing quality and avoid scar deformity after deep burn. A part of denatured dermis (non-necrotic) in deep partial-thickness burn, "mixed degree" burn, even in full-thickness burn wounds before forming eschar can be preserved and covered with autologous skin, thereby to avoid secondary damage to the structure of subcutaneous tissue and the junction of dermis-adipose, thus to result in good functions, appearance, and survival rate. After skin grafting, wound healing quality and appearance are improved, joint function and elasticity of skin are enhanced, the degree of scar contracture is relieved due to preservation of normal adipose tissue after escharectomy. The study of composite artifical skin will be actively developed in the future. Tissue-engineering skin and stem cells can be successfully used in patients with deep burns for scarless healing with restoration of physiological functions in a short period.

Natural Orifice Surgery: the next step in minimal invasiveness towards no scar surgery.

2009-08-05T17:54:00.001-07:00
Minerva Chir. 2009 Aug; 64(4): 355-64Forgione AThe possibility to operate into the abdominal cavity by means of flexible endoscopes introduced through natural orifices represents a major step forward in the continuous research for minimal invasive treatment attaining the unimaginable goal of no scar surgery. After several years of investigation in experimental settings, natural orifice surgery is becoming a valuable therapeutic option both as totally transluminal endoscopic approach or with the support of minimal transabdominal assistance. The promising operative results and the great interest determined among the patients always looking for effective treatment associated with less bodily trauma, postoperative pain and faster recovery, are pushing the development of dedicated technological solutions that will make natural orifice - no scar surgery more easy and reproducible to perform and applicable also to more advanced diseases. Natural orifice surgery has the potential to abolish the historical association of surgery to that of scar and pain representing a very appealing surgical option for the patients highly respectful of their body and psychological integrity.

Wound healing in the jugal mucosa of rats with a cold blade scalpel and an ultrasonic harmonic scalpel.

2009-08-04T17:34:00.001-07:00
Braz J Otorhinolaryngol. 2009 May-Jun; 75(3): 362-6Masi EC, Rocha SL, Mocellin M, Faria JLUltrasound harmonic scalpel has been recently introduced in otorhinolaryngological procedures. AIM: to assess macro and microscopic evolution of the healing process of wounds created in the jugal mucosa of rats by the use of ultrasound scalpel. METHOD: we used 30 Wistar rats in which we made mucosal incisions on the right jugal mucosa with the ultrasound harmonic scalpel (USHS) and on the left side with the cold blade scalpel (CBS). Macroscopic and microscopic evaluations were carried out on the third, seventh and fourteenth days of postoperative. For the microscopic evaluation we used HE to asses the inflammatory process and the Sirius Red approach for collagens type I and III. Anti-CD 3 antibodies and anti-factor VIII assessed the concentration of T-lymphocytes and neovessels. RESULTS: the USHS caused greater cell damage with reepitelization delay. Microscopy showed more intense inflammatory reactions and a loss in collagen build up, delay in scar maturation and a greater vessel neoformation. CONCLUSION: USHS brings about a greater lesion in the incision area; delayed regeneration; promotes greater inflammatory process and angiogenic activity; delays in fibroplasia and scar tissue maturation on the rats' jugal mucosa when compared to cold blade scalpel.

The spatial and temporal distribution of crop residue burning in the contiguous United States.

2009-08-04T04:49:00.001-07:00
Sci Total Environ. 2009 Aug 1; McCarty JL, Korontzi S, Justice CO, Loboda TBurning crop residue before and/or after harvest is a common farming practice however; there is no baseline estimate for cropland burned area in the contiguous U.S. (CONUS). We present the results of a study, using five years of remotely sensed satellite data to map the location and areal extent of crop residue burning in the CONUS. Our burned area approach combines 500 m Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Burn Ratio (dNBR) data, with 1 km MODIS active fire counts calibrated using coincident high resolution satellite data to generate area estimates. Our results show that cropland burning is an extensive and recurring annual event in several states in the CONUS. On average, 1,239,000 ha of croplands burn annually, which is equivalent to 43% of the annual average area of wildland fires in the U.S., as reported by the United States Forest Service for the same period. Several states experience high levels (>30,000 ha yr(-1)) of crop residue burning, including Arkansas, California, Colorado, Florida, Idaho, Kansas, Louisiana, North Dakota, Oklahoma, Oregon, South Dakota, Texas, and Washington. Validation with high resolution burn scar imagery and GPS data collected during targeted field campaigns showed a moderate to high-level accuracy for our burned area estimates, ranging from 78 to 90%. Our approach provides a more consistent methodology for quantifying cropland burned area at regional scales than the previously available U.S. national and state-level statistics on crop residue burning.

Cytokine Expression in Human Cardiac

2009-08-04T03:11:00.000-07:00

Cardiac myofibroblasts (CMF) play a key role in infarct repair and scar formation following myocardial infarction (MI) and are also an important source of proinflammatory cytokines. We postulated that interleukin-1 alpha (IL-1alpha), a potential early trigger of acute inflammation post-MI, could stimulate human CMF to express additional proinflammatory cytokines.

Further, we hypothesized that these effects may be modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). Human CMF were cultured from atrial biopsies from multiple patients.

Interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and cardiotrophin-1 (CT-1) mRNA expression and secretion were measured using quantitative real-time RT-PCR and ELISA. IL-1alpha (0.001-10 ng/ml, 0-6 h) stimulated IL-1beta, TNFalpha and IL-6 mRNA expression with distinct temporal and concentration profiles, resulting in increased cytokine secretion.

The response to IL-1alpha was much greater than with TNFalpha. Neither IL-1alpha nor TNFalpha treatment modulated CT-1 mRNA expression. Immunoblotting with phospho-specific antibodies revealed that IL-1alpha stimulated the ERK-1/2, p38 MAPK, JNK, PI3K/Akt and NF-kappaB signaling pathways.

Pharmacological inhibitor studies indicated roles for PI3K/Akt and NF-kappaB pathways in mediating IL-1beta expression, and for NF-kappaB and p38 MAPK pathways in mediating TNFalpha expression. IL-1alpha-induced IL-6 mRNA expression was reduced by p38 MAPK inhibition, but increased by ERK and JNK pathway inhibitors. IL-10 produced a consistent but modest reduction in IL-1alpha-induced IL-6 mRNA levels (not IL-1beta or TNFalpha), but this was not reflected by reduced IL-6 protein secretion. In conclusion, IL-1alpha stimulates human CMF to express IL-1beta, TNFalpha and IL-6 via specific signaling pathways; responses that are unaffected by IL-10 exposure.

Key words: cardiac fibroblasts, inflammation, signal transduction, cytokines.

Interleukin-1{alpha} Stimulates Pro-inflammatory Cytokine Expression in Human Cardiac Myofibroblasts.
Am J Physiol Heart Circ Physiol. 2009 Jul 31; Turner NA, Das A, Warburton P, O'Regan DJ, Ball SG, Porter KE

Transaxillary subfascial endoscopic approach for internal jugular phlebectasia in a child.

2009-08-03T21:09:00.001-07:00
Head Neck. 2009 Jun 17; Chang YT, Lee JY, Wang JY, Chiou CSBACKGROUND.: Surgical intervention for internal jugular phlebectasia is occasionally necessary in cases of phlebitis, thrombus formation, rupture of the lesion, and some cosmetic deformity. However, the resultant neck scar can be of suboptimal cosmesis, with consequent psychological distress, particularly for children. METHODS.: We described a 3-port transaxillary endoscopic technique performed under the fascia of the pectoralis major for excision of the dilated right internal jugular vein in an 8-year-old girl. RESULTS.: The preservation of the upper tributaries of the right internal jugular vein was helpful in draining the cerebral blood to the collaterals and in preventing postoperative craniofacial swelling immediately. Six months later, there were no signs of recurrence of other jugular veins, and the patient showed a correct hemodynamic compensation. CONCLUSION.: This technique offered an effective way to surgically manage internal jugular phlebectasia while avoiding the potential for poor cosmesis from any neck scar. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009.

The use of the artificial dermis

2009-08-03T20:44:00.001-07:00

The artificial dermis Integra, Johnson & Johnson Medical, Norderstedt, Germany is widely used in the treatment of excessive burn injuries. It is also used in reconstructive surgery when large soft-tissue defects could not be covered with local or free flaps.

In this article a 25-year old patient who presented with an early childhood burn of the trunk and lower extremity was treated with Integra((R)) in combination with the vacuum assisted closure (V.A.C.((R)), KCI, Texas, U.S.A.) and split thickness skin grafting. The combination of the artifical dermal substitute with negative pressure therapy has lead to a complete healing of Integra((R)) and the skin graft.

During the whole treatment sterile wound conditions were present and time-consuming dressing changes could be prevented. Hospital stay was shortened because the patient could be treated as an outpatient with an ambulant vacuum assisted closure device.

The use of the artificial dermis (Integra((R))) in combination with vacuum assisted closure for reconstruction of an extensive burn scar - A case report.
J Plast Reconstr Aesthet Surg. 2009 Jun 10; Leffler M, Horch RE, Dragu A, Bach AD (Hubmed.org)

The SCAR and WASp nucleation-promoting factors act sequentially to mediate Drosophila myoblast fusion.

2009-08-03T18:04:00.001-07:00
EMBO Rep. 2009 Jul 31; Gildor B, Massarwa R, Shilo BZ, Schejter EDThe actin nucleation-promoting factors SCAR/WAVE and WASp, together with associated elements, mediate the formation of muscle fibres through myoblast fusion during Drosophila embryogenesis. Our phenotypic analysis, following the disruption of these two pathways, suggests that they function in a sequential manner. Suppressor of cyclic AMP receptor (SCAR) activity is required before the formation of pores in the membranes of fusing cells, whereas Wiskott-Aldrich syndrome protein (WASp) promotes the expansion of nascent pores and completion of the fusion process. Genetic epistasis experiments are consistent with this step-wise temporal progression. Our observations further imply a separate, Rac-dependent role for the SCAR complex in promoting myoblast migration. In keeping with the sequential utilization of the two systems, we observe abnormal accumulations of filamentous actin at the fusion sites when both pathways are disrupted, resembling those present when only SCAR-complex function is impaired. This observation further suggests that actin-filament accumulation at the fusion sites might not depend on Arp2/3 activity altogether.

Keloids: pathogenesis

2009-08-03T01:23:00.001-07:00

Excess scar formation occurs after dermal injury as a result of abnormal wound healing. Hypertrophic scars and keloids both represent fibrotic skin conditions which can be very difficult, even frustrating, to treat. Identification of differences between hypertrophic scars, keloids and normal scars are a prerequisite for finding the correct therapeutical concept.

Despite the relatively high prevalence of keloids in the general population, the mechanisms underlying keloid formation are only partially understood. This fact is reflected in the multiple treatment modalities, of which no single treatment has proven to be widely effective.

Advances in our understanding of the wound healing process reveal new pathophysiological concepts for keloid formation. Our article presents an overview on physiological wound healing and the pathogenesis of scar formation, differentiates keloids from hypertrophic scars and reviews current hypotheses for keloid formation.

This information might assist in deciphering the complexity of keloid pathogenesis and help in the development of an efficacious therapeutical strategy.

Keloids: Current concepts of pathogenesis (Review).
Int J Mol Med. 2009 Sep; 24(3): 283-93Bran GM, Goessler UR, Hormann K, Riedel F, Sadick H (Hubmed.org)

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Towards no-scar cardiac surgery

2009-08-02T17:43:00.001-07:00

There is an ever-growing trend towards less-invasive procedures in all fields of medicine. We designed an animal study to prove the concept that trans-apical aortic valve replacement from an incision within the umbilicus through a single channel for instruments is feasible, which would be a major leap towards no-scar cardiac surgery.

In three adult pigs, after creating a single 3-cm incision at a place where the human umbilicus would be, we introduced a 30F sheath through a tunnel created by an endoscopic vein-harvesting device up to the cardiac apex, through it and up to the left ventricle simulating the approach for trans-apical aortic valve replacement.

We used a standard Amplatz nitinol occluder to seal the defect in ventricle wall later. The animals were followed up for 1h. Blood loss was minimal, and no tamponade occurred in any of the animals.

In addition, we performed a test with water column static pressure to evaluate the impact of preclotting on the sealing properties of the occluders: 1min flow-through was 2860+/-176ml for the standard occluders and 348+/-56ml for preclotted occluders

"Towards no-scar cardiac surgery - minimally invasive access through umbilicus for aortic valve replacement."
Eur J Cardiothorac Surg. 2009 Jul 27; Kalejs M, Ferrari E, von Segesser LK

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Keloids Show Regional Distribution of Proliferative and Degenerate Connective Tissue Elements.

2009-08-02T15:52:00.001-07:00
Cells Tissues Organs. 2009 Jul 29; Bux S, Madaree AKeloids, formed by the deposition of excessive scar tissue, are characterised by the presence of thick hyalinised collagen bundles. Contradictory reports about keloid morphology include: hyperproliferation of dermal fibroblasts versus few fibroblasts; rich as opposed to poor vascularisation; dilated against occluded microvessels; distinct collagen nodules versus their absence, and elevated levels of types I and III collagen as opposed to no change when compared with normal dermis. This study attempted to clarify the controversies concerning keloid morphology by examining entire keloids and establishing baseline histological characteristics. Keloidal specimens from 32 patients were processed and comprehensively examined using light microscopy. The results of the study showed that keloids comprise many distinct regions, categorized as the zone of hyalinising collagen bundles, fine fibrous areas, area of inflammation, zone of dense regular connective tissue, nodular fibrous area and area of angiogenesis. The microvascular supply to each of these regions was impaired and features of degeneration and necrosis of keloid fibroblastic cells and microvessels were ubiquitous. Impairment of the healing stage of chronic inflammation, inefficient healing by fibrosis, multiple and exaggerated phases of vascular and fibrous granulation and remodelling stages manifest in keloid formation. The uneven distribution of cells may be due to the generation of traction forces by keloid cells. These forces also modify DNA and protein synthesis, leading to an overproduction of extracellular matrix components. This study provides a structured basis for future ultrastructural and immunocytochemical research of keloids and other fibroproliferative disorders.

The effect of anterior abdominal wall scars on the vascular anatomy of the abdominal wall: A cadaveric and clinical study with clinical implications.

2009-08-02T07:29:00.001-07:00
Clin Anat. 2009 Jul 30; Rozen WM, Garcia-Tutor E, Alonso-Burgos A, Corlett RJ, Taylor GI, Ashton MWThe anterior abdominal wall integument is frequently used in a range of reconstructive flaps. These tissues are supplied by the deep and superficial inferior epigastric arteries (DIEA and SIEAs) and the deep and superficial superior epigastric arteries (DSEA and SSEAs). Previous abdominal wall surgery alters this vascular anatomy and may influence flap design. One hundred and sixty-eight patients underwent abdominal wall computed tomographic angiography (CTA) for preoperative imaging. Fifty-eight of these patients had undergone previous abdominal surgery, and were assessed for scar pattern and relationship to the course and distribution of all major axial vessels and perforators. Two cadaveric abdominal wall specimens with midline abdominal scars underwent contrast injection of the DIEAs and DSEAs, with subsequent CTA. The course and distribution of all cutaneous vessels were assessed. In all clinical and cadaveric cases, the vasculature of the abdominal wall had been altered by previous surgery. In the clinical cases, vascular architecture was universally altered in the region of the scar, often modifying the filling patterns of the abdominal wall and occasionally precluding the use of an abdominal wall flap. In both cadaveric specimens, regions of non-filling were evident upon contrast injection, highlighting the angiosomes not supplied by the DIEA or DSEA. Previous abdominal wall surgery necessarily alters the vascular architecture of the abdominal wall, and may alter the source vessels supplying cutaneous tissues. CTA was useful in identifying and delineating these changes, and may be used as a preoperative tool in this role. Clin. Anat. 2009. (c) 2009 Wiley-Liss, Inc.

Penile reconstruction: is the radial forearm flap really the standard technique?

2009-08-02T06:26:00.001-07:00
Plast Reconstr Surg. 2009 Aug; 124(2): 510-8Monstrey S, Hoebeke P, Selvaggi G, Ceulemans P, Van Landuyt K, Blondeel P, Hamdi M, Roche N, Weyers S, De Cuypere GBACKGROUND: The ideal goals in penile reconstruction are well described, but the multitude of flaps used for phalloplasty only demonstrates that none of these techniques is considered ideal. Still, the radial forearm flap is the most frequently used flap and universally considered as the standard technique. METHODS: In this article, the authors describe the largest series to date of 287 radial forearm phalloplasties performed by the same surgical team. Many different outcome parameters have been described separately in previously published articles, but the main purpose of this review is to critically evaluate to what degree this supposed standard technique has been able to meet the ideal goals in penile reconstruction. RESULTS: Outcome parameters such as number of procedures, complications, aesthetic outcome, tactile and erogenous sensation, voiding, donor-site morbidity, scrotoplasty, and sexual intercourse are assessed. CONCLUSIONS: In the absence of prospective randomized studies, it is not possible to prove whether the radial forearm flap truly is the standard technique in penile reconstruction. However, this large study demonstrates that the radial forearm phalloplasty is a very reliable technique for the creation, mostly in two stages, of a normal-appearing penis and scrotum, always allowing the patient to void while standing and in most cases also to experience sexual satisfaction. The relative disadvantages of this technique are the rather high number of initial fistulas, the residual scar on the forearm, and the potential long-term urologic complications. Despite the lack of actual data to support this statement, the authors feel strongly that a multidisciplinary approach with close cooperation between the reconstructive/plastic surgeon and the urologist is an absolute requisite for obtaining the best possible results.

[Comparison of annual risk for tuberculosis infection (1994-2001) in school children in Djibouti: methodological limitations and epidemiological value in a hyperendemic context]

2009-08-02T00:45:00.001-07:00
Med Trop (Mars). 2008 Dec; 68(6): 611-6Bernatas JJ, Mohamed Ali I, Ali IsmaÃ«l H, Barreh Matan AThe purpose of this report was to describe a tuberculin survey conducted in 2001 to assess the trend in the annual risk for tuberculosis infection in Djibouti and compare resulting data with those obtained in a previous survey conducted in 1994. In 2001 cluster sampling allowed selection of 5599 school children between the ages of 6 and 10 years including 31.2% (1747/5599) without BCG vaccination scar. In this sample the annual risk of infection (ARI) estimated using cutoff points of 6 mm, 10 mm, and 14 mm corrected by a factor of 1/0.82 and a mode value (18 mm) determined according to the "mirror" method were 4.67%, 3.64%, 3.19% and 2.66% respectively. The distribution of positive tuberculin skin reaction size was significantly different from the normal law. In 1994 a total of 5257 children were selected using the same method. The distribution of positive reactions was not significantly different from the gaussian distribution and 28.6% (1505/5257) did not have a BCG scar. The ARI estimated using cutoff points of 6 mm, 10 mm, and 14 mm corrected by a factor of 1/0.82 and a mode value (17 mm) determined according to the "mirror" method were 2.68%, 2.52%, 2.75% and 3.32 respectively. Tuberculin skin reaction size among positive skin test reactors was correlated with the presence of a BCG scar, and its mean was significantly higher among children with BCG scar. The proportion of positive skin test reactors was also higher in the BCG scar group regardless of the cutoff point selected. Comparison of prevalence rates and ARI values did not allow any clear conclusion to be drawn, mainly because of a drastic difference in the positive reaction distribution profiles between the two studies. The distribution of the skin test reaction's size 1994 study could be modelized by a gaussian distribution while it could not in 2001. A partial explanation for the positive reaction distribution observed in the 2001 study might be the existence of cross-reactions with environmental mycobacteria.

A rat excised larynx model of vocal fold scar.

2009-07-31T20:48:00.001-07:00
J Speech Lang Hear Res. 2009 Aug; 52(4): 1008-20Welham NV, Montequin DW, Tateya I, Tateya T, Choi SH, Bless DMPURPOSE: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. METHOD: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic fibroblast growth factor (bFGF), chronic vocal fold scar treated with saline (sham treatment), and unscarred untreated control. Following tissue harvest, histological and immunohistochemical data were collected to confirm extracellular matrix alteration in the chronic scar group; acoustic, aerodynamic, and high-speed digital imaging data were collected using an excised larynx setup in all groups. Phonation threshold pressure (P(th)), glottal resistance (R(g)), glottal efficiency (E(g)), vibratory amplitude, and vibratory area were used as dependent variables. RESULTS: Chronically scarred vocal folds were characterized by elevated collagen Types I and III and reduced hyaluronic acid abundance. Phonation was achieved, and data were collected from all control and bFGF-treated larynges; however, phonation was not achieved with 3 of 6 chronically scarred and 1 of 6 saline-treated larynges. Compared with control, the chronic scar group was characterized by elevated P(th), reduced E(g), and intralarynx vibratory amplitude and area asymmetry. The bFGF group was characterized by P(th) below control-group levels, E(g) comparable with control, and vocal fold vibratory amplitude and area symmetry comparable with control. The sham group was characterized by P(th) comparable with control, E(g) superior to control, and vocal fold vibratory amplitude and area symmetry comparable with control. CONCLUSIONS: The excised larynx model reported here demonstrated robust deterioration across phonatory indices under the scar condition and sensitivity to treatment-induced change under the bFGF condition. The improvement observed under the sham condition may reflect unanticipated therapeutic benefit or artifact. This model holds promise as a tool for the functional characterization of biomechanical tissue changes resulting from vocal fold scar and the evaluation of experimental therapies.

The effects of laser irradiation of cartilage on chondrocyte gene expression and the collagen matrix.

2009-07-31T17:53:00.001-07:00
Lasers Surg Med. 2009 Jul 28; Holden PK, Li C, Da Costa V, Sun CH, Bryant SV, Gardiner DM, Wong BJOBJECTIVES: Laser reshaping of cartilage is an emerging technology aimed at replacing conventional techniques for aesthetic and reconstructive surgery. Little is known about the mechanisms of wound healing following the photothermal heating during laser reshaping and, ultimately, how collagen remodels in the irradiated tissue. Healthy hyaline and elastic cartilage as found in the ear, nose, larynx, and trachea does not express collagen type I which is characteristic of fibro-cartilage and scar tissue. The aim of the study was to determine if collagen I and II gene expression occurs within laser irradiated rabbit septal cartilage. METHODS: Nasal septum harvested from freshly euthanized New Zealand White rabbits were irradiated with an Nd:YAG laser. After 2 weeks in culture, the laser spot and surrounding non-irradiated regions were imaged using immunofluorescence staining and evaluated using reverse transcription polymerase chain reaction (RT-PCR) to determine the presence of collagen I and II, and ascertain collagen I and II gene expression, respectively. RESULTS: All laser irradiated specimens showed a cessation in collagen II gene expression within the center of the laser spot. Collagen II was expressed in the surrounding region encircling the laser spot and within the non-irradiated periphery in all specimens. Immunohistochemistry identified only type II collagen. Neither collagen I gene expression nor immunoreactivity were identified in any specimens regardless or irradiation parameters. CONCLUSIONS: Laser irradiation of rabbit septal cartilage using dosimetry parameters similar to those used in laser reshaping does not result in the detection of either collagen I gene expression or immunoreactivity. Only collagen type II was noted after laser exposure in vitro following cell culture, which suggests that the cellular response to laser irradiation is distinct from that observed in conventional wound healing. Laser irradiation of cartilage can leave an intact collagen matrix which likely allows chondrocyte recovery on an intact scaffold. Lasers Surg. Med. (c) 2009 Wiley-Liss, Inc.

The Need for Flaps in Burn Surgery.

2009-07-30T20:59:00.001-07:00
Handchir Mikrochir Plast Chir. 2009 Jul 28; Hold A, Kamolz L, Frey MBACKGROUND: Due to the improvement of surgery and intensive care more and more patients survive even severe burn injuries. Therefore we have to pay attention not only to survival alone but also to the achievement of a good quality of life. Thereby, one of the most important aspects is sufficient tissue coverage. After appropriate debridement functionally important structures may be exposed. Therefore, these areas require more than split skin coverage. These cases necessitate flap coverage for preservation of function or, respectively, limb salvage. In secondary reconstruction flaps are commonly used for scar revision. The aim of this study is to give more detailed information about the need for flaps in burn surgery. PATIENTS AND METHODS: All burn patients of our burn centre who received free or local flap coverage between January 1997 and February 2008 were analysed retrospectively. We evaluated the following parameters: indication (acute or late), flap type (pedicled or free flap), localisation, cause of accident and complication rate. Small local flaps like Z-plasties have been excluded. RESULTS: 45 patients have been included into this study. They received 53 flaps. In 53% the cause of accident was flame, in 22% scald and in 24% electrical burn, whereby electrical burn injuries most frequently required flap coverage related to their incidence. Most of the flaps have been performed for primary reconstruction. More than half of all flaps have been used for the upper extremity, concerning just the hand in 36%, 19% for the lower extremity, 15% for the trunk and 11% for the head. There have been three total flap failures during the study period. In all other cases we reached good results. Two of these flap failures occurred during the vulnerable phase between the 6th and the 21st day after trauma. CONCLUSION: Limb salvage was the dominant indication for primary reconstruction compared to the improvement of function and aesthetics for secondary reconstruction. The timing of reconstruction has an important influence on the flap outcome and has to be considered when the decision for reconstruction is made. So, if possible, the period between the 6th and the 21st day should not be chosen for flap coverage.

The Use of Pressure and Silicone in Hypertrophic Scar Management in Burns Patients: A Pilot Randomized Controlled Trial.

2009-07-30T17:27:00.001-07:00
J Burn Care Res. 2009 Jun 5; Harte D, Gordon J, Shaw M, Stinson M, Porter-Armstrong AThis pilot study investigates whether pressure and silicone therapy used simultaneously are more effective in treating multiple characteristics of hypertrophic scars than pressure alone. A pilot randomized controlled trial was conducted. Twenty-two participants with hypertrophic burn scars were randomized to receive Jobskin pressure garments and Mepiform silicone sheeting or Jobskin pressure garments alone. The Vancouver Scar Scale (VSS) was used to measure multiple scar characteristics at baseline, week 12, and week 24. No statistically significant difference was found in the rate of change of the VSS scores between the pressure therapy (PT) group and the pressure therapy and silicone group at week 12 or week 24; however, the mean scores of both groups reduced over 24 weeks. There were no statistically significant changes in the VSS subscores (scar height, vascularity, pliability, and pigmentation) from baseline to week 12 or week 24. A statistically significant relationship was observed between the VSS score and TBSA burned (

Topical tamoxifen therapy in hypertrophic scars or keloids in burns.

2009-07-30T05:51:00.001-07:00
Arch Dermatol Res. 2009 Jul 28; Gragnani A, Warde M, Furtado F, Ferreira LMAs acute burn patients have experienced increasing survival rates, the number of patients who need specific care due to aberrant scarring is also increasing. The burned skin often responds with fibrotic tissue proliferation, which can lead to a hypertrophic scar or a keloid. Non-physiologic scars are mostly not acceptable for the burn patient. Intradermal and topical therapy in burns comprise the treatment of the skin injury and its possible texture, elasticity and color alterations with the aid of active substances that result in fibroblastic modulation. An alteration of cytokine levels may mediate these effects, and evidences suggest that keloid scar formation may be mediated, in part, by deranged growth factor activity, including that of transforming growth factor (TGF)-beta(1). The addition of tamoxifen, a non-steroidal anti-estrogen, usually used in breast cancer, to standard treatment may lead to improved wound healing in keloids by decreasing the expression of TGF-beta(1), with the consequent inhibitions of both fibroblast proliferation and collagen production. Topical tamoxifen citrate chemical treatment has been shown to improve scarring. However, prospective studies must be undertaken to validate the inclusion of tamoxifen into standard clinical practice.

Symptomatic fat necrosis and lipoatrophy of the posterior pelvis following trauma.

2009-07-30T02:38:00.001-07:00
Orthopedics. 2009 Jun; 32(6): Crawford EA, King JJ, Fox EJ, Ogilvie CMPosttraumatic fat necrosis and lipoatrophy can occur in the subcutaneous fat following falls, blunt injury, surgery, and minor procedures or injections. While these processes have no inherent serious medical consequences, they occasionally require treatment due to severe or concerning symptoms. Three patients (all women; average age, 47 years) who sustained blunt trauma to the pelvis and were diagnosed with posttraumatic fat necrosis or lipoatrophy were retrospectively identified from our orthopedic oncology records. All patients recalled blunt trauma to the posterior pelvis just prior to symptom onset; 2 patients fell down stairs and 1 fell from a bed. Chief symptoms were a painful mass, a painless mass, and chronic pain in the injured area. Magnetic resonance imaging (MRI) revealed atrophy of the subcutaneous fat in all cases and a small mass in 1 patient. A bright linear signal was seen on T2-weighted, fat-saturated images in 2 cases, likely representing scar tissue. One patient with chronic pain underwent surgery to provide better soft tissue coverage in the area of atrophic fat. The other 2 patients did not undergo surgical treatment: 1 was treated at a pain center for reflex sympathetic dystropy-type pain, and 1 remained pain free. Blunt trauma with subsequent fat atrophy and necrosis manifests as a mass, a subcutaneous fat defect, and even as chronic pain. Characteristic MRI findings are often sufficient for diagnosis, but any indeterminate masses should be further evaluated to rule out aggressive or malignant neoplasms. Chronic unrelenting pain despite treatment may be related to posttraumatic reflex sympathetic dystropy-like symptoms.

Total thyroidectomy for benign disease in the pediatric patient--feasible and safe.

2009-07-29T22:53:00.001-07:00
J Pediatr Surg. 2009 Aug; 44(8): 1529-33Raval MV, Browne M, Chin AC, Zimmerman D, Angelos P, Reynolds MPURPOSE: Total thyroidectomy (TT) is a safe and efficacious treatment of malignant thyroid disease in children. The role of TT in benign thyroid disease is less well-defined. The goal of this study was to compare the safety of TT performed for benign and malignant disease. METHODS: The medical records of 31 patients undergoing TT from January 2000 to June 2007 at a single center were reviewed. The benign cohort totaled 15 patients consisting of 12 with Graves' disease, 2 with hyperthyroidism, and 1 with large and symptomatic multinodular goiter. The malignant cohort totaled 16 patients consisting of 9 with malignant disease, 4 with a nodule and history of cancer or radiation exposure, and 3 with RET proto-oncogene mutations. RESULTS: The most common complication was transient hypocalcemia observed in 7 (46%) of 15 patients with benign disease and 9 (56%) of 16 patients with malignancy (P = .72). Permanent hypocalcemia, defined as need for calcium supplement 6 months postprocedure, was observed in 1 patient with benign disease (6.67%) and 1 patient with malignancy (6.25%; P = 1.0). A single parathyroid gland was reimplanted in 2 patients with malignancy and 2 patients with benign disease (P = 1.0). One case of keloid scar was noted, and no cases of recurrent laryngeal nerve palsy, nerve paralysis, tracheal injury, tracheostomy, or wound infection were encountered in either cohort. There were no cases of relapse hyperthyroidism in the benign cohort. CONCLUSIONS: Similar rates of postoperative complications can be expected with TT for benign thyroid disease as compared to TT for malignant disease. Total thyroidectomy is a safe treatment option for benign thyroid disease in children.

Trapeze-flap plasty: Effective method for postburn neck contracture elimination.

2009-07-29T17:28:00.001-07:00
Burns. 2009 Jul 2; Grishkevich VMThe new method for postburn neck contracture management is presented. The method is found to be most effective when using the local flap procedures on patients who cannot undergo complex and long surgical procedures that are aimed at both contracture elimination and neck skin restoration (children, elderly patients, patients with inadequate donor sites, and patients with cosmetically acceptable scar appearance). The method consists of the opposite transposition of trapezoid scar-fascial flaps which are prepared one on each antero-lateral neck surface. Both flaps include scars, fat, platysma and deep cervical fascia. As a result of the trapeze-flap plasty, the anterior surface of the neck is lengthened approximately by 100-200%, the contracture is eliminated and mentocervical angle and head movement are restored. The flaps have reliable blood circulation through the superficial cervical artery perforators, therefore flap loss is rare. The functional results were good in 24 out of 26 patients. The flaps surface does not decrease; therefore, the mild contracture becomes an exception.

Donor Site Sensitivity After Breast Reconstruction With Deep Inferior Epigastric Artery Perforator Flap.

2009-07-29T06:36:00.001-07:00
Ann Plast Surg. 2009 Jun 16; Tindholdt TT, TÃ¸nseth KAThe aim of this study was to examine pressure sensitivity at the donor site after breast reconstruction with deep inferior epigastric artery perforator (DIEAP). In a cross-sectional survey, 2 groups of patients were analyzed. The DIEAP group consisted of 30 women who had previously had secondary breast reconstruction with DIEAP flap after mastectomy for breast cancer. The control group consisted of 7 women with no previous abdominal incisions planned for secondary breast reconstruction with DIEAP. Pressure thresholds were tested within the margins of the abdominal wall using Semmes-Weinstein monofilaments. In the DIEAP group a pattern of higher pressure thresholds was observed in the proximity of the scar. Comparing the 2 groups, significant higher pressure thresholds were found in the DIEAP group in the scar on both sides and in the midline from the scar to the umbilical level. Our data show that the abdominoplasty performed during breast reconstruction with DIEAP reduces cutaneous sensitivity in the donor site area.

Wash functions downstream of Rho and links linear and branched actin nucleation factors.

2009-07-29T02:30:00.001-07:00
Development. 2009 Aug; 136(16): 2849-60Liu R, Abreu-Blanco MT, Barry KC, Linardopoulou EV, Osborn GE, Parkhurst SMWiskott-Aldrich Syndrome (WAS) family proteins are Arp2/3 activators that mediate the branched-actin network formation required for cytoskeletal remodeling, intracellular transport and cell locomotion. Wasp and Scar/WAVE, the two founding members of the family, are regulated by the GTPases Cdc42 and Rac, respectively. By contrast, linear actin nucleators, such as Spire and formins, are regulated by the GTPase Rho. We recently identified a third WAS family member, called Wash, with Arp2/3-mediated actin nucleation activity. We show that Drosophila Wash interacts genetically with Arp2/3, and also functions downstream of Rho1 with Spire and the formin Cappuccino to control actin and microtubule dynamics during Drosophila oogenesis. Wash bundles and crosslinks F-actin and microtubules, is regulated by Rho1, Spire and Arp2/3, and is essential for actin cytoskeleton organization in the egg chamber. Our results establish Wash and Rho as regulators of both linear- and branched-actin networks, and suggest an Arp2/3-mediated mechanism for how cells might coordinately regulate these structures.

Application of promoter swapping techniques to control expression of chromosomal genes.

2009-07-28T23:25:00.001-07:00
Appl Microbiol Biotechnol. 2009 Jul 25; McCleary WRThe ability to control the expression of chromosomal genes is important for many applications, including metabolic engineering and the functional analysis of cellular processes. This mini-review presents recent work on the application of techniques that allow researchers to replace a chromosomal promoter with one designed for a specific level of activity, thereby exerting precise transcriptional control while retaining the natural genetic context of a gene or operon. This technique, termed promoter swapping, involves the creation of a PCR product that encodes a removable antibiotic resistance cassette and an engineered promoter. Short homology sequences on the ends of the PCR fragment target it for homologous recombination with the chromosome catalyzed by phage-derived recombination proteins. After the PCR product is introduced by electroporation into an appropriate acceptor strain, antibiotic resistance selects the desired recombination products. The antibiotic resistance cassette is then removed from the strain by site-specific recombination leaving the engineered promoter precisely positioned upstream of a target gene but downstream of a short scar consisting of a single site-specific recombination site.

Human umbilical cord blood stem cells

2009-07-28T18:55:00.001-07:00
Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes involved in inflammation, wound healing and other pathological processes after neurological disorders. MMP-2 promotes functional recovery after spinal cord injury (SCI) by regulating the formation of a glial scar. In the present study, we aimed to investigate the expression and/or activity of several MMPs, after SCI and human umbilical cord blood mesenchymal stem cells (hUCB) treatment in rats with a special emphasis on MMP-2.

Treatment with hUCB after SCI altered the expression of several MMPs in rats. MMP-2 is upregulated after hUCB treatment in spinal cord injured rats and in spinal neurons injured either with staurosporine or hydrogen peroxide. Further, hUCB induced upregulation of MMP-2 reduced formation of the glial scar at the site of injury along with reduced immunoreactivity to chondroitin sulfate proteoglycans. Blockade of MMP-2 activity in hUCB cocultured injured spinal neurons reduced the protection offered by hUCB indicated the involvement of MMP-2 in the neuroprotection offered by hUCB.

Based on these results, we conclude that hUCB treatment after SCI upregulate MMP-2 levels and reduce the formation of the glial scar thereby creating an environment suitable for endogenous repair mechanisms.

"Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury."
Neurobiol Dis. 2009 Jul 22; Veeravalli KK, Dasari VR, Tsung AJ, Dinh DH, Gujrati M, Fassett D, Rao JS

The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction.

2009-07-28T17:30:00.001-07:00
J Mol Cell Cardiol. 2009 Jul 22; Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NGThe dynamic alterations in the cardiac extracellular matrix following myocardial infarction not only determine the mechanical properties of the infarcted heart, but also directly modulate the inflammatory and reparative response. During the inflammatory phase of healing, rapid activation of matrix metalloproteinases (MMP) causes degradation of the cardiac extracellular matrix. Matrix fragments exert potent pro-inflammatory actions, while MMPs process cytokines and chemokines altering their biological activity. In addition, vascular hyperpermeability results in extravasation of fibronectin and fibrinogen leading to formation of a plasma-derived provisional matrix that serves as a scaffold for leukocyte infiltration. Clearance of the infarct from dead cells and matrix debris is essential for resolution of inflammation and marks the transition to the proliferative phase. The fibrin-based provisional matrix is lysed and cellular fibronectin is secreted. ED-A fibronectin, mechanical tension and Transforming Growth Factor (TGF)-beta are essential for modulation of fibroblasts into myofibroblasts, the main collagen-secreting cells in the wound. The matricellular proteins thrombospondin-1 and -2, osteopontin, tenascin-C, periostin, and secreted protein acidic and rich in cysteine (SPARC) are induced in the infarct regulating cellular interactions and promoting matrix organization. As the infarct matures, matrix cross-linking results in formation of a dense collagen-based scar. At this stage, shielding of fibroblasts from external mechanical tension by the mature matrix network may promote deactivation and cellular quiescence. The components of the extracellular matrix do not passively follow the pathologic alterations of the infarcted heart but critically modulate inflammatory and reparative pathways by transducing signals that affect cell survival, phenotype and gene expression.

The Evolution of Osseous Metaplasia in Localized Cutaneous Nephrogenic Systemic Fibrosis: A Case Report.

2009-07-28T07:34:00.001-07:00
Am J Dermatopathol. 2009 Jul 23; Wiedemeyer K, Kutzner H, Abraham JL, Thakral C, Carlson JA, Tran TA, Hausser I, Hartschuh WGadolinium (Gd) is associated with nephrogenic systemic fibrosis (NSF), a severe disorder mimicking scleroderma with involvement of the skin, lungs, heart, liver, and muscles. There is strong evidence that specific Gd-containing contrast agents (GCCAs) used in magnetic resonance imaging can cause NSF when administered to patients with chronic kidney disease. We present the 8-year history of cutaneous NSF with osseous metaplasia that occurred in a 56-year-old man with dialysis-dependent renal failure who was exposed to GCCA [gadopentate dimeglumine (Magnevist; Bayer Schering Pharma AG, Pittsburgh, PA)]. Three months after exposure to GCCA, he developed pruritic, pigmented patches that slowly coalesced and darkened over 8 years. Although not recognized at onset, skin biopsy showed typical histology of NSF affecting the entire dermis: CD34/procollagen I spindle cells associated with fibrosis. Biopsy performed 6 years later showed superficial scar-like fibrosis that was CD34/procollagen I and had numerous elastocollagenous balls (refractile elastic fibers surrounded by coarse collagen). Biopsy 7 years later showed the superimposition of osseous metaplasia on elastocollagenous balls. Both of these later biopsies had typical NSF histology affecting the deep dermis and subcutis. Over time, there was progressive diminishment of CD34 and procollagen I+ cells and an increase in FXIIIa+ and CD68 cells. Scanning electron microscopy and energy-dispersive x-ray spectroscopy showed Gd deposits in all areas of typical NSF histology but not in the regions of scar-like fibrosis, elastocollagenous balls, or osseous metaplasia. We suspect that the later changes may represent a late, involuting stage of NSF.

Medial orbital wall reconstruction through subciliary approach: revisited.

2009-07-27T23:42:00.001-07:00
J Craniofac Surg. 2009 Jul; 20(4): 1280-2Hwang KThe aim of this study is to determine the safety and complication of subciliary approach through the retrospective review of our experiences. From 2005 through 2008, the subciliary skin-muscle flap methods were used in 30 patients undergoing medial orbital wall reconstruction. Preoperative and postoperative ophthalmic findings including diplopia, Hertel exophthalmometry, and occurrence of complications were checked. Resorbable polylactic acid sheet or porous polyethylene sheet was trimmed and molded in L shape, vertical portion to cover the medial wall defect and horizontal portion for stability in orbital floor.In the follow-up of diplopia, half of the patients (3 cases) presenting with diplopia improved during the first month of follow-up, and all of them improved by 6 month. For hypesthesia, all patients improved by 3 months. Enophthalmos of 1 patient improved after operation and did not recur. No patients complained of visible scar 6 months postoperatively, and no ectropion was observed.We think that medial orbital wall could be reconstructed safely through skin-muscle flap subciliary approach without resulting in ectropion or lacrimal canaliculus injury.

Type 3 Choroidal Neovascularization Associated with Fundus Flavimaculatus.

2009-07-27T15:52:00.000-07:00
Ophthalmic Res. 2009 Jul 23; 42(3): 152-154Quijano C, Querques G, Massamba N, Soubrane G, Souied EHAim: To describe a patient with type 3 choroidal neovascularization (CNV) associated with fundus flavimaculatus (FFM), who underwent treatment with intravitreal ranibizumab. Methods: A 78-year-old woman diagnosed with FFM presented at our department complaining of decreased vision and metamorphopsia in her left eye. Upon a complete ophthalmologic examination, including best corrected visual acuity (BCVA), fundus autofluorescence, fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT), the patient was diagnosed with type 3 CNV associated with FFM, and was submitted to intravitreal ranibizumab injections at monthly intervals. Results: Six months after 3 monthly injections of ranibizumab, the patient's BCVA improved from 20/64 to 20/32. FA and ICGA revealed a type 3 CNV closure, and the SD-OCT scan showed a fibrous scar replacing the type 3 CNV, with resolution of serous retinal detachment. Conclusion: This case represents the first demonstration of type 3 CNV associated with FFM. Based on our findings, intravitreal ranibizumab may be considered as a therapeutic option for this rare association.

Scar classification in cutaneous lupus erythematosus: morphological description.

2009-07-26T23:31:00.001-07:00
Br J Dermatol. 2009 Jul 14; Al-Refu K, Goodfield MSummary Background Scarring represents the single most debilitating aspect of discoid lupus erythematosus (DLE) in patients with cutaneous lesions alone. Despite this, there have been no studies which have attempted to classify the types of scars seen in this chronic disease. Objectives The aim was to classify the types of scars based on morphological description. Patients and methods Forty-five patients with histologically confirmed DLE were included in the study. In the assessment of the types of scars, the scars were scored initially according to their anatomical localization. Each anatomical area was assessed for the types of scars which occurred in these areas. Results Scars in patients with DLE were initially classified morphologically into six types according to the site of the scar and then each type was classified into subtypes according to the morphology of the scar. Scars were seen in the majority of the patients and scarring affected mostly areas including the scalp, other hairy areas such as the eyebrows, nonhairy areas, mucosa, fatty layers of the skin and the nails. This study demonstrated that scars may not only produce textural changes but may also produce pigmentary changes. It is possible that other types of scars may yet occur in DLE but have not so far been detected. Conclusions Early classification and identification of the types of scars in these patients may change management towards more aggressive therapy in those with continued disease activity, and it is possible that different types of scarring require different therapies.

Oral rehabilitation with bone graft and simultaneous dental implants in a patient with epidermolysis bullosa: a clinical case report.

2009-07-24T18:21:00.001-07:00
J Oral Maxillofac Surg. 2009 Jul; 67(7): 1499-502Larrazabal-MorÃ³n C, Boronat-LÃ³pez A, PeÃ±arrocha-Diago M, PeÃ±arrocha-Diago MEpidermolysis bullosa (EB) represents a group of mainly hereditary skin disorders, manifested by an exceptional tendency of the skin and mucosa to form bullae and vesicles after minor friction and trauma. Oral features include repeated blistering, scar formation, elimination of buccal and vestibular sulci, and alveolar bone resorption. The use of endosseous implants in the fixed prosthetic rehabilitation of patients with recessive dystrophic EB might provide a considerably better outcome than conventional removable prosthetic methods. This clinical report describes the fixed rehabilitation with 2 implants placed simultaneously with bone graft in a partially edentulous patient diagnosed with recessive dystrophic EB. The implants, with simultaneous bone graft, were placed to decrease the number of surgical operations required, avoiding soft tissue ulcerations and discomfort in the patient. This treatment option appears to be favorable for recessive dystrophic EB patients compared with other options involving removable prostheses, which irritate the oral mucosa.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with different types of scars and keloids.

2009-07-24T04:19:00.001-07:00
J Plast Reconstr Aesthet Surg. 2009 May 21; Ulrich D, Ulrich F, Unglaub F, Piatkowski A, Pallua NBACKGROUND: Hypertrophic scars and keloids are fibroproliferative skin disorders characterised by progressive deposition of collagen. Our study is designed to investigate the expression and concentration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in different types of scars and keloids. METHODS: Total RNA from 19 proliferative hypertrophic scar samples of patients with extended burns (total body surface area (TBSA): 21+/-12%), 18 mature hypertrophic scar samples from patients after elective surgery, 14 keloid samples and 18 normotrophic scar samples was, respectively, extracted, and then mRNA was isolated. Besides, biopsies were obtained from non-scarred skin of the patients and extraction of total RNA performed. Relative mRNA expression of MMP 2, MMP 9, TIMP 1 and TIMP 2 was measured with reverse transcriptase polymerase chain reaction (RT-PCR). Serum concentrations of MMP-1, -2, -9, TIMP-1, and -2 were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with extended hypertrophic scars after burn trauma presented a significantly higher TIMP-1 concentration (p

Methotrexate-induced primary cutaneous diffuse large B-cell lymphoma with an 'angiocentric' histological morphology.

2009-07-24T01:46:00.001-07:00
Clin Exp Dermatol. 2009 May 21; Pfistershammer K, Petzelbauer P, Stingl G, Mastan P, Chott A, JÃ¤ger U, Skrabs C, Geusau ASummary A patient with a 25-year history of rheumatoid arthritis and a 3-year history of methotrexate treatment developed a generalized papular rash. The papules rapidly became necrotic and then resolved, leaving a depressed scar. The rapid course of lesion development and regression was reminiscent of pityriasis lichenoides. Histology revealed a nodular infiltrate composed of a mixture of pleomorphic large B cells positive for CD20, CD30 and CD79a, and of small T cells positive for CD3 and CD4. The T cells had a striking angiocentric distribution, with some of the vessels exhibiting fibrinoid necrosis of the vessel wall reminiscent of lymphomatoid granulomatosis. However, B cells were consistently negative for Epstein-Barr virus (EBV) antigen expression. A thorough examination excluded involvement of organs other than the skin. Thus, this patient was classified as having a rare form of an EBV-negative primary cutaneous T-cell-rich B-cell lymphoma in association with methotrexate treatment.

Naive rat amnion-derived cell transplantation improved left ventricular function and reduced myocardial scar of postinfarcted heart.

2009-07-23T15:13:00.001-07:00
Cell Transplant. 2009; 18(4): 477-86Fujimoto KL, Miki T, Liu LJ, Hashizume R, Strom SC, Wagner WR, Keller BB, Tobita KStem cells contained in the amniotic membrane may be useful for cellular repair of the damaged heart. Previously, we showed that amnion-derived cells (ADCs) express embryonic stem cell surface markers and pluripotent stem cell-specific transcription factor genes. These ADCs also possess the potential for mesoderm (cardiac) lineage differentiation. In the present study we investigated whether untreated naive ADC transplantation into the injured left ventricular (LV) myocardium is beneficial as a cell-based cardiac repair strategy in a rat model. ADCs were isolated from Lewis rat embryonic day 14 amniotic membranes. FACS analysis revealed that freshly isolated ADCs contained stage-specific embryonic antigen-1 (SSEA-1), Oct-4-positive cells, and mesenchymal stromal cells, while hematopoietic stem cell marker positive cells were absent. Reverse transcription-PCR revealed that naive ADCs expressed cardiac and vascular specific genes. We injected freshly isolated ADCs (2 x 10(6) cells suspended in PBS, ADC group) into acutely infarcted LV myocardium produced by proximal left coronary ligation. PBS was injected in postinfarction controls (PBS group). Cardiac function was assessed at 2 and 6 weeks after injection. ADC treatment attenuated LV dilatation and sustained LV contractile function at 2 and 6 weeks in comparison to PBS controls (p < 0.05, ANOVA). LV peak systolic pressure and maximum dP/dt of ADC-treated heart were higher and LV end-diastolic pressure and negative dP/dt were lower than in PBS controls (p < 0.05). Histological assessment revealed that infarcted myocardium of the ADC-treated group had less fibrosis, thicker ventricular walls, and increased capillary density (p < 0.05). The fate of injected ADCs was confirmed using ADCs derived from EGFP(+) transgenic rats. Immunohistochemistry at 6 weeks revealed that EGFP(+) cells colocalized with von Willebrand factor, alpha-smooth muscle actin, or cardiac troponin-I. Our results suggest that naive ADCs are a potential cell source for cellular cardiomyoplasty.

Hysteroscopic Surgery of Ectopic Pregnancy in the Cesarean Section Scar.

2009-07-23T14:01:00.001-07:00
J Minim Invasive Gynecol. 2009 Jul-Aug; 16(4): 432-6Yang Q, Piao S, Wang G, Wang Y, Liu CSTUDY OBJECTIVE: To evaluate the effect of hysteroscopy in the treatment of caesarean section scar pregnancy. DESIGN: Retrospective review. PARTICIPANTS: Thirty-nine patients with cesarean scar pregnancy. INTERVENTIONS: Between January 2006 and June 2008, 39 patients with caesarean section scar pregnancy underwent hysteroscopic removal of conceptive tissues in our department. Their medical records were reviewed retrospectively. MEASUREMENTS AND MAIN RESULTS: The diagnosis was confirmed by serum human chorionic gonadotropic concentration and at ultrasonographic or magnetic resonance imaging. All patients underwent hysteroscopic removal of conceptive tissues under ultrasonographic guidance. Before surgery, 36 patients received 25mg of oral mifepristone, 25mg, twice a day for 3 days, and 3 patients received an injection of methotrexate salt, 50mg, and underwent preoperative bilateral uterine artery embolization. Results were reported as good in 37 patients; only 2 patients required additional surgery. CONCLUSION: Hysteroscopic removal of conceptive tissues implanted in a cesarean section scar seems to be a feasible and safe procedure that might be considered as a treatment option.

An intraoral surgical approach to the styloid process in Eagle's syndrome.

2009-07-23T07:00:00.001-07:00
Oral Maxillofac Surg. 2009 Jul 21; Chrcanovic BR, CustÃ³dio AL, de Oliveira DRPURPOSE: The purpose of this study is to present an alternative method to the extraoral surgical approach to remove the elongated styloid process, the intraoral surgical approach, and discuss their advantages and disadvantages. A literature review is also presented. PATIENTS AND METHODS: A casuistic of intraoral surgical approach to remove the elongated styloid process is presented in five patients. RESULTS: Four patients experienced postoperative moderate pain and trismus for 1 week. Bilateral surgery in one patient caused severe trismus, great discomfort, and moderate difficulty in breathing. All were followed up for 6 months and showed complete relief of the oral pharyngeal symptoms and complete improvement in functional ability. DISCUSSION: The advantages of the external approach are good visualization and reduced possibility of deep neck space infection. The disadvantages are an external scar, longer duration of surgery, and risk of injury to the facial nerve. The advantages of the intraoral approach are that the method is safe, simple, and less time consuming and an external scar is avoided. The disadvantages are possible infection of deep neck spaces, risk of injury to major vessels, and poor visualization. CONCLUSIONS: Intraoral resection of the styloid process is a safe treatment technique of Eagle's syndrome. It is not recommended the bilateral intervention at the same surgery, because of possible great discomfort at postoperative time.

Neural cell cycle dysregulation and central nervous system diseases.

2009-07-23T03:44:00.000-07:00
Prog Neurobiol. 2009 Feb 4; Wang W, Bu B, Xie M, Zhang M, Yu Z, Tao DThe cell cycle is a delicately manipulated process essential for the development, differentiation, proliferation and death of cells. Inappropriate activation of cell cycle regulators is implicated in the pathophysiology of a wide range of central nervous system (CNS) diseases, including both acute damage and chronic neurodegenerative disorders. Cell cycle activation induces the dividing astrocytes and microglia to activate and proliferate in association with glial scar formation and inflammatory factor production, which play crucial roles in the development of pathology in CNS diseases. On the other hand, in terminally differentiated neurons, aberrant re-entry into the cell cycle triggers neuronal death instead of proliferation, which may be a common pathway shared by some acquired and neurodegenerative disorders, even though multiple pathways of the cell cycle machinery are involved in distinct neuronal demise in specific pathological circumstances. In this paper, we first provide a concise description of the roles of cell cycle in neural development. We then focus on how neural cell cycle dysregulation is related to CNS diseases. Neuronal apoptosis is often detected in acute injury to the CNS such as stroke and trauma, which are usually related to the blockade of the cell cycle at the G1-S phase. In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Niemann-Pick disease type C, however, some populations of neurons complete DNA synthesis but the cell cycle is arrested at the G2/M transition. This review summarizes advances in findings implicating cell cycle machinery in neuronal death in CNS diseases.

Adenovirus-mediated METH1 gene expression inhibits hypertrophic scarring in a rabbit ear model.

2009-07-22T15:07:00.001-07:00
Wound Repair Regen. 2009 Jul-Aug; 17(4): 559-68Song B, Zhang W, Guo S, Han Y, Zhang Y, Ma F, Zhang L, Lu KHypertrophic scarring remains a major problem for patients who have suffered from surgeries or burns. Vascularization plays an important role in the early phase of hypertrophic scarring. Therefore, the inhibition of angiogenesis might be used as a preventive strategy. In this study, we assessed the effect of anti-angiogenesis resulting from adenovirus-mediated METH1 (metalloprotease and thrombospondin1) gene expression on the hypertrophic scar formation in a rabbit ear model of hypertrophic scarring. We first investigated the number of microvessel and microcirculatory perfusion in untreated scars on days 10, 30, 60, and 90 after epithelialization. Then, we examined the effect of anti-angiogenesis by adenovirus-mediated METH1 expression on hypertrophic scar formation by calculating the scar elevation index, counting the microvessel and argyrophilic nucleolar organizer region particle, and detecting the amount of collagen on days 30 and 60 after treatment. We found that untreated scar tissues at the proliferative phase (days 10-60 after epithelialization) had a significantly higher density of microvessel and microcirculatory perfusion than those at the mature phase (day 90 after epithelization) (both p

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist inhibits transforming growth factor-beta1 and matrix production in human dermal fibroblasts.

2009-07-22T04:50:00.001-07:00
J Plast Reconstr Aesthet Surg. 2009 Jul 17; Zhang GY, Cheng T, Zheng MH, Yi CG, Pan H, Li ZJ, Chen XL, Yu Q, Jiang LF, Zhou FY, Li XY, Yang JQ, Chu TG, Gao WYPeroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are increasingly used in patients with diabetes, and some studies have suggested a beneficial effect on organ fibrosis, but their effects on dermal cell growth and extracellular matrix (ECM) turnover are unknown. To investigate the effect of the PPAR-gamma agonist troglitazone on cell growth and matrix production in human dermal fibroblasts (HDF), HDF were cultured and grown in a different concentration of troglitazone. PPAR-gamma expression and matrix production were measured in HDF in the presence of troglitazone. The mRNA expressions of TGF-beta1, collagen I (Col I) and fibronectin (FN) were determined by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein of transforming growth factor-beta1 (TGF-beta1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of Col I and FN were determined by Western blotting. The mRNA expression of TGF-beta1, Col I and FN were significantly decreased in HDF in 15-30mumoll(-1) troglitazone compared to the control group with Dulbecco's modified Eagle's medium (P

Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms.

2009-07-22T01:12:00.001-07:00
Brain. 2009 Jul 16; Bacigaluppi M, Pluchino S, Jametti LP, Kilic E, Kilic U, Salani G, Brambilla E, West MJ, Comi G, Martino G, Hermann DMRecent evidence suggests that neural stem/precursor cells (NPCs) promote recovery in animal models with delayed neuronal death via a number of indirect bystander effects. A comprehensive knowledge of how transplanted NPCs exert their therapeutic effects is still lacking. Here, we investigated the effects of a delayed transplantation of adult syngenic NPCs-injected intravenously 72 h after transient middle cerebral artery occlusion-on neurological recovery, histopathology and gene expression. NPC-transplanted mice showed a significantly improved recovery from 18 days post-transplantation (dpt) onwards, which persisted throughout the study. A small percentage of injected NPCs accumulated in the brain, integrating mainly in the infarct boundary zone, where most of the NPCs remained undifferentiated up to 30 dpt. Histopathological analysis revealed a hitherto unreported very delayed neuroprotective effect of NPCs, becoming evident at 10 and 30 dpt. Tissue survival was associated with downregulation of markers of inflammation, glial scar formation and neuronal apoptotic death at both mRNA and protein levels. Our data highlight the relevance of very delayed degenerative processes in the stroke brain that are intimately associated with inflammatory and glial responses. These processes may efficaciously be antagonized by (stem) cell-based strategies at time-points far beyond established therapeutic windows for pharmacological neuroprotection.

Morphometric analyses of elastic tissue fibers in dermatofibroma: clues to etiopathogenesis?

2009-07-21T22:32:00.001-07:00
J Cutan Pathol. 2009 Jul 10; Pongpudpunth M, Keady M, Mahalingam MBackground: The etiopathogenesis of dermatofibroma (DF), a common benign fibrohistiocytic tumor, is debatable. The goal of this study was to ascertain the density of elastic tissue fibers in DF in an effort to investigate whether this provides an insight into its etiopathogenesis. Method: Three groups comprising eight cellular DFs, eight paucicellular DFs and eight scars (control group) were stained with a modified Verhoeffs-van Gieson (without counterstain), and elastic fibers in three randomly selected fields within the lesional area/case semiquantitatively analyzed and examined in a blinded fashion. Result: The mean density of elastic tissue fibers in cellular DF was 6.81 (1.38-15.89); in paucicellular DF, 2.46 (0.14-5.79) and in scar, 2.95 (0.97-10.69). Overall, significant differences in density of elastic tissue fibers were observed only between cellular DF and the other two groups (vs. paucicellular variant, p = 0.03 and vs. scar, p = 0.05). Morphological changes observed included thickness, clumping, elongation and waviness (cellular DF) and margination of elastic tissue fibers (paucicellular variant). Conclusion: While the jury still appears to be out regarding the etiopathogenesis of DF, the reduction in density of elastic tissue fibers in the paucicellular variant compared with its cellular counterpart lends credence to the concept of evolutionary stages of DF. Pongpudpunth M, Keady M, Mahalingam M. Morphometric analyses of elastic tissue fibers in dermatofibroma: clues to etiopathogenesis?

Microscopic inflammatory foci in burn scars: data from a porcine burn model.

2009-07-21T17:59:00.001-07:00
J Cutan Pathol. 2009 Jul 15; Wang XQ, Phillips GE, Wilkie I, Greer R, Kimble RMBackground: Hypertrophic scars in burn victims usually occur after delayed wound healing and the active phase of scar formation can persist substantially even after wound closure. Currently, the pathophysiology of the hypertrophic scar is not completely understood. This study investigated the inflammatory response in scar tissue at week 6 post-burn injury. Methods: A porcine deep dermal partial thickness burn model was used. At week 6 post-burn, a total of 528 scar biopsies from 72 burn scars (7-8 biopsies from each scar) and 174 normal skin biopsies from 18 pigs were collected and examined histologically. Results: Microscopic inflammatory foci were identified in 17% (89/528) of scar biopsies. These microscopic inflammatory foci do not contain any irritant materials, are composed largely of polymorphonuclear cells with other inflammatory cells including multinucleate giant cells and show acute on chronic inflammatory response that has not been described previously in burn scars. Importantly, they are present in a significantly lower number in burns surgically debrided than in burns which have not been debrided. Conclusions: This study identifies microscopic inflammatory foci in the porcine scar tissue layer and recommends thorough cleaning/debriding of burned necrotic tissue in order to minimize the formation of these inflammatory foci in scar tissue. Wang X-Q, Phillips GE, Wilkie I, Greer R, Kimble RM. Microscopic inflammatory foci in burn scars: data from a porcine burn model.