bluuebunny/crossref_metadata_2025_split huggingface dataset:
126 Scrotal and Penile Reconstruction using VAC Therapy
Authors: Snyder N , Gould LJ 
Published: March 2007

Fournier gangrene is a rapidly progressive necrotizing soft tissue infection that often leaves patients with a large integumentary deficit to their penis and scrotum. Treatment of the skin defect has been described in a multitude of ways including split thickness skin grafting, burying the testes in the thighs, thigh flaps, and a variety of myocutaneous and fasciocutaneous flaps.Many of the previously described techniques have worked well for smaller defects and for closure of wounds but fell short of aesthetic reconstruction of sexual organs. We describe a technique using split‐thickness skin grafts with suction dressings or bolster. This was employed using the VAC©(Vacuum Assisted Closure Device, KCI©). This technique creates a natural appearing scrotum that holds the testes away from the body in a physiologic manner and surfaces the penis with a seemingly natural appearance in a functional manner. The technique provides a nearly 100% graft take and greatly decreases hospital length of stay.A case report demonstrates a patient’s full recovery to his professional, social, and sexual life within six weeks of initial reconstructive treatment. Our technique provides a reliable treatment with good functional and aesthetic outcomes to a difficult problem.
128 Wound Healing Morphology in an Acute Wound Healing Study
Authors: Serena T. 
Published: March 2007

Background: Physiological healing in acute wounds generally occurs by granulation from the wound base and by migration of epithelium from the wound edges toward the center of the wound in a uniform, concentric fashion. The Wound Healing Cooperative Group (WHCG) compared this phenomenon in acute wounds treated with standard care versus acute wounds pharmacologically stimulated with growth factor therapy. Methods: With informed consent, 20 normal healthy volunteers underwent four 6 mm biopsies of the flexor surface of both forearms. The biopsy sites were randomly assigned to a control arm (daily bacitracin) or to one of three treatment arms: i) rhPDGF‐BB 0.01% gel Q.D., ii) rhPDGF‐BB Q.O.D., iii) daily rhPDGF‐BB (Q.D. × 7 days followed by bacitracin alone daily). Wound morphology was carefully examined and photographed daily until complete healing was achieved. Results: There were distinct differences in the morphological pattern of healing seen between control wounds and growth factor‐stimulated wounds. Acute wounds treated with bacitracin tended to heal in circumferential fashion, as predicted. Growth factor‐stimulated wounds, by contrast, exhibited accentuated angiogenesis (granulation), with non‐uniform epithelial islands streaming into the wound. Conclusion: This pilot study suggests that rhPDGF‐BB influences acute wound healing by promoting accelerated granulation and epithelialization. Accelerated healing is manifest by different healing morphologies. The biological basis for these differences requires further histological and molecular analyses. Acknowledgements: Funding from The Angiogenesis Foundation.
132 Differential Regulation of Osteopontin and Matrix Metalloproteinases During Diabetic Wound Healing
Authors: Sharma A. , Singh A. K. , Warren J. , Maheshwari R. K 
Published: March 2007

Delayed wound healing is a common complication of diabetes resulting in significant clinical morbidity. The diabetic wound exhibits impaired cellular infiltration and consequently inadequate granulation tissue formation. Additionally, altered patterns of apoptosis. In this study, we have evaluated the differential gene expression pattern in transgenic diabetic female mice, 5–6 weeks old, in a full thickness cutaneous punch wound model. We assessed the role of matrix metalloproteinases (MMPs) and differential gene expression pattern at 4th, 7th and 11th day post wounding. Supernatants obtained from diabetic wound tissue homogenates were subjected to zymogram analysis. The data showed that MMPs were expressed at higher level by 4th day post wounding, whereas expression of MMPs were down regulated towards the 11th day post wounding suggesting their role during early phase of wound healing.The pathway specific gene array data demonstrated differential regulation of several growth factors, transcription factors and other related genes such as fibroblast growth factors and their receptors, ID3 and restin respectively. The cytokine/extracellular matrix protein osteopontin (OPN), an important component of cellular immunity and inflammation also showed higher expression after 4 days post wounding. The expression of OPN remained at higher level after 11 days post wounding in diabetic mice, whereas the expression were down regulated to basal level in normal wounded animal suggesting that the expression of OPN was concomitant with the extent of healing. Other adhesion molecules such as integrin αV and PECAM‐1 were also differentially regulated. Though a single gene may not be solely responsible for any defect or impairment in healing as it is a very tightly controlled and regulated process, however, a detailed study of these gene(s) may shed some light to the delayed healing in diabetic mice. Acknowledgements: (These studies are supported by NIH Grant G174KT.)
144 The Upregulation of Wound Healing Related Genes in Venous Ulcerations Treated with Apligraf, a Possible Mechanism of Action
Authors: Serena T.E. , Finley C. 
Published: March 2007

Background: Apligraf, a bioengineered living skin construct, has been shown to accelerate the healing of chronic venous leg and diabetic foot ulcerations. However, to date the mechanism of action of Apligraf in the wound healing process is not well understood. Objective: The primary objective of this study was to determine the levels of expression of selected wound healing related genes in venous leg ulcers treated with Apligraf in comparison to ulcers treated with standard multi‐layer compression therapy alone. Gene chip technology was employed. Methods: Three patients were randomized into the Apligraf or standard treatment arms. A baseline 6 mm punch biopsy was obtained prior to the initial application of Apligraf or multi‐layer compression therapy. A second biopsy was obtained depending on the randomly chosen biopsy schedule (weeks 1, 2 or 4 following Apligraf application or initiation of compression). The biopsy specimens were snap frozen and later analyzed using microarray gene chip technology. Results: The patients treated with Apligraf demonstrated an up‐regulation of the genes thought to be important in the wound healing process. Conclusion: The results from this pilot study suggest that Apligraf may function by an up‐regulation of the genes involved in wound healing as opposed to compression therapy which works primarily in a mechanical fashion. Based on these results further study is needed.
147 Persistence and Expansion of Seeded Marrow Cells in Dermal Substrate
Authors: Liu PY , Wang XT , Ponte C , Tang JB , Badiavas EV 
Published: March 2007

Bone marrow cells have been used to potentiate wound healing in chronic wounds (Badiavas and Falanga, 2003). We postulate that the performance of these autografted cells may be enhanced by seeding them into scaffolding with normal skin architecture; indeed that the differentiation of the precursor cells may be determined by the juxtaposition of intact extracellular matrix. This might in turn lead to a prefabricated skin substitute capable of recapitulating fully functional skin.We are seeding murine gfp+ bone marrow cells, containing mixed mesenchymal and hematopoietic precursor cells into Alloderm®, a decellularized preserved skin graft. This seeding is potentiated by meshing the skin and gentle centrifugation of fresh marrow into the dermal aspect of the allograft. Other samples were merely co‐cultured with the cells in Dexter’s media. Duplicate samples were fixed and stained with DAPI at 1, 3, 7, and 14 days. Viewed under fluorescence, gfp+ cells are bright green.Comparing these images with DAPI‐staining allows viable cells to be identified which are gfp+. H&E micrographs were used to ascertain cellular morphology. Results: Scant cells were observed in the allografts at the early time points. The cells were pleiomorphic with large nuclei, resembling hematopoietic precursors(Fig 1). Later, at days 7 and 14, more abundant cells were apparent, including some in the interior of the dermis. This signifies either migration or seeding via centrifugation. The morphology of these cells is significantly different; the spindle shape suggests a fibroblast (Fig 2). In addition, the population of gfp+ cells has markedly expanded by day 14, attaining near confluence in some sections (Fig 3). No cells were seen in controls (Fig 4). Conclusion: True skin replacement will only be possible when the panoply of skin appendages can be recapitulated. The experiments presented here are evidence that pluripotential precursor cells can be seeded into dermal matrices providing an optimal environment for regeneration.imageimageimageimage
148 2‐Methoxyestradiol, an Endogenous Estrogen Metabolite, Regulates Apoptosis in Skin Microvascular Endothelial Cells
Authors: Philip A. , Horvat A‐M , Chowdhury M. 
Published: March 2007

Programmed cell death or apoptosis regulates the sequence of cellular events that are involved in the wound healing process. Understanding the mechanisms controlling apoptosis during tissue repair may lead to the development of modalities to improve healing and reduce scarring. 2‐Methoxyestradiol (2ME), a naturally occurring metabolite of 17‐ estradiol, has recently emerged as a promising anti‐proliferative and angiostatic agent with minimal toxicity at pharmacological doses. However, the mechanism by which 2ME induces its anti‐proliferative and apoptotic activities is uncertain, and its physiological function remains to be determined. In the present study we examined the effects of physiological and pharmacological concentrations 2ME in human skin microvascular endothelial cells.Our findings show that 2ME rapidly activates JNK and p38 MAP kinase pathways at both physiological and supraphysiological levels. Our results indicate that the rapid activation of p38 and JNK are not required for 2ME‐induced inhibition of DNA synthesis, caspase‐3 activation, or cell cycle arrest, and thus apoptosis, in microvascular endothelial cells. On the contrary, our results suggest that rapid activation of JNK and p38 MAP kinases likely mediates an early pro‐survival response to 2ME. The fine regulation of survival versus apoptotic signals may contribute to the ability of 2ME to elicit its effects in endothelial cells. Since endothelial cells play an essential role during wound healing, identification 2ME as a potent regulator of endothelial cell proliferation and function warrants further studies of its therapeutic potential as an agent to manipulate wound repair events.
006 Development of a Novel Matrix Metalloproteinase‐Inhibiting Wound Dressing
Authors: Skarja Gary A. , Gorbet Maud B. , Lawson‐Smith Rebecca K. , May Michael H. , Sefton Michael V. 
Published: March 2007

Rimon Therapeutics develops synthetic therapeutic polymers (Theramers™) that combine bioactivity with a broad range of desirable mechanical and physical properties. The MI Theramer™ is a polymer that modulates the activity of matrix metalloproteinases (MMPs).. Excessive proteolytic cleavage of extracellular matrix and growth factors resulting from elevated levels of MMPs is believed to contribute to the impaired wound healing associated with chronic, non‐healing wounds. MI Theramer™ beads suspended in ThermaGel™(a thermoreversible gel) make up MI‐Gel™ Dressing. The dressing may be applied as a liquid that is poured into a wound, where it will gel on contact. The dressing can be reliquified and removed easily without re‐injuring the wound by cooling it. In vitro inhibition of collagenase type IV (equivalent to MMP‐2) from clostridium histolyticum (Molecular Probes) was measured. A dose‐dependent inhibition of MMP‐2 activity was measured for MI Theramer™ beads alone and suspended in ThermaGel™ indicating that MMP‐2 is able to diffuse into the gel and bind to the beads suspended therein. In vivo efficacy was demonstrated by observing the degradation of glutaraldehyde cross‐linked gelatin tubes using a mouse subcutaneous pouch model. Gelatin zymography on extracts collected from the gelatin tubes co‐implanted with MI Theramer™ beads also showed reduced MMP‐2 and MMP‐9 activity in comparison to controls.The insoluble MI Theramer™ beads were able to modulate MMP activity both in vitro and in vivo. The beads retained their inhibitory activity when they were suspended in a novel thermoreversible gel (ThermaGel™). The combined MI‐Gel™ Dressing may have promise as a novel chronic wound healing product.
007 Rebalancing Wound Biochemistry Improves Healing: A Clinical Study Examining Effect of Promogran
Authors: Cullen B. , Kemp L. , Essler A. , Wallenfang‐Sohle K. , Stadler R. 
Published: March 2007

Normal wound healing is a carefully controlled balance of new tissue formation and destructive processes necessary to remove damaged tissue. Within this complex environment there are many points of regulation, which control the biological processes necessary to achieve wound repair. An alteration in any of these processes can result in an imbalance of the biochemical components, which ultimately results in delayed wound closure and the formation of a chronic wound. Therefore, we propose that an effective therapeutic approach would modify this hostile environment and redress this imbalance.In this study we have evaluated the effect of PROMOGRAN in vivo, in patients with venous leg ulcers. Wound fluid samples were collected and analyzed from a number of patients prior to and during treatment with PROMOGRAN.Our results have shown that wounds, which respond to PROMOGRAN treatment, have also shown a decrease in protease activity in the corresponding wound fluid samples. Whilst it is impossible to determine whether this reduction in protease levels is responsible for healing or merely symptomatic of other changes occurring within the wound, we have shown that a decrease in proteolytic activity is concomitant with healing.This study provides clinical evidence that PROMOGRAN can rebalance the chronic wound environment in situ and thereby promotes wound repair.
022 Warming Surgical Wounds: Effects on Healing and Wound Complications
Authors: Whitney J.D. , Dellinger E. P. , Wickline M. 
Published: March 2007

Aims: Compare postoperative local warming to standard incision care on: 1) healing response and 2) incidence of wound complications. Methods: This two group randomized pilot study (N = 54) tested the wound healing effects of post‐operative warming in patients having gastric bypass or colectomy procedures. Patients randomized to warming received their first 1‐hour treatment in the post anesthesia recovery unit followed by 5 additional treatments in the first 48 hours after surgery. Healing response was evaluated by hydroxyproline and mRNA for pro α 1(I) collagen content of a subcutaneous ePTFE implant removed on postoperative day 9. Patients were followed for the first two postoperative clinic visits (6–8 weeks). CDC Surgical Site Infection Criteria were used to evaluate wound infection and complications. Results: Six warmed (22%) and 10 standard care (37%) patients experienced healing problems.Incidence of Wound Infection by CDC classification.  Incidence of Wound Infection by CDC classification.

Group
Superficial
Deep Incisional
Organ Space

Warming
2
3
1

Standard Care
4
4
2

Mean hydroxyproline levels did not differ, though there was a trend toward higher amounts in warmed patients (332 ± 185 ng/cm ePTFE vs. 286 ± 165 ng/cm). Differences in mRNA for pro α 1(I) collagen approached significance (Chi‐Square 5.4, p = .06) with warmed patients showing more cells with abundant positive message. Conclusions. Clinical and cellular outcomes suggest local incision warming may benefit healing by reducing infection and influencing fibroblast collagen production.
011 Inflammation‐induced Angiogenesis: Potential Roles of IL‐8. and VEGF
Authors: Yao M. , Dueck M. , Martins‐Green M. 
Published: March 2007

Inflammation is invariably accompanied by angiogenesis; both are important in wound healing. However, it is not known how angiogenic factors that are present during the inflammatory phase of wound healing are involved in inflammation‐induced angiogenesis. In this study, we address the contribution of two such factors, interleukin‐8 (IL‐8/CXCL8) and VEGF, in inflammation‐induced angiogenesis. We determined the relative levels of these molecules during the first two weeks of the wound healing process in partial‐thickness skin wounds of rabbits. IL‐8 levels increase rapidly after wounding, reaching maximal levels after 24 hr; in contrast, VEGF levels peak at 3 days. We also determined the time course of the infiltration of various inflammatory cells and production of new blood vessels after wounding. Neutrophils were markedly increased 4 hr after wounding, and their level peaked at 24 hr. Monocyte infiltration peaked 48 hr after wounding and decreased by day 3. The number of blood vessels was significantly increased by day 3 after wounding and continued to increase through days 5 and 7.In order to determine the contribution of IL‐8 and VEGF to the angiogenic process, we performed the wounding experiments in the presence and absence of IL‐8 and VEGF antibodies. Treatment with IL‐8 antibodies blocked the early stage of blood vessel formation but did not alter the late stage; in contrast, VEGF antibodies blocked the late stage without altering the early stage. Currently, we are performing studies using inhibitors against IL‐8 and VEGF receptors to determine whether we observe similar results; we are also beginning to decipher molecular mechanisms involved in this process. This study suggests that IL‐8 and VEGF play complementary roles in stimulating angiogenesis during wound healing.
021 Contact Sensitivity in Patients with Leg Ulcerations: A North American Study
Authors: Saap L. , Fahim S. , Arsenault E. , Pratt M. , Pierscianowski T. , Falanga V. , Pedvis‐Leftick A. 
Published: March 2007

Background: Over the last two decades, there have been a number of studies in Europe on contact sensitivity in patients with chronic leg ulcerations with a frequency of positive patch test results ranging from 40 to 82.5%. The prevalence of sensitization has not been studied in North America. Furthermore, many of the newer dressings and wound care products in the market have not been studied for contact sensitivity in patients with chronic wounds. Objectives: 1) To determine the prevalence of allergen sensitivity in patients with history of leg ulcers in two North American study centers, 2) to compare our results to the European studies and to the North American Contact Dermatitis Group (NACDG) database and 3) to help delineate a standard battery of allergens for patch testing in North American leg ulcer patients Methods: 54 patients with an active or past leg ulcer were prospectively entered in the study. The patients were patch tested to both the NACDG Standard series, as well as, a comprehensive supplemental series of 48 allergens including wound care medicaments and dressings. Results: 63% of patients were sensitized to at last one allergen. The most common allergens were Balsam of Peru (29.6%), bacitracin (24.1%), fragrance mix (20.4%), wood tar mix (20.4%), propylene glycol (13.5%), neomycin sulfate (13%), benzalkonium chloride (13%), carba mix (11.1%), nickel sulfate (11.1%) and Duoderm CGF (11.1%). Duoderm CGF was the most allergenic dressing in our study group. Conclusion: There is a high incidence of positive patch tests in patients with past or current leg ulcerations. Using a modified leg ulcer series along with the standard NACDG series is very important in evaluating patients with leg ulcers.
Critical influences affecting response to various treatments in young children with ADHD: a case series
Authors: Heriot S. A. , Evans I. M. , Foster T. M. 
Published: March 2007

AbstractBackground  While the use of stimulant medication as a treatment for children with attention deficit hyperactivity disorder (ADHD) has been the most studied therapy in child psychiatry, there is debate about its use with young children. This study describes a series of cases seen in a normal clinical context, treated with one of four different treatment programmes.Methods  Sixteen pre‐school children diagnosed with ADHD and their parents were randomly assigned to receive one of four treatments: (1) 0.3 mg/kg methylphenidate, parent training programme; (2) 0.3 mg/kg methylphenidate, parent support programme; (3) placebo medication, parent training; and (4) placebo medication, parent support. Changes were assessed at the individual level, using clinical observations, parent and teacher rating scales and measures of parenting and family factors.Results  Children were more likely to improve when the treatment involved at least one active component (medication or parent training). However, there was notable variability in individual parental and child participants' responses to all treatment conditions, indicating the importance of interactions between treatment variables and other factors.Conclusions  Findings are discussed within the framework of a transactional model, and inferences are drawn about the limitations of the idea that there is a ‘best treatment’ that is universally applicable.
Access to and use of NHS Patient Advice and Liaison Service (PALS): the views of children, young people, parents and PALS staff
Authors: Heaton J. , Sloper P. , Clarke S. 
Published: March 2007

AbstractBackground  The English National Health Service Patient Advice and Liaison Service (PALS) was set up to provide patients and their relatives with a way of obtaining information or expressing concerns about their health care. This study examined children's, young people's and parents' access to and use of PALS, and how this could be improved.Methods  Qualitative and quantitative methods were used to obtain the views of children, young people, parents and PALS staff, on the inclusiveness of the service. These methods included discussion groups and interviews with 30 young people and 16 parents; a postal survey of PALS users, to which 171 (21%) parents responded; and telephone interviews with 14 PALS staff. The data were analysed using qualitative and quantitative methods, and the views of participants on key topics were examined.Results  Children and young people were found to be low users of PALS, but thought that the service was potentially useful. They and parents and PALS staff all highlighted ways in which access to and use of the service could be improved. Participants' views on the following topics are reported: awareness of PALS existence and role; access to and use of PALS; effectiveness of and satisfaction with PALS; and training of staff.Conclusions and recommendations  Patient Advice and Liaison Service has not been designed and developed in ways that are fully inclusive of children, young people and parents. Based on their views and experiences, and the suggestions of PALS staff, the authors recommend that access to and use of the service could be improved, increasing awareness of PALS, facilitating access to and use of the service, providing training for PALS staff on dealing with young people and their issues, and developing links between PALS and other organizations that deal with young people and parents.