Comparison of PHMB-containing dressing and silver dressings in patients with critically colonised or locally infected wounds.

OBJECTIVE: This study compares treatment with a polihexanide-containing biocellulose wound dressing (BWD+PHMB) versus the best local standard of silver dressings (Ag) in painful, critically colonised (wounds-at-risk) or locally-infected wounds. METHOD: Patients with wounds of various aetiologies, a baseline VAS pain score >4 and a semi-quantitative bacterial load of ++ or higher were randomly allocated to receive treatment with either BWD+PHMB or Ag. Patients with systemic infections and/or using systemic antibiotics were excluded. The primary endpoint, patient-reported pain (VAS total pain, including the sub-scores pain at night, during the day, before, and 15min after dressing changes), was compared between treatment groups and scored on days 0, 1, 3, 7, 14, 21 and 28. Secondary outcomes of bacterial load, wound bed and periwound skin condition, quality of life and dressing handling were assessed at the same visits. RESULTS: Thirty-eight patients (BWD+PHMB, n=21 [24 wounds]; Ag, n=17 [18 wounds]) were included in the analyses. Baseline variables showed no significant differences. Wound pain was reduced significantly in both groups, with a better pain reduction noted for BWD+ PHMB (p<0.001) before dressing changes. Compared with Ag, in the BWD+PHMB group critical colonisation and local wound infection had been reduced significantly faster and better (p<0.001) over the 28-day study period. Improved quality of life, good tolerability and no adverse events were demonstrated for both groups. CONCLUSION: Both BWD+PHMB and AG were effective in reducing pain and bacterial burden. However, that BWD+PHMB was significantly faster and better in removing the critical bacterial load, makes this dressing an attractive therapeutic option to treat critically colonised and locally-infected wounds.

Clinical efficacy of a new monofilament fibre-containing wound debridement product.

OBJECTIVE: To evaluate the wound debridement efficacy (that is, achievement of 100% granulation tissue on the wound bed) of a new monofilament fibre product (Debrisoft). METHOD: This multicentre, prospective, observational evaluation assessed the debridement efficacy, safety, patient comfort and user satisfaction of this new product. Time taken to perform the debridement procedure was also recorded. The new product was wetted with either saline or polihexanide and applied for 2-4 minutes, following which the usual dressing regimen was applied. Clinical outcome was scored by a trained clinician. Additionally, before and after photographs were assessed by one and the same clinician, who was blinded to the treatment given. The debridement outcomes achieved with the test product were compared with results obtained using other methods of debridement, both non-surgical and surgical, taken from an electronic database but using the same scoring systems as here. RESULTS: Sixty patients with chronic wounds requiring debridement were recruited, of whom 57 were included in the analysis. Debridement was effective in 93.4% (142/152) of the sessions, and the product remained intact in 95.4% (145/152). The average time for each debridement session was 2.51 minutes, markedly less than for the current debridement methods at the evaluation centres. Visible debris and slough were successfully removed with the test product. Patients reported no pain during the procedure in 45% of cases and slight discomfort for a short duration (2.0 minutes on average) in 55% of cases. CONCLUSION: The results indicate the potential for this monofilament fibre product to replace several modes of debridement, based on its efficacy, short procedure, ease of use and patient comfort. CONFLICT OF INTEREST: The evaluation protocol was proposed and supported by Lohmann & Rauscher GmbH, who provided the evaluation products. MS and MA are employees of Lohmann & Rauscher. The other authors declare to have no relevant financial interest in the evaluation. Apart from input to the protocol, the sponsors had no role in the conduct of the study, such as data collection, analysis, or preparation, review, or approval of the manuscript.

A clinical evaluation of the efficacy and safety of singlet oxygen in cleansing and disinfecting stagnating wounds.

OBJECTIVE: This cohort study evaluated the clinical efficacy of singlet oxygen, ActiMaris (AM) a hypertonic (3%) ionised (pH 9.8) sea water solution. It was assumed that when used for wound cleansing, disinfection and the reduction of inflammation, AM would be safe and effective. METHOD: Between May 2008 and May 2009, ambulant patients presenting at one of four wound healing centres were included in the study. Patients had critically colonised and/or infected, malodorous wounds, covered with slough/fibrin or wounds showing inflammation of the periwound skin. Wounds were assessed in terms of percentage changes in fibrin, slough and granulation tissue, they were assessed clinically and high resolution digital photographs were scored by a physician who was blinded to treatment allocation. Results were compared at baseline (week 0) and following 42 days of AM treatment (week 6). RESULTS: Seventy-three patients were included in the analysis. Dressing changes were at 2-day intervals on average, and the median treatment period was 46.04 days (range: 3-197). At 42 days, 33% (n=24) of included wounds had healed, 57% (n=42) had improved and 10% (n=7) remained stagnant. Cleansing and wound disinfection with AM was effective. In 31 patients (42%) wounds had showed clinical signs and symptoms of critical colonisation and/or infection at day 0, whereas at day 42 the infection was completely eradicated. Inflammation was reduced in 60% (n=44) of cases and patients did not report pain or discomfort when using AM. CONCLUSION: The use of singlet oxygen was shown to be safe and the results of this study indicate AM to be useful for wound cleansing, disinfection, reducing inflammation and promoting wound healing. CONFLICT OF INTEREST: The centres were supplied with the study product by the sponsor. The authors have no financial interest in writing this article.

Classification of wounds at risk and their antimicrobial treatment with polihexanide: a practice-oriented expert recommendation.

Currently, there are no generally accepted definitions for wounds at risk of infection. In clinical practice, too many chronic wounds are regarded as being at risk of infection, and therefore many topical antimicrobials - in terms of frequency and duration of use - are applied to wounds. Based on expert discussion and current knowledge, a clinical assessment score was developed. The objective of this wounds at risk (W.A.R.) score is to allow decision-making on the indication for the use of antiseptics on the basis of polihexanide. The proposed clinical classification of W.A.R. shall facilitate the decision for wound antisepsis and allow an appropriate general treatment regimen with the focus on the prevention of wound infection. The W.A.R. score is based on a clinically oriented risk assessment using concrete patient circumstances. The indication for the use of antiseptics results from the addition of differently weighted risk causes, for which points are assigned. Antimicrobial treatment is justified in the case of 3 or more points.

Clinical use of polihexanide on acute and chronic wounds for antisepsis and decontamination.

Polihexanide is an antimicrobial compound suitable for clinical use in critically colonized or infected acute and chronic wounds. Its beneficial characteristic is attributable particularly to its broad antimicrobial spectrum, good cell and tissue tolerability, ability to bind to the organic matrix, low risk of contact sensitization, and wound healing promoting effect. In addition, no development of microorganism resistance during polihexanide use has been detected to date, nor does this risk appear imminent. The aim of therapy using polihexanide is to reduce the pathogen burden in a critically colonized or infected acute or chronic wound. An increasing number of articles on the subject of wound antisepsis with polihexanide can be found in the medical literature. However, there is still little published information on the practical use of polihexanide-containing wound antiseptics. The purpose of this review article is to describe the handling and the different possibilities of use of polihexanide-containing preparations, including the currently approved indications, contraindications and reservations. The use of polihexanide is not the only therapeutic option in management of wounds; therefore, priority is also given to prior surgical debridement and clarification of the cause of the underlying disease, including appropriate therapy.

A practice-oriented recommendation for treatment of critically colonised and locally infected wounds using polihexanide.

UNLABELLED: The problem of wound infection presents a special challenge in the treatment of acute as well as chronic wounds. Typical complications not only jeopardise the successful outcome of treatment modalities as a whole; they may result in amputation or even become life-threatening. Polihexanide is an antimicrobial substance which is highly appropriate for use in critically colonised or infected acute and chronic wounds. This finding is based primarily on the broad antimicrobial spectrum and good cell and tissue compatibility of polihexanide, its capability of binding to organic matrix, the low risk of contact sensitisation, and the fact that it promotes wound healing. Furthermore, there has been no conclusive evidence to date of any pathogens developing resistances under the use of polihexanide. SUMMARY: Wound infections are special and challenging situations in therapy of acute and chronic wounds. Typical complications are risky not only for therapeutic process but also for amputation and viability of patients. Polihexanide is an exceedingly appropriate antimicrobial substance for using in critical colonised and local infected acute and chronic wounds. This evaluation is based on different properties of the compound like the broad antimicrobial spectrum, the excellent cell and tissue tolerability, the binding capacity to organic matrix, low risk of contact sensitisation and adjuvant effects to wound healing. Up to now there are no microbial resistances observed.

Role of the wet-to-dry phase of cleansing in preparing the chronic wound bed for dressing application.

The wet-to-dry phase is a method of cleansing that acts as an alternative to rinsing prior to the application of a modern wound dressing. Debris, exudate and pathogens are removed from the wound, reducing itching and inflammation.

Use of Allevyn heel in the management of heel ulcers.

OBJECTIVE: This small uncontrolled study examined the effectiveness of Allevyn Heel. METHOD: Twenty-two patients were recruited: 13 with heel pressure ulcers, four with diabetic heel ulcers, four with arterial heel ulcers and one 'other'. Ulcers were assessed before treatment and after the start of the dressing regimen at weeks two and four and at the end of the study. RESULTS: Patients were treated with Allevyn Heel for a mean of 47.2 days, and dressings were left in place for an average of 2.2 days before being changed. By the end of treatment, 32% of the ulcers had completely or almost healed, and a further 27% were showing evidence of granulation. Application was considered easy in 98% of instances, and 91% of the patients reported that Allevyn Heel was comfortable to wear. CONCLUSION: Allevyn Heel was found to be effective and easy to use. This extends the range of wounds that are suitable for management with Allevyn, although a larger-scale study is needed to confirm the utility of Allevyn Heel for these type of heel wounds. DECLARATION OF INTEREST: This study was supported by Smith and Nephew, Germany.

Z1/Z2 defects in 4H-SiC.

First-principles calculations are carried out on models for the Z(1)/Z(2) defects in 4H-SiC which are found in as-grown and irradiated n-type material. We show that an interstitial-nitrogen-interstitial-carbon defect is exceptionally thermally stable, bistable, and has negative-U character with donor and acceptor levels close to those attributed to the defect.

Nurses' views about pain and trauma at dressing changes: a central European perspective.

OBJECTIVE: This study investigated nursing and medical practitioners' perceptions of pain and trauma at dressing change in three German-speaking European countries: Austria, Germany and Switzerland. It follows a similar study by Hollinworth and Collier conducted in the UK. METHOD: A total of 3300 questionnaires were posted to practitioners in the three countries. All of the practitioners had attended at least one educational event on wound management organised by the researchers. The questionnaire contained closed questions about the participants' experience of dressing change and pain, their place of work and their freedom to select wound management products. RESULTS: A 15.1% response rate was achieved. The main aim at dressing change was to prevent trauma to the wound (30%) and to prevent infection (29%) and pain (21%). Dressing removal (51%) and wound cleansing (41%) were cited as the phases of dressing pain most likely to cause pain. Factors perceived to cause pain during dressing changes included dressings that adhere to the wound area (35%), particularly direct adherence to the wound (29%) and dried-out dressings (28%). Techniques used to prevent pain included rehydrating dressings. The responses also pointed to insufficient knowledge about low-adherent or non-adherent dressings among some respondents. CONCLUSION: The respondents perceived dressing removal and wound cleansing to be the most painful wound-care interventions. Their key objectives were to prevent pain and trauma at dressing changes. Lack of information on low- and non-adherent dressings needs to be addressed. DECLARATION OF INTEREST: This study was funded by Mölnlycke Health Care AG, Switzerland.

Modification of the HER2/NEU-derived tumor antigen GP2 improves induction of GP2-reactive cytotoxic T lymphocytes.

GP2 (IISAVVGIL), the p654-662 HER2/neu-derived tumor antigen, induces HLA-A2-restricted cytotoxic T lymphocytes (CTL) reactive to various epithelial cancers. The binding affinity of GP2 for HLA-A2, however, is very low. To improve the immunogenicity of GP2, we tested 10 different amino acid substitutions into GP2 at the C- and N- terminus. Five out of 10 modified peptides, especially those containing phenylalanine at position 1 (1F), showed a significantly improved binding affinity to HLA-A2. 1F-based modified peptides were well recognized by GP2-specific CTL. These peptides were used to stimulate peripheral blood lymphocytes from HLA-A2 healthy donors using peptide-pulsed autologous dendritic cells (DC). After 3 or more weekly stimulations, CTL activity against GP2 pulsed T2 (T2-GP2) and HER2/neu-overexpressing tumor cells was measured in (51)Cr release and IFN-gamma secretion assays. The modified peptides significantly enhanced GP2-specific CTL activity in some donors. In particular, the peptide with phenylalanine at position 1, leucine at position 2 and valine at position 10 (1F2L10V) maximized the CTL activity against both T2-GP2 and HER2/neu-positive tumor cells. Peptide 1F2L10V increased not only the binding affinity to HLA-A2 but also improved recognition of GP2. These data suggest that DC + modified GP2 may improve immune therapies for the treatment of HER2/neu overexpressing tumors.

Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by the retinoid CD437 (AHPN).

Retinoic acid (RA) induces differentiation of S91 melanoma cells through activation of RA receptor (RAR)gamma without affecting cell viability. The novel RARgamma-agonist CD437 (AHPN), however, also induces concomitant apoptosis through an unknown mechanism which was investigated here. By utilizing DNA microarray analysis, five apoptosis-associated, CD437-induced transcripts (CITs) were identified. Interestingly, all CITs are also regulated by p53 in a DNA damage response, and consistent with this interpretation, CD437 was found to cause DNA adduct-formation. However, p53 is not required for CD437-dependent regulation of CITs. Among this set of genes, induction of p21(WAF1/CIP1) is likely to be responsible for early S-phase growth-arrest of CD437-treated cells, whereas ei24 is a critical mediator of CD437-induced apoptosis in S91 cells. These data suggest an RAR-independent mechanism in which CD437 causes DNA adduct-formation, resulting in induction of a p53-independent DNA damage response, and subsequent growth-arrest and apoptosis. CD437-mediated DNA adduct-formation may also explain its apoptotic effects in other cell types.

Loss of T-cell receptor-CD3zeta and T-cell function in tumor-infiltrating lymphocytes but not in tumor-associated lymphocytes in ovarian carcinoma.

BACKGROUND: Impaired T-cell function has been noted in tumor-infiltrating lymphocytes (TIL). Recently, loss of function was found to be associated with modifications in T-cell receptor complex (TCR)-mediated signaling. A common feature is loss or reduced expression levels of the signaling chain, TCRzeta. We evaluated whether loss of function in TIL and tumor-associated lymphocytes (TAL) from patients with ovarian cancer is associated with changes in TCRzeta expression, and which factors can cause these defects. METHODS: TIL and TAL were isolated from multiple patients and evaluated for their proliferative capacity by stimulation with a polyclonal stimulus. In addition, expression of TCRzeta and CD3epsilon was evaluated in fresh TIL and TAL by the Western blot technique. Finally, various conditions within a tumor environment were tested for their effect on TCRzeta and CD3epsilon. RESULTS: TIL, but not TAL, were significantly impaired in their proliferative response, even when both populations were derived from the same patient (P <.05). Reduced proliferation levels were associated with loss of expression of TCRzeta but not of CD3epsilon. Exposure of normal T cells to relative ischemia or heat shock, or culture in medium without IL-2, did not significantly reduce expression of TCRzeta compared with CD3epsilon. However, coculture of T cells with tumor-derived macrophages or tumor-derived factors led to a selective loss of TCRzeta compared with CD3epsilon (P <.05). Further analysis suggested that oxides such as hydrogen peroxide secreted by macrophages may be responsible for loss of TCRzeta and high molecular weight factors secreted by certain tumors. CONCLUSIONS: TIL but not TAL show impaired T-cell function, which is associated with loss of TCRzeta. In addition to macrophages secreting oxides, loss of TCRzeta may be caused by tumor-derived soluble factors.

Expression and function of galectin-3, a beta-galactoside-binding protein in activated T lymphocytes.

A soluble beta-galactoside-binding lectin, galectin-3 has been shown to be involved in cell adhesion and activation of immune cells. Although galectin-3 is known to be expressed in various types of cells, it has not been shown whether galectin-3 is expressed in T lymphocytes. We present evidence here that galectin-3 is expressed in activated murine T lymphocytes including CD4+ and CD8+ T cells but not in resting T cells. Galectin-3 expression was induced by anti-CD3 mAb or mitogen and enhanced by common gamma-chain signaling cytokines, IL-2, IL-4, and IL-7, in activated T lymphocytes, whereas the inflammatory cytokines including TNF-alpha and IFN-gamma did not. Galectin-3 expression and proliferation were down-regulated by withdrawal of IL-2 and gamma irradiation. Antisense but not sense phosphorothioated oligonucleotides for galectin-3 inhibited galectin-3 expression and blocked proliferation of T cells significantly. This study suggests that up-regulation of galectin-3 plays an important role in proliferation of activated T lymphocytes.

Soft-tissue sarcomas.

Sarcomas of the soft tissues are challenging lesions for the surgical oncologist. Careful planning must be done at all stages of diagnosis and treatment, because every sarcoma is unique with respect to histologic type, size, and location. Pretreatment discussions in a multidisciplinary format are useful to ensure appropriate and effective management of these tumors.

B7.1 costimulation increases T-cell proliferation and cytotoxicity via selective expansion of specific variable alpha and beta genes of the T-cell receptor.

BACKGROUND: Optimal T-cell activation requires not only ligation of the T-cell receptor (TcR) but also delivery of costimulatory signals by various accessory molecules. The interaction of the costimulatory molecule B7.1 (CD80) with its receptor CD28 provides a strong positive signal to T cells. METHODS: The B7.1 gene was transduced into cultured human ovarian, breast, and pancreatic tumor cells by using a retroviral vector. Autologous as well as allogeneic naive T-cells were stimulated with either wild-type or B7.1-transduced tumor cells in a mixed lymphocyte tumor cell culture (MLTC). In addition to cytolytic activity, T-cell proliferation, T-cell subset composition, and the frequencies of TcR variable (V) alpha and beta genes were compared in T cells from both types of MLTC. RESULTS: Introduction of the B7.1 gene into tumor cells was successful in all tumors to a varying degree. Those tumors expressing high levels of B7.1 induced significantly higher levels of T-cell proliferation than wild-type tumor cells. T-cell subset composition did not markedly differ between T cells stimulated with wild-type tumor cells or B7.1-expressing tumor cells. However, T cells stimulated with B7.1-expressing tumor cells showed a significantly increased cytolytic potential. The increased cytotoxic T lymphocyte activity was associated with a higher frequency of specific TcR V alpha and V beta genes. In addition, B7.1 costimulation promoted oligoclonality among the responding T cells. CONCLUSIONS: These data suggest that costimulation through B7.1 promotes T-cell proliferation and cytotoxic activity through clonal expansions of T cells bearing antigen-specific TcR V alpha and V beta genes and through promotion of oligoclonality. The data also suggest that promoting B7.1-mediated costimulation is an important aspect of immune therapies.

Experiences with hydrofibres in the moist treatment of chronic wounds, in particular of diabetic foot.

BACKGROUND: Chronic wounds are an everyday problem in general medicine. Likewise, their persistence, painfulness and frequency of relapse are everyday problems which strain the stamina of patients and doctors to the point of desperation. Over recent years, the moist therapy concept has proven to be a major advance in wound treatment. The introduction of innovative wound dressings in the 1990's made it possible to substantially accelerate wound healing and couple it with a simultaneous alleviation of pain. PATIENTS: In the scope of our team's experience one such product is the hydrofibre. This paper offers information on the possibilities for using this material on the basis of 135 wound situations, 44% of which are within the context of diabetes mellitus. RESULTS: There was a positive influence on wound healing in 92% of the cases. This treatment result is analysed in terms of causal, topographic and iconographic aspects. CONCLUSION: Given the main focal points of our group of patients, it may be stated that hydrofibres are suitable for diabetic wounds.

Pancreatic cancer associated ascites-derived CTL recognize a nine-amino-acid peptide GP2 derived from HER2/neu.

BACKGROUND: The proto-oncogene HER2/neu encodes a 185 kDa transmembrane protein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such as pancreatic cancer. Previously, we demonstrated that CTL derived from breast, ovarian, and non-small cell lung cancer recognized a peptide derived from HER2/neu. The aim of this study was to evaluate whether this HLA-A2-binding peptide is a TAA in pancreatic cancer and if pancreatic cancer associated T-lymphocytes (TAL) are useful to generate tumor- and peptide-specific CTL. MATERIALS AND METHODS: TAL from malignant ascites of a HLA-A2+ pancreatic cancer patient whose tumor overexpressed HER2/neu were stimulated on solid-phase anti-CD3 and cultured in low-dose IL-2. Using repetitive autologous tumor cell stimulation, CTL were generated. RESULTS: CTL recognized autologous and allogeneic HER2/neu+ tumor cells in an HLA-A2 restricted fashion significantly. Furthermore, all CTL recognized p654-662 (GP2) derived from HER2/neu, but not the control peptide. CONCLUSIONS: These results demonstrate that this HER2/neu derived peptide is a TAA in pancreatic carcinoma. The identification of the HER2/neu derived peptide GP2 as a TAA in pancreatic cancer provides an opportunity for the design of novel immunotherapy and vaccine strategies. The possibility of generating peptide-specific CTL from malignant ascites enables future studies to identify more antigens in this disease.