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Biomedical subjects

K G Harding

Publications and source records attributed to K G Harding.

At least 19 recordsLinked to original sources
PubMed2002

Science, medicine and the future: healing chronic wounds.

Greater interest in wound healing is needed to ensure higher standards of basic care. Precise identification of the systemic, local, and molecular factors underlying the wound healing problem in individual patients should allow better tailored treatment. Allogeneic skin grafting and bioengineered skin equivalents are being used successfully in patients with venous leg ulcers and diabetic patients with foot ulcers.

Administration, Topical↗
PubMed2001

Inflammatory-cell subpopulations in keloid scars.

The aim of this study was to investigate the contribution of lymphocytes and macrophages to keloid scarring by morphologically characterising inflammatory cell subpopulations in keloid scars in comparison with normal skin. We took 3mm punch biopsies from the anterior forearms of eight normal healthy volunteers. Eight keloid scars were excised using an intralesional technique. All tissue was snap frozen in liquid nitrogen and serial sections were stained with a panel of anti-inflammatory cell monoclonal antibodies. The numbers of macrophages and lymphocytes and the proportions of the subpopulations were compared. Higher numbers of both macrophages and lymphocytes were found in keloid dermis (P=0.01 and P=0.02, respectively (Mann-Whitney U -test)). There was no significant increase in the expression of the lymphocyte-activation markers, CD25 and CD27. However, there was a significantly higher CD4(+):CD8(+)(Th:Ts) ratio (P= 0.046) in keloid tissue. This suggests that an imbalance in these inflammatory cell subpopulations may contribute to keloid scarring in man.

Adolescent↗
PubMed2001

Managing gravitational eczema and allergic contact dermatitis.

Venous leg ulceration is a common chronic problem in the community, and gravitational eczema is a common complication of it. The presence of gravitational eczema can lead to further ulceration and may also impair wound healing. Treatment often requires more than one topical preparation, to gain control and prevent relapse. Knowledge of the benefits and risks of these therapeutic modalities is essential, in this article we aim to provide a practical approach to the treatment of gravitational eczema. We also discuss allergic contact dermatitis, a common complication of gravitational eczema.

Administration, Topical↗
PubMed2000

Alginates from wound dressings activate human macrophages to secrete tumour necrosis factor-alpha.

Alginates are used to manufacture a number of wound dressings. Clinical observations indicate that they may initiate or accelerate healing of chronic wounds after treatment of underlying pathology. Wound granulation tissue contains large numbers of macrophages and they are thought to regulate the healing process. As purified alginates have been demonstrated to activate macrophages this study was initiated to determine whether alginates present within wound dressings may interact with wound macrophages. Alginate fibres taken from four commercially available dressings were co-cultured with the human histiocytic lymphoma cell line U937 following its differentiation with PMA. Activation was assessed by measurement of TNFalpha production. Two of the dressings, Seasorb and Tegagen, had a minimal effect whilst Sorbsan at 1 mg/ml induced 302 + 19 pg/ml TNFalpha. This effect was inhibited by polymyxin B indicating that activation was due to endotoxin contamination. Kaltostat induced production of 839 + 36 pg/ml TNFalpha. This effect was induced both by polymyxin inhibitable endotoxin and a direct interaction with the alginate fibres. These data indicate that some alginate containing dressings have the potential to activate macrophages within the chronic wound bed and generate a pro-inflammatory signal which may initiate a resolving inflammation characteristic of healing wounds.

Alginates↗
PubMed2000

The role of lymphocytes in human dermal wound healing.

BACKGROUND: Animal experimental data indicate a requirement for functionally active T lymphocytes to allow optimal healing of dermal wounds. Little evidence exists to confirm that this is the case in humans. Lymphocyte involvement in regulation of healing is probably mediated by release of secreted cytokines/growth factors, and we hypothesize that the cytokine profile requirement will be modulated as healing progresses. OBJECTIVES: As this is likely to be reflected in lymphocyte subset changes over the course of normal healing, we investigated the immunophenotype of lymphocyte subpopulations during wound healing. METHODS: Sequential biopsies were taken over 42 days from the margin of 12 wounds healing by secondary intention after pilonidal sinus excision. Serial biopsy sections were analysed by immunohistochemistry using lymphocyte-specific monoclonal antibodies, and lymphocytes were counted microscopically. RESULTS: Within 42 days, the mean decrease in wound volume was 87.5%. This was accompanied by significant changes in the wound margin lymphocyte population. Total numbers (mean +/- SEM) of T lymphocytes decreased from 36.8 +/- 9.8 cells per field at inclusion in the study to 25.9 +/- 3.0 immediately prior to wound closure, with a concomitant increase in B lymphocytes from 1 +/- 0.4 to 9.5 +/- 3.6 cells per field. The CD4/CD8 T-lymphocyte ratio fell from an initial level of 3.6 +/- 0.3 to 2.1 +/- 0.3 (mean +/- SEM) prior to closure. CONCLUSIONS: These data indicate that human wound-associated lymphocyte populations are modulated during healing; the increase in numbers of CD8+ T-suppressor lymphocytes is in accordance with previous animal data, indicating a role for these cells in downregulating healing as the wound closes. This study also documents an associated increase in B lymphocytes and healing of human wounds, with an as yet undefined role.

Antibodies, Monoclonal↗
PubMed2000

Defective extracellular matrix reorganization by chronic wound fibroblasts is associated with alterations in TIMP-1, TIMP-2, and MMP-2 activity.

Chronic leg wounds are characterized by defective remodeling of the extracellular matrix, failure of reepithelialization, and prolonged inflammation. The hypothesis that this defective extracellular matrix remodeling is associated with phenotypic differences in the activity of the matrix metalloproteinases and tissue inhibitors of metalloproteinases was studied in chronic wound and patient-matched normal fibroblasts in three-dimensional collagen lattice systems. Chronic wound fibroblasts exhibited no differences in morphology or proliferation (p > 0.1) compared with patient-matched uninvolved dermal fibroblasts. The ability of chronic wound fibroblasts to reorganize extracellular matrix was significantly impaired, however, in comparison to the uninvolved dermal fibroblasts (p < 0.01). This difference in extracellular matrix reorganization was not related to differences in proliferation within the collagen lattices (p > 0.05) or attachment to type I collagen (p > 0.1). Marked differences were evident in matrix metalloproteinase-2 activity between chronic wound and patient-matched normal fibroblasts. Whereas levels of pro-matrix metalloproteinase-2 were similar between the two fibroblast populations (p > 0.1), the chronic wound fibroblasts exhibited significantly decreased levels of the 62 kDa active form of matrix metalloproteinase-2 (p < 0.01). Reverse zymography and enzyme-linked immunosorbent assay demonstrated that the decreased matrix metalloproteinase-2 activity was associated with increased production of tissue inhibitors of metalloproteinase-1 and -2 by the chronic wound fibroblasts (p < 0.05). Increased production of tissue inhibitors of metalloproteinases in chronic wound fibroblasts was also reflected in decreased levels of matrix metalloproteinase-1 (p < 0.005). These data suggest that the impaired ability of chronic wound fibroblasts to reorganize extracellular matrix in vitro is related to decreased levels of active matrix metalloproteinase-2 and matrix metalloproteinase-1 resulting from increased production of tissue inhibitors of metalloproteinase-1 and -2 by chronic wound fibroblasts. These findings provide a mechanism to explain the impaired cellular responses and extracellular matrix reorganization observed in chronic leg wounds in vivo.

Cell Adhesion↗
PubMed2000

Pathophysiology of chronic bacterial osteomyelitis. Why do antibiotics fail so often?

In this review the pathophysiology of chronic bacterial osteomyelitis is summarised, focusing on how bacteria succeed so often in overcoming both host defence mechanisms and antibiotic agents. Bacteria adhere to bone matrix and orthopaedic implants via receptors to fibronectin and to other structural proteins. They subsequently elude host defences and antibiotics by "hiding" intracellularly, by developing a slimy coat, or by acquiring a very slow metabolic rate. The presence of an orthopaedic implant also causes a local polymorphonuclear cell defect, with decreased ability to kill phagocytosed bacteria. Osteolysis is determined locally by the interaction of bacterial surface components with immune system cells and subsequent cytokine production. The increasing development of antibiotic resistance by Staphylococcus aureus and S epidermidis will probably make conservative treatment even less successful than it is now. A close interaction between orthopaedic surgeons and physicians, with combined medical and operative treatment, is to be commended.

Biopsy, Needle↗
PubMed2000

Causes and effects of the chronic inflammation in venous leg ulcers.

The pathogenesis of venous leg ulcers is multifactorial. In this review article new physiological, molecular and cellular abnormalities in venous ulcers related to the chronic inflammation are presented and discussed. Venous hypertension causes disturbed microcirculation and pathological changes of the capillaries, which eventually locks the condition in a self-amplifying, detrimental cascade with persistent elevated levels and activities of pro-inflammatory cytokines and proteases preventing progress into a healing phase. As a consequence fibroblasts senescence and become less responsive to growth factors the older the ulcers become. Current data imply there is no deficiency but rather an unfavorable distribution of growth factors in venous ulcers. An imbalance in proteolytic enzymes and their endogenous inhibitors is a common finding in chronic venous leg ulcers. Variation in disease severity and concomitant ailments in this heterogeneous patient group may explain the contradictory results in the literature. Thus, to advance the areas of research further, longitudinal studies involving larger number of patients are required to identify the major pathogenic factors.

Chronic Disease↗
PubMed1999

Antibacterial activity of honey against strains of Staphylococcus aureus from infected wounds.

The antibacterial action of honey in infected wounds does not depend wholly on its high osmolarity. We tested the sensitivity of 58 strains of coagulase-positive Staphylococcus aureus, isolated from infected wounds, to a pasture honey and a manuka honey. There was little variation between the isolates in their sensitivity to honey: minimum inhibitory concentrations were all between 2 and 3% (v/v) for the manuka honey and between 3 and 4% for the pasture honey. Thus, these honeys would prevent growth of S. aureus if diluted by body fluids a further seven-fold to fourteen-fold beyond the point where their osmolarity ceased to be completely inhibitory. The antibacterial action of the pasture honey relied on release of hydrogen peroxide, which in vivo might be reduced by catalase activity in tissues or blood. The action of manuka honey stems partly from a phytochemical component, so this type of honey might be more effective in vivo. Comparative clinical trials with standardized honeys are needed.

Honey↗
PubMed1999

Clinical evaluation of a new pressure-relieving mattress.

In introducing a new mattress into practice it is important to evaluate its performance from both the patient's and nurse's perspective. A total of 20 patients admitted to the integrated medical unit were recruited and nursed on a new pressure-relieving mattress offering two modes of pressure relief (Duo). All patients had been recently admitted to hospital and were considered to be 'at very high risk' of developing a pressure ulcer, with an initial Waterlow score > 20. Data were collected on admission, mid-point (three to four days) and study exit (seven days). The primary objective was to investigate the condition of patients' skin and the mode of choice for pressure relief. The secondary objective was to investigate reasons for nurses' and patients' choices. Structured interviews were conducted with the patient, ward nurse and research nurse whenever possible. Nineteen patients maintained or improved their skin condition during the evaluation.

Aged↗
PubMed1999

The structure and composition of chronic wound eschar.

Wounds with a covering of eschar require debridement before optimal wound healing can proceed. There are several different methods available but these have been derived empirically with no direct evidence of the structure or composition of the tissue they are designed to remove, or of the potential autolytic mechanisms which are the targets for some of these treatments. The aim of this study therefore was to determine the composition of chronic wound eschar and hence identify potential targets for the induction of autolytic debridement. Chronic wound eschar was removed by surgical debridement and analysed using immunohistochemistry, polyacrylamide gel electrophoresis (PAGE) and gelatin zymography. Immunohistochemistry using antibodies specific for extracellular matrix (ECM) proteins revealed a definite tissue structure, consisting of many fibrous regions and fine fibrillar elements separated by areas of tissue which were of a more irregular and amorphous nature. An antibody specific for all leucocytes revealed the presence of leucocytes in the region of tissue closest to the wound bed. The presence of this leucocyte population correlated to elevated levels of gelatinase activity as identified by gelatin zymography. PAGE analysis identified various protein species in the range 3.5-60 kDa molecular weight. These data indicate that wound debridement is likely to require multiple enzyme specificities to degrade the eschar and that these enzymes may be supplied by inflammatory leucocytes infiltrating the eschar from the wound bed. The various protein species demonstrated by PAGE may represent ECM proteins, those with lower molecular weight possibly representing the degradation products of autolytic debridement.

Chronic Disease↗