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Biomedical subjects

Keith G Harding

Publications and source records attributed to Keith G Harding.

At least 19 recordsLinked to original sources
PubMed2006

The influence of diabetes and lower limb arterial disease on cutaneous foot perfusion.

OBJECTIVE: Peripheral arterial occlusive disease and peripheral neuropathy are major risk factors in diabetic foot disease. We evaluated the relative influences of noncritical lower limb arterial disease and peripheral neuropathy on cutaneous foot perfusion in diabetes. METHOD: Toe-brachial pressure indices, transcutaneous oxygen, and carbon dioxide tensions at foot and chest sites were measured in individuals with diabetes, with or without detectable peripheral neuropathy and with or without significant arterial disease on color duplex imaging. Subjects without diabetes, with and without arterial disease, were used as controls. RESULTS: A total of 130 limbs were studied during an 8-month period. Toe-brachial pressure indices reflected the presence of arterial disease in all groups. Foot transcutaneous oxygen values were reduced in diabetes and correlated with chest transcutaneous oxygen values. Low foot transcutaneous oxygen with elevated transcutaneous carbon dioxide values were only demonstrated in individuals with diabetes, arterial disease, and peripheral neuropathy. Toe-brachial pressure indices demonstrated a positive correlation with foot transcutaneous oxygen values, but values >1.2 demonstrated a negative correlation. CONCLUSIONS: We demonstrated two influences on cutaneous foot perfusion in diabetes: (1) a global microcirculatory dysfunction, reflected in low chest and foot transcutaneous oxygen values, and (2) macrovascular disease as indicated by reduced toe-brachial pressure indices and foot transcutaneous oxygen values. Further, the results demonstrated that in diabetic individuals without critical limb ischemia, impaired foot perfusion secondary to arterial disease is amplified significantly by coexisting microcirculatory disease.

Aged↗
PubMed2006

Wound dressings.

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Alginates↗
PubMed2006

Pressure ulcers.

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Bandages↗
PubMed2006

Wound assessment.

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Bacterial Infections↗
PubMed2006

Numerous keratinocyte subtypes involved in wound re-epithelialization.

The expression of different keratin intermediate filaments has been used to define keratinocyte maturation and different phenotypic subtypes involved in acute wound (AW) healing. Immunohistochemistry with specific anti-keratin monoclonal and polyclonal antibodies was used to examine AW in normal healthy volunteers (n = 16). In all wounds examined, basal keratinocytes and cells at the leading edge of the wound expressed keratins K5 and K14. However, suprabasal cells had a more complex pattern of keratin expression, which was dependent on their position relative to the wound and location within the suprabasal compartment of the epidermis. In general, K10 was expressed in suprabasal keratinocytes at the wound edge, but not in keratinocytes covering the wound center, which expressed K6, K16, and K17 in a complex fashion. Ki67 expression, a marker of cell proliferation, was restricted to basal and immediate suprabasal layers at the wound edge. Keratinocytes populated the wound bed below the scab by migration, which was supported by keratinocyte proliferation in the surrounding epidermis both at and adjacent to the wound edge.

Cell Differentiation↗
PubMed2006

Prediction and monitoring the therapeutic response of chronic dermal wounds.

A significant proportion of chronic wounds fail to heal in response to treatment of underlying pathologies combined with good wound care practice. Current prognostic tests to identify these wounds rely on the use of algorithms based on clinically measurable parameters such as wound dimensions and wound duration. Venous leg ulcers may be stratified into healing/non healing at 24 weeks of compression therapy and diabetic foot ulcer treatment outcome assessed using a 3-parameter algorithm. Accurate and reproducible measurement of wound area is required for these algorithms to have clinical utility. Whilst a number of attempts have been made to develop computerised wound-assessment techniques, wound tracing by clinicians combined with planimetry remains the standard methodology. Once treatment has been initiated, it is important to continuously monitor the wound to assess efficacy of treatment. This can be achieved by measuring wound area change over the first weeks of treatment to identify whether re-assessment of treatment strategy is required. A number of algorithms for assessing rate of wound area change have been evaluated to determine a surrogate endpoint for healing. Retrospective analysis of large patient groups indicates that approximately 75% correct prediction of healing outcome can be achieved.

Bandages↗
PubMed2006

Surgical treatment of hidradenitis suppurativa: case series and review of the literature.

The chronic and relapsing nature of hidradenitis suppurativa leads to physical and psychological damage. The absence of a proven cure further worsens the scenario. Patient 1 was a 28-year-old woman with a 10-year history of abscesses and non healing sinuses with foul-smelling discharge from her axilla, submammary and groin areas. This led to an episode of self-harm due to severe depression. After failed medical therapy, she was referred for surgery with wide excision of the skin and healing by secondary intention. Her wounds were managed by our specialist wound clinic with the use of topical and systemic antibiotics and thus remained free from symptoms. Patient 2 was a 32-year-old woman with a similar history for 15 years. Patient 3 was a 41-year-old man with a 20-year history of discharging sinuses and abscesses. All the patients had endured a long period of medical treatment and subsequently required surgery for a long-term relief of symptoms. This has undoubtedly led to psychological symptoms and a decrease in quality of life.

Adult↗
PubMed2005

Dystrophic calcification as a cause for non healing leg ulcers.

Despite advances in molecular biology and a repertoire of other therapeutic options, chronic venous leg ulcers remain a significant problem within our society. There are various reasons, both local and systemic, which contribute to the non healing nature of such wounds. Among them, dystrophic calcification (DC) or calcified deposits within the ulcer bed, although rare, is an overlooked and a seldom reported cause. In the presence of DC, wound healing cannot proceed through a timely and orderly manner resulting in a non healing ulcer. In this article, we discuss the aetiology, pathophysiology and the management options of this rarely reported condition. We also report their clinical prognosis using a series of patients with venous ulcers complicated by DC leading to difficulties in healing.

Aged↗
PubMed2005

Issues for debate.

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Evidence-Based Medicine↗
PubMed2005

Wound chronicity and fibroblast senescence--implications for treatment.

A proportion of chronic wounds fail to heal in response to standard therapy. For venous leg ulcers, a correlation exists between longer duration before treatment initiation and poor healing response to compression therapy. Differences identified between the healing wound microenvironment and that of the non healing chronic wound suggests that many potential mechanisms exist to impair healing. One contributory mechanism may be inhibition of fibroblast proliferation and induction of a stress-induced premature senescence phenotype by the continuing inflammation found in chronic wounds. Senescent fibroblasts exhibit an extracellular matrix degradative phenotype that contributes to wound chronicity. Accumulation of greater than 15% senescent fibroblasts has been described as a threshold beyond which wounds become hard to heal. The ratio of senescent : non senescent cells is therefore critical to determining response to treatment, and adjunctive therapies that modulate this ratio in favour of non senescent cells are likely to enhance therapeutic healing rates. A number of tissue-engineered dermal replacements contain non senescent fibroblasts and can donate cells to the wound environment additional to releasing growth factors and reversing the antiproliferative activity of chronic wound exudate. Recognition of the role of fibroblast senescence in wound chronicity may allow for identification of those wounds that will respond positively to these products.

Cellular Senescence↗
PubMed2005

An evaluation of the efficacy of methods used in screening for lower-limb arterial disease in diabetes.

OBJECTIVE: Foot-related disease is the most common cause for hospital admission among the diabetic population. Lower-limb peripheral arterial occlusive disease (PAOD) is a major risk factor in diabetic foot disease. Screening for PAOD commonly includes foot pulses and the ankle-brachial pressure index (ABPI) and/or the toe-brachial pressure index (TBI), but concerns persist regarding their accuracy. We evaluated the efficacy of several commonly used screening methods in different subject populations. RESEARCH DESIGN AND METHODS: We studied 130 limbs in 68 individuals with no critical ischemia over 8 months. Limbs were grouped on the basis of the presence or absence of diabetes, clinically detectable peripheral neuropathy, and PAOD identified on color duplex imaging. Comparative analyses of foot pulses, the ABPI, the TBI, and distal Doppler waveform analysis were performed. RESULTS: Foot pulses, the TBI, and qualitative waveform analyses were highly sensitive screening methods in individuals with and without diabetes. However, detectable peripheral neuropathy was associated with a reduced sensitivity and poor specificity of foot pulses, a reduction in sensitivity of the ABPI (71 to 38%), and a reduction in specificity of the TBI (81 to 61%) and qualitative waveform analysis (96 to 66%). Quantitative analysis failed to detect disease with severely damped and low-intensity signals. CONCLUSIONS: Screening tools that are effective in screening for lower-limb PAOD in the nondiabetic population are less efficacious in diabetes, particularly in the presence of detectable peripheral neuropathy. Qualitative waveform analysis and the TBI were demonstrated to be more effective screening methods than the ABPI and foot pulses particularly in high-risk limbs with detectable peripheral neuropathy.

Arterial Occlusive Diseases↗
PubMed2004

Bacteria and wound healing.

PURPOSE OF REVIEW: Wound healing is a complex process with many potential factors that can delay healing. There is increasing interest in the effects of bacteria on the processes of wound healing. All chronic wounds are colonized by bacteria, with low levels of bacteria being beneficial to the wound healing process. Wound infection is detrimental to wound healing, but the diagnosis and management of wound infection is controversial, and varies between clinicians. RECENT FINDINGS: There is increasing recognition of the concept of critical colonization or local infection, when wound healing may be delayed in the absence of the typical clinical features of infection. The progression from wound colonization to infection depends not only on the bacterial count or the species present, but also on the host immune response, the number of different species present, the virulence of the organisms and synergistic interactions between the different species. There is increasing evidence that bacteria within chronic wounds live within biofilm communities, in which the bacteria are protected from host defences and develop resistance to antibiotic treatment. SUMMARY: An appreciation of the factors affecting the progression from colonization to infection can help clinicians with the interpretation of clinical findings and microbiological investigations in patients with chronic wounds. An understanding of the physiology and interactions within multi-species biofilms may aid the development of more effective methods of treating infected and poorly healing wounds. The emergence of consensus guidelines has helped to optimize clinical management.

Bacteria↗