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Biomedical subjects

Keith G Harding

Publications and source records attributed to Keith G Harding.

36 records · Page 2Linked to original sources
PubMed2004

Wound problems due to zinc deficiency.

Zinc deficiency, though uncommon, can occasionally present in current medical practice. A 4.5-year-old boy with previous gastrointestinal surgery presented with diarrhoea, disinterest and dermatitis affecting the face and perineum. The clinical diagnosis was confirmed by the presence of a low serum zinc level. Administration of parenteral zinc led to rapid improvement in diarrhoea, demeanor and dermatitis. Further surgery was then undertaken, surgery had been postponed until normalisation of zinc levels due the association between zinc deficiency and poor postoperative wound healing.

Child, Preschool↗
PubMed2004

Early diagnosis is vital in the management of squamous cell carcinomas associated with chronic non healing ulcers: a case series and review of the literature.

The association between chronic ulcers and squamous cell carcinomas (SCCs) is well established. Their clinical presentations, however, are varied, ranging from innocously appearing lesions to overtly exophytic growths. We present a series of cases with heterogeneous clinical presentations and different treatment outcomes. Case series - patient 1 was a 69-year-old man with an 18-month history of static non healing venous leg ulcer, but no sinister features, biopsy was performed to rule out Marjolin's transformation, histology revealed SCC and treatment was simple excision and skin grafting; patient 2 was a 73-year-old lady with an 18-month history of non healing ulcer (innocuous appearance) over distal interphalangeal joint of index finger, histology revealed SCC with deeper extension and treatment was amputation of distal half of finger; patient 3 was a 73-year-old lady with a 12-month history of non healing fungating leg ulcer with irregular borders and everted edges, histology revealed SCC (tumour eroding tibia and distant metastasis) and treatment was above-knee amputation, radiotherapy and palliation. Whilst SCC is amenable to simple excision in the early stages, delay in diagnosis could result in loss of the affected digit or limb; an SCC which has metastasised is also life threatening. Therefore, a low threshold to biopsy static non healing ulcers or ulcers in unusual sites should be adopted even in those not manifesting any evidence of malignancy.

Aged↗
PubMed2004

Use of 16S ribosomal DNA PCR and denaturing gradient gel electrophoresis for analysis of the microfloras of healing and nonhealing chronic venous leg ulcers.

The bacterial microfloras of 8 healing and 10 nonhealing chronic venous leg ulcers were compared by using a combination of cultural analysis and denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA gene products. Cultural analysis of the microflora revealed that the majority of both wound types carried the aerobes Staphylococcus and Pseudomonas spp. (89 and 80%, respectively). Sequencing of 16S ribosomal DNAs selected on the basis of DGGE profiling allowed the identification of strains not detected by cultural means. Of considerable interest was the finding that more than 40% of the sequences represented organisms not cultured from the wound from which they were amplified. DGGE profiles also revealed that all of the wounds possessed one apparently common band, identified by sequencing as Pseudomonas sp. The intensity of this PCR signal suggested that the bacterial load of nonhealing wounds was much higher for pseudomonads compared to healing wounds and that it may have been significantly underestimated by cultural analysis. Hence, the present study shows that DGGE could give valuable additional information about chronic wound microflora that is not apparent from cultural analysis alone.

Base Sequence↗
PubMed2004

Analysis of skin wound images using digital color image processing: a preliminary communication.

This article presents the use of digital image processing using hue, saturation, and intensity measurements as a technique for the color analysis of chronic wounds on the skin. An adaptive spline technique was used to segment the wound boundary in the images of venous leg ulcers. This technique was further used to approximate the position of venous leg ulcers. The amount of slough within the wound site was quantified using the software developed and was compared with a grading system based on visual inspection by an experienced clinician, and the results were compared by deriving Kappa (K) statistic. There was moderate agreement over all grades between the computer and clinician. At lower grades 1 and 2, there was excellent agreement. The results from this preliminary study suggest that this analytical technique has the potential to image process chronic skin wounds.

Journal Article↗
PubMed2003

Diabetic foot ulcers.

Ulceration of the foot in diabetes is common and disabling and frequently leads to amputation of the leg. Mortality is high and healed ulcers often recur. The pathogenesis of foot ulceration is complex, clinical presentation variable, and management requires early expert assessment. Interventions should be directed at infection, peripheral ischaemia, and abnormal pressure loading caused by peripheral neuropathy and limited joint mobility. Despite treatment, ulcers readily become chronic wounds. Diabetic foot ulcers have been neglected in health-care research and planning, and clinical practice is based more on opinion than scientific fact. Furthermore, the pathological processes are poorly understood and poorly taught and communication between the many specialties involved is disjointed and insensitive to the needs of patients.

Diabetic Foot↗
PubMed2003

An analysis of replicative senescence in dermal fibroblasts derived from chronic leg wounds predicts that telomerase therapy would fail to reverse their disease-specific cellular and proteolytic phenotype.

The accumulation of senescent fibroblasts within tissues has been suggested to play an important role in mediating impaired dermal wound healing, which is a major clinical problem in the aged population. The concept that replicative senescence in wound fibroblasts results in reduced proliferation and the failure of refractory wounds to respond to treatment has therefore been proposed. However, in the chronic wounds of aged patients the precise relationship between the observed alteration in cellular responses with aging and replicative senescence remains to be determined. Using assays to assess cellular proliferation, senescence-associated staining beta-galactosidase, telomere length, and extracellular matrix reorganizational ability, chronic wound fibroblasts demonstrated no evidence of senescence. Furthermore, analysis of in vitro senesced fibroblasts demonstrated cellular responses that were distinct and, in many cases, diametrically opposed from those exhibited by chronic wound fibroblasts. Forced expression of telomerase within senescent fibroblasts reversed the senescent cellular phenotype, inhibiting extracellular matrix reorganizational ability, attachment, and matrix metalloproteinase production and thus produced cells with impaired key wound healing properties. It would appear therefore that the distinct phenotype of chronic wound fibroblasts is not simply due to the aging process, mediated through replicative senescence, but instead reflects disease-specific cellular alterations of the fibroblasts themselves.

Cell Adhesion↗
PubMed2003

New treatments for diabetic neuropathic foot ulceration: views from a wound healing unit.

The management of diabetic foot ulceration remains problematic despite advances in treatments. The evidence for many treatments is lacking and clinical experience remains important. Current diabetic foot ulcer management and an evaluation of new therapies are discussed. Research in wound healing and diabetic foot disease can complement each other in accurately evaluating and treating diabetic foot ulceration. This would aid in formulating personalized therapies, tailoring treatments to optimize the ulcer healing environment.

Bandages↗
PubMed2003

Managing patients unable to tolerate therapeutic compression.

Managing patients with venous ulceration who are unable to tolerate therapeutic compression bandaging is a challenging clinical problem. This study followed a group of 28 such patients who were treated with three layers of graduated Tubigrip as an alternative to therapeutic compression. It also investigated factors that influenced nurses in deciding to use this bandaging system. Patients were followed until their ulcers healed or for a maximum of 12 weeks. The decision to use three layers of graduated Tubigrip was based on 19 patients' desire to wear their normal shoes (67.9%) and the convenience of access to the ulcer by eight patients (28.6%) (to permit frequent dressing changes for large or infected ulcers, and for the daily application of steroidal creams to periulcer skin). Fourteen patients' ulcers had healed within the 12-week study period. The remaining 14 patients had a mean reduction in ulcer area of 4.6 cm(2) (SD = 7.4), and median of 2.3 cm(2) (range 28.5). The authors found three layers of graduated Tubigrip useful for managing patients who cannot tolerate therapeutic forms of compression.

Aged↗
PubMed2002

Differential expression of matrix metalloproteinases during impaired wound healing of the diabetes mouse.

A number of studies have shown elevated matrix metalloproteinase expression in chronic wound fluid compared to an acute wound; however, little has been done to characterize animal models in a similar manner and thus determine their usefulness. The diabetes mouse is an animal model of type II diabetes that shows impaired dermal wound healing and has been proposed as a model of human impaired wound healing. In this study we have determined the mRNA and protein expression profiles of matrix metalloproteinases 2, 3, and 9 during the first 10 d of dermal healing for the diabetes mouse and its normally healing littermate. Additionally, human wound fluid from diabetic chronic wounds and acute surgical wounds were studied to enable a comparison of the model to the human condition. We show that during the early stages of wound healing the diabetes mouse possesses significantly reduced protein levels of pro-matrix metalloproteinases 2 and 9 within the wound tissue and active matrix metalloproteinase 3 within the fluid. Pro-matrix metalloproteinase 3 levels are also significantly reduced in the diabetes mouse during the later stages of healing. These differences may be contributing to the impaired healing of the diabetes mouse; however, they differ from the human data presented here, which show elevated matrix metalloproteinase 2 and reduced matrix metalloproteinase 9 in human diabetic chronic wound fluid compared to acute wound fluid. Therefore, although clearly showing the importance of appropriate matrix metalloproteinase regulation for normal acute wound healing to occur, the diabetes mouse may not be an ideal model for study of matrix metalloproteinase involvement in human chronic wound healing.

Animals↗
PubMedDate not supplied

Wound healing and treatments for people with diabetic foot ulcers.

The factors that delay wound healing are multiple and relate both to diabetes and to the effect of its complications. Diabetic foot ulcers readily become chronic, and chronic ulcers have biological properties that differ substantially from acute ones. Much of the available information on the biology of wound healing relates to acute and experimental wounds and may not be directly relevant. It follows that there is limited evidence currently available to underpin protocols for the management of diabetic foot ulcers, or to guide choice of applications and dressings 1. Nevertheless, it is possible to define certain principles.GLYCAEMIC CONTROL: The first relates to glycaemic control. While chronic complications of diabetes such as peripheral vascular disease and neuropathy may be largely irreversible, aspects of structure and function of connective tissue and cells may be impaired by hyperglycaemia, and their function should be improved if normoglycaemia is achieved. PROMOTION OF HEALING: The second principle concerns attempts at active promotion of wound healing by (1) surgical revascularization, and (2) specific attempts to correct defined biological abnormalities thought to be hindering the healing process. These include the use of a variety of applications, dressings and technologies, which may stimulate healing by applying, or stimulating the release of, growth factors and cytokines. While this approach holds the greatest promise for the future, it will be dependent on defining defects which need correction in specific individuals, and having technologies available to address them. This field is in its infancy. WOUND CARE: The third broad principle concerns the management of the wound and its surrounding tissue in order to promote healing. This includes regular inspection, cleansing and removal of surface debris, elimination of pathogenic bacteria and creation of an appropriate environment to facilitate endogenous tissue regeneration. There are many applications and dressings that may be chosen to promote healing, but, whichever is selected, wound management has to be integrated into an effective programme of multidisciplinary care.

Debridement↗
PubMedDate not supplied

Potential role of anaerobic cocci in impaired human wound healing.

Although more than 80% of infected and 70% of noninfected leg ulcers have been shown to harbor anaerobic organisms, their role in mediating impaired wound healing in the skin is frequently overlooked. There is now increasing evidence that the gram-positive anaerobic cocci play a role (both directly and indirectly) in mediating impaired wound healing in vivo. This article discusses the mechanisms by which these microorganisms may interfere with the inflammation, repair, and remodeling phases of the wound healing process.

Bacteria, Anaerobic↗
PubMedDate not supplied

Comparison of oxidative stress biomarker profiles between acute and chronic wound environments.

Increasing evidence implicates excessive reactive oxygen species (ROS) generation and ROS-derived degradation products in the pathogenesis of many skin diseases. While numerous attempts have been made to identify prognostic biomarkers of wound healing in skin, these have met with limited success. This study examined the profiles of various oxidative stress biomarkers, namely total protein carbonyl content (from protein oxidation), malondialdehyde content (from lipid peroxidation), and the total antioxidant capacities, in acute wound fluid (n= 10) and chronic wound fluid (n= 12), using a rapid, noninvasive collection technique. Protein carbonyl content was quantified spectrophotometrically and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blotting, following 2,4-dinitrophenylhydrazine derivitization. Malondialdehyde levels were similarly quantified, following N-methyl-2-phenylindole derivitization. Total antioxidant capacity was determined via wound fluid inhibition of cytochrome C reduction by a superoxide radical flux. Acute wound fluid contained higher protein carbonyl content than chronic wound fluid, particularly evident following sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis under nonreducing and reducing conditions (p < 0.001 and p < 0.02, respectively), related to significantly higher protein levels (p = 0.0005) in acute wound fluid. Human serum albumin ( approximately 66 kDa) was identified as the most prominent protein oxidized in both acute and chronic wound fluid, which may contribute to the reduced albumin and total protein levels in chronic wound fluid. No significant difference (p > 0.1) in malondialdehyde levels or total antioxidant capacities were determined between acute and chronic wound fluids, although chronic wound fluid exhibited significantly higher total antioxidant capacities (p < 0.005), accounting for variations in wound fluid protein content. These findings suggest an adaptation in the antioxidant profiles of chronic wound fluid to counteract the loss of consumed antioxidants in the chronic wound environment. This study highlights the roles of ROS/antioxidants in skin wound healing, their possible involvement in chronic wounds and the potential value of ROS-induced biomarkers in wound healing prognosis.

Adult↗
PubMedDate not supplied

Effect of sharp debridement using curette on recalcitrant nonhealing venous leg ulcers: a concurrently controlled, prospective cohort study.

The objective of this study was to evaluate the effect of sharp debridement on the progression of recalcitrant chronic venous leg ulcers (CVLU) and to assess the feasibility of performing this procedure in an outpatient setting. We performed a prospective study of 55 CVLU (53 patients) over a 12-month period. The study group, which underwent debridement, contained 28 CVLU whose wound beds had slough, nonviable tissue, and no granulation tissue. The control group was 27 CVLU with minimal (15-20%) granulation tissue, but no slough or nonviable tissue. Treatments were otherwise similar. Age, body mass index, mean ulcer surface area (MSA) and mean ulcer duration were comparable in both groups. Ulcer measurements were taken at 4 weeks before debridement, at the time of debridement, and 4 and 20 weeks post-debridement. There was no change in the MSA from 4 weeks before to the time of debridement in either group. At 4 weeks post-debridement, the study ulcers showed a 6 cm(2) reduction in the MSA vs. a 1 cm(2) reduction in controls (P = 0.02). By week 20 post-debridement, the study ulcers achieved a 7.4 cm(2) reduction in the MSA vs. an increase of 1.3 cm(2) in controls (P = 0.008). Between weeks 8 and 20 post-debridement, 16% of study ulcers vs. 4.3% of control ulcers achieved complete healing. Infection rates and antimicrobial usage were similar. We conclude that sharp debridement is effective in stimulating healing of recalcitrant CVLU. It is safe, well tolerated, and can be performed in an outpatient setting.

Aged↗
PubMedDate not supplied

Efficacy and safety of the freeze-dried cultured human keratinocyte lysate, LyphoDerm 0.9%, in the treatment of hard-to-heal venous leg ulcers.

LyphoDerm (XCELLentis, Belgium) is an end-sterilized, freeze-dried lysate from cultured allogeneic epidermal keratinocytes, formulated into a hydrophilic gel. Its efficacy and safety were evaluated, in combination with standard care (hydrocolloid dressing and compression therapy), in 194 patients suffering from hard-to-heal (lasting more than 6 weeks and not responding to conventional therapy) venous leg ulcers. Two control groups received standard care, with or without vehicle, respectively. Patients had a median age of 67.5 years and the majority were females (61%). The median duration of the ulcer was 43 weeks and in 39% of the subjects it had been present for more than 1 year. Thirty-eight percent of the patients in the standard care + LyphoDerm group had complete ulcer healing within 24 weeks (primary end point) compared to 27% of patients in the standard care + vehicle pooled groups (P = 0.114) in the "as treated" intent-to-treat cohort (37% vs. 27% in the "as randomized intent-to-treat cohort; p = 0.137). In the subgroup of patients with enlarging ulcers, the difference between the two groups was significant (30% vs. 11%; p = 0.024 in the "as treated" intent-to-treat cohort and 31% vs. 9%; p = 0.005 in the "as randomized" intent-to-treat cohort). LyphoDerm was well tolerated and safe, and no differences in the frequency of adverse events were noted between the treatment groups. Although the primary objective of the study was not achieved, the exploratory analysis carried out in patients with enlarging ulcers suggests that LyphoDerm could offer a new prospect for the treatment of patients with venous ulcers that may prove to be a significant adjunct to the overall provision of care.

Adult↗
PubMedDate not supplied

Plantar pressure in off-loading devices used in diabetic ulcer treatment.

Four off-loading devices used for the treatment of diabetic forefoot ulcers were compared: a custom-molded insole shoe, a cast MABAL shoe, a prefabricated pneumatic walking brace, and a bivalved total contact cast (BTCC). It was anticipated that all devices would significantly reduce forefoot plantar pressure compared with a control shoe. Sixteen healthy volunteers participated. Plantar pressures were evaluated using the Pedar system, while walking speed was determined using an optoelectric timer. Peak pressure (PP) of ten plantar areas and pressure-time integral for the first metatarsal area were analyzed statistically using a repeated measures analysis of variance. Forefoot pressures were significantly reduced compared with the control shoe for all devices (p<0.001). PP was most reduced (by 65.8%) for the BTCC, and pressure-time integral was most reduced for the BTCC and cast MABAL shoe. Small but significant differences between devices in walking speed (p<0.05) could not explain the substantial PP differences between the different devices. Although all off-loading devices resulted in a significant reduction of forefoot plantar pressure, devices differed significantly in the magnitude of pressure reduction. Further research will have to reveal the level of off-loading sufficient for effective treatment of diabetic ulcers.

Adult↗
PubMedDate not supplied

The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing.

Wound healing involves a number of cellular and molecular events, many of which are controlled by soluble growth factors. In the process of healing, hepatocyte growth factor, a cytokine known to act as mitogen, motogen, and morphogen, has been postulated to play multiple roles during several stages of this complex biological process. Produced primarily by stromal fibroblasts, hepatocyte growth factor regulates angiogenesis, vascular permeability, cell migration, matrix deposition and degradation, and other biological processes. The current article discusses recent progress in understanding the multiple roles played by this growth factor in tissue repair.

Hepatocyte Growth Factor↗