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Herbal treatment for unhealing diabetic foot ulcers
Abstract
As the incidence of diabetes mellitus is increasing rapidly globally, complications related to this endocrine disorder are also mounting. Because of the large number of patients, foot ulcers developing in the feet of diabetics have become a public health problem. The predisposing factors include abnormal plantar pressure points, foot deformities, and predisposing trauma. Vulnerable feet usually suffer from vascular insufficiency and peripheral neuropathy. The complex nature of these ulcers deserves special care. The most useful prognostic feature for healing remains the ulcer depth. Ulcers heal poorly if they involve underlying tendons, ligaments or joints; and particularly, when gangrenous tissue is seen. Local treatment of the ulcer consists of repeated debridement and dressing. No 'miraculous' outcome is expected, even with innovative agents like synthetic skin covers, growth factors and stem cells. Simple surgery like split skin grafting or minor toe amputations may be necessary. Sophisticated surgery like flap coverages are indicated only for younger patients. The merits of an intact lower limb with an intact but abnormal foot have to be weighed against amputation and prosthesis in the overall planning of limb salvage or sacrifice. If limb salvage is the decision, additional means like oxygen therapy, and other alternative medicines, might be beneficial. Footwear should always be a major consideration as a means of prevention of ulcer formation.Surgeons used to assume that once a chronic foot ulcer fails to heal, amputation could be the best option to offer since the modern technology for prosthesis fitting is advance and convenient for the patients. In actual fact, diabetic patients with chronic unhealing ulcers are usually elderly people who are not only frail, but are expected to experience great difficulties adapting to the living status of an amputee.Therefore, if the chronic ulcer could be induced to heal and the affected limb salvaged, it is still the best option for the patient.Herbal medicine has been commonly used in both India and China, for the healing of chronic ulcers. Clinicians in Modern China have used the herbal preparation to promote wound healing. In our institute in Hong Kong, research on herbal treatment for chronic ulcers started in 1999, in the laboratory as well as in the hospital for patients. Results of the studies have been very encouraging. The good early results have led to a modification of the herbal formula, more laboratory studies and another clinical trial, using patients with less severe chronic ulcers.
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Diabetic patients with foot ulceration have a poorer prognosis than those without ulceration. The reason for this is unclear, but there is considerable interest in the putative links between infection and atherogenesis, and it is notable that diabetic foot ulcers (DFU) are often infected with Staphylococcus aureus and the main cause of death in DFU patients is ischaemic heart disease. We examined the 5 year survival of 71 diabetic patients who presented with foot ulcers that were newly infected (Sa group, n = 56) or not infected at all during the study period (non-Sa group, n = 15) with S. aureus. Twenty-nine patients (52%) infected with S. aureus died compared with three patients (20%) whose foot ulcers were not infected with S. aureus. The patients in the two groups were similar in age and duration of diabetes. The overall five year mortality rate was 10.4% per year for those infected, significantly higher than the average of 4.0% for patients without infection (p = 0.015). None of the patients was bacteraemic or died directly from sepsis. Infection of DFU by S. aureus may increase the risk of death in diabetic patients.
It is well known that hyaluronic acid and its principal receptor, CD44, are implicated in the regulation of the tissue repair process, but their role in the formation of chronic diabetic ulcers has not been studied. Hyaluronic acid metabolism and CD44 expression are regulated by lactate, where their increased production is considered to affect the properties of fibroblasts in non-insulin-dependent diabetes mellitus. The aim of our work was to investigate the possible role of hyaluronic acid and CD44, and their regulation by lactate, in the abnormal wound healing of diabetes. Fibroblasts were derived from uninjured skin from four non-insulin-dependent diabetic patients with ulcers and four without ulcers; and from four healthy age-matched volunteers. We observed that diabetic fibroblasts of both groups produced more L-lactate ( approximately 30%) and incorporated more (3)H-glucosamine into the medium hyaluronic acid ( approximately 28%) than controls. Fibroblasts of the diabetic group with ulcers, unlike those of the group without ulcers, showed significant increases in the high molecular weight hyaluronic acid accumulation in the pericellular matrix (30.5%, p < 0.01) and CD44 expression (27.0%, p < 0.05). Exogenous L-lactate dose-dependently, and equally for all fibroblasts lines, stimulated the accumulation of medium hyaluronic acid (3.7-fold) and CD44 expression (1.5-fold). However, fibroblasts from diabetic patients with ulcers were more (1.4-fold) sensitive to L-lactate in terms of CD44 expression, and responded to L-lactate by the increased accumulation of high molecular weight hyaluronic acid in the pericellular matrix (32.1%, p < 0.01). We propose that specific properties of fibroblasts from diabetic patients with ulcers may be involved in the increased susceptibility of these patients to chronic ulceration.
To determine the efficacy and safety of short-contact administration of topical tretinoin on foot ulcers in patients with diabetes.
Randomized, double-blind, placebo-controlled trial.
Outpatient clinic at a Veterans Affairs medical center.
Twenty-four volunteers with diabetic foot ulcers but without evidence of peripheral arterial disease or infection.
Patients were randomized to 4 weeks of daily treatment with either topical 0.05% tretinoin solution (Retin-A) or placebo saline solution. Photographs and assessment of wound size and appearance were assessed every 2 weeks for a total of 16 weeks.
The proportion of ulcers that healed in each group and the degree of change in ulcer size.
Twenty-two patients, with a total of 24 foot ulcers, completed the study. At the end of 16 weeks, 2 (18%) of 11 ulcers in the control group and 6 (46%) of 13 ulcers in the tretinoin treatment group healed completely. Topical tretinoin therapy significantly decreased ulcer area and depth compared with placebo treatment over the 16 weeks of the study (P < .01 for surface area; P = .02 for depth). Adverse effects mainly consisted of mild pain at the ulcer site.
Short-contact application of topical tretinoin improved the healing of foot ulcers in patients with diabetes. The tretinoin therapy was generally well tolerated, without serious local or systemic adverse effects.
Object: The purpose of this study was to determine the prevalence of fungal infection and ulcer on the feet of diabetic patients and the existence of correlation between ulcer and fungal infection. Methods: A total of 21,693 outpatients diagnosed as diabetes mellitus at the department of endocrinology of 32 hospitals were examined. The diabetic patients with foot problems were consulted to the department of dermatology. Physical examination and KOH preparation were performed. Results: 13,271 patients had certain kinds of foot problem, accounting for 61.2% of 21,693 diabetics examined. Of these, fungal foot disease were found in 10,403 that constituted 78.4% (48.0% of the entire diabetic population). Tinea pedis was the diagnosis in 6,496 (29.9%), onychomycosis in 7,783 (35.9%), and coexistence was in 3,883 (17.9%). Foot deformity was in 1,346 (6.2% of diabetics; 10.1% of foot disease), non-palpable pulse in 1,051 (4.8%; 7.9%), and foot ulcer was in 425 (2.0%; 3.2%), following in a descending order of frequency. Odds ratios for diabetic foot ulcer were 2. 5 in patients with the foot deformity, 1.6 with fungal foot disease and 2.2 with non-palpable pulse. Conversely, Odds ratios for fungal foot disease were 2.5 with foot deformity, and 1.6 with foot ulcer. A total of 5,486 patients paid a visit to the department of dermatology. Of these, 4,519 patients were diagnosed with fungal infection through physical examination and KOH smear by dermatologists. The population comprised of 2,272 males and 2,247 females, showing similar prevalence between sexes. However, age did have positive correlation regarding prevalence of fungal foot disease. The number of diabetic patients with toenail problems was 3,847 patients (70%) and onychomycosis was proven mycologically in 3,276. Onychomycosis of distal subungal type was the most common clinical finding, most frequently involving the great toenails. Abnormal skin findings of the foot were seen in 3,885(70.8%) and tinea pedis was found in 3,209 (58.5%), most commonly involving the soles. Conclusion: This study showed that fungal infection might be regarded as a risk factor of foot ulcer. Treatment of fungal infection in diabetic patients might prevent diabetic foot disease such as ulcer and reduce the disability, morbidity and mortality in diabetic patients.
Elevated glucose level is the main cause of extracellular matrix (ECM) derangement in various tissues in diabetes mellitus. The development of diabetic nephropathy is considered to be dependent on profibrotic cytokine, transforming growth factor-β1 (TGFβ1). Its excessive activation due to the up-regulation of thrombospondin-1 (TSP-1) in mesangial cells exposed to high glucose contributes to ECM accumulation. However, the role of TSP-1–TGFβ1 pathway in the development of glucose-induced imbalance of ECM homeostasis in skin connective tissue is not studied. We investigated the response of human skin fibroblasts to elevated glucose level (11.0 and 30.0 mM) in terms of: (1) the expression and secretion of fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1); (2) the accumulation of hyaluronic acid (HA) in pericellular matrix and in the conditioned medium; (3) TGFβ1 expression, secretion and activation; (4) TSP-1 expression and secretion. We demonstrated the up-regulation of FN and PAI-1 by elevated glucose and the stimulation of HA accumulation in both cellular compartments. However, we failed to demonstrate the increase of expression, secretion and activation of TGFβ1, and the increase of TSP-1 expression and secretion in fibroblasts exposed to high glucose. These results show that ECM derangement in skin fibroblasts due to high glucose is not determined by TGFβ1 and its activation by TSP-1.
The dynamics of DNA synthesis by connective-tissue fibroblasts of intact mice and in the wounds of experimentally wounded mice was studied after administration of potassium orotate under different conditions. Potassium orotate was shown to increase the number of DNA-synthesizing fibroblasts equally in intact loose connective tissue and during wound healing. Stimulation of DNA synthesis is also possible within the strictly defined limits of the genetically controlled reserve capacity of the cells.
Vibration perception threshold (VPT) values, measured at different anatomic locations on the foot and ankle, and the time to assess VPT and sensory perception using two difference modalities in 102 diabetic patients were compared. VPT was evaluated at the great toe, fifth metatarsal and ankle. Differences in VPT at these three sites, in addition to differences in duration of testing comparing single site (great toe) to multiple sites, and to standard SWMF testing were assessed. No significant difference in VPT between the great toe and fifth metatarsal was found for patients both with and without loss of protective sensation (LOPS). Mean VPT was significantly higher at the ankle compared with both the great toes and fifth metatarsals. However, the difference between ankle and great toe was not significant between patients with and without LOPS [3.9 +/- 11.2 (12%) vs. 3.0 +/- 10.8 (16%) volts, respectively, p > 0.6]. Testing of one site took approximately half the time of Semmes-Weinstein 10-gram monofilament wire SWMF testing (40.5 +/- 16.9 vs. 22.3 +/- 9.1 seconds, p < 0.01) and less than one third the time of three-site VPT testing (10.5 +/- 26.1 vs. 22.3 +/- 9.1 seconds, p < 0.01). There may not be a significant practical benefit in multiple site VPT testing when compared with single site testing on the great toe alone. The value of multiple site testing is further called into question when one notes that the great toe VPT remains the only site tested for sensitivity and specificity for ulceration.
Wound healing involves the activity of epithelial cells and fibroblasts. This process is particularly accompanied by an increase in the proliferative capacity of the fibroblasts and by the biosynthesis of constitutive proteins of connective tissue. To study the action of wound healing drugs on the growth of fibroblasts, they were cultured in a medium containing a suboptimal concentration of serum. Several growth factors (eye-derived growth factor and fibroblast growth factor) were compared with various healing products for their effects on the growth curve. Some products slightly increased the proliferation of fibroblasts, in comparison with the optimal growth obtained with growth factors.
Intérêt des fibroblastes en culture dans l'étude de produits cicatrisants
Les cellules épithéliales et les fibroblastes participent tous deux au processus de réparation tissulaire au cours de la cicatrisation. En ce qui concerne les fibroblastes, on observe particulièrement une augmentation de leur capacité proliférative et de leurs biosynthèses spécifiques. Afin d'étudier l'action des produits cicatrisants sur la croissance des fibroblastes, une culture de ce type cellulaire est réalisée dans un milieu contenant une concentration suboptimale de sérum. Les effets des facteurs de croissance (EDGF et FGF) sont comparés à ceux des produits cicatrisants (acide acexamique et extrait de Centella Asiatica) sur l'évolution de la prolifération.
Previous studies have shown that Wistar rats injected at birth (n0) with STZ (n0-STZ) develop as adults a noninsulin-dependent diabetic state characterized by a lack of insulin response to glucose in vivo, a mild basal hyperglycemia, and an impaired glucose tolerance. Our former in vivo studies using the insulin-glucose clamp technique revealed an increased insulin action upon hepatic glucose production in these animals. We have now cultured hepatocytes from these mildly diabetic rats in parallel with hepatocytes from control rats, to examine more closely basal and insulin-regulated glucose production and glucose incorporation into glycogen. In addition, we extended our investigation to other hepatic functions such as lipid synthesis and amino acid transport, which could not be studied in vivo. Although glucose production from glycogenolysis or gluconeogenesis in absence or presence of glucagon was identical in the two cell populations, glucagon-stimulated glycogenolysis was more sensitive to insulin action in diabetic hepatocytes. Similarly, insulin action on glucose incorporation into glycogen, lipogenesis, and amino acid transport were enhanced in diabetic hepatocytes. The hormone effect was manifested by an increase in the sensitivity and/or in the responsiveness, reflecting the multiplicity of the pathways whereby the insulin signal is transduced through the insulin receptor to multiple postreceptor sites. To gain insight into the possible mechanism of these disturbances, we evaluated the initial insulin receptor interaction and the kinase activity of the receptor beta-subunit. In accordance with our previous study on intact livers, we found no alteration in either of these parameters in n0-STZ rat hepatocytes. Thus, the present study clearly demonstrates that these diabetic rats exhibit a postreceptor hyperresponsiveness to insulin at the cellular level. It strengthens the notion that a beta-cell deficiency with glucose intolerance does not necessarily lead to a hepatic insulin resistance.
To determine if diabetes in the elderly is associated with increased prevalence of podiatric problems, a random sample of diabetic patients (n = 74) was compared to a group of elderly non-diabetic patients (n = 79). The two groups were comparable in age (range 70-90 years), smoking habits, and consumption of alcohol. The mean duration of diabetes was 14.5 +/- 11.7 years (+/- SD), and mean serum fructosamine level was 3.3 +/- 0.66 mmol/L. The number of medical diagnoses and medications used was significantly higher in the diabetic group. Diabetic patients had modestly higher prevalence of neuropathy, vascular disease, kidney disease, and eye complications. The most common podiatric problem in both groups was elongated toenails. The prevalence of podiatric problems such as cellulitis, amputation, tinea pedia, onychomycosis, calluses, bunions, and hammer toe deformity were not increased in diabetic patients. Active foot ulcers were more common in diabetic patients (13/74 vs 5/79, P less than 0.05). It is concluded that diabetes in the elderly, unlike in young patients, increases the risk of foot problems only marginally.
The objective of the present study was to evaluate the reliability of a modified version of the commercially available Biothesiometer, and to examine vibrotactile perception thresholds with respect to age and gender. A standardized protocol for measuring vibrotactile perception threshold was administered to 80 subjects, once a week over 4 weeks. Inter-session variability was stable (analysis of variance for repeated measures; P>0.05) and correlations were high (Pearson's: 0.87≤r≤0.90; P≤0.001). For sites on both hands and feet, there was a significant increase with age (0.19≤r
2≤0.52; P≤0.001). Five factor analysis of variance model showed that vibrotactile perception threshold was significantly different with stimulus site, age category and gender; no differences were observed with alcohol consumption or smoking status. The findings indicate that the measurements from this device are highly reproducible and sensitive to expected threshold differences with age and gender. The authors attribute this to technical improvements of the original apparatus, rigid adherence to test protocol and maintenance of standard conditions. This type of instrument would be useful in assessing vibrotactile perception loss in occupational health studies.
To evaluate sensitivity, specificity, clinical utility, and cost-effectiveness of magnetic resonance (MR) imaging in the diagnosis of osteomyelitis of the foot in diabetics.
MR studies of 62 feet (diabetics [n = 27], nondiabetics [n = 35]) in 59 patients were prospectively evaluated to detect the presence and extent of osteomyelitis. Biopsy (n = 41 feet) and clinical follow-up (n = 62 feet) were used to establish the diagnosis, select treatment, and determine outcome; sensitivity and specificity of MR imaging were calculated. A cost analysis was performed.
Sensitivity and specificity of MR imaging in the diagnosis of osteomyelitis were 82% and 80%, respectively, in diabetics and 89% and 94%, respectively, in nondiabetics. There was no recurrent infection at the surgical margin in 13 feet in which the area of limited resection had been delineated at MR imaging.
MR imaging shows good sensitivity and specificity for diagnosing osteomyelitis in diabetic feet, and it is competitively priced compared with other imaging modalities. Accurate delineation of extent allows limited surgical resection, making MR imaging clinically useful and cost-effective.
OBJECTIVE--Research into the health of minority ethnic groups is often restricted by methodological difficulties. These include the lack of accurate population denominators, the choice of an appropriate sampling frame, correctly assigning ethnic group, and biases in techniques used for sampling and investigation. This article reviews the available sources or mortality and morbidity data, and assesses their uses and limitations for research involving ethnic minority groups. Suitable sampling frames and review methods used to assign ethnicity are discussed. Sources of bias are high-lighted and methods used to overcome these biases are presented. CRITERIA FOR INCLUSION OF ARTICLES--Articles have been chosen which best illustrate the problems encountered and show how these problems can be addressed. CONCLUSIONS--The increased documentation of ethnic origin on routine data sources is welcomed, but attention must be paid to ensuring that congruent definitions in data collection are used. The worrying consequences of the Commission of European Communities directive, which describes the need for explicit consent to be obtained from subjects before data is used for anything other than its original purpose, are discussed.
An examination of the reproducibility of three tests for identifying patients at risk of diabetic foot complications is reported. One thousand and one patients attending a general diabetic outpatient clinic at the Royal Liverpool University Hospital underwent screening using the Semmes-Weinstein monofilaments, the biothesiometer, and palpation of pedal pulses. Two hundred and fifty-nine patients who were found to have a deficit on at least one of these tests were given a second appointment where the tests were repeated. Two hundred and twenty-nine patients attended for their second appointment. The expected range of variation in readings for the biothesiometer was 5 log hertz, sufficient variation to make the biothesiometer unacceptable as a screening instrument. The range of reproducibility for the four pedal pulses was from 68% to 81%, also an unacceptable level of variation. Over 85% of the results for the Semmes-Weinstein monofilaments were the same on the first and second measurement. Of the three instruments examined in this study, only the Semmes-Weinstein monofilaments have sufficient reproducibility in the clinical setting for them to be recommended for general use as a screening test for risk of diabetic foot complications.
The objective of this study was to characterize the leucocyte infiltrate which accumulates at the margin of chronic wounds. These leucocytes are a rich source of cytokines and growth factors, and an inappropriate function of these cells may contribute to the maintenance of wound chronicity. The leucocyte populations were stained immunohistochemically with monoclonal antibodies specific for surface receptors which give an indication of cellular function. Wound margin biopsies taken from chronic leg ulcers exhibited a localized infiltrate of CD45+ leucocytes associated with vascularized tissue in the dermis adjacent to the wound margin. Lymphocytes were identified in highest numbers in this area and CD45RO+ T lymphocytes predominated over B lymphocytes, which were either absent or present in very low numbers. In the majority of chronic wounds examined, CD4+ T lymphocytes were present in greater numbers than CD8+ T lymphocytes with a mean (± SD) ratio of CD4+ : CD8+ of 1.5 ± 0.6.
CD68+ macrophages were identified in all layers of the dermis at the chronic wound margin. In 60% of wounds examined, macrophages were negative for the activation associated markers CD16 (FcγIII receptor) and CD35 (C3b receptor). In those biopsies where CD16 and CD35 positive macrophages were observed these were preferentially located in the perivascular regions. These data indicate that as monocytes extravasate into chronic wound tissue they may be subjected to microenvironmental influences which either suppress or do not induce macrophage activation. Suppression of macrophage activation may lead to an inappropriate cytokine/growth factor secretion and contribute to the maintenance of wound chronicity.
During a 10-year period, 237 patients (129 women, 108 men) with a diagnosis of neuropathic (Charcot) arthropathy of the foot and ankle were treated in a tertiary care university hospital medical center. During this period, 115 of the patients (48.5%) were treated nonoperatively as outpatients with local skin and nail care, accommodative shoe wear, and custom foot orthoses. A total of 120 (50.6%) underwent 143 operations. Surgery included 21 major limb amputations, 29 ankle fusions, 26 hindfoot fusions, 23 exostectomies, and 23 debridements for osteomyelitis.
It is widely accepted that patients with diabetes are at risk for developing foot ulcers, which can lead to lower extremity amputation. Within the population of diabetic patients, it is widely accepted that patients with neuropathic (Charcot) arthropathy of the foot and ankle have one of the highest likelihoods of having to undergo lower extremity amputation. The current emphasis in care of the foot of a diabetic patient involves a multidisciplinary team approach combining patient education, skin and nail care, and accommodative shoe wear. As data from prophylactic programs become available, resource allocation and cost of care can be compared with this benchmark baseline.
This benchmark analysis can be used by those who are responsible for allocating resources and projecting healthcare costs for this “high utilization”/high risk patient population.
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.
The wound healing activity of two herbal formulations (Himax ointment and lotion) containing Indradaru extract, i.e. Arjuna bark (Terminalia arjuna, Family-Combretaceae), extract was evaluated for its wound healing potential in two types of wound models in rats (i) excision wound model and (ii) incision wound model. Both the formulations responded significantly in both the wound models tested. The results were also comparable to that of the standard drug nitrofurazone used as a standard drug for comparison in this present investigation. The results were also comparable in terms of wound contracting ability, epithelization period, tensile strength and regeneration of tissues at the wound area. Thus, this investigation con fi rms the use of the Himax ointment and lotion containing Terminalia arjuna extract as a wound-healing agent as known from folklore medicine.
Australian data are currently lacking regarding management guidance, resource usage and outcomes of patients with diabetes requiring hospitalization for management of acute foot complications.
The aims of the present study were to review hospital admissions for diabetes-related foot complications and current assessment and management of these complications, and to formulate recommendations for future models of care.
A retrospective review of patient records from 1 July 1999 to 30 June 2000 was carried out. Recorded assessment, investigations, management, amputation rates, referral rates and length of hospital stay were reviewed.
There were 69 admission episodes in 12 months (total patients n = 50). The mean age was 64 years, with 44 male patients (64%) and 25 female patients (36%). The mean diabetes duration was 11 years (range <1-47 years). The majority of patients had type 2 diabetes. Assessment for known risk factors for ulceration and amputation was variable with history of previous ulcer/amputation recorded for 24 (35%) admissions, results of neurological assessment recorded for 11 (16%) and assessment of pedal pulses documented for 51 (74%). Glycated haemoglobin was performed during 35 (51%) admissions. Patients were admitted under one of 11 different inpatient units and the average interdepartmental referral rate was one referral per patient per admission. The average length of stay was 17 days, with total bed days occupied 1163 days. Minor amputation was performed in 25 (36%) cases and major amputation in 8 (11%).
Clinical assessment, investigation and management of this population are highly variable. This has a significant impact on the final clinical outcome, and changes to current processes are required to overcome the substantial burden of diabetic foot disease.
The role of endogenously produced cytokines and growth factors in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine the functional capacity of skin cells in ulcer bed tissue compared to those in the edge of ulcers and skin distal to ulcers. Biopsies from leg ulcers of ten randomly selected patients were examined immunohistochemically for cytokines and growth factors produced by keratinocytes (KC) and vascular endothelial cells (EC). The phenotype of leukocytes infiltrating venous ulcers and the expression of vascular adhesion molecules responsible for extravasation were also studied. The expression of cytokines and growth factors by KC was similar in areas adjacent and remote from an ulcer. In the dermis adjacent to an ulcer, the expression of IL-1alpha, IL-1beta, IL-1Ra, EGF and PDGFa by EC was higher than the levels of expression in EC from the distant dermis. The expression of IL-6, TNFalpha and GM-CSF was comparable to that in cells from intact dermis. For all these factors staining was cytoplasmic, suggesting production in these areas. Ulcer bed tissue contained few fibroblasts and blood capillaries showing a high staining intensity for CD62E and CD106 EC adhesion molecules but no FGF2 expression (P<0.05). The intensity of staining for scavenging CD15+ elastase+ granulocytes and CD35+ (C3bR) activated macrophages in the ulcer bed was comparable to that in the margin but higher than that in the distant dermis (P<0.05), whereas staining for CD68+, HLA DR+, TGFbeta+ and CD54+ dermal macrophages was similar in all areas. There was reduced staining for CD4+ and CD8+ cells in the ulcer bed (P<0.05). There were no CD1a+ Langerhans cells in the epidermis encroaching upon the granulation tissue and there was reduced CD1a staining in the adjacent epidermis (P<0.05). In conclusion, there is chronic accumulation of scavenging cells with lack of remodeling of the granulation tissue and, at the same time, preserved cytokine and growth factor secretory potential of KC and dermal EC in non-healing venous leg ulcers.
To benchmark by year the likelihood that an individual with a diabetic neuropathic foot ulcer will heal over more than a 10-year period.
A cohort study within a multicentre wound care network of individuals with a diabetic neuropathic foot ulcer who were treated by a standard wound care algorithm. The main outcome was a healed wound by the 20th week of care stratified by calendar year.
We evaluated 27 193 individuals with a neuropathic foot ulcer. Between 1988 and 1990 approximately 66% of patients did not heal. By 1999 this percentage had decreased to 49%. The change in the rate of failure to heal is very closely associated with an increase over time in the proportion of patients seen with wounds identified as prognostically favourable using a previously published prognostic model (i.e. individuals with wounds < or = 2 cm2, wounds < or = 2 months old, and wounds of grade < or = 2). Nevertheless, even among those most likely to heal, the likelihood of failing to heal went from 62% prior to 1991 to 32% in 2000.
We have shown that individuals with a diabetic neuropathic foot ulcer seeking care are more likely to heal today than 10 years ago. The primary reason for this improvement is that individuals are seeking care when their wounds are most easily treated and these are now more likely to heal.
To design a multidisciplinary, evidenced-based, clinical guideline for the assessment, investigation and management of inpatients with acute diabetes related foot complications.
A systematic search of both published (identified by searching all major electronic databases and hand searching key journals) and unpublished literature (derived from national and internationally recognized experts) identified 266 articles specific to diabetes related foot complications. Of these, 126 (47%) were assessed to be methodologically sound and clinically relevant. A narrative summary with the articles tabulated according to their level of evidence was prepared. A multidisciplinary expert group of health professionals, with a known interest and recognized expertise in diabetes related foot complications, was established to assess the evidence.
The multidisciplinary expert group used the identified literature and clinical experience to create a comprehensive, evidence-based, clinical guideline for the assessment, investigation and management of acute diabetes related foot complications. Included within the guideline is a novel, diabetes specific classification system, which codes for the presence/absence and severity of the four principle causative factors (Neuropathy, Vascular compromise, Ulceration and Infection) in the development of acute diabetes related foot complications.
Through the creation and implementation of this evidence-based clinical guideline, specific for acute diabetes related foot complications, it is hoped that health professionals will be better equipped to make informed decisions for this patient population. This may benefit the individual and health system through reductions in amputation rate, length of hospital stay and health expenditure.
Diabetic foot ulceration represents a major medical, social and economic problem all over the world. While more than 5% of diabetic patients have a history of foot ulceration, the cumulative lifetime incidence may be as high as 15%. Ethnic differences exist in both ulcer and amputation incidences. Foot ulceration results from the interaction of several contributory factors, the most important of which is neuropathy. The use of the total-contact cast is demonstrated in the treatment of plantar neuropathic ulcers. Histological evidence suggests that pressure relief results in chronic foot ulcers changing their morphological appearance by displaying some features of an acute wound. Thus, repetitive stresses on the insensate foot appear to play a major role in maintaining ulcer chronicity. It is hoped that research activity in foot disease will ultimately result in fewer ulcers and less amputation in diabetes.
Gas chromatography (GC) was used to differentiate 100 isolates of Candida species (Candida parapsilosis, Candida albicans, Candida tropicalis, Candida famata and Candida glabrata) from 22 of 509 diabetic patients in whom the same species had been isolated from ulcer and interdigital spaces of the same and/or the other foot. All clinical isolates were identified by quantitative differences in the composition of six cell fatty acids (CFA). The values of the coefficients of variability (CV) of CFA show that the isolates from foot ulcers and interdigital spaces of the same diabetic patient probably belong to different chemotypes of the same Candida species.
Diabetes mellitus is the most common, non-communicable chronic disease globally. In African countries, peripheral neuropathy underlies most diabetic foot complications; however, peripheral vascular disease appears to be increasing, presumably a reflection of increasing urbanisation. We conducted this study to ascertain the occurrence of foot complications among diabetes patients in the African continent. Using various keyword combinations, we searched Medline (PubMed) databases and the archives of Muhimbili National Hospital, the major teaching hospital in Tanzania, for obscure diabetes literature on diabetes in Africa. We also reviewed available non-English literature and obtained relevant translations where appropriate. We found articles encompassing years 1960-2003. Foot complications such as ulceration, infection, or gangrene were generally associated with considerable long-term disability and pre-mature mortality. Rates of complications varied by country-foot ulcers: 4-19%; peripheral neuropathy: 4-84.4%; peripheral vascular disease: 2.9-78.7%; frequency of patients presenting with gangrenous foot ulcers: 0.6-69%; foot amputation rates: 0.3-45%. A study of diabetic patients in Tanzania showed mortality rates >50% among patients with severe foot ulcers, who did not undergo surgery. Other published data from Tanzania suggest that surgical intervention after the onset of gangrene may be too late to prevent death. Prevention and control programmes are needed to stem the rising occurrence of diabetic foot complications in Africa. Gangrenous diabetic feet require aggressive management and early surgical intervention. Early presentation by patients and prompt surgical intervention during less severe rather than during later stages of an ulcer may improve patients outcome and reduce mortality rates.
Foot infection is a huge economic and social burden for patients with diabetes. The etiology is multifactorial, necessitating a multidisciplinary team for successful treatment and prevention. Infection usually is a consequence rather than the cause of foot ulcers in patients with diabetes. Infection is a clinical diagnosis and can be categorized as mild cellulitis, moderate to severe cellulitis, and osteomyelitis. No single imaging technique is 100% sensitive or specific for the diagnosis of osteomyelitis. Infected foot ulcers require appropriate tissue and bone cultures to guide antibiotic therapy whereas uninfected ulcers, which may be colonized with bacteria, do not require antibiotics. Gram-positive organisms account for a substantial proportion of infections with increasing prevalence of methicillin-resistant Staphylococcus aureus in recent years. Osteomyelitis in patients with diabetes requires aggressive surgical intervention in addition to antibiotics. Duration of treatment varies from 2 to 6 weeks based on the severity of infection, along with surgical debridement. Prevention of foot ulcer and infection requires patient education, detection of neuropathy, glycemic control, and proper foot care with foot hygiene and appropriate footwear. The patient is an important member of the team and should be taught the importance of self examination and early reporting of foot problems.
To compare results of skin graft healing in diabetic ulcers between the meshed skin graft method and split thickness skin graft method. Duration of complete skin graft healing in both groups was recorded. The relations between ulcer size and complete skin graft healing duration were analyzed.
This research used a prospective randomized controlled study with 80 diabetic ulcer patients from January 2002-June 2003. Thirty-eight cases were treated by the meshed skin graft method with expansion ratio 1:3 and another 42 cases were treated with the ordinary split-thickness skin.
The means of complete healing duration were 19.84 +/- 7.37 days in the meshed skin group and 20.36 +/- 7.21 days in the normal split-thickness skin graft group. There was no statistically significant difference between the groups in duration of complete graft healing and efficacy of treatment. The cosmetic result was accepted in both skin graft methods. There was no statistically significant difference between wound size and complete skin graft healing duration.
The meshed skin graft method is as good for diabetic ulcer coverage as the ordinary split thickness skin graft.