Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in advanced diabetic foot ulcers (DFU) A double-blind trial was carried out to test two rhEGF dose levels in type 1 or 2 diabetes patients with Wagner's grade 3 or 4 ulcers, with high risk of amputation. Subjects were randomised to receive 75 (group I) or 25 mug (group II) rhEGF through intralesional injections, three times per week for 5-8 weeks together with standardised good wound care. Endpoints were granulation tissue formation, complete healing and need of amputation. Safety was assessed by clinical adverse events (AEs) and laboratory evaluations. Forty-one patients were included. After 5-8 weeks of treatment, 83% patients in the higher dose group and 61% in group II achieved useful granulation tissue covering more than 98% of the wound area. At long-term assessment, 13 (56.5%) patients healed in group I and 9 (50%) in group II. The mean time to complete healing in group I was 20.6 weeks (95% CI: 17.0-24.2) and 19.5 weeks (16.3-22.7) in group II. After 1-year follow-up, only one patient relapsed. Amputation was not necessary in 65% and 66.7% of groups I and II, respectively. The AEs rates were similar. The most frequent were sepsis (33%), burning sensation (29%), tremors, chills and local pain (25% each). rhEGF local injection enhances advanced DFU healing and reduces the risk of major amputation. No dose dependency was observed.
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PMID:Intralesional injections of Citoprot-P (recombinant human epidermal growth factor) in advanced diabetic foot ulcers with risk of amputation. 1795 79

This study tests the hypothesis that addition of a protease-modulating matrix enhances the efficacy of autologous growth factors in diabetic ulcers. Fifty-one patients with chronic diabetic foot ulcers were managed as outpatients at the Democritus University Hospital of Alexandroupolis and followed up for 8 weeks. All target ulcers were > or = 2.5 cm in any one dimension and had been previously treated only with moist gauze. Patients were randomly allocated in three groups of 17 patients each: Group A was treated only with the oxidized regenerated cellulose/collagen biomaterial (Promogran, Johnson & Johnson, New Brunswick, NJ), Group B was treated only with autologous growth factors delivered by Gravitational Platelet Separation System (GPS, Biomet), and Group C was managed by a combination of both. All ulcers were digitally photographed at initiation of the study and then at change of dressings once weekly. Computerized planimetry (Texas Health Science Center ImageTool, Version 3.0) was used to assess ulcer dimensions that were analyzed for homogeneity and significance using the Statistical Package for Social Sciences, Version 13.0. Post hoc analysis revealed that there was significantly greater reduction of all three dimensions of the ulcers in Group C compared to Groups A and B (all P<.001). Although reduction of ulcer dimensions was greater in Group A than in Group B, these differences did not reach statistical significance. It is concluded that protease-modulating dressings act synergistically with autologous growth factors and enhance their efficacy in diabetic foot ulcers.
J Diabetes Complications
PMID:Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial. 1796 12

Inflammation and wound healing are inextricably linked and complex processes, and are deranged in the setting of chronic, nonhealing diabetic foot ulcers (DFU). An ideal therapy for DFU should both suppress excessive inflammation while enhancing healing. We reasoned that biological simulation would clarify mechanisms and help refine therapeutic approaches to DFU. We developed an agent-based model (ABM) capable of reproducing qualitatively much of the literature data on skin wound healing, including changes in relevant cell populations (macrophages, neutrophils, fibroblasts) and their key effector cytokines (tumor necrosis factor-alpha [TNF], interleukin [IL]-1beta, IL-10, and transforming growth factor [TGF]-beta1). In this simulation, a normal healing response results in tissue damage that first increases (due to wound-induced inflammation) and then decreases as the collagen levels increase. Studies by others suggest that diabetes and DFU are characterized by elevated TNF and reduced TGF-beta1, although which of these changes is a cause and which one is an effect is unclear. Accordingly, we simulated the genesis of DFU in two ways, either by (1) increasing the rate of TNF production fourfold or (2) by decreasing the rate of TGF-beta1 production 67% based on prior literature. Both manipulations resulted in increased inflammation (elevated neutrophils, TNF, and tissue damage) and delayed healing (reduced TGF-beta1 and collagen). Our ABM reproduced the therapeutic effect of platelet-derived growth factor/platelet releasate treatment as well as DFU debridement. We next simulated the expected effect of administering (1) a neutralizing anti-TNF antibody, (2) an agent that would increase the activation of endogenous latent TGF-beta1, or (3) latent TGF-beta1 (which has a longer half-life than active TGF-beta1), and found that these therapies would have similar effects regardless of the initial assumption of the derangement that underlies DFU (elevated TNF vs. reduced TGF-beta1). In silico methods may elucidate mechanisms of and suggest therapies for aberrant skin healing.
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PMID:Agent-based model of inflammation and wound healing: insights into diabetic foot ulcer pathology and the role of transforming growth factor-beta1. 1797 Oct 13

Peripheral neuropathy is the main risk factor for foot ulceration in diabetic subjects. This study examined the association of peripheral arterial disease (PAD) with foot ulceration in a sample of diabetic subjects with peripheral neuropathy, and also if inflammatory markers would be associated with this event. We evaluated 32 type 2 diabetic individuals with abnormal 10-g monofilament exam, who were stratified in 2 groups according to history or presence of lower extremities ulcer. The group "with ulcer" (n = 18) included the ones that had active or cicatrized ulcer, or some lower-extremity amputation due to ulcer complications. In addition to the neurological examination and monofilament test, they were submitted to biothesiometry, lower extremity vascular assessment with Doppler, and laboratory determinations. No difference between the groups was found concerning sex distribution, mean age, and duration of diabetes diagnosis. The group with ulcer showed higher mean values of height (1.70 +/- 0.06 vs. 1.63 +/- 0.11 m, p = 0.044), vibration perception threshold measured in medial malleolli (40.9 +/- 13.0 vs. 30.6 +/-12.3 V, p = 0.040) than the group without ulcer. The groups did not differ regarding the mean values of the inflammatory markers. Response to patellae reflex was worse in the group with ulcer (p = 0.047), in which a higher proportion of individuals with abnormal toe-brachial index (p = 0.030) was observed as compared to those without ulcer. We concluded that PAD is associated with the presence of ulcer in neuropathic subjects. The assessment of digital arteries flow in lower limbs (in great toe) contributed to detect such association. Association of diabetic foot ulcers and inflammatory markers was not observed, but cannot be excluded due to limitations of sample size. Prospective studies should examine the sensitivity of the toe-brachial index to identify PAD in diabetic individual at risk of ulceration.
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PMID:[Analysis of factors associated with extremity ulceration in diabetic subjects with peripheral neuropathy]. 1815 90

The diabetic foot constitutes a tremendous challenge for patients, caregivers and the health care system. The International Consensus Document of 1999 was a milestone in the recognition of the importance and consequences of the diabetic foot. Since then, many original papers have been published in this area. Large cohort studies have given us a deeper understanding regarding factors related to the outcome of diabetic foot ulcers: according to these studies, the severity of diabetic foot ulcers is greater than previously reported. More than 50% of individuals' foot ulcers have signs of infection at admission, and one-third have signs of both peripheral artery disease (PAD) and infection. The co-morbidities increase significantly with increasing severity of the foot disease. However, the trend in all these studies is a successive improvement in healing rate (50-60% at 20 weeks follow-up, > 75% at 1 year). It is important to differentiate between neuropathic and neuro-ischaemic ulcers with regard to factors related to outcome and co-morbidities.Recent research has emphasized the importance of psychological factors in the development and outcome of diabetic foot ulcers. Studies have shown that perceptions of the individual's own risks based on symptoms, and their own beliefs in the efficacy of self-care, can affect foot-care practice.The importance and influence of the health care organization and reimbursement should not be underestimated, both in the prevention and management of diabetic foot lesions. The diabetic foot should be considered a lifelong condition, as having had one ulcer dramatically increases the risk of developing a new ulcer. In an individual with diabetes and a foot ulcer, the ulcer should be considered as a sign of multi-organ disease, and a holistic approach to both management and prevention is recommended.
Diabetes Metab Res Rev
PMID:The foot in perspective. 1838 11

Loss of pain perception is currently seen as a key factor in the development of diabetic foot ulcers. However, recent studies suggest that nerves play a central role in tissue homeostasis and can orchestrate complex reparative as well as destructive processes in the feet. Evidence is presented that suggests that denervation can result in altered capillary blood flow (in patients with type 2 diabetes), oxygen delivery, fluid filtration, and inflammatory responses. These processes could render the feet of diabetic patients with neuropathy more susceptible to tissue damage, infection and perhaps, in a subset of patients, to the development of acute Charcot neuro-osteoarthropathy (CN).
Diabetes Metab Res Rev
PMID:Neurovascular control and neurogenic inflammation in diabetes. 1844 83

It is frequently stated that diabetic foot ulcers should be managed by a multidisciplinary team, comprising individuals who can deliver all the necessary and wide-ranging skills: medical and surgical, podiatric, nursing and orthotic. Whilst there are some data to support this multidisciplinary approach there is little to guide us in ensuring the patient is seen by the right professional for the right treatment at the right time. This article will examine the evidence supporting the most effective use of the multidisciplinary team. It will look at medical managements of ulcers including dressings, offloading and the treatment of infection, either cellulitis or osteomyelitis. By contrast, the role of surgery in offloading, and the treatment of osteomyelitis will be examined, as well as the role of vascular surgery. The most important aspect of management choice, however, is the need to focus on the needs of the person with a diabetic foot ulcer rather than simply on the treatment of the ulcer in isolation. Other complications of diabetes, which may have an effect on wound healing such as glycaemic control, renal failure and visual disturbance will be explored.Finally, there will be discussion of the relevance of outcome measure, both of ulcers as well as those more patient-centred. The ways in which these can be used to monitor individual clinical responses to treatment will be described, as well as their potential use as an aid to comparison of the effectiveness of treatment protocols adopted in different centres.
Diabetes Metab Res Rev
PMID:The advantages and disadvantages of non-surgical management of the diabetic foot. 1844 84

The outcome of management of diabetic foot ulcers is poor and there is uncertainty concerning optimal approaches to management. We have undertaken a systematic review to identify interventions for which there is evidence of effectiveness. A search was made for reports of the effectiveness of interventions assessed in terms of healing, ulcer area or amputation in controlled clinical studies published prior to December 2006. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Selected studies fell into the following categories: sharp debridement and larvae; antiseptics and dressings; chronic wound resection; hyperbaric oxygen (HBO); reduction of tissue oedema; skin grafts; electrical and magnetic stimulation and ultrasound. Heterogeneity of studies prevented pooled analysis of results. Of the 2251 papers identified, 60 were selected for grading following full text review. Some evidence was found to support hydrogels as desloughing agents and to suggest that a systemic (HBO) therapy may be effective. Topical negative pressure (TNP) may promote healing of post-operative wounds, and resection of neuropathic plantar ulcers may be beneficial. More information was needed to confirm the effectiveness and cost-effectiveness of these and other interventions. No data were found to justify the use of any other topically applied product or dressing, including those with antiseptic properties. Further evidence to substantiate the effect of interventions designed to enhance the healing of chronic ulcers is urgently needed. Until such evidence is available from robust trials, there is limited justification for the use of more expensive treatments and dressings.
Diabetes Metab Res Rev
PMID:A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes. 1844 85

The incidence of diabetes is increasing and therefore patients with diabetic foot ulcers will become increasingly common in the community. The NHS model of Health and Social Care (Department of Health (DH), 2005) places a high emphasis on self care and disease management, and, as a long-term condition, diabetes mellitus requires efficient and effective management. The supervision and organization of the care of diabetic patients is multi-factorial and for this reason, a multi-disciplinary approach is essential for effective care, without which patients with diabetic foot ulcers are at high risk of complications. Diabetic wounds present differently to other chronic wounds; unless these are adequately assessed and treated, there may be devastating consequences for the patient--the most serious being major amputation and/or death. In the first article, accurate assessment was discussed; in this second article, the management of diabetic foot ulcers is explored.
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PMID:Management of the diabetic foot ulcer: exercising control. 1855 70

Diabetic foot disease is a major health problem, which affects 15% of the 200 million patients with diabetes worldwide. Diminished peripheral blood flow and decreased local neovascularization are critical factors that contribute to the delayed or nonhealing wounds in these patients. The correction of impaired local angiogenesis may be a key component in developing therapeutic protocols for treating chronic wounds of the lower extremity and diabetic foot ulcers. Endothelial progenitor cells (EPCs) are the key cellular effectors of postnatal neovascularization and play a central role in wound healing, but their circulating and wound-level numbers are decreased in diabetes, implicating an abnormality in EPC mobilization and homing mechanisms. The deficiency in EPC mobilization is presumably due to impairment of eNOS-NO cascade in bone marrow (BM). Hyperoxia, induced by a clinically relevant hyperbaric oxygen therapy (HBO) protocol, can significantly enhance the mobilization of EPCs from the BM into peripheral blood. However, increased circulating EPCs failed to reach to wound tissues. This is partly a result of downregulated production of SDF-1alpha in local wound lesions with diabetes. Administration of exogenous SDF-1alpha into wounds reversed the EPC homing impairment and, with hyperoxia, synergistically enhanced EPC mobilization, homing, neovascularization, and wound healing.
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PMID:Hyperoxia, endothelial progenitor cell mobilization, and diabetic wound healing. 1862 49


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