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

Sixty thousand to 118,000 lower extremity amputations are performed each year in the United States. The combination of peripheral vascular disease and diabetes mellitus accounts for most cases, with diabetic patients representing 45% to 70% of all nontraumatic, lower extremity amputations. The 3-year survival rate after amputation is only 50%. As podiatric physicians, we are directly involved in limb preservation. Progress has occurred in both the diagnosis and treatment of lower extremity, chronic, nonhealing ulcers. An aggressive, comprehensive amputation intervention program is critical to those patients with refractory wounds to prevent the emotional, functional, and economic costs of limb loss. Recent developments in recombinant growth factors are making it possible to decrease the morbidity and mortality associated with defective angiogenesis, fibroblastic proliferation, collagen remodeling, and epithelial regeneration. Widespread use of growth factors will first occur in topical applications. Absorbable sutures, as well as impregnated bandages, are a likely method of delivering the growth factors to the wound site. Biotechnology companies are developing a stable formulation for bFGF topical application. Clinical trials have begun at various teaching hospitals across the United States for treatment of venous stasis ulcers. U.S. and European firms are collaborating to conduct the clinical studies required to obtain regulatory approvals leading to the sale of topical recombinant bFGF. Although U.S. approval is pending, European use of EFG in the healing of corneal incisions began several years ago. In the future, use of recombinant EGF topically with burn patients may permit earlier reharvesting of healed donor sites as well as coverage of larger graft areas. As some growth factors affect specific processes of healing and cell types, it may be necessary to combine growth factors for complex wounds. PDGF application in combination with other growth factors to incisional wounds may decrease postoperative complications with wound dehiscence while mediating inflammation and repair. In vivo experimental findings suggest that combinations of PDGF and insulin applied topically to wounds may increase the rate of wound repair in diabetics. It is also possible that even the normal healing process may be accelerated, thereby shortening postsurgical convalescence. Approval for internal administration of growth factors will require additional research and thorough clinical trials. The ability of TGF-beta to promote collagen formation may also relate to a metabolic condition such as osteoporosis, in which inadequate formation of collagen or other components of the bone matrix may contribute to pathogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Growth factor impact on wound healing. 193 39

The use of topical metronidazole has been limited to the treatment of acne rosacea, infected foot ulcers associated with diabetes mellitus, varicose veins, postirradiation ulcers, and dental conditions since the Food and Drug Administration approved the drug in 1988. Because of this agent's apparent effectiveness in treating anaerobic bacterial infections in such ulcers, the authors believed that treatment of arterial insufficiency ulcers with a solution of topical metronidazole would be a rational approach. They describe a 30-year-old man in whom bilateral lower extremity cellulitis developed as a result of arterial insufficiency. The patient's ulcers were unresponsive to intravenously administered antibiotics and whirlpool therapy. However, when a topical solution of metronidazole was administered, the ulcers began to heal and epithelialization at the ulcer sites occurred. The authors review others' studies concerning clinical use of topical metronidazole and suggest that further study is warranted. To the authors' knowledge, topical metronidazole solution for the treatment of arterial insufficiency and venous stasis ulcers has not been previously reported.
 ...
PMID:Topical metronidazole for arterial insufficiency ulcers. 775 Nov 70

Despite the availability of various topical agents and of new technics for surgical correction, venous stasis ulcers are still characterized by high recurrent rates. Experimental data from wound healing studies demonstrate stimulation of wound healing after topical application of various growth factors (TGF beta, PDGF, EGF). The results of clinical studies suggest that topical use of an autologous platelet releasate (PDWHF) containing various growth factors accelerates healing. In this prospective study the stimulating effect of autologous PDWHF on epithelialization of small ulcers (group A, < 5000 mm2) and granulation of large ulcers before mesh grafting (> 5000 mm2) will be demonstrated. Inclusion criteria were the venous aetiology of the ulcer and the failure of conventional therapy for 6 month. Exclusion criteria were arterial occlusive disease, diabetes mellitus, acute wound infection, thrombocytopenia and pregnancy. There were 24 patients with 36 ulcers, caused by postthrombotic syndrome in one-third of cases and in two-thirds by severe insufficiency of the perforating veins. The ulcer had been present for more than in 10 years in 38% of cases, while there were 6 circumferential ulcers. The overall ulcer healing rate was 77% after a mean of 14 weeks. In group A 78% of the patients were healed after a mean of 16 weeks. In group B the mesh graft procedure was successful in 90% of the patients after a mean of 13 weeks. Compared with other conventional therapy studies, we achieved a higher healing rate. PDWHF seems to create ideal granulation tissue for mesh graft, indicated by a high uptake of the skin grafts.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Ulcus cruris venosum: surgical debridement, antibiotic therapy and stimulation with thrombocytic growth factors]. 776 Jun 47

Diabetes is accompanied by delayed wound healing and insufficient granulation tissue formation, possibly because of a defect in fibroblast function. We have previously shown that fibroblasts derived from chronic diabetic foot ulcers have lower proliferation compared with those from uninjured skin. The aim of this study was to investigate possible mechanisms explaining the impaired fibroblast proliferation observed in fibroblasts from non-insulin-dependent diabetes mellitus chronic wounds and normal fibroblasts cultured in high glucose. Fibroblasts from two groups of patients were studied: nondiabetic patients with chronic venous stasis ulcers and non-insulin-dependent diabetes mellitus patients with chronic diabetic wounds. Biopsies from both uninjured skin and wounds were taken from the same patients to serve as sources of fibroblasts. A fluorometric method was used to determine DNA content, and a spectrophotometric lactate oxidase method was used for lactate level analysis. We found a dose-dependent inhibition of normal fibroblast proliferation when adding conditioned media from non-insulin-dependent diabetes mellitus wound fibroblasts. The conditioned medium, from these cells showed elevated l-lactate levels, 6.3 +/- 0.7 mmol/L, compared with media derived from nondiabetic, 2.1 +/- 0.3 mmol/L (p < 0.01), and diabetic uninjured skin fibroblasts, 3.5 +/- 0.6 mmol/L, and from chronic nondiabetic wound fibroblasts 2.9 +/- 0.3 mmol/L. Addition of 6 mmol/L l-lactate to uninjured normal fibroblasts resulted in decreased DNA content (58 +/- 7%, p < 0.01). Previously we have shown that high glucose concentrations inhibit fibroblast proliferation and induce growth factor resistance. When increasing the amount of d-glucose in the media, l-lactate levels increased in all cell types. When the uninjured normal cells were treated with beta-hydroxybutyrate, the total DNA content decreased by 42 +/- 5% (p < 0.05), with no significant increase in the l-lactate levels. These observations indicate that l-lactate production may be of importance for fibroblast proliferation in vitro and may play a role in fibroblast proliferation in vivo.
 ...
PMID:Inhibited proliferation of fibroblasts derived from chronic diabetic wounds and normal dermal fibroblasts treated with high glucose is associated with increased formation of l-lactate. 977 56

Aging has significant effects on the healing ability of the geriatric population. When the elderly suffer injuries, they have a decreased metabolic reserve to handle the stress required to recover. Diseases of the elderly, such as malnutrition, diabetes mellitus, treatment of malignancies, and vascular disease, all impair tissue repair. The geriatric population is more prone to pressure ulcers, venous stasis ulcers, and other chronic wounds. This review discusses how changes in the elderly lead to impaired healing or chronic wounds. Prevention of these problems and their treatment are also discussed.
...
PMID:Management of the skin and soft tissue in the geriatric surgical patient. 2545 45

Chronic wounds affect over 4 million individuals and pose a significant burden to the US healthcare system. Diabetes, venous stasis, radiation or paralysis are common risk factors for chronic wounds. Unfortunately, the current standard of care (SOC) has a high relapse rate and these wounds continue to adversely affect patients' quality of life. Fortunately, advances in tissue engineering have allowed for the development of cell-based wound dressings that promote wound healing by improving cell migration and differentiation. As the available options continue to increase in quantity and quality, physicians should have a user-friendly guide to reference when deciding which dressing to use. The objective of this review is to identify the currently available biologic dressings, describe their indications, and provide a framework for integration into clinical practice. This review included 53 studies consisting of prospective and retrospective cohorts as well as several randomized control trials. Three general categories of cell-based biologic dressings were identified and nine brands were included. Cell-based biologic dressings have shown efficacy in a broad range of scenarios, and studies examining their efficacy have improved our understanding of the pathophysiology of chronic wounds. Amniotic and placental membranes have the widest scope and can be used to treat all subtypes of chronic wounds. Human skin allografts and bioengineered skin substitutes can be used for chronic ulcers but generally require a vascularized wound bed. Autologous platelet rich plasma (PRP) has shown promise in venous stasis ulcers and decubitus ulcers that have failed conventional treatment. Overall, more research is necessary to determine if these novel therapeutic options will change the current SOC, but current studies demonstrate encouraging results in the treatment of chronic wounds.
 ...
PMID:An update and review of cell-based wound dressings and their integration into clinical practice. 2809 May 13

The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed.
 ...
PMID:The molecular biology in wound healing & non-healing wound. 2871 79

Oxidative stress is hypothesized to be one of the main causes of the pathophysiologic alterations observed during impaired healing of wounds. In the present study, we aimed to measure systemic levels of free radicals in blood and anti-oxidant (AO) activity in the plasma of patients with chronic ulcers (venous stasis ulcers and arterial insufficiency ulcers) of lower extremities (CULEs). Oxidants and AO activity were measured in eighty-five consecutive patients with CVSUs of the lower extremities as they arrived randomly for routine visits to our ambulatory clinic. Values of oxidant and AO status in patients with CULEs were significantly different from normal. No significant differences in oxidant and AO values were found between patients with arterial ulcers or those with venous ulcers. A significant difference was found in AO values of diabetic patients with chronic venous ulcers compared with non-diabetic patients with chronic venous ulcers. No significant differences were observed when evaluating oxidant/AO values and smoking habits. Precise reasons why the association of diabetes and venous (but not arterial) ulcers was correlated with defective AO status in plasma are not known. Other data were also intriguing: diminished AO activity was observed in female patients, no significant differences in oxidant and values were found between patients with arterial ulcers or those with venous ulcers, no significant correlation was found between age and oxidant, as well as no significant differences were observed when evaluating oxidant/AO values and smoking habits.
 ...
PMID:Plasma Oxidative Stress in Patients With Chronic Vascular Cutaneous Ulcers. 3062 12

Pseudohyperaldosteronism, or Liddle syndrome, is a rare, autosomal dominant condition characterized by early-onset hypertension, often associated with hypokalemia and metabolic alkalosis. Martorell hypertensive ischemic leg ulcer is a rare, underdiagnosed ulcer characterized by subcutaneous arteriolosclerosis, classically appearing over the dorsolateral lower extremity or Achilles tendon in patients with hypertension and diabetes. It presents an important diagnostic challenge because it can appear grossly similar to other entities such as pyoderma gangrenosum or venous stasis ulcers, but requires surgical intervention. This article presents a case study of surgical management of a Martorell ulcer in a 69-year-old woman with Liddle syndrome. To the authors' knowledge, this is the first case reported in the literature of this rare ulcer occurring secondary to this rare cause of hypertension.
 ...
PMID:A Novel Association of Martorell Ulcer With Liddle Syndrome. 3162 69