Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72172/1/j.1524-475X.1999.00141.x.pd

Comparison of different bronchial closure techniques following pneumonectomy in dogs

The comparison of the histologic healing and bronchopleural fistula (BPF) complications encountered with three different BS closure techniques (manual suture, stapler and manual suture plus tissue flab) after pneumonectomy in dogs was investigated for a one-month period. The dogs were separated into two groups: group I (GI) (n = 9) and group II (GII) (n = 9). Right and left pneumonectomies were performed on the animals in GI and GII, respectively. Each group was further divided into three subgroups according to BS closure technique: subgroup I (SGI) (n = 3), manual suture; subgroup II (SGII) (n = 3), stapler; and subgroup III (SGIII) (n = 3), manual suture plus tissue flab. The dogs were sacrificed after one month of observation, and the bronchial stumps were removed for histological examination. The complications observed during a one-month period following pneumonectomy in nine dogs (n = 9) were: BPF (n = 5), peri-operative cardiac arrest (n = 1), post-operative respiratory arrest (n = 1), post-operative cardiac failure (n = 1) and cardio-pulmonary failure (n = 1). Histological healing was classified as complete or incomplete healing. Histological healing and BPF complications in the subgroups were analyzed statistically. There was no significant difference in histological healing between SGI and SGIII (p = 1.00; p > 0.05), nor between SGII and SGIII (p = 1.00; p > 0.05). Similarly, no significant difference was observed between the subgroups in terms of BPF (p = 0.945; p > 0.05). The results of the statistical analysis indicated that manual suture, stapler or manual suture plus tissue flab could be alternative methods for BS closure following pneumonectomy in dogs

Syndesome therapeutics for enhancing diabetic wound healing

Chronic wounds represent a major healthcare and economic problem worldwide. Advanced wound dressings that incorporate bioactive compounds have great potential for improving outcomes in patients with chronic wounds but significant challenges in designing treatments that are effective in long-standing, non-healing wounds. Here, we developed an optimized wound healing gel that delivers syndecan-4 proteoliposomes (“syndesomes”) with FGF-2 to enhance diabetic wound healing. In vitro studies demonstrated that syndesomes markedly increased migration of keratinocytes and fibroblasts isolated from both non-diabetic and diabetic donors. In addition, syndesome treatment led to increased endocytic processing of FGF-2 that included enhanced recycling of FGF-2 to the cell surface after uptake. The optimized syndesome formulation was incorporated into an alginate wound dressing and tested in a splinted wound model in diabetic, ob/ob mice. We found that wounds treated with syndesomes and FGF-2 had markedly enhanced wound closure in comparison to wounds treated with only FGF-2. Moreover, we show that syndesomes have an immunomodulatory effect on wound macrophages, leading to a shift towards the M2 macrophage phenotype and alterations in the wound cytokine profile. Together, these studies showed that delivery of exogenous syndecan-4 is an effective method for enhancing wound healing in the long-term diabetic diseased state

Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial

Background: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats. Objective: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway. Research Design and Methods: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing. Results and Conclusions: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1 alpha in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes.Sao Paulo Research Foundation (FAPESP)Sao Paulo Research Foundation (FAPESP)National Institute of Science and Technology (INCT)National Institute of Science and Technology (INCT)National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development (CNPq

Skin perfusion pressure measurement is valuable in the diagnosis of critical limb ischemia

AbstractPurpose: Critical limb ischemia (CLI) is equated with a need for limb salvage. Arterial reconstruction and major amputation are the therapies ultimately available to such patients. We studied whether measurements of skin perfusion pressure (SPP) can be used to accurately identify those patients with CLI who require vascular reconstruction or major amputation and distinguish them from patients whose foot ulcer would heal with local wound care or minor amputation.Methods: Fifty-three patients with a total of 61 limbs with a nonhealing foot ulcer (age range, 47 to 88 years; mean, 70.8 ± 9.8 years; 33 men, 20 women) who were referred to the Vascular Laboratory at Morristown Memorial Hospital for evaluation of arterial insufficiency were studied in a prospective, double-blinded fashion. Patients were included in the study if informed consent was obtained, and patients were excluded if there was uncontrolled sepsis or if they required guillotine amputation. The size and site of the foot ulcer was recorded. If gangrene was present, the location and extent was also noted. The pulses were examined and recorded, and the ankle-brachial index was determined for each limb. Measurements of SPP were made at the proximal margin of the ulcer in viable tissue (not in the bed of the ulcer). SPP measurements were made independent of the vascular surgeon's evaluation of the limb and were not part of his clinical decision regarding management of the foot ulcer. The SPP measurements were compared (Fisher's exact test) with the clinical decision for therapy (group I, arterial reconstruction or major amputation; or group II, wound debridement, minor amputation, or both). SPP was also compared with the outcome (ulcer healed or failed to heal) of therapy in group II. From contingency tables we calculated the sensitivity, specificity, positive and negative predictive values (PPV, NPV), and the overall accuracy of SPP measurement as a diagnostic test for critical limb ischemia.Results: There was no difference in the size or location of foot ulcers between groups I and II, nor was there a difference in ulcer size or location between limbs that healed and did not heal in group II. The prevalence of diabetes was similar in all groups and subgroups. The ABI was not predictive of the need for reconstruction or major amputation nor the outcome of local therapy. SPP measurements identified 31 of 32 limbs diagnosed as having CLI by clinical evaluation (i.e., group I, those limbs that required vascular reconstruction or major amputation). Of those patients who were clinically assessed as not having CLI (group II), SPP measurements diagnosed 12 of the 14 limbs that did not heal as having CLI (PPV, 75%) and 11 of 15 limbs that did heal as not having CLI (NPV, 85%). The sensitivity of SPP less than 30 mm Hg as a diagnostic test of CLI was 85%, and the specificity was 73%. The overall diagnostic accuracy of SPP less than 30 mm Hg as a diagnostic test of critical limb ischemia was 79.3% (p < 0.002, Fisher's exact test).Conclusions: We conclude that SPP measurement is an objective, noninvasive method that can be used to diagnose critical limb ischemia with approximately 80% accuracy. (J Vasc Surg 1997;26:629-37.