Francis Ko

Comparative evaluation of silver-containing antimicrobial dressings and drugs

Wound dressings containing silver as antimicrobial agents are available in various forms and formulations; however, little is understood concerning their comparative efficacy as antimicrobial agents. Eight commercially available silver‐containing dressings, Acticoat® 7, Acticoat® Moisture Control, Acticoat® Absorbent, Silvercel™, Aquacel® Ag, Contreet® F, Urgotol® SSD and Actisorb®, were tested to determine their comparative antimicrobial effectiveness in vitro and compared against three commercially available topical antimicrobial creams, a non treatment control, and a topical silver‐containing antimicrobial gel, Silvasorb®. Zone of inhibition and quantitative testing was performed by standard methods using Escherichia coli, Pseudomonas aeruginosa, Streptococcus faecalis and Staphylococcus aureus. Results showed all silver dressings and topical antimicrobials displayed antimicrobial activity. Silver‐containing dressings with the highest concentrations of silver exhibited the strongest bacterial inhibitive properties. Concreet® F and the Acticoat® dressings tended to have greater antimicrobial activity than did the others. Topical antimicrobial creams, including silver sulfadiazine, Sulfamylon and gentamicin sulfate, and the topical antimicrobial gel Silvasorb® exhibited superior bacterial inhibition and bactericidal properties, essentially eliminating all bacterial growth at 24 hours. Silver‐containing dressings are likely to provide a barrier to and treatment for infection; however, their bactericidal and bacteriostatic properties are inferior to commonly used topical antimicrobial agents.

Comparison of Silver Sulfadiazine, Povidone‐Iodine and Physiologic Saline in the Treatment of Chronic Pressure Ulcers

ABSTRACT: The presence of bacteria and local infection is an important factor in the local management of chronic pressure ulcers. For successful closure of the ulcer, the bacterial count should be 105 or less per gram of tissue in the granulating wound. In a prospective randomized study of 45 (eventually 40) hospitalized patients, silver sulfadiazine (Silvadene) cream and povidone‐iodine (Betadine) solution were compared to physiologic saline for effectiveness in preparing pressure ulcers for closure. Quantitative bacteriologic techniques on tissue biopsy specimens were used for objective evaluation. In 100 percent of the ulcers treated with silver sulfadiazine cream (15 patients) the bacterial counts were reduced to 105 or less per gram of tissue within the three‐week test period, compared to 78.6 percent in those treated with saline (14 patients) and 63.6 percent in those treated with povidone‐iodine solution (11 patients). Moreover, the ulcers treated with silver sulfadiazine cream responded more rapidly, with one‐third showing bacterial levels of <105 within three days, and half within a week.

Sequential Cytokine Therapy for Pressure Ulcers: Clinical and Mechanistic Response

OBJECTIVE To compare the healing response of sequential topically applied cytokines to that of each cytokine alone and to a placebo in pressure ulcers, and to evaluate the molecular and cellular responses. SUMMARY BACKGROUND DATA Because of a deficiency of cytokine growth factors in chronic wounds and the reversal of impaired healing in animal models, pressure ulcer trials have been performed with several exogenously applied growth factors. Because single-factor therapy has not been uniformly successful, combination or sequential cytokine therapy has been proposed. Laboratory data have suggested that sequential treatment with granulocyte-macrophage/colony-stimulating factor (GM-CSF)/basic fibroblast growth factor (bFGF) might augment the previously reported effect of bFGF alone. METHODS A masked, randomized pressure ulcer trial was performed comparing sequential GM-CSF/bFGF therapy with that of each cytokine alone and with placebo during a 35-day period. The primary measure was wound volume decrease over time. Cytokine wound levels and mRNA levels were serially determined. Fibroblast-populated collagen lattices (FPCLs) were constructed from serial fibroblast biopsies. Cellular ultrastructure was evaluated by electron microscopy. Changes in ease of surgical closure and its relative cost were determined. RESULTS Ulcers treated with cytokines had greater closure than those in placebo-treated patients. Patients treated with bFGF alone did the best, followed by the GM-CSF/bFGF group. Patients treated with GM-CSF or bFGF had higher levels of their respective cytokine after treatment. Patients with the greatest amount of healing showed higher levels of platelet-derived growth factor (PDGF) on day 10 and transforming growth factor beta (TGFbeta1) on day 36. Message for the bFGF gene was upregulated after treatment with exogenous bFGF, suggesting autoinduction of the cytokine. FPCLs did not mimic the wound responses. Ultrastructure of wound biopsies showed response to bFGF. Treatment with any of the cytokines improved the wound by allowing easier wound closure. This was most marked for the bFGF-alone treatment, with a cost savings of

Evaluation of burn blister fluid.

9,000 to

Periprosthetic breast capsules contain the fibrogenic cytokines TGF-β1 and TGF-β2, suggesting possible new treatment approaches

9,200. CONCLUSIONS Treatment with bFGF resulted in significantly greater healing than the other treatments in this trial. The clinical response appeared to be related to upregulation of the bFGF message and to increased levels of PDGF-AB, bFGF, and TGFbeta1 in the wounds and changes in ultrastructure. The resultant improvements could be correlated with cost savings.

Pseudomonas aeruginosa exotoxin A: its role in retardation of wound healing: the 1992 Lindberg Award.

Although edema is evident immediately after a burn, the diffusion of nutrient chemical constituents of the body is not impaired. Blister fluid, not unlike plasma or serum, contained all substances found in the body, including parenterally administered penicillin. The elevation of potassium and the cation to anion imbalance is primarily due to the Na/K cellular pump malfunction, and the destruction of the permeability of the cell membrane is most likely a direct result of complement and other cellular enzymes, which include the prostaglandins and thromboxanes. The elevated SGOT, CPK, and LDH indicated severe trauma to the cells in the immediate area of burn and possibly to the skeletal muscle. The presence of immunoglobulins indicated that high-molecular-weight proteins diffuse equally well during this edematous phase (IgM, 900,000; IgG, 190,000). Evidence of this nature strongly suggests that the integrity of the burn blister by maintained.

Further evidence for the role of fibrosis in the pathobiology of rhinophyma.

Periprosthetic breast capsules composed of fibrotic collagenous material with increased collagen production are not dissimilar to other fibrotic conditions occurring in other organs. Fibrosis in the lung, liver, kidney, and skin has been associated with overproduction of the fibrogenic isoforms of t

Down-regulating causes of fibrosis with tamoxifen: a possible cellular/molecular approach to treat rhinophyma.

Bacterial concentrations greater than 10(5) colony-forming units/gm of tissue prevent wound healing. However, it has not been determined whether it is the number of bacteria or a toxin produced by these organisms that impedes the wound healing process. Pseudomonas aeruginosa (PSAR), a burn wound pathogen, produces a dermonecrotic toxin, exotoxin A. Studies have indicated a role for exotoxin A in the pathogenicity of PSAR. We investigated the role of exotoxin A in the retardation of contraction. Acute granulating wounds were created on 90 Sprague-Dawley rats. The animals were equally divided into six groups and were treated topically as follows: group 1, sham: no infection, no treatment; group 2, exotoxin A; group 3, exotoxin A and antiexotoxin; group 4, autoclaved PSAR 10(6); group 5, 10(6) viable PSAR inoculated in the wound; group 6, 10(6) viable PSAR and antiexotoxin. Wound contraction was measured with the use of planimetry twice a week. Serial biopsies were performed on all wounds. Contraction rates revealed significantly (p < 0.05) retarded closure in the animals treated with exotoxin A and in the viable PSAR group when compared with the rates of the noninfected control groups. Animals treated with exotoxin A plus antiexotoxin A and those treated with live PSAR and antiexotoxin showed contraction rates identical to the control groups. These data suggest that exotoxin A in PSAR infections retards wound healing and that neutralization of the toxin restores the normal healing process.

Amnion-derived cellular cytokine solution (ACCS) promotes migration of keratinocytes and fibroblasts.

Recent evidence suggests that fibrosis may play an important role in the pathobiology of rhinophyma. The fibrogenic cytokine transforming growth factor (TGF)-&bgr;2 has been reported to be up-regulated in rhinophyma tissue. Of the three common isoforms of TGF-&bgr;, TGF-&bgr;1 and TGF-&bgr;2 are considered fibrogenic, whereas TGF-&bgr;3 has antiscarring properties. To provide further evidence for the role of fibrosis in the pathobiology of rhinophyma, specimens from 8 patients with rhinophyma were compared with nine specimens of normal nasal skin. Immunohistochemistry was used to compare intensity levels of TGF&bgr;1 and TGF&bgr;3 proteins, and quantitative reverse transcription–polymerase chain reaction was used to determine messenger ribonucleic acid (mRNA) expression levels of TGF&bgr;1 and TGF&bgr;3. TGF-&bgr;1 was elevated significantly in rhinophyma tissue (p < 0.001), whereas TGF-&bgr;3 was no different in the rhinophyma specimens compared with normal nasal skin (p = 0.06). TGF&bgr;1 mRNA expression was five-fold higher in rhinophyma tissue compared with normal skin (p < 0.001). The mRNA expression of TGF-&bgr;3 was the same for both pathological and normal tissue (p < 0.09). These data, together with previously published observations, present further evidence that fibrosis mediated by the fibrogenic cytokines TGF&bgr;1 and TGF&bgr;2 play a role in the pathobiology of rhinophyma and suggest a means of treatment by neutralizing or down-regulating these cytokines.

Toxic effects of capsaicin on keratinocytes and fibroblasts.

Fibrosis and proliferative scarring are prominent features of the severe forms of rhinophyma. Up-regulation of growth and fibroblast kinetics are hallmarks of fibrosis. Persistent overexpression or dysregulated activation of the fibrogenic isoforms of transforming growth factor β (TGF-β) is associated with the increased fibroblast function leading to fibrotic conditions such as rhinophyma. Tamoxifen, a synthetic nonsteroidal antiestrogen, can neutralize or down-regulate TGF-β. Fibroblast-populated collagen lattices (FPCLs) were constructed from fibroblasts cultured from rhinophyma or normal nasal skin. One-half of each set of FPCLs was treated with Tamoxifen. Lattice contraction was serially measured over 5 days, and the supernatants of the cultures were analyzed for TGF-β-2 by immunoassay. Tamoxifen significantly decreased fibroblast activity by decreasing contraction of the treated lattices (P < 0.05) and significantly decreased the production/secretion of TGF-β-2 by rhinophyma fibroblasts (P < 0.001). These results suggest a possible new cellular/molecular approach to the treatment of the fibrotic varieties of rhinophyma.