Paul D. Smith

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

URBAN ACTIVITY SPACES: ILLUSTRATIONS AND APPLICATION OF A CONCEPTUAL MODEL FOR INTEGRATING THE TIME AND SPACE DIMENSIONS

9,000 to

Maintenance of wound bacterial balance

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.

Neck rejuvenation revisited.

This work extends the conceptual argument for the use of ellipses to portray activity spaces and offers one example of how the ellipse construct can be used to analyze urban travel characteristics, based on observed trip making behavior and socio-economic variables. A problem in characterizing activity spaces has been in integrating the time and space dimensions into the same analytical framework while maintaining an understandable graphical representation of the space-time geographies envisioned by Hagerstrand and others. The ellipse allows this, as well as providing several quantifiable measures to be used for analyzing and characterizing activity spaces and urban travel behavior. In the current application, analysis of variance is used to analyze the resulting elliptic variables of 653 travelers. The results indicate that home location and household size are important factors in determining activity space characteristics and that the ellipse variables provide a different and useful approach for understanding urban travel behavior.

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

BACKGROUND There is a critical number of bacteria above which tissue responds with infection. This balance of 10(5) or fewer bacteria/g tissue is also required for wound healing to proceed normally. This study evaluated whether a chronic wound once in bacterial balance can maintain that balance over time. METHODS Serial biopsies for bacterial analyses were obtained weekly during a blinded, placebo-controlled cytokine clinical trial of pressure ulcers. To enter the trial ulcers had to be debrided and have a bacterial count of 10(5) or fewer bacteria/g tissue with no beta-hemolytic streptococci. RESULTS In all, 96% of cultures (350/363) remained at <10(2) bacteria/g tissue over the 5-week trial; 3% had 10(2) to 10(5), and only 1% had >10(5) bacteria/g tissue. CONCLUSION Chronic pressure ulcers, once debrided and brought into bacterial balance, will remain in bacterial balance if cared for and kept free of necrotic tissue.

Secretory state of gastric mucosa and resistance to injury by exogenous acid

Purpose: Restoration of the aesthetic neck contour is an integral component of facial rejuvenation. Multiple deformities of the neck and chin complex can make treatment of the cervical region daunting. An algorithmic approach to neck rejuvenation based on individual anatomic and clinical analysis is prudent. The authors created a simplified anatomic approach to the most common cervical deformities encountered in the patient seeking facial rejuvenation. Methods: Retrospective analysis of the senior authors (R.J.R.) technique evolution over the last 15 years was performed. The operative techniques used in neck rejuvenation were evaluated and the long-term postoperative results were reviewed. Results: Recurrent patterns of cervical deformity are present in patients presenting for facial rejuvenation. These patterns can be classified into categories based on specific anatomic deformities. Conclusions: Facial rejuvenation requires appropriate identification of deformity to effect the desired changes. Cervical deformities are classified into clinically useful categories based on careful preoperative analysis. A thorough understanding of the anatomic bases for the deformities allows the surgeon to choose the appropriate treatments to achieve consistent and reliable results.

Benign symmetric lipomatosis (Madelung's disease).

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

In vivo characterization of keratinocyte growth factor-2 as a potential wound healing agent.

The capacity of the stomach to resist the effects of highly acid solutions was assessed by comparing the effects of such solutions on spontaneously secreting, stimulated, and inhibited gastric mucosae of rabbits in vivo and frogs in vitro. Exposure of unstimulated resting mucosa to HC1, 120 mM, for 60 minutes produced superficial erosions in all rabbits, whereas such lesions were observed in only one of ten animals stimulated with histamine. Metiamide obviated the protective effect of histamine against ulcerations even though it did not reduce H+ secretion to zero. Exposure of inhibited isolated frog fundic mucosa to HC1 resulted in significant deterioration of electrical parameters, suggesting impairment of active transport processes and increased tissue permeability. These data are consistent with the hypothesis that actively secreting gastric mucosae from two species resist injury to exogenous acid more effectively than do resting or inhibited tissues, perhaps in part as a result of a greater alkaline tide.

Differentiating fat necrosis from recurrent malignancy in fat-grafted breasts: an imaging classification system to guide management.

Benign symmetric lipomatosis, also known as Madelungs disease, is a rare condition characterized by massive fatty deposits arranged symmetrically around the neck, shoulders, and arms. These patients might present for liposuction and body contouring. Although infrequently encountered in the average plastic surgeons practice, this condition should be considered when evaluating candidates for these procedures. The deformity is associated with chronic alcohol use and also with malignant tumors of the upper airways. The deformity is prone to recurrence and its surgical treatment often results in less than optimal aesthetic outcomes. Despite this fact, surgical removal via either direct excision or suction-assisted lipectomy provides the only real hope of palliation. This report describes a patient with this deformity and a review of the literature.

Toxic effects of capsaicin on keratinocytes and fibroblasts.

Human keratinocyte growth factor‐2 exerts a proliferative effect on epithelial cells and mediates keratinocyte migration. It has also been shown to increase both deposition of granulation tissue and collagen and maturation of collagen. Because these properties should affect the healing trajectory of wounds, this study set out to investigate the effects of keratinocyte growth factor‐2 on the healing of three different types of wounds. Human meshed skin grafts explanted to athymic “nude” rats, surgical incisions in Sprague‐Dawley rats, and acute excisional rat wounds inoculated with Escherichia coli were used. Two concentrations of recombinant human keratinocyte growth factor‐2 were compared to a vehicle control and keratinocyte growth factor‐1. Keratinocyte growth factor‐2 significantly accelerated the rate of epithelialization in the meshed skin graft model and effected a modestly more rapid gain in breaking strength of surgical incisions than keratinocyte growth factor‐1 or the vehicle control treatment. Neither keratinocyte growth factors accelerated wound closure by contraction of the excisional wounds. Based on these data, keratinocyte growth factor‐2 may be useful in accelerating healing in wounds healing mainly by the process of epithelialization such as venous stasis ulcers, partial thickness burn wounds, and skin graft donor sites. It might also accelerate the gain in incisional wound strength in acute surgical or traumatic wounds.