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Biomedical subjects

Vincent Falanga

Publications and source records attributed to Vincent Falanga.

At least 19 recordsLinked to original sources

Durometry for the assessment of skin disease in systemic sclerosis.

OBJECTIVE: To examine the validity of a durometer to objectively measure skin hardness in systemic sclerosis (SSc), and to compare digital durometry with the modified Rodnan skin score (MRSS) and ultrasonography. METHODS: Patients with SSc and healthy controls underwent durometry measurements in 3 assessments: a Latin square experiment to establish durometry's intra- and interobserver reliability compared with skin scoring (5 SSc, 1 control); a longitudinal cohort to assess sensitivity to change in skin hardness (13 SSc, 5 controls); and an ultrasound cohort to evaluate correlation between durometry, ultrasound-measured skin thickness, and clinical skin scoring (30 SSc, 12 controls). RESULTS: Intraobserver reproducibility was higher for durometry than for clinical skin scoring (intraclass correlation coefficient [ICC] 0.97 versus 0.85), whereas interobserver reproducibility was similar (0.75 versus 0.73). Interobserver reproducibility of durometry was good for all body areas (ICC 0.61-0.85), but for skin scoring it was moderate in the legs (0.51) and poor in the abdomen (0.08), feet (0.09), and fingers (0.27). Durometry scores correlated with clinical skin scores (Latin square: r = 0.44, P = 0.03; longitudinal cohort: r = 0.81, P < 0.001) and ultrasound-measured skin thickness (hands: r = 0.58, forearms: r = 0.63, upper arms: r = 0.40; P < or = 0.001 for all). Uninvolved skin in patients with SSc was harder than skin from controls (mean +/- SD 23 +/- 7 durometer units [DU] versus 19 +/- 6 DU; P < 0.0001). Finally, there was a strong correlation between change in MRSS and change in durometry score (r = 0.77, P = 0.002). CONCLUSION: Durometer-measured skin hardness correlates well with MRSS and ultrasound-measured skin thickness, provides greater reliability than MRSS, and is sensitive to changes in skin hardness over time. Durometry should be considered for use in clinical therapeutic SSc trials.

Arm↗

Wound healing and its impairment in the diabetic foot.

Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix deposition and remodelling. Cellular responses to inflammatory mediators, growth factors, and cytokines, and to mechanical forces, must be appropriate and precise. However, this orderly progression of the healing process is impaired in chronic wounds, including those due to diabetes. Several pathogenic abnormalities, ranging from disease-specific intrinsic flaws in blood supply, angiogenesis, and matrix turnover to extrinsic factors due to infection and continued trauma, contribute to failure to heal. Yet, despite these obstacles, there is increasing cause for optimism in the treatment of diabetic and other chronic wounds. Enhanced understanding and correction of pathogenic factors, combined with stricter adherence to standards of care and with technological breakthroughs in biological agents, is giving new hope to the problem of impaired healing.

Animals↗

Infectious occupational exposures in dermatology--a review of risks and prevention measures. I. For all dermatologists.

Dermatologists are at risk for exposure to infectious agents from a variety of sources throughout their workday. We review occupational infectious risks from percutaneous exposures, aerosolized infectious particles (eg, with laser surgery and dermabrasion), instrumentation, and cryotherapy. We also discuss current guidelines for management and postexposure prophylaxis of the more common occupational exposures, and conclude with an overview of means to minimize them.

Dermatology↗

Safety and efficacy of a bilayered skin construct in full-thickness surgical wounds.

This was a prospective, randomized, controlled clinical trial assessing the safety and efficacy of a living bilayered skin construct (BSC; Organogenesis, Canton, MA) in treating full-thickness surgical excision wounds. We enrolled 31 patients needing excision of a non-melanoma skin cancer. The patients consisted of 18 females and 13 males, with an average age of 67 years (range: 44 to 84 years). Patients were randomized to either receive a single application of BSC or to heal by secondary intention. Endpoints to assess efficacy included time to complete wound closure, intensity and duration of post-operative pain, cosmetic appearance, patient satisfaction, and quality of the healed wound. Endpoints to assess safety included infection at the wound site and rejection of the BSC. Findings indicate that BSC is safe in the post-operative treatment of acute surgical wounds for removal of non-melanoma skin cancer. The data also suggest that BSC may facilitate management by decreasing post-operative pain. It is unclear whether or not BSC decreases healing time of acute wounds or results in a better cosmetic outcome.

Adult↗

Contact sensitivity in patients with leg ulcerations: a North American study.

OBJECTIVES: (1) To determine the prevalence of allergen sensitivity in patients with past or present leg ulcers in 2 North American study centers vs European study findings and the North American Contact Dermatitis Group (NACDG) database and (2) to delineate a standard battery of allergens for patch testing in North American patients that is representative of the newer dressings and wound care products. DESIGN: Fifty-four patients, with or without dermatitis, were prospectively entered in the study. The patients were patch tested to the NACDG standard series and a comprehensive supplemental series of 52 allergens. SETTING: Wound healing clinics at Boston University Roger Williams Medical Center and University of Ottawa. RESULTS: Sixty-three percent (n = 34) of patients had 1 or multiple positive patch test results, and 37% (n = 20) had no positive patch test result. The most common allergens were Myroxylon pereirae (balsam of Peru) (30% [16/54]), bacitracin (24% [13/54]), fragrance mix (20% [11/54]), wood tar mix (20% [11/54]), propylene glycol (14% [7/52]), neomycin sulfate (13% [7/54]), benzalkonium chloride (13% [7/54]), carba mix (11% [6/54]), nickel sulfate (11% [6/54]), and control gel hydrocolloid (11% [6/54]). CONCLUSIONS: Comparable to European study findings, there is a high incidence of positive patch test results in patients with past or present leg ulcerations. The incidences of the most common allergens in our patient population were higher than those seen in the NACDG, except for nickel. Using a modified leg ulcer series along with the standard NACDG series is important in evaluating patients with leg ulcers.

Aged↗

Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes.

Increasing data suggest that glutamate might act as a cell-signaling molecule in non-neuronal tissues such as the skin. Here we demonstrate the presence of functional N-methyl-D-aspartate (NMDA)-type glutamate receptors in human keratinocytes. NMDA receptor expression strongly reflects the degree of cell-to-cell contact. Wounding polarizes the expression of NMDA receptors in keratinocytes involved in re-epithelialization, and the process of re-epithelialization is inhibited by NMDA receptor activation. We also demonstrate that squamous cell carcinomas lack NMDA receptors. Our data suggest that Ca2+ entry through NMDA receptors influences the cycle of keratinocyte proliferation, differentiation, and migration during epithelialization. Moreover, NMDA receptor activation might play a role in contact-mediated inhibition of growth, a process that is absent during neoplastic pathology. This receptor may serve as a pharmacological target for modulating keratinocyte behavior and treating cutaneous disorders.

Aniline Compounds↗

Protocol for the successful treatment of venous ulcers.

Venous ulcers affect up to 2.5 million patients per year in the United States. Although not usually fatal, these chronic wounds severely affect patients' quality of life because of impaired mobility and substantial loss of productivity. Although venous ulcers are typically small initially, they are often undertreated, progressing to larger ulcers that are associated with more serious complications requiring more complex treatments. In this report we detail the pathogenesis of venous ulcers together with potential complications, including exudate, erythema, cellulitis, dermatitis, pain, and possible malignancy. The clinician's regimen should always include a wide range of treatment modalities to ensure comprehensive care and effective wound closure. The treatment modalities and specific protocol for venous ulcers are discussed, and include topical dressings, antibiotics, debridement, compression therapy, and cellular therapy. These treatment modalities, in combination with early recognition and regular monitoring using digital photography and planimetry measurements, will ensure rapid healing and minimize complications and cost.

Bandages↗

Histologic progression of B16 F10 metastatic melanoma in C57BL/6 mice over a six week time period: distant metastases before local growth.

B16F10 murine metastatic melanoma in the tails of C57BL/6 mice after subcutaneous injection is a well-established model. However, the histologic progression from injected cells to established local growth of melanoma has not been studied systematically. We therefore have investigated the histologic changes and growth of B16F10 melanoma at the injection site over a six-week time period. One million B16F10 melanoma cells were injected subcutaneously into the dorsal aspect of tails of C57/BL6 mice. Mice were sacrificed at zero, 12, 24, 48, 72 and 96 hours, and at one, two, three, four, five and six weeks. Sections were stained with Hematoxylin and Eosin and immunostained with antibodies to S100. Beginning at time zero, melanoma cells were detected between the dermis and the myofascial bundle of the tail. At week four, distant metastases were clinically evident in the inguinal region, though injection site tumors did not become evident until week six. Histological analysis showed melanoma cells at the injection site at all time periods and no injection site tumor until week six. Indeed, the injection site tumors arose two weeks after distant metastases were clinically apparent. A progression of S100 positivity was also observed. S100 immunostaining was negative in all injection site of B16F10 cells until the cells underwent a morphologic change from small and monomorphic at the injection site, to large, pleomorphic cells at week six in the clinically evident injection site tumors. Inguinal metastases were also S100 positive at week four, though injection site cells were still S100 negative. We conclude that in this particular established model for melanoma, local growth at the injection site may occur after the development of regional metastases. This may prove to be a good model for investigation of local growth of tumor cells and their interaction with metastatic lesions.

Animals↗

Clinical classification of bioengineered skin use and its correlation with healing of diabetic and venous ulcers.

BACKGROUND: Chronic wounds are being treated with bioengineering skin constructs. Yet, there is no standard way of assessing these wounds. We developed a classification system to evaluate wounds after construct application. The classification system evaluates the early clinical effect of bioengineered skin and early construct appearance giving a total score named the skin substitute score. OBJECTIVE: Apply classification system to both venous and diabetic foot ulcers and determine whether classification system has validity and predictability for healing. METHODS: Evaluated serial photographs in 83 and 78 patients with diabetic foot ulcers and in 84 and 83 patients with venous ulcer on Days 7 and 14, respectively, treated with a bilayered bioengineered skin construct. Applied the classification system and determined the percentages of healed patients. RESULTS: There was a significant correlation between better skin substitute score and complete wound closure for both venous ulcers p=0.002 on Day 7 and p=0.01 on Day 14) and diabetic foot ulcers p=0.0005 on Day 7 and p<0.0001 on Day 14). CONCLUSION: Optimal clinical effect was associated with complete wound closure. As the clinical effect becomes less than optimal continued clinical persistence of the construct becomes important. This classification system seems to have validity in predicting complete wound closure in wounds treated with a bilayered bioengineered skin construct.

Adolescent↗

Treatment of chronic wounds with bone marrow-derived cells.

BACKGROUND: Recent evidence indicates that bone marrow contains stem cells with the potential for differentiation into a variety of tissues, including endothelium, liver, muscle, bone, and skin. It may thus be plausible that bone marrow-derived cells can provide progenitor and/or stem cells to wounds during healing. Our objective in this study was to establish proof of principle that bone marrow-derived cells applied to chronic wounds can lead to closure of nonhealing wounds. We applied autologous bone marrow cells to chronic wounds in 3 patients with wounds of more than 1-year duration. These patients had not previously responded to standard and advanced therapies, including bioengineered skin application and grafting with autologous skin. OBSERVATIONS: Complete closure and evidence of dermal rebuilding was observed in all patients. Findings suggesting engraftment of applied cells was observed in biopsy specimens of treated wounds. Clinical and histologic evidence of reduced scarring was also observed. CONCLUSION: Directly applied bone marrow-derived cells can lead to dermal rebuilding and closure of nonhealing chronic wounds.

Abdominal Wall↗

Participation of bone marrow derived cells in cutaneous wound healing.

Bone marrow has long been known to be a source of stem cells capable of regeneration of the hematopoeitic system. Recent reports, however, have indicated that bone marrow might also contain early stem cells that can differentiate into other organ tissues such as skin. While these studies have illustrated that bone marrow stem cells could find their way to the skin, they have not addressed the dynamics of how bone marrow stem cells might participate in the homeostatis and regeneration of skin. In this report we followed green fluorescent protein (GFP) labeled bone marrow transplanted into non-GFP mice in order to determine the participation of bone marrow stem cells in cutaneous wounds. Our results indicate that there are a significant number of bone marrow cells that traffic through both wounded and non-wounded skin. Wounding stimulated the engraftment of bone marrow cells to the skin and induced bone marrow derived cells to incorporate into and differentiate into non-hematopoietic skin structures. This report thus illustrates that bone marrow might be a valuable source of stem cells for the skin and possibly other organs. Wounding could be a stimulus for bone marrow derived stem cells to travel to organs and aid in the regeneration of damaged tissue.

Animals↗

Fibroblasts from chronic wounds show altered TGF-beta-signaling and decreased TGF-beta Type II receptor expression.

Chronic wounds are characterized by failure to heal in a defined time frame. However, the pathogenic steps leading from the etiological factors to failure to heal are unknown. Recently, increasing evidence suggests that resident cells in chronic wounds display a number of critical abnormalities, including senescence and unresponsiveness to the stimulatory action of transforming growth factor-beta1 (TGF-beta1). In this study, we have determined some of the mechanisms that might be responsible for unresponsiveness to TGF-beta1. Using Northern analysis and affinity labeling, we show that venous ulcer fibroblasts have decreased TGF-beta Type II receptor expression. This finding is not the result of genetic mutation, as shown by experiments with Type II receptor satellite instability. Decreased Type II receptor expression was accompanied by failure of ulcer fibroblasts to phosphorylate Smad 2, Smad 3, and p42/44 mitogen activating protein kinase (MAPK), and was associated with a slower proliferative rate in response to TGF-beta1. We conclude that venous ulcer fibroblasts show decreased Type II receptor expression and display abnormalities in the downstream signaling pathway involving MAPK and the early Smad pathway. These findings suggest ways to address and treat the abnormal cellular phenotype of cells in chronic wounds.

Cells, Cultured↗

Wound bed preparation: a systematic approach to wound management.

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or "stuck" at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management. This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues; the current status of wound bed preparation; an analysis of the acute and chronic wound environments; how wound healing can take place in these environments; the role of wound bed preparation in the clinic; the clinical and cellular components of the wound bed preparation concept; a detailed analysis of the components of wound bed preparation.

Cell Proliferation↗

Cutaneous concerns of scleroderma patients.

The clinical features of facial and oral involvement in scleroderma are striking. We conducted a survey of patients with systemic sclerosis (scleroderma). The purpose of our study was to ascertain what was most bothersome aesthetically to scleroderma patients. We also looked at the differences between age groups and genders. The survey was mailed to 1,000 individuals who subscribe to a national lay group organization. We received 303 completed surveys indicating the patient's age, gender, age at onset of disease, and a checklist of 14 physical variables involving the central face and non-face. The respondents were asked to rate their level of concern [on a scale of great (1) -moderate (2) -little (3) -none (4)] in regards to 14 different physical variables. The respondents consisted of 92% females and 8% males. The mean age was 59 years +/- 13 (SD), and the median age was 60. The mean and median age at diagnosis was 45 years +/- 15 (SD). The percentage of respondents expressing concern for specific features was the following: for thin lips (73%), mouth furrows (80%), loss of facial lines (68%), and a smaller, tighter mouth (77%). There was less concern over the non-face features. The percentage of respondents expressing no concern was the following: for absence of sweating (57%), skin darkening (50%), nail dystrophy (57%), and skin atrophy (63%). There was a highly statistically significant difference (p<0.0001) between those respondents concerned with central face features vs. non-face features. With advancing age and longer disease duration, there was increased concern over the aforementioned central face features (p<0.0001). The vast majority of patients with systemic sclerosis have great concerns over changing facial features, and this worsens with age.

Aged↗

Growth factors, signal transduction, and cellular responses.

The extraordinary advances in the field of growth factors and signal transduction have created new and promising therapeutic interventions. We intend to explain the difficult nomenclatures associated with growth factors and their mechanisms of action.

Growth Substances↗