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Biomedical subjects

V Falanga

Publications and source records attributed to V Falanga.

At least 91 records · Page 5Linked to original sources
PubMed1993

Solitary fibrosing paraspinal plaque: solitary morphoea profunda?

Solitary morphoea profunda is a recently described morphological variant of localized scleroderma. Two of the five reported patients had a solitary fibrotic plaque in the paraspinal region. We report a 16-year-old boy with a solitary fibrotic paraspinal plaque which, on histological examination, showed dermal and subcutaneous sclerosis, with a polymorphous infiltrate including plasma cells and eosinophils. Laboratory tests were either negative or normal, except for mild peripheral blood eosinophilia. Antinuclear antibodies were not detected, and the patient had no evidence of Borrelia infection. Magnetic resonance imaging (MRI) showed that the process involved the subcutaneous tissue, but did not extend to the underlying bone. As half of the patients with this entity (three of six) now described have had a solitary fibrotic plaque in a paraspinal location, we suggest that it may be premature to classify all these cases as being a variant of morphoea. We propose the use of the descriptive term solitary fibrosing paraspinal plaque, until the aetiology or aetiologies of this condition are better understood.

Adolescent↗
PubMed1993

Growth factors and wound healing.

BACKGROUND: Over the last decade, there has been an exponential increase in our knowledge of the biology of growth factors. The hope has been and remains that these potent biologic agents will effect a fundamental improvement in the way we treat wounds. OBJECTIVE: We will discuss the biology of growth factors and the dramatic effects these proteins have on cell proliferation, cell chemotaxis, and on the formation of extracellular matrix molecules. RESULTS: Growth factors are extremely potent biologic agents that show promise in accelerating wound repair in both animal and human studies. They improve granulation tissue, enhance tensile strength, and promote reepithelialization. Cosmetic effects are also to be expected by antagonizing and blocking the action of these peptides. CONCLUSION: Growth factors are likely to become an important therapeutic tool for the dermatologic surgeon.

Animals↗
PubMed1993

Venous ulceration.

BACKGROUND: In the last few years, interest in the pathogenesis and treatment of venous ulceration has been rekindled by novel observations in fibrinolysis and an explosive growth in wound care products, respectively. OBJECTIVE: The purpose of this work is to summarize the salient clinical features of venous ulceration, its proposed pathogenesis, and conventional as well as future treatment modalities. RESULT: Venous ulceration is an increasingly common condition. Its pathogenesis is related to failure of the calf muscle pump, and treatment is directed at effective leg compression, avoidance of contact dermatitis, and proper wound care. CONCLUSION: There is increased interest in both the pathogenic steps involved in venous ulceration and in treatment modalities. We suspect that incremental progress will occur in these areas in the next few years.

Humans↗
PubMed1993

Techniques of split-thickness skin grafting for lower extremity ulcerations.

OBJECTIVE: To discuss the role of skin grafts in the functional repair of lower extremity ulcerations. METHODS: The indications, types of skin grafts, and the methods of harvesting grafts are described. RESULTS: Detailed description of our method of bedside split-thickness skin grafting with both pinch and mesh grafts in hospitalized patients is given. We also discuss post-operative care and complications seen with skin grafting. CONCLUSION: Split-thickness skin grafting offers an important therapeutic option in the treatment of lower extremity ulcerations.

Humans↗
PubMed1993

Basal cell carcinoma arising in venous ulcers and mimicking granulation tissue.

BACKGROUND: Basal cell carcinoma (BCC) arising in venous ulcers is rare, and its appearance in this setting is not fully recognized. OBJECTIVE: The purpose of this report is to alert the clinician to the subtle clinical appearance of this tumor and to prompt a more rapid recognition. METHODS: We report five cases of BCC arising in venous ulcers of the lower extremity that we have observed over a period of 6 years. In all cases the tumor was diagnosed histologically. RESULTS: In all five cases the tumor had the appearance of seemingly healthy granulation tissue, which was often exuberant and translucent. The border of this apparent "granulation tissue" was rolled over the margins of the ulcer. CONCLUSION: Basal cell carcinoma arising in venous ulcers often has the appearance of translucent granulation tissue that extends beyond the ulcer's margins. These clinical characteristics should alert the clinician to the need for obtaining a biopsy of the ulcer bed.

Aged↗
PubMed1993

Growth factors and wound healing.

If one looks at the development of most drugs, it becomes evident that an extended period of time is necessary before the proper use and full range of activities of the drug in treating human disease become apparent. In many cases, initial treatment failures are due to faulty expectations as well as inadequate dosing and delivery systems. It is my opinion that growth factor therapy will follow a similar course but that it ultimately will have a role in the modulation of wound repair.

Animals↗
PubMed1993

The biology of skin grafts. Skin grafts as pharmacologic agents.

BACKGROUND: Skin grafting is commonly used to treat nonhealing wounds. However, how skin grafts help to heal wounds is not entirely known. Why epithelium from grafted skin is able to migrate and cover these wounds, while epithelium at the edge of nonhealing wounds is unable to, is a long unanswered biologic question. OBSERVATIONS: The recent use of cultured epithelial allografts has rekindled interest in the biology of skin grafts. Replaced, even in chronic wounds, by recipient epithelium, cultured epithelial allografts appear to work by providing a potent stimulus to healing imparted by the graft itself. Based on this, we have reassessed how skin autografts help to heal wounds and hypothesize that, in a similar fashion, autografts may work not only by replacing tissue but also by providing a stimulus for healing. CONCLUSIONS: We suggest that skin grafts may work not only as tissue replacement but as pharmacologic agents that provide a stimulus for healing. We believe that, someday, it may be possible to augment the stimulatory properties of donor skin to speed healing of the recipient wound.

Culture Techniques↗
PubMed1992

The effects of endothelin-1 on human dermal fibroblast growth and synthetic activity.

Endothelin-1 (ET-1) is the most potent vasoconstricting substance known, and is believed to have a fundamental role in the regulation of blood flow. It is a peptide produced and secreted by endothelial cells in response to hypoxia and injury, as well as by macrophages. These properties suggest that ET-1 may play a role during tissue repair. In this study, we have examined the effects of ET-1 on the growth and synthetic activity of human dermal fibroblasts. ET-1 stimulated DNA synthesis in serum-deprived cultures: this effect reached a mean value of 64% more than control (P < 0.01) at 2.5 ng/ml (10(-9) M) of ET-1. In contrast, the addition of ET-1 to fibroblasts at different densities and in 0, 3, or 10% fetal bovine serum (FBS) failed to increase cell counts. In 1% FBS, a 41% mean increase in cell counts compared to control values was observed in cultures treated with 2.5 ng/ml of ET-1 (P < 0.01). Incubation of dermal fibroblast cultures at 37 degrees C for 1 hr with increasing concentrations of 125I-ET-1 resulted in saturable binding and a half-maximal specific binding of 27.5 pM. Scatchard plot analysis of the binding showed a Kd of 224 pM and 11,400 high-affinity binding sites per cell. ET-1 had no effect on [14C]-glucosamine incorporation by fibroblasts and caused no increase in collagen synthesis, as measured by collagenase-sensitive [3H]proline incorporation and by salt precipitation of 3H-labeled collagen at acid and neutral pH successively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1992

Features of an autoimmune process in mid-dermal elastolysis.

Mid-dermal elastolysis is a rare disorder that is manifested clinically by wrinkling and histologically by the selective absence of elastic fibers in the mid dermis. We describe a young woman who developed abnormal wrinkling after augmentation mammoplasty with silicone implants. Histologic examination confirmed the diagnosis of mid-dermal elastolysis. In addition, a positive antinuclear antibody titer and a false-positive Lyme titer were subsequently detected. In a previously reported case a patient who had mid-dermal elastolysis also had an unusual false-positive pattern for Lyme disease. Silicone mammoplasty has been associated with connective tissue diseases. This report adds mid-dermal elastolysis to the list of diseases associated with augmentation mammoplasty and, along with the presence of autoantibodies, supports autoimmune involvement in mid-dermal elastolysis.

Adult↗
PubMed1992

Skin distribution and differential expression of transforming growth factor beta 1 and beta 2.

Transforming growth factor beta (TGF-beta) 1 and 2 have both become increasingly important in cutaneous biology, but their expression and distribution in human skin are not entirely clear. In this report, normal forearm skin from four volunteers was investigated for TGF-beta 1 and beta 2 immunostaining with antibodies that detect preferentially either cell- or matrix-associated forms of these peptides. Marked cell-associated TGF-beta 1 was found in the dermis, particularly around blood vessels and ducts; cellular TGF-beta 2 immunostaining was less prominent, and was predominantly around blood vessels. Neither TGF-beta 1 nor -beta 2 could be detected in the epidermis or epithelial structures, and the dermal matrix contained minimally detectable amounts of the two isoforms. In all cases, dermal matrix and cells contained greater amounts of TGF-beta 1 than TGF-beta 2. Previous studies have shown that both TGF-beta 1 and -beta 2 can induce dramatic increases in extracellular matrix, and both peptides have been implicated in the pathogenesis of fibrosis. We therefore investigated TGF-beta 1 and -beta 2 immunostaining in involved forearm skin of four patients with systemic sclerosis. Compared to normal skin, fibrotic specimens showed increased amounts of matrix and epidermal TGF-beta 1, but not TGF-beta 2. We conclude that TGF-beta 1 and -beta 2 expression in human skin is differentially regulated, and that their distribution is varied and complex.

Adult↗
PubMed1992

Transforming growth factor-beta differentially regulates the adhesiveness of normal and psoriatic dermal microvascular endothelial cells for peripheral blood mononuclear cells.

Lymphocytes adhere to dermal microvascular endothelial cells (DMEC) as the first step in their migration from the bloodstream into diseased skin. Psoriasis is characterized by an intense T-lymphocytic infiltrate in the dermis, which may be a consequence of the abnormal regulation of endothelial adhesiveness by cytokines released locally. In the present study, we investigated the effects of tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), IL-4, and transforming growth factor-beta 1 (TGF-beta) on the adhesiveness of DMEC isolated from psoriatic plaques or normal skin for human peripheral blood mononuclear cells (PBMC). The results showed that DMEC from both normal and psoriatic skin retain the capacity to adhere to 51Cr-labeled PBMC. Pretreatment of DMEC from normal skin with human recombinant IL-1 or TNF alone or in combination for 8 h significantly (p less than 0.01) enhanced their capacity to adhere to human PBMC. Similarly, treatment of normal DMEC with IL-4 also increased endothelial adhesiveness, although this cytokine required an incubation period of 24 h. In parallel studies, DMEC from psoriatic plaques were found to respond to the stimulatory effects of TNF, IL-1, and IL-4 in similar dose- and time-dependent manner. In contrast, although pretreatment of normal DMEC with TGF-beta (0.1 to 0.25 ng/ml) for 6 to 12 h significantly reduced (p less than 0.01) both the unstimulated and IL-1- and TNF-stimulated endothelial adhesiveness for normal PBMC, TGF-beta had no effect on the binding of unstimulated or cytokine-stimulated psoriatic DMEC to PBMC, even at concentrations as high as 2 ng/ml and incubation period of 36 h. These results suggest that cytokines stimulate the adhesiveness of DMEC through distinct pathways and provide evidence that TGF-beta may play an important regulatory role in the control of lymphocyte extravasation into normal skin. The altered responsiveness of psoriatic DMEC to TGF-beta may contribute to the intense dermal lymphocytic infiltrates in psoriasis.

Cell Adhesion↗
PubMed1992

Growth factors and chronic wounds: the need to understand the microenvironment.

The care of chronic wounds has become a major health issue in developed countries because of their increasingly elderly populations. There is hope that progress made in understanding and producing growth factors will lead to their successful use to induce faster and better healing of chronic wounds. This report will discuss growth factors in the context of their use in chronic wounds, and will focus on the importance of the wound microenvironment in determining the interactions between growth factors and wounds. We believe that a greater understanding of the chronic wound microenvironment will be of benefit in the optimal use of growth factors. In published studies, we have found that wound fluid taken from acute wounds stimulates fibroblast and endothelial cell proliferation, whereas fluid obtained from chronic non-healing wounds inhibits the growth of fibroblasts, endothelial cells, and keratinocytes. In this report, we describe the effect of these two types of wound fluid on the synthesis of extracellular matrix components. We hypothesize that the chronic wound microenvironment is generally non-conducive to cell growth, and that this may prevent a truly successful use of topical growth factors in chronic wounds. Novel approaches in the delivery of growth factors to wounds may be necessary to overcome these obstacles.

Cells, Cultured↗
PubMed1992

Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers.

A great deal of interest has been focused recently on the potential use of synthetic polypeptide growth factors to stimulate healing of chronic wounds. In this pilot double-blind randomized study conducted at a single center, we used human recombinant epidermal growth factor (h-EGF) to treat 44 patients with venous ulceration of the lower extremities. An aqueous solution (10 micrograms/mL) of h-EGF was applied topically to the ulcers twice a day until healing occurred or for a maximum of 10 weeks. Patients were evaluated weekly for measurements of ulcer size and for the formation of granulation tissue suitable for grafting. Nine patients were excluded from efficacy evaluation because of protocol violations. Therefore, 35 patients (17 h-EGF, 18 placebo) were evaluable for efficacy, and 44 patients (22 h-EGF, 22 placebo) were available for safety. The median baseline ulcer size for all patients was 18.5 cm2, and was not significantly different between h-EGF and placebo group (12.9 cm2 versus 19.2 cm2, respectively, P = .27). By study end, six (35%) of h-EGF treated patients and two (11%) in the placebo group had healed completely (P = .10). Another 6 patients (2 of 17 h-EGF, 4 of 18 placebo; P = .50) developed healthy granulation tissue that was suitable for grafting. The median ulcer size reduction was 7% for h-EGF versus 3% for placebo per week (P = .29), and 73% versus 33% at study end (P = .32). No untoward side effects were related to the application of h-EGF. We conclude that topical application of h-EGF, in the dose and manner used in this study, was safe but failed to significantly enhance re-epithelialization of venous ulcers. However, a greater reduction in ulcer size and a larger number of healed ulcers with the use of h-EGF are encouraging results.

Administration, Topical↗
PubMed1992

The effects of occlusive dressings on the recruitment of mononuclear cells by endothelial binding into acute wounds.

Mononuclear cell infiltration is a characteristic feature of wounds and may play an important role in the healing process. We have previously shown that the recruitment of peripheral blood mononuclear cells into wounded skin is an active, dynamic, and regulated process mediated at least in part by specific interactions between mononuclear leukocytes and specialized dermal microvascular endothelial cells in the wounded skin. The purpose of this study was to investigate the capacity of dermal microvascular endothelial cells in wounds exposed to air or covered with occlusive dressings to promote the adhesion of monocytes and lymphocytes. The results showed that dermal microvascular endothelial cells in both air-exposed and occluded wounds were capable of supporting peripheral blood mononuclear cell and monocyte adherence. However, in comparison with air exposed wounds, the level of peripheral blood mononuclear cell binding was significantly higher in occluded biopsies obtained at 0 to 9, 12, 15, and 21 days after wounding. In addition, monocyte and peripheral blood mononuclear cells binding to occluded wounds peaked earlier than peripheral blood mononuclear cell binding to air exposed wounds. These studies provide evidence that differences in the kinetics and magnitude of mononuclear cell adherence may account at least in part for the beneficial effects of occlusive dressing on wound healing.

Animals↗
PubMed1992

Pericapillary fibrin cuffs in venous ulceration. Persistence with treatment and during ulcer healing.

A recent hypothesis suggests that venous hypertension leads to ulceration through the formation of pericapillary fibrin cuffs, which are presumed to impede the exchange of oxygen and other nutrients. In this report, we evaluated by direct immunofluorescence the presence of pericapillary fibrin at the edge of venous ulcers during the course of treatment with elastic compression. In an initial group of 23 patients studied at baseline, pericapillary fibrin cuffs were detected in 20 (91%) of 22 patients. The intensity of fibrin staining, rated blindly on a scale of 0 to 3, could not be correlated with several baseline parameters, including the clinical presence and extent of lipodermatosclerosis, ulcer size, venous recovery time, and transcutaneous oxygen measurements (TcPO2) taken next to the ulcer. Eleven of this initial group of 23 patients were randomly selected to receive elastic compression treatment, and were evaluated for the persistence of pericapillary fibrin at 60 and 120 days. Although a reduction (mean +/- SD = 50.2% +/- 25.7) in ulcer size occurred in 10 of the 11 patients, pericapillary fibrin was still present at the ulcer edge and with undiminished intensity. We conclude that pericapillary fibrin cuffs in venous ulcers persist with compression treatment and in spite of healing, and are unlikely to be directly related to the development of ulceration.

Adult↗
PubMed1991

Stanozolol in treatment of leg ulcers due to cryofibrinogenaemia.

Five consecutive patients with cryofibrinogenaemia in association with painful leg ulcers and intravascular dermal thrombi were treated with stanozolol, an androgenic steroid with fibrinolytic properties. In all patients treatment was followed by rapid and striking pain relief and healing of the ulcers. Cryofibrinogenaemia was not detected on subsequent laboratory evaluation, and dermal intravascular thrombi had resolved on repeat histological examination.

Adult↗