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Biomedical subjects

V Falanga

Publications and source records attributed to V Falanga.

At least 73 records · Page 4Linked to original sources
PubMed1995

Split-thickness skin grafting of leg ulcers. The University of Miami Department of Dermatology's experience (1990-1993).

BACKGROUND: Skin grafting for large and recalcitrant lower extremity ulcers is a commonly used therapy. However, the success rate for grafts performed by dermatologists is largely unknown. OBJECTIVE: To analyze our experience with meshed split-thickness skin grafts for leg ulcers. METHODS: We retrospectively analyzed all hospitalized dermatology patients who underwent meshed split-thickness skin grafting for lower extremity ulceration due to a variety of causes performed by the Department of Dermatology at the University of Miami over a 3-year period (1990-1993). RESULTS: Twenty-nine patients with 36 ulcers were grafted. Greater than 90% of ulcers had initial graft take. At long-term follow-up, 52% of ulcers were healed, 26% were partially healed, and 22% recurred. CONCLUSION: We conclude that meshed split-thickness skin grafting is a safe and effective therapy for recalcitrant lower extremity ulcers.

Adolescent↗
PubMed1995

Enhanced collagen synthesis and transcription by peak E, a contaminant of L-tryptophan preparations associated with the eosinophilia myalgia syndrome epidemic.

The pathogenesis of the eosinophilia myalgia syndrome (EMS) remains unclear. Several abnormal constituents have been found in the L-tryptophan lots responsible for the illness, particularly, 1,1-ethylidenebis[L-tryptophan], also called peak E or EBT, and 3-phenylamino-alanine or peak 5. However, the role of these contaminants in the pathogenesis of EMS and in the development of fibrosis is unknown. We now report that peak E, a dimer of L-tryptophan, is a potent stimulus for human dermal fibroblast DNA and collagen synthesis. Peak E (0.1-1.0 microM) increased DNA synthesis up to four-fold (P = 0.0001) in a dose-dependent manner (r = 0.987). When added to monolayer cultures for 2 to 24 h, peak E (0.5 to 100 microM) caused a progressive, more than threefold increase in alpha 1(I) procollagen mRNA levels and collagenous protein. No increase in procollagen mRNA levels was found after the addition of another major L-tryptophan contaminant, peak 5, or with L-tryptophan itself. Transient transfection with a 2.5-kb alpha 1(I) procollagen promoter-luciferase construct showed that peak E causes a twofold upregulation of promoter activity (P = 0.022). Contraction of collagen gels, consisting of human dermal fibroblasts incorporated into a type I collagen lattice, was enhanced two-fold by exposure to peak E (P = 0.001). We conclude that a major constituent of contaminated batches of L-tryptophan, peak E, is a potent stimulus for fibroblast activation and collagen synthesis. This stimulatory action of peak E may provide a direct mechanism for the development of fibrosis in EMS.

Cells, Cultured↗
PubMed1994

Low oxygen tension decreases receptor binding of peptide growth factors in dermal fibroblast cultures.

We have investigated receptor binding of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta) in cultures of human dermal fibroblasts exposed to low (2%, hypoxia) or standard (20%) oxygen tension. Compared to standard oxygen, the binding of both 125I-TGF-beta and 125I-EGF in low oxygen tension was diminished by a mean of 65 and 62%, respectively (P < 0.02), and was reversed by reexposure of cultures to standard oxygen tension. Low oxygen tension decreased the number of binding sites of both EGF (mean = 44%) and TGF-beta (mean = 33%). Preincubation of the media in the two different oxygen conditions showed that alterations in the redox potential of the medium was not responsible for the changes observed in receptor binding. As shown by Northern analysis, diminished TGF-beta receptor binding in hypoxia was accompanied by up to a 10-fold decrease in mRNA levels of TGF-beta type II receptor. We conclude that low oxygen tension decreases EGF and TGF-beta receptor binding and synthesis.

Adult↗
PubMed1994

Dermatologic consultations in the hospital setting.

BACKGROUND AND DESIGN: Dermatologic practice occurs mainly in the outpatient setting. The reasons for, frequency, and impact of inpatient dermatologic consultation are largely unstudied. In this report, we prospectively studied dermatologic consultation in the major teaching hospital complex of a medical school. Over a period of 8 months, we prospectively recorded the demographics of the patients for whom consultation was requested, the provisional dermatologic diagnosis of the referring service, the final diagnosis of the dermatologic service, and the tests necessary to arrive at a final diagnosis. RESULTS: During a period of slightly over 8 months, dermatologic consultation was requested and delivered to 591 patients who were either hospitalized or being evaluated in the emergency department or other urgent care settings. The services requesting consultation most frequently were medicine (39%), pediatrics (14%), surgery (12%), psychiatry (6%), and neurology (3%). In 51% of consultations, the patients were younger than 45 years of age. Diagnostic tests, including Tzanck smear and potassium hydroxide preparation, confirmed the clinical diagnosis in up to 50% of cases. Dermatologic consultation changed dermatologic diagnosis and treatment in more than 60% of the patients. Generally, the dermatologic diagnoses most frequently missed by the referring service were common conditions with established treatment. CONCLUSIONS: Dermatologic consultation in the hospital setting improves dermatologic diagnosis and has an impact on treatment.

Adolescent↗
PubMed1993

The "trap" hypothesis of venous ulceration.

The pathogenesis of venous ulceration is unknown. We propose that macromolecules leaking into the dermis as a result of venous hypertension bind to or "trap" growth factors and matrix material, which then become unavailable for tissue repair and for the maintenance of tissue integrity.

Fibrin↗
PubMed1993

Low oxygen stimulates proliferation of fibroblasts seeded as single cells.

In standard tissue culture conditions (20% oxygen), single human dermal fibroblasts (one cell per well) do not proliferate. We now report that low oxygen tension is a potent stimulus for the proliferation and expansion of human adult and neonatal dermal fibroblasts seeded as single cells. This preferential single-cell proliferation in low oxygen is shown to be also a feature of human lung and dermal rodent fibroblasts, but not of human fibrosarcoma and immortalized 3T3 cells, which proliferate without difficulty in standard oxygen conditions. It is suggested that single-cell proliferation and its dramatic stimulation in low oxygen may represent a fundamental biologic process with an opportunity to better understand mammalian cell growth regulation.

3T3 Cells↗
PubMed1993

Low oxygen tension increases mRNA levels of alpha 1 (I) procollagen in human dermal fibroblasts.

Dermal fibroblasts exposed to low oxygen tension show upregulated synthesis of transforming growth factor-beta 1 (TGF-beta 1), an established stimulatory peptide in the formation of extracellular matrix proteins. In this report, procollagen synthesis was measured in cultures of confluent adult human dermal fibroblasts exposed to either standard (20%) or low (2%) oxygen tension. By Northern blot analysis the steady state levels of alpha 1 (I) procollagen mRNA were increased by 75 to 150% of control (standard oxygen) as early as 12 hours and more than 200% 96 hours after exposure of cells to low oxygen. Similar increases in procollagen mRNA levels were obtained in hypoxic fibroblast cultures in a collagen lattice. The stimulatory effect of hypoxia on procollagen mRNA levels in fibroblast monolayers was diminished by antibodies to TGF-beta, and could not be augmented further by the addition of TGF-beta 1, evidence that hypoxic fibroblasts may already be maximally stimulated by TGF-beta 1. We conclude that low oxygen tension enhances steady state mRNA levels of alpha 1 (I) procollagen, and that this effect is mediated at least in part by TGF-beta 1.

Antibodies↗
PubMed1993

Stanozolol causes rapid pain relief and healing of cutaneous ulcers caused by cryofibrinogenemia.

BACKGROUND: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcerations. The histology of these lesions is characterized by intravascular thrombi. OBJECTIVE: Our purpose was to test the efficacy of stanozolol, a drug capable of fibrinolytic enhancement, in treating cutaneous ulcers caused by cryofibrinogenemia. METHODS: Eight patients with cutaneous ulcerations from cryofibrinogenemia were treated with stanozolol. Plasma cryofibrinogen was measured before and during treatment with stanozolol. Histologic evaluation was also performed before treatment and in selected patients during treatment. RESULTS: After treatment, seven of the eight patients had healing of their ulcers, prompt reduction in their pain, and improvement in livedo reticularis and purpura. Four of the eight patients had no detectable plasma cryofibrinogen after treatment. In addition, dermal intravascular thrombi resolved. Stanozolol was well tolerated and had minimal side effects. CONCLUSION: We conclude that stanozolol is a safe and effective treatment of the cutaneous manifestations of cryofibrinogenemia.

Adult↗
PubMed1993

The clinical spectrum of lipodermatosclerosis.

Lipodermatosclerosis refers to the skin induration and hyperpigmentation of the legs that often occurs in patients who have venous insufficiency. Lipodermatosclerosis has also been termed hypodermitis sclerodermiformis and appears to be similar if not-identical to the recently described sclerosing panniculitis of the leg. There has been much confusion about the nature, clinical course, and treatment of lipodermatosclerosis. We believe that lipodermatosclerosis has an acute, inflammatory phase and a chronic, fibrotic stage, although a spectrum exists. Direct immunofluorescence studies of early and late lesions are helpful in that they show dermal pericapillary fibrin deposits without other immunoreactants. Treatment of lipodermatosclerosis consists of compression therapy with either graded stockings or elastic bandages. We and others have found that the anabolic steroid stanozolol improves this condition rapidly and consistently.

Humans↗
PubMed1993

Use of a durometer to assess skin hardness.

BACKGROUND: Skin induration is difficult to quantify. In patients with systemic sclerosis (scleroderma), a clinical skin severity score (0 = normal skin; 3 = maximal induration) has been in use for several years for assessment of skin involvement and therapeutic outcome. OBJECTIVE: The purpose of this study was to find a more objective method to assess skin hardness in patients with scleroderma. METHODS: Finger pads, forearms, and thighs of 12 sequential nonselected patients with scleroderma and eight normal control subjects were scored by an observer blinded as to group, and quadruplicate determinations of the degree of skin induration at these anatomic sites were made with a hand-held type O durometer. RESULTS: Consistently, these anatomic sites except for the forehead showed a direct relation between the skin severity score and the hardness measured with the durometer. The best results were obtained from the index finger pad where, compared with uninvolved skin, an increased skin severity score was associated with higher durometer readings (p = 0.0032, p = 0.0002, and p = 0.0005 for skin scores of 1, 2, and 3, respectively). CONCLUSION: The durometer is an effective and reliable method to assess skin hardness.

Elasticity↗
PubMed1993

Inhibition of cell proliferation by chronic wound fluid.

It has been proposed that occlusive wound dressings may enhance chronic wound repair by the stimulatory action of the fluid accumulating beneath the dressings. In this report, we investigated the in vitro proliferative effects of chronic wound fluid obtained from under a polyurethane membrane applied for 24 hours to venous ulcers in the ambulatory setting. By measuring cell counts and DNA synthesis, we found that chronic wound fluid inhibited the proliferation of human dermal fibroblasts (p = 0.008) and failed to stimulate the proliferation of microvascular endothelial cells (p = 0.03) and keratinocytes (p = 0.03). The inhibitory activity of chronic wound fluid on fibroblast proliferation was blocked after the fluid was heated to 100 degrees C, but not 56 degrees C, and was mainly restricted to a fraction of chronic wound fluid enriched in components less than 30 kd in molecular weight (p = 0.028). At concentrations ranging from 1% to 4% and in the presence of serum, chronic wound fluid decreased the viability of fibroblasts, as shown by a decreased ability of the cells to exclude trypan blue (p = 0.02), and the viability of endothelial cells, as shown by an increased release of tritiated adenine (p = 0.03). We conclude that the wound fluid obtained from beneath occlusive dressings applied to chronic wounds inhibits cell proliferation.

Journal Article↗
PubMed1993

Gene expression in low oxygen tension.

Low oxygen tension is a feature of many physiologic and pathologic conditions, including wound healing, fibrosis, and neoplasia. Increasing evidence suggests that low oxygen tension induces the transcription of a number of genes, and that this process depends on the cellular context. The proteins synthesized from these genes enable cells to adapt to the hypoxic environment and/or to fulfill their functional roles. The regulatory regions responsible for the induction of erythropoietin gene transcription and synthesis in response to hypoxia/anemia appear to be cis-acting deoxyribonucleic acid sequences located within the 5' and 3' flanking regions of the erythropoietin gene. Other proteins induced by hypoxia include cytokines (platelet-derived growth factor-beta chain, endothelin-1, transforming growth factor-beta), enzymes (tyrosine hydroxylase, glycolytic enzymes), and stress proteins. The molecular mechanisms of the hypoxia-induced expression of these genes are poorly understood. A heme protein may act as the oxygen tension sensor, or the redox state of certain nuclear transcription factors may function as second messengers.

Animals↗