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At least 19 recordsLinked to original sources
PubMed1995

The expression of platelet-derived growth-factor gene in Dupuytren contracture.

Dupuytren contracture is a disease of the palmar fascia characterized by nodular fibroblastic proliferation; its etiology and pathogenesis are poorly understood. Growth factors are polypeptides that regulate cell growth and differentiation and extracellular matrix production. Platelet-derived growth factor is known to cause fibroblastic proliferation, and it may be involved in the pathogenesis of Dupuytren contracture. The purpose of this study was to determine if the gene for the B chain of platelet-derived growth factor is expressed in Dupuytren contracture. Tissue from patients who had Dupuytren disease was examined immunohistochemically with the 5B5 antibody, which is a marker for fibroblasts. Polymerase chain reaction, gel electrophoresis, Southern blotting, and in situ hybridization were also used to study gene expression in the tissue as well as in normal fascia, A172 cells, and MRC5 cells. Total cellular RNA was extracted from tissue and cells. Polymerase chain reaction was done with oligonucleotide primers complementary to a portion of the platelet-derived growth-factor-B and platelet-derived growth-factor-receptor genes. The platelet-derived growth-factor-B gene was expressed in all six specimens from the patients who had Dupuytren contracture as well as in the A172 cells, but not in the normal fascia lata or the MRC5 cells. These results were confirmed with Southern blotting of the products of the reaction with a platelet-derived growth-factor-B probe. The gene for the platelet-derived growth-factor receptor was expressed by all tissues and cells studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗
PubMed1988

Cytogenetic studies in Dupuytren contracture.

Dupuytren contracture is a connective tissue disease mainly confined to Caucasians. It is characterized by nodular growth and proliferation of collagen in the palmar and plantar fascias. Autosomal dominance with variable penetrance is considered the most likely mode of inheritance. The goal of the present study was to examine the cytogenetics of this common benign neoplasia. Chromosome studies were performed on the nodular growth of eight patients with Dupuytren contracture, all of whom showed chromosome abnormalities that included numerical and structural clones, random numerical and structural aberrations, prophasing, and premature centromere separation. Numerical clones of trisomies 7 and/or 8, as well as some random structural aberrations, were considered to represent in vivo abnormalities, whereas most structural clones appeared likely to be the results of rapid and selective in vitro growth of particular cells. The disease process occurring in Dupuytren contracture was found to involve marked chromosome instability, as well as some in vivo clonal formation. Transverse fascial tissue, usually considered to be uninvolved in the disease process, unexpectedly showed all the same types of abnormalities as the nodular tissue. This indicates a more widespread distribution of disease in the tissues than previously suspected. The findings in the present study are similar to those in various malignant and benign types of tumorous growth and suggest the importance of further cytogenetic investigation into other conditions of benign growth.

Aneuploidy↗
PubMed2005

Imiquimod: a potential weapon against Dupuytren contracture.

Dupuytren disease is a proliferative fibroplasia of the subcutaneous palmar tissue, occurring in the form of nodular and cords. Evidence is certainly accumulating for raised levels in Dupuytren's tissue of growth factors known to stimulate fibroblasts, Interleukin-1, basic fibroblast growth factor, transforming growth factor-beta, prostaglandin-F2, prostaglandin-E2, platelet derived growth factor and connective tissue growth factor have been suggested to have a role. Immune modification of profibrotic cytokines would provide a novel means to treat dupuytren contracture. Imiquimod cream 5% (Aldara) is an immune modifier, that downregulates transforming growth factor-beta and fibroblast growth factor-2 (the two most important cytokine in producing fibrosis). Based on previous mentioned evidence we suggest: imquimod as a potential drug for dupuytren contracture treatment.

Adjuvants, Immunologic↗
PubMed1990

[Clinical aspects and surgical treatment of Dupuytren contracture].

The etiology of Dupuytren's contracture is still not clear. Many theories have been proposed, but no basic data are currently available that would make it possible to treat Dupuytren's contracture by other methods than surgical intervention. The surgical technique used in our clinic is described, and a postoperative treatment is also outlined. This paper is designed to propose an acceptable technique for practicing trauma and hand surgeons.

Dupuytren Contracture↗
PubMed1996

Regulation of proliferation and platelet-derived growth factor expression in palmar fibromatosis (Dupuytren contracture) by mechanical strain.

Palmar fibromatosis (Dupuytren contracture) causes fibrosis of specific palmar fascial bands. These bands are subjected to repetitive mechanical strain in situ. Primary cell cultures were derived from (a) palmar fibromatosis from eight patients, (b) uninvolved palmar fascia (Skoog's fibers) from four of these patients, and (c) normal palmar fascia from four additional patients. The cells were plated onto collagen-coated membranes either subjected to cyclic strain (25% maximal strain at 1 Hz) or without strain. Bromodeoxyuridine incorporation showed an increase in proliferation in all cultures subjected to strain. This increase was highest for palmar fibromatosis (10 to 40% nuclear incorporation, p = 0.02). Skoog's fibers and fascia from the normal individuals showed a trend (not significant) toward increase with strain (8 to 25%, p = 0.15 for Skoog's fibers, and 8 to 15%, p = 0.45 for normal fascia). Cyclic strain increased the expression of platelet-derived growth factor-A relative to glyceraldehyde-3-phosphate dehydrogenase in palmar fibromatosis (2.2 to 3.5, p = 0.05) and Skoog's fibers (0.8 to 2.0, p = 0.04). The expression of platelet-derived growth factor-B relative to glyceraldehyde-3-phosphate dehydrogenase was enhanced by cyclic strain only in the fibromatosis tissue (0.7 to 2.1, p = 0.04). The normal fascia did not express platelet-derived growth factor. Platelet-derived growth factor neutralizing antibody decreased bromodeoxyuridine incorporation in fibromatosis cultures subjected to cyclic strain to near levels for those grown in the absence of strain (38 to 16%, p = 0.05). Conditioned medium from fibromatosis cells grown under stain showed a trend toward increased proliferation in additional fibromatosis cultures compared with conditioned medium from fibromatosis cells grown without strain (9 to 15% nuclear incorporation, p = 0.20). The observed palmar fibromatosis contracture can be partially explained on the basis of the cell's response to cyclic strain, which may be mediated by platelet-derived growth factor.

Antibody Specificity↗
PubMed1997

Cytogenetic and interphase cytogenetic analyses reveal chromosome instability but no clonal trisomy 8 in Dupuytren contracture.

The results of cytogenetic and FISH analysis performed in 26 cases of Dupuytren contracture are reported. Clonal or sporadic chromosome changes were found in 18 cases (69%). Clonal changes consisted of: +2, +16, -10, -Y, add(1)(p23), del(2)(q21), t(3;16)(p21;q24), add (3)(p24), del(18)(q21), t(Y;14)(p12;q24), +mar. The results differ from those obtained in normal palmar fascia used as control, in which -Y and +Y were the only clonal changes found in 2 of 11 analyzed cases (18%). No clonal trisomy 8 was found. FISH analysis performed in 11 cases (centromeric probe specific for chromosome 8) failed to show the presence of a cell population with +8. Clonal and sporadic structural changes were different from case to case and no clustering breakpoint was observed. The significance of the chromosome instability leading to clonal and sporadic chromosome changes not specific to Dupuytren contracture are discussed.

Aged↗
PubMed1992

An insight into Dupuytren's contracture.

Dupuytren's contracture is a deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists since the early descriptions by Guillaume Dupuytren in 1831. It predominantly affects elderly, male caucasians, has a hereditary predisposition and has strong associations with diabetes, alcohol consumption, cigarette smoking and HIV infection. The major morphological features are an increase in fibroblasts, particularly around narrowed fibroblasts; a finding consistent with localised ischaemia. During ischaemia, adenosine triphosphate (ATP) is converted to hypoxanthine and xanthine, and endothelial xanthine dehydrogenase to xanthine oxidase (alcohol also mediates this change, a finding of particular relevance given the association of Dupuytren's contracture with alcohol intake). Xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and uric acid with the release of superoxide free radicals (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (OH.). These free radicals are highly reactive, with half-lives in the order of milliseconds and are toxic in high concentrations. A potential for free radical generation in Dupuytren's contracture was elicited by finding a sixfold increase in hypoxanthine concentrations in Dupuytren's contracture compared with control palmar fascia. In vitro studies affirmed the toxic effects of oxygen free radicals to Dupuytren's contracture fibroblasts, but also showed that, at lower concentrations (concentrations similar to those likely to occur in Dupuytren's contracture), free radicals had a stimulatory effect on fibroblast proliferation. Cultured fibroblasts were found to release their own O2-. These endogenously released free radicals were also found to be important in fibroblast proliferation. The collagen changes of Dupuytren's contracture were examined. The results established that fibroblast origin was unimportant, but that inhibition of type I collagen production at high fibroblast density accounted for the increase in type III/I collagen ratios observed by previous investigators. These biochemical and morphological observations throw new light on Dupuytren's contracture. They suggest that age, genetic and environmental factors may contribute to micro vessel narrowing with consequent localised ischaemia and free radical generation. Endothelial xanthine oxidase derived free radicals may both damage the surrounding stroma and stimulate fibroblasts to proliferate. Proliferating fibroblasts lay down and contract collagen in lines of stress.Progressive fibroblast proliferation and deposition of collagen is likely to encourage further microvessel narrowing with a positive feedback effect consistent with the progressive nature of the condition.

Capillaries↗
PubMed1997

[Results of surgical treatment for Dupuytren contracture].

Early and late results of surgical treatment for Dupuytren contracture within 53 hands in 47 patients aged 19-72 (mean 58) are presented. Early results depended on magnitude of deformity and late ones (3-7 years after surgery) depended on recurrence of the contracture. In patients who had rheumatoid arthritis or the results were slightly worse; pathological changes within the hand were to blame and not the recurrence of contracture itself. No difference in histopathology of this condition was observed between rheumatoid arthritis-group- and ankylosing spondylitis patients.

Adult↗
PubMed1991

The myofibroblast in Dupuytren's contracture.

Dupuytren's contracture nodules, but not cords, contain myofibroblasts. These cells, which combine many electron microscopic, physiologic, and immunohistochemical characteristics of fibroblasts and smooth muscle cells, are probably the active force of contraction. Prominent myofibroblasts and intracellular microtubules correlate with increased likelihood of clinical recurrence after surgery. Tissue culture of cells derived from Dupuytren's contracture myofibroblasts show consistently slower cell replication than from fibroblasts and show persistence of electron microscopic characteristics in early passages. Research in Dupuytren's contracture myofibroblasts has been done on human tissue and so has clinical correlation. Myofibroblast presence may help to predict recurrence of disease and suggests that palmar skin should be excised when adherent to disease nodules. The theory of myofibroblasts helps explain why the open technique often succeeds, and why full thickness skin grafts inhibit recurrent contracture.

Dupuytren Contracture↗
PubMed1985

[2-stage operative treatment of Dupuytren contracture].

The incidence of Sudeck-like complications after surgery for Dupuytren's contracture is discussed. In a series of 209 operations for Dupuytren's contracture some complications were observed in 26 cases. In 12 patients these complications could not be precisely explained. In the author's opinion they may illustrate the creation of a nerve-irritating source within the operative field. In order to avoid these complications a two-stage operation was proposed, especially for severe contractures in elderly patients. A preliminary fasciotomy relieves most of symptoms of the disease and may also serve as a so-called tissue test for eventual more radical procedures. The observation of 42 patients with severe contractures so treated confirms the usefulness of the method.

Dupuytren Contracture↗
PubMed1991

Dupuytren's contracture.

Dupuytren's contracture is a disease of the palmar and digital fascia that results in a flexion deformity of the fingers. Although the first case was reported more than 350 years ago, many questions remain unanswered. With our present state of knowledge, treatment remains empiric and operative intervention is the only successful mode of treatment. Controversies continue over the type of procedure used, as well as its timing. In light of the high rate of recurrence of flexion contractures after apparently successful operations, current research is being directed toward identifying a biochemical or histologic marker to indicate the probability of recurrence.

Dupuytren Contracture↗
PubMed1995

[Dupuytren contracture--current status in research and clinical practice].

Dupuytren's contracture is a disease of the connective tissue, especially of the palmar side of the hand. Today, by means of electron microscopy and histochemistry, several alternations specific of pathology of the disease can be shown, providing a better understanding. However, a revolutionary change of treatment is far out of reach. Dupuytren's diathesis can be influenced by none of today's known methods, and therapy is still empirical. Operative therapy is only indicated in functional impairment. Treatment should be done by well-trained surgeons and in case of extensive diathesis by carefully planning and longtime follow-up to avoid complications and eruption of the disease.

Dupuytren Contracture↗
PubMed1989

Dupuytren's contracture.

Dupuytren's contracture can be controlled by surgery and hand function can be markedly improved. Surgery is not, however, a definitive cure and patients should be so advised, especially when the disease starts in the younger age group.

Dupuytren Contracture↗