Comparison of palmar aponeuroses from individuals with diabetes mellitus and Dupuytren's contracture. (1/91)

It is well known that Dupuytren's contracture is often associated with diabetes mellitus. Palmar fascia from individuals with diabetes mellitus and/or Dupuytren's contracture as well as controls were subjected to differential scanning calorimetry, biomechanical and biochemical analysis. The collagen denaturation temperature of the palmar aponeurosis from individuals with diabetes mellitus in the presence (71.0 degrees C) or absence of Dupuytren's contracture (70. 6 degrees C) was increased as compared with controls (68.5 degrees C), while this parameter was significantly reduced (about 3.5 degrees C) in contracture bands of Dupuytren's contracture. Stress relaxation experiments revealed that the viscous fraction was slightly reduced in diabetes mellitus (6.5%) vs. controls (8.3%), whereas in Dupuytren's contracture, irrespective of additional diabetes mellitus, a pronounced increase of this parameter was seen (36.5% vs. 24.5%) in the presence of diabetes mellitus. The time constants were significantly elevated by both disorders, this increase being more pronounced in Dupuytren's contracture. Taken together, these changes can be explained by increased cross-linking in diabetes mellitus, while in Dupuytren's contracture other structural changes, such as increased collagen type III content and loss of fascicular organization, play an additional role besides the finding of reduced cross linking.  (+info)

Dupuytren's disease. A model for the mechanism of fibrosis and its modulation by steroids. (2/91)

Dupuytren's disease is a chronic inflammatory process which produces contractures of the fingers. The nodules present in Dupuytren's tissue contain inflammatory cells, mainly lymphocytes and macrophages. These express a common integrin known as VLA4. The corresponding binding ligands to VLA4 are vascular cell adhesion molecule-1 (VCAM-1) present on the endothelial cells and the CS1 sequence of the fibronectin present in the extracellular matrix. Transforming growth factor-beta (TGF-beta) is a peptide hormone which has a crucial role in the process of fibrosis. We studied tissue from 20 patients with Dupuytren's disease, four samples of normal palmar fascia from patients undergoing carpal tunnel decompression and tissue from ten patients who had received perinodular injections of depomedrone into the palm five days before operation. The distribution of VLA4, VCAM-1, CS1 fibronectin and TGF-beta was shown by immunohistochemistry using an alkaline phosphorylase method for light microscopy. In untreated Dupuytren's tissue CS1 fibronectin stained positively around the endothelial cells of blood vessels and also around the surrounding myofibroblasts, principally at the periphery of many of the active areas of the Dupuytren's nodule. VCAM-1 stained very positively for the endothelial cells of blood vessels surrounding and penetrating the areas of high nodular activity. VCAM-1 was more rarely expressed outside the blood vessels. VLA4 was expressed by inflammatory cells principally in and around the blood vessels expressing VCAM-1 and CS1 but also on some cells spreading into the nodule. TGF-beta stained positively around the inflammatory cells principally at the perivascular periphery of nodules. These cells often showed VLA4 expression and co-localised with areas of strong production of CS1 fibronectin. Normal palmar fascia contained only scanty amounts of CS1 fibronectin, almost no VCAM-1 and only an occasional cell staining positively for VLA4 or TGF-beta. In the steroid-treated group, VCAM-1 expression was downregulated in the endothelium of perinodular blood vessels and only occasional inflammatory cell expression remained. Expression of CS1 fibronectin was also much reduced but still occurred in the blood vessels and around the myofibroblast stroma. VLA4-expressing cells were also reduced in numbers. A similar but reduced distribution of production of TGF-beta was also noted. Our findings show that adherence of inflammatory cells to the endothelial wall and the extravasation into the periphery of the nodule may be affected by steroids, which reduce expression of VCAM-1 in vivo. This indicates that therapeutic intervention to prevent the recommencement of the chronic inflammatory process and subsequent fibrosis necessitating further surgery may be possible.  (+info)

Dermofasciectomy in the management of Dupuytren's disease. (3/91)

Dupuytren's disease may present with well-defined subcutaneous cords or as more diffuse disease with involvement of the skin. Fasciectomy is the procedure commonly carried out for the full range of disease, but is associated with rates of recurrence of up to 66%. We reviewed 143 rays in 103 patients undergoing dermofasciectomy for diffuse disease with involvement of the skin. We found recurrence in 12 rays (8.4% of rays; 11.6% of patients) during a mean follow-up of 5.8 years, eight as cords and four as nodules. We suggest that dermofasciectomy is a better method of disease control than fasciectomy for the more diffuse type of disease with involvement of the skin.  (+info)

Rheumatological complications associated with the use of indinavir and other protease inhibitors. (4/91)

Several cases are reported of rheumatological pathology (temporomandibular dysfunction, frozen shoulder, Dupuytren's disease, and tendinitis) most probably related to the intake of indinavir in HIV positive patients. A survey using an anonymous questionnaire of 878 people with HIV infection treated with antiretroviral drugs suggests that other protease inhibitors may also cause arthralgia.  (+info)

Genetic susceptibility in Dupuytren's disease. TGF-beta1 polymorphisms and Dupuytren's disease. (5/91)

Dupuytren's disease is a benign fibroproliferative disease of unknown aetiology. It is often familial and commonly affects Northern European Caucasian men, but genetic studies have yet to identify the relevant genes. Transforming growth factor beta one (TGF-beta1) is a multifunctional cytokine which plays a central role in wound healing and fibrosis. It stimulates the proliferation of fibroblasts and the deposition of extracellular matrix. Previous studies have implicated TGF-beta1 in Dupuytren's disease, suggesting that it may represent a candidate susceptibility gene for this condition. We have investigated the association of four common single nucleotide polymorphisms in TGF-beta1 with the risk of developing Dupuytren's disease. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping TGF-beta1 polymorphisms. DNA samples from 135 patients with Dupuytren's disease and 200 control subjects were examined. There was no statistically significant difference in TGF-beta1 genotype or allele frequency distributions between the patients and controls for the codons 10, 25, -509 and -800 polymorphisms. Our observations suggest that common TGF-beta1 polymorphisms are not associated with a risk of developing Dupuytren's disease. These data should be interpreted with caution since the lack of association was shown in only one series of patients with only known, common polymorphisms of TGF-beta1. To our knowledge, this is the first report of a case-control association study in Dupuytren's disease using single nucleotide polymorphisms in TGF-beta1.  (+info)

Wound infection by Prototheca wickerhamii, a saprophytic alga pathogenic for man. (6/91)

Biopsy of a wound infection of the palmar fascia in a young diabetic woman revealed characteristic periodic acid-Schiff-positive Prototheca species cells with a rosette configuration and internal septation. Prototheca wickerhamii was cultured repeatedly from the wound drainage and the biopsy tissue. Several diagnostic features distinguishing Prototheca species, saprophytic algae, from yeasts are: the formation of endospores by mitosis; greater variation in cell size (2 to 15 mum); the presence of cytoplasmic granules, particularly in old cultures; and the absence of budding forms and pseudomycelia. The organism was resistant to 5-fluorocytosine and the minimal inhibitory concentration of amphotericin B was 12.5 mug/ml. With the exception of the tetracycline group, all other 16 antibacterial agents tested appeared completely ineffective in vitro. A synergism between amphotericin B and tetracycline was clearly demonstrated by the use of the checkerboard method. Infection by Prototheca species may be more common than presently realized due to the common expedient of identifying yeast-like isolates as "yeast--not Candida albicans."  (+info)

Regulation of expression of alpha-smooth muscle actin in cells of Dupuytren's contracture. (7/91)

Our aims were to describe the distribution of alpha-smooth muscle actin (SMA)-containing cells in Dupuytren's tissue in vivo and to determine the effects of selected agents in regulating the expression of SMA in Dupuytren's cells in vitro. In selected hypercellular zones of Dupuytren's nodules up to 40% of the cells contained SMA, as shown by immunohistochemistry. A lower percentage (20%) of SMA-containing cells was found in regions of lower cellularity. A notable finding was that treatment in vitro of Dupuytren's cells with platelet-derived growth factor significantly reduced the content of SMA. Cells from the same patients showed a significant increase in expression of SMA in response to treatment with transforming growth factor, which confirmed recent findings. In addition, interferon-gamma, which has been previously used as a treatment for Dupuytren's disease in a clinical study, had no reproducible effect on the expression of this actin isoform. Our findings are of significance for the conservative management of contractures.  (+info)

Elevated levels of beta-catenin and fibronectin in three-dimensional collagen cultures of Dupuytren's disease cells are regulated by tension in vitro. (8/91)

BACKGROUND: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in the development of scar-like, collagen-rich disease cords within specific palmar fascia bands. Although the molecular pathology of DD is unknown, recent evidence suggests that beta-catenin may play a role. In this study, collagen matrix cultures of primary disease fibroblasts show enhanced contraction and isometric tension-dependent changes in beta-catenin and fibronectin levels. METHODS: Western blots of beta-catenin and fibronectin levels were determined for control and disease primary cell cultures grown within stressed- and attached-collagen matrices. Collagen contraction was quantified, and immunocytochemistry analysis of filamentous actin performed. RESULTS: Disease cells exhibited enhanced collagen contraction activity compared to control cells. Alterations in isometric tension of collagen matrices triggered dramatic changes in beta-catenin and fibronectin levels, including a transient increase in beta-catenin levels within disease cells, while fibronectin levels steadily decreased to levels below those seen in normal cell cultures. In contrast, both fibronectin and beta-catenin levels increased in attached collagen-matrix cultures of disease cells, while control cultures showed only increases in fibronectin levels. Immunocytochemistry analysis also revealed extensive filamentous actin networks in disease cells, and enhanced attachment and spreading of disease cell in collagen matrices. CONCLUSION: Three-dimensional collagen matrix cultures of primary disease cell lines are more contractile and express a more extensive filamentous actin network than patient-matched control cultures. The elevated levels of beta-catenin and Fn seen in collagen matrix cultures of disease fibroblasts can be regulated by changes in isometric tension.  (+info)

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