Chromosomal abnormalities in Dupuytren's contracture and carpal tunnel syndrome.

The cytogenetics of cell cultures derived from Dupuytren's tissue, adjacent palmar fascia and palmar skin from patients undergoing fasciectomy have been examined and the results compared to cell cultures established from palmar fascia, flexor retinaculum and palmar skin of patients undergoing carpal tunnel decompression. Chromosomal abnormalities were detected in cell cultures from Dupuytren's tissue in eight of the nine patients studied. Clones of cells trisomic for chromosome 8 were found in five of the nine patients. Trisomy 8 was also present in two of five flexor retinaculum cultures from carpal tunnel syndrome cases. These findings in both Dupuytren's contracture and carpal tunnel syndrome suggest the presence of chromosomal instability in the palmar fascia. The significance of the chromosomal abnormalities is however unclear, but they indicate a possible common pathway in the onset of pathological fibrosis.     

The effect of steroids on Dupuytren's disease: role of programmed cell death

This study compared the rates of proliferation and apoptosis of cells within nodules of Dupuytren's disease and nodules from patients that had been injected preoperatively with steroid (Depo-Medrone). It also compared the effects of steroids in apoptosis in cultured Dupuytren's cells and control fibroblasts from palmar fascia and fascia lata. Steroids reduced the rate of fibroblast proliferation and increased the rate of apoptosis of both fibroblasts and inflammatory cells in Dupuytren's tissue. Steroids also produced apoptosis of cultured Dupuytren's cells but not of palmar fascia and fascia lata cells.     

The collagen changes of Dupuytren's contracture

In Dupuytren's contracture there is an increase in the ratio of type III to type I collagen. The objective of this study was to determine if fibroblasts from patients with Dupuytren's contracture have an intrinsic aberration in collagen production or whether local factors govern the collagen changes in Dupuytren's contracture. Using a new collagen micro-method, we found that fibroblasts cultured from palmar fascia affected by Dupuytren's contracture produced similar collagen to fibroblasts derived from the palmar fascia of age- and sex-matched patients with carpal tunnel syndrome. Furthermore, the collagen changes of Dupuytren's contracture could be reproduced in all cell lines by increasing fibroblast density. At high fibroblast density, type I collagen production was inhibited: a finding that could account for the increased types III/I collagen ratio in Dupuytren's contracture. These results suggest that a genetic defect in collagen production is unlikely and that the important phenomenon is an increase in fibroblast density.     

Androgen receptors in Dupuytren's contracture.

Palmar fascia tissue and cultured cells from patients with Dupuytren's contracture and from normal subjects were characterized and analyzed for androgen receptor expression. Androgen receptors have never been studied in Dupuytren's myofibroblasts and may have a role in its high male predominance. Surgical samples were collected from eight patients undergoing surgery for Dupuytren's contracture and from four patients with carpal tunnel syndrome, used as control tissue. Immunohistochemical analysis was performed on tissue samples and on cell cultures with anti-androgen receptor, anti-alpha-smooth muscle actin, anti-fibronectin, and anti-type I and III collagen antibodies using the biotin avidin peroxidase method as revelatory system. Immunostaining for androgen receptors in tissue samples and cultured cells revealed nuclear reaction in many Dupuytren's myofibroblasts, but in few fibroblasts of the normal palmar fascia. In a double-labeling study, androgen receptors were seen to co-localize with alpha-actin in both cell cultures and tissue samples. We present the first evidence that the palmar fascia is a target tissue for androgen action and that the expression of androgen receptors in Dupuytren's contracture is considerably higher than in the normal palmar fascia. Further studies will need to evaluate whether the androgen-responsive state of the tissue is related to the high incidence of Dupuytren's contracture in the male sex.     

Non-Dupuytren's disease of the palmar fascia

The typical Dupuytren's disease patient is of Northern European descent with bilateral progressive multiple digital contractures and is genetically predisposed, with a family history. Palmar fascial proliferations sometimes present as a different entity without the typical Dupuytren's disease characteristics. We identified 39 patients (20 women and 19 men) over a 4-year period with "Non-Dupuytren's palmar fascial disease", with unilateral involvement, without family history or ectopic manifestations. Twenty-three patients presented with unrelated complaints and were discovered, incidentally, to have the condition. In 28 patients, prior ipsilateral hand surgery or trauma precipitated the condition. Other related factors were diabetes mellitus and cardiovascular disease. Ten patients had skin tethering and subcutaneous thickening akin to Dupuytren's nodules and 29 had palmar fascial thickening into ill-defined pretendinous cords. The diseased tissue was in the line of the ring finger in 30 patients. The time from insult to onset of contracture averaged 3.6 months and from onset to follow-up averaged 5.3 years. The condition was non-progressive, or partially regressive, in 33 patients. Seven patients had operations for unrelated conditions and underwent simultaneous fasciectomy without recurrence. Environmental factors, especially trauma, surgery and diabetes, are important in the pathogenesis of Non-Dupuytren's palmar fascial disease, but these patients do not appear to be genetically predisposed for Dupuytren's disease. Typical Dupuytren's disease and Non-Dupuytren's palmar fascial disease are two clinical entities that run different courses and do not share a similar prognosis. This should be taken into account in future epidemiological and outcome studies.     

Enzymes of glucose metabolism in palmar fascia and Dupuytren's contracture.

Several enzymes participating in glucose metabolism and some of the acid hydrolases were assayed in palmar fascia and Dupuytren's contracture with fluorometric microanalytical methods. The enzyme activities of glucose metabolism were lower in normal palmar fascia than in dermis. The fascia of Dupuytren's contracture exhibited a general increase in the enzyme activities of glucose catabolism. Little alteration was found in alanine aminotransferase and UDP-glucose dehydrogenase activity in the lesion. Lysosomal hydrolytic enzyme activities were increased five to ten times in Dupuytren's tissue. The dermis overlying Dupuytren's contracture exhibited an increase in the enzyme activities of glucose catabolism, but to a lesser degree than did the fascia of the lesion. The epidermis of involved palmar skin displayed normal enzyme activities.     

Dupuytren's cord involving the septa of Legueu and Juvara: a case report

A patient with Dupuytren's disease with involvement of the palmar fascial complex and digital contracture is described. A vertical cord had developed in the transverse ligament of the palmar aponeurosis fibers and the underlying septa of Legueu and Juvara. The cord was composed of a pretendinous band, transverse ligament of the palmar aponeurosis, and septum of Legueu and Juvara. The cord was attached deeply in the soft tissue confluence of the sagittal band, palmar plate, and interpalmar plate ligament. Involvement of the transverse ligament of the palmar aponeurosis and septa of Legueu and Juvara in Dupuytren's disease is rare. Understanding of the normal and pathologic fascial anatomy explains their simultaneous involvement and is necessary for complete ablation of the diseased tissue.     

Responsiveness of Dupuytren's disease fibroblasts to 5 alpha-dihydrotestosterone

PURPOSE: We recently showed that androgen receptors are expressed in Dupuytren's contracture. The aim of the present work was to test the responsiveness of Dupuytren's fibroblasts to 5 alpha-dihydrotestosterone (5 alpha-DHT), the active form of testosterone. RESULTS: Cultured palmar fascia cells from 10 patients with Dupuytren's contracture and 4 normal subjects were exposed to 5 alpha-DHT (10 or 100 ng/mL) for 1, 3, 7, and 15 days. Their phenotype was analyzed immunohistochemically for alpha-smooth muscle actin and androgen receptor expression and proliferation rates were studied. RESULTS: At 15 days the higher concentration of 5 alpha-DHT induced an increase in Dupuytren's fibroblast proliferation, whereas anti-alpha-smooth muscle actin exhibited the strongest expression. At the same time point androgen receptor expression decreased with the lower concentration and disappeared altogether with the higher dose of 5 alpha-DHT. CONCLUSIONS:The palmar fascia is a target tissue for androgen action via androgen receptors. Further studies are required to determine whether control of androgen receptor may control the evolution of Dupuytren's disease.     

Palmar fascial complex anatomy and pathology in Dupuytren's disease

Familiarity with the normal palmar fascial anatomy of the hand is necessary for understanding the convoluted pathologic changes that take place in Dupuytren's disease. This article includes a literature review and the findings of a study by the author of the fascial anatomy and pathology as related to Dupuytren's disease. Gross and microdissection of the palmar fascial structures were carried out with the aid of the operative microscope and an arthroscope, which allowed examination of the fine and undisturbed retinacular anatomy. The palmar fascial complex of the hand has five components: the radial aponeurosis, ulnar aponeurosis, central (palmar) aponeurosis, palmo-digital fascia, and digital fascia. The subtle constituents of each component are outlined and the transformation from normal to pathologic anatomy is clarified.     

掌腱膜挛缩症50例报告

目的讨论掌腱膜挛缩症的病因，病变特点及治疗方法。方法总结和分析经手术治疗的掌腱膜挛缩症５０例７８只手。其中包括取掌腱膜作病理检查的１１例。行掌腱膜大部切除、手掌及手指挛缩皮肤“Ｚ”成形术６３只手，掌腱膜及受累皮肤一并切除后行游离植皮术１５只手。结果术后平均随访６．４年，见挛缩解除，疗效肯定，无１例复发。１４只手产生并发症如神经损伤、皮下血肿、皮片成活不良及伤口Ⅱ期愈合等占１７．８％。组织学检查结果：均为致密结缔组织增生。结论掌腱膜挛缩症国人报道较少，常发生于中、老年，男性居多，手术治疗效果肯定。为减少并发症的发生，建议在屈曲挛缩已形成功能障碍时即应手术治疗     

Oestrogen and progesterone hormone receptors in Dupuytren''s disease

Dupuytren's disease is associated with alcoholism and chronic liver disease, conditions frequently associated with deranged steroid hormone metabolism. The possible influence of endogenous sex steroid hormones on the development of Dupuytren's disease has therefore been investigated. An analysis of diseased palmar fascia for oestrogen and progesterone receptors was undertaken in fifteen patients. Hormone specific receptors were not found in the palmar fascia of our patients with Dupuytren's disease, thus suggesting that other mechanisms or factors contribute to the pathogenesis of this fibrotic process.     

Dupuytren's contracture: morphological and biochemical changes in palmar aponeurosis

The palmar aponeurosis removed from ten patients with Dupuytren's contracture was studied using morphological and biochemical approaches. The histological characteristic of Dupuytren's contracture is the presence of numerous nodules among the lamellar structures of the collagen fibres. In the nodules, there are many active fibroblasts which are surrounded by immature fibres and metachromatic substances demonstrated by toluidine blue staining. Ultrastructurally, the active fibroblasts have the characteristics of myofibroblasts, as previously reported by Dr. Gabbiani. We found that some fibroblasts have intracellular collagen fibrils in the cytoplasm. When assayed by Siegel and Martin's method, lysyl oxidase activity of the palmar aponeurosis was significantly higher in Dupuytren's contracture than in normal hands. Biochemical studies such as electrophoretic analysis of mucopolysaccharides, determination of uronic acid and collagen contents were undertaken to compare the aponeurosis of Dupuytren's contracture with normal cases. The uronic acid contents were higher in Dupuytren's contracture than in the controls. However, no difference between the two groups was found in the collagen contents and in the composition of the mucopolysaccharides. These characteristic features; existence of myofibroblasts and intracellular collagen fibrils and increase in the activity of lysyl oxidase probably play a significant role in the establishment of flexion contracture of the fingers in Dupuytren's contracture.     

Pathogenesis of Dupuytren's contracture--a review]

Dupuytren's disease is a palmar fibromatosis bringing about irreversible finger contracture. Histopathologically, the disease is characterized by the presence of the two types of structures: nodules, containing of intensively proliferating cells, and fibrous cords, formed by thick bundles of collagen fibers. It seems that key role in the development of Dupuytren's contracture play alterations of palmar fibroblasts activity. These cells begin intensively proliferate and transform to myofibroblasts. The later ones sharing phenotypic features of fibroblasts and smooth muscle cells take part in remodelling of extracellular matrix and are a source of palmar contracture. The pivotal factors involved in changes of palmar fibroblasts functions seem to be growth factors (mainly TGF beta, PDGF and bFGF). However, the participation of reactive forms of oxygen in mentioned process is also considered.     

Skin tension in the aetiology of Dupuytren's disease; a prospective trial

Tension in the palmar fascia has been proposed as a factor causing Dupuytren's disease. If tension does stimulate the growth of new Dupuytren's tissue, relieving longitudinal tension should reduce the recurrence rate following surgery. Thirty patients with palmar Dupuytren's contracture of a single ray that affected only the metacarpophalangeal joint were divided into two groups. Both groups had a fasciotomy: one group through a transverse incision that was closed directly and the other through a longitudinal incision with Z-plasty closure. Half the patients (seven of 14) who had direct closure had recurrence at 2 years as compared to two of the 13 in the Z-plasty group. The trial was stopped at the interim analysis stage due to the high recurrence rate in the first group. These results are consistent with the tension hypothesis for the aetiology of Dupuytren's disease.     

Gene expression analysis of Dupuytren's disease: the role of TGF-beta2

Dupuytren's disease is characterised by nodular fibroblastic proliferation of the palmar fascia leading to contracture of the hand. Transforming growth factor beta (TGF-beta) is thought to play a role in its pathogenesis. We performed a cDNA microarray analysis of Dupuytren's diseased cord tissue with an emphasis on TGF-beta isoforms. Normal-appearing transverse ligament of the palmar fascia from adjacent to the diseased cord and palmar fascia from patients undergoing carpal tunnel release were used as controls. TGF-beta gene expression was confirmed by quantitative real-time polymerase chain reaction. Over 20 unique genes were found to be significantly up-regulated, including several previously reported genes. A dominant increase in TGF-beta2 expression was seen in the cord tissue, whereas TGF-beta1 and TGF-beta3 were found not to be significantly up-regulated. Quantitative real-time polymerase chain reaction confirmed these findings. This gene expression profile allows for further experiments that may eventually lead to gene therapy to block the development and progression of Dupuytren's disease clinically.     

Prostaglandins influence myofibroblast contractility in Dupuytren''s disease

This study investigated if the vasoactive prostaglandins, PGE2, and PGF2 alpha, were identifiable in association with nodular myofibroblasts of patients with Dupuytren's disease. Immunocytochemic studies, using antibodies specific for these prostaglandins, have confirmed their association with myofibroblasts. Radioimmunoassay was used to quantitate the prostaglandins. Our results indicate a significant increase of both prostaglandins, especially PGF2 alpha, in Dupuytren's palmar fascia when compared with control fascia. These endogenous prostaglandins may influence the contractile behavior of myofibroblasts in Dupuytren's disease to contribute to the pathobiology of this disorder.     

掌腱膜桡侧挛缩的临床特点与治疗

目的探讨掌腱膜桡侧挛缩的病变特点和临床疗效。方法对8例因掌腱膜桡侧挛缩行手术治疗的病例进行回顾性研究。8例的病变均位于虎口和大鱼际区域，表现为皮肤纠集、结节和条索，很少影响拇指的活动范围。均手术切除局部的掌腱膜条索。7例患者获得随访，平均随访25．1个月；1例失访。结果掌腱膜桡侧挛缩多与尺侧挛缩并发，手术治疗总体疗效较好，仅有1例复发。术后病理证实切除的组织为挛缩的掌腱膜。结论掌腱膜桡侧挛缩的发病部位集中于第一掌指关节的掌侧、大鱼际尺侧、虎口部位和大鱼际桡侧，未见累及指问关节，手术治疗可取得良好效果。     

Epidermal growth factor receptor (EGF-R) in Dupuytren's disease

The aim of this paper was to examine participation of the epidermal growth factor receptor (EGF-R) signal pathway in the pathogenesis of Dupuytren's disease. The study showed changes in the ratio of membrane EGF-R to its intracellular level during the different clinical stages of Dupuytren's contracture progression. Our observations of a high ratio of surface to intracellular EGF-R in the palmar aponeurosis of patients with second degree of Dupuytren's disease (Iselin's classification), which was significantly higher than this ratio in control palmar fascia (P=0.022), would suggest that EGF-R has a role in the involutional phase of the disease.