The importance of genetic susceptibility in Dupuytren's disease.

Dupuytren's disease (DD) is a progressive fibromatosis that causes the formation of nodules and cords in the palmar aponeurosis leading to flexion contracture of affected fingers. The etiopathogenesis is multifactorial with a strong genetic predisposition. It is the most frequent genetic disorder of connective tissues. We have collected clinical data from 736 unrelated individuals with DD who underwent surgical treatment from Germany and Switzerland. We evaluated a standardised questionnaire, assessed the importance of different risk factors and compared subgroups with and without positive family history. We found that family history clearly had the strongest influence on the age at first surgery compared to environmental factors, followed by male sex. Participants with a positive family history were on average 55.9 years of age at the first surgical intervention, 5.2 years younger than probands without known family history (p = 6.7 × 10(-8) ). The percentage of familial cases decreased with age of onset from 55% in the 40-49 years old to 17% at age 80 years or older. Further risk factors analysed were cigarettes, alcohol, diabetes, hypertension, and epilepsy. Our data pinpoint the importance of genetic susceptibility for DD, which has long been underestimated.

Changes in canine skeletal muscles during experimental tibial lengthening.

In 24 beagles, lengthening of the right tibia was performed by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day, with a distraction rate of 0.5 mm twice per day, and ended after 25 days. A control group of six additional dogs underwent tibial osteotomy and external fixation without distraction. Twelve animals with and three animals without leg lengthening were euthanized immediately after the distraction period of 25 days (Group A); the remaining 15 dogs were euthanized after an additional consolidation phase of another 25 days (Group B). From the distracted right leg and from the left control leg the tibialis anterior muscle, extensor digitorum longus muscle, peroneus longus muscle, and gastrocnemius muscle were removed and studied by means of routine histologic, histochemical, and immunohistochemical analyses, and electron microscopic examination. The muscles of the control group showed no differences between the right and left sides. However, in the other 24 dogs of Groups A and B, the authors saw marked alterations affecting only the lengthened muscles but not the muscles of the control limbs. These changes were highly significant and included muscle fiber degeneration and regeneration, target fibers, central cores, minicores, marked endomysial and perimysial fibrosis, and atrophy of Type 1 and Type 2 fibers. In the consolidation period (Group B) fiber type grouping indicated that reinnervation had occurred. In addition, an increase in satellite cells and myoblasts and proliferation of nuclei were observed. The findings of the current study indicate that leg lengthening results not only in muscle fiber degeneration followed by regeneration and reinnervation but also in formation of new muscle tissue.

Morphometric analysis of canine skeletal muscles following experimental callus distraction according to the Ilizarov method.

Muscle fiber diameter and fiber-type distribution were analyzed during callus distraction. The right tibia in 24 beagles was lengthened 2.5 cm by callus distraction after osteotomy and application of a ring fixator. Distraction was started at the fifth postoperative day, at a rate of two times for 0.5 mm per day. Twelve dogs that underwent limb-lengthening and three dogs in the control group that did not undergo limb-lengthening were killed at the end of the 25-day distraction phase (group A). The remaining dogs (12 that underwent limb-lengthening and three that did not) were killed after an additional consolidation period of 25 days (group B). The tibialis anterior, extensor digitorum longus, peroneus longus, and gastrocnemius muscles were removed from the right limb (which had undergone distraction) and the left control side of each animal. Crosscut cryostat sections were stained by adenosine triphosphatase at pH 4.3 and 9.4 to determine the size and distribution of types I and II fibers. Morphometric analysis of the muscle fibers was performed by a computer-assisted two-point technique. On the lengthened side, the muscles revealed marked atrophy affecting predominantly type-II fiber in the dogs in group A and affecting both fiber types in dogs in group B. Fiber density increased in both groups. In addition, fiber-type grouping indicative of reinnervation was obvious in group B. Fiber-type distribution in the dogs in group B showed a shift toward type I in the tibialis anterior (p = 0.043) and extensor digitorum longus (p = 0.034) muscles and a shift toward type II in the gastrocnemius (p = 0.038). The data show that tension-stress during tibial lengthening leads to atrophy of type-II fiber, reflecting disuse of muscle fiber in the distraction period as well as neurogenic atrophy followed by the reinnervation processes. Furthermore, the data are consistent with the occurrence of histoneogenesis during limb-lengthening resulting in an increase in fiber density.