Sorafenib in Dupuytren and Ledderhose Disease

Palmar and plantar fibromatosis are benign proliferative processes which present as a diffuse thickening or nodules of the hands and/or feet and may lead to flexion contractures, pain, and functional impairment known as Dupuytren and Ledderhose diseases, respectively. Current treatments are noncurative and associated with significant morbidity. Here, we report on the outcomes of 5 patients with advanced disease, no longer surgical candidates, treated with sorafenib. Sorafenib exhibited an expected safety profile. All 5 patients demonstrated objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline and all 5 patients reported subjective pain relief and/or functional improvement. Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRβ, a known target of sorafenib. The outcomes of these 5 patients suggest the safety and efficacy of a relatively well-tolerated oral agent in the treatment of Dupuytren and Ledderhose diseases and suggest the need for future controlled studies.     

Synovial chondromatosis of the elbow in a child

Synovial chondromatosis is cartilaginous metaplasia of mesenchymal remnants of synovial tissue of the joints. Its main characteristic is the formation of cartilaginous nodules in the synovium and inside the articular space (loose bodies). It usually presents between the third and fifth decades and is rare in children. It presents as a mono-articular pathology affecting large joints such as the knee, hip, and elbow. The main symptoms are pain, swelling, and limitation of movements in the affected joint. Diagnosis is made by panoramic radiographs, computed tomography scan, and mainly magnetic resonance imaging and on surgery. The authors describe of synovial chondromatosis presenting in the elbow of an 11 year-old girl which is unreported to the best of our knowledge.     

Endonuclease G is required for early embryogenesis and normal apoptosis in mice

Endonuclease G (EndoG) is a nuclear-encoded mitochondrial protein reported to be important for both nuclear DNA fragmentation during apoptosis and mitochondrial DNA replication. To evaluate the in vivo function of EndoG, we have investigated the effects of EndoG deficiency in cells and mice. We found that EndoG homozygous mutant embryos die between embryonic days 2.5 and 3.5. Mitochondrial DNA copy numbers in ovulated oocytes from EndoG heterozygous mutant and wild-type mice are similar, suggesting that EndoG is involved in a cellular function unrelated to mitochondrial DNA replication. Interestingly, we found that cells from EndoG heterozygous mutant mice exhibit increased resistance to both tumor necrosis factor alpha- and staurosporine-induced cell death. Moreover, spontaneous cell death of spermatogonia in EndoG heterozygous mutant mice is significantly reduced compared with wild-type mice. DNA fragmentation is also reduced in EndoG+/- thymocytes and splenocytes compared with wild-type cells, as well as in EndoG+/- thymus in vivo compared with that of the wild-type mice, on activation of apoptosis. These findings indicate that EndoG is essential during early embryogenesis and plays a critical role in normal apoptosis and nuclear DNA fragmentation.     

Early postoperative feeding and outcome in neonates

OBJECTIVES: The results of neonatal surgery in the Western world have rapidly improved over the past three decades. Early nutrition support is thought to be one of the key factors. We used transgastric, transanastomotic feeding jejunostomy tubes in every infant undergoing upper gastrointestinal surgery when the expected period of fasting has exceeded 7 d. METHODS: Newborns with duodenal atresia, malrotation, and jejunal atresia were treated consecutively between November 1998 and November 1999. We analyzed the outcome of such a practice. There were 17 consecutive babies recruited into the study. Ten babies had duodenal atresia, one associated with esophageal atresia and tracheo-esophageal fistula, six had malrotation, and one had jejunal atresia. The weights of the babies varied between 1.2 and 3.78 kg (mean = 2.1 kg) and they were referred between the ages of 1 and 23 d. Three babies were younger than 32 wk of gestation and weighed less than 1.5 kg; all had multiple bowel atresia, including one with associated pyloric atresia. None of these three survived. Enteral feeding was started by postoperative day 2 in 14 cases. Period of feeding varied between 3 and 20 d, with a mean of 10.4 d in the surviving babies. Three of the tubes had minor mechanical complications. RESULTS: The weight loss or gain during the period of hospitalization was not significant (P = 0.3) Breast milk was the most common nutrient. Thirteen of the 14 babies weighing more than 1.5 kg were discharged and are being followed; the remaining baby died from neonatal septicemia. Excellent results can be obtained with aggressive enteral nutrition support in newborns undergoing upper intestinal surgery. CONCLUSIONS: Transgastric, transanastomotic feeding jejunostomy was well tolerated by the newborns and is preferable to parenteral nutrition.