Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading.

Myostatin (GDF8) is a negative regulator of skeletal muscle growth and mice lacking myostatin show a significant increase in muscle mass and bone density compared to normal mice. In order to further define the role of myostatin in regulating bone mass we sought to determine if loss of myostatin function significantly altered the potential for osteogenic differentiation in bone marrow-derived mesenchymal stem cells in vitro and in vivo. We first examined expression of the myostatin receptor, the type IIB activin receptor (AcvrIIB), in bone marrow-derived mesenchymal stem cells (BMSCs) isolated from mouse long bones. This receptor was found to be expressed at high levels in BMSCs, and we were also able to detect AcvrIIB protein in BMSCs in situ using immunofluorescence. BMSCs isolated from myostatin-deficient mice showed increased osteogenic differentiation compared to wild-type mice; however, treatment of BMSCs from myostatin-deficient mice with recombinant myostatin did not attenuate the osteogenic differentiation of these cells. Loading of BMSCs in vitro increased the expression of osteogenic factors such as BMP-2 and IGF-1, but treatment of BMSCs with recombinant myostatin was found to decrease the expression of these factors. We investigated the effects of myostatin loss-of-function on the differentiation of BMSCs in vivo using hindlimb unloading (7-day tail suspension). Unloading caused a greater increase in marrow adipocyte number, and a greater decrease in osteoblast number, in myostatin-deficient mice than in normal mice. These data suggest that the increased osteogenic differentiation of BMSCs from mice lacking myostatin is load-dependent, and that myostatin may alter the mechanosensitivity of BMSCs by suppressing the expression of osteogenic factors during mechanical stimulation. Furthermore, although myostatin deficiency increases muscle mass and bone strength, it does not prevent muscle and bone catabolism with unloading.

Incidence and prognostic influence of lymph node micrometastases in rectal cancer.

AIMS: The aim of this study was to determine the rate of lymph node micrometastases and evaluate their prognostic significance in rectal cancer. METHODS: Patients with either Dukes A or B rectal carcinoma who had undergone curative resection by either low anterior resection or abdominal perineal resection between 1991 and 2000 were selected from a prospectively collated database. None of the patients had metastasis at the time of surgery and none received adjuvant or neoadjuvant therapy. A single section from each lymph node was stained with haematoxylin and eosin (H+E) and with CAM 5.2 by immunohistochemistry. Statistical analyses were performed with Chi-square test. RESULTS: A total of 774 lymph nodes with a median of 14 lymph nodes per patient were examined, from a cohort of 56 patients with a median age of 66 years. In the 56 patients in whom lymph node metastases were not detected by haematoxylin-eosin staining, cytokeratin staining was positive in 15 lymph nodes from 10 patients. Nine patients had disease recurrence at a median follow-up of 98 months. The presence of lymph node micrometastases by immunohistochemistry did not predict either disease-free (p=0.44) or overall survival (p=0.63). CONCLUSION: Immunohistochemical staining detects micrometastases in rectal cancer which are not observed with H+E staining. However, no significant relationship was observed between disease relapse and rectal micrometastases detected by immunohistochemistry.

Osteosynthesis for the unstable fracture of the hand.

Unstable, displaced, fractures of the hand present a challenge to surgeons all over the world. Retention of the reduction using a cast, splint or even K wire fixation is difficult during the period of bone healing: also a relatively prolonged period of immobilisation after such treatment leads to stiffness of the metacarpal and finger joints. The picture gets more complicated if the hand suffers more than one fracture. The unique ability of the hand to grasp and grip objects of different size and shape depends on the intact functional anatomy of the hand articulations. Thus accurate and stable reduction of metacarpal and phalangeal fractures is essential for early active mobility with a view to early return to work even before the recovery is complete, especially in the case of an industrial worker. We recommend osteosynthesis as a method of choice for treating such displaced, unstable fractures of the hand as shown by the present retrospective study of fifty patients. We suggest a simple practical method of assessing the results of treatment for severe fractures of the hand.

Flexor tendon sheath haematoma: a case report.

An open finger injury reported here was diagnosed as a division of the flexor tendons of the little finger. However, surgical exploration revealed intact tendons encased in a tense flexor tendon sheath haematoma. Decompression of the haematoma led to a satisfactory recovery of finger function.

Hand injury with paint-gun.

Paint-gun injuries are notoriously disabling, far more so than those caused by other foreign materials as they carry a high morbidity rate. Forty-three cases of high pressure injection injury due to paint-guns have been reported in the English literature. The four new cases reported here reflect the effects of injury by the epoxy resins, relatively recently introduced and widely used in heavy industry.

Lateral Monteggia fracture in children (case report).

A lateral Monteggia fracture in a child is reported. Between 1941 and 1977, only 16 such cases were reported in the literature. Of these, 2 cases needed open reduction of the fractured ulna. The present case needed osteotomy of a nearly healed fracture of the ulna and reconstruction of the orbicular ligament to stabilise the reduction of the radial head. No similar case has previously been described in a child. Prompt diagnosis and early reduction should yield good results by closed methods of treatment, but open reduction is necessary if the diagnosis is missed and treatment is delayed. Even after such delayed surgery, the final outcome in the present case was very satisfactory and the child regained full elbow function.

Osteosarcoma arising in a femur with melorheostosis and osteopathia striata.

Osteopathia striata is an asymptomatic autosomal dominant or sporadically inherited disorder that causes dense striations at sites of endochondral bone formation, with a predilection for the metaphyses of long bones. Melorheostosis is a mixed sclerosing dysplasia with disturbance of both endochondral and intramembranous ossification, in which disordered intramembranous ossification dominates. It presents typical radiological changes of cortical hyperostosis distributed along a sclerotome with variable associated cutaneous and clinical features. Overlap syndromes including one or more of these diseases are described. We report a 44-year-old man with both melorheostosis and osteopathia striata who presented with pain secondary to superimposed osteosarcoma. In reporting this case we discuss the relationship between sclerosing dysplasia and either coexisting or complicating sarcoma.

Transjugular liver biopsy: assessment of safety and efficacy of the Quick-Core biopsy needle.

BACKGROUND: We assessed the safety and efficacy of transjugular liver biopsy with the Quick-Core biopsy needle. METHODS: Fifty consecutive patients with liver failure and contraindications to percutaneous liver biopsy were referred for transjugular liver biopsy. Eighteen (36%) patients had thrombocytopenia (platelet range = 44-92/microL, mean = 66/microL), 31 (62%) patients had elevated prothrombin times (international normalized ratio range = 1.3-3, mean = 1.6), and 19 (38%) patients had ascites. The Cook Quick-Core biopsy needle was used. RESULTS: Average procedure time was 30 min. Transjugular access to the hepatic veins was successful in 49 of 50 cases. A transfemoral approach was used in one patient. Tissue specimens were satisfactory for histologic diagnosis in all cases. Established cirrhosis was present in 37 (74%) patients. The mean number of cores was 2.2 (range = 1-3). The mean number of portal triads per core was 10.4 (range = 6-20). There were no procedure-related complications. CONCLUSION: Transjugular liver biopsy with the Quick-Core biopsy needle is safe and effective in patients in whom the percutaneous route is contraindicated by coagulopathy or ascites.