Systematic review of the treatment of Kienböck's disease in its early and late stages.

PURPOSE: To perform a systematic review of the treatment of Kienböck's disease to test the hypothesis that none of the reported treatments for Kienböck's disease is superior with respect to outcomes of pain, motion, grip strength, and radiographic measures. METHODS: We searched PubMed, Medline, and the Cochrane Review for articles published between 1998 and 2008 reporting outcomes of treatment for Kienböck's disease. Patients were grouped by stage of disease. Early stages were defined as Lichtman stage I, II, and IIIa, and 'late' stages as IIIb and IV. The groups were then analyzed on the basis of treatment; procedures performed on subjects in the early group included vascularized bone grafting (VBG), metaphyseal core decompression, and radial osteotomy, whereas the procedures performed on subjects in the late group included VBG, radial osteotomy, partial arthrodesis, proximal row carpectomy, tendon ball arthroplasty, and nonsurgical treatment. RESULTS: We found no statistically significant difference between any of the treatment groups for subjective pain outcomes. In terms of objective measures, statistically significant improvement (p<.05) was seen in range of motion after radial osteotomy and VBG in early-stage patients and after all interventions, except partial arthrodesis and nonsurgical treatment, for late-stage patients. Grip strength was significantly improved in early-stage patients after radial osteotomy and VBG and for all late-stage patients, except among those managed nonsurgically. Changes in Stahl and carpal height index scores were not statistically significant regardless of intervention, except after radial osteotomy in the early group, where they statistically worsened. CONCLUSIONS: Based on retrospective data from uncontrolled studies, no active treatment is superior in the treatment of Kienböck's disease and there are insufficient data to determine whether the outcomes of any intervention are superior to placebo or the natural history of the disease.

Telomeric transgenes are silenced in adult mouse tissues and embryo fibroblasts but are expressed in embryonic stem cells.

In addition to their role in protecting the ends of chromosomes, telomeres also influence the expression of adjacent genes, a process called telomere-position effect. We previously reported that the neo and HSV-tk transgenes located adjacent to telomeres in mouse embryonic stem cells are initially expressed at low levels and then become gradually silenced upon passage in culture through a process involving DNA methylation. We also reported extensive DNA methylation in these telomeric transgenes in three different tissues isolated from mice generated from one of these embryonic stem cell clones. In the present study, we demonstrate that embryo fibroblasts isolated from two different mouse strains show extensive DNA methylation and silencing of the telomeric transgenes. Consistent with this observation, we also demonstrate little or no detectable expression of the HSV-tk telomeric transgene in somatic tissues using whole body imaging. In contrast, both telomeric transgenes are expressed at low levels and have little DNA methylation in embryonic stem cell lines isolated from these same mouse strains. Our results demonstrate that telomere-position effect in mammalian cells can be observed either as a low level of expression in embryonic stem cells in the preimplantation embryo or as complete silencing and DNA methylation in differentiated cells and somatic tissues. This pattern of expression of the telomeric transgenes demonstrates that subtelomeric regions, like much of the genome, are epigenetically reprogrammed in the preimplantation embryo, a process that has been proposed to be important in early embryonic development. Disclosure of potential conflicts of interest is found at the end of this article.