[Impact of soft tissue injury on results after osteosynthesis of intraarticular fractures of the base of the middle phalanx of the finger]. / Einfluss von Weichteilverletzungen auf die Ergebnisse operativ versorgter intraartikulärer Mittelphalanx - Basisfrakturen.

BACKGROUND: The aim of this study was to investigate retrospectively if soft tissue injuries have an impact on the functional results of surgically treated intra-articular fractures of the base of the middle phalanx. PATIENTS AND METHODS: From 1/2007 to 4/2010 we operated on 27 patients with intra-articular fractures of the base of the middle phalanx with pins, screws or external fixation analogous to Suzuki. 5 patients were excluded. 13 patients had no significant soft tissue injury (kWTV group), 9 patients had significant soft tissue damage including open fractures, skin lesions or/and severe soft tissue swelling (WTV group). Postoperative function and complications were analysed based on total active range of motion (TAM) and range of motion of the proximal interphalangeal joint (PIP-ROM) with regard to the Larsen score and clinical data. RESULTS: Fractures with soft tissue injuries had a significantly worse TAM outcome (p=0.04) than fractures without soft tissue injury (kWTV group: TAM 197.1°; WTV group TAM 231.2°) even if the functional results regarding the Larsen classification were excellent or good in both groups (kWTV 100%, WTV 88.9%). There were no significant differences regarding PIP-ROM of both groups. CONCLUSION: Soft tissue injuries have a negative impact on the functional results of surgical treated intra-articular fractures of the base of the middle phalanx. The influence on PIP-ROM might be less. Other factors might play a considerable role for PIP-ROM. With an adequate operative treatment most intra-articular middle phalanx fractures show good to excellent functional -results.

Evidence for radiosensitizing by gliotoxin in HL-60 cells: implications for a role of NF-kappaB independent mechanisms.

Radioresistance markedly impairs the efficacy of tumor radiotherapy and may involve antiapoptotic signal transduction pathways that prevent radiation-induced cell death. A common cellular response to genotoxic stress induced by radiation is the activation of the nuclear factor kappa B (NF-kappaB). NF-kappaB activation in turn can lead to an inhibition of radiation-induced apoptotic cell death. Thus, inhibition of NF-kappaB activation is commonly regarded as an important strategy to abolish radioresistance. Among other compounds, the fungal metabolite gliotoxin (GT) has been reported to be a highly selective inhibitor of NF-kappaB activation. Indeed, low doses of GT were sufficient to significantly enhance radiation-induced apoptosis in HL-60 cells. However, this effect turned out to be largely independent of NF-kappaB activation since radiation of HL-60 cells with clinically relevant doses of radiation induced only a marginal increase in NF-kappaB activity, and selective inhibition of NF-kappaB by SN50 did not result in a marked enhancement of GT-induced apoptosis. GT induced activation of JNKs, cytochrome c release from the mitochondria and potently stimulated the caspase cascade inducing cleavage of caspases -9, -8, -7 and -3. Furthermore, cleavage of the antiapoptotic protein X-linked IAP and downregulation of the G2/M-specific IAP-family member survivin were observed during GT-induced apoptosis. Finally, the radiation-induced G2/M arrest was markedly reduced in GT-treated cells most likely due to the rapid induction of apoptosis. Our data demonstrate that various other pathways apart from the NF-kappaB signaling complex can sensitize tumor cells to radiation and propose a novel mechanism for radiosensitization by GT, the interference with the G2/M checkpoint that is important for repair of radiation-induced DNA damage in p53-deficient tumor cells.