Assessing reproducibility for radiographic measurement of leg length inequality after total hip replacement

Leg length inequality (LLI) as a result of total hip replacement can cause considerable morbidity. Although LLI was described when the technique was popularised in the 1960s, it remains a significant challenge to arthroplasty surgeons. This study reviews the established practice for the measurement of LLI on plain antero-posterior radiograph, and compares these techniques to two methods used locally. The radiographs of 35 patients were measured using four techniques. All four methods yielded an interclass correlation co-efficient of ≥0.90 for inter reader reliability. This study shows that the four methods are comparable for reliability, while a composite method, measuring from the centre of femoral rotation to the inferior teardrop and then to the lesser trochanter, has the added advantage of providing extra information on component position as well as an overall measure of LLI

Potential for Tumorigenesis and Repair of Osteochondral Defects by iPS Cell Transplantation in Rat

Abstract Articular cartilage repair remains a challenge in the field of orthopedic medicine. Cell-based therapy for cartilage repair, such as autologous chondrocyte implantation, was established in the 1990s. However, the issue of the source from which the lesion-targeting cells are harvested remains a limitation of this approach as larger lesions require more cells for repair, and thus, more healthy tissue must be damaged to harvest the needed cells. Reprogramming of induced pluripotent stem (iPS) cells is a promising tool for cell-based regenerative therapy because of their proliferative capacity and pluripotency; however, these characteristics also create a risk of tumorigenesis. This study aimed to determine the probability of iPS cell-derived tumor occurrence as a function of injection or transplantation site, and to assess whether transplanted iPS cells can promote cartilage defect repair. Pluripotent mouse iPS cells (5x10 6 cells/ml) were subcutaneously injected or transplanted into experimentally induced lesions in the knee cartilage of immunodeficient rats. Subcutaneous teratoma formation was observed in 30% of animals (3 of 10) at 4weeks, and 41% of animals (7 of 17) at 12 weeks after iPS cell injection. Cartilage repair as indicated by modified Wakitani's score was similar in the cell-free group and in the iPS cell implantation group at 4 weeks [11.8 ± 1.8 (n = 8) vs. 10.3 ± 2.8 (n = 18)]. iPS cell implantation yielded a score of 7.8 ± 2.0 (n = 10) at 12 weeks, significantly better than the cell-free group [10.5 ± 0.6 (n = 4)]. There was no macro-or microscopic evidence of tumor formation at the cartilage repair site after iPS cell implantation. Although we could not use the iPS cells directly for cartilage repair, the results of our study indicate the potential for a new therapy for cartilage repair by developing iPS reprogramming technology

Identification of major dioxin-like compounds and androgen receptor antagonist in acid-treated tissue extracts of high trophic-level animals

We evaluated the applicability of combining in vitro bioassays with instrument analyses to identify potential endocrine disrupting pollutants in sulfuric acid-treated extracts of liver and/or blubber of high trophic-level animals. Dioxin-like and androgen receptor (AR) antagonistic activities were observed in Baikal seals, common cormorants, raccoon dogs, and finless porpoises by using a panel of rat and human cell-based chemical-activated luciferase gene expression (CALUX) reporter gene bioassays. On the other hand, no activity was detected in estrogen receptor α (ERα)-, glucocorticoid receptor (GR)-, progesterone receptor (PR)-, and peroxisome proliferator-activated receptor γ2 (PPARγ2)-CALUX assays with the sample amount applied. All individual samples (n = 66) showed dioxin-like activity, with values ranging from 21 to 5500 pg CALUX-2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ)/g-lipid. Because dioxins are expected to be strong contributors to CALUX-TEQs, the median theoretical contribution of dioxins calculated from the result of chemical analysis to the experimental CALUX-TEQs was estimated to explain up to 130% for all the tested samples (n = 54). Baikal seal extracts (n = 31), but not other extracts, induced AR antagonistic activities that were 8-150 μg CALUX-flutamide equivalent (FluEQ)/g-lipid. p,p′-DDE was identified as an important causative compound for the activity, and its median theoretical contribution to the experimental CALUX-FluEQs was 59% for the tested Baikal seal tissues (n = 25). Our results demonstrate that combining in vitro CALUX assays with instrument analysis is useful for identifying persistent organic pollutant-like compounds in the tissue of wild animals on the basis of in vitro endocrine disruption toxicity. © 2011 American Chemical Society

Small Interfering RNA Targeted to IGF-IR Delays Tumor Growth and Induces Proinflammatory Cytokines in a Mouse Breast Cancer Model

Insulin-like growth factor I (IGF-I) and its type I receptor (IGF-IR) play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs) for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2′-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD). Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2′-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines

Sea surface temperature control on the distribution of far-traveled Southern Ocean ice-rafted detritus during the Pliocene

The flux and provenance of ice-rafted detritus (IRD) deposited in the Southern Ocean can reveal information about the past instability of Antarctica's ice sheets during different climatic conditions. Here we present a Pliocene IRD provenance record based on the Ar/Ar ages of ice-rafted hornblende grains from Ocean Drilling Program Site 1165, located near Prydz Bay in the Indian Ocean sector of the Southern Ocean, along with the results of modeled sensitivity tests of iceberg trajectories and their spatial melting patterns under a range of sea surface temperatures (SSTs). Our provenance results reveal that IRD and hence icebergs in the Prydz Bay area were mainly sourced from (i) the local Prydz Bay region and (ii) the remote Wilkes Land margin located at the mouth of the low-lying Aurora Subglacial Basin. A series of IRD pulses, reaching up to 10 times background IRD flux levels, were previously identified at Site 1165 between 3.3 and 3.0Ma. Our new results reveal that the average proportion of IRD sourced from distal Wilkes Land margin doubles after 3.3Ma. Our iceberg trajectory-melting models show that slower iceberg melting under cooling SSTs over this middle Pliocene interval allowed Wilkes Land icebergs to travel farther before melting. Hence, declining SSTs can account for a large part of the observed IRD provenance record at Site 1165. In early Pliocene IRD layers, sampled at suborbital resolution around 4.6Ma, we find evidence for significant increases in icebergs derived from Wilkes Land during very warm interglacials. This is suggestive of large-scale destabilization of the East Antarctic Ice Sheet in the Aurora Subglacial Basin, as far-traveled icebergs would have to overcome enhanced melting in warmer SSTs. Our results highlight the importance of considering SSTs when interpreting IRD flux and provenance records in distal locations

A review of symptomatic leg length inequality following total hip arthroplasty

Leg length inequality (LLI) following total hip replacement is a complication which features increasingly in the recent literature. The definition of LLI is complicated by lack of consensus regarding radiological measurement, clinical measurement and the incomplete relationship between LLI and associated symptoms. This paper reviews 79 reports relating to LLI post hip replacement, detailing definitions and classification and highlighting patient populations prone to symptomatic LLI. While there is no universal definition of LLI, there is a broad consensus that less than 10 mm of difference on AP view plain radiographs is clinically acceptable. There are few techniques described that consistently produce a postoperative LLI of less than this magnitude. Where postoperative LLI exists, lengthening appears to cause more problems than shortening. In cases of mild LLI, non-surgical management produces adequate outcomes in the majority of cases, with functional LLI cases doing better than those with true LLI. Operative correction is effective in half of cases, even where nerve palsy is present, and remains an important option of last resort. Poor outcomes in patients with LLI may be minimised if individuals at risk are identified and counselled appropriately