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Heterotopic ossification (HO) is a frequent complication of total hip arthroplasty (THA). HO can cause pain, limitation of range of motion, and instability. Radiation therapy (RT) for HO prophylaxis is well established but may interfere with early porous ingrowth and pullout strength of implants, as suggested by two animal studies. Although shielding of the bone from irradiation may theoretically protect ingrowth, it has been found to reduce RT effectiveness. Despite the popularity of porous implants in THA, the frequency of HO, and use of RT in its prophylaxis, the effect of RT on porous implant fixation in THA has not been previously reported. At our institution, we use unshielded, single-dose, preoperative 700 to 800 centigrays RT for HO prophylaxis in high-risk patients. We hypothesize that this RT protocol is effective and the press-fit technique protects porous implants during early ingrowth; therefore, long-term implant fixation is not compromised.This was a retrospective study aiming to determine fixation of porous THA implants, healing of trochanteric osteotomies, and efficacy of HO prophylaxis with this RT protocol.Thirty-nine patients with follow-up of 24 to 144 months (average 59.7 months) were included. All 26 porous-coated femoral implants (11 revisions and 15 primary) were well fixed. There were 33 porous-coated acetabular implants (18 revisions and 15 primary). Thirty (91%) were well fixed, and three revision implants (9%) demonstrated radiolucent lines in two zones, but patients were clinically asymptomatic. All nine trochanteric osteotomies healed uneventfully. RT provided effective HO prophylaxis in 33 of 39 hips (85%).Single, low-dose, preoperative RT without shielding does not increase aseptic loosening of porous implants manufactured with plasma porous spray or nonunion of extended trochanteric osteotomies. This protocol provides effective HO prophylaxis in high-risk patients undergoing primary and revision THA.

Capillary hemangioma is a congenital malformation of the capillary. It commonly affects the face, eyelids, lips and skin. Adult capillary hemangioma involving the nasal cavity is rare and may be misdiagnosed as polyps or another tumor. This case report illustrated a middle-age adult patient in Malaysia who presents with unilateral nasal obstruction and intermittent epistaxis who later confirmed capillary hemangioma involving the right nasal septum. Endoscopic surgery excision of the hemangioma was successfully performed. There were no known risk factors present in him. A treating doctor in the outpatient clinic seeing symptoms such as unilateral nasal obstruction must consider alternative diagnosis such as hemangioma besides usual diagnosis of polyps.

Vascular endothelial cells play a critical role in bone formation and development. While the interplay between the endothelium and bone is complex and not yet fully understood, recent studies have revealed mechanisms behind endothelial influence on bone. Regulatory signals such as Vascular endothelial growth factor-A, matrix metalloproteinases, and fibroblast growth factors have been shown to influence the development, proliferation, and homeostasis of bone and the endothelium. Additionally, research in skeletal and systemic diseases and therapies has suggested the coupling of angiogenesis and proper bone development. Furthermore, advances in bone tissue engineering show the potential for implanted endothelial progenitor cells and signaling factors to accelerate fracture healing processes. Further investigations into the relationship between bone and vasculature could advance our understanding of bone formation, growth, and repair.

Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.

Aplikasi pengukuran telah banyak digunakan di sistem IOS maupun android. Namun, aplikasi pengukuran berbasis android tidak sebaik dengan aplikasi pengukuran berbasis sistem IOS. Beberapa orang masih meragukan keakuratan aplikasi ini karena terkadang hasil pengukuran tidak akurat dan masih banyak eror atau bug. Tujuan dari kegiatan ini adalah untuk mengembangkan aplikasi pengukuran berbasis android dengan tingkat keakuratan 90%. Apikasi pengukuran ini menerapkan AR (Augmented Reality). Proses pembuatan aplikasi menggunakan software android studio, library dan ARcore. Untuk Bahasa pemrograman yang digunakan yaitu Java Output. Pertimbangan menggunakan perangkat tersebut aplikasi pengukuran untuk smartphone berbasis Android dapat mengukur atau mengetahui dimensi benda bangun datar dan bangun ruang dengan satuan cm dan hasil pengukuran yang akurat. Kata Kunci: Augmented Reality, Android, Aplikasi, Pengukuran, Akura

CASE Heterotopic ossification (HO) is a pathological formation of bone in nonosseous tissue and is a common complication of orthopaedic procedures. Radiotherapy is often used to prevent HO despite the small risk of secondary malignancy. Here, we report a case of a patient who developed a periprosthetic, radiation-induced sarcoma after delivery of a single fraction of 7 Gy for HO prophylaxis. This sarcoma was found to lie entirely within the treatment field and occurred within 5 years of radiation. CONCLUSION Appropriate counseling regarding radiation-induced sarcoma formation should be provided to patients considering radiotherapy for this HO prophylaxis.

Half of the women who sustain a hip fracture would not qualify for osteoporosis treatment based on current DXA-estimated bone mineral density criteria. Therefore, a better approach is needed to determine if an individual is at risk of hip fracture from a fall. The objective of this study was to determine the association between radiation-free MRI-derived bone strength and strain simulations compared to results from direct mechanical testing of cadaveric femora. Imaging was conducted on a 3-Tesla MRI scanner using two sequences: one balanced steady-state free precession sequence with 300 μm isotropic voxel size and one spoiled gradient echo with anisotropic voxel size of 234 × 234 × 1500 μm. Femora were dissected free of soft-tissue and 4350-ohm strain-gauges were securely applied to surfaces at the femoral shaft, inferior neck, greater trochanter, and superior neck. Cadavers were mechanically tested with a hydraulic universal test frame to simulate loading in a sideways fall orientation. Sideways fall forces were simulated on MRI-based finite element meshes and bone stiffness, failure force, and force for plastic deformation were computed. Simulated bone strength metrics from the 300 μm isotropic sequence showed strong agreement with experimentally obtained values of bone strength, with stiffness (r = 0.88, p = 0.0002), plastic deformation point (r = 0.89, p 0.0001), and failure force (r = 0.92, p 0.0001). The anisotropic sequence showed similar trends for stiffness, plastic deformation point, and failure force (r = 0.68, 0.70, 0.84; p = 0.02, 0.01, 0.0006, respectively). Surface strain-gauge measurements showed moderate to strong agreement with simulated magnitude strain values at the greater trochanter, superior neck, and inferior neck (r = -0.97, -0.86, 0.80; p ≤0.0001, 0.003, 0.03, respectively). The findings from this study support the use of MRI-based FE analysis of the hip to reliably predict the mechanical competence of the human femur in clinical settings.

Case An 11-year-old female patient underwent bilateral in situ fixation for slipped capital femoral epiphyses using single, cannulated, stainless steel screws. She presented 12 years later with a large osteolytic lesion of the proximal femur, which only involved 1 side. Histological evaluation showed a foreign-body reaction and synovial lining. Infection was ruled out and dynamic hip screw stabilization, and bone grafting were performed. The bone graft healed, and the hardware was removed to prevent a similar reaction. In retrospect, postoperative radiographs at 7 weeks showed subtle osteolysis along the screw. Conclusion Intra-articular drilling, vertical screw placement into the posterior epiphysis, and the prominent screw head may have led to this unexpected complication.

SummaryA global rising organ shortage necessitates the use of extended criteria donors (ECD) for liver transplantation (LT). However, poor preservation and extensive ischemic injury of ECD grafts have been recognized as important factors associated with primary non-function, early allograft dysfunction, and biliary complications after LT. In order to prevent for these ischemia-related complications, machine perfusion (MP) has gained interest as a technique to optimize preservation of grafts and to provide the opportunity to assess graft quality by screening for extensive ischemic injury. For this purpose, however, objective surrogate biomarkers are required which can be easily determined at time of graft preservation and the various techniques of MP. This review provides an overview and evaluation of biomarkers that have been investigated for the assessment of graft quality and viability testing during different types of MP. Moreover, studies regarding conventional graft preservation by static cold storage (SCS) were screened to identify biomarkers that correlated with either allograft dysfunction or biliary complications after LT and which could potentially be applied as predictive markers during MP. The pros and cons of the different biomaterials that are available for biomarker research during graft preservation are discussed, accompanied with suggestions for future research. Though many studies are currently still in the experimental setting or of low evidence level due to small cohort sizes, the biomarkers presented in this review provide a useful handle to monitor recovery of ECD grafts during clinical MP in the near future.

Ongoing research is being conducted in the field of transplantation to discover novel, noninvasive biomarkers for assessment of graft quality before transplantation and monitoring of graft injury after transplantation. MicroRNAs (miRNAs) are among the most promising in this field. MiRNAs are small noncoding RNAs that function as important regulators of gene expression in response to cellular stress and disease. An advantage that makes miRNAs attractive candidates for biomarker research is their fast release from cells in response to stress and injury, which can occur via different routes. In the context of liver transplantation (LT), noninvasive measurement and stability of extracellular miRNAs in blood, bile, and graft perfusates has been linked to cell-type specific injury and early graft outcome following LT. Furthermore, specific intrahepatic miRNA expression patterns have been associated with graft survival and recurrent disease, like hepatitis C virus-related fibrosis and hepatocellular carcinoma. Therefore, miRNAs with strong predictive value and high sensitivity and specificity might be successfully applied to assess hepatic injury and to diagnose (recurrent) liver disease before, during and after LT. In this review, the current features and future prospects of miRNAs as biomarkers in and out of the liver are discussed.

Treatment options for arthrofibrosis following total knee arthroplasty include manipulation under anesthesia, open or arthroscopic arthrolysis, and revision surgery to correct identifiable problems. We propose preoperative low-dose irradiation and Constrained Condylar or Rotating-hinge revision for severe, idiopathic arthrofibrosis. Irradiation may decrease fibro-osseous proliferation while constrained implants allow femoral shortening and release of contracted collateral ligaments. Fourteen patients underwent fifteen procedures for a mean overall motion of 46° and flexion contracture of 30°. One patient had worsening range of motion while thirteen patients had 57° mean gain in range of motion (range 5°-90°). Flexion contractures decreased by a mean of 28°. There were no significant complications at a mean follow up of 34 months (range 24 to 74 months).

Ischemic-type biliary lesions (ITBLs) are a major cause of morbidity after liver transplantation (LT). Their assumed underlying pathophysiological mechanism is ischemia/reperfusion injury of the biliary tree, in which the portal circulation has been proposed recently to have a role. The aim of this study was to investigate whether early histological changes, particularly in the portal vein, predispose patients to ITBLs. A case-control study of 22 LT recipients was performed through a retrospective assessment of more than 30 histological parameters in 44 intraoperative liver biopsy samples taken after cold ischemia (time 0) and portal reperfusion (time 1). Eleven grafts developed ITBLs requiring retransplantation (the ITBL group), and 11 matched controls had normally functioning grafts 11 years after LT on average (the non-ITBL group). Additionally, 11 liver biopsy samples from hemihepatectomies performed for metastases of colorectal cancer (CRC) were assessed similarly. Analyses showed no significant histological differences at time 0 between the ITBL and non-ITBL groups. However, the time 1 biopsy samples from the ITBL group showed smaller portal vein branches (PVBs) significantly more often than the samples from the non-ITBL group, which also showed persisting paraportal collateral vessels. Larger PVBs and paraportal collateral vessels were also found in the CRC group. A morphometric analysis confirmed these findings and showed that PVB measurements were significantly lower for the ITBL group at time 1 versus the ITBL group at time 0 and the non-ITBL and CRC groups (they were largest in the CRC group). Thus, the PVB dimensions decreased in the ITBL group in comparison with the time 0 biopsy samples, and they were significantly smaller at time 1 in comparison with the dimensions for the non-ITBL and CRC groups. In conclusion, a smaller PVB lumen size in postreperfusion biopsy samples from liver grafts, suggesting a relatively decreased portal blood flow, is associated with a higher incidence of ITBLs. These findings support recent clinical studies suggesting a possible pathophysiological role of portal blood flow in the oxygenation of the biliary tree after LT.

As chronic hepatitis C patients with progressive disease can present themselves with normal ALT levels, more sensitive biomarkers are needed. MicroRNAs are newly discovered small noncoding RNAs that are stable and detectable in the circulation. We aimed to investigate the association between hepatocyte-derived microRNAs in serum and liver injury in patients with chronic hepatitis C. The hepatocyte-derived miR-122 and miR-192 were analysed in sera of 102 chronic HCV-infected patients and 24 healthy controls. Serum levels of miR-122 and miR-192 correlated strongly with ALT (R = 0.67 and R = 0.65, respectively, P < 0.001 for both). Median levels of miR-122 and miR-192 in HCV-infected patients were 23 times and 8 times higher as in healthy controls (P < 0.001 for both). Even within the HCV-infected patients with a normal ALT (n = 38), the levels of miR-122 and miR-192 were 12 times and 4 times higher compared with healthy controls (P < 0.001 for both). Multivariate logistic regression analyses showed that only miR-122 was a significant predictor of the presence of chronic HCV infection (P = 0.026). Importantly, miR-122 was also superior in discriminating chronic HCV-infected patients with a normal ALT from healthy controls compared with the ALT level (AUC = 0.97 vs AUC = 0.78, P = 0.007). In conclusion, our study confirmed that liver injury is associated with high levels of hepatocyte-derived microRNAs in circulation and demonstrated that in particular miR-122 is a sensitive marker to distinguish chronic hepatitis C patients from healthy controls. More sensitive blood markers would benefit especially those patients with minor levels of hepatocellular injury, who are not identified by current screening with ALT testing.

Background & Aims: Extracellular microRNAs (miRNAs) in serum and bile are currently under intense investigation for biomarker purposes in liver disease. However, the directions and pathways by which miRNAs are released from hepatic cells remains largely unknown. Here, we investigated the release of hepatocyte and cholangiocyte-derived miRNAs (HDmiRs and CDmiRs) into blood and bile during various (patho)physiological hepatic conditions. Methods: MiRNA release was analysed using longitudinally collected tissue and paired bile and serum samples (n = 124) that were obtained from liver transplant recipients during follow-up. Results: Cell-type specificity of HDmiRs and CDmiRs was confirmed in liver and common bile duct biopsies (P < 0.001). Analysis of paired bile and serum samples showed up to 20-times higher miRNA-levels in bile compared to serum (P < 0.0001). Fractionation of bile showed the majority of miRNAs being present in the unpelletable supernatant, where protein conjunctions protect miRNAs against degradation (P < 0.0001). During episodes of liver injury and histologically proven rejection in liver transplant recipients, relative HDmiR-levels in bile decreased while its levels in serum increased (P

Recent animal and human studies have highlighted the potential of hepatocyte-derived microRNAs (HDmiRs) in serum as early, stable, sensitive, and specific biomarkers of liver injury. Their usefulness in human liver transplantation, however, has not been addressed. The aim of this study was to investigate serum HDmiRs as markers of hepatic injury and rejection in liver transplantation. Serum samples from healthy controls and liver transplant recipients (n = 107) and peritransplant liver allograft biopsy samples (n = 45) were analyzed via the real-time polymerase chain reaction quantification of HDmiRs (miR-122, miR-148a, and miR-194). The expression of miR-122 and miR-148a in liver tissue was significantly reduced with prolonged graft warm ischemia times. Conversely, the serum levels of these HDmiRs were elevated in patients with liver injury and positively correlated with aminotransferase levels. HDmiRs appear to be very sensitive because patients with normal aminotransferase values (

Rapid liver regeneration is required after living-donor liver transplantation and oncologic liver resections to warrant sufficient liver function and prevent small-for-size syndrome. Recent evidence highlights the therapeutic potential of mesenchymal stem cells (MSC) for treatment of toxic liver injury, but whether MSC and their secreted factors stimulate liver regeneration after surgical injury remains unknown. Therefore, the aim of this study is to investigate the effect of human liver-derived MSC-secreted factors in an experimental liver resection model. C57BL/6 mice were subjected to a 70% partial hepatectomy and treated with either concentrated MSC-conditioned culture medium (MSC-CM) or vehicle control. Animals were analyzed for liver and body weight, hepatocyte proliferation, and hepatic gene expression. Effects of MSC-CM on gene expression in a human hepatocyte-like cell line (Huh7 cells) were analyzed using genome-wide gene expression arrays. Liver regeneration was significantly stimulated by MSC-CM as shown by an increase in liver to body weight ratio and hepatocyte proliferation. MSC-CM upregulated hepatic gene expression of cytokines and growth factors relevant for cell proliferation, angiogenesis, and anti-inflammatory responses. In vitro, treatment of Huh7 cells with MSC-CM significantly altered expression levels of similar to 3,000 genes. Functional analysis revealed strong effects on networks associated with protein synthesis, cell survival, and cell proliferation. This study shows that treatment with MSC-derived factors can promote hepatocyte proliferation and regenerative responses in the early phase after surgical resection. MSC-CM may represent a feasible new strategy to promote liver regeneration in patients undergoing extensive liver resection or after transplantation of small liver grafts.

Ischemic-type biliary lesions (ITBL) are the most frequent cause of nonanastomotic biliary strictures after liver transplantation. This complication develops in up to 25% of patients, with a 50% retransplantation rate in affected patients. Traditionally, ischemia-reperfusion injury to the biliary system is considered to be the major risk factor for ITBL. Several other risk factors for ITBL have been identified, including the use of liver grafts donated after cardiac death, prolonged cold and warm ischemic times and use of University of Wisconsin preservation solution. In recent years however, impaired microcirculation of the peribiliary plexus (PBP) has been implicated as a possible risk factor. It is widely accepted that the PBP is exclusively provided by blood from the hepatic artery, and therefore, the role of the portal venous blood supply has not been considered as a possible cause for the development of ITBL. In this short report, we present three patients with segmental portal vein thrombosis and subsequent development of ITBL in the affected segments in the presence of normal arterial blood flow. This suggests that portal blood flow may have an important contribution to the biliary microcirculation and that a compromised portal venous blood supply can predispose to the development of ITBL.

The People's Republic of China foresees a target of 30 GW for installed wind power capacity by 2010 (2008: 12 GW). This paper reports on the technical and economic potentials of wind power, the recent development, existing obstacles, and related policies in China. The barriers to further commercialization of the wind power market are important and may deter the 100 GW capacity target of the Chinese government by 2020. The paper concludes that the diffusion of wind power in China is an important element for not only reducing global greenhouse gas emissions, but also for worldwide progress of wind power technology and needed economies of scale.

Acetabular fractures with complete or incomplete quadrilateral plate separation frequently present with central displacement of the femoral head. Failure of stable fixation of medial wall fractures leaves residual subluxation despite reduction of other fracture components. Several fixation techniques may be either technically demanding or insufficient for stable fixation in conditions of comminution, osteoporosis, or neglected injuries. The proposed wire-plate composite uses a reconstruction spring plate over the pelvic brim for medial wall buttressing. One hole on its true pelvic limb provides a pulley to deviate a cerclage wire or cable passed through the greater sciatic notch into the true pelvis. This enhances buttressing against medial protrusion. Application through anterior approaches is simple and fixation is reliable in difficult fractures without the risk of joint penetration because all quadrilateral plate buttressing implants remain extraosseous.

En bloc resection of iliosacral sarcomas is a surgical challenge. There are substantial risks of inadequate margins, local recurrence, and nerve root loss when pelvic sarcomas involve sacral root canals and foramina. The decancellation technique uses principles similar to transpedicle decancellation in spinal deformity correction to perform the sacral osteotomy in iliosacral tumor resection. The technique aims at improving sacral margins and minimizing loss of neural function. We performed a decancellation osteotomy in five patients with sarcomas requiring difficult oblique or sagittal sacral osteotomies and selective root sacrifice. Through laminectomy and without anterior exposure, a precise full-thickness osteotomy of the sacrum was performed without major technique-related morbidities or complications. This was followed by formal pelvic resection and reconstruction. Surgical margins were adequate in all patients and all tumor-free nerve roots were preserved.

Background The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive acceptance criteria. Methods All adult recipients in the Netherlands in 2001–2006 with full-size OLT from DCD (n = 55) and DBD (n = 471) donors were included. Kaplan–Meier, log rank and Cox regression analyses were used. Results One- and 3-year patient survival rates were similar for DCD (85 and 80 per cent) and DBD (86·3 and 80·8 per cent) transplants (P = 0·763), as were graft survival rates (74 and 68 per cent versus 80·4 and 74·5 per cent; P = 0·212). The 3-year cumulative percentage of surviving grafts developing non-anastomotic biliary strictures was 31 per cent after DCD and 9·7 per cent after DBD transplantation (P < 0·001). The retransplantation rate was similar overall (P = 0·081), but that for biliary stricture was higher in the DCD group (P < 0·001). Risk factors for 1-year graft loss after DBD OLT were transplant centre, recipient warm ischaemia time and donor with severe head trauma. After DCD OLT they were transplant centre, donor warm ischaemia time and cold ischaemia time. DCD graft was a risk factor for non-anastomotic biliary stricture. Conclusion OLT using controlled DCD grafts and restrictive criteria can result in patient and graft survival rates similar to those of DBD OLT, despite a higher risk of biliary stricture.

Activating BRAF mutations have been reported in 40% of papillary thyroid carcinomas (PTCs). The involvement of BRAF pseudogene in thyroid tumorigenesis has not previously been studied. We investigated BRAF pseudogene expression in 68 thyroid tumors: 16 multinodular goiters, 43 classic PTCs, 6 follicular variants of PTC, and 3 anaplastic thyroid carcinomas. BRAF pseudogene function was studied by Western blots, soft agar assay, and tumorigenesis in nude mice. BRAF pseudogene expression was detected in 7 multinodular goiters, 18 classic PTC, and 1 follicular variants of PTC. There is an inverse correlation between BRAF pseudogene expression and BRAF mutation. The pseudogene transcripts were more frequently detected in tumors without BRAF mutation than those with BRAF mutation. Furthermore, BRAF pseudogene expression could activate the MAP kinase signaling pathway, transform NIH3T3 cells in vitro, and induce tumors in nude mice. These data suggest that BRAF pseudogene activation may play a role in thyroid tumor development.

We found HLA-DR5 to be present among 53% of 40 patients with goitrous autoimmune (Hashimoto's ) thyroiditis compared to 26% of 80 controls. No deviations from those expected in the incidences of HLA-A, B, C antigens were seen. In contrast HLA-DR3 was increased among 50 patients with atrophic thyroiditis (65%) compared to controls (24%). These findings stress the immunogenetic heterogeneity between the goitrous and atrophic varieties of thyroiditis.

One-hundred-and-forty-seven patients with autoimmune thyroiditis were studied with respect to HLA antigens as they related to various clinical features. HLA--B8 was found to be significantly increased among 59 patients with atrophic thyroiditis (57% vs. 26% for controls) but was identical to controls in 88 patients with goitrous thyroiditis (26%). No relation was found in either group between B8 and thyroid autoantibody titer or, in the case of goitrous thyroiditis, the rate of progression of the disease. Thus a link seems to be established between Graves' disease and atrophic thyroiditis in that both are significantly associated with HLA-B8. This study stresses the need to take clinical features into consideration when examining for HLA/disease associations.

In order to further elucidate the genetics of Graves' disease, we studied two families with several affected members, as well as tested the degree to which HLA haplotypes were shared in affected sibpairs. Further, we sought to identify the disease related haplotypes by determining the haplotypes shared among affected parent-child combinations. In one family, two affected sibs differed at four possible parental HLA haplotypes; no evidence of recombination was observed which could account for the result. In the other family, five siblings were affected. Four out of the five affected sibs shared the maternal haplotype HLA-A11, Bw51, Cw5, Cw-, DRw5, Bfs, GLO1, whereas three shared the paternal haplotype HLA-A1, B8, Cw-, DRw3, BfS and GLO1. Looking at haplotype sharing, two pairs of sibs were found to be HLA identical, whereas the fifth sib shared one haplotype with one of these pairs but not with the other. Out of 14 (eight of our own and six from the literature) affected sibpairs examined, nine were found to be HLA identical and four shared one haplotype, suggesting that the contribution of both paternal haplotypes may be necessary for the susceptibility to the disease. Fourteen parent-child combinations were studied; in only three out of 13 in which the shared haplotype could be ascertained was the haplotype B8 positive; this distribution is similar to controls. However, of the remaining 10 combinations which did not share a B8 positive haplotype, five were B8 positive at one or the other of the non-shared haplotypes.

The prospective controlled study was designed for comparing the influence of methimazole (MMI + placebo)(control group) and MMI + pentoxiphylline (PTX) with respect to grades of Thyroid Associated Ophthalmopathy (TAO). The control group consisted of 112 patients with hyperthyroidism (mean age 44.0 ± 12.4 yr, 83 females and 29 males). PTX treated group of 112 (mean age 47.7 ± 10.2 yr, 83 female and 29 male) hyperthyroid patients were treated with MMI + PTX. At the onset of the study there were no remarkable differences between the two treated groups. After six- and twelve-month observation periods the manifestations of TAO with moderate and severe forms were significantly lower in the PTX treated patients. Various risk factors were analyzed in both groups. Smoking by itself without genetic factors greatly increased the risk of TAO (OR: 7.1, CI 95% 9.3–5.4). If the smoking habit was associated with a genetic background, the manifestation of TAO significantly increased (OR: 9.2 CI 95%, 12.1–6.9, p < 0.0001)....

Activating BRAF mutations have recently been reported in 28-83% of papillary thyroid carcinomas (PTCs). However, it is not known whether aberrant BRAF splicing occurs in thyroid carcinoma. To investigate aberrant BRAF splicing and its association with BRAF mutation in thyroid tumours, we studied aberrant BRAF splicing and BRAF mutation from 68 thyroid tumours. BRAF(V600E) mutation was detected in 20 of 43 PTCs and all three anaplastic thyroid carcinomas (ATCs). There is a higher frequency of BRAF mutation in PTC patients with stage III and IV tumours compared with stage I and II. Novel BRAF splicing variants were detected in 12 PTCs, three follicular variants of PTC (FVPTCs), and one ATC, as well as in two thyroid carcinoma cell lines, ARO and NPA. These variants did not have the N-terminal auto-inhibitory domain of wild-type B-Raf, resulting in an in-frame truncated protein that contained only the C-terminal kinase domain and caused constitutive activation of B-Raf. These variants were significantly associated with advanced disease stage and BRAF(V600E) mutation (p < 0.001, Fisher exact test). Furthermore, expression of these variants in NIH3T3 and CHO cells could activate the MAP kinase signalling pathway, transform them in vitro, and induce tumours in nude mice. These data suggest that BRAF splicing variants may function as an alternative mechanism for oncogenic B-Raf activation. Combination of the BRAF(V600E) mutation and its splicing variants may contribute towards disease progression to poorly differentiated thyroid carcinoma.

Introduction and aim. Management of complicated wounds after tumor extipiration of pelvic and proximal lower limb musculoskeletal sarcoma represents an essential component in the outcome of these patients. The authors present modified vertical rectus abdominis musculocutaneous (VRAM) flap techniques to reconstruct extensive defects after debridment of these complicated wounds.Material and Methods. Over a period of 4 years (2002–2005), 5 men and 2 women were managed. Median age was 21 years (range 15–49). The patients were managed for complicated lower trunk, groin, and upper thigh wounds after resection of three pelvic chondrosarcomas as well as two pelvic and two proximal femur osteosarcomas. The modifications included a VRAM flap with lateral and tongue-like extension design of the skin paddle (5 cases) or a delayed extended VRAM flap (2 cases).Results. All flaps showed complete survival and healing with no ischemic events providing stable coverage. All patients were ambulant with good limb functions in terms of walking and gait after adequate rehabilitation, 2 needed support with crutches.Conclusion. The modified VRAM flaps offer reliable reconstructive tools for coverage of complex groin and thigh defects by providing larger well-vascularized soft tissue with acceptable donor site.

The thyrotropin receptor (TSHR) has a unique 50 residue (317–366) ectodomain insertion that sets it apart from other glycoprotein hormone receptors (GPHRs). Other ancient members of the leucine-rich repeat G protein-coupled receptor (GPCR) (LGR) family do exhibit ectodomain insertions of variable lengths and sequences. The TSHR-specific insert is digested, apparently spontaneously, to release the ectodomain (A-subunit) leaving the balance of the ectodomain attached to the serpentine (B-subunit). Despite concerted efforts for the last 12 years by many laboratories, the enzyme involved in TSHR cleavage has not been identified and a physiologic role for this process remains unclear. Several lines of evidence had suggested that the TSHR protease is likely a member of the a disintegrin and metalloprotease (ADAM) family of metalloproteases. We show here that the expression of ADAM10 was specific to the thyroid by specially designed DNA microarrays. We also show that TSH increases TSHR cleavage in a dose-dependent manner. To prove that ADAM10 is indeed the TSHR cleavage enzyme, we investigated the effect of TSH-induced cleavage by a peptide based on a motif (TSHR residues 334–349), shared with known ADAM10 substrates. TSH increased dose dependently TSHR ectodomain cleavage in the presence of wild-type peptide but not a scrambled control peptide. Interestingly, TSH increased the abundance of non-cleaved single chain receptor, as well higher molecular forms of the A-subunit, despite their enhancement of the appearance of the fully digested A-subunit. This TSH-related increase in TSHR digested forms was further increased by wild-type peptide. We have identified for the first time ADAM10 as the TSHR cleavage enzyme and shown that TSH regulates its activation. Copyright © 2007 John Wiley & Sons, Ltd.

Rotating-hinge knee prostheses have low survivorship and high complications except in primary arthroplasties in elderly patients. We retrospectively reviewed 142 single third-generation design, rotating hinge prostheses (11 primary procedures and 131 revisions) at 57 months follow up. Implant survival was 73 %. Successful two-stage reimplantation for prosthetic infection was 78.4% but new infection rate was 22%. The tibial component was durable while the femoral component was problematic. We observed only one patellar maltracking and no polyethylene wear. A third generation rotating-hinge arthroplasty reconstruction was reliable in complex problems. Outcomes in primary situations were excellent. Complications were the rule rather than the exception in revisions. With timely intervention, attention to soft tissue coverage, and realistic expectations, complications were contained and functional benefits were appreciable.

Chaos control here means to design a controller that is able to mitigating or eliminating the chaos behavior of nonlinear systems that experiencing such phenomenon. In this paper, an Adaptive Sliding Mode Controller (ASMC) is presented based on Lyapunov stability theory. The well known Chua's circuit is chosen to be our case study in this paper. The study shows the effectiveness of the proposed adaptive sliding mode controller.