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The purposes of this study was to determine the prevalence of the accessory anterolateral talar facet (AALTF); to evaluate the relationship between AALTF, focal abutting bone marrow edema (FABME), and sinus tarsi edema; and to study the prevalence of tarsal coalitions in patients with the AALTF utilizing ankle MR images. 5-T ankle MR images were reviewed for the presence of AALTF, FABME, sinus tarsi edema, tarsal coalition, and location and type of coalition (cartilaginous, fibrous, and osseous). Multivariate analysis was performed to examine the correlation between AALTF and the other variables. Three hundred ninety-one consecutive patients were included (age range 5–86 years; mean age 45 years). An AALTF was present in 3.6% (14/391) of patients. The AALTF prevalence was 2% in women and 6.6% in men. There was a significantly association between AALTF and FABME (9/14, p < 0.05), sinus tarsi edema (13/14, p < 0.05), and tarsal coalition (4/14, p < 0.05). AALTF is relatively often detected on MRI of the ankle and significantly associated with BME, sinus tarsi edema, and subtalar coalition. Patients with a tarsal coalition should be evaluated for the concurrent presence of an AALTF.

We examined the intertester reliability of patellofemoral compartment (PFC) osteoarthritis (OA) severity using magnetic resonance images (MRI) and a modified Kellgren and Lawrence (K&L) system. Second, we determined if these grades were associated with clinical tests of PFC involvement or self-reported pain/difficulty with stair climbing. Third, we assessed the association between PFC OA severity and knee pain or disability, after accounting for potential confounders including tibiofemoral OA severity. We examined the 9-year Osteoarthritis Initiative data from 114 subjects in the year prior to undergoing knee arthroplasty. The weighted kappa (κw) was used to determine intertester reliability, and the Pearson chi-square was used to assess associations among PFC OA scores and clinical tests. Multiple regressions were used to determine independent associations between self-reported pain/function and PFC OA. Reliability was substantial (κw = 0.73 (SE = 0.05)). Chi-square associations between PFC OA severity and clinical tests were not significant (p > 0.05). Multiple regression models between PFC OA and self-reported pain or function scores were not significant (p > 0.05). MRI-based measures of PFC OA were highly reliable indicating that musculoskeletal radiologists can reliably grade the PFCs of subjects using MRI. The extent of PFC OA is not associated with either clinical tests of PFC involvement or activities associated with PFC pain in persons with moderate to severe symptomatic tibiofemoral and PFC OA.

Despite being one of the most common indications for surgery, data on the types of meniscus tear that should be treated surgically are limited. Improving patient selection requires agreement on meniscus tear description. This study evaluates a simple MRI tear classification system for inter-observer agreement. Knee MRI examinations from 57 subjects from the Osteoarthritis Initiative cohort were reviewed by two sub-specialty trained, musculoskeletal radiologists. Based on two pulse sequences, each meniscus was classified by: tear or no tear; location of tear in anterior, middle or posterior third or multiple thirds; and displaced or non-displaced radial, horizontal, longitudinal or complex tear pattern. A tear was defined as signal abnormality extending to the surface on at least two images and displacement as more than 2 mm of extrusion or separation measured orthogonal to the tear plane. Kappa, weighted Kappa and percentage agreement were calculated. For the medial meniscus, Kappa and percentage agreement estimates were, respectively: the presence of tear, 0.79 and 89.5%; tear with displacement, 0.70 (weighted Kappa) and 66.0%; tear description, 0.47 and 61.4%; tear location, 0.64 and 79.0%. For the lateral meniscus, estimates were: the presence of tear, 0.75 and 89.5%; tear with displacement, 0.81 (weighted Kappa) and 86.0%; tear description, 0.56 and 78.9%; tear location, 0.74 and 87.7%. The strength of agreement between readers was moderate to substantial underscoring the challenge of meniscus tear classification.

Chapter 48 discusses diffuse idiopathic skeletal hyperostosis (DISH), which is a rarely symptomatic, benign condition of extensive ossification of ligament and tendon attachments to bone. It is primarily overlap of the imaging features of DISH and the seronegative spondyloarthropathies (SpA) that makes it a clinically significant entity. Imaging is frequently limited to radiographs of the spine acquired for unrelated reasons. MRI and CT are secondary imaging techniques most helpful in distinguishing DISH from the SpA and evaluating spine fractures. Treatment is rare, but surgical removal of anterior cervical spine ossifications may be required in cases of dysphagia.

Chapter 83 discusses lipidoses. The lipidoses are genetic diseases caused by enzyme deficiencies, which result in the cellular accumulation of lipids. These abnormal cells infiltrate tissues, including bone marrow, resulting in their dysfunction. Gaucher disease (GD) is the most common lysosomal storage disease (LSD) and lipidosis. Fabry disease (FD) is an X-linked recessive disease. Together, GD and FD account for 20% of LSDs. Nonspecific bone changes are detected using radiography, however, MRI is the most useful modality to evaluate involvement of the bone and bone marrow. MRI can also be used to detect treatment response. Enzyme replacement therapy (ERT) is the primary treatment for GD.

Chapter 47 discusses degenerative spondylosis and related conditions. Degenerative spondylosis encompasses the universal, age-related change in the intervertebral discs, facet joints, vertebral bodies, and alignment. Although these changes are often detected when imaging for back pain, they are not specific and may not be directly related to symptoms. Imaging is best obtained when signs or symptoms last longer than 6 weeks, there is neuromuscular impairment, or concern for infection or malignancy. MRI is the most sensitive technique to identify the potential causes of back pain. CT is appropriate in the posttraumatic setting when there is a high fracture risk. Conservative management guided by physical therapist is the standard of care in acute back pain.

Chapter 49 discusses spinal fixation hardware. The spine is the primary structural support of the human body. Traumatic, neoplastic, infectious, or degenerative disruption of the 3 columns of the spine causing pain and instability are the primary indications for spine surgery. Implanted hardware is used to provide short-term stability while osseous fusion of bone graft develops. Radiographs are routinely used for pre- and postoperative evaluation. Spinal fusion is used to restore and maintain disc space height, to decompress the spinal canal and neural foramina, to maintain normal lordosis, and to increase the stability of involved segments. Cross-sectional imaging is important for identified hardware and soft tissue complications.

Chapter 84 discusses mucopolysaccharidoses, which are genetic, lysosomal storage diseases resulting in the accumulation of glycosaminoglycans (GAG) in the soft tissues. Musculoskeletal complications of mucopolysaccharidosis (MPS) are common beginning in childhood. These result from abnormal ossification and periarticular GAG accumulation. Radiographs of the axial and appendicular skeleton (skeletal survey) are used for the baseline assessment of MPS disease. Progression of skeletal abnormalities is monitored with annual cervical spine MRI. Stem cell transplantation is the treatment of choice in MPS I, and enzyme replacement therapy (ERT) is the treatment of choice in MPS I Hurler-Scheie and Scheie, MPS II, and MPS VI.

Chapter 75 discusses bone marrow conversion and reconversion. The bone marrow is one of the largest organs in the body and it changes in composition throughout life. There is a normal conversion of hematopoietic bone marrow to fatty marrow with age. Various stressors or diseases can cause a reversal of this process or marrow reconversion. Marrow reconversion is often incidentally detected on MRI. Its imaging characteristics are important to distinguish from pathologic marrow infiltrative processes. Characteristic locations of marrow reconversion and the presence of focal or microscopic fat on MRI are useful features, but biopsy may still be required to exclude malignancy. Treatment is specific to the underlying disorder.

Chapter 74 discusses anemia conditions including sickle cell disease and thalassemia. Anemia is a condition of decreased oxygen delivery to organs caused by a deficit of functional red blood cells. It is a very common clinical condition and has a wide variety of causes. Of the common causes, the hemoglobinopathies have the most characteristic imaging findings. There are common imaging findings secondary to the compensatory increase in red blood cell and precursor number. Radiographs are a standard initial imaging study. MRI is the most sensitive imaging study for the sequelae of anemia. Iron deficiency anemia is treated with iron supplementation, aplastic anemia is treated by removal of the inciting agent, and painful crises of sickle cell are treated symptomatically.

Chapter 30 discusses rheumatoid arthritis (RA), which is the most common inflammatory arthritis and increases in incidence with age. Radiographs of the hand and feet are the primary imaging modality used for diagnosis and assessing response to treatment. The characteristic marginal erosions of the hands and feet of chronic disease are virtually diagnostic of RA. Ultrasound and MRI are highly sensitive and specific for the articular changes of RA. MRI is the only modality proven to identify bone marrow edema (BME), which is characteristic of early RA and predictive of future erosions. Early RA diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs) has resulted in a trend toward less severe imaging findings, fewer physical limitations and improved outcomes.

Chapter 32 discusses ankylosing spondylitis (AS), which is an inflammatory disease. It primarily affects white men. AS is a potentially debilitating disease that progresses to ankylosis of the axial skeleton if not appropriately diagnosed and treated. Large joint involvement is demonstrated in younger AS patients. AS results in progressive fusion, or ankylosis, of joints, which may be detectable on radiography. Pelvis and spine radiographs are a useful first study to identify the characteristic chronic findings of AS in the sacroiliac joints and spine. MRI, however, is the most sensitive modality to detect early inflammation and response to treatment.

Chapter 77 discusses histiocytoses, which are uncommon myeloid cell disorders. Langerhans cell histiocytosis (LCH) is the most common, with Erdheim-Chester disease (ECD) being less common. In LCH and ECD, the bones are most commonly involved. The imaging characteristics of the histiocytoses are nonspecific, and biopsy is often required for diagnosis. Radiography is standard for the initial assessment of suspected bone lesions. MRI is used to confirm a solid neoplasm, narrow the differential diagnosis, evaluate for risk of pathologic fracture, and guide biopsy. CT is usually performed in areas with lymphadenopathy. Treatment of skeletal disease is most commonly surgical and limited to symptomatic patients or those at risk for pathologic fracture.

Chapter 46 discusses joint arthroplasties and prostheses. Replacement of a native joint is often the definitive treatment of joint pain that does not respond to conservative measures. Joint replacement is the next most common orthopedic procedure after fracture reduction and fixation. Joint replacement anatomically may be total, partial, or compartmental. Regarding movement, it may be constrained, semiconstrained, or unconstrained. Radiography is the initial step in imaging evaluation with other modalities, especially CT and MRI, used when radiographs are inconclusive. Radiographs can detect particle disease, however, the damage caused by granulomas or pseudotumors are best evaluated with MRI using metal artifact reduction software (MARS).

Chapter 82 discusses parathyroid diseases and renal osteodystrophy. Parathyroid disease disrupts calcium homeostasis with systemic effects including abnormal bone metabolism. Secondary hyperparathyroidism, caused by chronic kidney disease, is the most common parathyroid disease. Diagnosis is primarily based on serum calcium, phosphate, and parathyroid hormone levels rather than imaging. However, there are characteristic findings that may suggest the diagnosis of parathyroid disease. Resorption of bone is the most important radiographic finding in primary hyperparathyroidism. Increase in bone density is the most specific radiographic and DXA finding in hypoparathyroidism. Treatment is dependent on disease, for example, parathyroidectomy is standard treatment for hyperparathyroidism, whereas hypoparathyroidism is treated with calcium supplementation.

Chapter 50 discusses sarcoidosis, which is a systemic disease that often involves the musculoskeletal system. The radiographic changes seen in sarcoid of the phalanges are characteristic, however, involvement of bone and other tissues may be occult or nonspecific. Tissue sampling is often required for diagnosis, especially when sarcoid resembles metastatic disease. The organ systems most commonly involved in sarcoid are the lungs, lymph nodes, skin and eyes. Radiographs are the standard first study used to evaluate symptomatic hand or foot involvement. Uncommon, palpable soft tissue lesions are best evaluated by MRI. Systemic corticosteroids are the primary treatment of active sarcoidosis.

Chapter 111 discusses imaging of articular cartilage. The importance of cartilage in normal joint function necessitates the use of high-resolution sequences for cartilage assessment. Cartilage loss is inferred on radiographs and CT images by the presence of joint space loss, altered alignment, and subchondral bone changes. MRI allows the direct assessment of articular cartilage structure and injury in contrast to the indirect visualization obtained with radiography and CT. Direct visualization in situ has helped to advance the treatment of injured cartilage, which is increasingly common in clinical practice. The imaging of cartilage composition may aid in the development of treatments that prevent or stabilize cartilage injury.

Chapter 78 discusses lymphoproliferative and myeloproliferative disorders, which are a disparate group of premalignant and malignant neoplasms originating in or metastasizing to the bone marrow. Included in this group of disorders is primary myelofibrosis, systemic mastocytosis, leukemia, and lymphoma. Because these tend to involve the marrow more often than the cortex, they are best detected by MRI and nuclear imaging techniques, including FDG-PET and CT. Distinguishing the disorders by imaging is often difficult because of the overlap in imaging findings. Imaging is beneficial to guide biopsy, which is crucial in diagnosis, and to assess treatment response.

Chapter 76 discusses plasma cell dyscrasias, which are currently incurable diseases resulting from the proliferation of plasma cells and the secretion of immunoglobulins with associated anemia and end-organ damage. These diseases are more common in men than women and more common in African Americans than whites. Multiple myeloma is the most common of the plasma cell dyscrasias. Blood and urine testing, bone marrow biopsy, and radiography are the primary tests used for diagnosis. Radiographs are the standard tools in disease staging and monitoring with advanced imaging used primarily for evaluating symptomatic patients with negative radiographs and patients in clinical trials.

Chapter 81 discusses thyroid diseases. Thyroid hormone is a regulator of normal physiology, including normal function of the musculoskeletal system. The most important causes of both elevated thyroid hormone levels (hyperthyroidism) and decreased hormone levels (hypothyroidism) are diseases of the thyroid gland. These are primarily diagnosed using serum testing and thyroid imaging. Muscle weakness is a common musculoskeletal complaint in both hyperthyroidism and hypothyroidism. In adults, osteoporosis is often evaluated in hyperthyroid patients using DXA, however, other musculoskeletal manifestations are often incidentally detected. Treatment options include radioactive iodine ablation of the thyroid gland, medical therapy, and surgery.

Chapter 33 discusses psoriatic arthritis, which is a seronegative spondyloarthropathy (SpA) affecting the peripheral and axial skeleton that may precede skin manifestations. Psoriatic arthritis is a challenging diagnosis because it often initially presents without psoriasis, lacks specific serologic markers, and resembles osteoarthritis and other inflammatory arthropathies. It is associated with joint erosions, destruction, and ankylosis often involving the distal interphalangeal (DIP) joints. Radiography is the primary imaging modality for initial diagnosis and monitoring disease progression and treatment efficacy. Skin and nail involvement and characteristic imaging findings are key criteria for diagnosis. MRI and US of symptomatic joints and/or MRI of the sacroiliac (SI) joints may be useful in clinically challenging cases.

Chapter 80 discusses pituitary diseases. Acromegaly and Cushing disease are the 2 pituitary diseases with the most significant effects on the musculoskeletal system. Acromegaly results in excess growth hormone with gradual bone and soft tissue overgrowth in adults. Cushing disease results in hypercortisolism resulting in osteoporosis, osteonecrosis, and myopathy. Osteoporosis and osteonecrosis are common sequelae of Cushing disease that can often be detected radiographically, but DXA and MRI are often used for confirmation and treatment planning. Both conditions require a high clinical suspicion to diagnose and are primarily treated surgically. Medical treatment with or without adjunctive radiation therapy is reserved for patients with unsuccessful surgical resection or unresectable disease.

Chapter 79 discusses bleeding diseases, which result from disruption of the normal blood clotting process. Genetic diseases that cause reduction or dysfunction of clotting factors (hemophilia A and B) and less commonly platelets (von Willebrand disease) are the major bleeding diseases of the musculoskeletal system. The most common bleeding disease of the musculoskeletal system, hemophilia, is caused by deficiency of either factor VIII or factor IX. Hemophilia commonly results in intraarticular hemorrhage resulting in hemophiliac arthropathy and less commonly intramuscular hemorrhage. Imaging of the joints and soft tissues, especially by MRI, is important in disease management.

Chapter 31 discusses juvenile idiopathic arthritis (JIA), which is a heterogeneous disease of joint inflammation. Initial radiographic evaluation is useful for excluding other diseases. Radiographs are sensitive to late findings of JIA, but not early changes of JIA. The monitoring of chronic disease, however, relies on modalities that do not result in ionizing radiation and are more sensitive to changes in the skeletally immature patient. MRI and US are both safe imaging techniques, which can detect inflammation in joints that are not well evaluated by radiography and can better classify the disease. US can also be useful for guiding intraarticular injections.

We examined the intertester reliability of patellofemoral compartment (PFC) osteoarthritis (OA) severity using magnetic resonance images (MRI) and a modified Kellgren and Lawrence (KL) system. Second, we determined if these grades were associated with clinical tests of PFC involvement or self-reported pain/difficulty with stair climbing. Third, we assessed the association between PFC OA severity and knee pain or disability, after accounting for potential confounders including tibiofemoral OA severity.We examined the 9-year Osteoarthritis Initiative data from 114 subjects in the year prior to undergoing knee arthroplasty. The weighted kappa (κReliability was substantial (κMRI-based measures of PFC OA were highly reliable indicating that musculoskeletal radiologists can reliably grade the PFCs of subjects using MRI. The extent of PFC OA is not associated with either clinical tests of PFC involvement or activities associated with PFC pain in persons with moderate to severe symptomatic tibiofemoral and PFC OA.

Multiple radiographic acquisition techniques have been evaluated for their effect on measurements of acetabular morphology. This cadaveric study examined the effect of two acquisition parameters not previously evaluated: beam center position and source-to-detector distance. This study also evaluated the effect of reader differences on measurements. Following calibration of measurements between two readers using five clinical radiographs (training), radiographs were obtained from two cadavers using four different source-to-detector distances and three different radiographic centers for a total of 12 radiographic techniques (experimental). Two physician readers acquired four types of measurements from each cadaver radiograph: lateral center edge angle, peak-to-edge distance, Sharp’s angle, and the Tonnis angle. All measurements were evaluated for intra-class correlation coefficient (ICC), kappa statistics for hip dysplasia, and factors that resulted in measurement differences using a mixed statistical model. After training of the two physician readers, there was strong agreement in their hip morphology measurements (ICC 0.84–0.93), agreement in the presence of hip dysplasia (κ = 0.58–1.0), and no measurement difference between physician readers (p = 0.12–1.0). Experimental cadaver measurements showed moderate-to-strong agreement of the readers (ICC 0.74–0.93) and complete agreement on dysplasia (κ = 1). After accounting for reader and radiographic technique, there was no difference in hip morphology measurements (p = 0.83–0.99). In this cadaveric study, measurements of hip morphology were not affected by varying source-to-detector distance or beam center. We conclude that these acquisition parameters are not likely to affect the diagnosis of hip dysplasia in a clinical setting.

Langerhans cell histiocytosis (LCH) is a complex disease entity comprised of three distinct clinical syndromes that demonstrate indistinguishable histology. These syndromes are: eosinophilic granuloma, which is predominantly osseous or pulmonary; Hand-Schûller-Christian's disease, which involves multiple organ systems and, most typically, the skull base; and Letterer-Siwe's disease, the most severe disease manifestation, which typically involves the abdominal viscera. This article reviews our current understanding of Langerhans cell histiocytosis by discussing the history, histology, etiology, and treatment of the disease. It focuses on the radiographic findings and imaging modalities that are the most useful in disease diagnosis and management.

SummaryMonoclonal antibodies that bind and inhibit nerve growth factor (NGF) have demonstrated both, good analgesic efficacy and improvement in function in patients with osteoarthritis (OA). Despite initial promising data, trials in OA had been suspended by the Federal Food and Drug Administration (FDA) due to concerns over accelerated rates of OA progression. Imaging will play a crucial role in future clinical trials to define eligibility of potential participants and to monitor safety during the course of these studies. This will require baseline and frequent follow-up radiographs of both, the index joints and other large weight bearing joints to identify subjects at risk prior inclusion and on study so treatment can be discontinued.This imaging overview in the form of an atlas describes and illustrates potential exclusionary joint imaging findings at eligibility and potential adverse joint events on radiography and magnetic resonance imaging (MRI) in studies investigating a-NGF compounds. The overarching goal of this atlas is to facilitate trial design and to promote a common language and understanding between potential expert readers. This first section of the atlas will focus on knee joint specific findings that are relevant to a-NGF studies.

Membrane-associated guanylate kinase homologs (MAGUKs) may play a role in cellular functions preventing tumorigenesis as indicated by the neoplastic phenotype caused by genetic loss of the MAGUK Dlg in Drosophila . To test this possibility, we examined the expression and subcellular localization of the tight junction MAGUK ZO-1, as well as the cell adhesion molecule E-cadherin, in paraffin-embedded breast cancer samples, using immunohistochemistry and confocal microscopy. As expected, normal tissue showed intense staining for ZO-1 at the position of the epithelial tight junctions, but this staining was reduced or lost in 69% of breast cancers analyzed ( n = 48). In infiltrating ductal carcinomas ( n = 38) there was a reduction in staining in 42% of well differentiated, in 83% of moderately differentiated and 93% of poorly differentiated tumors. ZO-1 staining was positively correlated with tumor differentiation ( P =.011) and more specifically with the glandular differentiation of tumors ( P =.0019). Reduction in ZO-1 staining was strongly correlated with reduced E-cadherin staining ( P = 4.9 × 10 −5 ). The results suggest that down-regulation of ZO-1 expression and its failure to accumulate at cell junctions may be causally related to cancer progression. To detect loss of heterozygosity, the ZO-1 gene tjp-1 was mapped relative to other markers in 15q13 and polymorphic markers flanking tjp-1 were identified. The marker D15S1019 showed loss of heterozygosity in 23% of informative tumors ( n = 13). Loss of a tjp-1 -linked marker suggests that genetic loss may, in some cases, be responsible for the reduction in ZO-1 expression in breast cancer.

s / Osteoarthritis and Cartilage 23 (2015) A82eA416 A360 eligibility and safety findings relevant for aNGF clinical trials. More than 400 images were reviewed to define the most relevant and characteristic imaging findings. Diagnoses of exclusion for eligibility due to potentially increased risk of RPOA are subchondral insufficiency fractures (SIF), atrophic OA and severe malalignment of the knee in the medial-lateral direction. Diagnoses relevant for safety after enrolment (i.e. joint safety findings), i.e. RPOA, SIF, osteonecrosis and pathologic fractures will also be discussed. Several of these diagnoses have non-specific findings on the radiograph or cannot be detected radiographically in early stages. Thus, in cases of inconclusive or suspicious radiography, an additional MRI examination may be acquired to rule out or confirm some of these diagnoses. Results: Early and late signs of diagnoses relevant for eligibility will be presented. Fig 3A. Radiograph of the hip joint shows superior JSN (arrows) without relevant osteophytes present. Fig 3B. Follow up image 12 months later shows near-complete destruction of the femoral head (arrows) and subsequent migration of the femur superiorly consistent with RPOA. Conclusions: Expert readers in aNGF programs need to be aware of relevant imaging findings. These include early signs of diagnoses relevant for RPOA on radiography, and other potential X-ray and MRI diagnoses relevant for eligibility and safety during aNGF studies. 591 PROLONGED JOINT RESIDENCY OF TRIAMCINOLONE ACETONIDE AFTER AN INTRA-ARTICULAR INJECTION OF FX006, A SUSTAINED RELEASE FORMULATION FOR THE TREATMENT OF OSTEOARTHRITIS N. Bodick y, J. Lufkin y, C. Willwerth y, J. Hauben y, A. Kumar y, P. Boen y, J. Bolognese z, C. Schoonmaker z, M. Clayman y. y Flexion Therapeutics, Burlington, MA, USA; zCytel Inc, Cambridge, MA, USA Purpose: Although available intra-articular (IA) corticosteroids are well established in the treatment of painful osteoarthritis (OA), limitations include short duration of pain relief (1-4 weeks), an effect consistent with the transient residency of these compounds in the joint and high plasma corticosteroid concentrations immediately following injection. FX006 is a novel IA sustained-release injectable formulation of 25% triamcinolone acetonide (TCA) in poly(lactic-co-glycolic acid) microspheres intended to prolong therapeutic concentrations of TCA in the joint and limit systemic exposure. In a previously described 6-week long clinical study, FX006 at 40 mg demonstrated maintenance of synovial concentrations of TCA consistent with pharmacologic activity for a period of at least 6 weeks, when levels of TCA produced by an equivalent dose of TCA IR were below the limit of quantitation. The current study extended these data on joint residency by measuring synovial fluid levels of TCA at later time points. Methods: In this multi-center, open-label study, patients with OA of the knee received a single IA injection of FX006 containing 10 or 40mg TCA, or 40mg of a standard, immediate-release suspension of TCA (TCA IR). A total of 50 patients were enrolled (FX006 10 mg: 10 patients, FX006 40 mg: 30 patients, TCA IR: 10 patients). Synovial fluid and plasma samples were obtained at baseline (pre-dose) and at the planned Final Visit at either Week 12, 16, or 20, depending on cohort assignment and availability of fluid in the knee. Concentrations of TCA were measured in plasma or in filtered synovial fluid samples using High Performance Liquid Chromatographic methods with Tandem Mass Spectrometry Detection and Automated Extraction, validated for the determination of TCA in human plasma and synovial fluid respectively. The quantitation limits of both assays were 50 to 50000 pg/mL. Results: In the FX006 10 mg group, 8 patients had synovial fluid available for analysis at Week 12. In the FX006 40 mg group, 6 patients had synovial fluid available for analysis at Week 12, 8 patients at Week 16 and 11 patients at Week 20. In the TCA IR group, 5 patients had synovial fluid available for analysis at Week 12. The concentrations of TCA achieved by 40mg FX006 in the synovial fluid atWeek 12 were 924 pg/mL, at Week 16, the IA concentrations of TCAwere 224 pg/mL and by Week 20 they were below the lower limit of quantitation (Figure; geometric means from the earlier 6-week study and the current study are merged). The IA concentration of TCA in patients receiving 40 mg of TCA IR at Week 12 was below the lower limit of quantitation. FX006 maintained a gradient between synovial and systemic plasma concentrations of TCA for 16 weeks.

A trichobezoar represents a mass of accumulated hair within the gastrointestinal tract. Isolated gastric trichobezoars, those with extension into the duodenum, and small intestinal trichobezoars have all been described. However, the presence of discrete gastric and intestinal trichobezoars has been rarely presented in the literature. This case report describes synchronous trichobezoars in the stomach and jejunum in a 9-year-old girl presenting with abdominal pain, anorexia, and vomiting. This case emphasizes the role of radiographic imaging in the diagnosis of trichobezoars and the importance of a complete clinical evaluation of the small bowel at the time of removal of an obstructing gastric bezoar.

Background A nursemaid's elbow most frequently occurs with transient longitudinal traction of the pronated forearm and extended elbow, which can be reduced by manipulation without sedation. There are circumstances in which the history is atypical and reduction of the elbow is unsuccessful. Imaging may be helpful in these cases. Methods A 33-month-old child was injured in a fall from a tire swing and sustained what was thought to be a nursemaid's elbow. Typical reduction maneuvers were unsuccessful. The patient underwent magnetic resonance imaging (MRI) with conscious sedation, which demonstrated the entrapment of the annular ligament in the radicapitellar joint. A presumed successful reduction was performed with confirmed reduction of the annular ligament by immediate MRI. Conclusions To our knowledge, this is the first case report on MRI being used to diagnose and confirm treatment of an atypical nursemaid's elbow. Level of evidence IV.

Proteins of the 4.1 family play a key role in the integrity of the cytoskeleton and in epithelial tissue movement, as shown by the disruption of the actin cytoskeleton in human erythrocytes caused by genetic loss of protein 4.1, and the failure of epithelial tissue migration during Drosophila embryogenesis caused by genetic loss of the 4.1 homolog Coracle. Here we report the genetic characterization of Yurt, a novel protein 4.1 family member in Drosophila that is associated with the plasma membrane of epithelial cells. Homozygous loss-of-function mutations in the yurt gene cause failure of germ-band retraction, dorsal closure, and head involution, associated with degeneration of the amnioserosa and followed by embryonic lethality. A mammalian homolog of Yurt is up-regulated in metastatic melanoma cells. These novel cytoskeletal proteins appear to play important roles in epithelial cell movements and in the morphogenetic tissue changes that depend on them.

ZO-1 is a tight junction membrane protein that plays a critical role in cell-cell interaction, proliferation, and differ entiation.To localize and evaluate the expression of ZO-1 in the normal human pancreas, in pancreatic ductal adenocarcinoma (PDAC), and in chronic pancreatitis (CP).Northern and Western blot analysis revealed ZO-1 expression in all six tested pancreatic cancer cell lines. Expression of ZO-1 mRNA was increased sixfold in PDAC samples in comparison with normal samples (p = 0.04). Confocal microscopy revealed the presence of ZO-1 in the apical and apicolateral areas of ductular cells in the normal pancreas. Similarly, in CP, ZO-1 was localized at apical and apicolateral areas of small proliferating ductular cells and large metaplastic ducts. In PDAC, however, ZO-1 expression was observed irrespective of whether the cancer cells formed duct-like structures or exhibited a diffuse infiltrating pattern. Metastatic pancreatic cancer cells within lymph nodes displayed variable staining patterns, ranging from apical and apicolateral to a diffuse membranous staining.These observations suggest that ZO-1 is overexpressed in PDAC and raise the possibility that this overexpression may confer a metastatic advantage to pancreatic cancer cells.

Protein 4.1 (also called band 4.1 or simply 4.1) was originally identified as an abundant protein of the human erythrocyte, in which it stabilizes the spectrin/actin cytoskeleton. The protein and its relatives have since been found in many cell types of metazoan organisms and they are often concentrated in the nucleus, as well as in cell–cell junctions. They form multimolecular complexes with transmembrane and membrane-associated proteins, and these complexes may be important for both structural stability and signal transduction at sites of cell contact.

We have determined the cDNA sequence, expression pattern, and chromosomal location of the human gene DLG4, encoding the postsynaptic density-95 (PSD95) protein. hPSD95 is a 723-amino-acid protein that is 99% identical to its rodent counterparts. This is the fourth human protein identified as showing significant similarity to the Drosophila tumor suppressor Dlg. These proteins constitute the DLG subfamily of the membrane-associated guanylate kinase protein family. The expression of DLG4 in neural tissue is consistent with the pattern observed for its rat homolog. However, DLG4 is also expressed in a wide range of nonneural tissues, suggesting that the protein may have additional roles in humans. Using radiation-hybrid mapping panels, we mapped the DLG4 locus to 17p13.1, a region associated with several diseases, the phenotypes of which are consistent with loss of PSD95 function.