Targeting nicotinamide N-methyltransferase decreased aggressiveness of osteosarcoma cells.

BACKGROUND: Osteosarcoma (OS) is a primary bone malignancy that mostly affects young people, characterized by high metastatic potential, and a marked chemoresistance that is responsible for disease relapse in most patients. Therefore, it is necessary to identify novel molecules to setup targeted strategies to improve the clinical outcome. The enzyme nicotinamide N-methyltransferase (NNMT) catalyses the N-methylation of nicotinamide and other analogs, playing a crucial role in the biotransformation of drugs and xenobiotics. NNMT overexpression was reported in a wide variety of cancers, and several studies demonstrated that is able to promote cell proliferation, migration and resistance to chemotherapy. The aim of this study was to explore the potential involvement of NNMT in OS. METHODS: Immunohistochemical analyses have been performed to evaluate NNMT expression in selected OS and healthy bone tissue samples. Subsequently, OS cell lines have been transfected with vectors targeting NNMT mRNA (shRNAs) and the impact of this downregulation on migration, cell proliferation, and response to chemotherapeutic treatment was also analysed by wound healing, MTT, SRB and Trypan blue assays, respectively. RESULTS: Results showed that OS samples display a significantly higher NNMT expression compared with healthy tissue. Preliminary results suggest that NNMT silencing in OS cell lines is associated to a decrease of cell proliferation and migration, as well as to enhanced sensitivity to chemotherapy. Data obtained showed that NNMT may represent an interesting marker for OS detection and a promising target for effective anti-cancer therapy.

The appropriate and sequential value of standard radiograph, computed tomography and magnetic resonance imaging to characterize a bone tumor.

Radiographs (XR), computed tomography (CT) or magnetic resonance imaging (MRI) are regularly analyzed to determine whether a bone lesion is benign or malignant. An online quiz was created providing 15 cases with a clinical summary, MRI, CT, and XR. After each image, participants were asked to rate the probability (0-100%) the bone tumor was malignant. Order and difficulty of the images were randomly determined. Probability statements regarding the diagnosis were actualized along the sequence of exam, to quantify how the degree of belief changed to account for evidence from those exams. 64 physicians participated and provided 154 assessments from 1 (n = 18) to 3 (n = 44) different cases. After the first image, participants favored the correct malignancy status at 70%; 80% after the second and 80% after the third one. Participants were more likely to favor the correct malignancy status when the lesion was malignant and when first confronted with XR or CT, rather than MRI, though the most predictive factor of correct diagnosis was the difficulty of the case. In conclusion, the additional information provided by successive imaging studies was moderate. XR or CT seemed more appropriate than MRI as first imaging study. Bypassing XR should be discouraged.

Preoperative ultrasonography and magnetic resonance imaging evaluation of the position of the neurovascular bundle for Dupuytren's disease of the fifth digit.

BACKGROUND: Dupuytren's contracture (DC) is a fibrosing disor-der that produces pathological subcutaneous nodules and cords in the normal fascia. The isolated occurrence of Dupuytren's disease of the fifth digit is uncommon. This study is aimed to describe the imaging features of an isolated digital cord of the small finger and its relationship with the neurovascular bundle. METHODS: A total of 13 hands in 13 patients who were clinically diagnosed with an isolated occurrence of Dupuytren's disease of the small finger were included between October 2008 and October 2013. Two independent radiologists used ultrasound and magnetic reso-nance imaging (MRI) to record size, signal or echogenicity, contrast enhancement or hyperemia, calcification, and anatomical features of the cord and its relationship with the neurovascular bundle. RESULTS: We found that ultrasound and MRI were accurate for the detection of the cords and neurovascular bundles in the small finger. The intermodality agreement between MRI and ultrasound was 100% for the detection of 6 spiraling bundles containing 13 isolated cords (46.2%). Among the subjects examined, 100% of the hands had ab-ductor digiti minimi (ADM) area involvement, and the distal insertion of the cord was on the ulnar side of the base of the middle phalanx. On MRI, all of the cords showed predominantly low signal intensity on both T1- and T2-weighted images. On ultrasound, the ulnar cord showed a hyperechoic or isoechoic appearance in 69.3% of hands and a hypoechoic appearance in 30.7% of hands. CONCLUSIONS: The spiraling of the bundle in the isolated occurrence of Dupuytren's disease at the small finger is a frequent occurrence. MRI and ultrasound are good imaging modalities for the evaluation of the relationship between the neurovascular bundle and the isolated cord.

Molecular analysis of endometrial inflammation in preterm birth.

Spontaneous preterm birth (sPTB) represents the 35%-45% of all preterm birth (PTB) cases and its etiology is unknown. We investigated if the expression level of endometrial cytokines and angiogenetic factors is related to the onset of sPTB.Endometrial tissues from non-pregnant women who experienced sPTB and from non-pregnant women who did not experience sPTB were collected and examined for their expression profile. With this aim, the PCR Array analysis was performed and data were confirmed by Real-Time PCR. Differential gene expression measurements (pathological vs control tissues) showed a significant up-regulation for genes codifying for two angiogenetic factors known as connective tissue growth factor (CTGF), and coagulation factor III (F3). An increased level of expression was detected both for tyrosine kinase endothelial (TEK) and for transforming growth factor beta 2 (TGF-ß2) genes but without reaching the statistical significance. The expression level of interleukin 10 receptor alpha (IL10RA) gene was slightly decreased in pathological group compared to control one but, as well as forTEK and TGF-ß2 measurements, without reaching the statistical significance. Our work is the first to correlate the imbalance in endometrial district of non -pregnant women with sPTB. These data could suggest a new point of view whence to read sPTB. We need additional clinical and biological studies to clarify sPTB pathogenesis.

Therapeutic outcome of CT-guided radiofrequency ablation in patients with osteoid osteoma.

OBJECTIVE: To assess the long-term outcome of computed tomography-guided radiofrequency ablation (CT-guided RFA) in patients with suspected osteoid osteoma (OO). MATERIALS AND METHODS: Single-center retrospective study. Patients with clinical suspicion and imaging diagnosis of osteoid osteoma were treated by CT-guided RFA using the same device with either a 7- or 10-mm active tip electrode. Specific precautions were applied in case of articular or spinal OO. Patients were contacted by phone to evaluate the long-term outcome in terms of pain, ability to perform daily activities (including sports), and long-term complications. Success was defined as the absence of residual pain and ability to perform daily activities normally. RESULTS: From 2008 to 2015, 126 patients were treated by CT-guided RFA for OO in our institution. Mean patient age was 26.1 years (SD = 11, range 1-53); mean delay to diagnosis was 16.9 months (SD = 15.2, range 1-120). Among patients who answered the follow-up call (n = 88), the overall success rate was 94.3%: 79/88 (89.8%) had primary success of the procedure, and 4/88 (4.5%) had a secondary success (repeat-RFA after pain recurrence). Mean follow-up time was 34.6 months (SD = 24.7, range 3-90). Few complications occurred: two mild reversible peripheral nerve injuries, one brachial plexus neuropathy, one broken electrode tip fragment, and one muscular hematoma. CONCLUSION: Osteoid osteoma can be effectively and safely treated by CT-guided RFA using the presented ablation protocol. Beneficial effects of the treatment persist at long-term follow-up.

Ultrasound of wrist and hand masses.

Ultrasound is a useful tool to investigate soft tissue masses in the wrist and hand. In most situations ultrasound helps distinguish between a cyst and a tissue mass. This article provides a simple clinical approach to the use of ultrasound imaging for the diagnosis and preoperative assessment of wrist and hand masses.

Tears at the myotendinous junction of the infraspinatus: ultrasound findings.

PURPOSE: Tears involving the myotendinous junction (MTJ) of the infraspinatus (IS) have been recently described on MRI. These occur centrally in the muscle belly, and are not associated with full thickness tears of the distal infraspinatus tendon. They also induce a rapidly progressive fatty infiltration of the muscles and amyotrophy. The purpose of this study is to assess the accuracy of ultrasonography in diagnosing MTJ tears of the infraspinatus and to describe the usual ultrasonographic appearance compared with MRI. MATERIALS AND METHODS: Retrospective study of 2403 US examinations of the shoulder (over 5 years). Fifteen patients with a reported suspicion of infraspinatus MTJ tears were included. MRI examination was available in all cases, CT arthrography in 13 cases, and one patient underwent surgical confirmation. RESULTS: All patients were sent for an ultrasound for suspect lesion of the tendons of the rotator cuff, with posterior pain in the infraspinatus fossa. All cases seen on ultrasonography were confirmed on MRI. CT arthrography confirmed the absence of tear of the IS tendon in all cases and did not reveal the MTJ tears. Two signs appeared to us as being of special interest: the "tadpole sign" on longitudinal views, and the "black eye sign" on sagittal views. The proximal retraction of the tendon at the MTJ is the anatomical explanation of both signs. CONCLUSION: Tears at the myotendinous junction of the infraspinatus are rare but can be diagnosed on US examination, provided that the sonographer pays attention to the infraspinatus fossa especially in cases of normality of the distal tendinous cuff.

MDCT imaging of calcinosis in systemic sclerosis.

Calcinosis is a typical feature of systemic sclerosis (SSc) and can be found in many different tissues including the superficial soft tissues, periarticular structures, muscles, and tendons. It can also provoke erosive changes on bones. Investigation is conducted most often with plain radiographs. However, when a more detailed assessment is necessary, multidetector computed tomography (MDCT) is helpful owing to its multiplanar reformat (MPR) ability. The purpose of this review is to provide an overview of the various appearances of calcinosis in SSc patients as visualized at MDCT.

Ultrasound-guided injection in osteoarticular pathologies: general principles and precautions.

In the past, needle aspirations or injections involving the motor system were always carried out either blind or guided by fluoroscopy. Over the last few years, sonography has begun to offer an interesting alternative. Its advantages are that it is a relatively inexpensive technique, while not emitting ionising radiation and being easily accessible. There has been a great deal of technical progress including high frequency transducers, which have led to performance improvements in terms of both diagnosis and treatment of pathologies of the motor system. Due to these technical advances and to sterile covers for the transducers, it is now possible to visualise and to aspirate or inject into a peripheral joint, a tendon sheath or a bursa with or without effusion. This technique does not require a contrast medium injection because the needle position can be checked directly. Minimally invasive, it allows a number of interventions to be carried out with a very low complication rate since the entire path of the needle is followed using sonography, which means that nerves, vessels and other structures can be avoided because they are visualised directly in real time.

The tendons: Interventional sonography.

While blind or fluoroscopically guided infiltration works well for intra-articular injections, injections into the tendon sheath are much more difficult. Ultrasound guidance with high-frequency transducers now allows visualization and infiltration of tendon sheaths. The interventional phase should be preceded by a diagnostic scan. Patients should be questioned to identify possible contraindications to the procedure and informed of the potential risks. Strict asepsis must be maintained for both patient and operator. This review includes separate discussions of the tendons in different areas of the body that are most commonly treated with ultrasound-guided injections, with descriptions of the lesions that are treated and the approach used for each. Interventional sonography is currently the only technique that allows visualization of the tendon being infiltrated. It requires training and experience as well as good knowledge of the indications and equipment used for the procedures, and the anatomy of the areas being treated.

[Spondyloarthropathy: MR imaging features]. / IRM et spondylarthropathie.

The new diagnostic criteria for ankylosing spondylitis include MRI. MRI frequently allows early diagnosis of inflammatory lesions in patients with normal plain films. In addition, MRI is useful for the detection and quantification of inflammatory and structural lesions, and to assess disease activity.

[Dedifferentiated chondrosarcoma: radiologic-pathologic correlation]. / Chondrosarcomes dédifférenciés: revue iconographique radio-pathologique.

Dedifferentiated chondrosarcomas are highly malignant tumors characterized by conventional low-grade chondrosarcoma with abrupt transition to foci that have dedifferentiated into a higher-grade noncartilaginous more aggressive sarcoma. The dedifferentiated component, an osteosarcoma or fibrosarcoma, determines the prognosis. Its identification is key for management. A diagnosis of dedifferentiated chondrosarcoma should be suggested by the presence of "tumoral dimorphism" with cartilaginous component and aggressive lytic component invading adjacent soft tissues.

[US evaluation of the hands and feet in rheumatoid arthritis]. / Comment je fais un bilan échographique des mains et des pieds dans la polyarthrite rhumatoïde?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive damage of synovial-lined joints and variable extra-articular manifestations. Synovitis is usually found in the wrist, metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints. For these reasons, we believe that ultrasound with power doppler can be used for the detection and monitoring of synovitis with a simplified "hands and feet" protocol. In this article, we will describe this protocol used daily in our institution for early diagnosis and therapeutic management of this disease.

[MR Imaging of the spine and sacroiliac joints in ankylosing spondylitis]. / IRM du rachis et des articulations sacro-iliaques dans la spondylarthrite ankylosante.

The new diagnostic criteria for spondyloarthropathy include MRI. MRI frequently allows early diagnosis of inflammatory lesions of the spine and sacroiliac joints in patients with normal plain films. Moreover, MRI is useful for the detection and quantification of inflammatory and structural lesions, and to assess disease activity.

[Fissures of the posterior labrum and associated lesions: CT arthrogram evaluation]. / Fissures du labrum glénoïdal postérieur et lésions associées de l'épaule: une étude en arthroscanner.

PURPOSE: To describe osseous, chondral and tendinous lesions associated with fissures of the posterior labrum. To better understand the pathological processes leading to fissure of the posterior labrum. Materials and methods. Retrospective study of 43 CT arthrograms performed in 43 patients that showed a fissure of the posterior labrum. The following associated lesions were noted: osseous and chondral remodeling of the humeral head and/or glenoid and articular surface fissures of the rotator cuff. Based on type of associated lesions, patients were separated into one of four pathological subgroups: posterior instability, posterosuperior or internal impingement, anterior instability and isolated fissure of the posterior labrum. RESULTS: Sixteen patients (37.2%) of patients showed posterior instability, 12 (27.9%) showed lesions of internal impingement, and 11 (25.6%) showed lesions of anterior instability. Only 4 patients (9.3%) had an isolated fissure of the posterior labrum. CONCLUSION: Posterior instability, internal impingement and anterior instability are the main pathologies leading to fissure of the posterior labrum, which seldom occurs in isolation. Evaluation of these associated lesions allows understanding of the underlying pathological processes leading to fissure of the posterior labrum.

[Harmonic sonography of rotator cuff tendons: are cleavage tears visible at last?]. / Echographie des tendons de la coiffe en mode harmonique: les clivages sont-ils enfin visibles?

PURPOSE: For some, cleavage tears remain a pitfall of sonography (US). The purpose of this study is to demonstrate the visibility of intratendinous tears of the supraspinatus and infraspinatus tendons and describe their imaging features on tissue harmonic US. MATERIALS AND METHODS: Prospective study of 52 patients with suspected cuff pathology who underwent US prior to CT-arthrography, CT-bursography or MR arthrography. The US examinations were performed using 7-15 MHz transducers with tissue harmonic mode (pulse subtraction). An intratendinous tear was suggested by the presence of a hypoechoic intratendinous line, extending from a partial or full thickness tear. Results from US were correlated to contrast material enhanced CT or MR findings. RESULTS: Ten cases of cleavage tears were detected on US compared to 18 on arthrographic examinations. False negative results occurred in poor US candidates (n=4), excessively retracted tendons (n=2) or postsurgical cuffs (n=2). Sensitivity was 55% and specificity was 94%, with PPV of 83% and NPV of 80% for the detection of intratendinous tear. The accuracy of US was lower for intratendinous tear associated with full thickness tears (5/11) compared to intratendinous tears associated with partial thickness tears (5/6). CONCLUSION: We demonstrate that cleavage tears are now visible on US using high-frequency transducers and tissue harmonic mode. However, the sensitivity remains too low, especially in patients with full thickness tear, postsurgical patients and patients that are poor candidates to US.

Identification of a chromosome 11q23.2-q24 locus for familial aortic aneurysm disease, a genetically heterogeneous disorder.

BACKGROUND: Aortic aneurysms cause significant mortality, and >20% relate to hereditary disorders. Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan and Ehlers-Danlos type IV syndromes, due to defects in the fibrillin-1 and type III procollagen genes, respectively. Other gene defects that cause isolated aneurysms, however, have not thus far been described. METHODS AND RESULTS: We studied 3 families affected by FAA. No family met the diagnostic criteria for either Marfan or Ehlers-Danlos syndrome. Echocardiography defined involvement of both the thoracic and abdominal aorta. In family ANA, candidate gene analysis excluded linkage to loci associated with aneurysm formation, including fibrillin-1, fibrillin-2, and type III procollagen, and chromosome 3p24.2-p25. Genome-wide linkage analysis identified a 2.3-cM FAA locus (FAA1) on chromosome 11q23.3-q24 with a maximum multipoint logarithm of the odds score of 4.4. In family ANB, FAA was linked to fibrillin-1. In family ANF, however, FAA was not linked to any locus previously associated with aneurysm formation, including fibrillin-1 and FAA1. CONCLUSIONS: FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.

Two years' air mutagenesis monitoring in a northwestern rural area of Italy with an industrial plant.

The mutagenicity of organic extracts from inhalable airborne particles, collected in a northwestern rural area of Italy in which an industrial plant producing chemical intermediates is present, was assessed during the years 1989 and 1990. The Ames plate test with Salmonella strains TA98 and TA100 with and without metabolic activation was used. Eight sites in the first and three sites in the second year were monitored once and twice a month respectively. Results show that the mutagenicity of air particulate matter reaches maximum values in the cold months and is not dependent on plant activities. In addition, a correlation analysis between mutagenicity data and number of vehicles seems to indicate traffic emissions as the main source of mutagens.