251 research outputs found

    UVA1 genotoxicity is mediated not by oxidative damage but by cyclobutane pyrimidine dimers in normal mouse skin

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    UVA1 induces the formation of 8-hydroxy-2′-deoxyguanosines (8-OH-dGs) and cyclobutane pyrimidine dimers (CPDs) in the cellular genome. However, the relative contribution of each type of damage to the in vivo genotoxicity of UVA1 has not been clarified. We irradiated living mouse skin with 364-nm UVA1 laser light and analyzed the DNA damage formation and mutation induction in the epidermis and dermis. Although dose-dependent increases were observed for both 8-OH-dG and CPD, the mutation induction in the skin was found to result specifically from the CPD formation, based on the induced mutation spectra in the skin genome: the dominance of C → T transition at a dipyrimidine site. Moreover, these UV-specific mutations occurred preferentially at the 5′-TCG-3′ sequence, suggesting that CpG methylation and photosensitization-mediated triplet energy transfer to thymine contribute to the CPD-mediated UVA1 genotoxicity. Thus, it is the CPD formation, not the oxidative stress, that effectively brings about the genotoxicity in normal skin after UVA1 exposure. We also found differences in the responses to the UVA1 genotoxicity between the epidermis and the dermis: the mutation induction after UVA1 irradiation was suppressed in the dermis at all levels of irradiance examined, whereas it leveled off from a certain high irradiance in the epidermis

    Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: a case report

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    <p>Abstract</p> <p>Introduction</p> <p><it>Aeromonas </it>species do not commonly cause disease in humans. However, when disease is seen, it often occurs in patients with underlying immunosuppression or malignancy and has a high fatality rate.</p> <p>Case presentation</p> <p>A 72-year-old Japanese woman with rheumatoid arthritis treated with tocilizumab (which has an immunosuppressive effect) presented with severe epigastric pain. She had a fever with chills, hypotension and jaundice. She was diagnosed with acute suppurative cholangitis and treated with cefoperazone-sulbactam and an endoscopic drainage was performed. Jaundice was slightly improved, but the shock state and inflammatory reactions were prolonged as typical of septic shock. On the second day after admission, an electrocardiogram showed ST segment elevation and echocardiography showed ventricular wall dysfunction. Coronary arteries were patent in coronary angiography and she was diagnosed with stress-induced cardiomyopathy. Blood cultures showed <it>Aeromonas hydrophila</it>. A stool culture was negative for <it>A. hydrophila</it>. On day six, her white blood cell count and neutrophils were normalized and cefoperazone-sulbactam treatment was halted. Left ventricular function normalized on day twelve and a laparoscopic cholecystectomy for cholelithiasis was performed on the 16th day of hospitalization. A culture from the bile showed <it>A. hydrophila</it>. Eighteen days after surgery, tocilizumab treatment was restarted and there were no complications. Two months after restarting tocilizumab, our patient is stable without any serious events.</p> <p>Conclusion</p> <p>We present a rare case of <it>A. hydrophila </it>sepsis and acute suppurative cholangitis in an elderly patient with gallstones and rheumatoid arthritis using tocilizumab. This clinical course may suggest that preemptive treatment for cholelithiasis prior to using molecular-targeting agents might be feasible in elderly patients.</p

    Sentinel Lymph Node Radiolocalization with 99mTc Filtered Tin Colloid in Clinically Node-Negative Squamous Cell Carcinomas of the Oral Cavity

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    The objective of this study was to evaluate the feasibility of sentinel lymph node biopsy by using a radiotracer lymphatic mapping technique in patients with squamous cell carcinoma of the oral cavity, and the diagnostic value of this technique. We studied twenty patients with previously untreated squamous cell carcinomas of the oral cavity and N0 necks. After the peritumoral injection of 99mTc filtered tin colloid preop-eratively, lymphoscintigraphy and intraoperative mapping using a gamma detector were performed to localize sentinel nodes. An open biopsy of the sentinel node was followed by complete neck dissection. We identified the sentinel nodes in 19 of 20 patients (95.0%) by lymphoscintigraphy and in all (100%) by intraoperative gamma detector. In all cases, the status of the sentinel node accurately predicted the pathologic status of the neck with the false negative rate being 0%. The negative predictive value for the absence of cervical metastases was 100%. In conclusion, our radio-localization technique of sentinel nodes using 99mTc filtered tin colloid in N0 squamous cell carcinomas of the oral cavity is technically feasible and appears to accurately predict the presence of the occult metastatic disease

    Imaging-guided chest biopsies: techniques and clinical results

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    Background This article aims to comprehensively describe indications, contraindications, technical aspects, diagnostic accuracy and complications of percutaneous lung biopsy. Methods Imaging-guided biopsy currently represents one of the predominant methods for obtaining tissue specimens in patients with lung nodules; in many cases treatment protocols are based on histological information; thus, biopsy is frequently performed, when technically feasible, or in case other techniques (such as bronchoscopy with lavage) are inconclusive. Results Although a coaxial system is suitable in any case, two categories of needles can be used: fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB), with the latter demonstrated to have a slightly higher overall sensitivity, specificity and accuracy. Conclusion Percutaneous lung biopsy is a safe procedure even though a few complications are possible: pneumothorax, pulmonary haemorrhage and haemoptysis are common complications, while air embolism and seeding are rare, but potentially fatal complications

    Portal Vein Aneurysm in a Patient with Cirrhosis Type C Controlled by Direct-Acting Antiviral Treatment

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    Introduction: Portal vein aneurysm (PVA) is a rare saccular or fusiform portal vein dilatation. The management and optimal treatment of PVA remain unknown. Case Presentation: A 53-year-old man with hepatitis C virus (HCV) infection was diagnosed with PVA measuring 28 mm in diameter. Under observation, his liver fibrosis progressed, and the PVA diameter gradually increased to 52 mm. The patient was treated with elbasvir-grazoprevir for 12 weeks, and HCV disappeared. After achieving sustained virological response, liver fibrosis improved and the PVA progression ceased. Conclusion: HCV clearance by direct-acting antiviral treatment not only regressed liver fibrosis but may have also restrained the progression of PVA in a patient with cirrhosis type C and PVA

    A loss of c-kit expression is associated with an advanced stage and poor prognosis in breast cancer

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    To evaluate the c-kit expression in breast cancer, 217 invasive ductal carcinomas of the breast were immunohistochemically stained for c-kit protein. The c-kit expression was positive in 59 (27%) of 217 tumours, while the c-kit expression was negative in 158 (73%) of 217 tumours. There was a significant correlation between a negative expression of the c-kit protein and lymph node metastasis (P<0.0001), and the incidence of a negative expression of the c-kit protein increased as the number of the metastatic lymph nodes increased (P=0.0003). The c-kit expression did not significantly correlate with the tumour size, nuclear grade, oestrogen receptor status, MIB-1 counts and p53 protein expression. A univariate analysis indicated the patients with the negative c-kit expression to have a worse disease-free survival (DFS) than those with the positive c-kit expression (P=0.0041), while a multivariate analysis determined lymph node metastases and the MIB-1 counts to be independently significant factors for DFS. In conclusion, a loss of the c-kit expression was found in about three-fourth of invasive ductal carcinoma of the breast and was associated with lymph node metastases. The prognostic implications of the c-kit expression seem to be due to fact that a loss of the c-kit expression is associated with an advanced stage of breast cancer
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