Verification of responses of Japanese medaka (Oryzias latipes) to anti‐androgens,vinclozolin and flutamide,in short‐term assays

Various testing methods for the detection of the endocrine disruptive activities of chemicals have been developed in freshwater fish species. However, a few relatively easier specific methods for detecting anti‐androgenic activities are available for fish. The aim of this study was to verify the papillary process in Japanese medaka (Oryzias latipes) as an indicator of the anti‐androgenic activity of chemicals. Japanese medaka were exposed to two types of anti‐androgenic compounds, vinclozolin and flutamide, using two short‐term assays; one was conformed to the existing short‐term reproduction assay using adult fish (adult test) and the other was a test based on the same methods but using juvenile fish at the beginning of exposure (juvenile test). Significant decreases in male papillary processes were observed in the juvenile test treated with the highest concentration of both antiandrogens (640 µg l^–1 vinclozolin and 1000 µg l^–1 flutamide); however, no significant effects were observed in the adult test. Consequently, our results indicate that papillary processes in Japanese medaka can be used as the end‐point for screening the anti‐androgenic activity of chemicals using juvenile fish for a specific period based on the existing short‐term reproduction assay. Copyright © 2013 John Wiley & Sons, Ltd.     

Early detection of doxorubicin-induced myocardial damage by ultrasound tissue characterization with integrated backscatter.

Doxorubicin (DXR) is one of the most effective antineoplastic agents, but its use is limited by its myocardial toxicity. Myocardial injury reduces the cyclic variation of integrated backscatter (CV-IBS) and so the present study was designed to investigate whether CV-IBS can be used to detect the early phase of myocardial damage in patients receiving DXR. Thirty-four subjects constituted the study population, none of whom showed clinically evident heart failure. CV-IBS was obtained for both the interventricular septum and the left ventricular posterior wall in the parasternal short-axis view. Standard echographic measures of left ventricular function were also made. Subjects without DXR exposure or evident cardiac diseases served as controls. The total dose of DXR administered per patient was 339+/-164 mg/m2 (range: 95-680 mg/m2). Conventional echographic parameters, including left ventricular wall thickness, dimensions, fractional shortening, and ejection fraction, showed no significant differences between the 2 groups. In contrast, CV-IBS was significantly decreased in the DXR group compared with the control group (septum: 4.7+/-1.7 vs 7.2+/-1.9 dB, p<0.0001; posterior wall: 6.7 +/-2.2 vs 8.0+/-1.6 dB, p<0.05). CV-IBS can be used as an early indicator of DXR-induced myocardial damage in patients demonstrating normal left ventricular systolic function.     

Rapid progression of hepatocellular carcinoma after transcatheter arterial chemoembolization and percutaneous radiofrequency ablation in the primary tumour region

We report one patient who showed rapid progression of hepatocellular carcinoma (HCC) after undergoing transcatheter arterial chemoembolization (TACE) and percutaneous radiofrequency ablation (PRFA) for a small HCC measuring 2.5 cm in diameter. Enhanced magnetic resonance imaging (MRI) following treatment showed complete tumour necrosis and did not reveal the presence of a tumour around the treated area. Furthermore, the serum alpha-fetoprotein (AFP) level decreased at the completion of therapy. However, the HCC advanced in a very short time. Numerous tumours around the treated area were observed on enhanced computed tomography (CT) 50 days after PRFA. It is strongly suspected that the tumour was disseminated through the portal system because of the presence pattern of tumours. We believe this to be the first case illustrating a hepatic cancer that progressed rapidly following TACE and PRFA.     

Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis

Mutated epidermal growth factor receptor (EGFR) and signaling pathways were associated with multiple brain and intra-pulmonary metastases, oncogenic progression and metastasis. However, features of metastasis to other organs and the independent prognostic influence of metastatic lesions were not elucidated in patients with lung cancer harboring EGFR mutations. Between January 2007 and April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma. Studied were 246 patients with available tumor EGFR mutation data who also underwent radiographic evaluation of lung, abdominal, brain, and bone metastases. The EGFR mutated group (N = 98) had significantly more metastatic lesions in the brain and bone than the wild-type group (N = 148): brain, 3 (1–93) versus 2 (1–32) median (range), P = 0.023; bone, 3 (1–43) versus 2 (1–27), P = 0.035, respectively. In addition, EGFR mutations were significantly more frequent in patients with multiple than non-multiple lung metastases (24/40 vs. 12/42, P = 0.004). Multivariate analysis showed that bone metastasis was a significant independent negative predictive factor of overall survival (OS) in patients with mutated [hazard ratio (HR) 2.04; 95 % confidence interval (CI) 1.17–3.64; P = 0.011] and wild-type EGFR (HR 2.09; 95 % CI 1.37–3.20; P < 0.001). In conclusion, patients with mutated EGFR had more lung, brain, and bone metastases, and bone metastasis was an independent negative predictor of OS.     

Basiliximab treatment for steroid‐resistant rejection in pediatric patients following liver transplantation for acute liver failure

An IL‐2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6–12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno‐occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF.     

Central pontine myelinolysis following pediatric living donor liver transplantation: A case report and review of literature

CPM is one of the most serious neurological complications that can occur after OLT and is characterized by symmetrical demyelinization in the basis pontis. The etiology of CPM remains unclear, although the rapid correction of the serum sodium and CNI concentrations may be associated with the development of CPM. With recent advances in MRI technology, early diagnosis of CPM has become possible. Here, we present the case of a five‐yr‐old female who developed CNI‐associated CPM after undergoing LDLT. A decreased level of consciousness and dysphasia was noted one wk after LDLT, and MRI revealed findings compatible with a diagnosis of CPM. The patient fully recovered from the neurological deficits related to CPM following the switch from the CNI to sirolimus. We propose MRI to be promptly considered for patients with abnormal neurological findings, together with the substitution of CNI with an mTOR inhibitor as a management regimen for CNI‐related CPM.     

Dynamic magnetic resonance imaging for the evaluation of synovitis in patients with rheumatoid arthritis

Objective. To investigate whether the findings of magnetic resonance imaging (MRI) reflect rheumatoid synovitis. Methods. Dynamic imaging enhanced with gadolinium—diethylenetriamine pentaacetic acid was performed on 10 affected knees of 9 patients with rheumatoid arthritis. Changes in signal intensity were correlated with pathologic findings in synovial biopsy specimens obtained during total knee arthroplasty. Results. Enhancement was greater in regions with a higher degree of fibrin exudation, cellular infiltration, villous hypertrophy, vascular proliferation, and granulation formation. Conclusion. Dynamic MRI can be used for assessing local disease activity in rheumatoid synovium.     

Three cases of COVID-19 patients presenting with erythema

Individuals infected with the novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2]) who develop coronavirus disease 2019 (COVID-19) experience many symptoms; however, cutaneous manifestations are relatively rare. The authors encountered three patients with COVID-19 who presented with erythema and suspected viral rash. In all cases, erythema appeared after the onset of the initial symptoms of COVID-19. Erythema was considered to be caused by COVID-19 and not a drug-induced eruption because, in all cases, erythema was relieved merely by external medicine and oral antihistamines, without discontinuing the original medication. The authors’ hospital accepted 69 COVID-19 patients between 22 February 2020 and 31 May 2020 and, of these, three (4.3%) exhibited eruptions, and all cases presented erythema. Except for seven patients who exhibited positive nasopharyngeal swab tests for SARS-CoV-2 RNA but no symptoms, three (4.8%) of the remaining 62 patients exhibited erythema. Although various types of eruptions have been reported in patients with COVID-19, erythema was the only type in our patients. Erythema in the three patients exhibited many similarities to that previously reported in COVID-19 patients, particularly in the manner it appeared and disappeared. For these reasons, these three cases were considered typical examples of erythema in patients with COVID-19. Considering previous studies and the three cases reported here, there is a high probability that SARS-CoV-2 can cause erythema.     

Development of type 1 diabetes in a patient treated with anti‐interleukin‐6 receptor antibody for rheumatoid arthritis

Interleukin‐6 is a pleiotropic cytokine that plays a pathogenic role in type 1 diabetes. Therefore, anti‐interleukin‐6 receptor antibody, tocilizumab, used for the treatment of rheumatoid arthritis, is considered a candidate for immune intervention in type 1 diabetes. Here, we report the case of a 73‐year‐old woman (HLA‐DR9‐DQ3 homozygote) with well‐controlled rheumatoid arthritis who developed type 1 diabetes while receiving tocilizumab treatment. At 57 years‐of‐age, the patient was diagnosed with rheumatoid arthritis, for which she underwent tocilizumab therapy that enabled complete suppression of her joint inflammation. A total of 17 months after starting tocilizumab therapy, she noticed polydipsia, polyuria, general fatigue and weight reduction (−2 kg/month), and was diagnosed with type 1 diabetes with diabetic ketoacidosis based on an arterial pH of 7.26, serum ketone body of 7,437 μmol/L, blood glucose level of 925 mg/dL, glycated hemoglobin of 13.2% and the presence of anti‐islet autoantibodies. This case report shows valuable insight regarding the effect of anti‐interleukin‐6 receptor antibody therapy on type 1 diabetes prevention.