Search

Introduction: Thyroid fine-needle cytology is the first line clinical method for thyroid nodule to select patients for surgery, because papillary carcinoma has diagnostic characteristics in cytology, such as nuclear enlargement, nuclear grooves and nuclear inclusions. However over-diagnosis of Hashimoto disease is well known fact to occur frequently.Materials and Methods: Morphometric analysis of cytological samples from Hashimoto disease, papillary carcinoma and benign adenomatous nodule were carried out 4 cases each using Papanicolaou stained conventional smear samples.Results: Sizes of clusters were evaluated by counting number of follicular cells in the cluster. It was larger in papillary carcinoma (63.3/cluster) and benign (43.9/cluster) than Hashimoto disease (18.9/cluster) (P=0.006). The nuclear diameter increased in Hashimoto disease and the average of the longest diameter was 6.5μm and the shortest was 5.5μm, which was overlapped with those of papillary carcinoma. The number of nuclear grooves increased from benign (

Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms. We report a very rare case with autoimmune hepatitis (AIH) complicated by CAEBV. A 50-year-old woman with systemic lupus erythematosus (SLE) complicated by AIH began to suffer from acute respiratory failure and her clinical symptoms improved rapidly in response to steroid treatment. However, during the gradual tapering of the steroid dose, a steady increase of the serum hepatobiliary enzyme levels subsequently was observed and the patient began to have continuous fever. Moreover, upper gastrointestinal endoscopy revealed multiple intractable gastric ulcers. When EBER-ISH was performed on liver biopsy and gastric mucosal biopsy specimens, EBER-positive lymphocytes were observed. When peripheral blood was examined, 2.1 × 106 copies/µg of EBV-DNA were observed in the CD4-positive T cells, confirming the diagnosis of CAEBV. A cooling therapy was started by steroid and cyclosporine. Thereafter, despite the start of CHOP therapy, she developed a malignant lymphoma (PTCL-NOS) and died of hepatic failure. When treatment-resistant AIH patients are encountered, not only AIH exacerbation but also CAEBV should be considered in the differential diagnosis.

We herein report the case of a 72-year-old woman with diffuse cutaneous systemic sclerosis (SSc) complicated by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who exhibited honeycomb lung without volume loss. On admission, chest computed tomography (CT) revealed honeycomb lung without volume loss in addition to increased density of the partition walls. A renal biopsy revealed global sclerosis and cellular crescent formation. Mononeuritis multiple subsequently occurred, and steroid pulse therapy with cyclophosphamide was administered. Repeat chest CT showed that the honeycomb lung was unchanged; however, overall reduced density of the partition walls was observed. It is necessary to recognise that vasculitis may develop in SSc patients who exhibit honeycomb lung without volume loss.

Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves’ disease. She was diagnosed with Graves’ disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves’ disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves’ disease, few reports about thyroid cancer accompanied by Graves’ disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves’ disease.

A 48-year-old female with a past history of systemic lupus erythematosus had developed autoimmune hepatitis (AIH) at the age of 45 years, and administration of PSL 30 mg/day was initiated. However, AIH exacerbation was suspected based on elevation of hepatic and biliary tract enzymes such as ALP (1207U/L) with a fever of 38 degrees C after tapering off the steroids to PSL 7.5 mg daily, and she was thus hospitalized. A liver biopsy was recommended, but she refused. Thus, we suspected concomitant AIH and autoimmune cholangitis (AIC). Although high-dose steroid treatment including steroid pulse therapy was administered, there was no improvement. We performed a liver biopsy on the 66th hospital day, after obtaining the patient's consent. Epithelioid granuloma was detected in the liver leaflet as the background of the AIH and AIC findings. In addition, acid fast bacteria were detected with auramine and Ziehl-Neelsen staining, raising the possibility of tuberculosis. Additionally, granuloma was also seen in her bone marrow, and miliary tuberculosis was suspected. Anti-tuberculous therapy with isoniazid, rifampicin, ethambutol and pyrazinamide was initially administered, but the regimen was changed to levofloxacin, ethambutol, and streptomycin due to the side effects of the earlier medications. Liver functions improved and the inflammatory reaction became negative. The patient was discharged on the 138th hospital day. Ultimately, no acid fast bacteria were detected with culture, PCR of her bone marrow, or liver biopsy. However, miliary tuberculosis was definitively diagnosed from the pathological findings and her clinical course. AIH was an underlying disease, and the discrimination from AIH exacerbation was difficult. Consequently, the diagnosis was miliary tuberculosis without the lung involvement and the main lesion was in the liver. It is important to take account of miliary tuberculosis in the differential diagnosis of fevers of unknown origin with elevation of hepatic and biliary tract enzymes, and to make a definitive diagnosis with a liver biopsy.

We herein report on a 69-year-old male who developed lung nocardiosis and brain abscessation. In April 2011, he was diagnosed as having systemic lupus erythematosus complicated by peripheral neuropathy. Immunosuppressive therapy with high-dose prednisolone was begun. In November 2011, he developed cryptococcal pneumonia and meningitis, which was treated with liposomal amphotericin and flucytosine for 4 weeks and was maintained with fluconazole. In April 2012, consolidation and peripheral atelectasis in the right middle lobe appeared. Bronchoscopy revealed edematous mucosa in the right middle bronchus and occlusive change of the right B4 and B5, but biopsy and culture results provided no etiological information. In late June, he developed an intermittent fever, and obstructive pneumonia of the right middle lobe was suspected. Nocardia species were detected from the sputum culture and were thought to be the causative pathogen. Brain CT and MRI revealed a contrast-enhanced lesion in the right cerebellar hemisphere. The patient was diagnosed as having lung nocardiosis and brain abscessation. Considering that the nocardiosis had developed under prophylaxis for Pneumocystis jirovecii pneumonia using one tablet per day of a sulfamethoxazole-trimethoprim combination, meropenem and amikacin were administered in addition to the sulfamethoxazole-trimethoprim combination for 6 and 4 weeks, respectively. After N. elegans had been identified from the sputum, antibiotics were switched to a sulfamethoxazole-trimethoprim combination and clarithromycin based on the susceptibility results. The patient's clinical and radiological findings were improved and have been well sustained.

To evaluate the possible correlation of malignant neoplasms and paraneoplastic rheumatologic syndromes.We studied a series of 10 patients with paraneoplastic rheumatological syndromes collected from our Division of Rheumatic Disease between 2006 and 2012.Our series consisted of four males and six females, with a mean age of 65.5 years (range, 57-78 years). Of the 10 patients recruited, six had hematological malignancies and four had solid cancers. Malignancies were diagnosed after rheumatic symptoms were reported in all patients. Compared to solid tumors, hemopathy was diagnosed at a later time point (16.2 vs. 7.3 months). Extra-articular symptoms were associated with rheumatologic musculoskeletal manifestations in 100% of the patients. Polyarthritis was the main rheumatologic musculoskeletal manifestation (50% of the patients). The other manifestations were oligopolyarthritis and polymyalgia rheumatic-like symptoms (20% of the patients). Symmetric arthritis was present in 60% of the patients, and the remaining patients developed asymmetric arthritis. Musculoskeletal manifestations completely regressed in 66.7% of the patients after cancer therapy. When tumor relapse was observed, rheumatic symptoms did not recur in any of our patients (100%).Rheumatic disorders with atypical clinical presentation in older patients, poor response to usual treatment and systemic features such as weight loss and clinical findings compatible with well-recognized paraneoplastic syndromes should alert clinicians to the possible coexistence of an occult malignancy. Especially in cases of paraneoplastic rheumatic/musculoskeletal manifestations associated with hemopathy, the primary disease is unlikely to have manifested yet, making the diagnosis difficult. Thus, caution is required.

Objectives. While there are a few reports describing 18F-fluoro-dexoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) findings in patients with adult-onset Still's disease (AOSD), no summary report has yet been published. In this study, we evaluated the usefulness of FDG-PET/CT for diagnosis and activity evaluation in patients with AOSD by summarizing the findings of our patients and those reported in the literature.Methods. Seven consecutive AOSD patients who had undergone PET/CT at our department between 2007 and 2012 were included. We evaluated FDG uptake for characteristic findings in patients with AOSD. In addition, we reviewed the literature on seven previously reported AOSD patients who had undergone PET/CT.Results. FDG accumulation was positive mainly in the bone marrow (100%), spleen (90.9%), lymph nodes (80.0%) and joints (75.0%). In addition, FDG uptake was positive in the pericardium, pleura, salivary glands, eyelids, muscle and major blood vessels. Six patien...

The clinical and therapeutic aspects of primary Sjögren syndrome (PSS) in patients with peripheral neuropathy were analyzed and the specifics of individual case studies are discussed.We retrospectively studied six patients (four women, two men; mean age 64.5 years) presenting with PSS with peripheral neurological involvement over a five-year period (2008-2012). All patients had neurological examinations, including nerve conduction studies, somatosensory evoked potentials, and sural nerve biopsies. Treatment regimens included corticosteroids, intravenous gammaglobulin, or immunosuppressive treatment.Peripheral neuropathy was observed in six (7.9 %) of 76 patients with SS as the underlying disease; three were cases of multiple mononeuropathy, two cases had sensory ataxic neuropathy, one of which was autonomic neuropathy, and one case was diagnosed as painful sensory neuropathy without sensory ataxia. Four of the six patients were diagnosed with SS after the onset of neurological symptoms. Individual peripheral neuropathies had distinct neurological, electrophysiological, and pathological characteristics. The effect of steroids and intravenous gammaglobulin differed depending on the case.In PSS patients, a precise diagnosis is important, because the therapeutic strategy and response varies depending on the type of neuropathy. In clinical practice, it is important to consider a diagnosis of SS when patients present with peripheral neuropathy.

Cytomegalovirus disease of the upper gastrointestinal tract (CMV-UGT) is a rare but significant complication in patients with rheumatic diseases. We reviewed records for January 2004 to December 2012 and investigated the occurrence of CMV-UGT in patients with rheumatic diseases to evaluate clinical characteristics, the value of the CMV antigenemia assay, and the association between immunosuppressive therapy and CMV-UGT. Ten CMV-UGT events (six gastric ulcer, two esophagitis, one gastritis, and one duodenal ulcer) in nine patients (three rheumatoid arthritis, three systemic lupus erythematosus, one dermatomyositis, one systemic sclerosis, and one overlap syndrome) were identified based on pathology. Mean age was 66.5 (range, 53-76) years. The CMV antigenemia assay was negative in five cases (50 %). All ten cases received glucocorticoids and six (60 %) received pulsed glucocorticoids. Mean prednisolone dose was 31.3 (range, 7.5-40) mg/day at diagnosis. Concomitant immunosuppressive agents were used in eight cases (80 %). Considering other published cases, the most common immunosuppressive drug was cyclophosphamide (ten cases; 45 %). Notably, two of our patients who were treated with low-dose glucocorticoids plus other milder immunosuppressive drugs (methotrexate and cyclosporine) also developed CMV-UGT. Life-threatening complications such as massive bleeding or perforated ulcer occurred in two patients. These results suggest that patients receiving intensive immunosuppressive therapy such as high-dose glucocorticoids and cyclophosphamide are at higher risk for developing CMV-UGT. Moreover, CMV-UGT can occur even with low-dose glucocorticoid therapy and relatively mild immunosuppressive agents. The value of the CMV antigenemia assay for predicting CMV-UGT appears to be limited.

Here, we present two Behcet’s disease (BD) patients with an uncommon complication: inflammation surrounding the spinous processes revealed by positron emission tomography/computed tomography (PET/CT). Both patients were treated successfully with 20 mg of prednisolone daily. Whether BD should be considered a form of spondylarthritis remains an open question. However, inflammation around the spinous processes should be regarded as a possible uncommon finding of seronegative spondyloarthropathy (SpA) in BD patients.

An association between thrombotic thrombocytopenic purpura (TTP) and Sjogren’s syndrome (SS) is rare. This is the first report of two patients with TTP who had inhibitory autoantibodies to ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) complicating primary SS. A rapid diagnosis of TTP, which is a potentially lethal condition, made it possible to treat the two cases successfully. Only eight similar cases with TTP complicating SS have been reported in the literature. The possible presentation of primary SS without classic sicca symptoms, but with haematological abnormalities including TTP, should be recognised. Furthermore, it is important to measure ADAMTS13 activity and anti-ADAMTS13 antibodies, because TTP with SS seems to be a concurrent overlapping autoimmune disorder. We suggest that plasma exchanges in combination with corticosteroids should be administered as early as possible, since they appeared to be effective in treating TTP with SS, including in our cases.

Resume Objectif Nous avons evalue les resultats de la tomographie par emission de positons couplee a la tomodensitometrie (TEP-TDM), utilisant comme traceur le fluorodesoxyglucose marquee au fluor 18 (18F) (FDG), dans les spondylarthropathies seronegatives (Spa), la pseudopolyarthrite rhizomelique (PPR) et la polyarthrite rhumatoide (PR). Methodes Nous avons etudie 53 patients hospitalises dans notre hopital entre 2006 et 2011 : 21 atteints de Spa, 16 atteints de PPR et 16 atteints de PR. L’activite inflammatoire de la maladie a ete evaluee en determinant l’accumulation du FDG a l’aide des scores standardized uptake values (SUVmax) et FDG, aux sites d’interet suivants : tuberosites ischiatiques, grands trochanters, apophyses epineuses, corps vertebraux, articulations sacro-iliaques. Resultats Le scores SUVmax des tuberosites ischiatiques etaient plus eleves dans la PPR par rapport aux Spa et a la PR. Les scores SUVmax des grands trochanters et des apophyses epineuses etaient significativement plus eleves dans la PPR que dans la PR (p Conclusions La detection par TEP-TDM d’anomalies inflammatoires siegeant aux tuberosites ischiatiques, aux grands trochanters et aux apophyses epineuses pourrait etre discriminante entre la PPR et la PR, mais pas entre les Spa et la PPR. Les anomalies mises en evidence par la TEP-TDM permettent de distinguer les Spa des PR et des PPR et sont utiles au diagnostic precoce des sacroiliites.

We assessed fluorine-18 ((18)F)-labelled fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) findings in patients with seronegative spondyloarthritis (SpA), polymyalgia rheumatica (PMR), and rheumatoid arthritis (RA).We studied 53 patients with SpA (n=21), PMR (n=16), or RA (n=16) admitted to our hospital between 2006 and 2011. Disease activity in the ischial tuberosities, greater trochanters, spinous processes, vertebral bodies, and sacroiliac joints (SIJ) were evaluated by determining FDG accumulation using maximum standardized uptake values (SUV(max)) and FDG scores.SUV(max) for ischial tuberosities was significantly higher in PMR than SpA or RA. SUV(max) for greater trochanters and spinous processes was significantly higher in PMR than RA (P0.001) and significantly higher in SpA than in PMR or RA for SIJ (P=0.01). No significant difference in vertebral scores was observed among groups (P=0.488). FDG scores yielded similar results. X-ray findings were consistent with PET/CT findings in 3/15 (20%) patients with sacroiliitis, whereas magnetic resonance imaging findings were consistent with PET/CT findings in 4/7 (57.1%) patients.PET/CT detection of inflammation in the ischial tuberosities, greater trochanters, and spinous processes discriminated between PMR and RA, but not between SpA and PMR. PET/CT findings can distinguish SpA from RA and PMR and are useful for the early diagnosis of sacroiliitis.

We report a case of dermatomyositis (DM) and hemophagocytic lymphohistiocytosis (HLH) complicated by central nervous system (CNS) lesions and review eight literature cases of DM and HLH. A 17-year-old woman, admitted to our hospital because of severe muscle weakness and high fever, was diagnosed with DM based on elevated serum levels of muscle enzymes and a typical skin rash. Pancytopenia, high serum ferritin and soluble interleukin (IL)-2 receptor, and hepatosplenomegaly were also noted. Bone-marrow examination was negative for hemophagocytosis. Steroid therapy combined with immunoglobulin i.v. was ineffective against the DM, pancytopenia, hepatic dysfunction, and hyperferritinemia. On the 27th hospital day, seizures and acute respiratory failure occurred. In the course of improving muscle enzyme levels after starting adjunctive treatment with cyclosporine, the patient suffered disturbed consciousness, dyskinesia, and tremor. Brain magnetic resonance imaging (MRI) revealed T2 hyperintense lesions in the pons. Additional cyclophosphamide pulse therapy successfully decreased serum ferritin. Unfortunately, the diffuse alveolar damage (DAD) confirmed by biopsy progressed and the patient died. Autopsy findings revealed DAD throughout both lungs, HLH liver lesions, and a hemorrhagic necrotic lesion of the pons in the brain. Even when pathological examination yields no findings of hemophagocytosis, it is important to comprehensively and rapidly diagnose HLH based on the clinical picture. Because DM complicated by HLH may be associated with abnormal production of cytokines and systemic autoimmune responses, it may be necessary to immediately administer additional immunosuppressive therapy. We describe and discuss the extraordinary, severe form of DM in our patient, along with cases in the literature.

Cynomolgus macaques, used in drug metabolism studies due to their evolutionary closeness to humans, are mainly bred in Asian countries, including Cambodia, China, and Indonesia. Cytochromes P450 (P450s) are important drug-metabolizing enzymes, present in the liver and small intestine, major drug metabolizing organs. Previously, our investigation did not find statistically significant differences in hepatic P450 metabolic activities measured in cynomolgus macaques bred in Cambodia (MacfaCAM) and China (MacfaCHN). In the present study, P450 metabolic activity was investigated in the small intestine of MacfaCAM and MacfaCHN, and cynomolgus macaques bred in Indonesia (MacfaIDN) using P450 substrates, including 7-ethoxyresorufin, coumarin, bupropion, paclitaxel, diclofenac, S-mephenytoin, bufuralol, chlorzoxazone, and testosterone. The results indicated that P450 metabolic activity of the small intestine was not statistically significantly different (2.0-fold) in MacfaCAM, MacfaCHN, and MacfaIDN. In addition, statistically significant sex differences were not observed (2.0-fold) in any P450 metabolic activity in MacfaCAM as supported by mRNA expression results. These results suggest that P450 metabolic activity of the small intestine does not significantly differ statistically among MacfaCAM, MacfaCHN, and MacfaIDN.

A 51-year-old male patient with no underlying illness developed a fever of 38-39 degrees C in June 2009. The fever persisted for 4 days and, because elevated hepatobiliary enzymes, leukocytopenia and thrombocytopenia were observed, along with chest CT findings of inflammation of the soft tissues surrounding the left pulmonary artery, the patient was admitted for further examination. Three days after admission, the patient's blood pressure rapidly decreased, resulting in respiratory failure. Rapid proliferation of the soft tissue surrounding the pulmonary artery and mediastinum was observed on an emergency chest CT. Malignant lymphoma was initially considered as a possible differential diagnosis; however, neither pleural effusion nor infiltration of malignant cells could be observed on bone marrow examination. In addition, because the patient responded well to antibiotics, a diagnosis of acute mediastinitis was reached. Mediastinal drainage was not performed because the quantity of accumulated fluid was small and because the patient, both in terms of his clinical symptoms and imaging results, showed improvement with the continuation of antibiotics alone. The patient was ambulatory and was discharged after 24 days of hospitalization. Acute mediastinitis often follows a rapidly progressive and fatal course without specific symptoms. In the event of unknown infection following an aggressive course, as in the present case, acute mediastinitis must be considered with the goal of early diagnosis and treatment.

We report three patients with dermatomyositis (DM) complicated with acute interstitial pneumonia (AIP). All of them complained of fever and acutely worsening dyspnea and were treated immediately by combination therapies with pulse therapy with methylprednisone (mPSL) followed by corticosteroids, biweekly intravenous pulse cyclophosphamide (IVCY) and cyclosporine A (CSA). They recovered rapidly soon after an initiation of this combination regimen. Early intervention with aggressive combination therapy is life-saving for the treatment of AIP in patients with DM.

We report a 33-year-old female who developed a movement disorder during maintenance therapy for systemic lupus erythematosus (SLE). She was diagnosed with SLE at the age of 25, and experienced an episode of SLE-associated hemophagocytic syndrome at age 27, which was successfully treated with intensive immunosuppressive therapy. In November 2012, during maintenance therapy with prednisolone (PSL) 5 mg/day and tacrolimus 0.5 mg/day, she developed acute-onset involuntary movements that were classified as chorea in combination with athetosis in her right limbs and right homonymous hemianopia, which subsided after about 1 h. Her laboratory tests on admission showed an elevated serum anti-double- stranded DNA antibody, positive serum anti-cardiolipin IgG, and an elevated IgG index in cerebrospinal fluid. Magnetic resonance imaging (MRI) showed no significant abnormality on admission, but an ischemic change in her left pallidum appeared on day 7. She was treated with a combination of high-dose corticosteroid, immunosuppressive agents (rituximab, cyclophosphamide, mycofenolate mofetil), antithrombotic therapy (heparin, cilostazol), and dopamine antagonists. Her symptoms remitted partially. Chorea in SLE is recognized as an anti-phospholipid-antibody-associated disorder. In our case, both immunological and ischemic mechanisms were thought to be involved.

Background and object The right nonrecurrent inferior laryngeal nerve (NRILN), which is usually associated with the right aberrant subclavian artery, is a risk factor of nerve injury during thyroid surgery. Therefore the presence of the NRILN should be diagnosed if possible before surgery. The aim of this study was to investigate the usefulness of computed tomography (CT) and ultrasonography (US) for preoperative diagnosis of the right-sided NRILN. Subjects and methods We reviewed 1,561 patients who underwent thyroid surgery, during which the right inferior laryngeal nerve was exposed, at Yamashita thyroid and parathyroid clinic from April 2006 to April 2012. All medical records, CT findings and ultrasonograms of these patients were reviewed retrospectively. Results We recognized 11 patients who had the right-sided NRILN from the total of 1561 patients (0.71%). Ten of 1086 patients who underwent CT, had a right aberrant subclavian artery. CT findings were enabled us to predict the existence of the right NRILN before surgery. The sensitivity and specificity of CT for detection of the right-sided NRILN were 100% and 100%. On the other hand, we could detect the bifurcation of the innominate artery in 116 of 140 patients with cervical US before surgery, and therefore could confirm that the right inferior laryngeal nerve of the 116 patients was normal. The bifurcation of the other patients was not detectable and one of the 24 patients only had the right-sided NRILN during surgery. The sensitivity and specificity of cervical US for detection of the right-sided NRILN were 100% and 83.5% respectively. Conclusions Although CT is extremely useful for preoperative diagnosis of the right-sided NRILN because of its accuracy, cervical US is also a good method for making sure that the right inferior laryngeal nerve is normal.

RATIONALE: Anti-aminoacyl transfer RNA synthetases (ARS) antibodies are a group of myositis specific autoantibodies. It also is frequently found in patients with complicating interstitial pneumonia. However, the clinical characteristics in these patients with anti-ARS antibody were not yet fully elucidated. METHODS: We retrospectively investigated clinical symptoms, radiological findings, treatments, and its outcome in 30 patients with anti-ARS antibody-positive interstitial pneumonia (ARS-IP) in our institution. The radiological patterns of interstitial pneumonia were evaluated with thin-sliced HRCT by two specialists. Anti-ARS antibodies were evaluated using RNA immunoprecipitation assey and anti-synthetase ELISA kit (BML, Japan). RESULTS: Mean age was 59.4 years (28-82), 60.0% were female. Nine patients were with anti-Jo-1, 7 with anti-EJ, 4 with anti-PL-12, 3 with anti-PL-7, 2 with anti- OJ, and 5 with unknown or anti-KS. Seven cases were diagnosed as having ARS-IP with dermatomyositis (DM), and 7 with polymyositis. There were no differences in the demographic features, laboratory data, HRCT findings, between ARS-IP with myositis and without. ARS-IP with myositis recurs more often than without myositis (p=0.019). Serum creatinine kinase (CK) levels were elevated in 13 patients. Patient achieved good responses to initial corticosteroid and immunosuppressant. Mean observation time was 64.9 months (4 months- 138 months). CONCLUSIONS: Most of the patients with interstitial pneumonia associated with anti-ARS antibodies showed remarkable responses to the therapy and favorable outcome.

(2012). The natural history of asymptomatic positron emission tomography: positive giant cell arteritis after a case of self-limiting polymyalgia rheumatica. Modern Rheumatology: Vol. 22, No. 6, pp. 942-946.

We report a rare case of intravascular large B-cell lymphoma (IVLBCL) with diffuse fluorodeoxyglucose (FDG) uptake in the lung by (18)FDG-positron emission tomography/computed tomography (PET/CT). CT showed nodular shadow, whereas diffuse FDG uptake in PET/CT suggested IVLBCL in the lung. A random skin biopsy provided histological evidence of IVLBCL. The patient responded well to combination chemotherapy. Only two cases of IVLBCL in which diffuse pulmonary FDG uptake was demonstrated have been reported previously. FDG-PET/CT plus random skin biopsy may be useful for the early diagnosis of IVLBCL with pulmonary involvement even without convincing radiological findings in the lung.

The clinical course of diffuse alveolar damage (DAD) was studied in six consecutive cases of dermatomyositis (DM) based on our hospital records over 8 years. Three patients had severe myopathy at presentation, and the other three patients showed clinically amyopathic DM (CADM). Interstitial pneumonia in all patients developed shortly after they manifested DM. DAD in five deceased patients, which was proven pathologically, did not respond to steroid therapy combined with cyclosporine or tacrolimus. Of these, two patients began receiving combination therapy before suffering respiratory symptoms, and one of them had elevated serum Krebs von der Lungen-6 (KL-6) levels before visible abnormalities appeared on a plain chest X-ray. Only one patient with CADM survived; this patient received intravenously administered pulse cyclophosphamide (IVCY) therapy intravenously for DAD from the early stage. Delayed adjunctive IVCY was ineffective for progressed DAD in the remaining five patients. Elevated serum ferritin levels were observed in all four patients examined and might have predicted the lethal DAD, as in a previous report. In conclusion, promptly beginning IVCY therapy may be beneficial for patients with DM and interstitial pneumonia who show elevated serum levels of ferritin or KL-6 with minimal pulmonary abnormalities.

Immunoglobulin G4 (IgG4)-related disease is a distinctive mass-forming disorder with frequent systemic involvement, most commonly in the pancreas, salivary glands and lacrimal glands. A few cases of dural involvement and one case of central airway stenosis have also been described. We report here a rare case of IgG4-related disease with intracranial hypertrophic pachymeningitis and irregular tracheobronchial stenosis. We review four previously reported cases of IgG4-related pachymeningitis. We currently lack international standards for the diagnosis of extrapancreatic IgG4-related disease. Based on the findings of the present case and those reported previously, we discuss the distinctive features of IgG4-related pachymeningitis.

Cynomolgus macaques, frequently used in drug metabolism studies, are bred mainly in the countries of Asia; however, comparative studies of drug metabolism between cynomolgus macaques bred in these countries have not been conducted. In this study, hepatic gene expression profiles of cynomolgus macaques bred in Cambodia (mfCAM), China (mfCHN), and Indonesia (mfIDN) were analyzed. Microarray analysis revealed that expression of most hepatic genes, including drug-metabolizing enzyme genes, was not substantially different between mfCAM, mfCHN, and mfIDN; only 1.1% and 3.0% of all the gene probes detected differential expression (>2.5-fold) in mfCAM compared with mfCHN and mfIDN, respectively. Quantitative polymerase chain reaction showed that the expression levels of 14 cytochromes P450 (P450s) important for drug metabolism did not differ (>2.5-fold) in mfCAM, mfCHN, and mfIDN, validating the microarray data. In contrast, expression of CYP2B6 and CYP3A4 differed (>2.5-fold, p < 0.05) between cynomolgus (mfCAM, mfCHN, or mfIDN) and rhesus macaques, indicating greater differences in expression of P450 genes between the two lineages. Moreover, metabolic activities measured using 14 P450 substrates did not differ substantially (

PURPOSE: We classified underlying diseases presenting as inflammation of unknown origin in division of rheumatic diseases. On the other hand, patients with malignant lymphoma (ML) varying in cause and symptoms are often admitted to our Rheumatology Division as cases of malignant disease presenting with fever of unknown origin. PATIENTS AND METHODS: Clinical records over 5 years were reviewed for 246 cases of undiagnosed inflammatory diseases at hospitalization. RESULTS: The 246 patients included 76 patients with infection, 116 with rheumatic disease, 8 with solid cancer, 9 with drug-induced fever, 10 with other disorders, and 27 with suspected ML. Of theses, malignant lymphoma (ML) was diagnosed in 20 patients (5 Mature T-cell and NK-cell neoplasms, 3 Hodgkin lymphomas, and 12 Mature B cell neoplasms including 5 Intravascular large B-cell lymphoma (IVLBCL)). The reasons for hospitalization were underlying collagen disease in 6 patients, medical workup for fever of unknown origin in 8 patients, and symptoms suggestive of collagen disease in 6. Nearly all of these patients presented with fever and other B symptoms, frequently with concurrent hypoxemia and hemophagocytic syndrome in IVLBCL. For diagnostic purposes, biopsy sites were determined by 18 fluorodexyglucose-positron emission tomography and computed tomography (FDG-PET/CT) in 13 patients, and findings on random skin biopsies were diagnostic in 3 of 5 patients with IVLBCL. Laboratory data on patients with B-cell lymphoma or peripheral T-cell lymphoma revealed tendencies for thrombocytopenia, elevated serum LDH, and increased soluble interleukin-2 receptor (sIL-2R). High serum ferritin values were more frequent in IVLBCL than in other B-cell lymphomas. CONCLUSION: ML ranked first among causes of inflammation of unknown origin at the division of Rheumatic Diseases, and FDG-PET/CT proved to be useful for biopsy site selection. IVLBCL was not uncommon, and our results show the usefulness of clinical features and random skin biopsies for rapid diagnosis.

The abilities of 2-(2-methylphenyl)-5,7-dimethoxy-4-quinolyl carbonylguanidine dihydrochloride (CAS 181048-29-3, MS-31-050) and 2-phenyl-8-(2-methoxyethoxy)-4-quinolyl carbonylguanidine bismethanesulfonate (CAS 181048-36-2, MS-31-038) in inhibiting Na(+)-H+ exchange, ischemia- and reperfusion-induced injury were determined and compared with those of 4-isopropyl-3-methylsulfonylbenzoyl guanidine methanesulfonate (CAS 159138-81-5, IMGM), a selective inhibitor of Na(+)-H+ exchange. MS-31-050 and IMGM exhibited comparable inhibitory effects on Na(+)-dependent pH recovery and antiarrhythmic effects during ischemia in anesthetized rats. In rats subjected to ischemia and reperfusion, MS-31-050 (10 mg/kg i.v.) significantly reduced the infarct size when given prior to the onset of ischemia. However, postischemic treatment with either MS-31-050 or IMGM failed to protect reperfused hearts. In contrast, MS-31-038 reduced the infarct size dramatically from 65.4 +/- 7.4% in control to 29.9 +/- 11.6% at 3 mg/kg and 9.8 +/- 3.4% at 10 mg/kg even when administered before the onset of reperfusion. These results suggest the beneficial effects of Na(+)-H+ exchange inhibitors on myocardial ischemia/reperfusion injury.

[(18) F]Fluorodeoxyglucose (FDG) is a tracer for glucose metabolism. Its distribution is not specific to cancer cells but is also observed in inflammatory tissue, including macrophages, capillaries, and fibroblasts. Rheumatoid arthritis (RA) is a systemic, chronic inflammation of the joints resulting in synovitis. The disease is characterized by fibrovascular proliferation leading to the formation of a pannus and causing high FDG uptake. Several clinical studies of RA have demonstrated that FDG uptake in affected joints reflects the disease activity of RA, with strong correlations between uptake and various clinical parameters having been noted. Furthermore, the use of FDG PET for the sensitive detection and monitoring of the response to RA therapy has been reported. FDG PET/computed tomography (CT) enables the detailed evaluation of disease in large joints throughout the whole body, which is a unique advantage of PET/CT. FDG PET/CT can also be used to detect high-risk disease complications, such as atlanto-axial joint involvement, at an early stage. The possible contribution of FDG PET to the management of patients with RA remains to be studied in detail.

We report a 57-year-old female case of intractable adult-onset Still’s disease (AOSD). Initial high-dose prednisolone therapy was ineffective, and macrophage-activation syndrome (MAS) manifested after one session of additional tocilizumab therapy. After successful treatment for MAS with lipo-dexamethasone and cyclosporin, tocilizumab therapy aided in the rapid reduction of the therapeutic steroid dose. Tocilizumab may be useful for maintenance therapy for AOSD, although its efficacy is unclear for the highly active phase of the disease.

A quantitative method for the determination of urea in human urine was studied. An ion chromatograph (IC) with a conductivity detector was used in this method, where the chromatograph was modified by placing a cation exchanger-an immobilized urease column on the injection loop with a 6-way valve in IC. A cation exchanger was prepared by the treatment of cedar sawdust with fuming sulfuric acid (exchange capacity, 1.2 meq g-resin−1). Immobilized urease was prepared by the adsorption of urease on cedar sawdust with triethylenetetramine (activity, 3500 U g−1). The reactor with a cation exchanger-an immobilized urease column could convert urea in urine to ammonium ion (conversion efficiency, 100%) even if a sample solution was passing through column at a 9 mL min−1 rate. Simultaneously, the above-mentioned reactor could also completely hold NH4+, Na+ and K+ in urine. The calibration curves of urea were very linear over 4.0 – 20 mg L−1. The urea concentration in urine could be determined within 7 min after developing the urine sample.

We report a 43-year-old female who developed pulmonary arterial hypertension (PAH) during intensive immunosuppressive therapy for systematic lupus erythematosus (SLE). She was diagnosed as SLE at the age of 32 years based on serological and hematological abnormalities, oral ulcers, and facial erythema. She experienced frequent flare-ups of disseminated discoid lupus between the ages of 33 and 36 years and developed immune thrombocytopenia at the age of 39 years. In 2007 when she was 43 years old, she developed lupus nephritis (LN) with elevated serum anti-double stranded DNA antibodies and urine protein of less than 1 g/day. Combination therapy for the LN with 35 mg/day prednisolone and intravenous cyclophosphamide (IVCY) led to renal remission. After the seventh monthly session of IVCY, she developed dyspnea on exertion. PAH was diagnosed based on enlarged main pulmonary arteries on the chest x-ray, right ventricular outflow and a peak tricuspid regurgitant pressure gradient exceeding 45 mmHg on echocardiography, an elevated plasma brain natriuretic peptide (BNP) level of 260 pg/ml, the exclusion of pulmonary thromboembolism, and no lung fibrosis. The PAH was treated successfully with bosentan. At present the tricuspid regurgitation has disappeared, and the plasma BNP level has normalized.

Rapidly progressive interstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM) is often lethal despite corticosteroid therapy combined with cyclophosphamide and cy...

To investigate the incidence and clinical features of methotrexate (MTX)-related lymphoproliferative disorders (MTX-LPDs) in patients with rheumatoid arthritis (RA).In total, 589 RA outpatients were examined at the National Center for Global Health and Medicine in the period from January 1990 to October 2010.MTX was used in 403 cases, and the duration of follow-up was 2379 person-years. Four patients developed MTX-LPDs; the incidence of MTX-LPDs was calculated as 0.00168/person-year and the standardized incidence as 8.21 (95% CI: 0.16-24.30). The mean total dosage of MTX was 1142 ± 871 mg, and the dosage at LPD onset was 7.4 ± 1.9 mg/week. The patients who developed MTX-LPDs had significantly shorter disease duration of RA compared with the patients who had not received MTX, but who had not progressed to LPDs (3.1 years vs. 12.5 years; P = 0.01). The following LPD subtypes were observed: diffuse large B-cell lymphoma (N = 2); Hodgkin's lymphoma (N = 1); and T-cell lymphoma (N = 1). After withdrawal of MTX, two of these patients showed spontaneous regression of the tumor, one did not have a recurrence, while the other patient relapsed and required chemotherapy.Our study revealed that MTX-LPDs are not rare complications of RA outpatients. The MTX-LPDs were associated with a relatively shorter RA duration, and half of them showed tumor regression after MTX withdrawal, which suggested an association with MTX. It is important to consider the possibility of MTX-LPD in RA patients who have received MTX.

Transglutaminase (TGase) is a family of enzymes that catalyzes cross-linking reaction between glutamine- and lysine residue of substrate proteins in several mammalian biological events. Substrate proteins for TGase and their physiological relevance have been still in research, continuously expanding. In this study, we have established a novel screening system that enables identification of cDNA sequence encoding favorable primary structure as a substrate for tissue-type transglutaminase (TGase 2), a multifunctional and ubiquitously expressing isozyme. By the screening, we identified several T7 phage clones that displayed substrate peptides for TGase 2 as a translated product from human brain cDNA library. Among the selected clones, the C-terminal region of IKAP, IkappaB kinase complex associated protein, appeared as a highly reactive substrate sequence for TGase 2. This system will open possibility of rapid identification of substrate sequences for transglutaminases at a genetic level.

The Futagoyama lava dome, one of the post-caldera central cones of Hakone volcano (Kanagawa, Japan), is though to have formed by a single eruption at 5 ka. However, in this study, we show that the dome formed over the course of at least three eruptions. We discovered a relatively old block-and-ash flow deposit (Hakone-Futagoyama Yamazaki block-and-ash flow deposit [Hk-FtY]) that originated from the Futagoyama lava dome, as indicated by its chemical composition and its age of 20,390 ± 40 yr BP. We also re-examined the source of the Shinanoya pyroclastic flow deposit, which was previously interpreted to be of Komagatake origin and was dated at 17,920 ± 320 yr BP (reference), and concluded that this deposit also originated from the Futagoyama lava dome. The recent eruptive history of Futagoyama suggests that its eruptions may have been synchronous with those of Kamiyama. In addition, the eruptive centers of Futagoyama and Kamiyama are aligned with each other along a linear trace.

The bottom topography of lake Ashi-no-ko, in the Hakone volcano caldera, was examined using the SeaBat8101 narrow multi-beam sonar system. The purpose of micro-topographical observations of the lake bottom is to understand the tectonic relations between the historical formation-process of the caldera and the strike-slip motion in the Tanna-Hirayama active fault system. At the southeastern part of the lake, west of the Dougashima, undulations at the bottom such as swells, hollows, and stairs extending in the northwest-southeast direction, were observed. These bottom-forms show a northern extension of the Hakonemachi active fault, running along the east side of lake Ashi-no-ko. They may correspond to one of the north spray faults of the Kita-Izu active fault system, which is the source of the A.D.1930 Kita-Izu earthquake, and to motions of the western margin of the Manazuru micro-plate, in relation to caldera formation as a strike-slip basin.

Single-crystalline diamond or a sintered diamond cutting tools are used for precision processing and for difficult processing materials because diamond is the hardest known material. Nevertheless, natural and synthesized diamonds are so expensive that their industrial applications are limited. Diamond films can be synthesized inexpensively using chemical vapor deposition (CVD), but synthesized diamond film has a rugged surface and a dull cutting edge, causing severe problems when used as a cutting tool.As described in this paper, the cutting edge of a diamond-coated cutting tool was reshaped to a sharpened form using electric discharge machining. To do so, the hot-filament CVD diamond film was made electrically conductive by doping with boron. The performance of this cutting tool was investigated using wood processing. Results show that the diamond-coated cutting tool prepared in this study was superior to a normal diamond-coated one in terms of cutting power consumption.

The prognosis of lupus nephritis (LN) was studied retrospectively in two LN categories, LN manifested initially at systemic lupus erythematosus (SLE) onset (I-LN) and LN of delayed manifestation after SLE onset (D-LN), based on a chart review (C) of 154 SLE (85 LN) patients with a mean observation of 20.8 ± 9.3 years and a questionnaire study (Q) of 125 LN patients outside our hospital with mean observation of 17.6 ± 9.2 years. In both study groups, half of I-LN patients were relapse-free by Kaplan–Meier analysis after initial therapy, and the relapsed I-LN patients responded to retherapy at higher 5-year relapse-free rates than those of patients receiving initial therapies for D-LN. At last observation, a higher frequency of prolonged remission was shown in I-LN compared with D-LN patients (C: 22/31, 71% versus 14/49, 29%, P < 0.01; Q: 65/89, 73% versus 11/33, 33% P < 0.01) and also a higher frequency of irreversible renal damage in D-LN compared with I-LN patients (C: 25/49, 51% versus 2/31, 6%, P < 0.001; Q: 14/33, 42% versus 6/89, 7%, P < 0.001), although class IV pathology was common in patients (C) in both LN categories. Onset time of lupus nephritis in the course of SLE may affect renal prognosis.

Among the isotypes of serum tartrate-resistant acid phosphatase (TRACP), only type 5b (TRACP-5b) is derived from osteoclasts, and it is necessary to develop an assay specific for this TRACP-5b for evaluation of osteoclastic activity. Recently, a novel assay system for TRACP-5b called the fragments absorbed immunocapture enzymatic assay (FAICEA) has been developed. With two unique monoclonal antibodies, one that is highly specific for TRACP-5b and another which absorbs inactive TRACP-5b fragments that interfere with measuring active TRACP-5b, this assay provides correct measurement of TRACP-5b activity in the serum without interference by the inactive fragments of TRACP-5b and other isotypes of TRACP, especially TRACP-5a. To study the reference data of Japanese subjects, we measured TRACP-5b activity in the serum of 320 men (age, 20-82 years) and 466 women [315 premenopausal (age, 18-55 years) and 151 postmenopausal (age, 45-77 years)] with this novel assay. In men, serum TRACP-5b activity did not vary significantly with age. The postmenopausal women had significantly higher serum TRACP-5b activity than the premenopausal women. The reference intervals (logarithmic mean +/-1.96 SD) for men, premenopausal women, and postmenopausal women were 1.7-5.9 U/l, 1.2-4.4 U/l, and 2.5-7.6 U/l, respectively.

Bound state of water in poly(vinyl alcohol) (PVA) hydrogel produced by repeated freezing and melting method was investigated by thermal analysis and Raman spectroscopy. Water frozen in PVA hydrogel showed the lowering of the melting temperature depending on PVA concentration. This water can be treated as a supercooled water, of which the melting enthalpy is different from that of normal water frozen at 0 °C. Accurate melting enthalpies of supercooled water estimated by the difference of thermal capacity of supercooled water and ice allowed us to determine the weight content of supercooled bound water. The weight content of supercooled water decreased with increasing PVA concentration, and alternatively that of non-freezable water increased. The maximum content of non-freezable water was 31.4 wt% for the 50 wt% PVA gel. The pore size filled with water was successfully estimated by thermodynamical equation. The diameter is 30.2 nm for 10 wt% gel, which is comparable to that derived from other experimental methods. Raman spectroscopy was used to investigate the hydrogen bond of water. With increasing concentration, the rate of water without hydrogen bond increased. This might be interpreted by the increment of surface area of water as the pore size is reduced. This also supports that the PVA hydrogel takes the pore model filled with water.

Hypoparathyroidism is a complication of thyroidectomy that causes hyperphosphatemia primarily due to enhanced reabsorption of phosphate in the kidney resulting from decreased parathyroid hormone (PTH) secretion. Fibroblast growth factor-23 (FGF23) is a hormone-like factor that is thought to play an important role in phosphate homeostasis. However, the changes and role of FGF23 in transient hypoparathyroidism after thyroidectomy are not clear. We examined changes in serum levels of calcium, phosphate, intact PTH, 1,25-dihydroxyvitamin D, and FGF23 in 12 patients (10 women, 2 men; mean age, 51 yr) who developed transient hypoparathyroidism after thyroidectomy. Serum phosphate reached its peak level (5.9 +/- 0.5 mg/dl) approximately 4 days after development of hypoparathyroidism, and this was followed by a peak in the serum FGF23 level (71 +/- 28 ng/l). Serum levels of calcium, phosphate, and FGF23 normalized after recovery of parathyroid function. There was a significant positive correlation between serum phosphate and FGF23 levels (P

We report a case of 58-year-old woman with a ruptured dissecting aneurysm of the middle colic artery (MCA). Her initial manifestation was sudden and severe right-sided abdominal pain, followed by hemorrhagic shock and acute anemia. Abdominal CT showed a right retroperitoneal hemorrhage. Emergency catheter angiography and therapeutic coil embolization of the middle colic artery were performed and micro aneurysms were enhanced in the jejunal branch. Immunological tests showed nothing abnormal. Follow-up angiography after 3 months showed that the micro aneurysms had disappeared. The patient was diagnosed as having segmental arterial mediolysis (SAM), because no definitive evidence of atherosclerosis and polyarteritis nodosa were observed. SAM is a rare disease of unknown etiology. The arterial lesions developing in elderly patients are characterized by segmental lysis of the abdominal splanchnic arteries resulting in aneurysms, and acute bleeding in a skip pattern. Multiple aneurysms and abdominal pain due to the rupture of these lesions in SAM resemble the clinical findings in polyarteritis nodosa. Differential diagnosis of the two diseases is important because steroid therapy is not beneficial for SAM.