Objective Body fat is an important source of hormones and cytokines (adipokines) that not only regulate the energy balance, but also regulate the inflammatory and immune responses. This study investigated the association of clinical conditions with serum levels of adipokines in patients with rheumatoid arthritis.
Methods Serum levels of resistin, leptin, and adiponectin were measured by enzyme-linked immunosorbent assay in 141 patients (110 women) who fulfilled the 1987 revised criteria of the American Rheumatism Association for the diagnosis of rheumatoid arthritis and in 146 normal controls (124 women). Then the correlations between adipokine levels and clinical parameters were evaluated.
Results The serum resistin level did not differ between the patients and controls. However, serum leptin levels were significantly higher in male and female rheumatoid arthritis patients than in the corresponding controls, while the serum adiponectin level was significantly higher in female patients than in female controls. Multivariate analysis revealed that predictors of an elevated resistin level were female sex and C-reactive protein (CRP), while the leptin level was related to the body mass index and CRP. Predictors of an elevated adiponectin level were the use of prednisolone and CRP, however, CRP was negatively associated with adiponectin in patients with rheumatoid arthritis.
Conclusion The serum levels of resistin and leptin were positively associated with CRP level in patients with rheumatoid arthritis, suggesting that these adipokines may act as pro-inflammatory cytokines in this disease. The serum adiponectin level was elevated in the patients, however, it was negatively associated with CRP level. In addition, the serum levels of resistin, leptin, and adiponectin were also associated with female sex, BMI and the use of prednisolone, respectively.

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Objective We previously reported that various types of interstitial pneumonia (IP) patterns contain intracytoplasmic eosinophilic inclusions or Mallory bodies (inclusions) that are ubiquitin positive (Ub+). In the present study, we examined tissues with the organizing pneumonia pattern (OP) to determine if they contain inclusions and Ub+ pneumocytes using lobectomized specimens.
Methods Tissues from 34 patients with secondary OP, which appeared in 33 carcinomas and 1 pulmonary abscess, were histologically evaluated for the type of intraluminal granulation tissue and the presence of erosions and inclusions. Granulation tissues were classified into polypoid, mural and occluded subtypes according to Basset's criteria and scored.
Results Inclusions were noted in 5.9% of the secondary OP cases with light microscope. Ub+ pneumocytes were detected after immunostaining and all inclusions were Ub+. Ub+ pneumocytes (inclusions) were noted in 14.7% of the secondary OP cases. OP contained pneumocyte erosions and inflammatory cell infiltration without a significant difference in the Ub+ and Ub- subgroups. Although there was no significant difference in the polypoid type of granulation tissue between the Ub+ and Ub- negative (Ub-) subgroups, the Ub+ subgroup had significant increases (p<0.05) in the mural-occluded type of granulation tissue (Ub+: 1.76 ± 0.64, n=5 vs. Ub-: 0.72 ± 0.87, n=29) as compared to the Ub- subgroup.
Conclusion Some patients with secondary OP had Ub+ inclusions as pneumocyte injury.

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Objective Renal angiomyolipomas (R-AMLs) are major complications of lymphangioleiomyomatosis (LAM). The objective of this study was to better understand the influence of R-AMLs in patients with LAM on the prognosis and other clinical factors related to respiration, and to investigate the management of R-AMLs in patients with LAM.
Patients and Methods We retrospectively investigated the clinical features of 7 patients with LAM [4 were TSC (Tuberous sclerosis complex)-LAM and 3 were S (sporadic)-LAM] complicated by R-AMLs admitted to our hospital from 1997 to 2008.
Results All patients were females and the mean age at diagnosis of LAM was 40.7 years (31.7 years for TSC-LAM and 52.7 years for S-LAM). Although 5 patients had symptoms related to R-AMLs, only 1 patient experienced symptoms related to R-AMLs at the time of diagnosis. Five patients had bilateral and 2 patients had unilateral R-AMLs. R-AMLs ruptured in 4 cases (3 patients were TSC-LAM) including 2 patients in whom they ruptured bilaterally, and who underwent bilateral nephrectomy. In 1 case, unilateral R-AMLs grew larger and appeared on the other side during the follow-up period.
Conclusion Although only rare cases of LAM show symptoms related to R-AMLs initially, R-AMLs are a notable complication. To avoid nephrectomy, R-AMLs should be diagnosed when they are small and should be followed up carefully by periodic echograms or CT scans.

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Purpose This study was designed to determine whether, among Japanese patients receiving medical treatment for carotid stenosis, symptomatic carotid stenosis was more strongly associated with subsequent neurological events than asymptomatic carotid stenosis.
Methods We consecutively registered Japanese patients with carotid stenosis of 50% or more as evaluated by digital subtraction angiography who were treated medically. We reviewed medical records regarding previous neurological events as well as other stroke risk factors and underlying diseases at admission. We monitored the occurrence and date of stroke and death after the first evaluation. We also attempted to obtain information from patients or their family members by means of a questionnaire or telephone survey.
Results Among 67 patients with carotid stenosis of 50% or more who were treated medically, follow-up was completed in 62 subjects (56 men, 6 women; median age, 72 years; mean follow-up period, 37.3 months). The number of patients with subsequent stroke with symptomatic carotid stenosis was five, while that with asymptomatic stenosis was four. A significantly higher rate of subsequent stroke was observed in patients with symptomatic carotid stenosis compared with those with asymptomatic stenosis (p=0.012). Cox proportional hazards model indicated that symptomatic carotid stenosis was significantly correlated with future neurologic events (p=0.019).
Conclusion In a Japanese population with carotid stenosis treated medically, symptomatic carotid stenosis is associated with future stroke more frequently than asymptomatic carotid stenosis.

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Objective Idiopathic normal pressure hydrocephalus (iNPH) is clinically important as a treatable gait disturbance or preventable dementia by shunt operation. We have recently reported that approximately 1.5% of the elderly living in a Japanese community showed ventriculomegaly with features of iNPH on MRI (VIM), which may represent a preclinical stage of iNPH. The purpose of the present study was to identify a possible genetic change in VIM subjects.
Methods Eight subjects with VIM and 10 healthy individuals were examined for copy number variations (CNV) with a CNV-targeted whole-genome oligonucleotide microarray (Agilent 400 K CNV array). Another panel of 100 healthy Japanese individuals was screened for CNV by whole-genome using the deCODE-Illumina CNV 370 K chip. Immunohistochemical examination of the human brain was performed using an avidin-biotin-peroxidase complex method.
Results Among several genetic changes observed, a copy number loss within the SFMBT1 gene was seen in half of the VIM cases (4 of 8 cases), that was rare among the Japanese control subjects (0/10 by Agilent 400 K CNV array or 1/100 by deCODE/Illumina CNV 370 K chip). Immunohistochemical examination of the human brain revealed that the SFMBT1 protein was localized mainly in the arterial walls, the ependymal cells, and the epithelium of the choroid plexus, all of which play a crucial role in the CSF circulation.
Conclusion A segmental copy number loss of the SFMBT1 gene may be involved in the pathological process in some individuals with VIM/iNPH.

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Objective Acute-onset diffuse interstitial lung disease (AoDILD) in patients with rheumatoid arthritis (RA) has been a serious concern, especially for those under treatment with biological agents which may affect the presentation and outcome of AoDILD, including Pneumocystis pneumonia (PCP). Therefore, we conducted a retrospective, multi-center study of AoDILD in RA patients receiving biological agents.
Methods Patients who developed AoDILD while receiving biological agents (infliximab, etanercept, adalimumab and tocilizumab) were enrolled in the study. Definite PCP was defined as patients who showed either P. jirovecii organisms in their respiratory samples by microscopic examination, or positive tests for both P. jirovicii DNA-PCR with respiratory samples and an elevated serum 1,3-β-D-glucan level above the cut-off value. Probable PCP was defined as either a positive test for P. jirovicii PCR or an elevated serum β-D-glucan level. Chest HRCT findings were evaluated and scored by two board-certified radiologists.
Results The final diagnoses for 26 patients examined were definite PCP for 13 patients, probable PCP for 11, and methotrexate-associated pneumonitis in 2 patients. Definite and probable PCP cases were clinically indistinguishable. Generalized, diffuse ground-glass opacity (GGO) is the characteristic HRCT finding in patients with definite or probable PCP, which was different from our previous findings in RA patients, mostly without biologics, showing GGO distributed in a panlobular or multilobular manner. The clinical outcome was favorable by treatment with trimethoprim-sulfamethoxazole and glucocorticoids.
Conclusion The possibility of PCP should be intensively investigated in RA patients developing AoDILD while receiving biological agents.

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Giant cell hepatitis is rare in adult patients. This form of hepatitis shows fast progression to cirrhosis. A 65-year-old woman was admitted to our hospital with jaundice. She was negative for hepatitis virus markers and positive for antinuclear antibodies. We diagnosed her as autoimmune hepatitis. Liver biopsy findings revealed typical features of interface hepatitis and giant cell hepatitis. Giant cells were positive for keratin 8/18, but not for keratin 19, keratin 7 or Ki-67. These results suggest that giant cell formation is associated with the fusion of matured hepatocytes rather than the active proliferation of immature cells.

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A 29-year-old Japanese female was diagnosed with systemic lupus erythematosus (SLE) at the age of 21 and went into remission after administration of prednisolone. Although no liver dysfunction had been observed upon diagnosis of SLE or during follow-up, an increase of hepatobiliary enzyme levels was seen eight years after the diagnosis of SLE. Antimitochondrial antibodies were positive. Cell infiltration around intrahepatic bile ducts and granuloma formation were observed in the liver. Therefore, she was diagnosed with primary biliary cirrhosis (PBC). Administration of ursodeoxycholic acid resulted in normalization of hepatobiliary enzyme levels. Development of PBC after SLE is extremely rare.

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We present the case of a patient who was referred to our hospital after she reported having passed a long, whitish object per rectum. Accordingly, capsule endoscopy was performed using the PillCam^® SB video capsule. A tapeworm of the species Diphyllobothrium nihonkaiense was detected; it appeared to be freely floating and unfolded in the jejunum and sometimes tangled or irregularly folded in the ileum. The stretching of the strobila by strong peristalsis in the ileum may have resulted in the separation of the caudal portion of the strobila, which descended into the colon and was eventually passed per rectum.

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Here we describe a 73-year-old woman with hypercalcemia caused by a hepatocellular carcinoma (HCC) secreting intact parathyroid hormone (iPTH). Serum tumor markers and dynamic CT findings indicated a diagnosis of HCC. The source of the elevated serum iPTH was not obvious. Transarterial chemoembolization (TACE) was effective against the HCC, and the serum iPTH level fell to within the normal range, suggesting a correlation between the carcinoma and the iPTH. About 2 months later, the tumor had grown and the serum calcium level increased leading to physical deterioration and death. This clinical course suggested that HCC can ectopically secrete iPTH.

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Paraneoplastic Cushing's syndrome caused by ectopic adrenocorticotropin (ACTH) production has been reported. However, most cases of this syndrome are diagnosed before first-line chemotherapy or at the time of disease recurrence. Here, we present a 53-year-old man who gradually developed the symptoms of Cushing's syndrome during effective chemotherapy for small cell lung cancer. His symptoms were controlled using mitotane, but his primary cancer progressed and he died 5 months after the start of chemotherapy. This very rare case of Cushing's syndrome associated with small cell lung cancer during effective chemotherapy is presented here.

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We report here the case of an 83-year-old man who was treated for unconsciousness and hypoglycemia (39 mg/dL) accompanied by marked elevation of serum immunoreactive insulin (IRI) (4,760 μIU/mL). We diagnosed his condition as insulin autoimmune syndrome (IAS, Hirata disease) because of a high insulin autoantibody (IAA) titer (>90%: bound/total) and no history of exogenous insulin administration. Reactive hypoglycemia occurred due to immediate association followed by dissociation between insulin and insulin autoantibodies after glucose or food intake. An α-glucosidase inhibitor in combination with frequent small meals reduced the postprandial hyperglycemia (glucose spike) and ameliorated the reactive hypoglycemia.

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Malignant vaginal melanoma is an extremely rare clinical condition, with less than 150 cases reported to date. A dialysis patient had primary vaginal melanoma with metastases to the papilla of Vater. Gastroduodenoscopy revealed a polypoid tumor. Histological findings revealed vimentin, S-100 protein, HMB45, MelanA-positive sarcoma-like cells. This staining pattern indicated that this tumor was a malignant melanoma of the papilla. Analysis of an autopsy specimen of the papilla of Vater revealed metastasis from the primary vaginal melanoma. Metastasis of a malignant tumor to the gastrointestinal tract, especially to the papilla, is uncommon. Melanoma should be considered in the differential diagnosis of primary gastrointestinal tract malignancy.

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Acute lung injury during pregnancy results in morbidity and mortality in both the mother and the fetus. Pneumocystis jirovecii pneumonia (PCP) is a rare disease but may occur in pregnant immune-suppressed women. Here, we describe a case of acute lung injury due to PCP and alveolar hemorrhage in a pregnant woman who was a human T lymphotropic virus type-1 (HTLV-1) carrier. PCP should be considered in the differential diagnosis of pulmonary complications during pregnancy in HTLV-1 endemic areas.

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A 78-year-old woman visited the division of cardiovascular disease in our hospital. She underwent a cardiac catheter examination, and a Swan-Ganz catheter was inserted. Several minutes later, she developed anaphylactic shock. She had no past history of latex allergy, but did have a banana allergy. Skin prick tests showed a positive reaction to an extract of latex gloves and an extract of the balloon of a Swan-Ganz catheter. Anaphylactic shock caused by the latex balloon of a Swan-Ganz catheter was diagnosed. It is necessary to pay attention to not only latex allergy but also fruit allergies with a cross-reactivity to latex.

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We report a 50-year-old woman with systemic lupus erythematosus (SLE) who developed stroke-like symptoms, including disturbance of consciousness and severe left hemiparesis. Despite the stroke-like symptoms, MR imaging showed quite atypical findings for stroke; broad high-intensity areas in the right fronto-parietal lobes on diffusion-weighted images were shown mainly as iso-intensity areas on the ADC map, without any findings of stenosis of the cerebral large arteries. The cerebral blood flow in these areas was significantly decreased, as evaluated by single photon emission computed tomography. The present case suggests that small vessel vasculopathies localized in the unilateral hemisphere could cause "stroke-like" symptoms in SLE.

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A 76-year-old woman presented with catatonia, refusal to eat due to delusion, and visual hallucination. Single photon emission computed tomography showed remarkable occipital hypoperfusion and frontal hyperperfusion. ¹²³I metaiodobenzyl guanidine myocardial scintigraphy revealed decreased uptake. She was diagnosed as probable dementia with Lewy bodies (DLB). Intravenous or oral L-dopa had no effect on catatonia. Amitriptyline and lorazepam improved catatonia and visual hallucination. Cerebral blood flow of the frontal and occipital lobes seemed to be normalized. Occipital hypoperfusion is one of the features of DLB. Although the mechanism of perfusion abnormality in DLB remains to be clarified, our case suggested that it might be reversible.

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