Objectives The aim of this study was to evaluate whether or not combination therapy of pegylated interferon (IFN) and ribavirin for chronic hepatitis (CH) C patients enhances the serum level of KL-6, a sensitive marker for interstitial pneumonia.
Methods CH C patients proven histologically and treated with combination therapy of pegylated IFN-alpha-2b and ribavirin, IFN monotherapy or untreated for 48 weeks were retrospectively selected in chronological order in groups of 25. Serum levels of KL-6 were measured by enzyme-linked immunosorbent assay by use of serum stored at -80°C before and at 12, 24, 36, 48 weeks after the initiation of treatment or follow up.
Results The average serum KL-6 levels in patients treated with combination therapy of pegylated IFN and ribavirin increased by 21% at 12 weeks after the start, 23% at 24 weeks, and 28% at 48 weeks. In patients treated with combination therapy of pegylated IFN and ribavirin, the serum KL-6 level significantly increased during treatment. Patients achieved an elevated serum KL-6 level of more than 450 U/ml with statistical significance when: 1) combination therapy was given (P=0.011), 2) serum KL-6 level pretreatment was high more than 300 U/ml (P=0.014).
Conclusion The present study suggests that onset of interstitial pneumonia should be carefully checked in the combination therapy of pegylated-IFN and ribavirin.

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Objective To assess the role of the p16 gene exon 2 homozygous deletion in malignant pleural effusions.
Methods The homozygous deletion of p16 gene was determined in 34 pleural effusions due to non-small cell lung cancer (NSCLC) and in 21 cases with tuberculous pleuritis by polymerase chain reaction (PCR), compared with the determination of exfoliated cytology in the same specimens.
Results The PCR analysis showed that the homozygous deletion of p16 exon 2 was identified in 15 of 34 malignant pleural effusions (44.11%), including 8 negative cytology and it was not found any tuberculous pleural effusions. The exfoliated cytology of pleural effusion was positive in 19 of 34 malignant cases (55.88%). By combining two methods, the diagnostic sensitivity was enhanced, from 55.88% (19/34) to 79.41% (27/34), whose positive rate was higher than only determination of p16 exon2 homozygous deletion or exfoliated cytology in malignant pleural effusions (p<0.001, p<0.05 respectively).
Conclusion Our data suggested that combining the examination of exfoliated cytology and homozygous deletion of p16 gene exon2 in pleural effusion can recruit and enhance the diagnostic value of pleural effusion cytology. The detection of the homozygous deletion of the p16 gene in pleural effusion may be a useful adjunct to the cytological and histological examinations of pleural effusion. In cases of undiagnosed exudative pleural effusion with a high clinical suspicion for malignancy, it is reasonable to examine the homozygous deletion of pleural fluid p16 gene. With p16 gene homozygous deletion in pleural effusion, it may be strongly highly likely to be malignant and have a higher metastatic potential.

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Objective Cigarette smoking increases the circulating white blood cell (WBC) count and the prevalence of metabolic syndrome. We investigated the association between cigarette smoking, WBC count, and metabolic syndrome as defined by the Japanese criteria.
Method Cross-sectional data from 3,687 men undergoing general health screening between 2005 and 2006 were analyzed.
Results After adjustment for age and total cholesterol, former and current smoking were associated with the highest WBC quartile (≥6.3 × 10³ cells/μL) with an odds ratio of 1.35 (95% CI 1.09-1.66, P=0.0055) and 4.45 (95% CI 3.69-5.37, P<0.0001), respectively. It was found that increased WBC count was a risk factor for metabolic syndrome; on the other hand, the current smoking was not found to be a predictor for metabolic syndrome, when each WBC count quartile was separately analyzed.
Conclusions Our data suggest that the risk for MetS, defined by Japanese criteria, might be estimated by the WBC count in Japanese men irrespective of their smoking status, although it should also be noted that the cigarette smoking increases the number of circulating WBC count.

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Objectives Complicated parapneumonic effusion or empyema is a troublesome disease with a high mortality. The most common involved microorganisms seem to have changed over recent decades, influenced by the introduction of new antibiotics, and the increase of immunocompromised hosts, and the elderly population. More epidemiological studies on the current bacteriology are needed to help us to empirically select adequate antibiotics.
Design A retrospective study via chart review in a university-affiliated tertiary medical center was conducted to assess the underlying bacterial pathogens and outcome of patients with complicated parapneumonic effusions or empyemas.
Results During the 43-month study period (from December 2000 to June 2004), 304 patients were diagnosed with complicated parapneumonic effusions or empyemas and the mortality of these patients was 23% (69/304). Among these 304 patients, a total of 292 microorganisms were cultured from the pleural fluid samples of 207 patients (to yield a positive microbiological culture rate of 68% (207/304). Isolated bacteria included aerobic Gram-negative bacteria (n=129), aerobic Gram-positive bacteria (n=105), anaerobic bacteria (n=51), and M. tuberculosis (n=7). Of these aerobic bacterial infections, Gram-negative bacteria were isolated more frequently from the older population and involved a significantly higher mortality rate and longer stay, compared to those with other bacteria (p=0.001 and p<0.001 respectively).
Conclusion The increasing incidence of infection with aerobic Gram-negative pathogens may cause more critical conditions in complicated parapneumonic effusions or empyemas.

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Objective: To investigate whether loxoprofen, one of the nonsteroidal anti-inflammatory drugs, prolongs the recovery process of naturally acquired upper respiratory tract infections (URTIs) in the clinical setting.
Methods: A double-blind, randomized, placebo-controlled trial was conducted in 23 outpatient facilities in Japan. Patients aged 18 through 65 years suffering from URTIs were randomly assigned to receive loxoprofen or its placebo. The primary outcome was duration of illness in days.
Results: A total of 174 patients were available for the analyses. Duration of illness was 8.94 ± 3.20 days in the loxoprofen group compared to 8.39 ± 3.39 days in the placebo group (P=.19). The number of days with limited daily activities was fewer in the loxoprofen group than in the placebo group (2.12 ± 2.05 days vs. 2.68 ± 2.54 days, P=.17). Although severe symptoms were less frequent on days 1, 2, and 3 in the loxoprofen group (27%, 33%, and 29%, respectively) than in the placebo group (32%, 39%, and 37%, respectively), symptoms were more frequent on days 6 through 12 in the loxoprofen group (difference, 5-13%). Adverse events were more common in the loxoprofen group (9.5% vs. 1.1%, P=.051).
Conclusion: Loxoprofen did not significantly modify the recovery process of URTIs except for a slight tendency to delay.

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Mesenteric ischemia is an uncommon etiology of abdominal pain. Celiac axis compression syndrome is an extremely rare cause of mesenteric ischemia. The primary pathological mechanism is the external compression of the celiac trunk by median arcuate ligament. The clinical manifestation of celiac axis compression syndrome includes postprandial pain, diarrhea, and body weight loss. The diagnosis of this disease is usually difficult and depends on the angiography findings. For treatment, only percutaneous transluminal angioplasty and surgical intervention have been suggested in reviews in the literature. We, herein, report an unusual case of celiac axis compression syndrome and also review the literature pertaining to this disease.

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Hepatolithiasis associated with cholangiocellular carcinoma is occasionally a calcium bilirubinate stone. Primary cholesterol hepatolithiasis associated with cholangiocellular carcinoma is rare; only 6 cases have been reported in the literature. A 55-year-old man was admitted to our hospital because of an elevated level of carbohydrate antigen 19-9. Various imaging studies demonstrated a mass in the segment VII of the liver. The patient underwent a curative surgical operation. Histopathological examination revealed that it was cholangiocellular carcinoma located in the periphery of the liver. A cholesterol stone was present, encircled by the cholangiocellular carcinoma. Minor inflammatory changes were observed around the stone.

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Non-caseating epithelioid granulomas have been described in a small number of patients with common variable immunodeficiency (CVID). We report a 26-year-old woman diagnosed with CVID nine years earlier, who developed non-caseating granulomas in the liver, bone marrow and skin. She was referred to our department for a fever of more than one year duration without apparent focus. Extensive search for underlying malignancy or occult infection was unremarkable. Empirical treatment with prednisone was begun and the patient showed a marked improvement. The literature on the association between CVID and non-caseating granulomatous disease, and the differential diagnosis of hepatic granulomas as a cause of fever of unknown origin, is also reviewed.

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We describe a 48-year-old man with nodular intrahepatic lesions accompanied by communication between the inferior vena cava and portal systems as well as absence of intrahepatic portal veins. After infection with malaria in childhood, end-to-side portacaval shunting had been performed to treat upper gastrointestinal bleeding at the age of 15 years. A biopsy specimen obtained under ultrasonographic guidance showed hyperplastic nodules suggestive of focal nodular hyperplasia. The estradiol concentration in the blood was elevated (55 pg/ml). This case suggests that portacaval shunting may be associated with hyperplastic liver nodules through hyperestrogenemia and abnormal hepatic hemodynamics.

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The patient was 71-year-old male under treatment at a clinic for hypertension, aortic regurgitation, alcoholic hepatitis and dental treatment. He mainly complained fever and anorexia. Since blood culture examination revealed Listeria monocytogenes and echocardiography exhibited vegetation at the mitral leaflet, the patient was diagnosed as infective endocarditis. Fever and inflammatory reaction were improved after penicillin administration; however, he had fever on the 24th hospital day. CT revealed type IIIb acute thoracoabdominal aortic dissection which was not observed on admission. The blood pressure was controlled with antihypertensive agents. He could leave the hospital on the 61st day.

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The case of a 35-year-old female patient who was diagnosed as schizophrenia treated with psychotrophic drugs nearly for 15 years is presented here. After the disease was diagnosed, the patient quit her university education and began to live inactively far from her social environment, usually spending lazy time at home. During this period, due to either the effects of drugs which have to be used on hormones affecting appetite and body weight or her decreased physical activity, her body weight increased by nearly 30 kg. Anthropometric measurements, biochemical parameters and food diaries were evaluated at the beginning of the nutritional counseling and then repeated periodically. Upon obtaining biochemical findings, collaboration with other units started. The patient was educated on nourishing healthy and controlling body weight, also to bring about lasting behavioral changes. At the beginning of the therapy, among the biochemical measurements, insulin resistance was defined and metformin treatment was begun. Metformin therapy contributed to the patient's adaptation to the diet and improved glucose tolerance. In this way, it was possible to cope with the insulin resistance caused by anti-psychotic pharmacotherapy (clozapine) and the obesity which had developed as a result of clozapine. During the 18-month therapy the patient lost 27 kg, her body fat was reduced by 10% (18 kg) and BMI returned to normal levels. It is known that, many medications used in psychiatric disorders affect appetite and body weight. As seen in our patient metformin therapy causes weight loss and decreases insulin resistance. Both the illness and the medications used for treatment could affect the hormones which play a part in controlling body weight and the cytokines, as a result could change food preference and eating behavior which ultimately pave the way to obesity.

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A 63-year-old woman was referred and admitted to our department for further examination of protein-losing enteropathy (PLE), which was diagnosed by alpha-anti trypsin test. Her symptoms were frequent vomiting, watery diarrhea and hypoproteinemia. Although intensive examination for PLE was performed in her previous hospital, the origin of the disease was not detected. Abdominal computed tomography revealed diffuse enlargement and swelling of the intestine wall and a 5-cm diameter mass with unclear margin, which involved the mesenteric arteries and veins. Total colonoscopy showed a diffuse edematous lesion with hemorrhage at the terminal ileum. Enteropathy-type T-cell lymphoma (ETL) was diagnosed based on a biopsy of the lesion and CD45 gating analysis. Immediate start of chemotherapy (CHOP) led to a transient regression of the tumor even though her symptoms were not improved. During the second cycle of CHOP, the patient died of massive hemorrhage throughout the intestine. The pathological study revealed that intraepithelial CD3-positive clonal T-cells were present in the lesion, indicating that this case could be associated with celiac disease. In light of the histological findings, we concluded that this was a case of ETL associated with celiac disease, which is extremely rare in Japan.

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Clinical assays are very important for the diagnosis and management of clinical disorders. Each assay system consists of a specific method to detect and/or quantify a substance of interest in the clinical specimen. However, clinical assays can be unfavorably influenced by non-specific activities concomitantly present in the specimen, which may mislead clinical decisions. Thus, it is very important to know how each assay works, and how and when the assay is non-specifically influenced. Here, we report three cases shown clinical data of thyroid function influenced by new type of assay interference.

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A 35-year-old man initially presented with cough and fever. Computed tomography (CT) revealed diffuse small cysts in the lung, and multiple nodules in the liver. Lung and liver biopsies revealed that pathology was consistent with Langerhans cell histiocytosis. Lung shadows increased despite cessation of smoking, whereas the liver involvement improved. After initiating treatment with prednisolone, the chest CT findings improved. However, the liver nodules started to increase while tapering prednisolone. Intravenous etoposide was started, and the liver nodules decreased markedly. The difference in the clinical course between the lung and liver lesions might have been the result of differences in the clonality of these two organs.

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We describe a 73-year-old woman with systemic sclerosis (SSc)-polymyositis (PM) overlap syndrome, primarily SSc followed by PM. She had suffered from SSc and had interstitial pneumonia (IP), which was stable. Eight years after the initial diagnosis of SSc, proximal muscle weakness, myalgia, and dyspnea on effort developed. A chest computed tomography (CT) showed reticular shadows, and serum markers of IP such as KL-6 and surfactant protein-D were elevated at 1,170 U/mL and 176 ng/mL, respectively. Bronchoalveolar lavage fluid showed a remarkably increased number of lymphocytes. Exacerbation of SSc-IP 8 years after the initial diagnosis of SSc is not usual, and a marked increase in the number of lymphocytes in bronchoalveolar lavage fluid is also uncommon in SSc-IP, indicating overlap of another connective tissue disease. The diagnostic criteria for PM were satisfied; thus, SSc-PM overlap syndrome was diagnosed. We emphasize the need to investigate whether another connective tissue disease has developed when symptoms or laboratory findings cannot be explained by the usual clinical course of an existing connective tissue disease.

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A 72-year-old man with tongue carcinoma complained of dyspnea on exertion 18 days after starting treatment with S-1. Chest radiograph and CT scan suggested diffuse interstitial lesions with ground glass opacity on both lungs. Bronchoalveolar lavage and transbronchial lung biopsy revealed moderate lymphocyte infiltration with granuloma. Drug lymphocyte stimulation test was positive against tegafur, one of the components of S-1. These findings were consistent with S-1-induced lung injury. Both his symptoms and the radiographic findings were resolved dramatically after high-dose corticosteroid therapy. Clinicians should be aware that S-1 has the potential to cause lung injury when it is included in chemotherapy.

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We report a Japanese patient with familial Mediterranean fever (FMF) who was successfully treated with the anti-tumor necrosis factor (TNF)-α monoclonal antibody, infliximab, and low-dose methotrexate. This patient was diagnosed as having FMF based on periodic fever with polyarthralgia typical of this disease and heterozygous mutations in the MEFV gene. Conventional treatment, such as colchicine and reserpine, failed to sufficiently control the FMF attacks. After starting infliximab (3 mg/kg) and low-dose methotrexate (6 mg/week), the frequency of the FMF attacks dramatically decreased and the clinical effect has remained unchanged for longer than 1 year. Combination therapy with infliximab and low-dose methotrexate may be a potent therapeutic option for FMF patients, particularly when conventional treatment is ineffective or cannot be employed because of adverse events.

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A 44-year-old woman developed a cardioembolic stroke. Transthoracic echocardiography demonstrated isolated noncompaction of the ventricular myocardium. Left ventricular systolic function was mildly depressed, which severely decreased during 3 months after discharge. The embolic stroke might occur when the ventricular systolic function had begun to deteriorate. The proper time to start anticoagulation in isolated noncompaction of ventricular myocardium patients may be when left ventricular systolic function decreases below normal.

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Although plasma cell disorders, such as hypergammaglobulinemia and monoclonal gammopathy of undetermined significance (MGUS), are reported to occur at higher incidences in patients with Type I Gaucher disease (GD) than in the normal population, pure light chain multiple myeloma (LCMM) has never been described in this context. Our case is the first to highlight a patient with LCMM who developed clinically apparent GD only following chemotherapy and hematopoietic stem cell transplantation. Renal complications are also exceedingly rare in GD, but nephrotic syndrome is one of the presenting features in this patient. The findings from this case will have important screening and diagnostic implications for both clinicians and patients.

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