Lactoferrin, a major whey protein, is a red iron-binding protein present mainly in external secretions such as breast milk and in polymorphonuclear neutrophils. The presence of lactoferrin in body fluids is proportional to the flux of neutrophils and its assessment can provide a reliable biomarker for inflammation. In gastrointestinal diseases increased fecal lactoferrin is a sensitive and specific surrogate marker for inflammatory bowel diseases in patients with chronic diarrhea and pain, and ascites lactoferrin can also provide a promising and reliable biomarker for bacterial peritonitis. Lactoferrin in pancreatic juice and stone could provide pathophysiological information of protein plug and stone formation in the pancreatic duct. Serum anti-lactoferrin autoantibody might contribute to the clarification of the pathogenetic mechanisms of autoimmune pancreatitis and liver diseases, although its diagnostic and prognostic value appears to be limited. Further studies will be necessary to elucidate the exact details.

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Background Obstructive sleep apnea syndrome (OSAS) is known to be a risk factor of cardiovascular events. However, the precise mechanism linking the two has not been fully elucidated.
Objective The aim of this study was to investigate the effect of hypoxic stress on the production of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) by monocytes.
Methods Thirty-three OSAS patients and 13 healthy control subjects were enrolled. The OSAS patients were classified as mild-to-moderate (13) and severe (20). Venous blood samples were collected before and after sleep as well as after long-term nasal continuous positive airway pressure (CPAP) treatment for the purpose of isolation of monocytes. Peripheral blood monocytes were isolated using standard methods. Monocytes were cultured under lipopolysaccharide stimulation for 24 hours, and TNF-α, MCP-1, and MMP-9 in the culture supernatants were determined by ELISA.
Results In severe patients, the TNF-α production by monocytes was significantly elevated as compared to that before sleep (p<0.01). In all OSAS patients, the TNF-α production after sleep was significantly correlated with AHI (p<0.01), ODI (p<0.01) and % time in SpO₂<90% (p<0.05), and inversely correlated with the lowest SpO₂ (p<0.01). The production of MCP-1 and MMP-9 by monocytes was significantly elevated compared to that before sleep in severe patients (p<0.05). The production of these mediators by monocytes was significantly decreased after long-term nasal CPAP treatment (p<0.05).
Conclusion These results indicate that OSAS-induced hypoxic stress activates the production of inflammatory mediators by monocytes.

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Objective In the present study, we tried to clarify the prevalence of selective serotonin reuptake inhibitor (SSRI) prescription and early discontinuation of SSRI in a outpatient unit where primary care physicians are working in Japan.
Materials and Methods Consecutive outpatients who newly visited the Department of General Medicine, Asahikawa Medical College Hospital, Asahikawa, Japan between April 2004 and March 2008 were analyzed. Each parameter such as age, sex, diagnosis, period of continuation of SSRI or reason why they discontinued SSRI was investigated.
Results Among 4670 patients, 126 patients (2.7%) had been prescribed SSRI because of depressive state (n=117) or panic disorder (n=9). Female patients with depression received SSRI (84/2714 = 3.10%) more frequently than male patients (33/1956 = 1.69%). Out of 117 patients with depression who had been prescribed SSRI, 28 (23.9%) patients discontinued SSRI within 4 weeks. Male patients (30.5%) discontinued SSRI within 4 weeks due to patient's decision more frequently than female patients (11.1%). The rate of patients who discontinued SSRI within 4 weeks due to patient's decision was particularly high (6/9; 67%) in male patients aged 20 to 29 years.
Conclusion These results suggest for the first time that there is a high prevalence of early discontinuation of SSRI in young male patients in Japan.

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A 33-year-old Japanese man was referred to our hospital after a huge intrapelvic tumor with bilateral hydronephrosis was found following persistent lumbago. Natural killer/T-cell lymphoma was suspected due to positive immunostaining for CD56, but CHOP therapy was ineffective. Re-evaluation of the tumor cells showed that they were positive for CD99, neuron-specific enolase, and synaptophysin and had a t(11 ; 22) (q24 ; q12) translocation, leading to the revised diagnosis of primitive neuroectodermal tumor (PNET). Systemic chemotherapies and radiation therapy were added to surgical resection, and no recurrence has been detected for 3 years. Taken together, PNET may be considered in adult patients with CD56-positive tumors.

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A 56-year-old man was admitted to our hospital for the surgical removal of renal cell carcinoma (RCC). He was diagnosed with acromegaly due to his characteristic clinical features, endocrine data, and the presence of pituitary tumor. He was found to have colon cancer and follicular thyroid tumor. Pathological examination of the pituitary tumor after transsphenoidal surgery was compatible with growth hormone (GH)-secreting pituitary adenoma. We also detected the transcripts and/or immunoreactivity of GH/insulin-like growth factor I components in the tumor specimen. This is a rare case of acromegaly associated with multiple tumors, including RCC, colon cancer and thyroid tumor.

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A 58-year-old man presented with a nodule in the right lung. Initially, the chest CT showed a ground-glass shadow. However, the shadow had become a solid nodule one month later. Histological examination revealed it was an inflammatory pseudotumor of the lung and subsequent surgery showed it to be an organizing pneumonia type. This disease is rare and in most cases is considered to be slow growing. Chest CT findings in the early stages have not been reported previously. Therefore, the present case is noteworthy in that we could confirm the CT findings in the early stages of this disease with rapid growth.

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We report a case of miliary tuberculosis associated with chronic neutrophilic leukemia (CNL). A 70-year-old woman was referred to our hospital complaining of a 1-month history of persistent fever and anorexia. Chest and abdominal computed tomography images revealed diffuse small nodular lesions in the bilateral lung fields and extreme splenomegaly. Sputum cultures isolated Mycobacterium tuberculosis. After anti-tuberculous therapy for 1 year, the patient underwent splenectomy for massive splenomegaly and progressive leukocytosis. The presence of the homozygous JAK2 V617F tyrosine kinase mutation was also demonstrated in the peripheral blood. She was finally diagnosed as having miliary tuberculosis associated with CNL based on the histopathological examination of spleen. The patient was treated with a daily dose of 500 mg of hydroxyurea. As a result, 18 months after the splenectomy, her leukocyte count was decreased and her clinical condition was markedly improved; there was no relapse of the CNL.

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We report a case of idiopathic pulmonary veno-occlusive disease (PVOD). The patient experienced progressively worsening dyspnea. Heart catheterization revealed severe pulmonary hypertension. High-resolution computed tomography (HRCT) showed diffuse, poorly identified centrilobular ground-glass opacities. Surgical lung biopsy led to the diagnosis of PVOD. A microscopic examination revealed occlusions of pulmonary veins and venules over a wide area with prominent loop-like capillary dilatations. These pathological findings may be correlated with the radiological characteristics of HRCT in this case.

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Real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with a dedicated EBUS bronchoscope has been reported as a minimally invasive and accurate method for sampling specimens from mediastinal and hilar lesions. Using this method, not only cytologic but also histologic specimens, which provide valuable information for a definitive diagnosis, can often be obtained. We report a case of an enlarged metastatic mediastinal lymph node from an unidentified primary papillary thyroid carcinoma that was accurately diagnosed by histological and immunohistochemical examination of tissue obtained by EBUS-TBNA.

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We herein report a rare occurrence of Addison's disease caused by acute adrenal gland tuberculosis occurring in association with miliary tuberculosis and the administration of rifampicin. An 82-year-old woman with miliary tuberculosis was treated with antituberculous chemotherapeutic agents including rifampicin (RFP), but she still demonstrated general malaise in addition to hyponatremia. Abdominal CT showed an enlargement of the right adrenal gland. However, after discontinuing RFP, the patient's symptoms improved. We carefully reinitiated the administration of RFP. The patient's condition thereafter did not worsen, and the treatment could thus be maintained. It is extremely important to immediately recognize adrenal crisis precipitated by the administration of RFP.

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We report two cases of biopsy-proven nonspecific interstitial pneumonia (NSIP) with anti-KS (asparaginyl-tRNA) antibody. Anti-KS antibody is the sixth anti-aminoacyl-tRNA synthetase (ARS) antibody. They showed interstitial pneumonia without clinical symptoms, and high resolution computed tomography (HRCT) of the chest demonstrated consolidation along bronchovascular bundles and volume loss in the bilateral lower lobes, which were suggestive of connective tissue diseases (CTD). One case of cellular NSIP responded to corticosteroid, but the other case of fibrotic NSIP required corticosteroid and cyclosporin. In patients with these HRCT findings, the measurement of anti-ARS antibodies could be helpful even in the absence of clinical symptoms suggestive of CTD.

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The biological agent tocilizumab, is a humanized, anti-human interleukin-6 receptor antibody. A 72-year-old woman developed cognitive impairment during the Phase III clinical trial of tocilizumab for the treatment of rheumatoid arthritis. MRI demonstrated hyperintense dissemination throughout the white matter on T2WI. An initial diagnosis of possible progressive multifocal leukoencephalopathy was made, but the PCR for JC virus DNA was negative in the CSF. The leukoencephalopathy might have been caused by a mechanism related to tocilizumab itself. It is strongly recommended to perform MRI if a patient develops any cognitive impairment during tocilizumab therapy.

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A 55-year-old man underwent radiation therapy due to malignant lymphoma of the neck. Eight years after the therapy he developed tetanus. It appears that the radiation therapy resulted in mandibular necrosis, and that this lesion may have been the infectious focus of tetanus. Treatment with penicillin G was very effective in the acute stage, and chronic administration of metronidazole prevented relapse of the disease. However in spite of injections of tetanus toxoid, symptoms of tetanus returned when the administration of metronidazole was discontinued because the infectious focus could not be completely removed. This is the first report of chronic relapsing tetanus associated with radiation-induced mandibular osteomyelitis, and demonstrates that tetanus can occur due to mandibular focus but the chronic administration of metronidazole can prevent relapse.

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We report 5 patients with eosinophil-associated gastrointestinal disorders (EGIDs) and asthma. All patients developed EGIDs while asthma remained clinically stable. Asthma severity was moderate persistent and severe persistent and 2 patients had intolerance to nonsteroidal anti-inflammatory drugs. By immunohistochemical analysis of the mucosa, eosinophils, macrophages, and T cells were found to be the major infiltrating cells. There was a lesser degree of infiltration of mast cells and B cells but no neutrophils. Compared with normal controls, increased counts of eosinophils and CD8⁺ T cells were found in the duodenum, and eosinophils, macrophages, and CD4⁺ T cells in the colon.

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"Tokyo 172" BCG vaccine designed for percutaneous inoculation is widely used in Japan. This vaccine is a much higher concentration of M. bovis BCG than that of the BCG vaccine designed for intradermal inoculation widely used in other countries. A patient who suffered from an ulcerous skin lesion as a result of the intradermal injection of "Tokyo 172" BCG vaccine accidentally was referred to our hospital. Systemic corticosteroid was administered with anti-tuberculous drugs, achieving a complete improvement of the skin lesion.

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Cystic fibrosis (CF), the most common lethal hereditary disorder in Caucasians, is quite rare in Southeast Asia including Japan. Here, we report three CF cases encountered in Nagasaki, Japan. Case 1; a 24-year-old man with dyspnea and cough was diagnosed as CF with a missense mutation Q98R in exon 4 and a polymorphic 125C in exon 1 in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Case 2; a 13-year-old woman born of consanguineous parents was diagnosed as CF with homozygous Q98R mutations in exon 4. Case 3; a 29-year-old woman complaining of cough and sputum was diagnosed as CF with a heterozygous R347H mutation in exon 7 and a polymorphic 125C in exon 1. These mutations have been previously reported in Caucasian patients, but are considered very rare. Although the numbers of individuals with CF are very limited, the profiles of CFTR mutations in those patients are likely diverse in Japan.

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