In the last decade, the dogma that no bacteria could grow in the acid milieu of the stomach has been destroyed by evidence that the infective agent, H. pylori, is responsible for gastric and duodenal disease. Studies on H. pylori infection suggest that some strains of intestinal bacteria may be responsible for intestinal ulceration and inflammation concomitant with inflammatory bowel diseases (IBD), i.e., ulcerative colitis and Crohn’s disease. Evidence for pathophysiological roles for certain strains of luminal bacteria result from a number of IBD animal models. Recent studies on innate immunity, including toll-like receptors and NOD isoforms, suggest that bacterial infections may contribute to intestinal inflammation in genetically susceptible hosts. This brief review focuses on the bacterial pathogenesis and the role of innate immunity in the etiology of IBD’s.

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Myeloid metaplasia with myelofibrosis (MMM) is a chronic myeloproliferative disorder (CMPD) characterized by progressive anemia, massive splenomegaly, both hepatosplenic and non-hepatosplenic extramedullary hematopoiesis (EMH), a leukoerythroblastic blood smear, circulating progenitor cells, and marked bone marrow stromal reaction including collagen fibrosis, osteosclerosis and angiogenesis. The overall median survival is 5 years although it might range from 2 to 15 years depending on the presence or absence of clinically defined prognostic factors. Death is often due to leukemic transformation, portal hypertension or infection. In addition to shortened survival, quality of life is often affected by frequent red blood cell transfusions, profound constitutional symptoms, and cachexia. Drug therapy and autologous hematopoietic stem cell transplantation (HSCT) are of only palliative value and have not been shown to improve survival. The role of allogeneic HSCT, both myeloablative and non-myeloablative, is actively being investigated. Both splenectomy and radiation therapy have defined therapeutic roles to control EMH-associated symptoms. Analysis of the molecular biology of the disease is underway with the aid of animal models leading to the identification of novel therapeutic targets. Among the novel agents tested, thalidomide seems the most promising although newer agents are on the horizon.

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  Objective  Although the diagnostic utility of serum IgG antibodies to Helicobacter pylori (H. pylori) is well established, the usefulness of IgA-based tests is less well documented. The aim of this study was to evaluate two commercially available ELISAs, both for IgG and IgA.
  Patients and Methods  Rapid urease test and histology analysis were performed in 183 patients. A patient was considered to be H. pylori-positive when either biopsy test was positive, and considered to be noninfected when both tests were negative. Intestinal metaplasia was determined by dye endoscopy with methylene blue. ELISA testing was performed using the EPI HM-CAP IgG and PP-CAP IgA assays and EIAgen IgG and IgA assays.
  Results  Sensitivity was 94.7, 93.9, 94.8, and 97.0% for HM-CAP IgG, PP-CAP IgA, EIAgen IgG, and EIAgen IgA, respectively. Although sensitivity was excellent for both IgG and IgA antibodies, specificity of both IgA EIAs was low (PP-CAP 72.6%, EIAgen H. pylori IgA 59.2%). Three of 101 H. pylori-infected patients were PP-CAP positive and HM-CAP negative and four were EIAgen H. pylori IgA positive and EIAgen IgG negative. Of eight noninfected patients in whom intestinal metaplasia was found, PP-CAP IgA results were positive in three of five patients with a HM-CAP IgG negative result and EIAgen IgA was detected in one of four patients with an EIAgen IgG negative result.
  Conclusions  Since some patients have IgA positive but IgG negative results, great care should be taken not to underestimate the prevalence of H. pylori infection from the results of IgG serology.

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  Introduction  Although many clinical trials have demonstrated that anticoagulant therapy substantially reduces the risk of ischemic stroke in patients with atrial fibrillation (AF), some physicians are reluctant to use anticoagulants. We investigated attitudes of physicians in Japan toward anticoagulant therapy in chronic AF patients.
  Methods  We conducted a survey at the annual meeting of the Japanese Society of General Medicine. We presented subject physicians with 8 vignettes of chronic AF patients and requested that they indicate their most favored choice of therapy from among 6 strategies including warfarin and aspirin.
  Results  We distributed 209 questionnaires and received 139 replies (67% response rate). For all 8 vignettes presented, only 26% of the respondents preferred to use anticoagulant therapy in AF patients. Longer clinical experiences and responsibility at a teaching hospital were associated with negative attitude toward anticoagulant therapy, while experience of preventive therapy in patients with thromboembolism due to AF and strong influence of clinical trials of anticoagulant prophylaxis on their practice were associated with positive attitude toward the therapy. Among patient characteristics in the vignettes, a risk of thromboembolism was positively associated with preference for anticoagulant therapy, but an advanced age and a risk of bleeding complications were negatively associated with the preference for the therapy.
  Conclusions  The physicians in Japan in this survey, especially those with longer clinical experiences or responsibility at a teaching hospital, have a negative attitude toward anticoagulant therapy in chronic AF patients. An advanced age and a risk of bleeding complications of patients are deterrent factors to the use of anticoagulant therapy.

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  Objective  To demonstrate that calcium channel blockers can improve insulin resistance clinically, we investigated the effects of the calcium channel blockers, amlodipine, manidipine and cilnidipine on serum levels of steroid hormones and insulin.
  Subjects and Methods  Thirty hypertensive obese patients [15 men and 15 women; mean age 55.9 years, mean body mass index (BMI) 27.6] were divided into three groups and treated with either 5 mg of amlodipine, 20 mg of manidipine or 10 mg of cilnidipine. Blood pressure (BP), fasting plasma glucose (FPG), HbA_1c, fasting serum immunoreactive insulin (F-IRI), insulin resistance index [as assessed by the homeostasis model assessment (HOMA-R)], serum DHEA, serum DHEA-S, plasma ACTH, serum cortisol, plasma renin activity (PRA), and serum aldosterone, were measured before and after 1, 2, 3 and 6 months of treatment.
  Results  In all three groups, BP decreased significantly after 1 month and F-IRI and HOMA-R decreased significantly after 2—3 months. A concurrent rise in serum DHEA and DHEA-S levels was also observed, however, the differences were not significant. No changes in FPG, HbA_1c, ACTH, cortisol, PRA or aldosterone levels were observed during treatment.
  Conclusions  We conclude that amlodipine, manidipine and cilnidipine all improve insulin resistance and consequently increase serum levels of DHEA and DHEA-S.

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A 52-year-old man presented with diarrhea and 20 kg weight loss in one year. Enteroscopy showed diffuse yellow-white shaggy mucosa in the duodenum and jejunum. Biopsies of the duodenal mucosa revealed massive infiltration within the lamina propria by foamy macrophages strongly positive for periodic acid-Schiff stain. Electron microscopy demonstrated numerous bacilli within macrophages of the lamina propria. Tropheryma whipplei DNA was detected by polymerase chain reaction. The definitive diagnosis of Whipple’s disease was made. Antibiotic therapy dramatically improved his clinical picture. This is the first Japanese case with Whipple’s disease diagnosed by electron microscopy and polymerase chain reaction.

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A 25-year-old Japanese man with adult-onset idiopathic hypogonadotropic hypogonadism is reported. He had been delivered normally, had normal puberty, and experienced erectile dysfunction at age 24 years. Brain MRI revealed no abnormal findings and endocrinological data supported the diagnosis of isolated gonadotropin deficiency. Although most patients with idiopathic hypogonadotropic hypogonadism have a hypothalamic dysfunction, the lesion in this case may be considered to be in the pituitary since repetitive GnRH loading failed to increase serum LH and FSH.

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Here, we report a 28-year-old woman who transiently showed lactate dehydrogenase (LDH)-linked immunoglobulin during postpartum thyroiditis. She demonstrated high levels of serum LDH (794 IU/l) and thyroid hormones 7 months after delivery. Electrophoretic isoenzyme analysis of LDH showed an abnormal broadband caused by LDH-linked immunoglobulin (IgG-κ). Transient thyrotoxicosis due to postpartum thyroiditis improved without any specific treatment, and elevated serum concentration of LDH decreased to the normal level (395 IU/l) with disappearance of LDH-linked IgG. LDH-linked immunoglobulin may also appear at the postpartum period.

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We report a case of peripheral primitive neuroectodermal tumor (pPNET), which belongs to the pPNET/Ewing’s sarcoma family, arising in the chest wall of a 69-year-old man. He had high levels of serum neuron-specific enolase and pro-gastrin-releasing peptide, which are believed to be useful diagnostic blood markers for small cell lung carcinoma (SCLC). Microscopically, the tumor was composed of solid nests and sheets of monotous, primitive, small round cells with a few rosettes, making it difficult to distinguish from SCLC. Immunohistochemically, the tumor cells showed intense cell membranous immunoreactivity for MIC2 protein (CD99). EWS/FLI-1 chimeric mRNA that originated from the characteristic t(11;22)(q24;q12) chromosomal translocation was detected by RT-PCR and nucleotide sequence analysis. These results confirmed the diagnostic validity of the present tumor being a pPNET, thus raising the possibility that in the past, pPNETs which have arisen in the chest have been mistakenly diagnosed as SCLC.

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Therapy-related acute myeloid leukemia (t-AML) with t(8;21) and therapy-related myelodysplastic syndrome (t-MDS) with trisomy 1q due to der(1;7) developed in the same patient with T-cell lymphoma at intervals of six years. After the development of t-MDS with trisomy 1q, during complete remission of t-AML, the number of megakaryoblasts increased to maximally 74% of leukocytes in the blood. This is a very rare case of two separate therapy-related myeloid malignancies (early t-AML and late t-MDS) and is also a notable case of t-MDS with trisomy 1q due to der(1;7) accompanied by megakaryoblastic proliferation.

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A 75-year-old Japanese woman with polycythemia vera was admitted to our hospital in January 2003 with suspected pulmonary thromboembolism. After administration of heparin, platelet count decreased from 1, 694×10⁹/l on admission to 60×10⁹/l on hospital day 14. The patient developed acute limb embolism and transient cerebral ischemic attack on days 17 and 25, respectively. Signs and symptoms mimicked those of disseminated intravascular coagulation. Antibodies against heparin and platelet factor 4 complexes were detected in serum, and a diagnosis of heparin-induced thrombocytopenia and thrombosis was made. Argatroban treatment improved thrombocytopenia and hypercoagulable state.

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Cytoplasmic vacuolation was seen in patients with a variety of plasma cell dyscrasia. We report here a case of leukemic non-secretory multiple myeloma with many azurophilic granules. By electron microscopy, the myeloma cells were found to have a well-developed rough endoplasmic reticulum and a clear Golgi apparatus, and azurophilic granules were identified as phagocytic vacuoles. In addition to myeloma markers, the cells were positive for B cell-associated, myeloid and stem cell markers. The diagnosis is difficult because of its misleading morphology and unusual surface markers. We consider that electron microscopy is useful for the identification of cell lineage in this disorder.

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A 57-year-old man was admitted with severe anemia and hypergamma globulinemia. After a diagnosis of multiple myeloma and autoimmune hemolytic anemia was made, chemotherapy rapidly decreased the M-protein level and improved his anemia with normalization of the direct Coombs test. The immunoglobulin binding to the patient’s red cells was immunoglobulin G kappa chain like the myeloma M-protein. However, monoclonal immunoglobulin G derived from short-term culture of the patient’s bone marrow mononuclear cells did not bind to a panel of red cells. Therefore, the relationship between the M protein produced by his myeloma cells and hemolysis remained unclear.

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Focal myositis is a rare disease with unknown etiology and a broad spectrum. Here, we present two cases in monozygotic twins who complained of recurrent pain of their calves and showed histological signs of inflammation and MRI image compatible with the diagnosis of focal myositis. The occurrence of twin cases not living in the same household suggests a genetic susceptibility to the disease.

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We report a case of a 71-year-old man who presented with cerebellar dysfunction. He was diagnosed as having squamous cell carcinoma of the lung (T2N3M0, Stage III_B). No anti-onconeural antibodies were found in his serum. Cerebral spinal fluid (CSF) examination showed mild mononuclear pleocytosis alone. Magnetic resonance imaging (MRI) of the brain and spinal cord revealed no abnormalities. At autopsy, there was complete disappearance of Purkinje cells with reactive astrocytosis. These findings are compatible with paraneoplastic cerebellar degeneration (PCD). To our knowledge, no case of PCD has been reported previously in patients with squamous cell carcinoma of the lung.

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We report a case of a 77-year-old man with deteriorating dementia caused by repeated multiple small cerebral embolisms from a thoracic aortic atheroma. Multiple small embolisms were confirmed by diffusion-weighted magnetic resonance imaging (DWI). The patient ultimately died due to aortic dissection. Pathological examinations revealed that no causative embolic source for multiple embolisms could be detected other than severe atheromatous ulcer in thoracic aorta. This case demonstrates that severe aortic atheroma has the potential to precipitate deterioration of vascular dementia.

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Familial Mediterranean fever (FMF) is a recurrent self-limiting polyserositis. Polyarteritis nodosa (PAN) complicating FMF is very rare. Here, we present a 17-year-old male patient with FMF who subsequently developed PAN 2 weeks after hepatitis A infection. This case was also complicated with perirenal haematoma, and right nephrectomy was performed. The clinical condition of the patient was improved after therapy with intravenous and oral corticosteroid and intravenous cyclophosphamide. However, the FMF attacks and vasculitic skin lesions again occurred while he was using colchicine plus immunosuppressive agents a few months later. Interferon-alpha therapy was administered and the attacks were resolved within 3 months. He has not experienced any other symptom during the follow-up period of 28 months.

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We report a case of pyothorax caused by Nocardia (N.) otitidiscaviarum infection in a 69-year-old man with rheumatoid vasculitis, who was regularly treated with prednisolone in our hospital. Initially, the patient responded poorly to intravenous imipenem/cilastatin (IPM/CS), minocyclin (MINO), and oral trimethoprim-sulfamethoxazole (TMP-SMX), but later improved after treatment with levofloxacin (LVFX) and gentamicin sulfate (GM) according to in vitro susceptibility tests. To our knowledge, this is the first description of pyothorax caused by N. otitidiscaviarum infection. It is a rare disease, but recognition of the disease in immunocompromised patients and the prompt initiation of appropriate treatments based on isolation of the pathogen and susceptibility testing can lead to a successful outcome.

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A 49-year-old healthy Japanese woman presented with hemorrhagic diarrhea because of Shiga toxin producing Eschericia coli infection, and then hemolytic uremic syndrome (HUS) developed in the patient. She was successfully treated with continuous hemodiafiltration, plasma exchange, and endotoxin adsorption therapy. An analysis of previous case reports suggests that females aged between 16 and 65 years are at an increased risk of HUS resulting from hemorrhagic colitis. We propose that adult female patients with hemorrhagic colitis should be carefully monitored regardless of their medical history, physical presentation, or laboratory data.

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A 22-year-old Japanese man noticed pyrexia and diarrhea after travel to Guinea. Notable physical findings included hepatosplenomegaly. Treatment with oral quinine and minocycline was started after definitive diagnosis of falciparum malaria by blood smear. Initially, parasitemia and body temperature decreased but by the third night of therapy his temperature increased to 40°C with a slight increase of parasite count. When quinine treatment was changed to atovaquone/proguanil, his temperature dropped immediately and complete plasmodial elimination was confirmed on microscopic examination. Subsequent recrudescence of the disease was not observed. It was concluded that the antimalarial treatment with atovaquone/proguanil might become invaluable in Japan.

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