During the past few years remarkable progress has been achieved in the understanding of the pathogenic mechanisms leading to vascular inflammation and injury in ANCA-associated vasulitides (AAV): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg Strauss syndrome (CSS). In this paper we review the immunopathology of these diseases by describing the role of autoantibodies (ANCA), dysregulation and abnormalities at the cellular level, genetic background and environmental factors that predispose to autoimmune response.
(Internal Medicine 38: 759-765, 1999)

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Objective The aim of this study was to clarify the role of transesophageal echocardiography in detecting cardiac sources of embolism in elderly stroke patients. Methods We performed transesophageal echocardiography in 77 patients≥70 years old (mean 76.9) with ischemic stroke and investigated embolic sources. Thirty-seven patients were in sinus rhythm (SR) and 40 in atrial fibrillation (Af). Results Left atrial spontaneous echo contrast was detected in 73% of Af and in 14% of SR (p<0.01). Left atrial thrombus was present in 10% of Af and none of SR (p<0.05). Patent foramen ovale, atrial septa) aneurysm, and aortic atherosclerotic plaque≥4.0 mm in thickness in the proximal aortic arch were more commonly found in patients with SR. Conclusions In elderly ischemic stroke patients, 1) Left atrial spontaneous echo contrast and thrombus are more commonly detected in patients with Af, reflecting left atrial enlargement and blood stasis, and 2) atrial septal aneurysm, patent foramen ovale and aortic atherosclerotic plaque≥4.0 mm in thickness in the proximal aortic arch are important findings in patients with SR.
(Internal Medicine 38: 766-772, 1999)

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Objective We examined whether changes in plasma norepinephrine (NE) concentration contribute to the development of nitrate tolerance in human coronary arteries. Methods Patients with stable angina were randomized to receiving nitrate (isosorbide dinitrate: ISDN or nitroglycerin: TNG) infusion for 30 minutes (group A), 48 hours (group B), or 78 hours (group C). Coronary diameters were measured angiographically at baseline (CT), during maximum dilation by ISDN (Nl), at the end of nitrate infusion (N2) and after additional ISDN (1 mg) injection (N3). Results In groups A and B, Nl, N2, and N3 were greater than CT, and there was no significant difference between Nl, N2, and N3 for each group. In group C, Nl and N3 were greater than CT, but there was no difference between CT and N2, in the development of nitrate tolerance. In group A, NE increased significantly during nitrate infusion (304±163 vs. 418±273 pg/ml). NE did not change in groups B and C. Conclusion The change in NE concentration is not a primary contribution to the development of nitrate tolerance.
(Internal Medicine 38: 773-779, 1999)

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Objective To summarize the features of asbestos-related lung cancer. Patients Thirty-one lung cancer patients with occupational exposure to chrysotile asbestos fibers. They worked or had worked in one asbestos factory or its subcontracters. Result All patients were male with mean age of 60.6 when diagnosed, and all except one were current or ex-'heavy' smokers. Histological types were fairly evenly divided into adeno-, squamous and small cell carcinoma and 24 (78%) of patients showed 'peripheral type' lung cancers. Regarding clinical stages, 20 patients (65%) were classified as III or IV (advanced stage). Tumor shadow(s) was detected on chest X-ray in 22 patients (71%), and in 5 patients with 'negative' chest X-ray, chest CT was necessary to recognize a primary tumor. Seventeen patients (55%) did not undergo periodical check-ups. Conclusion Occupational asbestos exposure is interpreted as one of the important risks for lung cancer and frequent and accurate observation is necessary.
(Internal Medicine 38: 780-784, 1999)

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Objective To clarify the extent of asymptomatic cerebrovascular involvement in systemic lupus erythematosus (SLE). Patients and methods Cerebral magnetic resonance imaging (MRI) findings and ultrasonography findings of 100 patients with SLE lacking present or past clinical neurologic deficits were compared with 66 age-matched volunteers to determine the combined intima-media thickness (IMT) of the common carotid artery, and tests for anti-cardiolipin antibodies (aCL). Results Thirty-eight patients, but only 2 controls, showed imaging abnormalities. Among 23 SLE patients with cerebrovascular lesions by MRI who underwent single-photon emission computed tomography (SPECT), 14 showed hypoperfusion of the lesion. The IMT value and prevalence of aCL did not differ between the 55 SLE patients tested and controls. SLE disease activity index (SLEDAI) as assessed by a quantitative clinical index was significantly greater in patients with brain lesions than in those without. Conclusion The prevalence of asymptomatic brain lesions in SLE patients is high, and shows a relationship to disease activity.
(Internal Medicine 38: 785-795, 1999)

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Helicobacter pylori (H. pylori) infection plays a decisive role in primary gastric B-cell lymphoma especially of mucosa-associated lymphoid tissue (MALT)-type. We treated a 47-year-old male patient with primary gastric B-cell lymphoma associated with H. pylori infection. Although antibiotic therapy for eradication of H. pylori caused great improvement in the low-grade MALT lymphoma-like lesion, the small areas of high-grade lesion rapidly formed a new bulky mass in only 8 weeks. This suggests that eradication of H. pylori is not effective for high-grade lymphoma.
(Internal Medicine 38: 796-799, 1999)

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A 69-year-old male diabetic patient had an abnormally low HbA_1C value of 2.8%, which was inconsistent with his elevated fasting plasma glucose of 8.2 minol/l. Hb analysis disclosed that the abnormal Hb was Hb Ube-2 [α68 (E17) Asn → Asp] and it accounted for 21.5% of the total Hb. Since the glycated abnormal Hb emerged at the same position as did HbF on high performance liquid chromatography, the HbA_1C value was falsely low. The present case demonstrates that Hb Ube-2 is one of the abnormal Hbs in which caution should be exercised when monitoring diabetic control.
(Internal Medicine 38: 800-803, 1999)

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A 59-year-old man was admitted to our hospital because of muscular pain, weakness, and anorexia. He had been treated with 600 mg/day of fosfestrol, a synthetic estrogen, for 10 years for prostatic carcinoma. Endocrinological studies demonstrated adrenocortical insufficiency due to inadequate ACTH secretion. After initiation of glucocorticoid replacement therapy, his symptoms subsided rapidly. To our knowledge, an association between estrogenic agents, including fosfestrol, and secondary adrenocortical insufficiency has not been previously reported. Physicians who treat patients with long-term and high-dose strong estrogenic agents should be cautious about the possible emergence of secondary adrenocortical insufficiency.
(Internal Medicine 38: 804-807, 1999)

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A 56-year-old Japanese woman with congenital nephrogenic diabetes insipidus (CNDI) is reported. She was diagnosed with CNDI accompanied by advanced gastric cancer. After total gastrectomy, approximately 500 ml fluid per hour was necessary to prevent dehydration. Urinary volume was decreased by administration of hydrochlorothiazide. We detected a novel mutation in the vasopressin V2 receptor gene of her chromosomal DNA. A substitution from G to A was found at the 631 nucleotide position, altering codon 12 from glycine (G ?? G) to glutamic acid (G ?? G) in the first extracellular domain. This missense mutation appeared to be the cause of her resistance to arginine vasopressin.
(Internal Medicine 38: 808-812, 1999)

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A 56-year-old woman was hospitalized for recurrent hemoptysis. She had been suffering from bronchiectasis for 4 years. Pseudomonas aeruginosa was persistently detected in her sputum. Serum was positive for Myeloperoxidase antineutrophil Cytoplasmic antibody (MPO-ANCA) and bactericidal/permeability-increasing protein antineutrophil Cytoplasmic antibody (BPI-ANCA). She underwent lung resection. Histopathologically, the resected lung showed bronchiectasis with pulmonary fibrosis but did not show vasculitis. Her serum became negative for the ANCAs after the operation. To date, she has no recurrence of hemoptysis. We discuss this case of bronchiectasis with MPO-ANCA and BPI-ANCA and suggest a possible role for ANCAs in chronic airway infection.
(Internal Medicine 38: 813-816, 1999)

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A 79-year-old female presented with persistent dry cough, and a chest radiograph showed a mass shadow in the right upper lung. Bronchoscopic examination revealed that the right main bronchus was severely obstructed by a polypoid tumor, which was diagnosed pathologically as squamous papilloma. After the failure of the attempted endobronchial snare to remove the tumor, right upper lobectomy was performed. The polymerase chain reaction (PCR) examination showed the presence of human papilloma virus type 11 DNA in the resected tumor, suggesting that this virus was the cause of this solitary squamous papilloma of the lung.
(Internal Medicine 38: 817-819, 1999)

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A 67-year-old woman with severe pain in the peripheral extremities was admitted to our hospital. Radiography of the peripheral extremities revealed multiple osteolytic lesions. Antibody to human T cell leukemia virus type-I (HTLV-I) was positive, and right radial bone biopsy showed infiltration of adult T cell leukemic (ATL) cells. Irradiation therapy was effective in the osteolytic lesions. In the present case, elevation of IL-6 was detected, suggesting that IL-6 produced by ATL cells is related to their proliferation in the bone, and local osteolysis.
(Internal Medicine 38: 820-823, 1999

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A 65-year-old man developed severe lumbago and a loss of appetite two months before presentation. A computerized tomograph at admission revealed soft tissue masses destroying the Th12, L4 and L5 vertebral bones. We diagnosed the lesions to be metastatic bone tumors, but the primary focus could not be determined. Just after the irradiation treatment, abnormal lymphocytes were detected in the peripheral blood cells. Under the suspicion of adult T-cell leukemia/lymphoma (ATL), we thus performed a lymph node biopsy. The specimens were histologically composed of Ki-1 positive anaplastic large cell lymphoma (ALCL). The lymphoma cells demonstrated a biclonal integration of HTLV-1 proviral DNA. After 6 cycles of chemotherapy, the patient has demonstrated a partial and favorable remission from ATL.
(Internal Medicine 38: 824-828, 1999)

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We report a case of cerebral aspergillosis which originated from the sphenoid sinus, and involved a progressive decrease of visual acuity. The neurological signs indicated a cavernous sinus invasion. After extensive intracranial surgery we treated the residual aspergillosis with a high oral dose of itraconazole (800 mg/d for 4 months, followed by 400 mg/d for 5 months). The neurological impairments of the patient gradually subsided with the resolution of the fungal lesion shown on MRI. The successful therapy indicated that itraconazole has a significant role in the treatment of advanced cerebral aspergillosis if it is used in high doses (16 mg/kg/d for adults).
(Internal Medicine 38: 829-832, 1999)

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Mycobacterium fortuitum is a well-documented cause of nosocomial infection. However, no studies have reported peritonitis with M. fortuitum as a postoperative complication. We describe a case of peritonitis with M. fortuitum biovariant peregrinuni following gastric cancer surgery. Gram-positive bacterial infection coexisted. Although the source of the infection was unclear, the patient was successfully treated with drainage tube exchange and combination therapy consisting of sparfloxacin, clarithromycin, and imipenem/cilastatin sodium. Thus for postoperative infectious pathogens, not only bacteria but also nontuberculous mycobacteria should be considered.
(Internal Medicine 38: 833-836, 1999)

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