To date, in the investigation of the role of S. aureus in WG, we face a paradoxical situation. On the one hand, clinical results obtained from treatment of WG patients with co-trimoxazole and studies assessing the impact of S. aureus on disease relapses strongly suggest that this bacterium contributes to disease pathophysiology. On the other hand, laboratory investigation of the possible mechanisms by which S. aureus is involved in WG is scarce, despite the fact that knowledge and tools to study this microorganism are abundant. In the present review, we discuss recent works investigating the possible pathophysiologic contribution of S. aureus to WG. Moreover, we propose a number of possibly relevant pathways of interaction of this bacterium with lymphoid and nonlymphoid cells of the WG host.
(Internal Medicine 42: 771-780, 2003)

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Objective Unexpectedly low values of HbA_1c measured by HPLC compared with their blood glucose levels were found in three related persons. We investigated whether this discrepancy was due to abnormal hemoglobin.
Patients and Methods HbA_1c was measured by latex agglutination and ordinary HPLC. For further examination, a hemoglobin specimen from the 82-year-old female case was prepared and analyzed by PolyCAT A chromatography, ESI/MS and MS/MS. The HbA_1c levels of the three cases measured by HPLC were lower than those measured by latex agglutination. The elution profiles on HPLC of the three gave an unusual peak between HbA_1c and HbA₀.
Results PolyCAT A chromatography revealed two additional peaks which were not present in normal hemolysates. These peaks were revealed to correspond to abnormalities of HbA₀ and HbA_1c. The amounts of HbA₀ and HbX were almost the same (1 : 0.85) and their glycation ratios were almost equal (5.2% and 5.9%). ESI/MS showed that the woman's intact globin contained an abnormal β^x-chain in addition to the normal α^A- and β^A-chains. The molecular weight of this abnormal β^x-chain was 58 Da lower than that of the normal β^A-chain. Glutamate at the 22nd amino acid residue of the β^A-chain was replaced by alanine in the abnormal β^x-chain.This variant of Hb was revealed to be the same as HbG-Coushatta (β-22 Glu→Ala) from the library of variant Hb. Family studies showed that the variant was inherited as a dominant trait.
Conclusion The dissociation was due to underestimation of HbA_1c in the measurement by HPLC which excluded glycated variant Hb.
(Internal Medicine 42: 781-787, 2003)

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Objective The aim of this study was to investigate whether or not the purine degradation in the skeletal muscle during forearm exercise is augmented in patients with diabetes mellitus (DM).
Methods We used the semi-ischemic forearm test to examine the release of lactate (ΔLAC), ammonia (ΔAmm) and hypoxanthine (ΔHX) before exercise, 0, 4, 10, and 60 minutes after exercise in eleven diabetic patients and seven normal controls.
Results The sum of the increased HX (DM vs Controls: 26.1±21.2 vs 7.8±5.9 μmol/l, p<0.05) was greater in diabetic patients. When patients were divided into the excessive response group (n=7) and normal response group (n=4), the maximum increments in ΔHX and Δ Amm in the excessive response group (16.8±3.2 μmol/l and 122±60 μmol/l were greater (p<0.05) than those in the control group (3.6± 3.0 μmol/l and 32±34 μmol/l) and the normal response group (2.9±2.9 μmol/l and 27.4±12.7 μmol/l). ΔLAC both in the excessive response group (5.4±1.5 mmol/l) and the normal response group (3.6±1.0 mmol/l) were higher (p<0.05) than that of the control group (1.7±0.5 mmol/l). The prevalence of diabetic retinopathy was higher in the excessive response group than in the normal response group (75% vs. 25%).
Conclusion These data suggest that patients with DM, especially with microangiopathy have augmented purine degradation during the semi-ischemic forearm test. Factors responsible for the augmented purine degradation in these patients remain to be determined.
(Internal Medicine 42: 788-792, 2003)

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Objective To compare the efficacy and safety of two antiplatelet regimens, ticlopidine alone (200 mg daily) and ticlopidine (100 mg daily) plus aspirin (81 mg daily), in patients with ischemic stroke from the Tokai district of Japan.
Methods A randomized comparative study was performed from April 1992 until December 1995, with follow-up for an average of 1.59 years (maximum: 0

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Objective To detect amyloid deposits in the early phase of illness, we investigated the usefulness of abdominal fat aspiration biopsy along with genotyping of serum amyloid A (SAA) in patients with rheumatoid arthritis (RA).
Patients and Methods We performed abdominal fat aspiration biopsy with phenol Congo red staining and determined inflammatory markers, including CRP and SAA, in 217 patients with an RA history longer than 5 years (mean age, 64.1±10.6 years). Genotypes of SAA1 and 2 were investigated in 127 patients with RA by a polymerase chain reaction-restriction fragment length polymorphism analysis.
Results In the abdominal fat aspiration biopsy 17 patients (7.8%) demonstrated amyloid deposits, which were confirmed as AA type by immunostaining on biopsied tissues from other organs, and nine of them showed no clinical symptoms ascribable to amyloidosis. RA patients with amyloidosis showed significantly higher serum levels of CRP (p<0.05) and SAA (p<0.0001) than those without amyloidosis. In the genotyping, amyloid deposition was significantly correlated with the frequency of SAA1.3 (p<0.005 vs. 1.1, p<0.05 vs. 1.5). Comparison of inflammatory markers between the number of SAA1.3 alleles showed that the SAA/CRP ratio and SAA concentration were higher in the 1.3 homozygote than in the others (p<0.05). Two patients demonstrated amyloid deposits at the second abdominal fat biopsy one year after the first, and their SAA1 genotypes were 1.3/1.5 and 1.3/1.3.
Conclusion In RA patients confirmed as having SAA1.3, serial examinations with abdominal fat aspiration biopsy might contribute greatly to the early detection of amyloidosis during the long-term follow-up.
(Internal Medicine 42: 800-805, 2003)

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Objective To study the epidemiologic manifestations of a large outbreak of Legionnaires' disease due to an inadequate circulating and filtration system for bath water.
Patients In June 2000 at Ishioka City, Ibaraki Prefecture, a large outbreak of Legionnaire's disease occurred, as a result of an inadequate circulating and filtration system for communal bath water. This outbreak was the worst ever experienced in Japan, involving a total of 34 patients (20 confirmed, 14 probable), 3 of whom died.
Measurements and Results Legionella pneumophila serogroup 1 was isolated from sputum culture in two patients. Bacteriological culture of the public bath water subsequently yielded large numbers of Legionella species. Cleavage of genomic DNA showed that restriction fragment patterns coming from clinical and environmental isolates of L. pneumophila serogroup 1 were closely related, focusing the inquiry to a public bathhouse where a circulating filtration system was suspected as the source of infection.
Conclusions It was later concluded that the circulating filtration system adopted for bath water was marred by a serious design flaw that subsequently caused the mass outbreak. Specifically, a line of the bath water was being returned to the bath without undergoing heat exchange or sterilization by chlorine; and the Legionella species that had proliferated in the filter and the bright stone filtration unit were allowed to return to the bath, eventually culminating in a mass infection.
(Internal Medicine 42: 806-811, 2003)

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Idiopathic retroperitoneal fibrosis (IRF), usually affects the ureter, although the biliary tree, duodenum and vasculature may also be susceptible. This case report describes a 64-year-old man with IRF, who presented painless watery diarrhea, radiological features of obstructive jaundice and duodenal obstruction, and ultimately an obstruction of the inferior vena cava. We employed tamoxifen for his treatment, but the disease progressed and the patient died of multiple organ failure two years after the onset. While the cause of IRF in this patient was obscure, we suspected his painless watery diarrhea indicated chronic ischemia of the small bowel, and the findings of an abdominal CT scan were extremely valuable in indicating IRF.
(Internal Medicine 42: 812-817, 2003)

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A 46-year-old man presented with a huge splenic artery dissecting aneurysm that had been incidentally found and was successfully resected before rupture. The histopathologic findings were compatible with segmental mediolytic arteriopathy (SMA). Simultaneous involvement of the left renal and right common iliac artery was observed. The patient was also found to have an adrenocortical adenoma, gastrointestinal stromal tumor, hepatocellular carcinoma and schizophrenia. The relationship between SMA and other accompanying diseases was discussed.
(Internal Medicine 42: 818-823, 2003)

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We describe the use of short-term epoprostenol in a 61-year-old man with primary pulmonary hypertension. The patient was on a ventilator because of respiratory distress. Continuous infusion of epoprostenol was started and it initially reduced the pulmonary artery pressure by 32%. Epoprostenol was tapered, and even after discontinuation, the pulmonary artery pressure was controlled. The ventilator was removed, and the patient remained well on home oxygen therapy 3 months after discharge.
(Internal Medicine 42: 824-826, 2003)

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We report a 73-year-old woman with primary cardiac leiomyosarcoma in the left atrium and ventricle. The tumor progressed very rapidly for 2 months after initial clinical evaluation. Obstruction of the left ventricular outflow tract and mitral stenosis were induced by the tumor. Urgent surgical resection was performed because she had cardiogenic shock due to paroxysmal atrial fibrillation. We could not resect the tumor completely because of severe invasion. She refused postoperative chemotherapy and radiotherapy, and died suddenly at home 89 days after surgery. To our knowledge, this is the first observation of mitral stenosis concomitant with obstruction of the left ventricular outflow tract in a patient with primary cardiac leiomyosarcoma.
(Internal Medicine 42: 827-830, 2003)

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Paraneoplastic Gushing's syndrome caused by ectopic adrenocorticotropin production has been reported in association with a variety of malignant tumors. However, most cases of this syndrome are associated with neuroendocrine tumors such as small-cell lung cancer (SCLC), carcinoid tumors, and medullary carcinoma of the thyroid. We present a 49-year-old man who developed Cushing's syndrome associated with adenocarcinoma of the lung. He had a wide variety of clinical symptoms and comorbidity related to this syndrome during the course, and died 4 months after the diagnosis. This is a very rare case report of Cushing's syndrome associated with adenocarcinoma of the lung.
(Internal Medicine 42: 831-833, 2003)

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A 61-year-old woman had been coughing up blood-tinged sputum since May 1998. Chest radiography and computed tomography (CT) scans revealed a solitary mass (3 cm in greatest dimension) in the right lower field, accompanied by a surrounding area of ground glass and reticular appearance. Surgical lung biopsy was performed to the surrounding area. The pathological diagnosis was pulmonary ossification of the dendriform type. Alveolar macrophages obtained from her lung differentiated into tartrate-resistant acid phosphatase (TRAP)-positive multinucleated giant cells (MGCs) in the presence of autologous T cells or of macrophage colony stimulating factor (M-CSF) and interleukin-4 (IL-4). This results suggest the possibility that monocytes/macrophages may have the ability to form osteoclasts in the presence of cytokines that may be involved in the development of pulmonary ossification.
(Internal Medicine 42: 834-838, 2003)

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Although cigarette smoking is a recognized cause of acute eosinophilic pneumonia (AEP), and an increase in eosinophils in the lung is a common occurrence in AEP, early-phase neutrophilia in AEP is not well understood. We describe three cases of cigarette smoke (menthol type)-induced AEP with neutrophilia in the lungs or blood. Increased in-vitro production of the neutrophil chemoattractant interleukin (IL)-8 by human bronchial epithelial cells (HBECs) was correlated with neutrophilia. We suggest that IL-8 released from HBECs is involved in neutrophilia in the lung in AEP, and is newly recognized as an important factor in the early phase of AEP development.
(Internal Medicine 42: 839-845, 2003)

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This is a report of a patient with occupational hypersensitivity pneumonitis (HP) caused by Konjak flour and powdered Hijikia fusiforme. A 56-year-old man had worked as a Konnyaku manufacturer for 38 years, and suffered from dyspnea on exertion. Konnyaku is a paste made from Konjak flour, powdered Hijikia fusiforme, quicklime, and powdered scallop shell. The diagnosis of HP was confirmed immunologically by the detection of serum precipitins to powdered Hijikia fusiforme, and by the positive result of in vitro lymphocytic proliferative response for Konjak flour using peripheral blood lymphocytes. To our knowledge, this is the first case report of Konnyaku manufacturer's lung.
(Internal Medicine 42: 846-849, 2003)

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A 57-year-old woman was admitted to our hospital because of severe dyspnea due to pulmonary hemorrhage and rapidly progressive renal failure. The patient was positive for perinuclear pattern anti-neutrophil cytoplasmic antibody (p-ANCA) and was manifested with gastrointestinal bleeding and brain hemorrhage. Thus, she was diagnosed as having microscopic polyangiitis (MPA). Laboratory examination demonstrated severe thrombocytopenia, increased prothrombin time and a high concentration of fibrin degradation products. In addition, the elevated plasma levels of D-dimer, thrombinantithrombin complex and plasmin-plasmin inhibitor complex led us to make a diagnosis of disseminated intravascular coagulation (DIG). Complication of DIC was considered to have caused further deterioration in bleeding tendency due to MPA in the present case. The patient was treated with plasma exchange, hemodialysis, administration of corticosteroid including pulse therapy and cyclophosphamide. Continuous infusion of gabexate mesilate proved effective for improvement of systemic bleeding tendency. However, she finally died of severe infectious diseases. In conclusion, it is suggested that ANCA-associated vasculitis could be accompanied by DIC and gabexate mesilate may be a useful therapeutic agent for these disorders.
(Internal Medicine 42: 850-855, 2003)

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A 37-year-old Japanese woman was referred from another clinic to confirm the diagnosis of myotonia congenita. She had experienced cold-induced myotonia and muscle stiffness from early childhood. Of her three children, her elder son and her daughter have clinical features similar to hers. They experience neither grip nor percussion myotonia during warm weather, whereas myotonia is provoked by cold. Her younger son has no symptoms. DNA analyses of the SCN4A gene showed a C to T transition at nucleotide position 3938 in exon 22 of SCN4A (Thr1313Met) in all three affected family members, but not in the unaffected son. Paramyotonia congenita, the prevalence of which is very low in Japan, was diagnosed based on their clinical features and DNA analysis results.
(Internal Medicine 42: 856-861, 2003)

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An asthmatic patient with corticosteroid treatment for 45 years presented with slowly progressive limb muscle atrophy. His muscle symptoms were involved in four limbs and tongue, and deep tendon reflexes were exaggerated. Biopsied muscle pathology indicated the presence of neurogenic muscular atrophy in combination with corticosteroid myopathy. Furthermore, 8-hydroxy-deoxyguanosine (8-OH-dG) was prominently increased in mitochondrial and nuclear DNA. An aerobic exercise test demonstrated remarkable serum lactate elevation, which was attenuated by the administration of coenzyme Q₁₀- These findings are consistent with the assumption that long-term corticosteroid administration potentially induces not only myopathy but also motor neuron involvement as in mitochondrial diseases.
(Internal Medicine 42: 862-866, 2003)

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A 70-year-old man who suffered from osmotic demyelination syndrome (ODS) is presented. Dyspnea, pseudobulbar palsy and motor weakness were seen. MRI in the acute stage revealed focal abnormal high-signal lesions in the pons, thalamus and bilateral cortical areas on T1-weighted and FLAIR images. With corticosteroid therapy he recovered from his dyspnea and severe pseudobulbar palsy, and the spastic quadriplegia gradually improved. One year later the brain lesions had disappeared on T1-, T2-weighted and FLAIR images. To detect the cortical or subcortical lesions in ODS, FLAIR imaging should be performed routinely.
(Internal Medicine 42: 867-870, 2003)

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Hemimedullary infarction, which presents Babinski-Nageotte syndrome, has been mainly reported to result from atherosclerotic occlusion of the vertebral artery. A 54-year-old housewife with right nuchal pain developed Wallenberg's syndrome followed by left hemiparesis. Diffusion-weighted magnetic resonance imaging documented fresh infarcts in the right hemimedulla and right dorsal cerebellum. Angiography revealed dissection of the right vertebral artery as a cause of the infarcts. Anterograde progression of the dissection might cause stepwise evolution of her neurological symptoms.
(Internal Medicine 42: 871-874, 2003)

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A 31-year-old, right-handed woman had frequent focal painful seizures involving the right hand without any movement. EEG demonstrated an ictal activity arising from the left centroparietal region. No cerebral structural abnormality was seen on MRI. Ictal single photon emission CT showed markedly increased activity in the left perirolandic cortex, which remained active following the ictal symptoms when the EEG seizure pattern had completely disappeared. It is concluded that the painful seizures in the present patient originated from the primary somatosensory cortex. The prolonged increase of regional blood flow in the perirolandic area may reflect the possibility of persistent subclinical epileptogenicity.
(Internal Medicine 42: 875-879, 2003)

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We report a 16-year-old woman with secondary generalization of partial seizure, who complained of an auditory disturbance after carbamazepine (CBZ) administration. She had been taking sodium valproate (VPA) from the age of 15. However, her seizures remained poorly controlled. We changed her antiepileptic drug from VPA to CBZ. At 1 week after CBZ administration, she noticed that electone musical performances were heard as a semitone lower. When oral administration of CBZ was stopped, her pitch perception returned to normal. If she had not been able to discern absolute pitch, she might have been unable to recognize her lowered pitch perception. Auditory disturbance caused by CBZ is reversible and very rare.
(Internal Medicine 42: 880-883, 2003)

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We reported a sixty-year-old man who developed acquired stuttering after a brainstem infarction. Infarctions were detected in the midbrain and upper pons. Neurogenic stuttering of this patients indicated that the midbrain and upper pons could be lesion sites responsible for acquired stuttering. We speculated that the reticular network extending from the brainstem to the frontal cortices, and the periaqueductal gray matter could be closely related regions generating neurogenic stuttering.
(Internal Medicine 42: 884-887, 2003)

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We report a patient with reactive systemic AA amyloidosis secondary to rheumatoid arthritis who showed fatal acute pancreatitis with a cystic formation in the pancreas head. The pancreatitis rapidly worsened despite intensive treatment and resulted in death. In this patient severe deposition of amyloid in the gastrointestinal tract was considered to play an important role in the pathogenesis of the acute pancreatitis. This is an unusual complication in patients with AA amyloidosis, but we should consider it as a possible diagnosis when patients with AA amyloidosis show recurrent or intractable pain in the upper abdomen.
(Internal Medicine 42: 888-892, 2003)

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A patient with bronchial asthma developed cholecystitis. Laboratory investigations revealed marked eosinophilia (6, 615/mm³), an elevated anti-neutrophil cytoplasmic antibody level and renal dysfunction (blood urea nitrogen 14 mg/dl, creatinine 1.4 mg/dl). Following cholecystectomy, histopathological examination revealed a marked inflammatory cell infiltrate composed mainly of eosinophils with evidence of invasion of the wall of the gall bladder and granuloma formation of arterioles. A diagnosis of Churg-Strauss syndrome was made and she was treated with 60 mg of prednisolone per day. A renal biopsy was performed one year later in view of persistent renal dysfunction. Pathological analysis revealed a pauciimmune glomerulonephritis with interstitial changes but no crescent formation.
(Internal Medicine 42: 893-896, 2003)

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A 36-year-old woman with ulcerative colitis presented with fever, chest and back pain, and fatigue sensation of the arm. Her upper limb pulses were absent. Angiography showed multiple aneurysms of the aorta and its branches, consistent with Takayasu's arteritis. She showed HLA-B35 but no B52, which is the typical haplotype among the coexistence cases of both diseases. Prednisolone was effective. The possible pathogenic association of the disorders is discussed.
(Internal Medicine 42: 897-898, 2003)

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Acute hepatitis E is caused by infection with hepatitis E virus, which is endemic in developing countries. Recently, the number of cases with acute hepatitis E is increasing in Japan due to increased travel to the endemic areas. This paper reports a case of a Japanese man with acute hepatitis E who had a history of traveling to south China. Serum creatine phosphokinase was elevated on admission without symptoms of muscle damage (isoenzyme MM 100%), and normalized in parallel with resolution of hepatitis, raising the possibility of an association between elevation of creatine phosphokinase and acute hepatitis E. However, we need to investigate further the incidence of elevation of serum creatine phosphokinase in many cases with acute viral hepatitis including hepatitis A, B, and C to determine whether muscle disorder is characteristic of acute hepatitis E.
(Internal Medicine 42: 899-902, 2003)

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A Japanese woman developed prolonged fatigue, neck and shoulder pain, headache, pyrexia, insomnia, anorexia, lymphadenopathy, and diarrhea for two months. She had experienced various stressors before these symptoms developed. Serological test demonstrated that she had acute parvovirus B19 infection. Major depressive disorder was also diagnosed by a psychiatrist. Her symptoms disappeared after administration of selective serotonin reuptake inhibitors and oriental herbs, although human parvovirus B19 viral genome has been present in her serum for nine months. These findings suggest that parvovirus B19 causes clinical features similar to those of chronic fatigue syndrome in cases who have prior life stressors.
(Internal Medicine 42: 903-905, 2003)

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