The international consensus report on diagnosis and treatment of asthma was published in 1992 (Clin Exp Allergy 22: 1-72). According to the report, asthma is a chronic inflammatory disorder of the airways in which many cells play a role, including mast cells and eosinophils. Airway inflammation causes various symptoms of asthma which are usually associated with widespread but variable airflow obstruction and causes an associated increase in airway responsiveness to a variety of stimuli. The definition of asthma, provided in this report, is an epoch-making revision of the conventional recognition of asthma based on respiratory physiology and does not contradict the empirical knowledge that asthma responds well to steroid therapy.
One reason, which led airway inflammation to be understood as a major factor in the pathophysiology of asthma is the technological advance and the widespread use of bronchoscopes. The use of bronchoscopy as a research tool has markedly improved the understanding of the pathology of asthma. It became also possible to link biopsy findings to autopsy findings in patients who died of asthma.
However, it is relatively difficult to repeat a biopsy of the airway mucosal membranes in individual asthmatic patients. Here, animal models of asthma play a significant role. Findings from animal models can provide a clue for the development of new anti-asthmatic drugs.
This paper will deal with the paradigm of allergic asthma and focus on recent topics of interleukin (IL)-4 and IL-5, which seem to play a central role in allergic asthma. The causative relationship between airway inflammation and hyperresponsiveness will be discussed.
(Internal Medicine 42: 636-643, 2003)

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Objective It is unknown why most amoebic liver abscess (ALA) cases occur in alcohol drinkers. In experimental studies, the presence of 'iron' potentiates the invitro growth of Entamoeba histolytica (E. histofytica), and is also known to increase its in-vivo invasiveness in animal infections. Chronic alcoholism increases the hepatic iron deposition. We hypothesized that ALA occurs more commonly in livers with a high iron load as in alcoholics. To test this hypothesis we compared the levels of iron between ALA and non-ALA cases belonging to alcoholic and non-alcoholic groups.
Methods Out of a total of 48 ALA cases, 34 (70%) were alcoholics and 14 (30%) were non-alcoholics. After applying exclusion criteria, serum iron and liver iron stores were quantified in 20 ALA cases (10 alcoholic and 10 non-alcoholics) and compared with 20 non-ALA cases (10 alcoholics and 10 non-alcoholics).
Results All patients of ALA had serum iron values within the normal range but higher than non-ALA cases. In the liver tissue, most patients with ALA had higher (grade II or III) iron deposition, than non-ALA cases (mostly grade I). Thus, patients with ALA, with or without alcohol indulgence, had higher iron levels when compared to the non-ALA cases.
Conclusion It appears that the higher incidence of ALA in alcoholic livers is possibly due to their higher iron content.
(Internal Medicine 42: 644-649, 2003)

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Objective Various antiviral therapies, including interferon therapy, are being conducted to treat chronic hepatitis C and suppress the onset of hepatocellular carcinoma. However, interstitial pneumonia is beginning to be recognized as one of the adverse reactions of this therapy, and is one of the complications associated with chronic hepatitis. Therefore, we measured the level of KL-6, an interstitial pneumonia marker, in patients with HCV-associated chronic disease, and then determined the possibility of utilizing serum KL-6 as a predictive factor for interstitial pneumonia and the clinical significance of KL-6 in HCV-associated chronic disease.
Subjects and Methods The subjects were 308 patients who were diagnosed with chronic liver disease through biochemical blood tests and abdominal diagnostic imaging. All patients tested positive for either the HCV antibody or HCV-RNA, and those who were suspected of having autoimmune hepatitis were excluded. One hundred eighty-five patients had chronic hepatitis (average age: 56±14 years), while 123 patients had liver cirrhosis (average age: 64±9 years). The purpose of the present study was explained to every subject, and informed consent was obtained.
Results The mean KL-6 level for chronic hepatitis patients without interstitial pneumonia was 283.5±131.4 U/ml, while that for cirrhotic patients without interstitial pneumonia was significantly higher, at 377.6±212.1 U/ml (p<0.0001). In addition, with a cut-off value of 500 U/ml, the ratio of high KL-6 for the chronic hepatitis patients was 5.41% (10/185), while that for the cirrhotic patients was significantly higher, at 20.33% (25/123) (p<0.0001). Furthermore, the mean KL-6 level for patients with a serum hyaluronic acid level of less than 100 ng/ml was 258.4±124.6 U/ml, while that for patients with a serum hyaluronic acid level of 100 ng/ml or above was significantly higher, at 381.0±197.3 U/ml (p<0.0001).
Conclusion Although KL-6 is a marker of interstitial pneumonia, the results of the present study suggest that, in HCV-associated chronic disease, this marker reflects hepatic fibrosis better than pulmonary fibrosis.
(Internal Medicine 42: 650-654, 2003)

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Objective Diabetic patients with severe autonomic nervous disorder show delayed gastric emptying accompanied by diabetic gastroparesis, which decreases the electric activity of the stomach associated with gastric motility. It is reported that epalrestat, an aldose reductase inhibitor, is useful for treating diabetic neuropathy. Therefore, we evaluated whether this drug improves the decreased gastric motility in diabetic patients.
Methods The present study evaluated the electrogastrograms (EGG) and autonomic nervous activity in 15 healthy volunteers (N group), and in 15 diabetic patients before and after the administration of epalrestat (DM group). Autonomic nervous activity was evaluated by spectral analysis of heart rate variability. The EGGs were recorded before and after oral administration of epalrestat (3 months or more) in the DM group.
Results The dominant frequency of EGG was 3 cycles/min (cpm) in the N group. However, these 3 cpm waves disappeared with bradygastria, and postprandial increases in the peak powers of EGG were not observed in the DM group. Both the amplitude of 3 cpm waves and the postprandial peak powers were significantly increased after the administration of epalrestat. The parameters of autonomic nervous activities (LF power, HE power, and the LF/HF ratio) were significantly lower in the DM group before the administration of epalrestat than in the N group. However, these parameters were improved after the administration of epalrestat.
Conclusion Since gastroparesis is a form of diabetic dysautonomia, complication by gastroparesis may influence blood sugar control and the absorbance of oral antidiabetics. Epalrestat significantly increased the amplitude of 3 cpm waves on EGG and improved the spectral analytical parameters of heart rate variability. These findings suggest that epalrestat is useful for the treatment of diabetic gastroparesis.
(Internal Medicine 42: 655-664, 2003)

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Objective High-dose trimethoprim-sulfamethoxazole (TMP-SMX) is known to cause hyperkalemia by blocking amiloride-sensitive sodium (Na) channels in distal nephrons. The purpose of this study was to establish whether the standard dose of TMP-SMX could cause electrolyte disorders.
Methods and Patients Serum Na, potassium (K) and creatinine (Cr) levels were examined retrospectively in 53 of 77 patients prescribed TMP-SMX, before and after taking the antibiotic combination.
Results Electrolyte disorders (Na <135 mEq/l and/or K>5.0 mEq/l) were found in 14 of the 53 patients (26.4%) during TMP-SMX treatment. The average dose was 145.7±24.9 mg/day. The dose of TMP was significantly larger in patients with electrolyte disorders (267.7±84.2 mg vs. 101.9±9.38 mg, p=0.0024). Electrolyte disorders were also seen in 9.1% and 22.2% of patients given the low dose (TMP <80 mg) or standard dose (TMP 80-120 mg) of TMP-SMX, respectively. Electrolyte disorders were seen in 85.7% of patients with renal dysfunction (Cr >1.2 mg/dl), compared with 17.5% of patients with normal renal function (p=0.0008). Logistic regression analysis showed that the dose of TMP and the presence of renal dysfunction increased the incidence of electrolyte disorders with an odds ratio of 2.35 and 80.29, respectively.
Conclusion Electrolyte disorders, particularly hyperkalemia and hyponatremia can be detected in patients given TMP-SMX. These disorders are more frequent in patients given high doses, but can also be detected after low-dose administration. Renal dysfunction accelerates the incidence of electrolyte disorders induced by TMP-SMX.
(Internal Medicine 42: 665-669, 2003)

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Objective To investigate whether the combined therapy according to the guideline proposed by American Thoracic Society (ATS) and Japanese Society for Tuberculosis (JST) is clinically appropriate for Mycobacterium avium complex (MAC) pulmonary disease.
Patients Seventy-one patients in whom MAC pulmonary disease was diagnosed at Kawasaki Medical School and our associated ten hospitals were prospectively studied.
Results Seventy-one patients with Mycobacterium avium complex (MAC) pulmonary disease were 27 males and 44 females with a mean age of 64.4 ±10.2 years old. Patients received 400 mg/day or 600 mg/day of clarithromycin plus ethambutol, rifampicin, and initial streptomycin for 12 months. Among 71 patients who received more than 12 months of therapy, 41 patients (57.7%) converted their sputum to negative within six months after the initiation of this regimen, 16 of 41 patients (39.0%) relapsed, and 23 of 71 patients (32.4%) obtained clinical improvement on chest X-ray and/or clinical symptoms. The mortality rate had a comparatively good prognosis with a low incidence of 2.8%. Although the species of pathogen (M. avium or M. intracellulare) did not significantly affect the conversion rate or clinical improvement, the infectious form with or without respiratory underlying disease, the characteristics and extent of lesion on chest X-ray, and the dose of clarithromycin significantly influenced the conversion rate or clinical improvement. There were no problems concerning adverse reactions for this regimen.
Conclusion This combined therapy, according to the guideline proposed by ATS and JST, was one of the effective treatments compared to the clinical effect of only antituberculous drugs through this study. However, this combined therapy was unsatisfactory compared to the clinical effect for pulmonary tuberculosis. The development of new companion drugs for MAC pulmonary diseases is needed.
(Internal Medicine 42: 670-675, 2003)

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Objective To determine whether the guidelines for community-acquired pneumonia published by the Infectious Disease Society of America (IDSA) and the Japanese Respiratory Society (JRS) are applicable to stratifying the mortality risk of patients visiting a tertiary emergency center in Japan.
Methods Patients were categorized into three risk groups (low, intermediate and high) based on the IDSA guidelines and three severity groups (mild, moderate and severe) using the JRS guidelines. The mortality rates among each set of groups were then compared using 30-day follow-up data.
Patients Ninety-seven consecutive patients with pneumonia who visited the emergency room and were admitted to our hospital were retrospectively identified.
Results Based on the IDSA guidelines, the patients were categorized into a high, intermediate, or low-risk group (38.1%, 51.5% and 10.3%, respectively). Cumulative mortality rates were 18.9% for the high-risk group and 4.0% for the moderate-risk group (p=0.02); no deaths occurred in the low-risk group. Based on the JRS guidelines, the patients were also classified into a severe, moderate, or the mild-severity group (69.1%, 25.8% and 5.2%, respectively). The mortality rate was 13.4% in the severe group, whereas no deaths occurred in the moderate or mild-severity groups.
Conclusion The IDSA and JRS guidelines allow short-term mortality risks to be recognized at a tertiary emergency center in Japan.
(Internal Medicine 42: 676-680, 2003)

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Objective Repeated nocturnal hypoxia is implicated in the pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS). We hypothesized that circulating vascular endothelial growth factor (VEGF) levels are affected by nocturnal hypoxemia in patients with OSAS.
Methods We examined the serum VEGF levels in patients with OSAS and in control subjects. We also tested the effects of oxygen or air administration on the subjects' VEGF levels.
Patients and Materials Twenty-four OSAS patients (mean age 54.2±3.6 years) and 24 age-matched control subjects (53.2±3.6 years). Their serum samples were tested.
Results Serum VEGF levels at 8 : 00 AM were significantly higher in OSAS patients than in controls (p<0.01). VEGF levels decreased from 515±31 (pg/ml) to 178±16 (pg/m) (p<0.01) in OSAS patients whose nocturnal hypoxemia was found to be improved by administration of 2 l/min of oxygen during the night. However, the administration of compressed air affected neither the VEGF level nor nocturnal oxygen desaturation in OSAS patients.
Conclusion These results indicate that circulating VEGF levels are elevated in OSAS patients, primarily due to nocturnal hypoxemia.
(Internal Medicine 42: 681-685, 2003)

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Objective To confirm the clinical usefulness of [¹²³I]metaiodobenzylguanidine ([¹²³I]MIBG) myocardial scintigraphy in the antemortem differential diagnosis between patients with Alzheimer's disease (AD) and those with dementia with Lewy bodies (DLB).
Patients and Methods We compared cardiac [¹²³I]MIBG uptake in 10 patients with AD with that in 10 patients with DLB. We selected the patients with AD or DLB by using stringent diagnostic criteria that combined commonly used clinical criteria with tau protein levels in cerebrospinal fluid and radiographical examinations.
Results The heart to mediastinum ratio of [¹²³I]MIBG uptake in all the patients with DLB was significantly lower than that in the patients with AD (p<0.01).
Conclusion This study confirms that [¹²³I]MIBG myocardial scintigraphy is useful in the antemortem differential diagnosis of AD and DLB.
(Internal Medicine 42: 686-690, 2003)

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A 47-year-old woman had idiopathic granulomatous gastritis characterized by serpiginous aphthoid ulcer with satellite aphthous ulcers at the antrum to angulus with noncaseating epithelioid granulomas including giant cells in the gastric mucosa. No definite etiologic factors could be detected; systemic sarcoidosis, Crohn's disease, infections (tuberculosis, syphilis and fungus), neoplasm, and foreign body reaction were excluded by additional investigations. However, the patient was found to be infected with H. pylori. Despite the success of H. pylori-eradication, the granulomatous lesion took a long time to heal for at least 17 months or more. The relation between granulomatous gastritis and H. pylori was discussed. There was no apparent evidence of granuloma in the other organs during clinical and follow-up studies for over three years.
(Internal Medicine 42: 691-695, 2003)

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A 59-year-old woman was diagnosed with incomplete type Behçet's syndrome in 1994. The patient was hospitalized with pharyngitis and fever in August 2000, and was treated using non-steroidal anti-inflammatory drugs (NSAIDs). Symptoms improved and she was discharged. After only 3 weeks, she reported swallowing disturbance due to retrosternal pain. Esophagoscopy revealed multiple shallow oval ulcerations in the middle esophagus. Colonoscopy revealed aphthous lesions in the rectum. Prednisolone (0.5 mg/kg) was initiated for treatment of esophageal involvement. Symptoms gradually improved and subsequent esophagoscopy revealed complete healing of esophageal ulcerations.
(Internal Medicine 42: 696-699, 2003)

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A 62-year-old woman had acromegaly and developed congestive heart failure with cardiomyopathy, mitral regurgitation due to chordae rupture, coronary artery disease and sick sinus syndrome. Since congestive heart failure was resistant to medical therapy, mitral valve replacement, aortocoronary bypass surgery and implantation of permanent pacemaker were performed one month after her admission. Although acromegalic patients with cardiomyopathy are usually resistant to therapy, we successfully treated the patient by the surgeries. It appears that all these diseases resulted from an elevated plasma concentration of growth hormone. Untreated acromegaly for more than ten years may contribute to multiple complications such as those in the present patient.
(Internal Medicine 42: 700-703, 2003)

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A 48-year-old woman with transient thyrotoxicosis, having a slightly high thyroidal ^99mTc uptake (3.9% at 20 m) or radioactive iodine uptake (RAIU) (17.3% at 4 hour) and subacute thyroiditis (SAT)-like symptoms, signs and histological diagnosis (extensive cellular destruction and granulomatous inflammatory change), showed positive TRAb (59.9%) and TSAb (194%) activity. The high levels of TRAb and slightly high RAIU were still observed after one month of prednisolone treatment. Nine months later, the TRAb and TSAb levels finally normalized and her thyroid function has remained normal since then. We suspect that the slightly high RAIU were due to the presence of both the TRAb and the TSAb and the course of this case might mimic neonatal Graves' disease.
(Internal Medicine 42: 704-709, 2003)

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A 51-year-old woman presented with flexion contractures of the legs. Physical examination showed decreased passive movements of the bilateral hip and knee joints without muscle spasms or neurological abnormalities. Laboratory evaluation showed no response of ACTH or plasma cortisol to stimulation with CRH or insulin. Diagnosis of isolated adrenocorticotropic hormone deficiency was made. The patient was started on prednisolone 5 mg daily, and flexion contractures of the legs rapidly disappeared. Although the musculoskeletal manifestation of this patient is similar to that of stiff-person syndrome, flexion contracture of the legs associated with adrenocortical insufficiency seems to be a separate disease entity from stiff-person syndrome.
(Internal Medicine 42: 710-713, 2003)

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We report 7 cases of adrenal tumors with concurrent increases in cortisol and aldosterone secretion, which we have examined over the last 2 years. We also present the pathology of excised specimens based on immunohistochemical staining, as well as endocrinological findings. Four patients were male and 3 female; 6 were first diagnosed as suffering from primary aldosteronism (PA) and one as adrenal preclinical Cushing's syndrome (PCS). Plasma cortisol concentrations at midnight were greater than 2 μg/dl in 6 patients and more than 1 μg/dl in the dexamethasone suppression test with an 8 mg dose in all patients. This indicates that dexamethasone did not inhibit the secretion of cortisol. No increase in renin activity was seen in the renin-producing irritable test in any of the patients. Immunohistochemical staining showed not only the presence of aldosteronoma, but also the expression of P-450c17, which is involved in the biosynthesis of cortisol, indicating that both cortisol and aldosterone were concurrently synthesized. With regard to the function of adrenal tumors, we suggest that concurrent .secretion of cortisol and aldosterone are not rare and that immunohistochemical examination of the surgicallyextirpated specimen is important for diagnosis.
(Internal Medicine 42: 714-718, 2003)

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A 59-year-old man was referred for evaluation of nephrotic syndrome. The patient was diagnosed to have rheumatoid arthritis and had been treated for 10 years. Renal biopsy showed mesangial proliferation with small nodular formations, which were determined as fibrillary deposits (average diameter: 20 nm) by electromicroscopy. Congo-red stain was negative. The laboratory findings revealed hypocomplementemia and lambda type of Bence-Jones protein in urine without other systemic diseases including multiple myeloma. Immunosuppressive therapy did not attenuate the nephrotic-range proteinuria. Such a case of fibrillary glomerulonephritis with hypocomplementemia is rare.
(Internal Medicine 42: 719-722, 2003)

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A 64-year-old woman with periodontal disease was admitted because of fever, right chest pain, and bloody sputum. Her chest radiograph revealed a nodular shadow in the right middle lung fields. From the results of a needle aspiration biopsy, she was diagnosed with a lung abscess due to Actinomyces odontolyticus (A. odontolyticus) and Streptococcus spp. The patient improved quickly with antibiotics. To our knowledge, only nine cases of pulmonary infection due to A. odontolyticus have been reported, and we report the first case in Japan. Although respiratory disease caused by A. odontolyticus is rare, the association of this organism should be considered even in healthy individuals.
(Internal Medicine 42: 723-725, 2003)

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Two patients showing abnormal fluorine-18-fluorodeoxyglucose (FDG) uptake due to Mycobacterium avium complex (MAC) infection are presented. Intense focal FDG uptake in the lung field could have been caused by an infectious disease such as MAC. This should be considered as a possibility when FDG whole-body scans of patients with pulmonary nodules are interpreted. To our knowledge, this is the first description of an FDG-positron emission tomography (FDG-PET) image of MAC infection of the lung.
(Internal Medicine 42: 726-729, 2003)

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A 66-year-old man with hepatocellular carcinoma (HCC) showed marked thrombocytosis (110.7×l0⁴/μl). Bone marrow (BM) aspirates demonstrated an increase of mature megakaryocytes (MgK). The serum thrombopoietin (TPO) level was increased to about 100-fold that of the normal level in the terminal stage. However, the platelet count gradually decreased to 13.5×10⁴/μl. The autopsy specimen revealed normoplastic BM with decreased MgK, mainly consisting of the immature type, and it was negative for tumor cells. Liver specimen showed markedly fatty metamorphosis. Immunohistochemical staining of TPO demonstrated that hepatocytes were weakly stained and HCC cells strongly stained, suggesting TPO-producing HCC.
(Internal Medicine 42: 730-734, 2003)

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Castleman's disease is a rare and poorly understood condition involving lymph nodes at various sites, predominantly in the mediastinum. Individuals with this disease often present with lymphadenopathy and general symptoms suggestive of lymphomatous disease, and they are at risk of developing malignant lymphoma. It is thus important to distinguish Castleman's disease from other lymphoproliferative disorders. ⁶⁷Ga scintigraphy is a noninvasive and practical diagnostic tool for the investigation of patients with lymphoproliferative disorders. However, the value of this technique for the diagnosis of Castleman's disease is not clear. Here, we describe five consecutive patients with various types of Castleman's disease and show that none of these individuals exhibited ⁶⁷Ga uptake. Our results suggest the potential value of ⁶⁷Ga scintigraphy in both the diagnosis and management of Castleman's disease.
(Internal Medicine 42: 735-739, 2003)

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We describe a patient with chronic myelogenous leukemia (CML) who developed extramedullary blast crisis, and was successfully treated with imatinib mesylate (STI571). A 42-year-old man had been diagnosed with chronic phase Philadelphia chromosome (Ph)-positive CML and treated with interferon-α. He achieved partial cytogenetic response. Two years after the diagnosis, he presented with superficial lymphadenopathy in his neck and supraclavicular regions. Lymph node biopsy disclosed the infiltration of myeloblasts. Although the patient's bone marrow was without increasing blasts at that time, cytogenetic response was no longer observed. STI571 at a dose of 600 mg/day was initiated, and led to the complete disappearance of lymphadenopathy within a month and also to major cytogenetic response in the bone marrow (90% Ph-negative metaphases). Subsequently, the patient underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor and was in complete remission without evidence of extramedullary disease 12 months after transplantation.
(Internal Medicine 42: 740-742, 2003)

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A 45-year-old Japanese woman with multiple sclerosis (MS) manifested hypersomnia in a relapse of MS. Magnetic resonance imaging revealed new bilateral hypothalamic lesions, and the hypocretin-1 level in the cerebrospinal fluid (CSF) was significantly low. Methylprednisolone pulse treatment successfully resolved the hypersomnia and the left hypothalamic lesion, and it normalized the hypocretin-1 level in the CSF. These findings suggest that the hypothalamic hypocretin (orexin) system may be crucial to maintaining the arousal level and that lesions in the system can cause hypersomnia in MS.
(Internal Medicine 42: 743-745, 2003)

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In a patient with acute cardioembolic stroke, ultrasonographic studies demonstrated the disappearance of an oscillating intraluminal thrombus lodged at the carotid bifurcation. Following the commencement of immediate anticoagulation, the thrombus completely dissolved over two weeks without further deterioration in the patient's symptoms. Neurosonographic studies are useful for the detection and follow-up of an intraluminal thrombus in acute stroke patients undergoing anticoagulant therapy.
(Internal Medicine 42: 746-749, 2003)

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A case of cyclosporin A (Cys A)-induced posterior encephalopathy developed into persistent abulia despite rapid and marked improvement of abnormal T2- and FLAIR MRI hyperintense regions. Diffusion-weighted MRI signal intensity was also high at the onset. This change is atypical in Cys A-induced encephalopathy and was thought to predict poor recovery from the encephalopathy. Persistent abulia was probably due to marked hypoperfusion in the whole cortex including bilateral frontal lobes and basal ganglia as detected by SPECT. Apart from the breakdown of the blood-brain barrier, direct toxicity of Cys A to the brain may play a role in the pathogenesis of chronic, irreversible encephalopathy.
(Internal Medicine 42: 750-755, 2003)

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We describe here an extremely rare case of primary amyloidosis which presented moderate pleural effusion and high fever. A 71-year-old man was admitted to our hospital because of exertional dyspnea, fatigue and fever. A chest X-ray showed right-sided moderate pleural effusion. A thoracocentesis revealed an exudative pleural effusion. Cytology and cultures of the effusion were negative. External drainage failed to control the effusion. To determine the etiology of the effusion and fever, bronchoscopy was performed. Biopsies of the tracheal wall showed amyloid deposition. The pleural effusion might have been due to the inflammation and the disturbed lymphatic drainage caused by the amyloid deposition. Treatment with melphalan (6 mg) and prednisolone (35 mg) for 4 days every 6 weeks decreased the fever and alleviated his symptoms.
(Internal Medicine 42: 756-760, 2003)

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We describe a 17-year-old woman with a family history of FMF who suffered from recurrent fever accompanied by pains in the left chest and abdomen. During a five-year period she experienced attacks about once every six months. The metaraminol provocative test was positive. Genomic DNA extracted from peripheral blood lymphocytes from both her and her parents were analyzed by polymerase chain reaction (PCR), followed by cycle sequencing. We detected a mutation (ATG to ATA) in codon 694 in exon 10 of the FMF gene, MEFV, that resulted in a substitution of isoleucine for methionine (M694I) in both her and her father. This is the first Japanese case of FMF with a mutation in MEFV identified in the family history.
(Internal Medicine 42: 761-764, 2003)

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