Objective To evaluate the usefulness of renal biopsy in the overall management of patients with diabetes mellitus (DM), we examined the relationship between the clinical parameters and histopathological findings of renal biopsy samples.
Methods Renal biopsy specimens were obtained from 109 type 2 diabetic patients with proteinuria. Samples were divided into the following two groups: Diabetic Nephropathy (DN) group (n=80) had typical diabetic lesions without other renal diseases, complication group (n=29) had diabetic lesions with other renal diseases. Furthermore, DN group was subdivided into two subgroups: slow progressive group (SP group, n=32), the level of serum creatinine (s-Cr) was normal at the time of renal biopsy and three years after renal biopsy, and fast progressive group (FP group, n=14), the level of s-Cr was normal at the time of renal biopsy but more than doubled three years after renal biopsy.
Results The level of total protein was significantly lower and HbAlc significantly higher in the DN group than in the Complication group. However, other clinical parameters were not significantly different between the two groups. Urinary protein, systolic and diastolic blood pressure in FP group were significantly higher than in SP group. The percentage of sclerotic glomeruli, the severity of mesangial expansion, tubular injury and cell infiltration were significantly greater in FP than in SP group.
Conclusions Our results indicated that a complete evaluation of renal pathology in DM could not be made by clinical parameters only, and that the progression of DN could be accurately predicted by histopathological evaluation. Therefore, this study emphasizes the importance of renal biopsy in the overall management of patients with DM and/or DN.
(Internal Medicine 40:1077-1084, 2001)

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Objective The mechanism of neutrophil adhesion to the endothelium during the earliest stages of acute inflammation, especially before the induction of adhesion molecules on endothelial cells, remains unknown. We studied the possible involvement of platelets in this process.
Methods Neutrophils were added to human umbilical vein-derived endothelial cells (HUVEC) with or without adherent platelets in the presence or absence of adhesionblocking monoclonal antibodies (mAbs). Adhesion of neutrophils to HUVEC at dynamic flow conditions was assessed using a flow chamber.
Results 1) Thrombin-activated platelets adhered to resting HUVEC at dynamic flow conditions through platelet glycoprotein IIb/IIIa and RGD proteins. 2) Neutrophils tethered to P-selectin induced on thrombin-activated platelets, which were immobilized on HUVEC. 3) Activated neutrophils adhered, via LFA-1, to ICAM-1 on HUVEC. 4) Activated platelets induced interleukin (IL)-8 secretion by HUVEC.
Conclusions Immobilized platelets on the vessel wall with induced P-selectin on the surface biochemically and functionally promote the adhesion of neutrophils to endothelial cells.
(Internal Medicine 40:1085-1092, 2001)

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Objective KL-6 is reported to be excreted from the lung alveolar and bronchial epithelial cells and may be a good marker for monitoring disease activity of interstitial pneumonia. This study was designed to ascertain the clinical significance of serum KL-6 levels in interstitial pneumonia associated with anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis.
Methods Serum KL-6 levels were determined by an enzyme-linked immunosorbent assay.
Patients We examined 20 healthy subjects, 13 patients with perinuclear (myeloperoxidase, MPO) ANCA-related vasculitis and 12 dermatomyositis (DM)/polymyositis (PM) patients as disease controls in this study. Six out of 13 patients with ANCA-related vasculitis had interstitial pneumonia.
Results Serum levels of KL-6 in ANCA-positive patients with interstitial pneumonia were significantly elevated, while they remained as low as those of healthy subjects in ANCA- positive patients without interstitial pneumonia. Similarly, KL-6 levels in sera were higher in 12 dermatomyositis/polymyositis patients with interstitial pneumonia, while they remained low in DM/PM patients without interstitial pneumonia. Moreover, the elevated serum KL-6 level was reduced during the convalescence induced by glucocorticoid therapy and reflected the disease activity of interstitial pneumonia associated with ANCA-related vasculitis.
Conclusion These data suggest that the measurement of serum KL-6 levels may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonia of patients with ANCA-related vasculitis.
(Internal Medicine 40:1093-1097, 2001)

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We report two cases of drug-induced hepatitis refractory to therapy of ursodeoxycholic acid and prednisolone, who were relieved of icterus and pruritus immediately by the oral administration of colestimide. Their liver dysfunction was not improved, by withdrawal of causative drugs or by treatment with prednisolone and ursodeoxycholic acid. Colestimide (3.0 g/day), a strong basic anion-exchange resin, was orally taken before breakfast and evening meal, leading to rapid and complete relief of icterus and pruritus. These cases suggested that colestimide would be useful for patients with cholestasis in drug-induced hepatitis, because this agent has few side effects and it is easy to take.
(Internal Medicine 40: 1098-1103, 2001)

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A 74-year-old woman was admitted to our hospital because of interstitial pneumonia. She had a 14-year history of primary biliary cirrhosis (PBC) diagnosed histologically, with a positive test for anti-mitochondrial antibodies and elevated biliary enzyme activity. She also had a 7-year history of rheumatoid arthritis and a 26-year history of Sjögren's syndrome. Though the symptoms of these complications improved, the interstitial pneumonia deteriorated very quickly and the patient died of respiratory failure due to acute exacerbation of interstitial pneumonia when the activity of PBC decreased. We report this case because it is relatively rare for PBC to be complicated by severe interstitial pneumonia, and it may offer insight into the ethiology of these diseases.
(Intrenal Medicine 40:1104-1108, 2001)

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Polymyositis has been associated with various viral infections, and a spectrum of immune-related diseases may occur with hepatitis C (HCV) infection. Both polymyositis and HCV infection may be accompanied by pulmonary fibrosis. An association between polymyositis and malignancy has also been reported. We report a 55-year-old woman acompanied cryoglobulinemia with HCV infection and manifesting polymyositis, pulmonary fibrosis and malignant lymphoma. Steroid therapy was effective to improve interstitial pneumonia, polymyositis, and liver function.
(Intrenal Medicine 40:1109-1112, 2001)

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We treated a 66-year-old man and a 69-year-old woman with high output cardiac failure due to aortocaval fistula. They underwent nephrectomy 40 and 36 years ago, respectively. They suffered from heart failure for a very long time. However, the etiology was not elucidated until recently. The aortogram revealed massive shunt from the aorta to the inferior vena cava via the right renal artery. Three-dimensional computerized tomography clearly delineated the aortocaval fistula. Surgical closure of the fistula promptly improved heart failure. We stress the importance of history taking concerning nephrectomy and the importance of abdominal auscultation in high output cardiac failure.
(Internal Medicine 40:1113-1116, 2001)

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A 63-year-old man who had experienced cerebral infarction and myocardial infarction at an early age, and repeatedly underwent coronary angioplasty was admitted to our hospital for cardiac evaluation. A coronary angiography showed complex multi-vessel disease with significant stenosis in all major vessels and coronary-artery bypass grafts. A funduscopic examination to evaluate hypertensive and diabetic changes revealed angioid streaks. Therefore, a skin biopsy was performed despite the absence of characteristic skin lesions. Histopathologic examinations revealed calcification and fragmentation of elastic fibers. Therefore, he was finally diagnosed as having pseudoxanthoma elasticum 25 years after the onset of cardiovascular disease.
(Internal Medicine 40: 1117-1120, 2001)

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An 81-year-old man with ischemic dilated cardiomyopathy complained of frequently awakening from sleep due to choking; subsequent polysomnography revealed Cheyne-Stokes respiration (CSR) with sleep apnea. With continuous positive airway pressure (CPAP) through a nasal mask, both the CSR and symptoms disappeared. After 6-12 months, chest X-ray and echocardiographic findings continued to improve without any change in pharmacological treatment. For three years, CPAP had been effective to eliminate CSR during sleep. Long-term CPAP treatment, which is rarely applied for congestive heart failure in Japan, is useful in alleviating the adverse effects of CSR and, thereby, maintaining a good quality of life in these patients.
(Internal Medicine 40:1121-1127, 2001)

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Invasive pulmonary aspergillosis (IPA) is an acute infection of Aspergillus species to the lungs. It generally occurs in immunocompromised hosts, especially with neutropenia. We report a 30-year-old puerperant, who developed IPA from agranulocytosis. She had been treated for threatened labor with ritodrine and cefepime, one of which induced agranulocytosis. After vaginal delivery of twins, pneumonia emerged in the right lower lobe. She was diagnosed to have IPA according to the halo sign on computed tomography (CT) and positive circulating antibody against Aspergillus, and was treated successfully with oral itraconazole followed by surgical resection. It is important to note that IPA might arise in otherwise immunocompetent hosts when neutropenia is long-standing.
(Internal Medicine 40:1128-1131, 2001)

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A 61-year-old man was admitted to our hospital with a 6-month history of productive cough. He, along with his wife, had been involved with Shiitake mushroom cultures for a period of 12 years. On admission, chest radiography showed bilateral fine-nodular shadow and CT scans showed reticulonodular opacities and a ground-glass appearance predominantly in the subpleural area in both lungs, and a mass in the left S6. Resected pathological specimens obtained by left lower lobectomy revealed lung adenosquamous carcinoma (stage IB), interstitial changes accompanied with lymphocyte proliferation and fibrosis, and granuloma with giant cells. Serum precipitins for Shiitake mushroom antigens were positive. The productive cough improved after the hospital admission and occurred again when he returned to work with the Shiitake mushroom production. Therefore, chronic hypersensitivity pneumonitis (HP) caused by Shiitake mushroom spores was diagnosed. Moreover, his wife was found to have HP caused by mushrooms at this time. There are only two previous reports of chronic HP caused by Shiitake mushroom in Japan, and this is the first case of chronic HP associated with lung cancer.
(Internal Medicine 40:1132-1135, 2001)

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We report a patient with an initial relapse of acute promyelocytic leukemia (APL) who achieved a second complete remission (CR) after treatment with arsenic trioxide. The patient, a 66-year-old woman diagnosed as having relapsed APL, received arsenic trioxide intravenously at a dose of 10 mg/day. At day 36, the patient achieved a second CR. The side effects were slight neuralgia and mild skin erythematous changes, which improved following cessation of the drug. Although arsenic trioxide may be effective for relapsed APL, it should be used with caution because of various complications.
(Internal Medicine 40:1136-1139, 2001)

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A 66-year-old man developed progressive painful dysesthesia in his hands and feet over 3 months. His vibration sense was impaired and sensory nerve action potentials of the limbs were not evoked. Biopsy of the peroneal nerve revealed sensory neuropathy. Positive anti-Hu antibody facilitated delineation of a right hilar mass and a metastatic lymph node in thoracic CT scan. He was diagnosed as small cell lung cancer associated with paraneoplastic sensory neuropathy. A complete response was achieved through chemotherapy (carboplatin and etoposide) and subsequent radiation therapy. Notably, his neurological conditions, although not changed during the hospitalization, gradually improved afterwards.
(Internal Medicine 40:1140-1143, 2001)

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks (TIA) and strokes, and vascular dementia with Notch3 gene mutations as the cause of the disease. To date, there are only a few Japanese families ever reported with a mutation in the gene. Here, we report two more Japanese CADASIL families carrying a missense mutation in the Notch3 gene (R141C) with a unique lesion in the corpus callosum. This is the first report of two unrelated Japanese CADASIL families with a R141C mutation in the Notch3 gene. Although the disease is very rare among the Japanese population, our result suggests a possible relationship of this particular mutation (R141C) with the lesions of the corpus callosum.
(Internal Medicine 40: 1144-1148, 2001)

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We report a 63-year-old man with acute disseminated encephalomyelitis (ADEM), initially showing depression for one and a half months but subsequently meningoencephalitis followed by acute-onset myelopathy. Neuroradiological examinations of the brain demonstrated no focal lesion causative for his depression, while cerebrospinal fluid revealed elevated levels of inflammatory cytokines in parallel with disease activity. Because depression is usually a rare initial symptom for patients with ADEM, an increased production of inflammatory cytokines in the central nervous system as well as age-related alterations of immune response might have played an important role in the development of depression in this elderly patient.
(Internal Medicine 40: 1149-1153, 2001)

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A 33-year-old man died following sudden unexpected rupture of a saccular thoracic aortic aneurysm. The patient had been treated as suspicious Behçet's disease (BD) for 9 years, however, the medication was discontinued at the age of 24. Autopsy disclosed multiple aneurysms at the descending thoracic and abdominal aorta. Histopathologically, infiltration of inflammatory cells and destruction with loss of elastic and muscle fibers of the aortic medial wall were seen. Taking the clinical course into account, all the postmortem findings were compatible with those of vasculo-BD. It is important that medical follow-up should be implemented even for childhood-onset patients who do not satisfy criteria of BD.
(Internal Medicine 40: 1154-1157, 2001)

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Cognitive behavioral therapy temporarily alleviated symptoms of a chronic fatigue syndrome patient but the anxiety about rehabilitation into work became stronger and his symptoms worsened. This patient was successfully rehabilitated by fasting therapy. Natural killer cell activity and serum acylcarnitine levels recovered after fasting therapy. Though fasting therapy transiently increased physical and mental subjective symptoms, the patient gained self-confidence by overcoming difficulties after fasting therapy. A combination of cognitive behavioral therapy and fasting therapy is promising as a treatment for chronic fatigue syndrome.
(Internal Medicine 40: 1158-1161, 2001)

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