Acute glomerulonephritis (AGN) is a representative disease of acute nephritic syndrome characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension. The prototype of AGN is acute poststreptococcal glomerulonephritis (APSGN). "Nephritogenic streptococci" are defined as organisms that are cultured from a patient who develops AGN. Although only a limited number of M-types of streptococci have been recognized as "nephritogenic streptococci", all M-types of streptococci may have nephritogenic potential because the genes for major putative nephritogenic antigens such as SPEB and NAPlr are found to be present in all group A streptococci thus far examined. Pathogenic mechanisms for APSGN involving both humoral and cell-mediated immunity have been recently proposed. The role of humoral immunity is presumed to be mediated by the in situ formation of nephritogenic streptococcal antigen-antibody complexes and circulating immune complexes. While in the cellular immune component a role for delayed-type hypersensitivity has been suggested to contribute to the pathogenesis of APSGN.
(Internal Medicine 39: 687-694, 2000)

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Strongyloidiasis is an intestinal parasitic disease caused by Strongyloides stercoralis. Basically, detecting larvae of S. stercoralis in feces makes definitive diagnosis. The ordinary agar plate culture method developed at our department is much simpler to handle and much more sensitive than the conventional filter paper culture method. It is considered to be the most useful method in the diagnosis of Strongyloidiasis and in evaluation of the eradicating effect. Among chemotherapeutic agents, thiabendazole representing the benzimidazole compounds is most effective. However, it has a problem in safety, since its adverse effects and liver dysfunction occur with a high incidence, and it can be severe. Regarding the effects of mebendazole, albendazole and ivermectin, a study was conducted which included many patients. A high incidence of liver dysfunction was observed with mebendazole, and eradicating effect was not sufficient with albendazole. Ivermectin is different from benzimidazole compounds in a pharmacokinetic profile. However, ivermectin showed a strong anthelmintic effect with the least toxicity. We therefore consider ivermectin is the most useful drug for the treatment of Strongyloidiasis.
(Internal Medicine 39: 695-700, 2000)

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Objective In this study the sensitivity and specificity of immunochemical tests for colorectal neoplasia were evaluated in retrospective and prospective studies.
Methods Four types of fecal blood tests - a chemical test (Hemoccult II) and three different immunochemical tests including a test which detects hemoglobin and transferrinwere performed in the retrospective study. In the prospective study the test for hemoglobin and transferrin was used for all patients that underwent total colonoscopy.
Patients One hundred seven patients with colorectal neoplasia, 57 with gastroduodenal bleeding, and 62 with normal digestive tracts were examined retrospectively. One thousand two hundred and ninety-eight nonspecifically symptomatic patients whose endoscopic examination was negative for hemorrhagic lesions in the upper digestive tract were examined prospectively.
Results In the retrospective study, sensitivities for the detection of colorectal cancers and adenomas with diameters ?? 10 mm using the tests which detect hemoglobin and transferrin were 98% and 89%, respectively. These were the highest sensitivity among the four tests. The specificity of this test was 97%, which was higher than that of the Hemoccult II test. In the prospective study, the sensitivities of the tests for hemoglobin and transferrin for the detection of colorectal cancers and adenomas with diameters ?? 10 mm were 79% and 33%, respectively. The specificity was 95%.
Conclusions The test for hemoglobin and transferrin showed the highest sensitivity and specificity for colorectal neoplasia in the retrospective study. The sensitivity and specificity of this test were not so high in the prospective study, but they may be clinically applicable in the evaluation of patients with various nonspecific symptoms.
(Internal Medicine 39: 701-706, 2000)

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Objective In this prospective, non-controlled observational study, we evaluated the middle- to long-term results of placement of inferior vena cava (IVC) filter devices in Japanese patients.
Methods and results In 42 Japanese patients with deep vein thrombosis (DVT) or pulmonary thromboembolism (PTE) who underwent percutaneous insertion of IVC filters, follow-up examinations at fixed intervals of 2 years were performed, and the data was evaluated including complications. There were no fatal complications during IVC filter implantation. About 5% of patients with an inserted IVC filter developed symptomatic PTE, another 5% developed asymptomatic PTE. The trapped thrombus was demonstrated in about 22% of the inserted IVC filters. Lower rates of PTE development, occlusion of IVC, and captured thrombus were found in the cases where concurrent use of anticoagulation therapy with filters was used. Trapped thrombi were found in half of IVC filters inserted prophylactically for proximal femoral venous thrombosis.
Conclusion These experiences with IVC filters suggest that they are safe and effective for the prevention of PTE in the Japanese population.
(Internal Medicine 39: 707-714, 2000)

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Objective The diagnosis of amyloidosis still relies on biopsy, but there has been a growing demand for the development of a specific noninvasive diagnostic technique. Hepatocyte growth factor (HGF) acts on a variety of epithelial cells in multiple ways and is predominantly produced by mesenchymal cells and macrophages. In the present study, we measured the serum HGF level in patients with amyloidosis and investigated its usefulness for the diagnosis of this disease.
Methods The subjects were 18 patients diagnosed as having amyloidosis by biopsy. We also measured serum HGF in 47 patients with chronic glomerulonephritis, 32 patients on hemodialysis, and 24 healthy volunteers. The serum HGF level was measured using an HGF ELISA kit.
Results The serum HGF level of patients with amyloidosis was significantly increased compared with that of healthy volunteers, patients with chronic glomerulonephritis, and hemodialysis patients (2.26±2.73 ng/ml versus 0.20±0.04 ng/ml, 0.23±0.08 ng/ml, and 0.18±0.07 ng/ml respectively, p<0.0001). There was no significant difference between amyloid light-chain and amyloid A amyloidosis, but the serum HGF level of amyloidosis patients who died within 1 year of measurement was significantly higher than that of patients who lived for more than 1 year (2.83±2.85 ng/ml versus 0.49±0.26 ng/ml, p<0.01).
Conclusions The serum HGF level was significantly elevated in both amyloid light-chain and amyloid A amyloidosis and was a very useful indicator of suspected amyloidosis as well as a potential prognostic indicator. The serum HGF level may become a useful indicator for diagnosing amyloidosis.
(Internal Medicine 39: 715-719, 2000)

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Objective To clarify attitudes toward smoking, and views on smoking intervention among medical students, as well as to teach them the harmful effects of smoking.
Subjects and Methods We carried out an anonymous questionnaire among 2nd and 5th year Japanese medical students and 1, 137 of them responded.
Results Smoking prevalence was 25.1% in men and 8.8% in women in the 2nd year and 43.1% and 9.3%, respectively, in the 5th year. Most respondents thought smoking is harmful to health, but smokers were more likely to think it is not so harmful. In both groups, 97% of the respondents knew lung cancer was related to smoking. Apart from this, knowledge of smoking-related diseases (pulmonary emphysema, coronary heart disease, peptic ulcer, and neonatal death) increased by the 5th year but the rates of recognition were generally less than 50%. Many of them learned about the deleterious effects mainly at places other than medical class (80.2% in the 2nd, 44.9% in the 5th year). About 90% intended to perform smoking intervention in the future, but only one-third were actively interested. More than 70% of the respondents thought that doctors should carry out smoking cessation advice depending on the disease, while the rate of those who thought so irrespective of the disease did not reach 20%. Smokers thought less actively about smoking intervention than current nonsmokers.
Conclusion The awareness of the harmful effects of smoking and intention to perform smoking intervention in the future as doctors seemed unsatisfactory among Japanese medical students.
(Internal Medicine 39: 720-726, 2000)

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Objective Silent or asymptomatic cerebrovascular disease is believed to be an important risk factor for symptomatic stroke and vascular dementia. Although non-specific complaints such as mild to moderate headache and/or dizziness may also be caused by silent stroke, which remains a topic of controversy.
Methods To investigate the relationship between silent brain infarcts and non-specific complaints, we assessed findings on magnetic resonance images using a common protocol in the following three groups of subjects; Group 1: 78 subjects with non-specific complaints, Group 2:47 subjects with vascular risk factors, and Group 3: 75 normal subjects without any subjective complaints or vascular risk factors. In addition to silent stroke, deep white matter lesions on MRI were also evaluated. All subjects were recruited from 12 institutes of the study group located at various parts of Japan.
Results Silent brain infarcts were demonstrated in 44 %, 43%, and 20% of subjects in Groups 1, 2, and 3, respectively. In Group 1, the average number of infarcts per individual who had silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group 2 or 3.5 in Group 3 (p<0.0167). White matter lesions were found in 68%, 49%, and 11% in Groups 1, 2, and 3, respectively, indicating that non-specific complaints are more closely related to deep white matter lesions than to silent infarct lesions. Such white matter lesions were found more frequently in subjects with depressive state than in non-depressed subjects (67% vs. 39%, p=0.0155).
Conclusion The present results suggest that deep white matter lesions, rather than silent brain infarcts, appear to be important in producing headache and/or dizziness of non-specific cause and also to be related to the depressive state.
(Internal Medicine 39: 727-731, 2000)

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Objective More than 80 unrelated, but all Caucasian, patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), originating from various communities around the world, have been molecularly identified. To clarify the occurrence of CADASIL in Orientals, we investigated Japanese families presenting as CADASIL.
Methods We performed the PCR-SSCP and sequence analyses using genomic DNA, isolated from venous blood of participants under informed consent.
Patients We identified two unrelated Japanese families with CADASIL, including 5 affected members through 2 generations.
Results Each of the affected individuals developed recurrent strokes without risk factors resulting in progressive dementia, pseudobulbar palsy, and gait disturbances which started after the fifth decade of life. Although affected individuals had no vascular risk factors, they showed various degrees of narrowing of retinal arteries. Their MRI/CTs showed characteristics of the disease; bilateral small infarcts in the thalamus, basal ganglia, brain stem, and deep white matter in addition to the findings of leukoaraiosis. On SPECT imaging, there was severe hypoperfusion in the cortex as well as in the white matter. Ultrastructural studies revealed an abnormal deposition of granular osmiophilic materials (GOM) within the basal lamina of pericytes in muscular capillaries. On PCR-SSCP and sequence analyses, a heterozygous Argl33Cys mutation was present, in the affected individuals, in the exon 4 of Notch3 gene which is the hot spot region for CADASIL mutations in Caucasian families. None of the non-affected members nor the 50 Japanese normal controls revealed this mutation.
Conclusion Thus, our results confirm that CADASIL is a geographically widespread disorder caused by a Notch3 mutation.
(Internal Medicine 39: 732-737, 2000)

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We describe a case of pulmonary lymphangiomyomatosis (LAM) with chylothorax that developed in a 46-year-old Japanese woman. This patient exhibited clinical symptoms of dyspnea and chest X-ray showed right pleural effusion. Thoracocentesis demonstrated chylous effusion. Chest computed tomography (CT) scan revealed multiple cystic lesions. Subsequent thoracoscopy revealed the chylorrhea from swelled vessels on the diaphragm. The clinical diagnosis, based on histological examinations with biopsy specimens obtained by thoracoscopy, was pulmonary LAM. Although the hormone therapy was not effective, chylous effusion was improved by the pleurodesis. Pulmonary LAM developing chylothorax is rare in Japan.
(Internal Medicine 39: 738-741, 2000)

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A 75-year-old Japanese woman was referred to us because of an anterior mediastinal mass. Crusts and shallow erosions developed 10 months earlier on her upper chest, back, and scalp. Pemphigus foliaceus was diagnosed based on histological examination of skin biopsy specimens and positivity for serum anti-desmoglein 1 antibody by enzymelinked immunosorbent assay. Neurological examination and electromyography ruled out myasthenia gravis. Total thymectomy was performed, and the postoperative pathology studies showed mixed lymphoepithelial thymoma. One year after the resection, the eruption and alopecia improved and the serum anti-desmoglein 1 antibody titer decreased, suggesting a beneficial effect of thymectomy on thymomarelated pemphigus.
(Internal Medicine 39: 742-747, 2000)

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A 30-year-old woman with primary antiphospholipid syndrome (PAPS) presented with cerebral ischemia, thrombocytopenia, anemia and proteinuria. Administration of warfarin potassium, without concomitant corticosteroid administration, significantly improved all of these symptoms along with a decrease in the titers of antiCL-β2-GP-I antibodies and a shortening of prolonged APTT. Therefore, the antiphospholipid antibodies in this patient could have been evoked by vitamin-K-dependent coagulation factors or plasma proteins which are assumed to undergo conformational changes exposing cryptic epitopes. This case report provides clues to the mechanisms underlying the production of antiphospholipid antibodies in patients with PAPS.
(Internal Medicine 39: 748-753, 2000)

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Palmar fasciitis and polyarthritis (PFA) is a rare paraneoplastic rheumatic syndrome characterized by flexion contractures of both hands and thickening of palmar fascia. Several reports have suggested that this syndrome is a tumor-associated autoimmune disorder. We report a 44-year-old Japanese man who presented with flexion contractures of both hands associated with thickening of palmar fascia and polyarthritis. These clinical pictures were suggestive of PFA associated with occult neoplasm. Upper gastrointestinal endoscopic examination revealed advanced gastric cancer. Resection of the cancer resulted in a gradual resolution of palmar fasciitis and polyarthritis. This clinical course suggests an underlying tumor-related immunologic process in this syndrome.
(Internal Medicine 39: 754-757, 2000)

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