Aging is often seen as disadvantageous in human history. However, longevity reduces medical costs of the whole life compared with that of short life. Therefore, in order to reduce medical cost, we have to take care of the elderly in order to promote health and longevity. Health problems in the elderly should be solved by both medical and elderly care facilities. However, few studies have analyzed the care problems of the elderly. In this review, we describe the recent methods of care for the elderly.
(Internal Medicine 42: 932-940, 2003)

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Objective The efficacy of thymosin alpha 1 (Tα₁) in patients with chronic hepatitis B still requires confirmation. We, therefore, evaluated the efficacy of therapy in patients with chronic hepatitis B.
Methods Sixteen patients were randomly assigned into one of two groups, treated with O.Smg of Tα₁ (low dose group; n=8) or 1.6 mg Tα₁ (high dose group; n=8), administered six times weekly for two weeks, followed by twice weekly for another 22 weeks. Responders were defined as patients having clearance of hepatitis B e antigen by radioimmunoassay and negativity of hepatitis B virus (HBV)-DNA by branched DNA signal amplification and normalization of serum alanine aminotransferase (ALT) 24 months after initiation of Tα₁ therapy. Transient acute exacerbation was defined as an increase of more than 300 IU/l in serum ALT level during Tα₁ therapy.
Results The response rate was 37.5% (6/16). Tα₁ therapy had a significant effect when, 1) transient acute exacerbation was present (p=0.0029), 2) the serum HBV-DNA level was <100 Meq/ml prior to the commencement of Tα₁ therapy (p=0.0063). The difference between low and high dose groups was not statistically significant (p=0.608).
Conclusion The results of this trial show that: 1) a 24-week course of Tα₁ could be a worthwhile strategy for chronic hepatitis B patients with a serum HBV-DNA level of less than 100 Meq/ml; and 2) patients with a transient acute exacerbation during Tα₁ therapy generally often respond well.
(Internal Medicine 42: 941-946, 2003)

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Objective This study examined the role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in the autoimmune process of bile duct destruction in the early stages of primary biliary cirrhosis (PBC).
Materials and Methods Ten PBC liver samples and five control samples were studied. Immunohistochemical studies of ICAM-1 and LFA-1, and Western blot of ICAM-1 were performed. Immunoelectron microscopy was conducted using inununoglobulin-gold and silver staining. Human ICAM-land LFA-1 peptide nucleic acid probes were used for in situ hybridization.
Results In PBC liver samples, immunohistochemistry showed aberrant ICAM-1 expression on bile duct epithelial plasma membrane and also luminal sites of endothelial plasma membrane of terminal portal venules. Western blot confirmed ICAM-1 protein expression. LFA-1-positive lymphocytes were associated with epithelial cells of septal and interlobular bile ducts. Immunoelectron microscopy localized ICAM-1 on the luminal and basal surfaces as well as on lymphocytes around damaged bile duct epithelial cells, and LFA-1 on lymphocytes around damaged bile ducts. Messenger RNA expression of ICAM-1 was demonstrated in bile ducts, and LFA-1 in lymphocytes around bile ducts.
Conclusion De novo expression of ICAM-1 and LFA-1 at protein and mRNA levels in PBC may imply an inductive role of ICAM-1 through binding with its ligand LFA-1 in the extravasation of activated lymphocytes and lymphocyte-mediated bile duct destruction.
(Internal Medicine 42: 947-954, 2003)

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Objective A synthetic analogue of calcitriol, 22-oxacalcitriol (OCT), strongly suppresses parathyroid hormone (PTH) secretion. This study investigated the influence of OCT on PTH secretion and bone metabolism in 12 hemodialysis patients with secondary hyperparathyroidism.
Methods OCT was intravenously injected after every hemodialysis session (three times weekly) for 22 weeks. The levels of the following parameters were measured: intact PTH, whole PTH, whole PTH/7-84 PTH ratio, adjusted calcium, phosphorus, alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), intact osteocalcin (OC), type I collagen carboxyterminal propeptide, tartrate-resistant acid phosphatase (TRAP), cross-linked C-terminal telopeptides of type I collagen, and interleukin-6.
Patients The subjects were 12 hemodialysis patients (8 men and 4 women) with an intact PTH level of more than 460 pg/ml, a normal serum calcium level, and a serum phosphorus of less than 7 mg/dl.
Results The levels of intact PTH, whole PTH, whole PTH/7-84 PTH ratio, ALP, BAP, OC, and TRAP were significantly decreased after OCT administration, while adjusted calcium was significantly increased. Serum phosphorus and the other parameters showed no significant changes.
Conclusion OCT effectively suppressed the PTH level and bone metabolism parameters in hemodialysis patients with secondary hyperparathyroidism.
(Internal Medicine 42: 955-959, 2003)

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Objective We conducted a large-scale cross-sectional study to assess the prevalence of Chlamydia pneumoniae and clarify the association between seropositivity and risk factors, such as smoking status, physical activity and body mass index in Japanese rural districts.
Methods A total of 1, 063 men and 1, 573 women aged 18-94 years participated in 1999. Serum index values (ID) of IgA and IgG antibodies to C. pneumoniae were measured by ELISA. Index values were categorized as "negative" (ID<1.10), "positive" (ID ?? 1.10) and "high positive" (ID ?? 3.00). Logistic regression analysis was performed to estimate the crude and adjusted odds ratios for C. pneumoniae seropositivity.
Results The overall prevalence of C. pneumoniae IgA seropositivity was 52.5%, and that of IgG was 55.2%. Each seropositivity significantly increased with age. The prevalence among men was significantly higher than in women in C. pneumoniae IgG "high positive" subjects. Compared with never-smokers, the adjusted odds ratio of current smokers was 2.00 (95%CI: 1.45-2.77) for C. pneumoniae IgA seropositivity. The adjusted odds ratio of the higher tertiles of physical activity for C. pneumoniae IgG seropositivity was 1.42 (1.12-1.80) compared with the lower tertiles. In "high positive" subjects, smoking was associated with both immune complexes.
Conclusion We confirmed a high prevalence of C. pneumoniae seropositivity among healthy Japanese adults. The results indicated that smoking and high physical activity were associated with C. pneumoniae infection.
(Internal Medicine 42: 960-966, 2003)

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A 15-year-old girl presented with acute hepatic failure showing ascites and hepatic encephalopathy, accompanied by hemolytic anemia. She was diagnosed as having fulminant Wilson's disease (FWD). Plasma exchange (PE), continuous hemodiafiltration (CHDF) and D-penicillamine administration were started immediately. Copper [24, 000 μg] was removed by PE and CHDF over three days, which relieved the jaundice and the consciousness disorder. A successful liver transplant followed. FWD progresses rapidly and often liver transplantation is the only possible therapy. In this case, PE and CHDF were an effective therapy bridge until liver transplantation.
(Internal Medicine 42: 967-970, 2003)

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A man with a 20-year history of recurrent irondeficiency anemia complicated by Helicobacter pylori-positive Ménétrier's disease was observed over a 10-year clinical course, during which time he was successfully treated for the anemia and a gastric Helicobacter pylori (H. pylori) infection through eradication. Considering the satisfactory therapeutic results in this case, we performed eradication therapy on another H. pylori-positive atrophic gastritis case with a 24-year history of irondeficiency anemia of unknown etiology, and again, complete remission was obtained. The clinical evidence from these two cases suggests that the gastric H. pylori infection was deeply involved in the pathogeneses of the iron-deficiency anemia. We believe that these case reports will provide useful information on H. pyloriinvolved pathology in the fields of hematology and gastroenterology.
(Internal Medicine 42: 971-977, 2003)

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A 40-year-old woman was admitted with altered consciousness and hyperammonemia after she had delivered her first baby. DNA analysis of the citrin gene and enzymatic assay of argininosuccinate synthetase in the liver led to a diagnosis of adult-onset type II citrullineniia (CTLN2). She was also found to have hepatocellular carcinoma (HCC) and underwent palliative surgery consisting of partial liver section of the HCC. Delivery may be a trigger for the development of CTLN2, while certain pathologic conditions associated with citrin gene abnormality are likely to induce hepatocellular carcinoma in patients with this disorder.
(Internal Medicine 42: 978-982, 2003)

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We report a primigravida woman with acute myocardial infarction caused by coronary artery spasm induced by intravenous administration of methyl ergometrine maleate just after delivery. Despite the frequent usage of ergot derivatives to promote uterine contractions, cardiac complications related to this drug are rare. Myocardial infarction may be overlooked in young women in the early postpartum period. Careful monitoring and prompt evaluation should be performed when this drug is administered for obstetrical purposes.
(Internal Medicine 42: 983-986, 2003)

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Arteriovenous fistula of internal thoracic vessels is rare. We report a case of a 77-year-old woman with a fistula between the left internal thoracic artery and vein after a mediastinal needle biopsy through the anterior chest wall. The incidence of internal thoracic arteriovenous fistulas seems to be increasing because the number of cardiac and thoracic surgical procedures is increasing. It is important to consider an internal thoracic arteriovenous fistula as part of the differential diagnosis in patients with continuous murmur in the parasternal area.
(Internal Medicine 42: 987-990, 2003)

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A 52-year-old man presented with vomiting, general fatigue and hyponatremia. His symptoms and signs were consistent with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Endocrine studies revealed hypopituitarism and administration of hydrocortisone resulted in a marked polyuria. The patient was diagnosed as masked diabetes insipidus. The lymphocytic hypophysitis was also diagnosed on the basis of MRI findings and anti-pituitary antibody. Six months later, these abnormalities disappeared. Diabetes insipidus may exist in a case of hyponatremia due to contrastive SIADH. Such patients may recover spontaneously and careful follow-up is required, avoiding a long-term treatment by monotonous continuation of hormonal replacement.
(Internal Medicine 42: 991-995, 2003)

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A 34-year-old man was diagnosed with clinical Gushing's syndrome based on circadian fluctuation of plasma adrenocorticotropin and serum cortisol levels and Liddle's-method. The presence of ectopic adrenocorticotropin production was suspected. Urine 5-hydroxyindoleaceturic acid level was high. Chest computedtomography scan revealed a mass in the right upper lung. 111In-pentetrotide scintigraphy demonstrated marked accumulation in the right upper lung. We suspected an adrenocorticotropin-producing bronchial carcinoid. Plasma adrenocorticotropin and serum cortisol levels decreased immediately following resection of the tumor. Adrenocorticotropin production by tumor cells was confirmed by immunohistochemistry. This case indicates ¹¹¹In-pentetrotide scintigraphy could be successfully used to identify and localize ectopic adrenocorticotropinproducing bronchial carcinoid.
(Internal Medicine 42: 996-1005, 2003)

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A 42 year-old man with lumbago and fever had hydronephrosis due to a mass surrounding the abdominal aorta, associated with pachymeningitis and a suprasellar tumor. He was given a diagnosis of multifocal fibrosclerosis, involving both retroperitoneal and intracranial fibrosis. He responded to treatment with corticosteroid and cyclophosphamide. The intracranial lesions seemed to be rare, but important manifestations of the systemic disease, and were clearly visualized by magnetic resonance imaging. The phenotype of the infiltrated lymphocytes was CD4⁺, supporting the hypothesis that autoimmunity was involved pathogenetically. We propose a comprehensive category termed "inflammatory fibrotic disease" including both systemic and localized diseases.
(Internal Medicine 42: 1006-1010, 2003)

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Although pheochromocytoma in a patient with endstage renal disease (ESRD) is considered extremely rare, we recently encountered 4 ESRD patients with pheochromocytoma. Three were symptomatic, and in the fourth patient the tumor was discovered as an adrenal incidentaloma. Plasma catecholamine levels were significantly increased in two patients. In each case, ¹³¹I-MIBG scintigraphy showed accumulation of the radionuclide in the adrenal tumor, which was identified by MRI or CT scanning, and adrenalectomy was conducted without serious complications. Although paroxysmal hypertension is a common symptom in patients with ESRD, pheochromocytoma must be eliminated by careful evaluation.
(Internal Medicine 42: 1011-1015, 2003)

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A 19-year-old man was admitted due to acute respiratory failure. He had started cigarette smoking (CS) about three weeks prior to onset. Multiple nodular shadows and patchy infiltrations were found on chest computed tomography. His respiratory state improved promptly by intravenous methylprednisolone. He resumed CS soon after discharge without any symptoms. We suspected CS-induced acute eosinophilic pneumonia and performed broncho-alveolar lavage (BAL) about one month after onset. The proportion of eosinophils in BAL fluid was 72%. A second BAL was performed about 18 months after onset and BAL fluid included no eosinophils, despite the fact that he had continued CS.
(Internal Medicine 42: 1016-1021, 2003)

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Acute respiratory distress syndrome (ARDS) developed following intravenous gemcitabine monotherapy in a 75-year-old man with non-small cell lung cancer. The total dose of gemcitabine was 1, 500 mg, and the latent period from starting gemcitabine to pulmonary toxicity was three days. The chest radiographs and high resolution computed tomographic scan revealed bilateral groundglass opacity. He died on the fourteenth post-chemotherapeutic day due to respiratory failure. Postmortem examination of the lung revealed mixed exudative and fibrotic stages of diffuse alveolar damage. Pulmonary toxicity from gemcitabine can be acute and fatal.
(Internal Medicine 42: 1022-1025, 2003)

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A 50-year-old Japanese man with Grave's disease had been taking propylthiouracil (PTU) for 10 years prior to the diagnosis of pneumonia. He noticed dyspnea on exertion and had a dry cough for at least 2 years and then suddenly developed high fever and dyspnea at rest. Clinical symptoms, chest radiographs, chest computed tomography and lung function revealed interstitial pneumonia. The symptoms were completely resolved after withdrawal of PTU, and consequently he was diagnosed with PTU-induced interstitial pneumonia. He also showed moderate myeloperoxidase (MPO)- antineutrophil cytoplasmic antibody (ANCA) positivity without any signs of vasculitis before as well as after PTU withdrawal. Although PTU-induced interstitial pneumonia is quite rare, with only 3 cases, including the present patient, so far reported, respiratory involvement should be considered in patients treated with PTU.
(Internal Medicine 42: 1026-1030, 2003)

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After chemotherapy and radiotherapy for non-Hodgkin's lymphoma during a one-year period, a 66-year-old man developed synchronous triple lung cancers in both lungs. Of the three resected tumors, one was advanced large cell carcinoma with neuroendocrine morphology, and the other two were early squamous cell carcinoma without lymph node metastasis. Although he received repeated chemotherapy for lung cancer, the patient died of hepatic failure due to multiple liver metastases. Autopsy revealed disseminated metastasis of the large cell carcinoma with neuroendocrine morphology throughout the entire body, but no recurrence of malignant lymphoma or squamous cell carcinoma was found. To our knowledge, this is the first report of triple lung cancers occurring after treatment for malignant lymphoma.
(Internal Medicine 42: 1031-1034, 2003)

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Familial occurrence of inclusion body myositis is extremely rare, and only a few cases in Western countries have been reported. In these reports, a strong association of this disease with DR3 (DRB 1*0301/0302) and the efficacy of immunosuppressants suggested that an immune pathomechanism is involved in the disease. We, for the first time, report two Japanese sisters who suffered myopathy clinicopathologically similar to inclusion body myositis. One sister received corticosteroid and azathioprine and the therapy relieved dysphagia. Both of our patients had DR15(2)/4 (DRB1*1502/0405), suggesting a distinct genetic association with the disease in the Japanese population.
(Internal Medicine 42: 1035-1038, 2003)

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We describe a unique patient whose clinical and laboratory findings fulfill diagnostic criteria of adult onset Still's disease and at the same time, this case was complicated by aseptic meningitis with neutrophilic pleocytosis in cerebrospinal fluid, as well as sensorineural hearing loss. The symptoms of the patient improved greatly with prednisolone therapy. Some studies in the literature suggest that this disease may lead to aseptic meningitis with neutrophilic pleocytosis.
(Internal Medicine 42: 1039-1041, 2003)

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The etiopathogenesis of extrahepatic manifestations including vasculitis in the context of HCV infection is still unknown. We report a case with lethal extrahepatic manifestations due to chronic hepatitis C virus (HCV) infection. The patient presented leukocytoclastic vasculitis, sensorimotor neuropathy and membranoproliferative glomerulonephritis with positive rheumatoid factor but lacked cryoglobulin. Hypocomplementaemia and deposition of IgM and C3 in the vascular lesion and glomeruli suggested that immune complex disease played a role in the pathogenesis of extrahepatic manifestations independent of cryoglobulin. Although HCV was successfully eliminated by treatment with interferon α, she died of cryptococcal infection.
(Internal Medicine 42: 1042-1046, 2003)

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A 68-year-old healthy man was admitted because of liver abscess and aeromonas bacteremia accompanied by pulmonary embolism. Aeromonas sobria was isolated from blood. Coagulation parameters were normal and a lower limb venogram showed no evidence of thrombosis. Septic embolism originating from the liver abscess was considered as the possible cause of pulmonary embolism. The patient was successfully treated with antibiotics.
(Internal Medicine 42: 1047-1049, 2003)

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