Object: The aim of this study was to examine the efficacy and the changes of amino acid sequences of the interferon sensitivity-determining region (ISDR) by prolonged interferon (IFN) treatment in patients who have serum hepatitis C virus (HCV)-genotype 1b and a high level of serum HCV-RNA. Methods: Inclusion criteria were biopsy-proven chronic hepatitis, positive HCV-RNA, and an abnormal serum aminotransferase level. Twenty-five patients received 6 MU of natural IFN-α daily for 8 weeks, followed by three times weekly for 40 weeks (1, 056 MU). One patient was withdrawn from the study due to IFN side effects. Therefore, the remaining 24 patients (group 1) were studied the efficacy of IFN administration and changes of ISDR. As a control, 22 patients (group 2) treated with natural IFN-α for 24 weeks for the same period were studied retrospectively. Patients were defined as complete responders (CR) if serum HCV-RNA levels were negative for 6 months after IFN therapy. Results: According to this criterion, CR was 25% (6/24) in group 1 and 9.1% (2/22) in group 2. The normalization rates of alanine aminotransferease (ALT) for six months after termination of IFN was 41% (10/24) in group 1 and 18.2% (4/22) in group 2. Regarding the changes of ISDR in patients with no CR, the change rates of ISDR were 16.7% (3/18) in group 1 and 10% (2/20) in group 2. Conclusion: We concluded that prolonged IFN therapy was effective for patients with HCV-genotype 1b and a high level of serum HCV-RNA.
(Internal Medicine 38: 461-466, 1999)

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Object: The association of obesity and hypertension is well recognized. However, the nature of the relationship between increased body weight and blood pressure (BP) elevation has remained obscure. Patients and Methods: We evaluated BP, insulin sensitivity, insulin clearance and fasting plasma insulin concentration in 19 younger (over 40 years) and in 15 older (more than 40 years) obese subjects to determine the relationships between BP and other factors. Insulin sensitivity and clearance were determined with the euglycemic clamp technique. Results: BP was not associated with insulin sensitivity although most of the subjects showed insulin resistance. In the younger obese group, a positive correlation between diastolic BP and body mass index (kg/m²) was found (r=0.740; p=0.043). In the older obese group, systolic and diastolic BP were correlated with fasting plasma insulin levels (r=0.705; p=0.003; r=0.574; p=0.025, respectively), and systolic BP was inversely correlated with insulin clearance (r=-0.715, p=0.003). Conclusion: These results suggest that insulin is an important factor in BP elevation in older obese subjects, but not in younger obese subjects.
(Internal Medicine 38: 467-471, 1999)

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Object: To study the effects of the intravenous administration of methylcobalamin, an analogue of vitamin B₁₂, for uremic or uremic-diabetic polyneuropathy in patients who are receiving maintenance hemodiaiysis. An ultra-high dose of vitamin B₁₂ has been reported to promote peripheral nerve regeneration in experimental neuropathy. Methods: Nine patients received a 500μg methylcobalamin injection 3 times a week for 6 months. The effects were evaluated using neuropathic pain grading and a nerve conduction study. Results: Serum concentrations of vitamin B₁₂ were ultra-high during treatment due to the lack of urinary excretion. After 6 months of treatment, the patients' pain or paresthesia had lessened, and the ulnar motor and median sensory nerve conduction velocities showed significant improvement. There were no side effects. Conclusion: Intravenous methycobalamin treatment is a safe and potentially beneficial therapy for neuropathy in chronic hemodiaiysis patients.
(Internal Medicine 38: 472-475, 1999)

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A 47-year-old woman with heterozygous Fabry's disease with pre-excitation syndrome has been followed up for 15 years. Diagnosis was confirmed by the typical electron microscopic feature of the endomyocardial specimen and a decreased plasma α-galactosidase activity. As the disease progressed, the interventricular septum thickened from 11 to 17 mm as measured by echocardiography, while the AH interval was prolonged from 80 to 140 msec. In Fabry's disease, the PR interval has been reported to be variable from short PR to AV block. Therefore, this case may be helpful to understand the time course in the AV conduction abnormalities with the progression of Fabry's disease.
(Internal Medicine 38: 476-481, 1999)

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The patient, a 24-year-old man, had suffered from hunger, sweating, tachycardia and palpitation for three years. He was diagnosed as having Graves' disease (GD) and treated with methimazole (MMI) for 3 months. He noted that palpitation and perspiration seemed to particularly occur when he was hungry, and thus he was examined to determine whether these symptoms were caused by hypoglycemia. As a markedly elevated immunoreactive insulin level and the presence of insulin antibody in serum were found, he was diagnosed as having insulin autoimmune syndrome (IAS). HLA typing revealed the patient to be positive for group Bw62/Cw4/DR4, which is reportedly a specific HLA type in MMI-treated euthyoroid GD patients with IAS. In spite of the continuation of MMI treatment, the % binding of IRI decreased and the hypoglycemic episode disappeared. In contrast to the previously reported MMI induced IAS in GD cases, MMI is unlikely to have exacrebated IAS in the present case, although his HLA combination is identical to that of the previous cases.
(Internal Medicine 38: 482-485, 1999)

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We present here a case of prominent hypercalcemia accompanied by hypothalamic tumor and Graves' disease. A 24-year-old man with hypothalamic tumor showed hypopituitarism, central diabetes inspidus (DI) and hyperthyroidism. Nausea, loss of thirst and appetite, and general fatigue were found with the unveiling of hypercalcemia and hypernatremia. Parathyroid hormone (PTH) and lα-dihydroxyvitamin D levels were suppressed with a normal range of PTHrelated protein values. One-desamino-(8-D-arginine)-vasopressin (DDAVP) and half-saline administration normalized hypernatremia, while hypercalcemia was still sustained. Administration of cortisone acetate and thiamazole reduced the elevated serum Ca level. In the present case, concurrent hyperthyroidism was assumed to accelerate skeletal mobilization of calcium into the circulation. Hypocortisolism and central DI was also considered to contribute, to some extent, to the hypercalcemia through renal handling of Ca.
(Internal Medicine 38: 486-490, 1999)

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A 21-year-old man was admitted to Kure National Hospital with nephrotic syndrome in September 1996. He had suffered from an intractable pruritic skin rash and recurrent subcutaneous abscesses caused by the hyperimmunoglobulin E syndrome since the age of 18 months. Renal biopsy gave a diagnosis of membranoproliferative glomerulonephritis. Steroid therapy decreased urinary protein loss and hypoproteinemia, and his pruritic skin rash was improved. Patients with hyperimmunoglobulin E syndrome have a defective immune response, especially to Staphylococcus aureus infection. Continuous antigen stimulation may have caused this patient's renal histological damage as in immune complex glomerulonephritis.
(Internal Medicine 38: 491-494, 1999)

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A 35-year-old man with immunoglobulin A (IgA) nephropathy who developed hemolytic uremic syndrome (HUS) presented with transient elevation of serum creatinine, thrombocytopenia, and hemolytic anemia with fragmented red cells with nephrotic syndrome. Hemolytic anemia and the temporarily deteriorated renal function were improved after hemodialysis and plasma exchange. Histological findings were consistent with HUS and IgA nephropathy. Including this case, we reviewed the cases of HUS accompanied by glomerular diseases reported from 1969 to 1996. Surprisingly, most cases showed nephrotic syndrome at the onset of HUS. Several possible relationships between HUS and nephrotic syndrome are discussed.
(Internal Medicine 38: 495-499, 1999)

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A 33-year-old man with a 4-year history of Crohn's disease presented with marked ascites and an abdominal tumor. Two M-protein peaks, immunoglobulin (Ig) G-κ and IgA-κ, were detected in the serum. Neoplastic lymphoplasmacytic cells were infiltrated in the bone marrow and ascites. Histological examination of the abdominal tumor showed marked proliferation of lymphoplasmacytic cells that were positive for either IgG or IgA. Moreover, DNA sequences of the expressed IgG and IgA genes were different in the complementarity-determining region 3. These results suggest that chronic inflammation in Crohn's disease contributes to the simultaneous development of biclonal lymphoplasmacytic immunocytoma of the small intestine.
(Internal Medicine 38: 500-503, 1999)

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We describe a 51-year-old man with myotonic dystrophy (MyD) associated with insulinoma. In addition to the typical symptoms of MyD, he showed hypoglycemic attacks after meals. The radiological examination and selective blood sampling revealed an insulinoma in the head of the pancreas. The tumor was resected and histopathologically diagnosed as an insulinoma. In Southern blot analysis, CTG repeat of the myotonin protein kinase gene in the insulinoma showed the longest expansion, followed by normal tissue of the pancreas, muscle and white blood cells. Therefore, microsatellite instability was the most prominent in the tumor cells.
(Internal Medicine 38: 504-506, 1999)

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We report an autopsy case of T-cell lymphoma with diffuse white matter infiltration. Cranial magnetic resonance (MR) images showed atrophy of the brain with a diffuse, non-enhancing, T2-high signal intensity lesion in the cerebral white matter. Intra-axial infiltration of T-cell lymphoma should be considered a differential diagnosis in patients with these MRI findings.
(Internal Medicine 38: 507-511, 1999)

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A case of human T cell leukemia virus type I (HTLV-1) associated myelopathy (HAM)/tropical spastic paraparesis (TSP) with 14-year history of systemic lupus erythematosus (SLE) is reported. For 9 years, the numbness of the feet and sacral region progressed with occasional urinary incontinence and constipation. She was admitted to hospital due to gait disturbance and aggravation of SLE and the diagnosis of HAM/TSP was confirmed, indicating that HTLV-1 infection is associated with the development of not only HAM/TSP but also SLE.
(Internal Medicine 38: 512-515, 1999)

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Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown origin, characterized by a typical spiking fever, evanescent salmon-colored rash, polyarthralgia, and myalgia. Calcinosis cutis and gastrointestinal involvement have rarely been noted in AOSD. We herein describe a 54-year-old woman who demonstrated repeated disseminated intravascular coagulation (DIC), and adult respiratory distress syndrome (ARDS), associated with AOSD. The patient also revealed a remarkable degree of digital Calcinosis cutis and intestinal pseudoobstruction. A connective tissue disease, such as systemic sclerosis, might have been the underlying factor in the latter two symptoms.
(Internal Medicine 38: 516-520, 1999)

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