We evaluated whether prolonged oral administration of a novel analog of thyrotropinreleasing hormone (TRH), TA-0910, may change the pituitary-thyroid axis in human subjects with brain stroke. The subjects were given one oral dose of 2.5-20 mg of TA-0910 daily for 8 weeks, and then blood levels of TA-0910, thyroid hormones and thyrotropin (TSH) were measured. Plasma levels of TA-0910 were elevated with increasing doses. After administration of TA-0910, the basal levels of thyroid hormones and TSH had a tendency to increase and decrease, respectively, but those changes remained in the normal range. The secretion of TSH in response to TRH was not significantly affected by TA-0910 administration. No significant changes in other pituitary hormones were observed after TA-0910 administration. The present data indicate that prolonged oral administration of TA-0910 did not significantly alter the pituitary-thyroid axis in subjects with brain stroke.
(Internal Medicine 32: 681-685 1993)

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Hemosiderinuria caused by intravascular hemolysis is a characteristic clinical feature of an acquired hemolytic disorder, paroxysmal nocturnal hemoglobinuria (PNH). We examined the deposition of hemosiderin (iron) in the kidneys of 6 patients with PNH using magnetic resonance imaging (MRI). Three patients with autoimmune hemolytic anemia (AIHA), a hemolytic disorder showing extravascular hemolysis, served as controls. In five of the six patients with PNH, a characteristic T2-weighted MRI of the kidneys, suggesting the deposition of iron (hemosiderin) predominantly in the renal cortex, was obtained. Hemosiderin-deposition was not revealed in the kidneys of any of the patients with AIHA. We conclude that MRI is a sensitive means of detecting hemosiderin deposited in the renal cortex of patients with PNH and that this feature is considerably specific for diseases showing intravascular hemolysis, as represented by PNH.
(Internal Medicine 32: 686-690, 1993)

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The effects of an angiotensin-converting enzyme inhibitor, alacepril, on cardiovascular and plasma catecholamine responses to mental stress were studied. A mental arithmetic test (MAT) was carried out in 9 patients with essential hypertension before and after treatment with alacepril, 25 mg once daily for 2 weeks, and in 9 age- and sex-matched normal subjects. Systolic blood pressure at rest and during MAT and the change in plasma norepinephrine concentrations during MAT were significantly greater in the hypertensive subjects than in the normal subjects. Alacepril significantly reduced systolic blood pressure, both at rest and during MAT, as compared to before treatment in the hypertensive subjects. Furthermore, alacepril significantly attenuated the change in plasma norepinephrine concentrations during MAT (from 127±76 pg/ml to 66±42 pg/ml, p‹0.05). These results suggest that alacepril significantly suppresses the augmented cardiovascular and sympathetic nervous responses to mental stress in patients with essential hypertension.
(Internal Medicine 32: 691-694, 1993)

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Eleven hemodialysis patients who developed refractory secondary hyperparathyroidism, despite conventional vitamin D therapy, were treated with large oral doses of 1, 25-dihydroxycholecalciferol [1, 25(OH)₂D₃]. Therapeutic regimen was a single oral dose of up to 8.0 μg administered once weekly following hemodialysis. A maximum serum level of 1, 25(OH)₂D occurred four hours after the 8.0 μg dose. A positive correlation (Y=84.3X-22.1: P<0.01) was found between the maximal serum 1, 25(OH)₂D concentration (Cmax) and the dose of 1, 25(OH)₂D₃ when plotted on a logarithmic scale. Forty-eight hours after the administration of the 8.0 μg dose, the parathyroid hormone (PTH) level and the alkaline phosphatase activity (ALP) were markedly decreased without evidence of hypercalcemia. A significant inverse relationship was found between the Cmax of 1, 25(OH)₂D and the percent change in the PTH level measured after 48 hours, either with carboxy-terminal (C-PTH) or the highly sensitive mid-portion assay (HSPTH). From these results, the level of serum 1, 25(OH)₂D required to blunt the rise in serum PTH was 168 pg/ml and 203 pg/ml, respectively; these serum levels were achieved by the oral administration of doses of 6.0-8.0 μg or higher. There were no adverse effects of treatment. Following this study, one patient was continuously treated with 8.0 μg of 1, 25(OH)₂D₃ orally once a week for 18 months. There was a therapeutic effect (as evidenced by PTH suppression, ALP suppression and the disappearance of subjective complaints) without the development of severe hypercalcemia or hyperphosphatemia. This treatment may help to prevent or treat secondary hyperparathyroidism in patients receiving long-term dialysis.
(Internal Medicine 32: 695-701, 1993)

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An open study was conducted to evaluate the changes in in vivo and in vitro responses to house-dust-mite (HDM) after rush immunotherapy (RI). A 7-day RI protocol using an extract containing HDM allergen was administered to 12 subjects with HDM-sensitive asthma, and the effects on bronchial responsiveness and serum antibody levels were evaluated up to 16 or 20 weeks after RI. The levels of HDM-specific IgG, IgG1 and IgG4 antibodies were significantly elevated from 4 or 8 weeks after RI. Provocative doses causing a 20% fall in FEV₁ (PD₂₀) by allergen inhalation were elevated in all subjects at 16 to 20 weeks after RI. There was a high correlation between the increase in log-PD₂₀ and the increase in the ratio of HDM-specific IgG₄ to IgG1 (r=0.68, p<0.05). The results suggest that RI elicits the improvement of allergen-specific bronchial responsiveness and the increase in serum antibody levels within a relatively short period.
(Internal Medicine 32: 702-709, 1993)

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The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B (AMPHB) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a randomized, controlled trial was studied. One hundred and six consecutive, evaluable patients were randomly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily, or amphotericin B only. A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group (34.6% vs 56.9%; P<0.05). The mean number of days that the patients received empirical antibiotic therapy was shorter in the study group (23 days vs 30 days; P<0.05). The percentage of patients with a gram-negative bacterial infection (9.6% vs 27.5%; P<0.05) or a fungal infection (17.3% vs 37.3%; P<0.05) was decreased in the study group. This new combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy.
(Internal Medicine 32: 710-715, 1993)

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Here we report a 58-year-old man with chronic myelogenous leukemia in the chronic phase, who developed acute respiratory failure following administration of high dose natural interferon σ (6, 300×l0⁴ units/week). Radiological and histological findings were consistent with acute interstitial pneumonia (AIP). Although the pathogenesis remains unclear, it is important to watch for the possible development of AIP when employing interferon σ therapy, especially at high doses.
(Internal Medicine 32: 716-718, 1993)

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Most cases of spontaneous bacterial peritonitis (SBP) in association with nephrotic syndrome are children. The complication of SBP in adults with nephrotic syndrome is extremely rare. Herein, we report a 25-year-old man with nephrotic syndrome and chronic renal failure who suffered from SBP. Citrobacter freundii was isolated from ascites. Irreversible deterioration of renal function followed the development of SBP, though the peritonitis was cured with antibiotic treatment. This case suggests that SBP is a rare, but serious complication of adult nephrotic syndrome with ascites.
(Internal Medicine 32: 719-721, 1993)

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We report a 57-year-old manwith Fisher's syndrome in whom both peripheral and central nervous system (CNS) lesions were detected. Clinical electrophysiological examinations including peripheral conduction studies, SEPs and BAEPs indicated conduction delay in the CNSas well as in the peripheral nerve.
(Internal Medicine 32: 722-724, 1993)

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Double filtration plasmapheresis (DFPP) therapy was administered to a patient with autoimmune hepatitis (AIH)-systemic lupus erythematosus overlap. The patient had suffered from recurrent AIH attacks with an interval of 3-4 months despite massive corticosteroid administration. After vigorous removal of immunoglobulins by DFPP procedures combined with immunosuppressive therapies, clinical and laboratory findings of AIH were remarkably improved. DFPP might be an optional modality in the treatment of AIH patients, especially for those who are resistant to and/or cannot tolerate massive corticosteroid or immunosuppressive therapies.
(Internal Medicine 32: 725-729, 1993)

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A patient with adult Still's disease and Sjögren's syndrome failed to respond to conventional doses of corticosteroids. Therefore intravenous pulse methylprednisolone combined with oral cyclophosphamide was given which subsequently resolved the flare of rashes, fevers, and arthritis. This combination therapy may be a useful therapy to consider in patients with adult Still's disease who are resistant to conventional treatment and may allow a reduction in daily corticosteroid requirement.
(Internal Medicine 32: 730-732, 1993)

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A case of acute myeloid leukemia (AML)with an unusual phenotype which was negative for a panel of myeloid antigens determined by flow cytometry, but was strongly positive for myeloperoxidase has recently been reported. We herein describe a case of AML with this unusual phenotype at diagnosis; relapse occurred with the acquisition of CD13 and CD33 expressions. Morphological features of the blasts at relapse seemed to be more compatible with myeloblasts than those at diagnosis. These phenotypic and morphological changes are suggestive of asynchronous differentiation, clonal evolution or clonal change of leukemic cells.
(Internal Medicine 32: 733-736, 1993)

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Pancreatic polypeptidioma, a pancreatic endocrine tumor, is an extremely uncommon disease and its clinical features and responses to therapy are not well known. We present a 33-year-old woman with disseminated pancreatic polypeptidioma, who subsequently showed various signs and symptoms of metastases, including bone pain, cranial nerve palsy, spinal block, and hematuria, and died 22 months after the presentation. Responses to various therapeutic regimens including hepatic arterial embolization, radiation therapy, systemic chemotherapy, and administration of interferon-α or somatostatin analogue, are discussed. Particular note in this case is a prompt response of bone metastases to the radiotherapy.
(Internal Medicine 32: 737-741, 1993)

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A 32-year-old adult case of glomerulocystic kidney disease (GCK) is reported. He had brain and muscle atrophy, probably due to congenital malformation. Progressive renal failure developed and he died. Autopsy disclosed multiple tiny cysts exclusively in the renal cortices. Microscopic study revealed that the cysts were dilated Bowman'sspaces. This case is the 12th adultcase reported in the world.
(Internal Medicine 32: 742-744, 1993)

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A case of isolated angiitis of the central nervous system (CNS) which first presented as intracranial hemorrhage during cesarean section is reported. Only one case of isolated angiitis of the CNS in post partum has been reported to date. Although a headache in labor and puerperium usually suggests subarachnoid hemorrhage, isolated angiitis of the CNS should be considered in the differential diagnosis.
(Internal Medicine 32: 745-748, 1993)

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A 36-year-old woman gradually developed dysphagia and muscle weakness of the lower extremities. Diagnosis of polymyositis was given from elevation of serum creatine kinase and pathological findings of a muscle biopsy. Despite oral prediiisolone and intravenous pulse methylprednisolone therapy, her muscle weakness persisted, and then pulse intravenous cyclophosphamide (IVCY) therapy was initiated and repeated five times in total, which resulted in significant improvement in muscle strength. Thereafter, weekly administration of methotrexate at low dosage further normalized the serum creatine kinase level. We may conclude that IVCY and low-dose weekly methotrexate together could be an alternative in refractory polymyositis.
(Internal Medicine 32: 749-752 1993)

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