Since its first rigid definition in 1961 by Petersdorf and Beeson, fever of unknown origin (FUO) has been a major clinical challenge. In this clinical investigation, a retrospective study was conducted on 153 patients meeting the classic criteria of FUO. Collagen-vascular disease was found to be the most common cause of FUO, a change since our last study conducted from 1971 to 1982, replacing infection as the most common disease category of FUO. FUO in elderly patients was also analyzed. By comparing previously documented studies, we observed a new variation in the diseases that are possible causes of FUO. This report will define the present status of FUO in Japan, as well as a comparison with our previous study and other documented studies to determine the shift in the spectrum of diseases causing FUO.
(Internal Medicine 33: 67-73, 1994)

View full abstract

In this survey involving 10 hospitals, we analyzed data on 80 Japanese patients from the Shin'etsu area (Nagano-ken and Niigata-ken) who were observed for fever of unknown origin (FUO). Our objectives were to identify the underlying causes and the relevant diagnostic methods. Fourteen of the patients died of the underlying illness. The cause of the FUO was infection in 43 patients, allergic or autoimmune disease in 13, neoplasm in 7, miscellaneous causes in 3, and undetermined in 14. FUO was self-limited in 13 patients and persistent in one patient. Methods successfully used to establish the final diagnosis in 66 patients were: evaluation of the clinical course or response to treatment in 16, serologic tests in 12, bacteriologic studies in 10, biopsy in 9, cytologic examination in 6, conventional radiology in 6, necropsy in 3, endoscopy in 2, and biochemical testing in 2.
(Internal Medicine 33: 74-76, 1994)

View full abstract

Twenty-two patients with Parkinson's disease with predominantly unilateral signs in the upper extremities were studied by means of transcranial magnetic stimulation. The mean central motor conduction time (CMCT) on the clinically affected side determined by F wave technique was significantly shorter (p<01) than that of the other side at rest. However, the mean CMCT during slight voluntary contraction was not significantly different in the two sides. Amplitudes of motor evoked potentials and F waves tended to be higher on the clinically affected side than on the other side. We conclude that reduced CMCT and high F wave amplitudes reflect hyperexcitability of the anterior horn cells in patients with Parkinson's disease.
(Internal Medicine 33: 77-81, 1994)

View full abstract

Serum vitamin B₁₂ levels and unsaturated vitamin B₁₂ binding capacities were measured in 24 patients with multiple sclerosis (MS), 73 patients with other neurological disorders and 21 healthy subjects. There was no decrease in the vitamin B₁₂ levels, however, a significant decrease in the unsaturated vitamin B₁₂ binding capacities was observed in patients with MS when compared with other groups. A massive dose of methyl vitamin B₁₂ (60 mg every day for 6 months) was administered to 6 patients with chronic progressive MS, a disease which usually had a morbid prognosis and widespread demyelination in the central nervous system. Although the motor disability did not improve clinically, the abnormalities in both the visual and brainstem auditory evoked potentials improved more frequently during the therapy than in the pre-treatment period. We therefore consider that a massive dose methyl vitamin B₁₂ therapy may be useful as an adjunct to immunosuppressive treatment for chronic progressive MS.
(Internal Medicine 33: 82-86, 1994)

View full abstract

A sensitive method of non-radioactive in situ hybridization using digoxigenin-labeled oligonucleotides is described for the detection of mRNA within human renal biopsy specimens. Although non-radioactive in situ hybridization typically has the drawback of low sensitivity, we increased the sensitivity of this method, providing a practical alternative to the use of radiolabelled probes. The four main points are: 1) assessment of the efficiency of labeling, 2) optimization of the probe concentration for hybridization, 3) requirement of deproteinization of tissues with HC1 and proteinase K, and 4) the use of a four-layer immunoperoxidase staining system. This technique was found to clearly localize individual mRNA positive cells within cryostat tissue sections. A variety of controls including sense probes, excess unlabeled anti-sense probes, and RNase-treatment demonstrated the specificity of the technique. This improved method is a powerful technique for detecting mRNA within human renal tissue and will be most useful in the study of gene expression in the pathogenesis of renal diseases.
(Internal Medicine 33: 87-91, 1994)

View full abstract

A case of primary ocular and central nervous system malignant lymphoma was reported which was first manifested as bilateral uveitis ten months before the neurological symptoms appeared. The lesion of lymphoma in the central nervous system was clearly demonstrated as a heavy accumulation of N-isopropyl-¹²³I-p-iodoamphetamine by single photon emission computed tomography. Since most brain tumors reportedly show a low uptake of N-isopropyl-¹²³I-p-iodoamphetamine, single photon emission computed tomography with N-isopropyl-¹²³I-p-iodoamphetamine could be helpful in making the diagnosis, as well as in visualizing primary central nervous system malignant lymphoma.
(Internal Medicine 33: 92-96, 1994)

View full abstract

A rare case of radiologically occult lung cancer in the peripheral region beyond bronchoscopic visibility is reported. A 69-year-old female was referred because of positive sputum cytology. Despite detailed bronchoscopic and otorhinoralyngologic examinations, the source of malignant cells was not localized. During the follow-up period, squamous cell carcinoma of the lung periphery was detected radiologically three years after its presence was detected in sputum. Awareness of the existence of this type of cancer and careful follow-up are important in the management of patients with positive sputum cytology and no evidence of cancer.
(Internal Medicine 33: 97-99, 1994)

View full abstract

Octreotide acetate, a long-acting somatostatin analogue, is effective in controlling and markedly reducing the symptoms of carcinoid crisis. We report a patient with carcinoid syndrome with prolonged survival for 4.5 years with high dose octreotide therapy and survived for 7.5 years after the first flushing, in spite of episodes of severe carcinoid crisis. Dose escalation was required in order to control carcinoid symptoms, and the final dosage was 5, 950 μg/day. Although administration of such a high dosage of octreotide has never been reported before, we found that octreotide could be used at this dosage safely without inducing serious side effects, and probably prolonged the patient' s survival. Our experience with this case indicates that octreotide acetate is an effective drug in controlling carcinoid crisis and prolonging survival without serious side effects.
(Internal Medicine 33:100-102, 1994)

View full abstract

A 52-year-old female with congenital Stomatocytosis showed hemolytic anemia, an increased mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC), reticulocytosis and an increased osmotic fragility. Lipid and protein content of membranes, the activities of membrane-associated enzymes in erythrocytes and the elution pattern of hemoglobin were normal. Erythrocyte Na⁺ influx was moderately increased and Na⁺ efflux, particularly ouabain-insensitive Na⁺ "leak-out" was also increased. K⁺ concentration of erythrocytes was abnormally low with a slightly increased Na⁺ content. These phenotypes are very rare, and should be classified as a variant type.
(Internal Medicine 33:103-106, 1994)

View full abstract

A 78-year old male with ureteral carcinoma manifesting hypercalcemia is reported. He was diagnosed as having ureteral carcinoma of the left side 2 years previously and was treated by nephrectomy with ureterovesicostomy. In October 1991, he was admitted for anorexia. A clinical examination revealed recurrence of the ureteral carcinoma with metastasis to the rectum and liver. His serum calcium level was elevated (13.9 mg/dl). In addition to rehydration and furosemide, treatment with eel-calcitonin and prednisolone failed to decrease his serum calcium level. Finally, he was administered mithramycin but he died 13 days later. He had no evidence of bone metastasis or hyperparathyroidism. Nephrogenic cAMP and urinary parathyroid hormone-related protein (PTHrP) were markedly elevated. Immunohistochemical study demonstrated expression of PTHrP in the tumor cells. Thus, the hypercalcemia was thought to be mediated by PTHrP secreted from the neoplastic tumor. Although there have been several reports of ureteral carcinoma associated with humoral hypercalcemia of malignancy, this is considered to be the first case associated with elevation of PTHrP.
(Internal Medicine 33:107-109, 1994)

View full abstract

We report a 19-year-old woman who presented with headache, vomiting, and elevated blood pressure; pheochromocytoma and von Recklinghausen's neurofibromatosis were diagnosed. Her mother had the same skin lesions and was also found to have pheochromocytoma. Both patients underwent surgical resection and the postoperative courses were uneventful; the daughter subsequently married and delivered a healthy child. Although both pheochromocytoma and von Recklinghausen's disease are derived from neuroectoderm and are inherited disorders, concomitant familial occurrence of these two diseases is very rare, only three families have been reported previously worldwide.
(Internal Medicine 33:110-114, 1994)

View full abstract

Two cases of malignant lymphoma complicated with capillary leak syndrome following super high-dose chemotherapy and administration of granulocyte colony-stimulating factor (G-CSF) are presented. Subsequent to the nadir of granulocytes, and at the stage of rapid increase of granulocytes, the symptoms of fever, hypotension, dyspnea, pleural effusion and edema appeared, and laboratory data revealed hypoxia, hypocapnia and hypoalbuminemia. In addition, an abscesslike lesion was observed in the liver in one patient. After the administration of G-CSF was ceased or decreased, and pulse therapy with methylprednisolone was initiated, these symptoms disappeared quickly.
(Internal Medicine 33:115-119, 1994)

View full abstract

A 30-year-old Japanese homosexual AIDS patient was admitted to hospital because of Kaposi's sarcoma and mild diarrhea on February 4, 1993. Mud-like stool with blood and mucous was recognized after admission. Although serologic tests for Entamoeba histolytica were negative, trophozoites of E. histolytica were identified in his bloody stool. Daily doses of 1, 000 mg of metronidazole were given orally for 6 days and then 750 mg for 4 days, and good results were observed. His CD4 count was 19.5/mm³. Symptomatic amebic colitis was easily treated and good results were obtained even with the extremely diminished CD4 count. This is the first published report of symptomatic amebic colitis in an AIDS patient in Japan.
(Internal Medicine 33:120-122, 1994)

View full abstract

We describe a familial occurrence of primary hyperparathyroidism. The proband is a 60-yearold woman who had a parathyroid adenoma. Her older sister had a parathyroid adenoma with cementifying jaw fibroma and her younger sister died of parathyroid adenocarcinoma with pulmonary metastasis at the age of 38. We have not yet obtained evidence for other endocrine disorders suggesting multiple endocrine neoplasia (MEN) in this pedigree. The proband is complicated with Wilms' tumor. It is now widely accepted that respective predisposed genes of MEN type 1 and Wilms' tumor, and PTH gene are located on chromosome 11. The manifestation observed in this case may be related to mutational abnormalities on chromosome 11.
(Internal Medicine 33:123-126, 1994)

View full abstract

A 25-year-old Japanese woman had both ulcerative colitis and Takayasu's disease and was positive for HLA-A24, BW52, and DR2. She was found to have thickening of the wall of the carotid artery on contrast-enhanced computerized tomography of the neck and chest. Prednisolone, beraprost, and sulfapyridine achieved rapid remission of both diseases.
(Internal Medicine 33:127-129, 1994)

View full abstract