The final cascade of amyotrophic lateral sclerosis (ALS) coincides with the onset of clinical neurological deficits and involves multifactorial interactive mechanisms. These terminal events include excitotoxicity, free radical accumulation and possibly immunological disturbances. They are probably predated by months or years by thus far unidentified triggers. Selective vulnerability of the corticomotneuronal system in ALS is likely due to degradation of several gene products essential to transmitter, receptor and nerve growth factor maintenance specific to this functional system. Therapeutic strategies involve neuroprotection, symptomatic and combination neuronal therapy targeted to the final cascade of ALS.
(Internal Medicine 34: 824-832, 1995)

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Sarcoidosis is a systemic disease. Clinical manifestations and prognosis are heterogeneous in sarcoidosis patients from various populations. This suggests that genetic factors and/or environmental factors seem to play important roles in the pathogenesis. Sarcoidosis is characterized as a hyperimmune response to unknown agent(s) at the lesion sites. Regarding pulmonary lesions, macrophage-T lymphocyte alveolitis precedes epithelioid cell granuloma formation. In this review, reports presented in international meetings were introduced to compare population differences; we attempted to review the issues which relate to disease susceptibility in patients with sarcoidosis. In addition, we discussed the possible causative agents, whether T cell receptor expression reflects antigen driven immune responses, and what type of biological active materials may be critical in determining the disease activity and/or prognostic factors, with particular focus on the population differences.
(Internal Medicine 34: 833-838, 1995)

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We describe here 3 patients with central nervous system infection caused by herpes simplex virus type 2 (HSV-2); one patient with brainstem encephalitis and two with recurrent transverse thoracic myelitis. All three patients showed increased IgG antibodies to HSV in the cerebrospinal fluid (CSF). HSV-2 DNA was demonstrated in the CSF by polymerase chain reaction (PCR) amplification. Upon treatment with acyclovir, one patient with myelitis partially recovered and the others completely recovered. It is important to recognize the wide spectrum of clinical manifestations of HSV-2 infection in the central nervous system (CNS).
(Internal Medicine 34: 839-842, 1995)

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Three siblings of a consanguineous parents with involuntary movements are reported. The mother had only a very slight neck tremor, without any other neurological abnormality, and the father had died. The 38-year-old son (Case 1) complained of involuntary movements at the age of 6. His involuntary movements were observed in the tongue, perioral region and upper and lower extremities: jerky movements with dystonic features. The 46-year-old elder brother (Case 2) experienced involuntary movements at the age of 18. Involuntary movements were observed in the upper extremities; he also had torticollis and tremulous movements in the neck, and jerky movements in the perioral region. They showed gait disturbance and dysarthria. The 35-year-old sister (Case 3) also experienced involuntary movements. When she was writing, her involuntary movements were obvious: dystonia and myoclonic jerks. Tremor in the neck was also seen. Their intelligence was below average. We concluded that this family had hereditary torsion dystonia, with myoclonus, and low intelligence. This condition may be associated with an autosomal recessive gene.
(Internal Medicine 34: 843-846, 1995)

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We studied the relationship between various T lymphocyte functions and granuloma formation in 5 lung tissue and 4 lymph node tissue samples from patients with sarcoidosis by immunohistological methods. In the lesion of sarcoidosis, T cells were positive for αβTCR, but γβTCR-positive T cells were rarely observed. The results of analysis of functional subsets showed that T cells in the internal area of granuloma were predominantly helper/inducer subset (CD4⁺ CD45RA^-). On the other hand, cytotoxic T cells (CD8⁺CD45RA^-CD11b^-) were present in abundance in the outer boundaries of granuloma. In addition, suppressor-inducer T cells (CD4⁺CD45R A⁺) were present in the surrounding areas. However, T cells of various subsets were present sporadically outside the granulomas. We also studied the distribution of T cells expressing activation-related antigens. The results showed that T lymphocytes in the internal area of granulomas more frequently had these antigens than did T lymphocytes in the external area. These findings suggested that T cells infiltrating into the sarcoidosis lesion demonstrated a layer-like distribution based on functional subsets. These findings also confirm that activated T cells were more abundantly distributed in the internal area of sarcoid granuloma than in the external area.
(Internal Medicine 34: 847-855, 1995)

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Therapeutic efficacy of intermittent and continuous injection of isosorbide dinitrate (ISDN) was compared in 22 patients (mean age 64±10, 18 males and 4 females) with unstable angina at rest. They were randomized into 2 groups that received either continuous (10 mg/h, group A) or intermittent (10 mg/10 min every 2 hours, group B) injection of ISDN for 3 days (phase 1). Each injection protocol was switched (phase 2) and subsequently switched back to the initial protocol (phase 3) in a cross-over fashion. The serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-ISMN were measured serially during both intermittent and continuous injection protocols. In addition, the incidence and duration of angina and changes in systolic blood pressure were analyzed. There were 3 treatment-failure cases during the intermittent injection period and 1 during the continuous injection period. Three of these treatment-failure cases developed small acute myocardial infarcts despite emergent coronary arteriography followed by intra-coronary thrombolysis and percutaneous balloon angioplasty. There was no difference in therapeutic efficacy between continuous and intermittent ISDN in terms of the incidence, duration of angina attacks and the number of patients whose angina was suppressed. After bolus injection of ISDN (10 mg/10 min), the serum concentration of ISDN increased rapidly and returned to the control level at 60 minutes after the injection. The serum 5-ISMN and 2-ISMN concentrations also increased immediately after injection and then decreased gradually reaching statistically insignificant level to the control values at 60 minutes after injection. With continuous injection, ISDN and its metabolites increased gradually and reached similar but slightly lower serum concentrations to the peak levels during intermittent injection. We conclude that the therapeutic efficacy of intermittent and continuous injection of ISDN is similar in patients with unstable angina.
(Internal Medicine 34: 856-862, 1995)

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A 40-year-old female patient with Werner's syndrome (WS) suffering from thyroid cancer and myelodysplastic syndrome (MDS) is reported. She had been diagnosed as having WS complicated with thyroid cancer seven years previously. Total thyroidectomy and radioactive iodine (¹³¹I, 100 mCi/year) therapy for seven years had slowed the progression of thyroid cancer. She suffered a sudden onset of MDS at the age of 40 years. After six months she died from overt leukemia. We found an additional chromosome aberration of chromosome 10 in the progression of leukemia from MDS.
(Internal Medicine 34: 863-867, 1995)

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A 73-year-old man was admitted because of near-drowning in a hot springs bath. Transient severe hypercalcemia and polyuria were seen during the first hospital day. It seemed that the hypercalcemia was due to acute intoxication from calcium contained in the water of the spring absorbed mainly through the alveoli. To our knowledge, this is the first case of acute hypercalcemia complicating a near-drowning in a hot spring. Analysis of serum and urine electrolytes during the polyuric phase revealed saline diuresis, which was probably due to interference by the hypercalcemia of the reabsorption of sodium and free water.
(Internal Medicine 34: 868-871, 1995)

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We describe a patient with hypersensitivity vasculitis due to ofloxacin therapy; the vasculitis was associated with elevated transaminase and IgA levels. Cyclophosphamide and intravenous pulse prednisolone resulted in clinical improvement.
(Internal Medicine 34: 872-874, 1995)

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A 64-year-old man who had been diagnosed as having acute myelocytic leukemia (M2 in the FAB classification) developed central nervous system involvement of intramedullary spinal cord during hematological remission. Magnetic resonance imaging showed a low signal intensity mass on Tl-weighted images and a high signal intensity mass on T2-weighted images. The mass was slightly enhanced by gadolinium-diethylenetriaminepentaacetic acid. His neurological symptoms were slightly improved by intrathecal and systemic chemotherapy combined with external irradiation, although the size of the mass did not change.
(Internal Medicine 34: 875-878, 1995)

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A 55-year-old Japanese woman with familial hypobetalipoproteinemia associated with hypothyroidism was admitted to the hospital because of orthopnea and congestive heart failure. Thyroid function testing revealed hypothyroidism, but she exhibited low levels of serum cholesterol (111 mg/dl) and apolipoprotein (apo) B (48.5 mg/dl). No abnormal bands were detected with gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis of very low density lipoprotein, low density lipoprotein and high density lipoprotein followed by immunoblotting with anti apo B polyclonal antibody. In this case, apo B structural abnormality could not be identified.
(Internal Medicine 34: 879-882, 1995)

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A 75-year-old woman with epigastric pain and tarry stool was admitted to our hospital, where upper gastrointestinal endoscopic study revealed multiple gastric ulcers. The endoscopic biopsy specimens obtained on the seventh hospital day disclosed a few typical intranuclear cytomegalovirus inclusions. Cytomegalovirus-DNA was detected using polymerase chain reaction in a biopsy specimen. No immunologic abnormalities were demonstrated by any laboratory tests. While only a few cases of cytomegalovirus-associated gastric ulcer in non-immunocompromised hosts have been reported, this entity may be more frequently detected when careful histological examination is performed in the active stage rather than postponed until after healing of the ulcer.
(Internal Medicine 34: 883-885, 1995)

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A 58-year-old man was revealed to have multiple liver tumors with elevated prostatic acid phosphatase (PAP) during a medical examination. The tumors were of neuroendocrine nature, but no abnormal findings were obtained in other organs in which neuroendocrine tumors develop frequently. Repeated transarterial embolization was partially effective. However, the tumors became resistant to the therapy three years later, continued growing and ruptured. Autopsy disclosed neuroendocrine tumors in the pancreas, which were immunohistologically positive for PAP. Neuroendocrine tumors of the pancreas and liver producing PAP are rare; this case is reported with a review of literature.
(Internal Medicine 34: 886-891, 1995)

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A 19-year-old man was diagnosed as having severe aplastic anemia and received high-dose methylprednisolone treatment without hematological response. A second course of high-dose mPSL treatment together with granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) was then started and resulted in trilineage blood cell response. Ten months after the combination therapy thrombocytopenia developed and cytogenetic analysis showed 45, XX, -7, indicating an evolution to myelodysplastic syndrome (MDS) associated with monosomy 7. G-CSF and EPO treatment together with immunosuppression may be an effective therapy in SAA patients, but such a therapy may increase the risk of evolution to MDS.
(Internal Medicine 34: 892-895, 1995)

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A 51-year-old male with a recurrent medullary thyroid carcinoma (MTC) showed high serum levels of calcitonin (CT) and carcinoembryonic antigen (CE A) but with concomitant normocalcemia. The CT activities of the patient's serum in vivo (hypocalcemic activity in rats) and in vitro (cyclic AMP-increasing activity in cultured human mammary tumor, T47D) were much lower than those expected from the patient's CT level. High performance liquid chromatography (HPLC) with radioimmunoassay (RIA) detection gave a broad spectrum of molecular weights of CT-like polypeptides in the 3 kDa to 200 kDa range with separation from CEA, suggesting that the mechanism for CT production in MTC is an obscure one.
(Internal Medicine 34: 896-900, 1995)

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A male patient, aged 58, without any discernible underlying disease developed a massive hemorrhage in the retroperitoneal cavity and in the femoral muscle. The hemorrhagic tendency of the patient was found to be due to the acquired anti-Factor VIII specific autoantibody in the blood. A concentrate of an activated prothrombin complex (FEIBA: Factor eight inhibitor bypassing activity) was administered and produced a remarkable effect in stemning the bleeding tendency of the patient. Immunosuppressive therapy was also effective for the control of the bleeding.
(Internal Medicine 34: 901-903, 1995)

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We report a case of non-insulin-dependent diabetes mellitus (NIDDM) complicated with idiopathic hypoparathyroidism. A 74-year-old male was hospitalized because of diplopia. He was revealed to have NIDDM. The levels of serum Ca and intact-PTH were 6.3 mg/dl and <5 pg/ml, respectively. Brain computed tomography revealed abnormal calcification in the cerebral basal ganglia and the cerebellum. After recovery from hypocalcemia, the endogenous insulin secretion was normalized. It is suggested that the pathogenesis of NIDDM in this patient may have been related to an insulin secretory defect as a result of hypocalcemia in addition to the hereditary risk.
(Internal Medicine 34: 904-907, 1995)

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Systemic calciphylaxis is a rare, poorly understood syndrome of progressive peripheral ischemic necrosis and medial arterial calcification in patients with end-stage renal disease. We report a patient with this syndrome which developed following corticosteroid administration and who ultimately required amputation of the four extremities. Furthermore, cerebral, myocardial, splenic, and intestinal infarctions also developed in parallel with the increment of visceral arterial calcification. No evidence of noticeable hyperparathyroidism or elevation of serum calcium-phosphate product was observed. We speculated that, in addition to diabetes mellitus and chronic renal failure while undergoing dialysis therapy, the administration of corticosteroids might act synergistically to cause calciphylaxis.
(Internal Medicine 34: 908-912, 1995)

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Tumor metastasis to the hypophyseal system has rarely been reported with either clinical or radiographic evidence. A 52-year-old woman presented with polydipsia, polyuria, and loss of appetite. She was diagnosed as having diabetes insipidus caused by pituitary micrometastasis of lung adenocarcinoma. After she had been treated with radiation therapy to the pituitary gland, the gland size was reduced as confirmed by magnetic resonance imaging, and her urine volume decreased. However, meningitis carcinomatosa appeared later. This was a rare case of secondary diabetes insipidus due to pituitary metastasis of lung cancer.
(Internal Medicine 34: 913-918, 1995)

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We report a family with Becker muscular dystrophy (BMD) presenting with cardiac involvement. The proband was a 41-year-old Japanese man who was hospitalized with exertional dyspnea and muscle weakness. Cardiac examination showed findings consistent with dilated cardiomyopathy. Dystrophin immunohistochemical analysis showed a discontinuous patchy staining pattern in cardiac and skeletal muscles biopsied from the proband. His brothers had high creatine kinase (CK) activity and abnormal electrocardiogram. Dystrophin gene analysis revealed that the proband and his brothers had G-to-T transversion at the terminal nucleotide of exon!3. We conclude that the mutated dystrophin gene may cause cardiac involvement as a symptom precedent to skeletal muscle involvement.
(Internal Medicine 34: 919-923, 1995)

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A 26-year-old man with Graves' hyperthyroidism associated with central diabetes insipidus (DI), initially showed hypercalcemic crisis. Initially, very low serum levels of intact parathyroid hormone (PTH) and 1, 25-dihydroxy vitamin D₃ and a moderate rise of serum C-terminal PTH related protein (C-PTHrP) were observed which strongly suggested a humoral hypercalcemia of malignancy due to PTHrP. However, the serum C-PTHrP level later became normal. Mild hyperprolactinemia, no responses of growth hormone (GH) to insulin-induced hypoglycemia despite a normal growth hormone releasing hormone (GRH) test and mild thickening of the pituitary stalk on magnetic resonance imaging were observed. Thus, an autoimmune nature of his central DI is considered; it is noteworthy that the serum C-PTHrP level may be elevated by renal failure in patients with hypercalcemia due to causes other than PTHrP.
(Internal Medicine 34: 924-928, 1995)

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