Chronic respiratory failure is defined on the basis of gas exchange in the lung. Recent studies have suggested serious clinical problems in patients with disabling dyspnea not necessarily related to gas exchange. Home oxygen therapy not only prolongs life expectancy but also improves the quality of daily life. In Japan, pulmonary emphysema, sequelae of pulmonary tuberculosis, and interstitial pneumonia/pulmonary flbrosis are the 3 major diseases currently treated by home oxygen therapy. Respiratory failure caused by interstitial pneumonia/pulmonary fibrosis and lung cancer is on the increase and is also treated by home oxygen therapy. Clinical problems on mechanisms and treatment of chronic respiratory failure are reviewed from recent data.
(Internal Medicine 35: 436-442, 1996)

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To investigate the influence of alcohol intake on tumor growth of hepatocellular carcinoma (HCC) in patients with type C cirrhosis, we examined the tumor volume doubling time (TVDT) of 35 nodules from 35 cases of HCC, calculated through ultrasonographic imaging. The patients were divided into two groups according to their drinking habit; 21 habitual drinkers (alcohol group; 80g ethanol/day for 5 years), and 14 patients without alcohol abuse (non alcoholic group). The average value of TVDT in the alcoholic group was 78±47 days, although that of the non alcoholic group was 142±60 days. A statistically significant difference (p<0.01) was found between the two groups. Of the 21 habitual alcohol drinkers, 8 refrained from drinking after detection of HCC; their TVDT was about 30 days shorter than those who continued alcohol intake. In conclusion we found that alcohol intake was closely related to the tumor growth of HCC in patients with type C cirrhosis.
(Internal Medicine 35: 443-448, 1996)

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In order to evaluate the role of RET proto-oncogene in the development and growth of pheochromocytomas, we examined mutations in RET and expression of RET in 7 cases of sporadic pheochromocytomas. Tumors were screened for mutations in exons 10 and 11 and codon 918 which are identified in multiple endocrine neoplasia types 2A and 2B. No mutations were found in these regions in all of the sporadic pheochromocytomas examined. On the other hand, RET mRNA was detected in all pheochromocytomas and the levels of RET expression were higher in 5 of 7 pheochromocytomas than in normal adrenal medulla, indicating that RET is overexpressed in a sizable portion of sporadic pheochromocytomas. These results suggest that high levels of expression of RET may have relevance to the development or growth of sporadic pheochromocytomas.
(Internal Medicine 35: 449-452, 1996)

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We examined the relationships among dyspnea ratings in daily life, the physiologic state, and anxiety and depression of fifty-two patients with chronic obstructive disease (COPD) during longterm domiciliary oxygen therapy (LTOT). Clinical ratings of dyspnea were assessed by the visualanalog scale (VAS) during eight types of basic behavior in indoor daily life. Analysis of the physiologic state included forced expiratory volume in 1 second (FEV_1.0), and arterial blood gas (PaO₂, PaCO₂) at rest while breathing room air. The hospital anxiety and depression (HAD) scale, which consists of 14 questions, was used to assess the degree of anxiety (HAD-A) and depression (HAD-D). The mean age of the patients was 69.5±10.8 year (SD), and the duration of LTOT was 944±739 days. The mean values were 0.77±0.45 L for FEV_1.0, 57.7±7.4 Torr for PaO₂, and 47.4±8.1 Torr for PaCO₂. FEV_1.0 was correlated with PaCO₂ (r=-0.548, p<0.0001), but it was not correlated with PaO₂. High correlation was noted between HAD-A and HAD-D (r=0.693, p<0.0001), whereas correlation was not noted between HAD and the physiologic state. VAS was significantly correlated with FEV_1.0 (r=0.320, p<0.05), as well as with HAD-A (r=0.358, p<0.01) and HAD-D (r=0.444, p<0.01). Dyspnea ratings were found to be influenced by anxiety and the depression state, and also by the degree of flow limitation in patients with COPD during LTOT. In contrast, the physiologic state scarcely influenced the anxiety and depression state. Thus, psychotherapy may play an important role in the reduction of dyspnea sensation, which is an important determinant of quality of life.
(Internal Medicine 35: 453-458, 1996)

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Metastasis to the skin from lung cancer is less common than metastasis to other organs. We clinically reviewed 16 cases of skin metastasis. The incidence of skin metastasis was 2.8% among all 579 cases of lung cancer. Large cell carcinoma showed the greatest tendency to spread to the skin and epidermoid carcinoma showed the least tendency. The most common sites for skin lesions were the back. Almost all lesions ranged from 1 to 5 cm in diameter. Clinical manifestation of skin metastasis was nodular type in all cases. At the development of skin metastasis, all cases were accompanied by metastasis to other organs. There was only a slight response to combination chemotherapy carried out 5 cases for lung cancer, and most lesions were progressive. Median survival after skin involvement was approximately 4 months.
(Internal Medicine 35: 459-462, 1996)

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Genetic diagnosis of a family of β-thalassemia (β⁹⁰ GAG→TAG) was carried out by allelespecific polymerase chain reaction (AS-PCR). The proband, her daughter and granddaughter were proved to be heterozygotes of normal and mutant alleles. As some nonsense mutations express a decreased amount of mRNAs, we determined the expression level of the mutant mRNA of (β-thalassemia (β⁹⁰ GAG→TAG), by application of a combination method of reverse transcription PCR (RT-PCR) and dot-blot hybridization with allele-specific oligonucleotides. The mutant mRNA was not markedly reduced. In conclusion, 1) individuals with the mutant β-globin gene were diagnosed successfully by AS-PCR, and 2) a significant amount of the mutant β-globin mRNA was synthesized.
(Internal Medicine 35: 463-467, 1996)

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We describe a hepatitis B virus carrier who satisfied the criteria of autoimmune hepatitis proposed by the International Autoimmune Hepatitis Group. A 43-year-old Japanese female showed human leukocyte antigen typing including DR4 in addition to hypergammaglobulinemia, presence of autoantibodies, and liver histology suggestive of autoimmune hepatitis. Moreover, the predominant presence of hepatitis B core antigen in nuclei rather than in cytoplasm of hepatocytes suggested less of a possibility of liver cell damage related to hepatitis B virus infection. She completely responded to immunosuppressive therapy and no clinical or biochemical relapse has been recognized to date.
(Internal Medicine 35: 468-471, 1996)

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A case of pituitary apoplexy occurring after subtotal thyroidectomy in an acromegalic woman with a large adenomatous goiter is described. The patient had severe apnea because the large goiter was causing airway compression. Prior to the planned hypophysectomy, a subtotal thyroidectomy was performed to relieve tracheal stenosis. Shortly after the operation, the patient developed a headache that lasted for several days. The serum levels of growth hormone and somatomedin-C spontaneously normalized seventeen days after this episode and have remained normal for two years. Pituitary apoplexy was thought to have caused the observed results without deterioration of the pituitary function.
(Internal Medicine 35: 472-477, 1996)

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Two rheumatoid arthritis (RA) patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during the course of infection are herein reported. One patient developed SIADH during the course of a localized cutaneous herpes zoster infection while the other developed SIADH in conjunction with Staphylococcus simulans septicemia. We consider that the development of SIADH was strongly associated with superimposed infections in the underlying RA. This is the first report discussing the association of SIADH and infections in RA patients in which SIADH is diagnosed by measurement of plasma ADH.
(Internal Medicine 35: 478-481, 1996)

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A 31-year-old man who had been under regular hemodialysis for 6 months was diagnosed as Williams syndrome (WS) by fluorescence in situ hybridization (FISH) chromosomal analysis. The association of WS and chronic renal failure (CRF) is only rarely encountered. Endocrinological examinations revealed hypergonadotropic hypogonadism. Prolonged and exaggerated responses of adrenocorticotropin (ACTH) to insulin-induced hypoglycemia and corticotropin releasing hormone (CRH) were also noted. While most of the endocrinological abnormalities observed in this patient could be attributed to altered endocrine circumstances in CRF, some findings stand in contrast. Furthermore, the testicular biopsy specimen showed severe hypospermatogenesis. Endocrine disorders observed in this patient may be at least in part, responsible for various clinical features underlying WS.
(Internal Medicine 35: 482-488, 1996)

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We report a patient who exhibited proteinuria and renal failure 93 months after receiving an allogeneic bone marrow transplantation (BMT) from his HLA-identical brother. A renal biopsy specimen revealed segmental sclerosis, mesangiolysis, subendothelial lucency in the glomeruli, fibrosis and small round cell infiltration in the interstitium, and hyaline droplets in the intimal spaces of arterioles and small arteries. These histological findings were consistent with late onset BMT nephropathy. This nephropathy may represent a more serious problem in the near future in Japan, since the number of BMT performed has been increasing with the establishment of a bone marrow bank.
(Internal Medicine 35: 489-493, 1996)

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We report the first case of Kamisyoyo-san-induced adult respiratory distress syndrome (ARDS). A 59-year-old female was given Kamisyoyo-san for treatment of seborrheic dermatitis. She then presented with a respiratory illness having clinical, radiologic and functional characteristics of ARDS. Bronchoalveolar lavage fluid showed an increased number of lymphocytes, neutrophils and eosinophils. The lymphocyte stimulation test with Kamisyoyo-san was positive.
(Internal Medicine 35: 494-496, 1996)

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We report a case with adult respiratory distress syndrome (ARDS) associated with increased levels of squamous cell carcinoma-related antigen (SCC) in the serum and bronchoalveolar lavage fluid (BALF). ARDS was likely induced by ibuprofen, based on the presence of pancytopenia and a weakly positive drug lymphocyte stimulating test (DLST). High serum and BALF levels of interleukin (IL)-8, neutrophil elastase as well as SCC were detected. Corticosteroid therapy resulted in clinical improvement, resolution of pulmonary infiltrates on chest roentgenogram and normalization of serum and BALF levels of IL-8, neutrophil elastase and SCC.
(Internal Medicine 35: 497-501, 1996)

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Visceral leishmaniasis is a chronic infectious disease caused by a protozoan parasite of the genus Leishmania, characterized by intermittent fever, monocytosis, hepatosplenomegaly and hypergammaglobulinemia. This morbid condition is rather difficult to diagnose correctly, especially at its early stage, because it is rarely encountered in Japan. Recently we treated a case of visceral leishmaniasis in which the patient was misdiagnosed as malignant lymphoma, and went through splenectomy and steroid administration, which made the diagnosis more difficult.
(Internal Medicine 35: 502-506, 1996)

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A sporadic Japanese case of myotonia congenita with painful muscle cramps is reported. Electromyographic examinations disclosed myotonic discharge with dive bomber sounds at insertion, and high-amplitude, high-frequency motor unit potentials during the muscle cramps. Biopsied muscle specimens and EMG findings showed non-specific mild myopathic changes. There was no abnormal expansion of CTG repeat within the myotonic dystrophy gene. This patient's disorder closely resembles Becker's myotonia congenita Type II though the family history of was non contributory.
(Internal Medicine 35: 507-511, 1996)

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A case of cibenzoline-induced myasthenia-like syndrome is reported. A 67-year-old woman with renal failure and no previous disorder of neuromuscular junction complained of fatigue during climbing up a flight of stairs and experiencing heavy eyelids after administration of 100 mg/day of cibenzoline. Repetitive nerve stimulation tests revealed decrement at 5-10 Hz. After reduction of the dosage, myasthenia-like signs and symptoms disappeared. The peak cibenzoline concentration was still high even after the dose reduction (666.4 ng/ml). In conclusion, cibenzoline, at a high plasma level, may induce myasthenia-like syndrome without any disorder of the neuromuscular junction.
(Internal Medicine 35: 512-514, 1996)

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A patient with a history of cerebrovascular disease, hypertension, and previous gastrectomy developed metabolic alkalosis and myoclonus. His medications included the anti-hypertensive agents nicardipine hydrochloride, delapril, prazosin; dihydroergotoxin and ticlopidine for cerebral infarction; estazolam for insomnia; azuren-L-glutamine compound and S-M powder. In addition, he had taken 12 grams per day of Ohta's Isan® antacid, which contained 625 mg sodium bicarbonate per 1.3g of antacid powder over a 6-month period. This antacid is commonly used in Japan. This is the first report of a case of metabolic alkalosis and myoclonus secondary to ingestion of a commercially available antacid in Japan.
(Internal Medicine 35: 515-516, 1996)

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We report an unusual case of cytomegalovirus (CMV) interstitial pneumonitis (IP) occurring in a 51-year-old Japanese woman with systemic lupus erythematosus (SLE). She developed hypoxemia after intensive immunosuppressive therapy with prednisolone and cyclophosphamide. Fine crackles were audible in the lower lungs bilaterally. Chest X-ray and computed tomography confirmed the presence of IP. CMV-antigenemia was confirmed by immunological staining of leukocytes using the peroxidase-labeled monoclonal antibody, HRP-C7. Hypoxemia improved gradually on methylprednisolone pulse therapy and gancyclovir, and CMV-antigen positive leukocytes disappeared from the peripheral blood. Data suggest the importance of CMV as a cause of IP in SLE, and the usefulness of the assay for CMV-antigenemia with C7-HRP for rapid diagnosis.
(Internal Medicine 35: 517-520, 1996)

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