We evaluated the renal handling of urate in 12 Japanese renal hypouricemia patients, and studied the relationship between the renal handling of urate and the urinary pH. The patients were classified into the 4 subtypes of renal hypouricemia: (defective presecretory reabsorption (Pre), defective postsecretory reabsorption (Post), enhanced tubular secretion (Secretion), and defective presecretory and postsecretory reabsorption (Pre&Post) as based on a pharmacological test. Seven patients showed acid urine with a urinary pH of less than 5.9, although this was not accompanied by any abnormality of blood pH, partial pressure of carbon dioxide (PaCO₂), or blood HCO₃^-. The urinary pH in the morning significantly correlated with the ratio of urate clearance to creatinine clearance in the morning, whereas the urinary urate concentration in the morning did not correlate with the urinary pH in the morning. In the Pre&Post patients, the urate excretion was higher and the urinary pH was more acidic compared to the other subtypes. The administration of K⁺-, Na⁺-citrate significantly alkalized the urinary pH in the patients with renal hypouricemia. These results suggest that the acidic urine was significantly related to the Pre&Post subtype of renal hypouricemia with the higher urate excretion, and that this subtype might be a risk factor for complications in renal hypouricemia. The alkalization of urine might be a useful treatment for the complication of renal hypouricemia.
(Internal Medicine 37: 726-731, 1998)

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There are two types of coughs, productive and non-productive; the former is caused by excess airway secretions. The analysis of cough may provide important clues not only to aid diagnosis, but also for the selection of drugs for treatment. In this study, cough sounds recorded in a free acoustic field from patients with productive cough and non-productive cough due to chronic airway diseases were compared with those of voluntary cough of healthy subjects and were analyzed by sound spectrogram and time-expanded waveform. All cough sounds could be separated into two or three phases. The implementation of the novel technique to record cough sounds in the free acoustic field and to analyze the sounds of the high frequency range enable recognition of the characteristics of the cough sounds in phase 2 of the cough.
(Internal Medicine 37: 732-735, 1998)

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We performed a cross-sectional survey of stroke and acute myocardial infarction (AMI) in Okinawa, Japan with a census population of about 1.2 million. A total of 3, 644 cases of first-ever stroke and 898 cases of initial acute myocardial infarction (AMI) were detected. The age-adjusted annual incidence rate for stroke was 105 per 100, 000 standard population of Japan, and that of AMI was 26. The case-fatality rate of stroke within 28 days of onset was 12.8%, and that of AMI was 22.2 %. Of the stroke cases, 51.4 % were diagnosed as brain infarction, 38.7 % as brain hemorrhage, and 9.3% as subarachnoid hemorrhage. The diagnosis of stroke subtypes were confirmed by computed tomography or magnetic resonance imaging in 98.4% of all stroke cases. In Okinawa, the incidence rate of AMI was still considerably lower than that in the Western population, and the rate of stroke was similar to that in the Western population.
(Internal Medicine 37: 736-745, 1998)

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In a previous report we suggested that muscle fibers in distal myopathy with rimmed vacuoles (DMRV) were degraded by both lysosomal proteolysis (cathepsins) and Ca²⁺-dependent, nonlysosomal proteolysis (ealpain). Given recent evidence of abnormal ubiquitin accumulation in rimmed vacuoles, we examined the role of the ATP-ubiquitin-dependent proteolytic pathway (proteasomes) in myofiber degradation in this myopathy. Immunohistochemically, proteasomes (26S) were located in the cytoplasm in normal human muscle, but the staining intensity was weak. Quantitative analysis showed more reactivity for proteasomes in DMRV muscles and, to a lesser extent, in muscles from muscular dystrophy, polymyositis, and amyotrophic lateral sclerosis patients. In DMRV, proteasomes often were located within or on the rim of rimmed vacuoles, and in the cytoplasm of atrophic fibers. Ubiquitin accumulation was marked within rimmed vacuoles and was seen less extensively in the cytoplasm of atrophic fibers. The latter proteins colocalized well. In other diseased muscles, proteasomes and ubiquitin showed a positive reaction in the atrophic or necrotic fibers. The results indicate increased proteasome and ubiquitin in these muscle fibers as well as in other diseased muscle fibers. We suggest that the ATP-ubiquitin-proteasome proteolytic pathway as well as the nonlysosomal ealpain and the lysosomal proteolytic pathway may participate in the muscle fiber degradation in DMRV.
(Internal Medicine 37: 746-752, 1998)

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We observed 3 diabetic patients with intolerable dizziness followed by nausea and vomiting immediately after an initial administration of the alpha-glucosidase inhibitor, voglibose. These symptoms did not recur after discontinuation of the drug. Adverse effects as observed in these cases have not been reported previously. Since the 3 patients were relatively old (average age, 72 years old) and had various degrees of micro- and macroangiopathies, these side effects may have been associated with increased micro- and macrocirculatory disturbances in their central nervous systems through alpha-glucosidase inhibition of this agent.
(Internal Medicine 37: 753-756, 1998)

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A 24-year-old man who had uveitis and showed intrathoracic lymph node swelling on a chest X-ray, was admitted to our hospital for further examination. Transbronchial lung biopsy specimens revealed non-caseating granulomas compatible to sarcoidosis. As the renal function became progressively worse, a specimen was obtained by renal biopsy. It showed a granuloma formation, and was diagnosed as renal sarcoidosis. A high level of interleukin(IL)-6 was detected in his urine. After oral administration of prednisolone, the renal function improved, and the urinary IL-6 level was reduced. These findings suggest that in sarcoidosis associated with renal failure, steroid therapy is effective and that IL-6 plays an important role in the pathogenesis of renal involvement of sarcoidosis.
(Internal Medicine 37: 757-761, 1998)

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A 47-year-old man presented with acute renal failure following oxalate ingestion. Nausea and hematoemesis appeared four hours after attempted suicide and acute oliguric renal failure ensued the following day. The patient underwent four sessions of hemodialysis and then reverted to normal state. Histopathologic examination of renal biopsy specimen revealed the degeneration of the renal tubular epithelial cells associated with intracellular calcium oxalate crystal deposition. Most of the renal tubules were patent despite the intraluminar crystal deposition. These findings suggest that dysfunction of the renal tubular epithelial cell plays a more important role than tubular obstruction in developing acute renal failure.
(Internal Medicine 37: 762-765, 1998)

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We describe a 60-year-old woman with leg pain. Although metastatic bone tumor and atypical cells mimicking signet-ring cells in the bone marrow picture were observed, systemic survey revealed no primary lesion. The patient died two months after admission from systemic progress of the disease. Autopsy revealed a small focus of adenocarcinoma within the right upper lobe of the lung and systemic metastases without any particular changes in the gastrointestinal tract. The tumor cells of the lung were diffusely positive for cytokeratin 7, whereas cytokeratin 20 immunoreactivity was weak and focal, and that supported the lung origin of the present tumor. Moreover, the tumor cells in the bone marrow showed a similar pattern in immunoreactivity. These findings suggest that cytokeratin 7 and cytokeratin 20 immunoreactivity is helpful for the premorten diagnosis of the metastatic tumor of unknown origin.
(Internal Medicine 37: 766-769, 1998)

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We applied a new technique of three-dimensional (3-D) transcranial power Doppler imaging to demonstrate the middle cerebral artery (MCA) in the 2 stroke patients. In the first patient, the 3-D power Doppler study clearly showed the horizontal portion, bifurcation, proximal portion of the upper and lower trunks, and the major branches of the lower trunk of the MCA. In the second patient, the 3-D power Doppler clearly revealed the proximal bifurcation of the left MCA. The 3-D transcranial power Doppler seems to be useful in making clear 3-D images of the MCA.
(Internal Medicine 37: 770-773, 1998)

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Carbamazepine (CBZ) is a drug frequently used to treat variety of neurological diseases or symptoms. Among its adverse effects, auditory disturbance is described rarely. In the present report, we describe an 18-year-old girl who noted false lowering of perceived pitch after starting CBZ treatment for epilepsy, and review the literature reporting CBZ-associated abnormal pitch perception.
(Internal Medicine 37: 774-775, 1998)

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This is the first magnetic resonance imaging (MRI) report of nemaline myopathy in which muscle atrophy was not apparent clinically in the lower extremities because of subcutaneous fat. The patient is a 38-year-old woman who was admitted to our hospital because of muscle weakness of the four extremities. Until the age of 17 years, she was asymptomatic except that her running speed was slow. The T₁-weighted image of muscle MRI at the mid-thigh level showed hyperintensity of the quadriceps femoris muscle and relatively spared hamstring muscle. The T₂-weighted image of muscle MRI at the maximum diameter of the lower leg showed hyperintensity of the tibialis anterior muscle and a relatively spared triceps surae muscle. The biopsy specimen of the right deltoid muscle showed nemaline bodies and type II fiber deficiency.
(Internal Medicine 37: 776-779, 1998)

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We report a 31-year-old woman who developed myopathy and neuropathy during pregnancy. She was diagnosed as having mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). A T-to-C transition mutation at nucleotide position 3271 was detected in the mitochondrial gene. Her symptoms subsided spontaneously and she delivered a male infant at 38 weeks of gestation. Prior reports on mitochondrial diseases with pregnancy are very rare, probably because of the early onset of the disease. The metabolic changes during pregnancy increase the stress on the mitochondrial function, particularly in patients with impaired mitochondrial function. Therefore pregnancy can aggravate mitochondrial diseases.
(Internal Medicine 37: 780-783, 1998)

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Satoyoshi syndrome consists of painful intermittent muscle spasms, alopecia and diarrhea. The age of onset is commonly less than 20 years of age. Adult onset of this syndrome is rare. We report a 65-year-old Japanese woman with Satoyoshi's syndrome of adult onset. Satoyoshi's syndrome of adult onset shows no skeletal abnormalities, in comparison with the classical pediatric cases. The clinical features in our patient revealed the benign and long-term course of muscle spasm and alopecia. This progression differed markedly from the other patients of adult onset. Thus, the severity of Satoyoshi's syndrome is variable in adult onset cases, and this diagnosis should be considered in adults with various and unexplained muscle spasms.
(Internal Medicine 37: 784-787, 1998)

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Nalon-Ace® and other nonsteroidal anti-inflammatory drugs (NSAID) containing bromvalerylurea (BVU) are sold as over-the-counter (OTC) drugs and are obtainable without prescription in Japan. A 32-year-old woman was diagnosed as having chronic BVU intoxication due to habitual use of Nalon-Ace®. In addition to cerebellar ataxia and pyramidal signs well known in this condition, she showed an as yet non-described dystonic posture of the neck. Laboratory tests revealed an elevated concentration of serum organic bromide, iron deficiency anemia, and hyperchloremia. Brain magnetic resonance imaging (MRI) revealed definite cerebellar atrophy. We should consider the possibility of chronic BVU intoxication in peculiar neurological cases like ours.
(Internal Medicine 37: 788-791, 1998)

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A 66-year-old man was admitted with destructive arthropathy, and calcium pyrophosphate dihydrate was demonstrated in the synovial fluid specimen. He was found to have a hyponatremia. The serum sodium concentration was 121 mmol/ι, plasma arginine vasopressin (AVP) 6.6 pmol/ι, and serum interleukin (IL)-6 96 pg/ι. The clinical findings suggest the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). However, destructive arthropathy with increased values of C-reactive protein and IL-6 is the only background of SIADH in this patient. We suggest the possibility that IL-6 produced at inflammatory lesions may have stimulated an excessive release of AVP resulting in the hyponatremia and hypochloremia of SIADH.
(Internal Medicine 37: 792-795, 1998)

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