Urinary albumin fragments (uAF) from patients with NIDDM were analyzed as a possible factor in the early discovery of diabetic nephropathy before emergence of microalbuminuria. SDS-PAGE and immunoblot assay were employed for detection of uAF. Samples from 252 patients with NIDDM, 158 patients with non-diabetic diseases, and 48 healthy volunteers were examined; uAF were detected in 139 (55.2%), 94 (59.5%), only one (2.1%), respectively. In diabetic patients with normoalbuminuria, uAF were detected in 48 out of 159 cases (30.2%). Two years after the initial study, 3 of the 17 diabetic patients (17.6%) with normoalbuminuria and uAF showed micro- or macroalbuminuria. It was concluded that detection of uAF might be useful for the early detection of diabetic nephropathy in NIDDM.
(Internal Medicine 34: 463-468, 1995)

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We studied the efficacy of the long-term administration of 14-membered ring macrolides in treating patients with diffuse panbronchiolitis (DPB) (34 patients) and bronchiectasis (BE) (40 patients). Oral administration of erythromycin (400 or 600 mg), roxithromycin (150 or 300 mg) or clarithromycin (200 or 400 nig) given daily for at least 2 months, was evaluated. The efficacy of erythromycin, roxithromycin, and clarithromycin in DPB was 19/24 (79%), 6/7 (86%), and 2/3 (67 %), respectively. Efficacy of these agents in BE exceeded 50 %. We determined the effect of these macrolides on the activity of polymorphonuclear leukocytes (PMNs) obtained from healthy volunteers. There were no significant differences between the effects of these 14-membered ring macrolides and josamycin, a 16-membered ring macrolide which was previously found to be ineffective in treating DPB. Thus, the effectiveness of the 14-membered ring macrolides in treating DPB appears to depend on mechanism(s) other than alterations in PMN activity.
(Internal Medicine 34: 469-474, 1995)

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To evaluate dipstick urinalysis as a predictor of subsequent kidney and urinary tract disorders in apparently healthy adults, we designed a cross-sectional, prospective, and retrospective study within a cohort. The severity of proteinuria was significantly (p<0.01) associated with the amount of pathological casts, whereas hematuria without proteinuria was not. The frequency of subsequent serum creatinine increase (0.3 mg/dl/5 years or more) was significantly enhanced (from 0.4% to 7.3% along with the severity of proteinuria, whereas it was not related to the severity of hematuria. Patients who subsequently developed renal failure and glomerulonephritis exhibited hematuria (11.1-32.1%) less frequent than proteinuria (62.3-83.3%). Even those with renal tumors or stones showed infrequent (14.3-27.9%) hematuria. Thus, urine protein and occult blood have different implications in mass screening.
(Internal Medicine 34: 475-480, 1995)

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The levels of α1-antichymotrypsin (ACT) in cerebrospinal fluid (CSF) from 66 sporadic Alzheimer's disease (AD) patients and 54 normal controls were measured by enzyme immunoassay and compared. There was no correlation (r=0.259, n=54) between the ACT level and normal aging. The levels of ACT were significantly higher in the total AD group (p<0.01) than in the normal control group. Dividing AD patients into early onset AD (n=27) and late onset AD groups (n=39), the mean level of CSF ACT in the late onset AD group was significantly higher than that in the normal control group (p<0.001) and that in the early onset AD group (p<0.01). Thus, the level of ACT in CSF is closely associated with late onset AD.
(Internal Medicine 34: 481-484, 1995)

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Forty-four patients with catheter-related infection admitted to Hokusho Central Hospital between 1985 and 1991 were studied retrospectively. The rate of catheter-related fungemia or bacteremia to all corresponding cases of fungemia and bacteremia increased from 7.7% in 1985 to 28.8% in 1991. The isolated pathogens were Candida parapsilosis (8 strains), Candida tropicalis (6 strains), methicillin-resistant Staphylococcus aureus (MRSA) (6 strains), methicillin-sensitive S. aureus (MSSA) (5 strains) and Streptococcus epidermidis (3 strains). Bacteremia occurred after catheterization of the femoral vein for a mean duration of 37 days. The period was significantly shorter than that after catheterization of the subclavian vein (56 days). The major isolates from the subclavian vein were Candida spp. (14/17, 82.4%), followed by MRSA (1/17, 5.9%) and MSSA (1/17, 5.9%), while isolates from the femoral vein were Candida spp. (6/16, 37.5%), MRSA (5/16, 31.3%) and MSSA (3/16, 20.8%). Catheter removal alone did not improve the clinical condition, particularly in MRSA bacteremia; the combination of antimicrobial therapy and removal of the catheter was necessary for a better prognosis.
(Internal Medicine 34: 485-490, 1995)

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Infections in immunocompromised hosts have been an important clinical problem. Patients with liver cirrhosis and/or hepatocellular carcinoma are at a high risk of infection due to multiple factors. Five hundred and two patients admitted with liver cirrhosis and/or hepatocellular carcinoma were evaluated for infection. The infection rate was not influenced by the etiology of hepatic diseases or the presence of hepatocellular carcinoma, however, it increased with the advance of clinical stages of liver cirrhosis and hepatoma. The respiratory tract and urinary tract were the most common sites of infection, being involved in 50 % and 28 % of cases, respectively. The major pathogens of respiratory tract infection were S. aureus, H. influenzae, and P. aeruginosa. Gram-negative bacteria was the common isolate from sputum and urine, and S. aureus was also common in gram-positive bacteria. The infection rate was high in patients who died although infections could rarely be implicated as the direct cause of death. These findings should be a guide for the clinicians in treating patients with liver cirrhosis and/or hepatocellular carcinoma who exhibit signs of infection.
(Internal Medicine 34: 491-495, 1995)

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We investigated the specificity of various autoantibodies in antimitochondrial antibody (AMA)-negative patients with primary biliary cirrhosis (PBC). We examined sera from 144 patients with PBC, 17 of whom were AMA negative by indirect immunofluorescence. The AMA-negative group showed a significantly higher positivity for smooth muscle antibody, but not for antinuclear antibody, as compared with the AMA-positive group. IgG class anti-PDH by enzyme-linked immunosorbent assay (ELIS A) were detected in 13 % of the AM A-negative group. However, all PBC patients showed positive IgG, IgA, and/or IgM class anti-M2 to the four M2 proteins by immunoblotting. These results suggest that the detection of IgG and IgM class anti-PDH and that of antibodies to the four M2 proteins increases the positivity of this ELISA method, and that detection of IgG, IgA, and IgM class anti-M2 to the four M2 proteins by immunoblotting is useful in diagnosing AMA-negative patients with PBC.
(Internal Medicine 34: 496-501, 1995)

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Recurrent rhabdomyolysis due to decreased glycolysis occurred during strenuous exercise in patients with lactate dehydrogenase A subunit (LDH-A) deficiency. We report the features of oxidative metabolism of four patients from two families in whom the severity of the disease differed. Enzyme activities of muscle LDH were decreased to <5 % of control. There was no difference in the gene abnormality. Maximal oxygen uptake in the patients with severe and mild symptoms was approximately 73% and 92% of control. Respiratory exchange ratio was increased to more than 1.0 during maximal exercise. These findings suggest that in these patients, the oxidative functions of glycogenolysis in which pyruvate is required for fuel of maximal oxidative metabolism are preserved, and that disease severity may be related to the degree of muscle oxidative capacity.
(Internal Medicine 34: 502-506, 1995)

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This study was undertaken to design the optimal criteria for practical guidelines for lymph node metastasis evaluation in epidermoid lung cancer. Resected lymph nodes (n=214) were analyzed by preoperative computed tomography (CT) images and postoperative histopathological findings. Definite criteria were defined by efficiency, and possible criteria by receiver operating characteristic (ROC) analysis. Statistical values of highest efficiency in 214 lymph nodes revealed that the minor axis offered the best criteria (minor axis 13 mm; efficiency 93%). ROC curve using the minor axis which showed the highest values of sensitivity and specificity in the optimal criteria (minor axis 9.3 mm; sensitivity 76%, specificity 76 %). The criteria of the paratracheal lymph nodes were smaller than those of tracheobronchial and subcarinal nodes. In conclusion, it is desirable to evaluate metastasis of lymph nodes by the minor axis, and criteria should be considered changeable to accommodate the anatomical location in epidermoid lung cancer.
(Internal Medicine 34: 507-513, 1995)

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We report an outbreak of transient thyrotoxicosis that occurred between June and September 1993, in Matsuyama City, Ehime Prefecture. One hundred fifty-nine cases of thyrotoxicosis were identified, all in individuals without goiter. Thyroid autoantibodies were absent, and the serum thyroglobulin level was depressed. Ultrasonography of the thyroid disclosed no abnormal findings, while scintigraphy of the thyroid with ^99mTc revealed poor uptake. About ten days after the onset, the serum thyroid hormone levels were normalized. No significant elevation of serum viral antibodies was found. These observations suggest that a thyrotoxicosis factitia may have been the cause of the present outbreak.
(Internal Medicine 34: 514-519, 1995)

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Renal function was assessed in 329 inpatients who were presumably free of renal disease or water-electrolyte imbalance and the relationship between renal function and aging and sexual differences were investigated. Serum creatinine levels were slightly increased with aging, and were significantly higher in males than in females. Urinary creatinine excretion significantly decreased with aging; this decline was more pronounced in males. Urinary creatinine excretion was significantly higher in males. Creatinine clearance also decreased significantly with aging and this tendency was still observed after correction for body surface area. Sexual differences played no part in creatinine clearance. There was a significant increase in the serum β₂-microglobulin level with aging. In addition, the Ccr of the aged Japanese population was lower in comparison with western counterpart. The findings suggest the need for special consideration in conducting clinical tests or administering drugs to this segment of the population in Japan.
(Internal Medicine 34: 520-527, 1995)

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Daytime blood pressure (BP) in 31 male patients with obstructive sleep apnea syndrome (OSAS) was measured and the effects of nasal continuous positive airway pressure (CPAP) treatment on daytime BP were studied. Subjects were 48±10 (mean±SD) years old and weighed 80±13 kg. The mean systolic BP and diastolic BP were 135±15 mmHg and 88±14 mmHg, respectively and daytime hypertension was present in 12 (38%) subjects. Apnea index (AI) and the lowest oxygen saturation during sleep were significantly more severe in the hypertensive (HT) than in the non-hypertensive (NHT) patients (p<0.05). AI was significantly correlated with diastolic BP (p<0.05) and the mean and lowest oxygen saturation during sleep were significantly correlated with both systolic (p<0.05) and diastolic BP (p<0.01). After nasal CPAP treatment for two weeks, both systolic and diastolic BP were significantly reduced; the former from 135±15 mmHg to 126±10 mmHg (p<0.005) and the latter from 88±14 mmHg to 78±6 mmHg (p<0.001). These data form direct evidence that daytime hypertension is partially induced by OSAS and is reversible with nasal CPAP treatment.
(Internal Medicine 34: 528-532, 1995)

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We previously reported a case of Addison's disease associated with acquired immunodeficiency syndrome (AIDS) (Endocr J, 41: 13, 1994). A 46-year-old man with hemophilia B and AIDS was diagnosed as Addison's disease. The positive cytomegalovirus (CMV) antigen in urine suggested that CMV adrenalitis may have caused the adrenal insufficiency. Despite treatment with ganciclovir, the patient died one year later. Autopsy findings revealed that the typical inclusions of CMV were seen in the lung, adrenal glands (both cortex and medulla) and small intestine. Here, we describe the subsequent clinical course and postmortem findings of this case.
(Internal Medicine 34: 533-536, 1995)

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We report 7 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who showed significant clinical improvement by plasma exchange (PE). Their clinical features were extensively varied but fulfilled the diagnostic criteria for CIDP. The patients could be divided into 2 subgroups based on the mode of effectiveness of PE; one group consisted of those who once achieved complete remission, but required highly frequent PEs for long-term maintenance of remission and the others were those who showed persistent and complete remission with several sessions of PE alone. These findings raise issues about the long-term therapeutic goals to be achieved by PE for CIDP patients, particularly on supportive therapy other than PE, as well as the optimization of frequency and duration of PE.
(Internal Medicine 34: 537-541, 1995)

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We describe a case of phlegmonous colitis occurring in a 70-year-old man with liver cirrhosis, hepatocellular carcinoma and acute promyelocytic leukemia. He developed an acute abdominal emergency and died during the first day of admission. Autopsy revealed a colon lesion characterized by suppurative inflammation associated with marked edema and hemorrhage in the submucosa. These findings were identical both macroscopically and microscopically to those of phlegmonous colitis.
(Internal Medicine 34: 542-545, 1995)

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A case of 77-year-old female with multiple myeloma (IgG-k) developed acute myelomonocytic leukemia (AMMoL) following a myelodysplastic stage after chemotherapy with melphalan-cyclophosphamide combinations for 6 years. The leukemic blast cells expressed both myeloid antigens (CDllb, CD13, CD14, CD15, CD33 and CD34) and T/B lymphoid antigens (CD2, CD4, CD22 and PCA1). Cytogenetic analysis revealed a chromosome deletion -7. Analysis of immunoglobulin genes showed the heavy chain genes in germ line configuration. These findings indicate that the AMMoL was a therapy-related stem cell leukemia and was a clonal origin genetically different from multiple myeloma irrespective of plasma cell phenotype.
(Internal Medicine 34: 546-549, 1995)

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A rare case of Aspergillus aneurysm of the central nervous system (CNS) leading to subarachnoid hemorrhage (SAH) is reported. An 83-year-old woman developed visual disturbance and headache. Computed tomographic scans showed no evidence of aneurysm or tumor in the intracranium. She suddenly died from SAH. Autopsy revealed massive SAH due to ruptured Aspergillus aneurysm of the middle cerebral artery. Aspergillus was suggested to have extended from the paranasal sinuses. Aspergillosis of CNS should be considered in patients with neurological symptoms such as visual disturbance and trigeminal neuralgia, especially in cases of the aged or immunocompromised.
(Internal Medicine 34: 550-553, 1995)

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A 64-year-old woman developed multiple brain abscesses of the basal ganglia associated with Klebsiella pneumoniae septicemia. Magnetic resonance (MR) images showed three different stages of the brain abscesses. The images of early cerebritis of this site mimicked lacunar infarctions or dilated Virchow-Robin spaces. The differentiation of the brain abscess from lacunae and dilated Virchow-Robin spaces is discussed, together with the evolution of the brain abscesses on MR images.
(Internal Medicine 34: 554-558, 1995)

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We report a 50-year-old female who suffered from reversible hypothyroidism accompanied by isolated ACTH deficiency. There were no findings indicating a complication of autoimmune thyroiditis. Replacement of maintenance dose of glucocorticoid not only led to improvement of thyroid function, but also caused a transient decrease in T₃ and an increase in reverse T₃, suggesting that chronic cortisol deficiency may impair thyroid function, and that the maintenance dose, as well as pharmacological doses of glucocorticoids may influence T₄ deiodination. The findings of this case suggest that thyroid function should be re-evaluated to avoid unnecessary replacement of thyroid hormone, a few months after glucocorticoid replacement.
(Internal Medicine 34: 559-563, 1995)

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We present a 63-year-old man with chronic pancreatitis and the rare complication of giant subcapsular splenic hematoma. The hematoma showed no size reduction for 6 weeks. Then, the hematoma was infected with pseudomonas aeruginosa after the recurrence of the pancreatitis, and it finally ruptured. This case suggested that in cases of giant subcapsular splenic hematoma with chronic pancreatitis reductive pressure treatment should be administered as early as possible.
(Internal Medicine 34: 564-568, 1995)

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A 53-year-old woman with polymyositis associated with thymoma subsequently developed pure red cell aplasia (PRCA). She was hospitalized because of fever and muscle weakness, and diagnosed as having polymyositis by muscle biopsy. Remarkable clinical improvement followed administration of prednisolone. Progressive anemia became evident, however, while prednisolone was being tapered. Erythroid aplasia and the presence of thymoma confirmed the diagnosis of PRCA. Further examinations revealed that cytotoxic T cells may play an important role in the pathogenesis of this case.
(Internal Medicine 34: 569-573, 1995)

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A case of pulmonary arteriovenous fistula (PAVF) with pulmonary hypertension (PH) occurring in an adult woman is described. Resection of PAVF was not performed and she has been followed up for 5 years, receiving repeated right cardiac catheterization. We discuss the causal relationship of PH and the development of PAVF.
(Internal Medicine 34: 574-576, 1995)

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Five patients suffering from painful alcoholic neuropathy showed severe painful sensory disturbance in their extremities. Although their pain was not ameliorated by the typical usual analgesic agents, oral mexiletine (MX) therapy was remarkably effective for the pain (especially tingling and aching sensation) without major side effects. This study indicated that the minimum effective dose was 300 mg per day and the effective concentration of MX in plasma was 0.66±0.15 μg/ml in these patients. Thus, oral MX therapy can be a reliable treatment for pain in alcoholic neuropathy.
(Internal Medicine 34: 577-579, 1995)

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We present a 32-year-old-woman with Cushing's disease and sarcoidosis. She had been diagnosed as having Cushing's disease in 1985. She had transsphenoidal surgery followed by pituitary radiation. Subsequently her plasma cortisol level gradually decreased to normal range. In 1991, she manifested bilateral hilar lymphadenopathy on chest X-ray, erythema nodosum, subcutaneous nodules and granulomatous uveitis. From the histological findings of the skin lesions, the patient was diagnosed as having sarcoidosis. Interestingly, an inverse relationship between the disease activity of sarcoidosis and the level of serum cortisol in Cushing's disease was observed in the clinical course of this patient. Co-existence of Cushing's disease and sarcoidosis is very rare. Since the therapeutic significance of steroids in sarcoidosis has been well established, this case provides insight to the relationship between sarcoidosis and steroids.
(Internal Medicine 34: 580-583, 1995)

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A 65-year-old woman noticed a rapidly enlarging neck mass with tenderness and complained of dyspnea. She was diagnosed as having anaplastic thyroid carcinoma. She died of respiratory failure 14 days after admission. Marked leukocytosis and hypercalcemia were observed in the clinical course. Both serum granulocyte-colony-stimulating factor and parathyroid hormone-related protein levels were elevated. The cancerous tissue was also immunohistochemically stained for both peptides. We conclude that the leukocytosis and hypercalcemia of this patient were induced by these two factors produced by the tumor.
(Internal Medicine 34: 584-588, 1995)

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Hereditary hemorrhagic telangiectasia (Osier-Weber-Rendu disease) is a bleeding disorder attributed to a vascular developmental abnormality. It is transmitted as an autosomal dominant trait. A 63-year-old female was admitted because of repeated episodes of severe anemia which resulted from bleeding of telangiectases in the gastric mucosa. Conventional therapies including endoscopical microwave coagulation and ethanol injection were not effective. The persistent anemia necessitated frequent blood transfusion. Estrogen was orally administrated and blood transfusion became unnecessary. Thus, estrogen therapy should be considered as one of the effective treatments for recurrent severe anemia due to hereditary hemorrhagic telangiectasia.
(Internal Medicine 34: 589-592, 1995)

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A hypercalcemic patient with adult T-cell leukemia was treated with deoxycoformycin (DCF) in a dose of 5 mg/m2 daily for three days. Several days later, severe thrombocytopenia appeared abruptly and then microangiopathic hemolytic anemia ensued. Subsequently, renal failure and hypertension developed, and the patient died seven weeks after DCF therapy. Needle necropsy of the kidney showed glomerular damage including swelling of endothelial cells, mesangiolysis and segmental collapse. This is the second reported case of hemolytic-uremic syndrome due to DCF.
(Internal Medicine 34: 593-596, 1995)

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A 59-year-old man was admitted for evaluation of mild exertional angina in the morning. During graded treadmill exercise stress testing, the patient had reproducibly intermittent chest pains associated with ST-segment elevations in leads II, III and aV_F. A baseline coronary angiogram showed a coronary narrowing of 90% in the middle segment of the right coronary artery. The coronary narrowing was immediately resolved by an intracoronary injection of nitroglycerin. This was a very rare case of variant angina with intermittent ST-segment elevations and chest pains which were reproducibly demonstrated during exercise and the recovery phase of treadmill testing.
(Internal Medicine 34: 597-601, 1995)

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