Disappearance of the hepatitis B e antigen (HBeAg) typically signals the remission of chronic hepatitis B; however, HBeAg defective variants have been identified in patients with HBeAg negative chronic hepatitis (CH). We studied the changes in the hepatitis B virus (HBV) genome associated with HBeAg clearance in four asymptomatic carriers (ASC) and in four patients with CH. Three ASC had a precore stop codon variant with the core region being wild-type or deleted. The other ASC had wild-type precore and core region. In all ASC, HBV levels were reduced markedly with two ASC converting HBV negative status via polymerase chain reaction. In contrast, patients with CH had continued high titers of HBV. In two patients, the precore region remained wild-type, but the core region contained a cleavage site mutation or was deleted. The precore variant was present in both ASC and CH, perhaps suggesting that it does not significantly influence hepatitis B activity.
(Internal Medicine 34: 319-325, 1995)

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Lactate dehydrogenase A subunit (LDH-A) deficiency is an inherited metabolic myopathy of glycolysis. The severity of this disease varies from case to case. We reported non-consanguineous male sibling cases who had severe muscle pain and rhabdomyolysis during anaerobic exercise. Genetic analysis revealed 20 base pair deletion of the sixth exon of the LDH-A gene. There was no difference in the gene abnormality between our patients and previously reported female cases who had history of consanguinity and lower degree of symptoms. The differences in disease severity were not due to genomic abnormality in our two families.
(Internal Medicine 34: 326-329, 1995)

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Pulmonary diffusing capacity for CO (DL_CO) and cardiac output (Q) were simultaneously measured by a noninvasive rebreathing method (RB) in 15 normal subjects and in 60 patients, including cardiac diseases (CD), bronchial asthma (BA), chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (PF). DL_CO and Q were tested by the single breath method (SB) and the dye-dilution method (Dye), respectively. DL_CO(RB) correlated well with DL_CO (SB) (r=0.890, p<0.001). Q(RB) also correlated well with Q(Dye) (r=0.909, p<0.001). Factors affecting DL_CO (RB) were age, height, body surface area, O₂ consumption, Q, hematocrit (Hct) and Q&built;Hct, among which Q&built;Hct was the prominent influential determinant. DL_CO per lung volume was smaller in COPD and PF than in BA or healthy subjects, while, the ratio of DL_CO/(Q&built;Hct) was significantly higher in COPD than in PF. Simultaneous measurements of DL_CO and Q offer comprehensive characterization for functional changes in lung parenchyma.
(Internal Medicine 34: 330-338, 1995)

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Insulin sensitivity, metabolic clearance rate of insulin (MCR-I) and basal posthepatic insulin delivery rate (BIDR) were investigated by means of euglycemic clamp technique in 8 normal subjects and 8 patients with hyperthyroid Graves' disease. The mean (±SD) steady-state glucose infusion rate (SSGIR) was lower in hyperthyroid Graves' patients than in normal subjects (228.9±57.0 vs. 290.9±49.4 mg/m²/min, p<0.05). Both MCR-I and BIDR were higher in hyperthyroid Graves' patients than in normal subjects (1162.9±517.1 vs. 463.5±103.9 ml/m²/min, p<0.005; 17.7±12.6 vs. 3.6±0.9 mU/m²/min, p<0.01, respectively). Plasma free T₄ levels showed a close correlation with MCR-I (r=0.77, p<0.05) and BIDR (r=0.81, p<0.05), respectively, in Graves' patients. These findings indicate that hyperthyroidism is characterized by not only a decrease in insulin sensitivity, but also an increase in basal insulin secretion and the metabolic clearance rate of insulin, which are correlated with plasma free T₄ levels.
(Internal Medicine 34: 339-341, 1995)

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Haptoglobin (Hp) polymorphism and its relationship to malaria infections was examined in Solomon Islanders under 25 years of age. The slide positive rate for malaria was 48% (53/111): Plasmodium vivax (Pv) 21 cases, Plasmodium falciparum (Pf) 16 cases and the remaining 16 were a mixture of Pv/Pf/P. malariae. Of 111 subjects examined, 17% (19 subjects) were ahaptoglobinemic (HpO). No association was observed between HpO and parasitemia, gender, anemia, serum insulin-like growth factor-1 (IGF-1) level, blood glucose level and enlargement of the spleen. These results suggest that malaria may not be the major cause of HpO in the people of the Solomon Islands.
(Internal Medicine 34: 342-346, 1995)

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We examined the T-cell subsets in the peripheral blood, spleen and lymph nodes during the course of experimental allergic neuritis (EAN) by using two-color analysis. In the acute phase, the percentages of CD4⁺ major histocompatibility complex (MHC)-II⁺ cells and CD8⁺ MHC-II⁺ cells in the lymph nodes of EAN rats were significantly higher than in the control rats. In the recovery phase, the percentages of CD4⁺ CD45RC⁺ cells and CD8⁺ CD45RC⁺ cells in the lymph nodes in EAN rats were significantly higher than in the control rats. However, significant changes of the T-cell subsets were not detected in either the spleen or the peripheral blood during the course of EAN. These results suggest that CD4⁺ MHC-II⁺ cells, CD8⁺ MHC-II⁺ cells, CD4⁺ CD45RC⁺ cells and CD8⁺ CD45RC⁺ cells may play a role in the course of EAN. The relationship between these double staining cells and EAN is discussed.
(Internal Medicine 34: 347-351, 1995)

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We investigated the changes in cellular components and neutrophil chemotactic factors in pleural fluid from 19 lung cancer patients who received intrapleural injection of OK-432 to treat malignant pleurisy. Not only neutrophil chemotactic activity (NCA) but also neutrophil count and percentage were increased significantly at 6 hours after OK-432 injection. The neutrophil count was significantly correlated with NCA level. The levels of C5a and IL-8 in pleural fluid were increased significantly after OK-432 injection. The increased IL-8 level was associated with a increase of both NCA and neutrophil count. OK-432 treatment also induced a marked increase of IL-1β and IL-6 in pleural fluid. Thus, intrapleural injection of OK-432 induced production of neutrophil chemotactic factors (IL-8 and C5a) and cytokines (IL-1β and IL-6), which eventually attracted neutrophils into the pleural space. These observations suggest that neutrophil migration mediated by these factors and cytokines may contribute to the sclerosing effects of OK-432 treatment.
(Internal Medicine 34: 352-356, 1995)

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To investigate the role of mast cells in the development of summer-type hypersensitivity pneumonitis (SHP), which is the most common type of hypersensitivity pneumonitis in Japan, bronchoalveolar lavage fluid (BALF) cells from 13 patients with this disease was studied by light and electron microscopy. The proportion and number of BALF mast cells recovered from SHP patients were significantly greater than those from patients with sarcoidosis and from control subjects. The BALF mast cells from the SHP patients showed various ultrastructural changes such as the transformation of granules, cytoplasmic vacuolation, and an increase of lipid droplets. These findings appeared to reflect activation and degranulation of bronchoalveolar mast cells, suggesting that mast cells play a role as inflammatory cells in the development of SHP.
(Internal Medicine 34: 357-363, 1995)

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This study aims to determine the clinical factors that may affect renal function and patient survival in 82 multiple myeloma patients. The patients were divided into 3 groups according to their renal function during the initial 8 weeks after diagnosis: Group 1, 54 patients with serum creatinine (S-Cr) <177 μmol/L; Group II, 11 with S-Cr≥177 μmol/L and receiving no dialysis; Group III, 17 undergoing dialysis treatment. Clinical status at diagnosis, subsequent renal function and patient survival were compared. Bence Jones proteinuria (BJP) was found in all patients in Groups II and III, compared to 67% of patients in Group I (p<0.05, I vs II or III). Hypercalcemia, hyperuricemia and intravenous administration of contrast medium, together with BJP each constituted independent risk factors of renal dysfunction. The incidence of hypercalcemia in Group II was significantly higher than in the other 2 groups. Patient survival was 26.8±23.7 months in Group I, 8.1±10.3 in II and 12.1±16.6 in III (p<0.05, I vs II or III). Renal function and patient survival depended on the initial renal function. Renal function was likely compromized in the presence of BJP.
(Internal Medicine 34: 364-370, 1995)

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In an attempt to study the natural course of Hashimoto's thyroiditis and simple goiter, 74 euthyroid patients with Hashimoto's thyroiditis and 212 patients with simple goiter were followed for 10 years. In 204 patients with simple goiter (96.2%) it remained as a simple goiter throughout the observation period, whereas 8 patients (3.8%) later had Hashimoto's thyroiditis as evidenced by the appearance of circulating thyroid autoantibodies. These 8 patients had HLA typing significantly different from that of control subjects. None of the patients with simple goiter had hyperthyroid Graves' disease despite the fact that 17.5% of those patients had mild to moderate exophthalmos with either Moebius' sign or von Graefe's sign. In contrast, 12 patients with Hashimoto's thyroiditis (16.2%) had exophthalmos with Moebius' sign and/or von Graefe's sign, and 4 of 12 such patients later had hyperthyroid Graves' disease. TSH binding inhibitory immunoglobulin was detected in 3 of 4 such patients with hyperthyroid Graves' disease. Forty-nine patients with Hashimoto's thyroiditis (66.2%) still remained euthyroid but 20 of those (27.0%) turned into hypothyroidism during the 10-year follow-up.
(Internal Medicine 34: 371-375, 1995)

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A 67-year-old woman with pulmonary embolism was suspected to have β-thalassemia based on microcytosis, hemolysis and a negative red cell stability test. The DNA sequencing analysis of β-globin gene, however, revealed the deletion of three nucleotides within codon 127-128, leading to substitution of glutamine and alanine residues at 127 and 128 by proline, namely Hb Gunma. This mutant is characterized by the fact that no abnormal hemoglobin is detected in the circulating blood, and is classified as a thalassemic hemoglobinopathy. The present case showed a relatively hemolytic manifestation.
(Internal Medicine 34: 376-379, 1995)

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We present a case of fat embolism syndrome following vegetable oil injection for augmentation mammaplasty. Although vegetable oil is a stable neutral fat under usual storage conditions, it caused fat embolism and pulmonary injury in this patient. We investigated this mechanism by compound analysis of the injected oil, transbronchial lung biopsy and special staining of alveolar macrophages. This is the first description of the human response to vegetable oil injection. These data should aid in the investigation of the side effects of many types of lipids which may be applied to humans for various purposes in the future.
(Internal Medicine 34: 380-383, 1995)

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Chronic idiopathic neutropenia (CIN) is a disorder characterized by severe neutropenia and a maturational arrest of the neutrophil precursors in the bone marrow. We examined the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the growth and maturation of the myeloid progenitor cells from a patient with CIN. The patient's marrow cells showed poor colony forming activity, but a normal differentiating capacity to the stimulation with rhG-CSF, although they displayed a normal colony forming capacity in the presence of GM-CSF. Our observation indicates the distinct effect of rhG-CSF on the growth and maturation of the myeloid progenitors from a CIN patient.
(Internal Medicine 34: 384-387, 1995)

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We treated a 51-year-old woman who had rapidly progressive respiratory distress with an interstitial shadow on chest roentgenogram. Pathologically, open lung biopsy specimens showed an acutely changed lesion such as interstitial inflammatory thickening, polypoid intraluminal organizing exudates, and also honeycombing which was not recognized on chest computed tomogram. These findings were considered unconformable to acute interstitial pneumonia (AIP), bronchiolitis obliterans organizing pneumonia (BOOP), and also usual interstitial pneumonia, although the clinical diagnosis was AIP or BOOP. We diagnosed a rapidly progressive interstitial pneumonia showing an acute lung injury pattern like AIP and BOOP. She showed significant recovery with corticosteroid and cyclophosphamide.
(Internal Medicine 34: 388-392, 1995)

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A 66-year-old woman who presented with malignant cardiac tamponade of unknown origin was eventually found to have a tiny squamous cell carcinoma of the thymus. Thus, even a small thymic carcinoma can exhibit highly aggressive behavior. It should be included in the differential diagnosis of malignant cardiac tamponade of unknown origin.
(Internal Medicine 34: 393-395, 1995)

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Nonmedullary thyroid carcinoma was diagnosed in three of nine cases of primary hyperparathyroidism. In all three cases, diagnosis of primary hyperparathyroidism was made before that of thyroid carcinoma. In the first case, follicular carcinoma was incidentally detected during parathyroidectomy. In the second case, thyroid tumor was discovered during imaging studies for hyperparathyroidism. Papillary carcinoma and ectopic parathyroid was diagnosed postoperatively. In the third case, a thyroid lesion had been mistaken for a putative parathyroid lesion, but the diagnosis of papillary carcinoma was obtained. These cases suggest that preoperative examination for hyperparathyroidism should be carefully evaluated, considering possible concomitant thyroid lesions.
(Internal Medicine 34: 396-400, 1995)

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We examined the long-term effects of octreotide, a somatostatin analogue, on ventilation in a case of cirrhotic hypoxemia. After daily administration of octreotide for one month, the dyspnea on exertion was notably ameliorated, although pulmonary gas exchange was only slightly improved. The octreotide therapy reduced the hypoxic ventilatory drive, which may be one reason for the relief of the dyspnea sensation.
(Internal Medicine 34: 401-405, 1995)

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Ectodermal dysplasia syndrome (EDS) is a rare hereditary disease, with symptoms brought about by dysplasia of ectodermal tissue (such as skin, teeth, nails, and hair). This report details the cases of two siblings (41 and 43 year old sisters) with autosomal recessive and hydrotic EDS complicated by esophageal achalasia, postoperative stenosis of esophagus, true keloids, renovascular hypertension, incomplete malrotation of the bowel, and demyelination of the brain.
(Internal Medicine 34: 406-409, 1995)

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In 1986, a 26-year-old female had been diagnosed as having Graves' disease and had been treated with methimazole for four months. After the treatment with propylthiouracil for another four months, she had been treated with methimazole once again. She was in complete remission for two years. She again experienced symptoms of hyperthyroidism, and treatment with methimazole was started again. On the thirteenth day after treatment, she experienced hypoglycemic attacks with skin eruption. The plasma glucose was 57 mg/dl, ¹²⁵I-Insulin binding 69%, free IRI 196 μU/ml. The patient had the HLA-DRB1 ^*0406.
(Internal Medicine 34: 410-412, 1995)

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A 24-year-old woman with familial thyroxine-binding globulin (TBG) deficiency associated with hyperthyroidism is reported. Thyroid-stimulating hormone (TSH)-binding inhibitor immunoglobulin (TBII) was negative, whereas thyroid-stimulating antibody (TS Ab) was positive. Serum thyroxine-binding globulin (TBG) levels were extremely low, and remained low even after the normalization of thyroid function with methimazole (MMI) treatment. The serum TBG level of the mother of patient was also below the normal lower limit. Genetic analysis revealed single nucleotide deletion, common among Japanese with complete TBG deficiency (TBG-CD), from the allele-specific amplification of the TBG genes of the patient.
(Internal Medicine 34: 413-417, 1995)

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Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma (IBL-T) occurred in a 60-year-old female after a 4-year follow-up of idiopathic eosinophilia and upper pharyngeal inflammatory tumor with infiltration of mature eosinophils. Gene analysis of tumor cells revealed rearrangement of both IgH and TCRβ genes. The patient died of lymphoma seven months after the onset of the illness, in spite of chemotherapy against lymphoma. The relationship between eosinophilia and the pathogenesis of IBL-T, as well as the significance of the rearrangement of both IgH and TCRβ genes are discussed.
(Internal Medicine 34: 418-423, 1995)

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A 66-year-old man presented with Graves' disease and widespread localized myxedema. Extensive lesions were present on the legs, feet, hands, and face. TSH receptor antibody (TBII) was markedly positive and the serum hyaluronic acid level was very high. Intravenous steroid pulse therapy was followed by oral therapy with gradual tapering. This regimen markedly improved the skin lesions and resulted in a decrease of the serum hyaluronic acid level. The findings suggest that steroid pulse therapy is effective for the treatment of extensive localized myxedema. In addition, the serum hyaluronic acid level may be a useful parameter for the follow-up of patients with this condition.
(Internal Medicine 34: 424-429, 1995)

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We treated a married couple who developed Mycoplasma pneumonia at the same time, and whose clinical courses and serum soluble interleukin-2 receptor (sIL-2R) levels were markedly different. The 30-year-old wife developed acute respiratory failure and her sIL-2R levels were extremely increased. After pulse therapy, her clinical state was improved, with a marked decrease in sIL-2R. In contrast, the 36-year-old husband, also suffered from the pneumonia with a moderate increase of sIL-2R, and recovered without any complications. The difference in their clinical states may be reflected in their serum sIL-2R levels, a marker of T cell activation in vivo.
(Internal Medicine 34: 430-435, 1995)

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As the chest symptoms and electrocardiographic changes of hypertrophic cardiomyopathy are occasionally very similar to those of angina pectoris, there are some difficulties in the diagnosis and treatment of cases of ischemic heart disease associated with hypertrophic cardiomyopathy. Here we report a case of vasospastic angina pectoris associated with hypertrophic cardiomyopathy diagnosed by coronary spasm provocation test performed by intracoronary administration of acetylcholine. In the treatment of such cases, beta blockers, which have the effect of decreasing the oxygen demand of the heart and the potential to induce coronary spasm, must be administered carefully.
(Internal Medicine 34: 436-440, 1995)

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We report a 63-year-old woman, with a partial type of common atrioventricular canal and mitral stenosis, who was hospitalized because of dyspnea on exertion. Two-dimensional echocardiogram showed an ostium primum atrial septal defect with two well-formed AV valves located at the same level. However, both anterior and posterior mitral leaflets were markedly thickened with a thickened subvalvular apparatus, and the commisures were fused. Echocardiographic measurements demonstrated a mitral valve area of 1.48 cm² with mild mitral regurgitation. Cardiac catheterization demonstrated mild pulmonary artery hypertension with a large left to right shunt (72%) at the atrial level. The combination of the partial type of common atrioventricular canal and mitral stenosis is rare; only one similar case has been reported previously in the literature.
(Internal Medicine 34: 441-145, 1995)

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This case report describes a 68-year-old man with Cushing's syndrome due to adrenocorticotropic hormone (ACTH)-independent bilateral adrenocortical macronodular hyperplasia (AIMAH). He was referred to our hospital for evaluation of bilateral enlargement of the adrenal glands found incidentally by computed tomography (CT). He had a ten-year history of hypertension. Although he was normokalemic and did not show Cushingoid features, the diagnosis of ACTH-independent Cushing's syndrome was established by endocrinological examinations. His plasma cortisol showed no diurnal rhythm and was unsuppressible by high-dose (8 mg/day) dexamethasone. Plasma ACTH was undetectable and did not respond to corticotropin-releasing hormone. Excised adrenal glands were markedly enlarged (right 28 g and left 64 g). Macroscopic appearance of the glands showed multiple yellowish nodules typical for AIM AH; microscopic findings were also compatible with AIMAH. The present case indicates that patients with AIMAH sometimes do not show typical Cushingoid features and therefore AIMAH can be found incidentally from ultrasound or CT examination of the abdomen.
(Internal Medicine 34: 446-450, 1995)

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A 36-year-old woman with primary biliary cirrhosis (PBC)-CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia) overlap syndrome complicated by Sjögren's syndrome and arthritis is reported. She had suffered from Raynaud's phenomenon, sclerodactyly, morning stiffness, arthralgia and sicca symptoms since 34 years of age. She exhibited an increased level of alkaline phosphatase and hyperglobulinemia at 2.8 g/dl without any symptoms, and histological findings from the biopsy specimen of the liver were consistent with those of PBC. Her human leukocyte antigen (HLA) typing was DR8 homozygous.
(Internal Medicine 34: 451-154, 1995)

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A 17-year-old male had fever of unknown origin (FUO) for 3 months with positive c-reactive protein, lymph node swelling, and hepatosplenomegaly. Biopsy specimens of the liver and lymph node disclosed nonspecific inflammation. Lymph node swelling and hepatosplenomegaly subsided gradually, while vascular murmur and pulselessness appeared. Computerized tomography and magnetic resonance imaging showed thickened arterial wall, while angiography disclosed arterial narrowing. From these findings he was diagnosed to have Takayasu's arteritis. The therapy with prednisolone was effective. Takayasu's arteritis is rarely manifested by hepatosplenomegaly and lymphadenopathy in its prepulseless stage.
(Internal Medicine 34: 455-459, 1995)

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