In order to establish the therapeutic plasma concentration of famotidine, the 24-h intragastric pH response to low-dose intravenous (i. v.) continuous infusion of 40 (group A) or 20 mg/day (group B), administered over more than two days, was studied in 10 adult patients with active gastric ulcers (GU). In group A, the mean age was 64.8 years and in group B, 54.2 years. On the second day, 4 blood samples were collected for famotidine assay and 24h intragastric pH monitoring was performed. Results : the mean 24h pH did not differ significantly (P<0.01) between group A at 6.9 and group B at 7.2. In group A, the percentage of time with pH above 6.0 and above 7.0 were 94.8 and 59.0, respectively, and the mean famotidine dose and plasma concentration were 0.81 mg/kg/day and 140.89ng/ml. In group B, the percentage of time with pH above 6.0 and 7.0 were 97.6 and 65.4, and the mean dose and famotidine concentration were 0.34mg/kg/day and 45.42 ng/ml. In conclusion, in fasting patients with active gastric body ulcers, continuous infusions of low-dose famotidine maintain both the therapeutic plasmatic concentration and the intragastric pH to near anacidity level.
(Internal Medicine 31 : 299-303, 1992)

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We investigated the prognosis of patients with congestive heart failure (CHF) and the factors which influence the prognosis of Japanese patients with this condition. From among the patients admitted to our hospital from January 1, 1978 to December 31, 1985, the 298 patients who were diagnosed having CHF were investigated. Patients with CHF had a rather poor prognosis, with the 1-year, 3-year, and 5-year cumulative survival rates being 76%, 60%, and 49%, respectively. The factors influencing the prognosis of patients with CHF were the type of underlying heart disease, the left ventricular ejection fraction, the left ventricular end-diastolic dimension, and the central venous pressure. Survival rates differed significantly depending on the type of underlying heart disease. The cumulative 5-year survival rate was 35% for coronary artery disease, 40% for dilated cardiomyopathy, 53% for rheumatic valvular heart disease, and 80% for hypertensive heart disease.
(Internal Medicine 31 : 304-309, 1992)

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Okinawa Prefecture is an endemic area of Strongyloides stercoralis infection. Since treatment of this infection remains unsatisfactory, we evaluated the efficacy of ivermectin. Twenty-three patients were treated with a single oral dose of ivermectin (mean±SD, 105.5±20.8 mcg/kg of body weight), followed by a second dose two weeks later. The rate of cure was 85.7% at 2 weeks after the first treatment, and 90.5% at 2 weeks after the second treatment. Side effects occurred in 2 patients (8.7%), but they were mild and transient. The results indicate that ivermectin might be useful and relatively safe for the therapy of Strongyloides stercoralis infection as an alternative to thiabendazole or mebendazole.
(Internal Medicine 31 : 310-312, 1992)

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Among 1, 153 consecutive patients, 22 patients (1.9%) who complained of chronic fatigue for a period of over 6 monthes without detectable causes were studied. Ten patients (0.86%) satisfied the criteria of chronic fatigue syndrome (CFS) and were classified to be definite cases of CFS. The other patients were classified as probable cases. In order to clarify the role of Epstein-Barr virus (EBV) as a cause of CFS, we measured various antibodies for EBV. The definite cases had significantly higher titers of early antigen complex (EA)-IgG than both the probable cases and controls. We proposed the EA-IgG/EBNA ratio as the indicator of activation of EBV and attempted to estimate the degree of fatigue by the EA-IgG/EBNA ratio. The highest ratio value (16.0) of the 22 patients ratios was the most serious case. In general, the ratio correlated with the degree of fatigue. Based on these rasults, it was concluded that a relationship does exist between CFS and EBV.
(Internal Medicine 31 : 313-318, 1992)

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The prophylactic efficacy of ofloxacin (OFLX) therapy was evaluated in 51 granulocytopenic episodes in 22 patients with hematological malignancies during post-remission chemotherapy in a prospective, randomized, controlled trial. Oral administration of OFLX plus amphotericin-B (AMPH) and polymyxin-B (PL) reduced episodes of fever and infection more than did the control regimen with PL and AMPH alone (p<0.01), and the reduction in the incidence of infection was evident even in patients showing severe granulocytopenia (p<0.01). Furthermore, the first fever after the onset of granulocytopenia in the OFLX regimen developed later than that in the control regimen (p<0.05). Clinically, the prophylactic efficacy was 92% for the OFLX regimen and 40% for the control regimen (p<0.01). These findings suggest that OFLX is a promising prophylactic agent following post-remission chemotherapy. Patient hemomyelogram findings similar to those of patients with other malignancies may imply that OFLX is widely effective in granulocytopenic patients taking aggressive chemotherapy.
(Internal Medicine 31 : 319-324, 1992)

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Eleven patients with intractable ascites were treated by intravenous reinfusion of concentrated autogenous ascitic fluid. The ascitic fluid was drained and centrifuged for removal of cells by a cell separater. Cell-free ascitic fluid was frozen in a medical freezer at -15°C and thawed at room temperature. The fraction at the initial stage of melting contains a high concentration of protein and was thus collected and reinfused to the patient. In this initial fraction, the recovery rate of albumin was 42.0 ± 9.0% and the concentration of protein was 7.1 ± 2.4 g/dl. This frozen method is inexpensive and time saving, because it does not use a filter. Ascites was ameliorated in all patients with 1 to 19 times of reinfusion. Therefore, when renal function is not disturbed, the frozen method may be indicated for management of intractable ascites.
(Internal Medicine 31 : 325-332, 1992)

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The cellular composition of bronchoalveolar lavage (BAL) fluid was observed in 28 patients with house dust mite-sensitive asthma. The proportion of neutrophils in the BAL fluid was significantly higher in the patients between the ages of 50 and 59 and those over 60 than in the patients younger than age 39. There was a significant difference in the number of neutrophils in patients aged 30-39 years and in those over 40 at the onset of disease. The cellular composition varied among the three types of asthma ; the mean percentage of cells in the BAL fluid was 1.1% neutrophils and 21.3% eosinophils in type Ia (simple bronchoconstriction), 9.1% neutrophils and 23.0% eosinophils in type Ib (bronchoconstriction + hypersecretion), and 34.4% neutrophils and 12.0% eosinophils in type II (bronchiolar obstruction). The results suggested that an increased frequency of both neutrophils and eosinophils correlates with the mechanism of hypersecretion, and that a marked increase in the proportion of neutrophils is involved in bronchiolar obstruction.
(Internal Medicine 31 : 333-338, 1992)

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A cell line of plasma cells with high ammonia (NH₃) production (KHM-4) was established from a patient with multiple myeloma complicated by hyperammonemia and abnormal serum concentrations of amino acids. Surface marker studies of KHM-4 cells showed that the cells were positive for cytoplasmic immunoglobulins (IgA kappa), HLA-DR, and T 10. Secretion of ammonia by the KHM-4 cells was detected by the addition of L-glutamine and L-arginine into the culture medium of amino acid-free RPMI 1640. In the presence of L-glutamine, KHM-4 cells secreted a greater amount of ammonia than the T cell line, CEM. However, production of ammonia by L-arginine was not observed in other cell lines. These observations provide evidence for the existence of a peculiar amino acid metabolism in the myeloma cells causing hyperammonemia and serum amino acid disturbance.
(Internal Medicine 31 : 339-343, 1992)

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Sixteen patients with dilated cardiomyopathy were examined hemodynamically in order to clarify the relationship between the exercise capacity and the effects of afterload reduction at rest using supine graded bicycle exercise testing before and after sublingual administration of 10 mg nifedipine. 1) The integration of work loads was weakly correlated with the stroke index (r=0.64), heart rate (r=-0.58) and plasma norepinephrine concentration at rest (r=0.49), but not with the left ventricular ejection fraction, cardiac index, pulmonary arterial diastolic pressure or the mean arterial pressure at rest. 2) Changes in stroke index and heart rate after administration of nifedipine correlated well with the integration of work loads (r=-0.84, r=0.81, respectively). Thus, in patients with dilated cardiomyopathy changes in stroke volume and heart rate due to afterload reduction at rest were better predictors of exercise capacity than the baseline left ventricular hemodynamic parameters.
(Internal Medicine 31 : 344-348, 1992)

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We analyzed the clinical features of multiple sclerosis (MS) prospectively seen between July 1986 and October 1989 on Hokkaido island, the northernmost part of Japan. Clinical features were generally considered to be intermediate between the previous Japanese reports and those of Western countries. Devic's disease was rare and simultaneous bilateral visual loss at on set was not too common this series, differing from that previously reported of Japanese MS. The high incidence of acute transverse myelopathy and lesser involvement of the cerebellum, however, support the previous view. Further clinical and epidemiological studies will be necessary on this island.
(Internal Medicine 31 : 349-352, 1992)

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A 53-year-old man was admitted with impairment of breathing following laryngeal edema. Serum levels of CH₅₀ (22 U/ml), C4 (3 mg/dl), C1-INH protein (10.6 mg/dl) and C1-INH activity (LT 25%) were low. Complement study of the patient's family members revealed that he was one of 5 patients in 3 generations with hereditary angioneurotic edema (HANE). Administration of the androgen derivatives Danazol (600 mg/day) and Oxymetholone (30 mg/day) effectively increased serum levels of C1-INH activity and C4. Though eruption and hepatic dysfunction attributable to administration of the drugs appeared, these side effects improved after withdrawal of the drugs. Subsequently, the treatment with Danazol at a low dose (100 mg/day) was resumed, and the patient has had no episodes of edema for the past 3 years. Regarding the familial cases of HANE, fewer than 20 have been reported in Japan.
(Internal Medicine 31 : 353-356, 1992)

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A 64-year-old man was admitted to our hosiptal because of possible liver cirrhosis. His serum cholinesterase was anomalously low with a ΔpH of 0.1 (normal range ; 0.8-1.1). His enzyme was more heat-labile than the normal controls. Km value of his enzyme for benzoylcholine was 1.1×10^-5 mol/l, while that for normal controls was 2.3× 10^-6 mol/l. In addition, isozymic alteration of his enzyme was observed. Sequencing of the white blood cell DNA of the patient showed a point mutation at nucleotide 1093 (GGA to CGA), which changes codon 365 from glycine to arginine.
(Internal Medicine 31 : 357-362, 1992)

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A 73-year-old male was admitted to Hyogo College of Medicine Hospital for further evaluation of chest x-ray abnormalities. Chest roentgenogram taken at admission showed right lower lobe atelectasis and bronchoscopic examination revealed an endobronchial tumor obstructing the left lower lobe bronchus. The biopsy specimen showed cribriform adenoid cystic carcinoma. The serum CA19-9 level was markedly elevated at admission, leading to immunohistochemical analysis of the biopsy specimen. As a result, in the tumor, CA19-9 was positively stained. This is probably the first reported case of adenoid cystic carcinoma of the bronchus which produces CA19-9.
(Internal Medicine 31 : 363-367, 1992)

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A case of primary gastric lymphoma is reported. The lymphoma was of the diffusely infiltrating type extending from the supraangular region to the prepyloric region of the stomach. The patient refused gastrectomy, therefore combined treatment with BACOP chemotherapy and radiotherapy was carried out. Complete remission was achieved without any major complications. The patient has remained free from relapse for over 20 months.
(Internal Medicine 31 : 368-372, 1992)

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Alpha-interferon was used for anti-cancer or anti-viral therapy in two patients with preexisting Autoimmune thyroid disease and in seven patients with chronic viral hepatitis who had no history of thyroid dysfunction. Primary hypothyroidism developed in the two patients who had a history of autoimmune thyroid disease, while no changes in thyroid function were observed in the other seven patients. Modulation of the immune system by alpha-interferon may have been responsible for the development of hypothyroidism in these two patients. Therefore, autoantibodies to the thyroid and the thyroid function should be assessed in patients undergoing alpha-interferon therapy.
(Internal Medicine 31 : 373-376, 1992)

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A 26-year-old woman who received methimazole treatment for Graves' disease is discussed. Two months following treatment, her serum GOT level rose to 45 K.U, her GPT to 60 K.U, and her lactate dehydrogenase (LDH) to 645 W.U ; a hepatic disorder was then suspected. Later, the serum GOT and GPT concentrations decreased to a normal range, but her serum LDH continued to maintain a high level. An LDH isoenzyme analysis showed an abnormally broad band between LDH 3 and 5, and electroimmunosyneresis revealed that IgG (κ) was bound to the LDH. The IgG that was linked to the LDH is suspected to have been the result of her underlying autoimmunity, the methimazole treatment, and the development of her hepatic disorder. Thus, this IgG was thought to be the autoantibody to LDH.
(Internal Medicine 31 : 377-379, 1992)

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A 54-year-old woman with anemia, diabetes mellitus and liver dysfunction was admitted to our hospital. Numerous binucleated erythroblasts in the bone marrow, a positive serum acidified test, and the presence of anti I and anti i antigens on the surface of her erythrocytes indicated that she had congenital dyserythropoietic anemia (CDA) Type II. Hemochromatosis was confirmed by a liver biopsy. This case is a sibling of a patient with CDA Type II reported by Omine et al in 1981 (Acta Haematol Jpn 44 : 1). They report that no physical or hematological abnormalities were found when she was examined at the age of 29 years. Twenty-five years later, she developed CDA Type II and hemochromatosis. This case indicates that long-term observation of the family members of a patient with CDA Type II is necesary.
(Internal Medicine 31 : 380-384, 1992)

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A case of Cushing's syndrome associated with chronic respiratory failure is presented. Although arterial blood gas analysis showed severe metabolic alkalosis, hypoxemia and mild hypercapnia, the patient had no evidence of pulmonary disease or neuromuscular disorder. Voluntary hyperventilation and inhalation of 100% oxygen (O₂) revealed normalized arterial oxygen tension (PaO₂). Following the recovery from metabolic alkalosis by the treatment with potassium chloride, PaO₂ was elevated and arterial carbon dioxide tension (PaCO₂) was lowered. Therefore, it was strongly suggested that the main cause of chronic respiratory failure was compensatory alveolar hypoventilation as a response to metabolic alkalosis.
(Internal Medicine 31 : 385-390, 1992)

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Abscess formation is uncommon in eosinophilic lung disease. In this paper we present a case of chronic eosinophilic pneumonia in which bronchofiberoscopy revealed scattered small abscesses in the large airways. Pathological examination revealed the presence of inflammatory cells with eosinophilic infiltration in both the bronchial mucosa and lung parenchyma.
(Internal Medicine 31 : 391-393, 1992)

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A patient with hypogonadotropic hypogonadism and anosmia (Kallmann's syndrome) is described. Anosmia has been believed to be due to hypoplasia of the rhinencephalon. This anatomical defect was demonstrated in vivo in a patient with Kallmann's syndrome by magnetic resonance imaging (MRI).
(Internal Medicine 31 : 394-396, 1992)

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A-39-year-old man was admitted to our hospital because of a markedly decreased level of serum cholinesterase found incidentally by a blood test. Detailed examination did not reveal severe liver disease, malignant tumor, infection or organophosphate compound poisoning. Investigation of three generations of his family revealed two homozygous and five heterozygous family members with the cholinesterase deficiency gene E₁^s indicating familial serum cholinesterase deficiency.
(Internal Medicine 31 : 397-399, 1992)

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A 77-year-old woman who complained of dysphagia was found to have an aneurysm in the descending aorta. Magnetic resonance imaging (MRI) demonstrated the state of thrombi, a thin and irregular soft tissue signal between the aneurysm and the esophagus, which suggested an esophago-aneurysmal fistula revealed by the operation. MRI was effective in the evaluation of the status of aneurysm.
(Internal Medicine 31 : 400-403, 1992)

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Dramatic efficacy of cyclosporin was observed in a patient with inflammatory pseudotumour in the liver. The 30-year-old male patient had suffered several attacks of high fever, polyarthralgia and lymph node swelling since 1981. In February 1989, abdominal CT showed multiple space-occupying lesions in his liver, and histopathology of the biopsied liver showed infiltration of plasma cells and lymphocytes with proliferation of collagen fiber, which was comparable to an inflammatory pseudotumour. In May 1990, a treatment regimen of cyclosporin A along with prednisolone was begun because he had been diabetic since March 1990. Within a few days of treatment, the high fever and polyarthralgia subsided, and leucocytosis of 32, 000/mm³ and the increased CRP of 17.7mg/dl were normalised within one month. A reduction of the size of the space-occupying lesions in the liver was observed on abdominal CT taken one month after cyclosporin treatment.
(Internal Medicine 31 : 404-406, 1992)

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Three patients of Cushing's syndrome with severe disproportionate hypertrophy of the interventricular septum are reported. All three underwent adrenalectomy and the diagnosis of Cushing's syndrome was confirmed by the presence of adrenal adenoma. All three showed hypertension before the adrenalectomy and two remained hypertensive following adrenalectomy. Before the operations the electrocardiograms revealed inverted T waves in broad leads, and mechanocardiogram systolic and diastolic dysfunction. After the adrenalectomies, abnormal findings on electrocardiograms were normalized and septal hypertrophy was completely regressed. It appears that not only high aortic pressure but also excessive plasma cortisol may be an etiologic factor of the left ventricular hypertrophy in Cushing's syndrome.
(Internal Medicine 31 : 407-413, 1992)

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A 66-year-old male with chronic pericarditis accompanied by idiopathic retroperitoneal fibrosis was originally admitted for cardiac tamponade. A firm diagnosis was obtained only after the patient's sudden death when autopsy was performed. Chest X-rays showed cardiac enlargement and pleural effusion. Echocardiogram revealed bright echo density on the myocardium.
(Internal Medicine 31 : 414-417, 1992)

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A 53-year-old woman was admitted because of Raynaud's phenomenon, polyarthralgia and polymyalgia. Biopsy specimens of the liver and thyroid gland revealed characteristic findings of primary biliary cirrhosis (PBC) (stage I by Scheuer's classification) and chronic thyroiditis. Her clinical features were also complicated by scleroderma (type I by Barnett's classification) and Sjögren's syndrome (Sjs) with keratoconjunctivitis sicca. Thyroid hormone replacement therapy led to improvement in thyroid function, normalization of the biliary tract enzymes and alleviation of subjective symptoms.
(Internal Medicine 32 : 418-421, 1992)

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A case of severe pulmonary alveolar proteinosis (PAP) with interstitial involvement, mediastinal lymphadenopathy and an elevation of carcinoembryonic antigen (CEA) in the bronchoalveolar lavage (BAL) fluid and the serum is presented. Alveolar macrophages may play a major role in these rare and seemingly unrelated findings.
(Internal Medicine 31 : 422-425, 1992)

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The occurrence of rhabdomyolysis and acute renal failure associated with cytomegaloviral infection is rare. A 27-year-old housewife was admitted to our hospital with complaints of thirst, muscle weakness, abdominal pain and oliguria. There was no past history of diabetes, drinking, fever or drug habituation and a negative family history. Laboratory tests revealed myoglobinuria, hyper-pancreatic type amylaseuria, hyperglycemia, azotemia and highly increased creatine phosphokinase in the plasma. She was treated with hemodialysis and insulin therapy. Serological studies showed a 4-fold increase in cytomegalovirus antibody titers 4 weeks after admission. Muscle biopsy specimens showed hyaline degeneration and infiltration of T cell lymphocytes in the muscle. Renal biopsy specimens showed acute tubular necrosis and some myoglobin casts. No cytomegalovirus antigen was found in renal specimens by immunofluorescence study. From these results, it was determined that a systemic cytomegalovirus infection triggered pancreatitis which caused diabetic ketoacidosis, rhabdomyolysis and acute renal failure.
(Internal Medicine 31 : 426-430, 1992)

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A 16-year-old girl was admitted with the complaints of headache, chest pain, low abdominal pain and left hemi-numbness. Her blood pressure was high and plasma renin activity and aldosterone levels were elevated. Renal angiography revealed vascular stenoses and microaneurysms although the renal artery and its main branches were not involved. Polyarteritis nodosa (PN) was strongly suspected and oral prednisolone and intravenous pulse therapy of cyclophosphamide were started. The second renal angiography which was performed 11 days after the therapy was started, showed marked improvement of vascular lesions. This is a case which suggests that the angiographic findings of PN can improve very rapidly with therapy.
(Internal Medicine 31 : 431-433, 1992)

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A 38-year-old male patient with chronic myelocytic leukemia in the first chronic phase underwent bone marrow transplantation (BMT) from an HLA identical sibling. He developed chronic graft-versus-host disease and his condition gradually deteriorated. Fourteen months after BMT, acute progressive anemia, thrombocytopenia, reticulocytosis, increased serum lactic dehydrogenase and increased serum bilirubin were revealed following treatment with cyclosporine A (240mg/day i.v.), prednisolone (60mg/day i.v.) and azathioprine (1OOmg/day p.o.). Red blood cell fragmentations were also found microscopically. At that time, the serum cyclosporine A trough level was 1, 300ng/ml by the polyclonal antibody RIA method. These symptoms were resolved by discontinuation of cyclosporine A and administrations of aspirin, cilostazol, and dipyridamole as anti-platelet agents. We consider this phenomenon to be microangiopathic hemolytic anemia due to a serum high cyclosporine A level which resulted from the concomitant use of cyclosporine A with prednisolone.
(Internal Medicine 31 : 434-437, 1992)

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To examine the alteration of the plasma free-catecholamine level during hemopurification in a patient with pheochromocytoma, the levels of plasma free-catecholamine and total catecholamine in the filtrate were monitored pre- and post-hemopurification. Approximately 100μg of total catecholamine was removed by the hemopurification procedure though the high level of plasma-free catecholamine remained unaltered.
(Internal Medicine 31 : 438-440, 1992)

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