Objective A retrospective study was performed to evaluate the effects of using long-term long acting nitrates without a dose-free interval in treating patients undergoing thrombolytic therapy for acute myocardial infarction (MI).
Patients and Methods A total of 297 patients taking prescribed medication for secondary prevention of the MI were selected for the study. They were divided into a nitrate group consisting of 222 patients who had continuously received long-acting nitrates without a dose-free interval, and a control group consisting of 75 patients who were not able to use the long-acting nitrates because of adverse effects. The primary endpoint was cardiac events, either cardiac death or a nonfatal MI, in five years.
Results The incidence of primary endpoint in five years was 13.4 percent in the nitrate group and 6.2 percent in the control group, a 2.2-fold increase in risk. However, the difference was not significant. After adjustment for age, there was no statistically significant difference between the incidence of primary endpoint in the nitrate group (9.8%) and that in the control group (5.7%). A Cox proportional-hazards regression analysis revealed that the long-acting nitrates were not related to the incidence of primary endpoint (p=0.23).
Conclusion The administration of long-term long-acting nitrates without a dose-free interval had no benefit of reducing the incidence of cardiac events of patients undergoing thrombolytic therapy for acute MI.
(Internal Medicine 39: 877-884, 2000)

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Objective To clarify the differences in immunological and psychobehavioral characteristics of HTLV-1 carriers and non-carriers with persistently low natural killer (NK) cell activity.
Methods The individuals with persistently low NK cell activity were divided into HTLV-1 carriers and non-carriers. NK cell activity, lymphocytic proliferation, lymphocyte subsets (CD4+, CD8+, CD16+, CD20+, CD56+), and psychobehavioral responses were examined.
Patients Of 296 outpatients with physical complaints, 30 patients with persistently low NK cell activity (10 HTLV-1 carriers and 20 HTLV-1 non-carriers) and 20 healthy controls negative for HTLV-1 antibody and with normal NK cell activity were randomly selected.
Results In HTLV-1 carriers with persistently low NK cell activity, no significant differences were observed in NK cell subsets (CD16+ and CD56+) and psychobehavioral responses compared with the healthy controls. In HTLV-1 non-carriers, NK cell subsets were significantly low, and depression, anxiety and fatigue were significantly greater than in healthy controls.
Conclusions These findings suggest that persistently low NK cell activity in HTLV-1 carriers might be reduced due to the HTLV-1 infection. On the other hand, the reduction in the NK cell activity in HTLV-1 non-carriers appears to be related to depression, anxiety, and fatigue.
(Internal Medicine 39: 885-890, 2000)

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Objective The mechanisms by which cessation of cigarette smoking may improve regional cerebral blood flow (rCBF) and the details of the possible relationship remain unclear. Xenon-133 inhalation was used to determine rCBF in six smokers at baseline (during smoking) and again 6 and 9 years after they had quit smoking (quitter group). A control group of eight nonsmokers (nonsmokers group) underwent similar serial determinations.
Results Regional CBF in quitters had decreased significantly after the 6 years, but improved significantly after 9 years, when abstinence had been maintained from 4 to 6 years. In the nonsmokers group rCBF did not change significantly over 9 years.
Conclusion Cessation of cigarette smoking improves cerebral circulation, but this effect requires several years.
(Internal Medicine 39: 891-893, 2000)

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Objective To estimate the annual prevalence of viral and other neurological infections at large hospitals in Japan during the period from 1989 to 1991.
Methods A nationwide questionnaire survey on the numbers of inpatients with viral and other neurological infections was sent for completion to the chiefs of Departments of Internal Medicine, Neurology and Pediatrics at all hospitals with more than 200 beds.
Results The average annual number of inpatients (and the number per 10⁶ population) with encephalitis in large hospitals was estimated to be 2, 200±400 (17.7±13.2), while it was 32, 000±16, 000 (258±129) for meningitis, and 650±50 (5.2±0.4) for myelitis. Among the inpatients with encephalitis, meningitis, and myelitis, an unknown etiology was the most common (51.2% in encephalitis, 73.2% in meningitis, and 36.3% in myelitis), followed by a viral etiology for all three diseases.
Conclusion The first estimate was made of the annual prevalence of viral and other neurological infections and their etiology in Japan.
(Internal Medicine 39: 894-900, 2000)

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Objective To investigate how patients with bacteremic sepsis are managed in a tertiary care teaching hospital.
Patients and Methods Prospective observational study on patients with bacteremic sepsis. Clinical and microbio-logical characteristics of bacteremic sepsis were analyzed in relation to prognosis. Severity of the illness was quantitatively analyzed by the APACHE (Acute Physiology, Age, Chronic Health Evaluation) III scoring system. Also investigated was how closely physicians paid attention to acute physiological alterations in patients.
Results The 28-day mortalities in fifty hemodynamically stable patients and in twenty-three septic shock patients were 26% and 52%, respectively (p=0.028). Gram-positive organisms accounted for 54% of all organisms, with the mortality and incidence of septic shock being the same as with Gram-negative infections. The mean APACHE III score was 42.9 in survivors, and 76.5 in non-survivors (p < 0.001). Although serum levels of C-reactive protein and acute physiology score (APS) was significantly higher in non-survivors than in survivors, the correlation with APACHE III score was more prominent in APS. The number of vital signs recorded was 1.67 in physicians and 3.6 in nurses (p < 0.001).
Conclusions The present study proved that the APACHE HI score accurately discriminates between survivors and non-survivors of patients with sepsis. By addressing the need for an objective evaluation of severity of illness, it strongly recommends that physicians should be made aware of physiologically defined sepsis and that they should pay closer attention to patients' physiological alterations to identify the development of sepsis in critically ill patients.
(Internal Medicine 39: 901-909, 2000)

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A 61-year-old man with a mixed carcinoid-adenocarcinoma of the liver is described. Microscopic examination of the lesion showed a differentiated adenocarcinoma with distinct carcinoid components that stained positively for argyrophil. The tumor cells contained serotonin granules on immunohistochemical studies. Detailed examination disclosed no primary tumor in the gastrointestinal tract or in any other organ. Resection was considered impractical because there were multiple tumors. The patient received chemotherapy six times (cisplatin 60 mg/m², epirubicin 40 mg/m² per month). The multiple tumors gradually shrank. At the time of this writing, the patient is still alive. To our knowledge, this is the first reported case of mixed carcinoid-adenocarcinoma of the liver.
(Internal Medicine 39: 910-913, 2000)

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We report two patients with gastrointestinal stromal tumors (GISTs) of the small intestine that expressed c-kit protein (CD117). One was a 68-year-old woman with epigastralgia and vomiting. A submucosal tumor of the upper jejunum was detected, and partial resection was carried out. The histology revealed a GIST negative for CD34 but positive for CD117. The other was a 42-year-old woman with progressive anemia, melena and lower abdominal pain. Intussusception was detected, and a partial resection was carried out. A submucosal tumor of the lower jejunum was noted. The histology revealed a GIST positive for both CD34 and CD117.
(Internal Medicine 39: 914-919, 2000)

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A 52-year-old man developed malignant peritoneal mesothelioma 17 years after radiotherapy for seminoma of the testis. Although asbestos exposure is considered to be the major risk factor for the development of malignant mesothelioma, prior therapeutic radiation has also been postulated as a causative factor. The unexplained appearance of ascites or pleural effusion within a previously irradiated area should be considered suggestive of malignant mesothelioma in any long-term survivor of cancer. In addition, the patient suffered a deep vein thrombosis four years before the diagnosis of mesothelioma. Deep vein thrombosis is a common complication of malignant disease, and is often the first clue to occult malignancy.
(Internal Medicine 39: 920-924, 2000)

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A 48-year-old male presented with an acute change in mental status due to a marked elevation of plasma NH₃ and was diagnosed with citrullinemia with amino acid analysis of blood. Hemodialysis and hemodiafiltration were performed, but serum chemical analysis did not show any improvement which led us to terminate dialysis following intensive care for 3 days. Surprisingly, NH₃ level had decreased by 6 days after admission, coinciding with normalization of the size of the pupils. Since spontaneous remission had never been discussed, we discuss this relatively rare, but clinically significant entity with regard to its acute phase management and its potential reversibility.
(Internal Medicine 39: 925-929, 2000)

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A 23-year-old male with congenital hepatic fibrosis died because of progressive cholestatic liver damage. Pathologically, marked extension of fine fibers along the sinusoids in addition to fibrosis in Glisson's sheath, miniaturization and pseudo-glandular formation of hepatocytes as parenchymal damage, and nodular regenerative hyperplasia were considered as the cause of rapid aggravation of liver damage or portal hypertension.
(Internal Medicine 39: 930-935, 2000)

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A 51-year-old man was admitted to our hospital with complaints of severe chest pain, nausea, and vomiting. These symptoms had progressed rapidly and he was in shock. It was necessary to make a correct diagnosis as early as possible. However, the hemodynamic condition of the patient deteriorated rapidly before a definitive diagnosis could be established in spite of conventional therapies. Under hemodynamic assistance with percutaneous cardiopulmonary support (PCPS), a final diagnosis of esophageal perforation was made by esophagography. Our report illustrates a new application of PCPS for highly selected cases of noncardiogenic shock as a "bridge" until an accurate diagnosis is made and a specific treatment is applied.
(Internal Medicine 39: 936-939, 2000)

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A 68-year-old woman developed acute pulmonary edema due to severe acute aortic valvular regurgitation. At the time of emergency surgery, it turned out to result from spontaneous avulsion of the aortic valve commissure. Later, the patient was diagnosed to have pseudoxanthoma elasticum based on typical skin lesions. Connective tissue abnormalities associated with pseudoxanthoma elasticum might have contributed to the development of the avulsion of the aortic valve in this particular patient.
(Internal Medicine 39: 940-942, 2000)

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We report a case of slowly progressive insulin-dependent diabetes mellitus in an elderly patient with Graves' disease. A 69-year-old man presented with apathetic thyrotoxicosis and weight loss. Laboratory findings indicated insulin-dependent diabetes mellitus (IDDM) with Graves' disease. Human leukocyte antigens DR4 and DR9, which are recognized as markers for IDDM with autoimmune thyroid disease, were detected. The clinical course of the IDDM was compatible with the slowly progressive type. Onset of this disease during old age is rare, and such cases should be analyzed with a thyroid function test because the symptom of thyrotoxicosis may be masked in the elderly.
(Internal Medicine 39: 943-946, 2000)

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A 35-year-old man who had been a carpenter and a cabinet worker for over 15 years, was referred to our clinic with a 4-month history of cough, chest tightness and difficulty in breathing which occurred within minutes of exposure to African cherry wood (Makore). He developed a dual asthmatic reaction on specific challenge test with an extract of African cherry wood dust. Thus, the diagnosis of occupational asthma due to exposure to African cherry wood dust was confirmed by the specific challenge test. The mechanism of asthma due to African cherry wood dust exposure is not clear.
(Internal Medicine 39: 947-949, 2000)

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A rare case of follicular dendritic cell (FDC) sarcoma is reported. A 71-year-old woman was admitted for evaluation of constipation. Computerized tomography showed cervical, supraclavicular, retroperitoneal, and paraaortic lymphadenopathies. Histological findings from a cervical lymph node revealed Hodgkin's disease at first. But tumors that arose both in the cervical and the left interscapular regions during the chemotherapy were immunohistochemically confirmed to be of follicular dendritic cell origin. The ultrastructural findings were consistent with those of FDC sarcoma. FDC sarcoma is a rare nonlymphoid cell-derived malignant tumor originating from the lymphoid tissue. The diagnosis of FDC sarcoma is most accurately established by immunohistochemical methods, using its specific markers.
(Internal Medicine 39: 950-955, 2000)

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A 28-year-old woman was hospitalized with dysarthria and oro-mandibular and upper limb dystonia. Approximately 8 years prior to the current admission, the woman became severely hyponatremic due to traumatic subarachnoid hemorrhage-related SIADH. Brain MRIs showed a signal increase in the central pons, thalamus and striatum on T2 weighted images compatible with central pontine and extrapontine myelinolysis. From a few months after that event, dystonia progressed slowly over the subsequent 8 years. We speculate that the particular damage chiefly to the myelin structures by myelinolytic process may have caused an extremely slow plastic reorganization of the neural structures, giving rise to progressive dystonia.
(Internal Medicine 39: 956-960, 2000)

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Crigler-Najjar disease (CN) type I is characterized by persistent unconjugated hyperbilirubinemia from birth. The male patient here was diagnosed with this disease as a neonate and had been treated by phototherapy. At age 16 he suddenly developed generalized convulsions, followed by impaired cognitive function. The serum level of bilirubin was extremely high (total bilirubin: 41.7 mg/dl) and there were no other detectable causes responsible for the metabolic encephalopathy. He received bilirubin adsorption therapy several times, and the bilirubin encephalopathy improved in response to the fall in the serum level of bilirubin. After this he underwent a successful liver transplantation in Australia, and recovery of his mental faculties was satisfactory. Within the subsequent 3 years epileptic abnormal discharges on the electroencephalogram disappeared. Phototherapy alone can not prevent the rise in the serum level of bilirubin in adolescent or adult patients with CN type I, therefore such patients tend to experience life-threatening bilirubin encephalopathy. To save patients with the acute onset type of bilirubin encephalopathy, sufficient bilirubin adsorption followed by liver transplantation appears to be the most recommended therapeutic approach.
(Internal Medicine 39: 961-965, 2000)

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The blood coagulation system has been shown to be activated in subacute exacerbations of Binswanger disease (BD). In our previous study, the antithrombin drug argatroban ameliorated the neurological exacerbations in a BD patient with antiphospholipid antibody syndrome. We have further examined the therapeutic efficacy of argatroban in 3 BD patients with subacute exacerbations, but without any immune-mediated prothrombotic complications. In 1 out of these 4 patients, treatment with sodium ozagrel, an antiplatelet drug was applied, but was ineffective. In all patients, argatroban treatment reduced the levels of the hemostatic markers, with a corresponding improvement in cognitive dysfunction and gait disorders. These results suggest that the antithrombin effect is true also for BD patients not compromised by the immune-mediated prothrombotic condition.
(Internal Medicine 39: 966-969, 2000)

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A 66-year-old woman diagnosed as having Hashimoto's disease and rheumatoid arthritis manifested interstitial pneumonia. We diagnosed Sjögren's syndrome and primary biliary cirrhosis as complications in this case. Steroid therapy was relatively effective for the interstitial pneumonia which was in an active state; however, during tapering of the steroid, there was a relapse and also severe dry throat. Cyclophosphamide was added and was effective in the prevention of recurrence. Even after discontinuation of steroid therapy, her general condition is stabilized. It is very important to carefully investigate other organ involvement as a prognostic factor in cases in which there are multiple autoimmune diseases.
(Internal Medicine 39: 970-975, 2000)

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A 51-year-old Japanese man with Churg-Strauss Syndrome (CSS) diagnosed by pleural biopsy is described. He was hospitalized because of high fever and bilateral knee, elbow and shoulder joint pain. Chest roentgenogram and chest computed tomography (CT) scan revealed bilateral massive pleural effusion. Pleural biopsy revealed eosinophilic infiltration and necrotizing granulomas. He was treated with oral prednisolone and his symptoms improved. This is the first report of CSS diagnosed by pleural biopsy.
(Internal Medicine 39: 976-978, 2000)

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A 73-year-old man was admitted to our hospital because of pleural effusion and nephrotic syndrome. Sjögren's syndrome (Sjs) was diagnosed based on a positive test for antibodies to Ro and La, and the result of labial salivary gland biopsy. The pleural effusion showed a high number of lymphocytes and high liters of antibodies to Ro and La. By immunohistochemistry, it was determined that infiltrating CD3⁺ cells predominated over infiltrating CD20⁺ cells in the pleura. Nephrotic syndrome was also present, which, as confirmed by renal biopsy was due to advanced diabetic nephropathy. Here, we report a case of Type II diabetes mellitus and primary Sjs complicated by pleural effusion, discuss the available treatment for pleural effusion.
(Internal Medicine 39: 979-984, 2000)

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Churg-Strauss syndrome, an uncommon condition, occurs even more rarely in association with pregnancy. One month postpartum, a 25-year-old Japanese woman was hospitalized for dyspnea, fever, diarrhea, and complaints of dysesthesia in the right lower limb and right lumbar and abdominal region. Marked eosinophilia was present. Symptoms of bronchial asthma had developed early in the pregnancy, which concluded with delivery of a healthy baby at 39 weeks of gestation. Churg-Strauss syndrome was diagnosed and prednisolone was administered with a good response leading to remission. Three years after the first pregnancy, low-dose steroid therapy was continued through another pregnancy. The patient delivered another healthy baby at 39 weeks of gestation, this time with no exacerbation of symptoms.
(Internal Medicine 39: 985-990, 2000)

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A 51-year-old type 2 diabetic patient with a scrotal subcutaneous abscess is reported. He was diagnosed as having diabetes mellitus five years earlier. He had left scrotal swelling and pain with granulocytosis, elevated C-reactive protein and hyperglycemia. He was successfully treated with incision and drainage (Streptococcus agalactiae was identified in the pus), débridement, antibiotics, immunoglobulin and insulin. This case resembled Fournier's gangrene, an infective necrotizing fasciitis of the perineal, genital or perianal regions. Diabetes mellitus is a basic disorder often associated with Fournier's gangrene. Scrotal subcutaneous abscess should be prevented from progressing to Fournier's gangrene with early and appropriate treatment.
(Internal Medicine 39: 991-993, 2000)

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A 70-year-old woman with fever was admitted to our hospital. She was diagnosed as miliary tuberculosis and treated with antituberculous drugs. After seven weeks of therapy, she developed a sudden sharp upper abdominal pain and shock. Angiography of the celiac artery showed two hepatic artery pseudoaneurysms with extravasation. The hemorrhage was successfully stopped by microcoil emboli/ation. The clinical course suggested that miliary tuberculosis had caused the pseudoaneurysms. Although aneurysms rarely occur as a complication of miliary tuberculosis, they should be diagnosed as early as possible because of the high rate of rupture and associated high mortality rate.
(Internal Medicine 39: 994-998, 2000)

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