Objective Due to the increased incidence of pulmonary tuberculosis in association with corticosteroid therapy during the last five years in our associated hospitals, we studied the clinical characteristics of these patients.
Patients Fourteen cases of pulmonary tuberculosis were collected which occurred in association with corticosteroid drugs in our associated hospitals during the last 10 years; four patients (2.1 %) from April 1991 to March 1996 and 10 patients (4.3%) from April 1996 to March 2001.
Results The average age of the 14 patients was 74.1 years old and the male:female ratio was 9:5. Regarding underlying diseases, respiratory diseases (7 patients) were the most frequent and a past history of pulmonary tuberculosis was recognized in six patients. The duration of corticosteroid administration ranged from two months to seven years and the total dose of corticosteroids ranged from 1.20 g to 12.05 g. Pulmonary tuberculosis was detected by chance during a health examination in eight patients and radiological findings showed an infiltration shadow without cavity located in a portion other than the predominant location in four patients. A microbiological examination was smear positive in eight patients but tolerance was not shown to any antituberculous drugs. The prognosis was poor because the mortality rate was high, but the cause of death was not related to the progress of pulmonary tuberculosis.
Conclusion Careful observation of patients is considered to be important because pulmonary tuberculosis in association with corticosteroid drugs was found among inpatients, there was no relationship to the total dose or duration of administration of corticosteroid drugs, there were no clinical symptoms, and the patients exhibited atypical radiographic findings.
(Internal Medicine 41: 1103-1110, 2002)

View full abstract

Objective We assessed the usefulness of high-resolution computed tomography (HRCT) and ferritin determinations in bronchoalveolar lavage (BAL) fluid for diagnosis of welder's pneumoconiosis.
Patients and Methods We investigated 11 patients with welder's pneumoconiosis who were 34 to 67 years old and had been welding for 17 to 45 years. Ten patients were current smokers. We performed chest radiography and HRCT, and measured serum ferritin on all 11 patients. We obtained BAL fluid in 9 cases and transbronchial lung biopsy (TBLB) specimens in 7. Ferritin concentrations in BAL fluid were compared with those in welders without pneumoconiosis and other pneumoconiosis cases.
Results HRCT revealed small centrilobular nodules in 9 cases, mild fibrotic changes in 3, and emphysematous changes in 3. Serum ferritin concentrations were elevated (>240 ng/ml) in 10 cases. Ferritin concentrations in BAL fluid were higher in welder's pneumoconiosis than in the occupational control group.
Conclusion In welder's pneumoconiosis, small centrilobular nodules are frequently seen on HRCT, and ferritin shows elevations in serum and/or BAL fluid. Such ferritin determinations are of value in diagnosis.
(Internal Medicine 41: 1111-1117, 2002)

View full abstract

Objective We attempted to evaluate the feasibility (therapeutic efficacy, tolerance, and clinical courses after treatment) of pirfenidone, an anti-fibrotic drug for patients with chronic pulmonary fibroses such as idiopathic pulmonary fibrosis (IPF).
Methods Open-label one-year treatment for compassionate-use. Patients or Materials: Oral pirfenidone (40 mg/kg body weight) was administered to 8 patients with advanced IPF and 2 with interstitial pneumonia associated with diffuse systemic sclerosis. The plasma concentration of the drug was serially followed. Radiographic scores, pulmonary functions, and arterial blood oxygen pressure were compared at three time points: at one-year before treatment, at the time of entry, and at one-year after entry.
Results While pirfenidone did not show a definite therapeutic effect on overall survival (2 years after entry). During one-year treatment, there was no significant deterioration in terms of chest radiographic scores and arterial oxygen pressure, and the drug was well tolerated with minimal adverse effects within the ranges observed in this study, plasma pirfenidone concentrations did not seem to relate to the appearance of adverse effects or differences in therapeutic effects.
Conclusion The feasibility of Pirfenidone as a therapeutic drug was confirmed for patients with advanced pulmonary fibrosis.
(Internal Medicine 41: 1118-1123, 2002)

View full abstract

Objective Recent studies reported that hyperesthesia may be an indicator of early diabetic polyneuropathy. Using the current perception threshold (CPT) test, which stimulates peripheral sensory nerve fibers by three different frequencies (2, 000, 250, and 5 Hz), we investigated the relationship between hyperesthesia and glucose metabolic impairment in a community.
Methods The number of subjects, aged 40 to 79 years, was 2, 074. The CPT values at each frequency were classified into three categories (hyperesthesia, normal, and hypoesthesia). Subjects were also subgrouped into three groups (normal, insulin resistance, and diabetes) according to glucose metabolic status, and those with hypoesthesia at each frequency were excluded in the analyses.
Results The prevalence of hyperesthesia at 2, 000, 250, and 5 Hz in male diabetic subjects were 14.1, 15.6, and 7.7%, respectively, and 22.2, 24.5, and 16.4% respectively in female diabetic subjects. In logistic regression analysis adjusted for age, females with diabetes showed a significantly high odds ratio (OR) for hyperesthesia at 2, 000 Hz (OR, 2.42; 95% confidence interval (95%CI), 1.18 to 4.97) and 250 Hz (OR, 2.65; 95%CI, 1.31 to 5.37). In male diabetic subjects, a significantly high odds ratio for hyperesthesia was seen at 250 Hz (OR, 2.09; 95%CI, 1.07 to 4.05).
Conclusion Our results suggested that hyperesthesia may emerge coupled with developing diabetes, supporting the precedent hypothesis.
(Internal Medicine 41:1124-1129, 2002)

View full abstract

Objective Cerebrovascular disease (CVD) is a serious complication of acute leukemia, and the underlying conditions are different from the common risk factors for CVD. The aim of this study was to characterize the clinical and pathological features of CVD in patients with acute leukemia.
Patients or Materials In our series of 116 autopsied cases of acute leukemia during the period between January 1978 and December 1998, we had 14 patients who had CVD during the course of acute leukemia. The neuropathological and clinical features of those patients were examined.
Results Neuropathological examination showed hemorrhagic infarction due to disseminated aspergillosis or mucormycosis (5 cases), multiple hemorrhages due to leukemic cell infiltration (2 cases) and a single massive hemorrhage with petechial hemorrhages in various regions of the brain (4 cases). Three patients had CVD due to miscellaneous causes. Clinicopathological correlation revealed that fungal disseminations occurred under agranulocytosis, while leukemic cell infiltration occurred under a marked leukocyotosis (peripheral white blood cell count >100, 000/μl). Four patients with coagulopathy, including three with disseminated intravascular coagulation (DIC) had a single massive hemorrhage.
Conclusion Our study demonstrated that there were at least three types of CVD with specific Clinicopathological features. Hemorrhagic infarction under agranulocyotosis was due to disseminated aspergillosis or mucormycosis. Multiple cerebral hemorrhages under marked leukocyotosis was due to leukemic cell infiltration into the brain. Massive cerebral hemorrhage was associated with coagulopathy including DIC.
(Internal Medicine 41:1130-1134, 2002)

View full abstract

Objective The present study was designed to determine the chronological sequence of interstitial pneumonia, skin involvement, and muscle involvement associated with polymyositis/dermatomyositis (PM/DM).
Methods We examined our own cases of histologically confirmed interstitial pneumonia associated with PM/DM. In addition, a review of the literature was done to evaluate other cases of histologically confirmed interstitial pneumonia associated with PM/DM. Lung involvement was the first clinical symptom for all of our 8 patients.
Results Including the literature review and our 8 cases, there were 94 patients with PM/DM in whom interstitial pneumonia was histologically confirmed (36 PM, 50 DM, and 8 amyopathic DM). Chronological evaluation between the diagnosis of PM/DM and lung involvement demonstrated that most lung involvement occurred just before or just after the diagnosis of PM/DM. Interstitial pneumonia was preceded in 35 of 87 evaluable patients [21 cases with PM (61.8%), 14 cases with DM and amyopathic DM (40.2%)]. In 60 of 87 evaluable patients (69.0%), lung involvement occurred as a clinical manifestation at the diagnosis of PM/DM.
Conclusion The present data demonstrate that interstitial pneumonia was frequently the initial onset in patients with PM/DM.
(Internal Medicine 41:1135-1141, 2002)

View full abstract

A 51-year-old woman with autoimmune pancreatitis is reported in whom treatment with ursodeoxycholic acid (UDCA) was beneficial. Complaining of epigastric discomfort, she presented with liver dysfunction of the cholestatic type, and diabetes mellitus. Pancreatic imaging revealed a diffuse swelling of the body, an irregular narrowing of the main pancreatic duct, and a terminal stricture of the common bile duct. Histologically, the biopsied pancreas was replaced by fibrous tissue with a small amount of mononuclear cell infiltration. She had anti-carbonic anhydrase-II antibody and anti-lactoferrin antibody. After treatment with UDCA, her liver dysfunction and diabetes mellitus improved and the pancreas size was reduced. Steroid therapy is usually indicated for this disorder, but UDCA may be given as an alternative choice.
(Internal Medicine 41: 1142-1146, 2002)

View full abstract

A 58-year-old man with a 64-month history of unclassified cardiomyopathy developed congestive heart failure (CHF) and had been dependent on long-term intravenous positive inotropes. Combined pimobendan and carvedilol administration resulted in marked symptomatic improvement from New York Heart Association functional class IV to I. Echocardiograms showed improvement of left ventricular (LV) ejection fraction from 15 to 48%, and LV enddiastolic diameter from 6.7 to 4.9 cm. This mode of therapy not only improved LV contractile function but also normalized LV volume, which was an unusual clinical course compared with the general course of advanced CHF.
(Internal Medicine 41: 1147-1152, 2002)

View full abstract

A 60-year-old man was admitted to our hospital with marked hypercalcemia. He had no symptoms that might be caused by hypercalcemia. Plasma concentrations of calcium and intact parathyroid hormone were 15.2 mg/dl and 103 pg/ml, respectively. Radiological examinations revealed no abnormal findings. His calcium-creatinine clearance ratio was calculated to be 0.004, thus he was diagnosed as having hypocalciuric hypercalcemia. Familial hypocalciuric hypercalcemia was a plausible diagnosis, however, gene analysis of his calcium-sensing receptor (CaSR) revealed no mutation. The patient was thought to be a case of hypocalciuric hypercalcemia without mutation in the CaSR gene.
(Internal Medicine 41: 1153-1157, 2002)

View full abstract

A 69-year-old man with proteinuria, hematuria and abnormal renal and hepatic function developed acute renal failure. His clinical and laboratory examinations showed splenomegaly, edema, anemia and polyclonal hypergammaglobulinemia with high IgG levels. Renal biopsy showed interstitial nephritis with predominant B cell and plasma cell infiltration without monoclonality. After corticosteroid treatment, the patient showed remission in clinical symptoms and laboratory findings. However, one year later, he developed mantle cell lymphoma (MCL) with typical lymphocyte markers of cyclin Dl and CDS. When evaluated retrospectively, this patient appeared to have multicentric Castleman's disease initially and developed MCL later.
(Internal Medicine 41: 1158-1162, 2002)

View full abstract

A case of polycystic kidney disease (PKD) associated with Klippel-Trenaunay-Weber syndrome is described. A 58-year-old man with chronic renal failure experienced urinary retention following gross hematuria. Intermittent drainage was necessary for significant urination for five days. Thereafter his urinary retention was relieved, but renal failure progressively developed and hemodialysis was started. Right hydronephrisis and hydroureter disappeared one month later. In spite of relief of obstruction, of which the cause was likely blood clots, renal function was not restored. Obstructive nephropathy was most likely explicable for notable deterioration in renal function. Our case might have susceptibilities to PKD development in terms of angiogenesis.
(Internal Medicine 41: 1163-1166, 2002)

View full abstract

We report a case of IgA nephropathy with renal failure in which the deterioration of renal function was inhibited by the addition of angiotensin II receptor blocker (ARB) losartan. Before administration of losartan, the mean decline in the patient's glomerular filtration rate (GFR) was 0.64 ml/min/1.73 m²/month. Losartan treatment was started when serum creatinine rose above 4.0 mg/dl. With this treatment the serum creatinine level has remained stable for 3.5 years, and the mean decline in GFR was 0.06 ml/min/1.73 m²/month. We document successful retardation of renal failure with the use of losartan. Our experience suggests that dialysis therapy can be delayed significantly in patients using this drug.
(Internal Medicine 41: 1167-1170, 2002)

View full abstract

A woman was admitted for acute renal failure and erythematous lesions. She was diagnosed with sarcoidosis after analysis of biopsy specimens revealed noncaseating epithelioid granulomas, elevated serum angiotensin-converting enzyme levels, and bilateral hilar lymphadenopathy. Serum concentrations of ionized calcium and 1, 25-dihydroxyvitamin D₃ [1, 25-(OH)₂D₃] were extremely high. Serum intact osteocalcin concentration and urinary deoxypyridinoline excretion were within reference ranges. Treatment with prednisolone induced a prompt improvement with normalization of serum concentrations of ionized calcium and 1, 25-(OH)₂D₃. Serum intact osteocalcin concentration was markedly suppressed and urinary deoxypyridinoline excretion increased. It is possible suppressed bone resorption may be associated with overproduction of 1, 25-(OH)₂D₃.
(Internal Medicine 41: 1171-1174, 2002)

View full abstract

A 79-year-old woman was admitted to hospital due to a four-month history of a cough and dyspnea on exertion. Chest CT scans revealed ground glass opacity with thickened interlobular septa in both lungs. Bronchoalveolar lavage fluid (BALF) had milky appearance and revealed large acellular eosinophilic amorphous bodies positively stained with periodic acid-Schiff (PAS). Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) were present in sera and BALF from the patient. Ambroxol was started in a daily dose of 45 mg orally. Her oxygen saturation improved and abnormal shadows in CT scan disappeared 6 months after beginning the therapy.
(Internal Medicine 41: 1175-1178, 2002)

View full abstract

A 56-year-old man was admitted with cough, fever, myalgia, and arthralgia. Chest computed tomography demonstrated bilateral diffuse ground-glass opacities predominantly in the upper lungs. Subpleural non-segmental consolidation was observed in the late phase. Hypersensitivity pneumonitis was suspected, and an environmental provocation test with the incidental use of a home ultrasonic humidifier was positive. Unlike typical hypersensitivity pneumonitis, serum KL-6 levels were normal. Although several microorganisms were isolated from the humidifier water, there was no evidence for immune sensitization. We detected high amounts of endotoxin in the humidifier water, which may have contributed to the lung injury of this patient.
(Internal Medicine 41: 1179-1182, 2002)

View full abstract

We describe a case of Philadelphia chromosome-positive chronic myeloid leukemia (Ph-positive CML) expressing p190^BCR-ABL. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of bone marrow cells showed a 472-bp band using primers specific for the p190^BCR-ABL but not p210^BCR-ABL transcript. Sequencing analysis revealed that the PCR product was derived from the fusion between BCR exon e1 and ABL exon a2 (e1a2). CML expressing p190^BCR-ABL is relatively rare. In a review of the literature, it may be grouped into 2 categories; approximately half of the patients exhibited prominent monocytosis and intermediate hematological phenotype between CML and chronic myelomonocytic leukemia, and the remaining patients showed no monocytosis.
(Internal Medicine 41: 1183-1187, 2002)

View full abstract

Virus-associated hemophagocytic syndrome (VAHS) is reported to be a rare complication in hepatitis A virus infections. We encountered two patients with hepatitis A virus-associated hemophagocytic syndrome (HAV-AHS). Although hemophagocytosis associated with other types of virus infections is fatal, the present patients with HAV-AHS recovered well without any treatment. Thrombocytopenia is an initial important finding of VAHS which is not rare in patients with acute hepatitis A. If bone marrow aspiration is performed more frequently, more HAV-AHS will be diagnosed. Further investigations are necessary to clarify the clinical features of HAV-AHS in more patients.
(Internal Medicine 41: 1188-1192, 2002)

View full abstract

We report a patient with dissecting aneurysm who presented with a sudden severe headache without any neurological symptoms. Although brain computed tomography (CT) scan and MRI were negative, magnetic resonance angiography (MRA) showed a pseudocavity in a segment of the left vertebral artery. In addition, the dissecting wall of the left vertebral artery was clearly visualized in the original images of MRA. Our findings indicate that brain CT, MRI or cerebral angiography alone are sometimes inadequate for the diagnosis of vertebral dissecting aneurysm, and that MRA and its original images are necessary to establish the correct diagnosis.
(Internal Medicine 41: 1193-1195, 2002)

View full abstract

A case of POEMS syndrome in a 49-year-old Japanese woman is reported. The patient exhibited prominent edema in her legs at night, but her edema usually improved by the following morning. The plasma concentrations of VEGF in the patient showed diurnal fluctuations; plasma VEGF levels peaked at night and decreased in the daytime. Immunocytochemical study demonstrated the expression of VEGF in IgA- and λ-positive plasma cells in bone marrow. The results indicate that VEGF was produced at least by plasma cells and that VEGF production was regulated by circadian rhythm in synchronization with the development of edema.
(Internal Medicine 41: 1196-1198, 2002)

View full abstract

Graves' disease (GD) has been reported to be frequently complicated with other autoimmune diseases. However, it is rarely complicated with scleroderma-polymyositis overlap syndrome. Recently, we encountered a 35-year-old woman who developed GD and immune thrombocytopenic purpura during follow-up observation of scleroderma-dermatomyositis overlap syndrome. Platelet counts recovered after high-dose γ-globulin therapy and bolus methylprednisolone therapy. The present case is the first report of a combination of scleroderma, dermatomyositis, GD, and immune thrombocytopenic purpura. The patient was anti-Ku antibody-positive and had relatively low natural killer T cell counts, both of which might contribute to the complication of multiple autoimmune diseases.
(Internal Medicine 41: 1199-1203, 2002)

View full abstract

A 13-year-old girl with Graves' disease, whose younger sister had systemic lupus erythematosus, developed polyarthralgia, fever, neutropenia, hypergammaglobulinemia, and microscopic hematuria after treatment with propylthiouracil (PTU) for 2 years. Myeloperoxidaseanti-neutrophil cytoplasmic antibodies were strongly positive. Anti-single- and anti-double-stranded DNA antibodies were positive, whereas LE cells and anti-Sm antibodies were negative. PTU was discontinued and all symptoms subsided gradually. Two years later, the microscopic hematuria had disappeared completely. Both patients had the identical HLA-DR alleles (HLA-DR9). These present two cases in siblings suggest that both sisters had lupus diathesis, and that the elder sister developed a PTU-induced lupus-like syndrome.
(Internal Medicine 41: 1204-1208, 2002)

View full abstract

Kaposi's sarcoma (KS) is the most prevalent AIDS-associated tumor. We report a 44-year-old Japanese man with advanced AIDS-associated KS, which was spread over bilateral pulmonary parenchyma. He was initially treated with combination chemotherapy with a partial response. Upon the recurrence of his KS two months after the completion of the combination chemotherapy, the patient received paclitaxel, which brought about a complete response. Highly active antiretrovial therapy (HAART) was initiated three months before the combination chemotherapy, and the CD4+ T-cell count had risen before starting paclitaxel. His clinical course suggests that paclitaxel was highly effective for KS disease control as previously reported, and that immune restoration with HAART is crucial in the treatment of KS.
(Internal Medicine 41: 1209-1212, 2002)

View full abstract