Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder molecularly defined by the BCR-ABL gene and its products. The protein encoded by this chimeric gene is a constitutively activated tyrosine kinase that alters multiple signal transduction pathways inducing malignant transformation. Until recently, treatment options for patients with CML consisted of hydroxyurea, interferon-based therapies or allogeneic stem cell transplantation (alloSCT). Treatment decisions were generally based on the age of the patient and the phase of the disease. Recently, several new therapies have been developed that may change the natural history of CML and patient prognosis. In particular imatinib mesylate (STI571, Gleevec) an oral Bcr-Abl kinase inhibitor, has demonstrated activity in all phases of CML, and may replace interferon and alloSCT as the initial therapy for this disease. Other agents and therapies with potential value, either alone or in combination, include polyethyleneglycol (PEG) interferon, homoharringtonine, decitabine, oral cytarabine, and growth factor modulation. In this article, we discuss the biological and clinical characteristics of CML, as well as the different therapeutic alternatives for patients with this disorder.
(Internal Medicine 41: 254-264, 2002)

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A variety of pathological changes have been observed in the central airways, peripheral airways and lung parenchyma of patients with chronic obstructive pulmonary disease (COPD). The characteristic changes in the central airways include inflammatory cellular infiltration into the airway wall and mucous gland enlargement. In the peripheral airways, various morphological changes are observed, including mucous plugging, epithelial abnormalities, inflammatory cellular infiltrates, fibrosis and distortion; these changes lead to airway narrowing. In the lung parenchyma, emphysema defined as alveolar destruction and airspace enlargement is present. Although the major sites of airflow limitation in patients with COPD are most likely the peripheral airways, lesions in both the peripheral airways and the lung parenchyma contribute to chronic airflow limitations.
(Internal Medicine 41: 265-269, 2002)

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Objective and Methods We examined the prognostic significance of electrocardiographic predictors (number of leads with ST depression, maximal ST depression, QT dispersion), C-reactive protein, fibrinogen, myosin light chain 1 and creatine kinase MB fraction in 62 patients with unstable angina showing ST depression during an anginal attack.
Results During the 90-day follow-up period, 15 patients (24%) exhibited new cardiac events (death, myocardial infarction or urgent revascularization). Using multivariate analysis, the number of leads with ST depression [relative risk 6.305 (95% confidence intervals 1.831-21.71), p<0.01] during an anginal attack was found to be an independent risk factor to predict cardiac events. Other predictors did not have prognostic significance.
Conclusion The number of leads with ST depression during an anginal attack is an independent risk predictor for new cardiac events in high risk patients with unstable angina.
(Internal Medicine 41: 270-276, 2002)

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Objective To evaluate the difference in the clinical features of mediastinal emphysema as classified into three groups based on etiology; patients in whom it was spontaneous with unknown etiology (A group), those in whom it was secondary to bronchial asthma (B group), and those in whom it was secondary with other respiratory diseases (C group).
Patients Forty-three cases (45 episodes) with mediastinal emphysema treated at Kawasaki Medical School Kawasaki Hospital between April 1985 and March 2000 (A group: 17 cases, B group: 17 cases, C group: 9 cases).
Results The average ages of the A and B groups were of little significance. Most of the patients in the A group were males with a thin body. Three patients in the A group had episodes of pneumothorax or mediastinal emphysema in their past history. Five patients in the A group had Hamman's sign on physical examination. In all of the patients in the C group, mediastinal emphysema was accompanied by subcutaneous emphysema, whereas only eight patients in the A group had subcutaneous emphysema. The prognosis was good for A and B groups because the mediastinal emphysema disappeared within 10 days, but was poor in the C group because its disappearance was very late compared with that in the other two groups and skin incision was required in three patients in the C group due to severe subcutaneous emphysema.
Conclusions We suggest that the existance and kind of underlying diseases significantly affect the method of treatment and the prognosis.
(Internal Medicine 41: 277-282, 2002)

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Objective To clarify the efficacy of chemotherapy after radiation therapy in immunocompetent patients with primary central nervous system lymphoma (PCNSL).
Patients and Methods A retrospective analysis of 22 PCNSL patients was performed. Twenty-two patients were divided into a combined treatment (chemotherapy after radiation) group and a radiation group. The survival curves, calculated according to the Kaplan and Meier method, were compared using the Log-rank and Wilcoxon statistical analyses.
Results Eight patients were treated with radiation therapy alone, and their median survival time (MST) after diagnosis was 21.9 months. Fourteen patients were treated with chemotherapy after radiotherapy. Six patients received chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP), while 6 patients received carboplatin-based chemotherapy and 2 patients received methotrexate-based chemotherapy. The MST of these 14 patients was 34.4 months, which was not significantly better than that of the radiation therapy group (p=0.159). Leukoencephalopathy occurred in 3 patients, who received whole brain radiation.
Conclusion The use of chemotherapy after radiation has up to now been thought to be a standard treatment modality but CHOP or carboplatin-based chemotherapy did not improve the survival time.
(Internal Medicine 41: 283-289, 2002)

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Objective A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL].
Methods MCNU (33.3 nig/m², div) on day 1 and MPH (4 mg/m², po), CPM (66.7 mg/m², po) and PSL (30 mg/m², po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks.
Patients or materials From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled.
Results Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p<0.0001) and that of MMPP (21/47=44.7%, p=0.0196). A plateau attainment was observed in 49.4%. The percentage of the patients who attained plateau was significantly increased in the MMCP arm than in the VMCP arm (19.1%, p=0.0017) but was not in comparison with that of MMPP arm (42.6%, p=0.6790). Patients treated with MMCP survived significantly longer than those treated with VMCP or MMPP (p=0.0009 by generalized Wilcoxon test, p=0.0023 by log-rank test) with median survival for MMCP being 31.6 months, for VMCP 22.5 months, and for MMPP 22.9 months. No significant differences were observed with respect to adverse effects among the three regimens.
Conclusion The newly designed MMCP is a candidate as an induction chemotherapy for multiple myeloma.
(Internal Medicine 41: 290-294, 2002)

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Objective We investigated the clinical aspects of adult human parvovirus (HPV) B19 infection.
Patients and Methods We retrospectively reviewed the charts of 21 consecutive patients [4 males, aged 32 to 43 years (average 38.0 years), and 17 females, aged 15 to 43 (average 34.2)] with adult HPV B19 infection who visited our outpatient department between July 1997 and June 1998. All diagnoses of adult HPV B19 infection were based on positive anti-HPV B19 IgM antibody in serum and/or positive HPV B19 DNA in peripheral blood.
Results The predominant signs and symptoms of the patients were: fever (81.0%), arthralgia/myalgia (61.9%), skin rash (47.6%), general fatigue (42.9%), lymph node swelling (38.1%) and edema (38.1%). Six patients had the following underlying diseases or complications: pregnancy, myoma uteri, cervical cancer of the uterus, lupus diathesis/endometriosis, hereditary spherocytosis, and multiple sclerosis. The following abnormal laboratory findings (more or less than normal limits) were observed: anemia (81.0%), leukopenia (33.3%), elevated transaminases (28.6%), and elevated lactate dehydrogenase (LDH) (57.1%). Six patients were considered to have persistent infection.
Conclusion HPV B19 can infect healthy adults and causes more predominant signs and symptoms (arthralgia, myalgia and fever) than in children, and adult HPV B19 infection can be suspected from the familial history and clinical findings. Accordingly, more attention must be paid to adult HPV B19 infection, particularly when erythema infectiosum is prevalent in children.
(Internal Medicine 41: 295-299, 2002)

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A 39-year-old man with lipoprotein lipase (LPL) deficiency (height 177.7 cm, body weight 67 kg, and body mass index 21.2 kg/m²) showed severe hypertriglyceridemia (2, 032 mg/dl). LPL activity and concentration were markedly low in postheparin plasma. LPL gene analysis revealed a homozygous mutation, Asp204 → Glu in exon 5. Fasting plasma glucose (81 mg/dl) and insulin (2.7 (μU/ml) levels were normal. Plasma glucose pattern during oral glucose (75 g) tolerance test was normal, however 30 minutes after glucose-loading the insulin secretion unexpectedly increased to 89.4 μU/ml. These data suggested that chylomicronemia might be related to a hyper-response of insulin secretion to glucose without obesity.
(Internal Medicine 41: 300-303, 2002)

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A 64-year-old woman developed hypertension and hypokalemia, due to ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) with excessive secretion of 18-hydroxydeoxycorticosterone and corticosterone. Plasma cortisol did not show a diurnal rhythm, and was not suppressed by dexamethasone (8 mg). Plasma cortisol responded to ACTH and was increased by hypoglycemia without modifying ACTH levels. Radiological studies demonstrated that adrenal glands were enlarged with macronodules. Although the patient exhibited a low plasma renin activity and aldosterone levels, hypokalemia and hypertension were observed. Hormonal findings would support the hypothesis that the tumor of AIMAH originated from cells of the upper zona fasciculata.
(Internal Medicine 41: 304-308, 2002)

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A 53-year-old woman was admitted to our hospital complaining of cough, low grade fever, chest pain and sicca symptoms. A chest radiograph showed an abnormal shadow and chest computed tomography revealed a tumor in left S⁶. She was diagnosed as Sjögren's syndrome by sialography and histological findings of labial biopsy. The surgically resected tumor specimen showed proliferation of lymphoid cells with lymphoepithelial lesions, which were positive for CD20 and kappa light chain. Kappa light chain-positive amyloid was found within the tumor. The tumor showed rearranged kappa light chain genes. The diagnosis was pulmonary mucosa associated lymphoid tissue lymphoma with amyloid production.
(Internal Medicine 41: 309-311, 2002)

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We examined (CTG)_n lengths in various tissues from a 70-year-old man with myotonic dystrophy type 1 (DM1) who had a small 60-70 (CTG)_n expansion in his leukocytes. He died of renal cell carcinoma 5 years after a total laryngectomy for laryngeal carcinoma. Southern blot and polymerase chain reaction analyses were done on tissues obtained at autopsy. In the various normal tissues, (CTG)_n lengths were almost all the same size, whereas the renal cell carcinoma and metastatic tissues had longer lengths. When compared with the lengths in leukocytes about 5 years previously, (CTG)_n lengths in the normal tissues were the same size. These findings suggest that both somatic instability and age-dependent (CTG)_n expansion in DM1 patients with a small expansion may be less dominant than in patients with large expansions.
(Internal Medicine 41: 312-318, 2002)

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A case of pleuropericarditis caused by Actinomyces israelli is described. The patient first underwent left upper lobectomy because of pulmonary actinomycosis. Seven months later, cardiac tamponade developed. Culture of the bloody pericardial effusion resulted in positive growth of Actinomyces israelli. He was successfully treated with penicillin G, ampicillin, and minocyclin. However, right pleural effusion appeared two months later. Cultures of the effusion again yielded positive growth of the same bacteria. However, the strain had gained resistance to any antibiotics that had been effective before. Accordingly, pleurodesis with minocyclin was undertaken, which was fortunately effective for controlling the pleural effusion.
(Internal Medicine 41: 319-322, 2002)

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