Monitoring twenty-six chronic myeloid leukemia patients by BCR-ABL mRNA level in bone marrow:a single hospital experience.

Chronic myeloid leukemia (CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib is effective to control the tyrosyl phosphorylation of the protein related to the cell signaling. BCR-ABL mRNA is overexpressed in the minimal residual disease (MRD), known as an early sign of relapse. Between December 2005 and June 2008, we measured BCR-ABL mRNA levels in the bone marrow (BM) from patients by quantitative real-time polymerase chain reaction (RQ-PCR) in Aomori Prefectural Central Hospital. Eighty-six samples from 26 patients were collected. Among the 26 CML patients, 11 patients (42%) were in the pretreatment group. Seven (64%) of the 11 patients achieved complete molecular response (CMR). In the post-treatment group consisting of the remaining 15 patients, 9 (60%) patients achieved CMR. The patients receiving imatinib at a dose over 300 mg per day required 13 (6-77) months [median (range)] to achieve CMR. On the other hand, the patients receiving a dose below 300 mg per day required 29.5 (11-84) months [median (range)]. When BCR-ABL mRNA was detected during the treatment course of patients with CMR, careful observation of BCR-ABL mRNA was useful for tracking the clinical course of patients. In conclusion, the BCR-ABL mRNA level was useful for monitoring the clinical course in 26 patients with CML.

Peripheral pulmonary papillary adenocarcinoma with prominent cilia: report of a rare case that was difficult to diagnose preoperatively.

BACKGROUND: In pulmonary cytology, the existence of cilia is considered cytologic evidence of benign cells because it is generally considered that cilia could not be identified by light microscopic observation of pulmonary adenocarcinoma. However, we encountered a rare exceptional case of pulmonary adenocarcinoma with cilia. CASE: A 55-year-old woman with bloody sputum was admitted. Computed tomography revealed a lung tumor. Although transbronchial brushing cytology showed atypical cells suggestive of malignancy, some atypical cells had cilia, so we could not diagnose them as cancer cells. After antibiotic therapy, the tumor was surgically excised. Imprint cytology showed similar atypical ciliated cells. Histologically, the tumor was diagnosed as papillary adenocarcinoma with cilia and diffuse pleural dissemination was observed. Electron microscopic observation identified cilia. The patient died due to aggravation of cancer, which was confirmed on autopsy. CONCLUSION: This rare case of peripheral pulmonary papillary adenocarcinoma with cilia could not be diagnosed as cancer cell on cytology. Pulmonary papillary adenocarcinoma with cilia should be considered in the differential diagnosis of atypical cells in pulmonary cytology.

Hippocampal sclerosis with four-repeat tau-positive round inclusions in the dentate gyrus: a new type of four-repeat tauopathy.

Hippocampal sclerosis is defined as selective neuronal loss and gliosis of the hippocampus with heterogeneous etiologies, including neurodegenerative tauopathies. We report a 78-year-old woman who presented with depression, in whom postmortem examination revealed almost complete loss of neurons with gliosis in the subiculum and CA1-3 regions of the hippocampus and abundant neuronal cytoplasmic inclusions in the dentate gyrus. The inclusions were round, slightly basophilic and argyrophilic, resembling Pick bodies. However, they were Gallyas- and 4-repeat tau-positive, and 3-repeat tau- and ubiquitin-negative. To our knowledge, the histopathological features in this case were different from those in hippocampal sclerosis or 4-repeat tauopathies reported previously. It is likely that this case is a new variant of 4-repeat tauopathy presenting with hippocampal sclerosis.

WT1 mRNA level in peripheral blood is a sensitive biomarker for monitoring minimal residual disease in acute myeloid leukemia.

The Wilms' tumor gene 1 (WT1) encodes a transcription factor that is involved in normal cellular development and cell survival. WT1 mRNA is overexpressed in the minimal residual disease (MRD) of patients with hematopoietic malignancy patients, particularly acute myeloid leukemia (AML). MRD represents the condition with the low levels of leukemia cells in the bone marrow and is known as a sign of recurrence. In hematopoietic malignancies, definition of remission is based on the lack of MRD at submicroscopic level. Between December 2005 and June 2008, we started to measure WT1 mRNA levels in the peripheral blood (PB) from patients by quantitative real-time PCR in Aomori Prefectural Central Hospital. Three hundreds and eight samples from 95 patients were evaluated. The patients included AML (55 patients), acute lymphoblastic leukemia (11), myelodysplastic syndrome (20), malignant lymphoma (5), chronic myeloid leukemia (1), prostatic carcinoma (1), and leukopenia (2). Among the 55 AML patients, 21 patients were pretreated with remission induction therapy. In the clinical course of 21 patients, timely therapeutic approaches could be started for relapse by the early detection of WT1 mRNA overexpression before the morphological findings were apparent. Monitoring WT1 mRNA is helpful to identify patients at high-risk relapse. High overall survival rate (71.2%, 15/21, median: 24.6 months, range 1.1-35.6 months) was achieved in 3 years. The overall survival rate of 34 post-treatment patients was 61.7% (median: 23.5 months, range 0.13-126.5 months after treatment start). In conclusion, the WT1 mRNA level is a sensitive biomarker for monitoring MRD.

[A case of posttraumatic forehead cavernous angioma].

Cavernous angiomas of the bone are rare tumors. Skull cavernomas are even less frequent. Most cavernous angiomas of the bone are congenital tumors. In a review of the literature, we found only one case report of de novo generation of a skull cavernous angioma. We present a case of a 25-year-old woman who had experienced a head injury, and 7 years later exhibited a skull tumor at the exact region of the injury. We performed tumor resection and cranioplasty. Follow-up examinations revealed no recurrence or neurological defects. Pathological findings showed a cavernous angioma-like lesion with some atypical details. We finally diagnosed the lesion as a de novo cavernous angioma. Our case suggests that fine injury may result in de novo generation of bone cavernomas.

[A successful surgical case of a hypothalamic hamartoma with gelastic seizure: a case report].

Gelastic seizure is a rare form of epilepsy defined as automatic bouts of laughter without mirth commonly associated with a hypothalamic hamartoma. Surgical treatment of hypothalamic hamartomas is associated with a high risk of complications because of the close vicinity of adjacent structures such as the optic tracts and mammillary bodies. This case was an 11-year-old girl who presented with gelastic seizure and complicated partial seizure. She developed gelastic seizure at a frequency of 10 bouts per day. She was found to have an elliptical mass close to the left hypothalamus. The signal intensity on magnetic resonance imaging (MRI) was consistent with hypothalamic hamartoma. The patient underwent surgical resection by a subtemporal approach. Pathological findings confirmed the diagnosis of hypothalamic hamartoma. Postoperative MRI demonstrated that the hypothalamic hamartoma was successfully resected. Twenty four months after surgery, complicated partial seizure in this patient has improved to Engel's class 1a and gelastic seizure has improved to Engel's class IIIa.

Intracranial peripheral-type primitive neuroectodermal tumor.

A 15-year-old man presented with headache. Magnetic resonance (MR) imaging revealed a large extraaxial tumor with cyst at the right frontotemporal region. The solid part of the tumor was homogeneously enhanced on T(1)-weighted MR imaging after injection of gadolinium. Digital subtraction angiography of the external carotid artery revealed sunburst appearance corresponding to the tumor, which was fed by the right middle meningeal artery. His headache worsened and computed tomography revealed enlargement of the tumor and intracystic hemorrhage, so emergent operation was performed. At surgery, the tumor strongly adhered to the dural membrane, and was obviously extraaxial. The tumor and cyst were gross totally removed. The attachment site at the dura mater was resected. Histological examination showed solid growth of small round cells with uniform round nuclei and minimal cytoplasm. Immunohistochemical staining showed the cells were positive for MIC-2 (CD99). The MIB-1 labeling index was 53%. The histological diagnosis was peripheral-type primitive neuroectodermal tumor (pPNET). Following surgery, radiation therapy and chemotherapy were given. Ewing's sarcoma and pPNET form a family of small round cell tumors arising in the bone or soft tissue. MIC-2 is a useful marker in the differential diagnosis. Good prognosis may be attained if complete surgical excision of intracranial pPNET is achieved.

Ectopic recurrence of dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease): a case report.

Lhermitte-Duclos disease is a rare clinical entity characterized by slow deformation of the cerebellar lesion. A 53-year-old woman presented with Lherimitte-Duclos disease manifesting as ataxic gait, occipital headache, and loss of consciousness. Magnetic resonance imaging demonstrated striated and laminar pattern lesions in the right cerebellar hemisphere and vermis. She underwent subtotal removal of the vermis compressing the brainstem, but the cerebellar hemisphere appeared normal and was preserved. Histological findings were consistent with Lherimitte-Duclos disease. Two years later, magnetic resonance imaging revealed enlargement of the right hemispheric lesion. Intraoperative appearance of the hemisphere demonstrated marked enlargement of the folia. Subtotal removal was performed. Histological examination showed no malignant findings. Lhermitte-Duclos disease may recur, and should be carefully followed up as a low-grade neoplasm, not as a hamartomatous disorder.

[In-vitro susceptibilites to levofloxacin and various antibacterial agents of 18,639 clinical isolates obtained from 77 centers in 2004].

A total of 18,639 clinical isolates in 19 species collected from 77 centers during 2004 in Japan were tested for their susceptibility to fluoroquinolones (FQs) and other selected antibiotics. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae showed a high susceptible rate against FQs. The isolation rate of beta lactamase non-producing ampicillin-resistant H. influenzae was approximately three times as large as those of western countries. Most strains of Enterobacteriaceae were also susceptible to FQs. The resistance rate of Escherichia coli against FQs has however been rapidly increasing so far as we surveyed since 1994. The FQs-resistant rate in methicillin-resistant Staphylococcus aureus (MRSA) showed approximately 90% except for 36%. of sitafloxacin while FQs-resistant rate in methicillin-susceptible S. aureus (MSSA) was around 5%. The FQs-resistant rate of methicillin-resistant coagulase negative Staphylococci (MRCNS) was also higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), however, it was lower than that of MRSA. In Pseudomonas aeruginosa clinical isolates, 32-34% from UTI and 15-19% of from RTI was resistant to FQs. Acinetobacter spp. showed a high susceptibility to FQs. Although FQs-resistant Neisseria gonorrhoeae have not been increased in western countries, it is remarkably high in Japan. In this survey, isolates of approximately 85% was resistant to FQs.

[Intracranial granulocytic sarcoma in a patient with acute myeloid leukemia].

Granulocytic sarcoma (GS) is extramedullary tumor composed of immature leukemic cells. GS is presenting usually as a complication during the course of hematologic neoplasm, such as acute myeloblastic leukemia as well as myeloproliferative and myelodysplastic syndrome. The tumor was also called chroloma based on the green color of the tumorous mass. Central nervous system manifestations of GS are extremely rare. We report a 41-year-old man with acute leukemia type M7, who developed GS in the right occipital lobe after complete remission was achieved. Operative findings revealed the color of the hard tumor was greenish, which suggested the tumor was chroloma. Histological findings showed the tumor was GS. The majority of reported cases of GS in acute myeloid leukemia were M2 FAB classification and have chromosome translocation. Our patient was M7 FAB classification, not have specific chromosome translocation. GS occurrence in AML: M7 patient was extremely rare. This is the first case report of AML: M7 with GS in the central nervous system.

[In vitro susceptibilites to levofloxacin and various antibacterial agents of 11,475 clinical isolates obtained from 52 centers in 2002].

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.

Fatal rupture following intra-aneurysmal embolization for the distal posterior inferior cerebellar artery aneurysm with parent artery preservation.

This 70-year-old female was admitted to our hospital 1 day after a sudden consciousness disturbance. Computed tomography (CT) showed subarachnoid hemorrhage (SAH), and angiogram revealed an irregular-shaped aneurysm at the lateral medullary segment of the left posterior inferior cerebellar artery (PICA). The patient was treated by intra-aneurysmal embolization with Guglielmi detachable coil (GDC) with parent artery preservation. Post-operative angiogram showed obliteration of the aneurysm except for the neck remnant, but she presented with rerupture 19 days after the onset and died 3 days later. Postmortem examination revealed massive hematoma around the aneurysm, which compressed medulla oblongata from behind. Histological assessment showed the 'entry' where the aneurysmal wall lacked internal elastic lamina, providing evidence of dissecting aneurysm. The present case suggests that embolization of distal PICA aneurysm with parent artery preservation should be avoided because radiological evaluation may fail to rule out the possibility of dissection, where the aneurysmal wall is affected not only at the 'entry' but also in the adjacent region.

Cavernous angioma presenting as epilepsy 13 years after initial diagnosis.

A 22-year-old man presented with tonic-clonic seizure and was admitted to our hospital. He had suffered from frequent headaches, and had been diagnosed with a brain tumour on MRI 13 years ago. However, neither further examination nor follow-up neuroimaging study have been performed. Computed tomography and magnetic resonance imaging demonstrated an intraaxial tumor with granular calcification in the right frontal lobe, attached to the adjacent dura mater, which was enlarged compared with the lesion on CT 13 years before. The lesion was surgically excised through right frontal craniotomy. Histopathological analysis indicated cavernous angioma. In cavernous angioma in younger children, more aggressive surgical indications than in adults may be favorable both to prevent haemorrhagic complications and to confirm pathologic diagnosis.

A case of calvarial eosinophilic granuloma with rapid expansion and wide skull invasion: immunohistochemical analysis of Ki-67.

A 15-year-old male visited our neurological service with progressive occipitalgia. Computed tomography showed an osteolytic lesion at the occipital cranium, which grew rapidly during a month. Magnetic resonance imaging showed the lesion as low intensity on T1- and high intensity on T2-weighted images. The mass was soft and successfully removed with surrounding cranium. Histological examination revealed an eosinophilic granuloma with wide skull invasion. Immunohistochemical analysis on the specimen disclosed Ki-67 expression with labeling index of 6.2%. Relatively high proliferative activity in the present case indicates that the local replication of Langerhans' cells as well as inflammatory response contributes to the expansion of calvarial eosinophilic granuloma. This is the first report demonstrating the result of Ki-67 expression on calvarial eosinophilic granuloma.

[Activities of antimicrobial agents against 8,474 clinical isolates obtained from 37 medical institutions during 2000 in Japan].

A survey was conducted to determine the antimicrobial activity of fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates obtained from 37 Japanese medical institutions in 2000. A total of 25 antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams, minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin, sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85% against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%. However, many of the common pathogens were still susceptible to fluoroquinolones, such as Streptococcus pneumoniae (including penicillin-resistant isolates), Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin-susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin-resistant isolates). About 85% of P. aeruginosa isolated from RTI were susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to antimicrobial agents clearly indicated trend for increasing resistance to fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI, although fluoroquinolones are still effective against other organisms and P. aeruginosa from RTI as has been demonstrated in previous studies.

[A case presenting brain abscess with multiple infectious aneurysms].

We report a case presenting a brain abscess with multiple infectious aneurysms. A 59-year-old man was transferred to our hospital suffering from left hemiparesis. MRI demonstrated a huge mass in the right frontal lobe with marked brain edema in the surrounding area. Diffusion-weighted image revealed heterogenous intensity, which is not typical in cases of brain abscess. Surgical removal was planned, and preoperative angiography was performed. Angiography demonstrated aneurysms at the distal branch of both the right middle cerebral artery and the anterior cerebral artery. These aneurysms were surgically resected, and the abscess was totally removed. Postoperative course was uneventful. Left hemiparasis was resolved, and there was no ischemic lesion seen on postoperative MRI. In the treatment of brain abscess, stereotactic aspiration has recently been preferred to removal by craniotomy. We conclude that cerebral angiography might be necessary to evaluate cerebrovascular complications including infectious aneurysms, in cases presenting atypical findings in neuroimaging study.

[Characterization of anti-DNA antibody on IgG3-kappa type M-protein in a patient with rheumatoid arthritis].

A 66 year-old male patient with rheumatoid arthritis, was admitted due to bronchial pneumonia. Anti-nuclear antibody and anti-DNA antibody were both detected in the patient's serum and many LE-like cells were found in the pleural effusion. In addition, M-proteins(IgG-kappa type, IgM-kappa type) were detected in both serum and pleural effusion by immunofixation electrophoresis. Purified IgG fraction by gel filtration(Superdex 200HR) showed high titer of anti-nuclear antibody(x160) and anti-DNA(39.2 AU/ml) antibody. Furthermore, anti-DNA antibody was detected in the fraction III(fraction of M-protein) by ion-exchange chromatography. In conclusion, these results indicate that M-protein(IgG3-kappa type) contains anti-DNA antibody and it is suggests that M-protein induces the production of LE like cell in this case.

[Recovery of facultatives and anaerobes from frozen specimens with a polymicrobial nature].

Microbiological examination of frozen specimens is sometimes carried out in clinical microbiology and the result is used as an aid of diagnosis and/or treatment of polymicrobial infections. The study was carried out to reevaluate the merit of freezing specimens in clinical microbiology. A total of 10 specimens with a polymicrobial nature were included in this study. Before and after freezing specimens, we isolated facultative and anaerobic bacteria using a set of primary isolation media, consisting of three aerobic agar plates (MacConkey agar, blood agar and chocolate agar) and four pre-reduced anaerobic agar plates (HK Blood agar, HK blood agar with paromomycin (PM) and vancomycin (VM), phenyl ethyl-alcohol (PEA) agar and Bacteroides bile esculin (BBE) agar). All the procedures were done in a properly controlled anaerobic chamber. The number of isolates before and after freezing was 79 and 70, respectively. Among the strains isolated before freezing, 33 strains were recovered on the same kin of media artery freezing, without a remarkable decrease in the quantity. But 26 strains were not recovered and 2 strains were recovered with a remarkable decrease. Among 26 strains, 15 strains could be successfully backed up on the different kind of media. In conclusion, an anaerobic technique with an anaerobic chamber and a set of isolatin plates including blood agar, chocolate agar, HK blood agar, PEA blood agar, HK blood agar with PM and VM enable us to estimate the bacteriology before freezing from frozen specimens.