NEW DEVICE TO PERFORM COAGULATION AND IRRIGATION SIMULTANEOUSLY DURING ENDOSCOPIC SUBMUCOSAL DISSECTION USING AN INSULATION‐TIPPED ELECTROSURGICAL KNIFE

Background: Although bleeding is an unavoidable complication of endoscopic submucosal dissection (ESD), endoscopic hemostasis using an insulation‐tipped electrosurgical knife (IT) knife is impossible because an insulator is mounted at the tip of the knife. We have developed a new type of hood which could perform both coagulation and irrigation simultaneously. Methods: Our new device was fabricated by drilling a side hole in the cap portion of a conventional transparent hood followed by attaching a machined papillotomy knife to the exterior surface of the hole. Results: Our new hood was useful for hemorrhage during ESD using IT knife. Conclusions: With this method, endoscopic hemostasis using IT knife is easy, as hemostatic procedure can be performed under irrigation and coagulation using conventional endoscopy.     

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.     

An 81-year-old man with personality change, dementia, and gait disturbance with diffuse leukoaraiosis of the cerebral white matter]

We report an 81-year-old patient with progressive dementia, disinhibition, and gait disturbance. He showed visuospacial disorientation, apathy, and gait disturbance at 76 years of age. When he was 77 years old, he was diagnosed Parkinson's disease and treated with the 1-dopa, the dopamine agonist, the amantadin, and the anti-cholinergic drug. These treatments didn't improve his motor disturbances. His motor disturbances, apathy, and abnormal behavior progressed gradually. He was admitted to the hospital at the age of 77. He was severely demented and akinetic. Sometime, violent behavior and hallucination were seen. The brain MRI showed frontotemporal lobe atrophy and severe leukoaraiosis of the frontal white matter. At 79 years of age, he became mute and bedridden. When he was 80 years old, large infarction occurred in his occipital lobe. He died due to renal failure and respiratory suppression at 81 years of age. His brain was examined pathologically. At the neurological CPC, the chief discussant arrived at the conclusion that his diagnosis was Binswanger's disease. Other possibilities discussed were FTD, CBD, and progressive subcortical gliosis. The post-mortem examination revealed diffuse white matter degeneration due to atherosclerotic change of the small artery, many lacunar infarctions, and severe infarction of the occipital lobe. These findings led the diagnosis of Binswanger's disease and cerebral infarction.     

CCR1 acts downstream of NFAT2 in osteoclastogenesis and enhances cell migration.

We found that a chemokine receptor gene, CCR1, acts downstream of NFAT2 in RANKL-stimulated RAW264 and bone marrow cells. The upstream regulatory region of CCR1 showed RANKL-dependent and CsA-suppressible promoter activity. Downregulation of the expression and function of CCR1 suppressed cell migration. INTRODUCTION: We previously reported that the expression of NFAT2 induced by RANKL is a key process for progression to multinucleated cells in an in vitro osteoclastogenesis system. Identifying the target genes of NFAT2 would thus be informative about the differentiation process. We focused here on chemokine and chemokine receptor genes that act downstream of NFAT2 in RAW264 cells as well as osteoclast precursors prepared from bone marrow cells. MATERIALS AND METHODS: RAW264 mouse monocyte/macrophage line cells were cultured with or without cyclosporin A (CsA) in the presence of RANKL or glutathione S-transferase (GST). Osteoclast precursors were prepared from bone marrow cells. RANKL-inducible and CsA-suppressible genes were searched for by microarray analysis, and expression was confirmed by quantitative RT-PCR. Promoter activity was measured by luciferase gene reporter assay. Short interfering (si)RNA for CCR1 was introduced in RAW264 cells. Cell migration activity was examined using a Boyden chamber assay. RESULTS AND CONCLUSIONS: We identified the chemokine receptor gene CCR1 as a gene showing significant differential expression profiles in osteoclastogenesis in the presence versus the absence of CsA, an inhibitor of NFAT. This property was unique to CCR1 among the chemokine and chemokine receptor genes examined in both RAW264 and bone marrow cells. The upstream regulatory region was isolated from CCR1, and its RANKL-dependent and CsA-suppressible promoter activity was confirmed. The functional significance of CCR1 was assessed by monitoring the migration of cells in a transwell migration assay, and this activity was abolished when either CsA- or CCR1 siRNA-treated cells were used. Moreover, treatment with a Galpha inhibitor pertussis toxin (PTX) or methiolynated-regulated on activation, normal T cells expressed and secreted (Met-RANTES), an antagonist of CCR1, suppressed multinucleated cell formation in the bone marrow cell system. Together, these results suggest that the CCR1 signaling cascade is under the control of NFAT2 and seems to enhance the migration of differentiating osteoclasts.     

What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography?

OBJECTIVES: The objective was to determine the prognostic value of rubidium-82 (82Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI). BACKGROUND: 82Rb PET MPI accurately diagnoses coronary artery disease (CAD). However, there are limited data evaluating its prognostic value. METHODS: Follow-up (3.1 +/- 0.9 years) was obtained in 367 patients who underwent dipyridamole 82Rb PET MPI. Patients were divided into groups based on their summed stress score (SSS): group I, normal (<4); group II, mild (4 to 7); and group III, moderate (8 to 11) to severe (> or =12). RESULTS: There were significant differences among patients in the 3 SSS groups for hard events (cardiac death and myocardial infarction [MI]) (p < 0.001) and total cardiac events (hard events, revascularization and hospitalization) (p < 0.001). The annual hard events rates were 0.4%, 2.3%, and 7.0% in the normal, mild, and moderate-severe groups, respectively. In adjusted survival models, 82Rb PET SSS was the strongest predictor of total cardiac events and a significant predictor of hard events. Among patients referred for PET after 99mTc single-photon emission computed tomography, the annual total event rate was higher with abnormal versus normal SSS on PET (15.2% vs. 1.3%, p < 0.001). In patients with obesity, the annual total event rate was 11.1% with an abnormal scan and 1.5% with a normal scan (p < 0.001). CONCLUSIONS: This study shows that 82Rb PET MPI has significant prognostic value for predicting cardiac events, including death and MI. It also seems to have prognostic value in patients whose diagnosis remains uncertain after single-photon emission computed tomography MPI and in obese patients. The prognostic value of PET MPI may improve the management of cardiac patients.     

Genetic changes in JC virus possibly associated with progressive multifocal leukoencephalopathy]

Progressive multifocal leukoencephalopathy (PML) is a fetal demyelinating disease in the central nervous system. PML was once a rare disease, but it is now relatively common among AIDS (acquired immunodeficiency syndrome) patients. The immunological state of patients mainly contributes to the pathogenesis of PML. Genetic changes of the etiological agent, however, may also be involved in the development and progression of the disease. The major genetic changes possibly associated with PML include the regulatory region rearrangement and the VP1 loop mutation. Both changes have been identified as genetic changes usually occurring in JCV (JCvirus) DNAs from the brain and cerebrospinal fluid of PML patients. Although it remained to be clarified how these changes are involved in the pathogenesis of PML, accumulating evidence suggests that the VP1 loop mutation is associated with the progression of PML. Here we overview studies (mainly those performed by ourselves) on these genetic changes.     

A Case of Glucagonoma with Liver Metastasis: Complete Response to Dacarbazine

Abstract: We report a case of glucagonoma syndrome with liver metastasis, who responded completely to dacarbazine chemotherapy. A 77-year-old woman complained of itching skin eruptions (diagnosed as necrolytic migratory erythema) and weight loss. She was found to have glucose intolerance, anemia, hypoproteinemia and hyperglucagonemia. Abdominal CT and celiac arteriography showed a hypervascular tumor in the pancreatic tail and a metastatic tumor in the left hepatic lobe. Immunohistochemical examination of the metastatic liver tumor obtained by laparoscopic biopsy revealed the tumor cells to be positive for glucagon. The patient was treated with 20 courses of 300 mg/day intravenous dacarbazine for 5 consecutive days followed by a 4 week drug-free interval. No major side effects were noted. Treatment resulted in disappearance of the skin lesions and correction of anemia, glucose intolerance, hypoproteinemia and hyperglucagonemia. Follow-up abdominal CT showed complete resolution of both the primary pancreatic tumor and the metastatic liver tumor. We suggest that dacarbazine be considered as the treatment of choice for metastatic glucagonoma.     

Neural correlates of cross-modal binding

Little is known about how the brain binds together signals from multiple sensory modalities to produce unified percepts of objects and events in the external world. Using event-related functional magnetic resonance imaging (fMRI) in humans, we measured transient brain responses to auditory/visual binding, as evidenced by a sound-induced change in visual motion perception. Identical auditory and visual stimuli were presented in all trials, but in some trials they were perceived to be bound together and in others they were perceived as unbound unimodal events. Cross-modal binding was associated with higher activity in multimodal areas, but lower activity in predominantly unimodal areas. This activation pattern suggests that a reciprocal and 'competitive' interaction between multimodal and unimodal areas underlies the perceptual interpretation of simultaneous signals from multiple sensory modalities.     

WIDESPREAD ECZEMA VACCINATUM ACQUIRED BY CONTACTS A Report of an Autopsy Case

A4-moth-old male infant predisposed to allergic dermatitis acquired widespread eczema vaccinatum by contacts with a recently vaccinated sibling. He died of acute purulent peritonitis following a perforation of multiple duodenal ulcers. Fluorescence immunocytochemical and electron microscopic studies on the skin lesions revealed the presence of viral antigens and numerous virus particles compatible morphologically with those of the mature form from the same batch of smallpox vaccine given to the sibling. A large number of virus particles in the developmental form were also predominantly scattered in the cytoplasm of cells at the stratum malpighii of the epidermis as well as in neutrophils and macrophages in the skin lesions. The virus isolation from the skin lesions was done by using the HeLa cells and the human embryonic lung fibroblasts. No abnormal laboratory data were noted in immunoglobulins. On the basis of atrophy of the thymus and other lymphatic tissues and an appearance of large pyroninophilic cells in association with blastoid transformation, the authors discussed a possible participation of the disturbance of cellular immunity secondary to the virus infection in the development of the disease. ACTA PATH. JAP. 29 : 435–455, 1979.     

Parent-to-child transmission is relatively common in the spread of the human polyomavirus JC virus.

JC polyomavirus (JCV), the causative agent of progressive multifocal leukoencephalopathy, is ubiquitous in the human population, infecting children asymptomatically and then persisting in renal tissue. In most adults, renal JCV replicates and the progeny are excreted in urine. We used this urinary JCV to elucidate the routes of JCV transmission. A 610-bp JCV DNA region (IG region) encompassing the 3'-terminal sequences of both T-antigen and VP1 (major capsid protein) genes was amplified by means of PCR from urine specimens collected from all members of seven families. JCV strains were then unequivocally identified by the nucleotide sequences of the amplified IG regions. We could identify 18 distinctive JCV strains from 27 individuals. Different JCV strains were detected from all unrelated persons. However, the same viral strain was detected from one (four families), two (one family), or three offspring (one family) as well as from the fathers (three families) or from the mothers (three families). In total, the JCV strains detected in half of the JCV-positive children were identified in their parents. Since most humans are infected during childhood, these findings indicated that JCV is transmitted frequently from parents to children. We roughly estimated that 50% of JCV transmission occurs by this route and that the other 50% occurs outside the family.