Delayed Treatment with YM90K,an AMPA Receptor Antagonist,Protects against Ischaemic Damage after Middle Cerebral Artery Occlusion in Rats

The neuroprotective effect of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione monohydrochloride] has been examined in a rat middle cerebral artery occlusion model. Intravenous infusion of YM90K (2·5–20mgkg^?1h^?1 for 4 h) starting immediately after occlusion of the middle cerebral artery significantly reduced the cortical infarct volume 24 h after occlusion compared with the control group. The protection at the highest dose was 39% (P<0·05). Similar protective effects were observed when YM90K (20mgkg^?1h^?1 for 4 h) was delayed up to 2 h after middle cerebral artery occlusion (45% reduction, P<0·05). CNS1102 [N-(1-naphthyl)-N′-(3-ethylphenyl)-N′-methylguanidine hydrochloride], a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, also reduced the cortical infarct volume when 1·3mgkg^?1 was administered by intravenous bolus injection immediately after middle cerebral artery occlusion, followed by intravenous infusion at 0·785 mgkg^?1h^?1 for 4 h (35% reduction, P<0·05). This neuroprotective effect was not observed when administration was delayed 1 h after middle cerebral artery occlusion. These results suggest that AMPA receptors might play a more important role than NMDA receptors in the late development of neuronal cell damage after focal cerebral ischaemia and that AMPA receptor blockade would be one beneficial strategy in treating acute stroke.     

Clinical Significance of QRS Duration During Ventricular Pacing

To clarify the clinical significance of an abnormally prolonged paced QRS duration, we studied 114 patients who had undergone pacing for atrioventricular block (AVB). Patients were divided into two groups: group I consisted of 29 patients with at least one paced QRS duration greater than or equal to 180 msec during the follow-up period; group II consisted of 85 patients with paced QRS durations less than 180 msec. The clinical background, QRS complexes before pacing, and the echocardiographic findings were assessed. Males (P less than 0.05), those with H-V block (P less than 0.05) and a wider QRS complex of conducted and escape beats (both P less than 0.01) were dominant in group I. The incidence of underlying heart disease was greater in group I than in group II (83% vs 32%, P less than 0.01). Reduced left ventricular ejection fraction (LVEF) and increased left ventricular end-diastolic dimension (LVDd) were more prominent in group I than in group II (LVEF 0.49 +/- 0.17 vs 0.68 +/- 0.10, P less than 0.01, LVDd 57.1 +/- 7.9 mm vs 48.5 +/- 5.6 mm, P less than 0.01). The paced QRS duration correlated with LVEF (r = -0.61) and LVDd (r = 0.81). A paced QRS duration greater than or equal to 180 msec was sensitive and specific for a LVEF less than 0.5 (83.3% and 85.2%) and LVDd greater than or equal to 60 mm (100% and 81.4%). We conclude that patients with a prolonged paced QRS duration have more serious heart disease, and the paced QRS duration can be a useful indicator of impaired LV function.     

Efficacy and Safety of Propiverine and Solifenacin for the Treatment of Female Patients with Overactive Bladder: A Crossover Study

Objectives: To evaluate the clinical efficacy and tolerability of propiverine and solifenacin in female patients with overactive bladder (OAB). Methods: A prospective nonrandomized crossover study of propiverine 20 mg and solifenacin 5 mg was conducted. Female OAB patients were assigned alternately to treatment with propiverine for 8 weeks then solifenacin for 8 weeks (Group P‐S) or solifenacin for 8 weeks then propiverine for 8 weeks (Group S‐P). At baseline, 8th week and 16th week, symptoms were assessed using overactive bladder symptom score (OABSS). Results: A total of 121 patients were enrolled. Overall, 38 patients (31.4%) discontinued or dropped out and 83 patients were available for analysis (39 in Group P‐S and 44 in Group S‐P). In both groups, the total score and each score of OABSS were significantly improved after 8 weeks compared with baseline. In only Group P‐S (changing over from propiverine to solifenacin), urgency score in the 16th week was further improved significantly compared with the 8th week. The most bothersome symptom at baseline was urgency incontinence (50.6%), followed by urgency (37.3%). Even after symptom improvement, more than half of the patients were bothered by urgency or urgency incontinence. The incidence of adverse events of moderate and severe grade was higher during propiverine treatment than solifenacin (11.1% vs 2.9%, P = 0.039). Conclusion: Propiverine 20 mg and solifenacin 5 mg were effective for treating female OAB patients. Urgency was further improved after switching from propiverine to solifenacin, but not after switching from solifenacin to propiverine. Solifenacin was better tolerated than propiverine.     

Focused Ultrasound Thalamotomy for Tremor-dominant Parkinson’s Disease: A Prospective 1-year Follow-up Study

Transcranial magnetic resonance (MR)-guided focused ultrasound (FUS) therapy is an emerging and minimally invasive treatment for movement disorders. There are limited reports on its long-term outcomes for tremor-dominant Parkinson’s disease (TDPD). We aimed to investigate the 1-year outcomes of ventralis intermedius (VIM) thalamotomy with FUS in patients with TDPD. Patients with medication-refractory TDPD were enrolled and underwent unilateral VIM-FUS thalamotomy. Neurologists specializing in movement disorders evaluated the tremor symptoms and disability using Parts A, B, and C of the Clinical Rating Scale for Tremor (CRST) at baseline and at 1, 3, and 12 months. In all, 11 patients (mean age: 71.6 years) were included in the analysis. Of these, five were men. The median (interquartile range) improvement from baseline in hand tremor score, the total score, and functional disability score were 87.9% (70.5–100.0), 65.3% (55.7–87.7), and 66.7% (15.5–85.1), respectively, at 12 months postoperatively. This prospective study demonstrated an improvement in the tremor and disability of patients at 12 months after unilateral VIM-FUS thalamotomy for TDPD. In addition, there were no serious persistent adverse events. Our results indicate that VIM-FUS thalamotomy can be safely and effectively used to treat patients with TDPD. A randomized controlled trial with a larger cohort and long blinded period would help investigate the recurrence, adverse effects, placebo effects, and longer efficacy of this technique.     

Expression of vascular endothelial growth factor-C in human hepatocellular carcinoma

Background/Aims: Vascular endothelial growth factor‐C (VEGF‐C) is thought to be an important factor in tumor angiogenesis/lymphangiogenesis, but its role in hepatocellular carcinoma (HCC) has not yet been fully investigated. Methods: We immunohistochemically examined VEGF‐C expression in surgically resected tissues of 90 HCC. Results: In the 78 HCC with a single histological grade, VEGF‐C expression was significantly stronger in poorly differentiated HCC than in well‐ (P = 0.003) or moderately differentiated HCC (P = 0.0002). A ‘nodule‐in‐nodule’ case presented VEGF‐A expression in the well‐differentiated component and VEGF‐C expression in the moderately–poorly differentiated component. According to nodular diameter, VEGF‐C expression was significantly higher in nodules of 3.0 cm or larger (P = 0.0263). Extrahepatic metastases seen in seven cases expressed VEGF‐C. In 20 of the 28 cases who were able to be followed up, the frequency of intrahepatic recurrence tended to be higher and extrahepatic metastasis was significantly higher in the cases who had VEGF‐C expression in the tumor casts of the intrahepatic portal/hepatic vein branches than other cases without the expression (P = 0.0139). Disease‐free survival time tended to be shorter in cases with VEGF‐C expression in tumor casts of the portal/hepatic vein than in those without VEGF‐C expression (P = 0.053; log–rank test). Conclusions: VEGF‐C expression is related to the progression of HCC, and VEGF‐C expression in tumor casts of the intrahepatic portal/hepatic vein is considered to be a factor indicating recurrence/metastasis sites.     

Diagnosis of Chronic Pancreatitis by Endoscopic Ultrasonography

Abstract: This study evaluates the usefulness of endoscopic ultrasonography in the diagnosis of chronic pancreatitis. 52 patients with chronic pancreatitis, which included 15 cases of mild pancreatitis, 19 cases of moderate pancreatitis and 18 cases of advanced pancreatitis, were diagnosed by endoscopic retrograde cholangiopancreatography and further investigated by endoscopic ultrasonography. The 4 main findings of 1) dilatation of the main pancreatic duct, 2) irregularity of the main pancreatic duct, 3) inhomogeneity of the pancreatic parenchyma and, 4) irregular configuration of the pancreas were reviewed. In all of the 18 cases of advanced pancreatitis, irregularity of the main pancreatic duct, inhomogeneity of the pancreatic parenchyma and irregular configuration of the pancreas were seen. 89% of these patients had dilatation of the main pancreatic duct. In the patients with moderate pancreatitis, on the other hand, all 4 findings occurred with a frequency of between 58% to 95%. In the patients with mild pancreatitis, irregularity of the main pancreatic duct, inhomogeneity of the pancreatic parenchyma and irregular configuration of the pancreas occurred at a rate of 40% to 93%, and dilatation of the main pancreatic duct occurred rarely in only 13% of the patients. We were able to detect abnormalties in the pancreatic parenchyma by endoscopic ultrasonography even in the early stages of chronic pancreatitis, and this suggests that this technique may be useful in the diagnosis of mild pancreatitis, which usually causes quite minor abnormal changes in the main pancreatic duct.     

Goniodomin A,an Antifungal Polyether Macrolide,Increases the Filamentous Actin Content of 1321N1 Human Astrocytoma Cells

Goniodomin A, a polyether macrolide isolated from the dinoflagellate Goniodoma pseudogoniaulax, caused morphological change in 1321N1 human astrocytoma cells. Observation by scanning electron microscopy revealed that the shape of the cell became refractile from flat in response to goniodomin A. This morphological change was accompanied by the outgrowth of a needle-like structure from the cell surface. Goniodomin A increased the intracellular content of filamentous actin in a concentration- and time-dependent manner. It also caused the change in filamentous actin distribution in the cells. The elongation of filamentous actin was observed in goniodomin A-treated cells. These results suggest that goniodomin A induces morphological change by increasing the content of filamentous actin in non-muscle cells.     

Update on Cutting Balloon Angioplasty

Cutting balloon (CB) is a unique balloon catheter with 3 or 4 metal blades on its surface making controlled endovascular surgical incisions that show promise of causing less vessel wall injury and less intimai proliferation. Multicenter randomized trials have revealed that CB angioplasty with multiple inflations achieved better lumen enlargement than single inflation and reduced coronary dissection more than plain old balloon angioplasty (POBA). Follow-up results showed CB angioplasty had a smaller late loss and loss index, resulting in lessened restenosis and target lesion revascularization rates. The main indication of CB angioplasty is basically a noncalcified lesion with concentric plaque; however, it could be applied effectively to some lesions unsuitable for POBA including in-stent restenosis, small vessel, long diffuse lesion, or ostial lesion. Additional evaluation would be necessary to determine the role of CB angioplasty in the stent era.     

Benign Strictures of the Intrahepatic Bile Ducts Managed with Percutaneous Transhepatic Cholangioscopy: A Case Report

Benign strictures of the intrahepatic bile ducts were detected, by percutaneous transhepatic cholangioscopy combined with forceps biopsies, in a patient who presented symptoms suggesting cholangitis. The patient was successfully treated by non-operative stricture dilation techniques, with the aid of cholangioscopy. In this paper, the usefulness of percutaneous transhepatic cholangioscopy for the management of benign biliary strictures is discussed.