肝疾患における糖鎖抗原CA-50の意義に関する検討

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1130号, 学位授与年月日：平成3年6月19日,学位授与年：199

肝硬変症に伴う胃粘膜病変の成因における血管作動性物質の関与

金沢大学医学部附属病院臨床的には胃粘膜病変と門脈血行動態について明らかとした。食道静脈瘤を含む上行性短絡路の血流が少ない例はGastropathyが高度であり、門脈圧亢進症において胃粘膜病変は単に門脈圧の程度のみではなく、側副路の発達パターンの相違も胃粘膜病変を規定する要因であることが示された。また胃内環境を規定する大きな因子である胃内pHは肝病態が進展した例においては夜間の逆転現象が消失するなど特異なパターンを示し、胃酸分泌制御機構の破綻が明らかとなった。その背景として門脈圧亢進による消化管ホルモンの分泌代謝異常、胃粘膜血液のうっ滞、それに引き続く血管作動性物質の関与が考えられた。さらに肝硬変症時の胃粘膜障害の大きな要因と仮説を立てたエンドトキシンについて、門脈圧亢進時側副路である奇静脈内の濃度を測定した。しかしながら肝病態の安定している対象例においては奇静脈内エンドトキシン濃度は末梢血濃度と差は認められなかった。一方エンドトキシンの阻害作用を有するUlinastatin投与によるショック肝ラットを用いた実験では、肝血流、胃粘膜血流ともに上昇することを明らかし、胃粘膜血流の低下、それに引き続く胃粘膜病変の成因としてエンドトキシンが重要な役割を果たしていることが考えられたが、今後さらに直接的な関連の検討を予定している。肝硬変ラット、および門脈圧亢進症ラットにおいて、胃粘膜内のプロスタグランヂン濃度を測定した。コントロールラットに比較し、PGE1、PGE2濃度の低下が認められ、Portal hypertensive gastropathyの成因に関与していることが示された。当初主検討項目と予定していたエンドセリン、PAFについては現在実験を開始したばかりであり、また血管内皮弛緩因子nitric oxide(NO)とともに今後検討してゆく予定である。研究課題/領域番号:05770349, 研究期間(年度):1993出典：研究課題「肝硬変症に伴う胃粘膜病変の成因における血管作動性物質の関与」課題番号05770349（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-05770349/）を加工して作

Digeneans Found in Freshwater Fishes of the Uji River at Uji, Kyoto Prefecture, and the Takami River at Higashiyoshino, Nara Prefecture, Japan

Freshwater fishes of 20 species collected in the Uji River at Uji, Kyoto Prefecture, and the Takami River at Higashiyoshino, Nara Prefecture, in 1999 and 2000 were examined for helminth parasites. Digenans of eight species (seven identified and one unidentified) in seven genera in four families found are described and illustrated. The life cycle and host and locality records of each of them are discussed. Genarchopsis anguillae Yamaguti, 1938 (Derogenidae) is regarded as a synonym of G. goppo Ozaki, 1925

Rapid Formation of Cerebral Microbleeds after Carotid Artery Stenting

Background: Recent studies reported that cerebral microbleeds (CMBs), i.e. small areas of signal loss on T2*-weighted gradient-echo (GE) imaging, could develop rapidly after acute ischemic stroke. We hypothesized that CMBs rapidly emerge after carotid artery stenting (CAS). Objective: We investigated the frequency of and predisposing factors for CMBs after CAS. Methods: We retrospectively examined MRI before and after CAS in 88 consecutive patients (average age: 71.7 ± 7.2 years, average rates of carotid stenosis: 72.6 ± 12.8%) who underwent CAS for carotid artery stenosis between March 1, 2009, and September 30, 2010. We defined new CMBs as signal losses that newly appeared on the follow-up GE. We examined the association of new CMBs with demographics, risk factors, and baseline MBs. Results: Among 88 patients, 18 (20.5%) had CMBs initially, and 7 (8.0%) developed new CMBs right after CAS. New CMBs appeared on the same side of CAS in all of the 7 patients. New CMBs appeared significantly more frequently in the CMB-positive group than in the CMB-negative one (22% vs. 4%, p = 0.03) on the pre-CAS MRI. Multivariate analysis also revealed that the presence of CMBs before CAS was an independent predictor of new development of CMBs after CAS (odds ratio: 8.09, 95% confidence interval: 1.39–47.1). Conclusion: CMBs can develop rapidly after CAS, especially in patients with pre-existing CMBs. Since the existence of CMBs prior to CAS suggests a latent vascular damage which is vulnerable to hemodynamic stress following CAS, particular attention should be paid to the prevention of intracerebral hemorrhage due to hyperperfusion after CAS

切除不能進行胃癌に対する化学療法有効例の治癒形態の検討

大学院医学系研究

A fatal case of progressive steatohepatitis, possibly chemotherapy- associated steatohepatitis related to gemcitabine

金沢大学医薬保健研究域医学系We report the case of an 80-year-old female suffering from pancreatic cancer who developed severe non-alcoholic steatohepatitis (NASH) resulting in fatal hepatic failure after anti-cancer chemotherapy with gemcitabine. Hepatic encephalopathy appeared 1 year after the chemotherapy, and the patient developed progressive liver failure and eventually died. Radiological examination showed severe fatty liver. Histopathological examination of a liver needle necropsy showed almost panlobular macrovesicular fatty change. Ballooning degeneration and necrosis of hepatocytes accompanying neutrophil infiltration, Mallory bodies, and a few bile plugs were found in zone 3. Marked perivenular and pericellular/perisinusoidal fibrosis and extensive bridging fibrosis were also found. Together, these findings indicated steatohepatitis at a precirrhotic stage. Because the patient had no history of drinking in excess, we made a diagnosis of NASH, in particular, chemotherapy-associated steatohepatitis (CASH). Gemcitabine is a pyrimidine nucleoside antimetabolite with anti-cancer activity. A few reports have mentioned fatal hepatotoxicity caused by gemcitabine, but, to our knowledge, this is the first report of steatohepatitis, possibly associated with gemcitabine. Physicians treating patients with this drug should be aware of the possibility of steatohepatitis. © Springer 2010

Clinical Usefulness of the VS Classification System Using Magnifying Endoscopy with Blue Laser Imaging for Early Gastric Cancer

Background. Blue laser imaging (BLI) enables the acquisition of more information from tumors’ surfaces compared with white light imaging. Few reports confirm the validity of magnifying endoscopy (ME) with BLI (ME-BLI) for early gastric cancer (EGC). We aimed to assess the detailed endoscopic findings from EGCs using ME-BLI. Methods. We enrolled 386 consecutive patients with 417 EGCs that were diagnosed using ME-BLI and resected by endoscopic submucosal dissection. Using the VS classification system, three highly experienced endoscopists (HEEs) and three less experienced endoscopists (LEEs) evaluated the demarcation line (DL), microsurface pattern (MSP), and microvascular pattern (MVP) within the endoscopic images of EGCs obtained using ME-BLI, assigning high-confidence (HC) or low-confidence (LC) levels. We investigated the clinicopathological features associated with each confidence level. Results. The HEEs’ evaluations determined the presence of DL in 99%, irregular MSP in 96%, and irregular MVP in 96%, and the LEEs’ evaluations determined the presence of DL in 98%, irregular MSP in 95%, and irregular MVP in 95% of the EGCs. When DL was present, HC levels in the Helicobacter pylori- (H. pylori-) eradicated group and noneradicated group were evident in 65% and 89%, a difference that was significant (p<0.001). Conclusions. In the diagnosis of EGC with ME-BLI, the VS classification system with ME-NBI can be applied, but identifying the DL after H. pylori was difficult

経頚静脈的管肝内門脈大循環短絡術による portal hypertensive gastropathy の変化

金沢大学医学系研究科荻野, 英

Low-Dose Intravenous Alteplase in Wake-Up Stroke

Background and Purpose—We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods—This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results—Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P>0.999), respectively. Conclusions—No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions