Publications by authors named "Haruhiko Takahashi"

19 Publications

  • Page 1 of 1

Hemodynamic features of an intracranial aneurysm rupture predicted by perianeurysmal edema: A case report.

Surg Neurol Int 2021 10;12:49. Epub 2021 Feb 10.

Department of Neurosurgery, Niigata University, Brain Research Institute, Niigata, Japan.

Background: Perianeurysmal edema (PAE) has been suggested as an indicator of potential aneurysm rupture; however, the hemodynamic features of these aneurysms are still unknown. A computational fluid dynamic (CFD) analysis was performed to evaluate the hemodynamic features of a very rare case of a ruptured middle cerebral artery (MCA) aneurysm with PAE.

Case Description: A 65-year-old woman presented with disturbed consciousness. A subarachnoid hemorrhage due to an azygos anterior cerebral artery (ACA) aneurysm rupture was suspected. An unruptured MCA aneurysm with PAE was identified in the left temporal lobe. Although the ACA aneurysm was clipped to prevent re-bleeding, the MCA aneurysm subsequently ruptured 6 days later. Clipping of the MCA aneurysm was performed, and hemosiderin deposits suggestive of sentinel bleeding were found on the surface of the aneurysm dome. CFD analysis revealed unstable hemodynamic stress at the expanded bleb area after rupture, localized to the rupture site. Moreover, this analysis revealed flow impingement with pressure elevation and low wall shear stress, which indicated increased inflammation and aneurysm wall thinning that likely led to rupture.

Conclusion: Hemosiderin deposits at the aneurysm wall and PAE indicates leakage from a cerebral aneurysm. Hemodynamic stress at the aneurysm may promote an inflammatory response and lead to wall weakening accompanied by PAE. Based on our findings, we recommend that surgical intervention should be considered as the first line of treatment for such aneurysms to prevent rupture.
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http://dx.doi.org/10.25259/SNI_780_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911146PMC
February 2021

Delayed Bleeding of Unruptured Intracranial Aneurysms After Coil Embolization: A Retrospective Case Series.

World Neurosurg 2021 Feb 20. Epub 2021 Feb 20.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Objective: Delayed bleeding of unruptured intracranial aneurysms (UIAs) after coil embolization is rare; this study aimed to analyze the occurrence of delayed bleeding of UIAs after coil embolization.

Methods: We retrospectively analyzed patients with UIAs after coil embolization between January 2002 and December 2018 and assessed the features of UIAs with delayed bleeding after coil embolization.

Results: Analysis included 307 patients with 335 UIAs. Mean follow-up was 7.1 ± 4.9 years, and total follow-up was 2365 aneurysm-years. There were 271 (80.9%) aneurysms located in the anterior circulation and 64 (19.1%) aneurysms located in the posterior circulation. Significant differences were observed between the 2 groups in terms of maximum size of the aneurysm (P < 0.01), width of the aneurysm neck (P < 0.01), and number of retreatment cases (P < 0.01). During the follow-up period, delayed bleeding occurred in 4 aneurysms (annual bleeding rate of 0.17%); all were located in the posterior circulation. The original size was not relatively large (mean 8.6 ± 2.4 mm). All aneurysms bled within 5 years (mean 35 ± 9.6 months) after the initial treatment. Two were de novo aneurysms that developed adjacent to the coiled aneurysms and were not detected on follow-up magnetic resonance angiography.

Conclusions: Cautious follow-up of UIAs with digital subtraction angiography is important, articularly within the first 5 years after the procedure. If there are changes in the anatomic outcomes, short-term reassessment or additional treatment should be actively considered, particularly for aneurysms in the posterior circulation.
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http://dx.doi.org/10.1016/j.wneu.2021.02.061DOI Listing
February 2021

Possibility of Worsening Flow Diversion Effect Due to Morphological Changes of a Stented Artery With Multiple Overlapping Stents for Partially Thrombosed Vertebral Artery Aneurysms.

Front Neurol 2020 15;11:611124. Epub 2020 Dec 15.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Morphological changes of a stented artery can cause a flow diversion effect to reduce intra-aneurysmal flow; however, there is a potential for the negative effect of increased intra-aneurysmal flow. We present cases with multiple overlapping stents for a partially thrombosed vertebral artery aneurysm and characterize the hemodynamic properties of a recurrent case by focusing on the morphological changes of the stented artery. Between October 2017 and April 2019, four consecutive cases of symptomatic unruptured large and giant partially thrombosed vertebral artery aneurysms were treated with multiple overlapping low-profile visualized intraluminal support stents and no coils. Both angiographic and clinical outcomes were assessed. Computational fluid dynamics analysis was performed to clarify hemodynamic features. The degree of pressure elevation was calculated as the pressure difference (Pd). Wall shear stress (WSS) was also calculated. In three of the four cases, successful flow reduction was achieved with no morphological change of the stented arteries. The patients' symptoms were gradually improved. The remaining case required additional stents after the initial treatment. In the recurrent case, Pd was noticeably elevated at the aneurysm neck after treatment, and WSS was generally increased in the area due to altered blood flow into the aneurysm dome caused by morphological changes of the stented artery. Overlapping stents can be used for the treatment of large and giant thrombosed vertebral artery aneurysms with flow diversion effect; however, morphological changes of the stented artery requires careful attention as it may lead to an increase in the intra-aneurysmal flow, causing negative outcomes.
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http://dx.doi.org/10.3389/fneur.2020.611124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770215PMC
December 2020

Histological subtype of gastric adenocarcinoma: two cases of mixed fundic and pyloric mucosa-type adenocarcinoma.

Ecancermedicalscience 2020 13;14:1143. Epub 2020 Nov 13.

Department of Gastroenterology, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyoin Chikushino, Fukuoka 818-8052, Japan.

Adenocarcinomas with differentiation towards fundic or pyloric glands are rare histological subtypes. We herein describe two cases of new histological subtypes: mixed fundic and pyloric mucosa-type adenocarcinoma detected in uninfected patients. The first patient was a woman in her 40s. A glossy, reddish, nodular lesion with a flat elevated whitish area was detected at the gastric fundus. When the nodular lesion was visualised with magnifying narrow-band imaging (M-NBI), an absent microvascular pattern plus an irregular microsurface pattern with a demarcation line was observed. The second patient was a woman in her 60s. A glossy, reddish, elevated lesion was detected at the gastric body. M-NBI finding was a regular microvascular pattern plus a regular microsurface pattern with a demarcation line. Histological examination of the resected specimens from both cases showed a very well- to well-differentiated adenocarcinoma which has differentiation towards the mixed fundic and pyloric mucosa. The histological and serological findings of both cases indicated the absence of infection. The present two cases demonstrate further evidence of a new histological subtype of gastric adenocarcinoma: mixed fundic and pyloric mucosa-type adenocarcinoma, which has distinct characteristic endoscopic findings.
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http://dx.doi.org/10.3332/ecancer.2020.1143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738269PMC
November 2020

Histological Architecture of Gastric Epithelial Neoplasias That Showed Absent Microsurface Patterns, Visualized by Magnifying Endoscopy with Narrow-Band Imaging.

Clin Endosc 2021 Mar 24;54(2):222-228. Epub 2020 Nov 24.

Department of Pathology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.

Background/aims: The objective of this study was to elucidate the histological structure of the absent microsurface patterns (MSPs) that were visualized by magnifying endoscopy with narrow-band imaging (M-NBI).

Methods: The study included consecutive gastric epithelial neoplasias for which M-NBI findings and histological findings could be compared on a one-to-one basis. The lesions were classified as absent MSPs and present MSPs based on the findings obtained using M-NBI. Of the histopathological findings for each lesion that corresponded to M-NBI findings, crypt opening densities, crypt lengths, crypt opening diameters, intercrypt distances, and crypt angles were measured and compared.

Results: Thirty-six lesions were included in the analysis; of these, 17 lesions exhibited absent MSP and 19 lesions exhibited present MSP. Comparing the histological measurements for absent MSPs vs. present MSPs, median crypt opening density was 0.9 crypt openings/mm vs. 4.8 crypt openings/mm (p<0.001), respectively. The median crypt length, median crypt opening diameter, median intercrypt distance, and median crypt angle were 80.0 μm vs. 160 μm (p<0.001), 40.0 μm vs. 44.2 μm (p=0.09), 572.5 μm vs. 166.7 μm (p<0.001), and 21.6 degrees vs. 15.5 degrees (p<0.001), respectively.

Conclusion: Histological findings showed that lesions exhibiting absent MSPs had lower crypt opening density, shorter crypt length, greater intercrypt distance, and larger crypt angle.
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http://dx.doi.org/10.5946/ce.2020.090DOI Listing
March 2021

Unilateral oculomotor nerve palsy caused by arterial compression accompanying subarachnoid hemorrhage: a case report.

Acta Neurochir (Wien) 2021 03 5;163(3):813-816. Epub 2020 Nov 5.

Department of Neurosurgery, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Niigata, 951-8585, Japan.

Unilateral oculomotor nerve palsy, often caused by aneurysmal compression, is one of the decisive findings for confirming the site of a ruptured aneurysm. However, arterial compression can also cause unilateral oculomotor nerve palsy. Here, we present the case of a 59-year-old woman with a ruptured right internal carotid-posterior communicating artery aneurysm accompanied by contralateral oculomotor nerve palsy. The nerve was found to be compressed by the posterior cerebral artery and was isolated from the ruptured aneurysm. When confirming a ruptured aneurysm based on the evidence of unilateral oculomotor palsy, the arteries surrounding the nerve must be thoroughly assessed.
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http://dx.doi.org/10.1007/s00701-020-04633-xDOI Listing
March 2021

[Surgical Case of Accidental Infantile Acute Subdural Hematoma Caused by Household Minor Head Trauma:Hyperperfusion during Postoperative Hemispheric Hypodensity, Namely "Big Black Brain"].

No Shinkei Geka 2020 Sep;48(9):841-847

Department of Neurosurgery, Nagano Red Cross Hospital.

We experienced a case of an accidental infantile acute subdural hematoma caused by household minor head trauma(Nakamura type I intracranial hemorrhage)with postoperative hemispheric hypodensity lesion(Big Black Brain)whose pathophysiology was analyzed using perfusion MRI. A ten-month-old boy was admitted to our hospital in a comatose state. His mother revealed that the boy suffered a fall from a sofa bed. A CT scan indicated massive acute subdural hematoma in the left cerebral hemisphere. Emergency craniotomy and hematoma evacuation were performed. On postoperative day 3, CT revealed hemispheric hypodensity, and the boy suffered from status epilepticus. MRI on the following day showed widespread white matter hyperintensity in diffusion-weighted images, and MRA demonstrated dilation of the middle cerebral artery. Perfusion MRI using the dynamic susceptibility contrast method revealed a marked increase in cerebral blood flow in the left hemisphere. These abnormal MRI and MRA findings disappeared on postoperative day 13. Status epilepticus also improved upon administration of multi-antiepileptic drugs. Fundoscopy findings on postoperative day 3 showed small bilateral petechial or brush retinal hemorrhages. However, whole-body examination did not show any problems, and was consistent with the mother's account. Thus, we judged non-abusive head trauma. Although follow-up MRI showed diffuse atrophy of the left cerebral hemisphere, the boy aged well without obvious paresis or verbal developmental delay as judged by a follow-up more than a year later. Based on these results, we speculated that hyperperfusion caused by dilation of the cerebral artery was related to the postoperative hemispheric hypodensity, namely "Big Black Brain".
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http://dx.doi.org/10.11477/mf.1436204281DOI Listing
September 2020

Safety and feasibility of the distal transradial approach: A novel technique for diagnostic cerebral angiography.

Interv Neuroradiol 2020 Dec 13;26(6):713-718. Epub 2020 May 13.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Purpose: We aimed to evaluate the safety and feasibility of the distal transradial approach (DTRA) as a novel technique for cerebral angiography based on our institutional initial experience.

Methods: We retrospectively analyzed our institutional database of consecutive diagnostic cerebral angiographies performed with DTRA from December 2018 to August 2019. Patient demographics and clinical and procedural data were recorded.

Results: In total, 51 diagnostic cerebral angiographies in 51 patients (age, 15-83 years; mean age, 59.4 years, SD 13.5; 35 (69%) females) were performed or attempted with DTRA. Ultrasound evaluation showed that the mean inner distal radial artery diameter was significantly smaller than the mean inner forearm radial artery diameter (2.19 mm vs. 2.56 mm, P < 0.001). Cannulation via the distal radial artery was successful in 47 (92%) procedures. In the four procedures that failed, operators converted to the ipsilateral transradial approach without repositioning or redraping. Selective catheterization of the intended vessel was achieved in 64 (91%) of 70 vessels. In the remaining six, operators achieved the objective of the examination with angiography injecting from proximal and conversion to another approach was not required. One patient experienced temporary numbness around the puncture site after the procedure. No radial artery occlusion was identified in the patients who underwent ultrasound evaluation.

Conclusion: Our results demonstrate that DTRA could become a standard approach for diagnostic cerebral angiography owing to the low complication rate and the high cannulation success rate.
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http://dx.doi.org/10.1177/1591019920925709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724605PMC
December 2020

Antacids may increase the appearance of white opaque substance in -eradicated gastric epithelial neoplasia.

Endosc Int Open 2019 Sep 29;7(9):E1144-E1149. Epub 2019 Aug 29.

Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan.

 White opaque substance (WOS) in gastric epithelial neoplasia is helpful for qualitative diagnosis of neoplasia. We hypothesized that WOS of neoplasia is strongly influenced by acid recovery after eradication, similar to that of gastric intestinal metaplasia. The aim of this study was to investigate whether antacids increase the appearance of the WOS in -eradicated neoplasia.  A total of 38 gastric epithelial neoplasias (12 adenomas and 26 adenocarcinomas) detected after eradication were retrospectively evaluated. Presence or absence of WOS was evaluated by magnifying endoscopy with narrow band imaging before and after antacid administration. The pH of collected gastric juice was also measured. Study endpoints were (1) prevalence of WOS in the neoplasia before and after antacid administration, and the histological difference (adenoma and adenocarcinoma); and (2) relationship between the prevalence of WOS and gastric juice pH.  WOS prevalence increased from 0 % (0/38) to 44.8% (17/38) after antacid administration. WOS prevalence in adenomas was more significantly increased compared to that in adenocarcinomas (83.3 % vs 26.9 %,  = 0.0077). Prevalence of WOS in gastric neoplasias was only observed at neutral levels of gastric juice pH, and WOS was not observed at strong acidic levels.  Antacid administration may increase the appearance of WOS in gastric epithelial neoplasia (especially adenomas) detected after eradication with acid recovery.
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http://dx.doi.org/10.1055/a-0961-7916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715435PMC
September 2019

[A Case of Subdural Empyema with Cerebral Arteritis and Brain Ischemia in the Middle Cerebral Artery Distribution, Secondary to Odontogenic Maxillary Sinusitis].

No Shinkei Geka 2019 Feb;47(2):205-210

Department of Neurosurgery, Tachikawa General Hospital, Tachikawa Medical Center.

We present a rare case of subdural empyema with cerebral arteritis and brain ischemia in the middle cerebral artery distribution secondary to odontogenic maxillary sinusitis. A 32-year-old man was admitted to our hospital because of high fever and generalized convulsions. Computed tomography(CT)and magnetic resonance imaging(MRI)showed subdural empyema at the left convexity, with a small amount of air. An interruption of the right maxillary sinus floor corresponding to the alveolar process was evident on coronal CT. He was diagnosed as having subdural empyema caused by odontogenic maxillary sinusitis. MR angiography showed stenosis of the left middle cerebral artery(MCA). Despite antibiotic administration, he became drowsy and developed aphasia with right hemiparesis. Repeat MRI showed enlargement of the encapsulated subdural empyema with increased midline shift to the right. We performed prompt surgical evacuation with craniotomy, endoscopic drainage of the sinusitis, and tooth extraction. A hyperintense lesion was observed on subsequent diffusion-weighted imaging in the left MCA distribution. After repeat drainage of the re-enlarged subdural empyema, he was discharged without apparent neurological deficits. This case indicates that subdural empyema from odontogenic sinusitis requires a suitable imaging study of the brain, head, and neck region, and a multidisciplinary approach involving a neurosurgeon, otolaryngologist, and oral surgeon. Prompt initiation of appropriate antibiotic therapy with surgical intervention is recommended for treatment of subdural empyema from odontogenic sinusitis.
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http://dx.doi.org/10.11477/mf.1436203918DOI Listing
February 2019

Intracerebral Hematoma Occurring During Warfarin Versus Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

Am J Cardiol 2016 Jul 5;118(2):222-5. Epub 2016 May 5.

Department of Research and Development, Tachikawa Medical Center, Nagaoka, Japan. Electronic address:

The neuroradiological findings and its outcomes of intracerebral hemorrhage (ICH) were compared between the non-vitamin K antagonist oral anticoagulant (NOAC) therapy and warfarin therapy. In the latest 3 years, 13 cases of nonvalvular atrial fibrillation on NOAC therapy were admitted for ICH. For comparison, 65 age- and gender-comparable patients with ICH on warfarin therapy were recruited. Three NOACs had been prescribed: dabigatran (n = 4), rivaroxaban (n = 2), and apixaban (n = 7). The average ages were 76 ± 9 and 78 ± 8 years in the warfarin (n = 65) and NOAC groups (n = 13), respectively. There was no difference in the clinical features, including the CHADS2 score or HAS-BLED score: 2.62 ± 1.31 versus 2.62 ± 1.33, or 1.09 ± 0.43 versus 1.00 ± 0.41, for the warfarin and NOAC groups, respectively. The volume of ICH <30 ml was found in 84.6% of the patients on NOACs, but it was found in 53.8% of the patients on warfarin (p = 0.0106). The expansion of hematoma was limited to 7 patients (10.8%) of the warfarin group. A lower hospital mortality and better modified Rankin Scale were observed in the NOAC group than in the warfarin group: 1 (7.7%) versus 27 (41.5%; p = 0.0105) and 3.2 ± 1.4 versus 4.5 ± 1.6 (p = 0.0057), respectively. In conclusion, ICH on NOAC therapy had smaller volume of hematoma with reduced rate of expansion and decreased mortality compared with its occurrence on warfarin.
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http://dx.doi.org/10.1016/j.amjcard.2016.04.034DOI Listing
July 2016

Long-term course of Crohn's disease in Japan: Incidence of complications, cumulative rate of initial surgery, and risk factors at diagnosis for initial surgery.

J Gastroenterol Hepatol 2015 Dec;30(12):1713-9

Department of Community Health and Clinical Epidemiology, St. Mary's College, Kurume, Japan.

Background And Aims: Intestinal complications of stenosis or fistula may occur during the course of Crohn's disease (CD), and surgery is performed in a fair number of patients. The risk factors for initial surgery in a Japanese hospital-based cohort of CD patients were evaluated.

Methods: This study was a single-center, retrospective, cohort study. The subjects were 520 patients who underwent inpatient and outpatient treatment at our hospital, had a definitive diagnosis of CD, and no previous surgery. Three parameters were investigated: (i) cumulative incidence of stenosis and fistula; (ii) cumulative rate of initial surgery for each disease type; and (iii) risk factors at diagnosis for initial surgery.

Results: (i) Stenosis and fistula increased with time, with stenosis or fistula appearing in about half of the patients after 5 years. (ii) The cumulative rate of initial surgery was about 50% after 10 years. (iii) The patient factors at diagnosis of current smoker, upper gastrointestinal disease, stricturing, penetrating, moderate to severe stenosis of the jejunum, moderate to severe stenosis of the ileum, and moderate to severe stenosis of the terminal ileum were risk factors for initial surgery.

Conclusions: Stenosis or fistula appeared in about half of the patients after 5 years from diagnosis. When upper gastrointestinal disease or complicated small intestinal lesions are seen at the time of diagnosis, the cumulative rate of initial surgery is significantly higher.
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http://dx.doi.org/10.1111/jgh.13013DOI Listing
December 2015

Mucosal healing of ileal lesions is associated with long-term clinical remission after infliximab maintenance treatment in patients with Crohn's disease.

Dig Endosc 2015 Jan 17;27(1):73-81. Epub 2014 Jul 17.

Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.

Background And Aim: The aim of the present study was to endoscopically evaluate ileal mucosal healing during maintenance therapy with infliximab in order to investigate the clinical significance of endoscopic examination of ileal lesions in Crohn's disease patients.

Methods: This study retrospectively analyzed 54 patients who mainly had active ulcers of the ileum on endoscopy at baseline who were responsive to infliximab induction and who received infliximab maintenance therapy. Mucosal healing was defined as no ulcer or only ulcer scar. At the time of follow-up endoscopy after starting infliximab, endoscopic score, mucosal healing, and clinical remission were evaluated. On long-term follow up, correlations between mucosal healing and long-term clinical remission, and between mucosal healing and the need for major abdominal surgery, were also evaluated.

Results: Ileal mucosal healing and complete mucosal healing were significantly correlated with clinical remission (P = 0.046, P = 0.0001, respectively). The rate of long-term clinical remission was significantly higher in patients with complete mucosal healing (P = 0.025). The rate of major abdominal surgery for strictures was significantly lower in patients with complete mucosal healing (P = 0.044).

Conclusions: Complete mucosal healing after 1-2 years was a predictive factor for long-term clinical remission up to 4 years after starting infliximab. A lack of complete mucosal healing was a predictive factor for major abdominal surgery for strictures. The present study suggests that endoscopic evaluation of ileal lesions is useful for long-term prognosis of Crohn's disease patients.
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http://dx.doi.org/10.1111/den.12313DOI Listing
January 2015

Second peak in the distribution of age at onset of ulcerative colitis in relation to smoking cessation.

J Gastroenterol Hepatol 2014 Aug;29(8):1603-8

Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino-City, Japan.

Background And Aim: The prevalence of ulcerative colitis (UC) is increasing steadily in Japan. In Western countries, a bimodal distribution, with UC onset peaks in youth and middle age, is observed, and smoking cessation is reported as a risk factor for UC. However, there are few reports on a bimodal distribution of onset age among Japanese patients. Therefore, the distribution of onset age and factors related to late onset (i.e. onset at 50 years old or later) were investigated in UC patients in Japan.

Methods: A questionnaire survey of UC patients was conducted to investigate the distribution of the age of onset and factors that may be related to UC onset in a Japanese university hospital.

Results: Among 465 UC patients, 343 patients responded. In the distribution of onset age, a large peak was seen in patients aged 10-20s, and small peaks were seen at age 40-44 years and then in 50-60s. In addition, the onset age was older in the UC patients diagnosed in 2001 or later than in those diagnosed in 2000 or earlier. Late onset was more common among the UC patients diagnosed in 2001 or later (vs 2000 or earlier: interaction odds ratio = 4.98, 95% CI: 2.21-11.25, P < 0.01) and among former smokers (vs never-smokers: interaction odds ratio = 2.93, 95% CI: 1.40-6.14, P < 0.01) on multivariate analysis.

Conclusions: Similar to UC patients in Western countries, a bimodal distribution of onset age was also observed in Japanese UC patients, and smoking cessation may partly contribute to the increase in late-onset UC patients in recent years in Japan.
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http://dx.doi.org/10.1111/jgh.12616DOI Listing
August 2014

Impact of CYP3A5 genetic polymorphisms on the pharmacokinetics and short-term remission in patients with ulcerative colitis treated with tacrolimus.

J Gastroenterol Hepatol 2014 Jan;29(1):60-6

Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan.

Background And Aim: The pharmacokinetics of tacrolimus (Tac) differ among individuals, and genetic polymorphisms of cytochrome P-450 (CYP) 3A4, CYP3A5, and ABCB1 are thought to be involved. The aim of this study was to clarify whether these genetic polymorphisms affect the pharmacokinetics of Tac in patients with ulcerative colitis.

Methods: The subjects in this study were 45 patients with moderate-to-severe ulcerative colitis who were resistant to other therapies and were treated with Tac. The subjects were tested for genetic polymorphisms of CYP3A4, CYP3A5, and ABCB1, and the relationship between Tac pharmacokinetics and the remission rate was investigated.

Results: Of the 45 subjects, 24 (53.3%) were CYP3A5 expressers (Exp), and 21 (46.7%) were non-expressers (Non-Exp). The trough level and the dose-adjusted trough level on days 2-5 were significantly higher in the Non-Exp group than in the Exp group (10.16 ± 5.84 vs 4.47 ± 2.50 ng/mL, P < 0.0001, 139.36 ± 77.43 vs 61.37 ± 41.55 ng/mL per mg/kg/day, P < 0.0001). The percentage of patients achieving the optimal trough level on days 2-5 was significantly higher in the Non-Exp group than in the Exp group (40.0% vs 4.3%, P = 0.01). This trend was also observed on days 7-10. On multivariate analysis, factors associated with achievement of the optimal trough level were food non-intake and Non-Exp of CYP3A5. The remission rate was significantly higher in the Non-Exp group than in the Exp group (47.6% vs 16.7%, P = 0.046).

Conclusions: CYP3A5 genetic polymorphisms affected the pharmacokinetics of Tac, so that the short-term clinical remission rate was different between Exp and Non-Exp of CYP3A5.
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http://dx.doi.org/10.1111/jgh.12361DOI Listing
January 2014

Smoking, alcohol drinking, green tea consumption and the risk of esophageal cancer in Japanese men.

J Epidemiol 2006 Sep;16(5):185-92

Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Sendai, Japan.

Background: Although smoking and alcohol drinking are established risk factors of esophageal cancer, their public health impact is unclear. Furthermore, the effect of green tea is controversial.

Methods: The present study was based on a pooled analysis of two prospective cohort studies. A self-administered questionnaire about health habits was distributed to 9,008 men in Cohort 1 and 17,715 men in Cohort 2, aged 40 years or older, with no previous history of cancer. We identified 38 and 40 patient cases with esophageal cancer among the subjects in Cohort 1 (9.0 years of follow-up) and Cohort 2 (7.6 years of follow-up), respectively. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of the risk of esophageal cancer incidence.

Results: Cigarette smoking, alcohol drinking and green tea consumption were significantly associated with an increased risk of esophageal cancer. Compared with men who had never smoked, never drunk alcohol or green tea, the pooled multivariate HRs (95% confidence intervals) were 5.09 (1.80-14.40) (p for trend <0.0001), 2.73 (1.55-4.81) (p for trend=0.0002), or 1.67 (0.89-3.16) (P for trend=0.04) for men who were currently smoking > or =20 cigarettes/day, drinking alcohol daily, or drinking > or =5 cups green tea/day, respectively. The population attributable fractions of esophageal cancer incidence that was attributable to smoking, alcohol drinking and green tea consumption were 72.0%, 48.6%, and 22.1%, respectively.

Conclusions: Among the variables studied, smoking has the largest public health impact on esophageal cancer incidence in Japanese men, followed by alcohol drinking and green tea drinking.
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http://dx.doi.org/10.2188/jea.16.185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683705PMC
September 2006

Synthesis and antiviral activities of 1'-carbon-substituted 4'-thiothymidines.

Bioorg Med Chem 2004 Oct;12(20):5309-16

School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

4-Thiofuranoid glycals substituted at the 1-position with methyl (5), (t-butyldimethylsilyloxy)methyl (7), and acetoxymethyl (8) groups were prepared from the 3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl) (TIPDS)-4-thiofuranoid glycal (3) by way of LDA-lithiation. N-Iodosuccimide-initiated electrophilic glycosidation between silylated thymine and these 1-carbon-substituted 4-thioglycals gave the respective beta-anomers (9, 10, and 13) stereoselectively. Tin radical-mediated removal of the 2'-iodine atom from these products provided the corresponding 1'-branched 4'-thiothymidine derivatives (11, 12, and 14) in good yields. The 1'-hydroxymethyl derivative (15) served as a precursor for the preparation of the formyl (16), cyanoethenyl (17), and cyano (19) derivatives. Among the deprotected 1'-branched 4'-thiothymidines (20-25), the 1'-methyl analogue 20 showed the most potent anti-HSV-1 activity, but it was much less active than the parent compound 4'-thiothymidine.
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http://dx.doi.org/10.1016/j.bmc.2004.07.057DOI Listing
October 2004

4-Thiofuranoid glycals: versatile synthons for stereoselective synthesis of 4'-thionucleosides.

Nucleosides Nucleotides Nucleic Acids 2003 May-Aug;22(5-8):763-5

School of Pharmaceutical Sciences, Showa University, Shinagawa-ku, Tokyo, Japan.

Beta-anomers of 4'-thionucleosides have been synthesized stereoselectively, through PhSeCl- or N-iodosuccimide (NIS)-initiated electrophilic glycosidation to 3,5-O-(di-t-butylsilylene)-4-thiofuranoid glycal (1). This synthetic method has been applied to the synthesis of those analogues branched at the anomeric position using 1-C-carbon-substituted 3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-4-thiofuranoid glycals (11-14) prepared based on lithiation of 10.
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http://dx.doi.org/10.1081/NCN-120022629DOI Listing
December 2003

Stereoselective synthesis of the beta-anomer of 4'-thionucleosides based on electrophilic glycosidation to 4-thiofuranoid glycals.

J Org Chem 2002 Aug;67(17):5919-27

School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

Three types of 4-thiofuranoid glycal with different 3,5-O-silyl protecting groups were prepared and their electrophilic glycosidation was investigated. The 3,5-bis-O-(tert-butyldimethylsilyl)-4-thiofuranoid glycal (5) was obtained through mesylation of 2-deoxy-4-thio-D-erythro-pentofuranose (4) and subsequent base-promoted elimination, while thermal elimination of sulfoxide derivatives was suitable for the preparation of 3,5-O-(tetraisopropyldisiloxane-1,3-diyl) (9) and 3,5-O-(di-tert-butylsilylene) (11) 4-thioglycals. The glycosidation reactions of these 4-thioglycals were carried out, in the presence of either PhSeCl or NIS, by using silylated derivatives of uracil, thymine, cytosine, and N(6)-benzoyladenine. Among the three 4-thioglycals, 11 was found to be an excellent glycosyl donor, forming the desired beta-anomer exclusively irrespective of the nucleobase employed.
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http://dx.doi.org/10.1021/jo020037xDOI Listing
August 2002