Risk factors for reflux esophagitis after eradication of Helicobacter pylori.

Objective: While there is an association between successful eradication of Helicobacter pylori (HP) and reflux esophagitis (RE), risk factors associated with RE remain obscure. The aim of this study is to determine risk factors associated with the development of RE after HP eradication.Materials and methods: Among all patients treated with successful HP eradication from 2008 to 2016, we retrospectively analyzed those who were free from RE at initial esophagogastroduodenoscopy (EGD) and who were followed up with EGD after eradication. Patients were classified according to the presence or absence of RE at the follow-up EGD. RE was defined as mucosal breaks proximal to the squamous-columnar junction. Demographic data, underlying diseases, medications and endoscopic findings at the initial EGD were compared between patients with and without RE.Results: Among 1575 patients, 142 (9.0%) had RE at the follow-up EGD. The time interval from HP eradication until EGD ranged from 4 to 24 months. The endoscopic grade of RE was higher in males than in females. Multivariate analysis revealed that male sex (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.24), body mass index ≥25 kg/m2 (OR, 2.91; 95% CI, 2.00-4.22), use of calcium channel blockers (OR, 1.70; 95% CI, 1.12-2.55), and hiatal hernia (OR, 3.46; 95% CI, 2.41-5.00) were associated with the development of RE.Conclusions: Calcium channel blocker use was found to be a risk factor for the development of RE after eradication of HP.

Total dosage of gardenia fruit used by patients with mesenteric phlebosclerosis.

BACKGROUND: Mesenteric phlebosclerosis (MP) is a disease characterized by fibrotic change or calcification of the mesenteric vein. Recently, there has been an increase in case reports of MP related to herbal medicine usage. Long-term intake of gardenia fruit (GF) is suspected as a possible cause. However, many GF users do not develop this disease and the association between GF and MP remains unclear. In this study, we investigated for the first time the dosage of GF used by patients with and without MP. METHODS: We used a medical chart review study design to assess the association between GF and MP. We reviewed patients with a history of intake of herbal medicines containing GF. Among these patients, we selected patients who were examined by colonoscopy and abdominal plain computed tomography (CT). We investigated the findings of colonoscopy, CT scan and histological examination. We assessed the total dosages of GF alongside the duration of ambulatory visit, the administration period of herbal medicine containing GF and pre-existing disease in order to compare MP cases and non-MP patients. RESULTS: Ten MP cases and 42 non-MP patients were analyzed. We summarized clinical findings of MP cases. All MP cases used more GF than non-MP patients and were administered more than approximately 5,000 grams of GF in cumulative dosage. CONCLUSIONS: This study indicated that excessive intake of GF contributes to and/or accelerates the development of MP suggesting that long-term usage of GF in excessive amounts increases the risk of MP.

Therapeutic strategy for Crohn's disease with a loss of response to infliximab: a single-center retrospective study.

BACKGROUND/AIMS: Infliximab (IFX) is an effective treatment for maintaining clinical remission in patients with initially moderate-to-severe Crohn's disease (CD). However, a certain number of patients become unresponsive to IFX, subsequently requiring intensified therapy. The aim of this study was to compare the short- and long-term therapeutic efficacy of intensified regimens in CD patients who fail to respond to IFX. METHODS: The clinical courses of 33 CD patients who failed to respond to treatment with IFX were investigated retrospectively. An intensified regimen involving doubling the dose of IFX was chosen in 13 patients (DD group) versus shortening the IFX interval in 13 patients (SI group) and switching to adalimumab (ADA) in 7 patients (SA group). RESULTS: The clinical response and rate of clinical remission at 4 weeks were 62 and 54% in the DD group, 77 and 62% in the SI group and 57 and 43% in the SA group, respectively (p = 0.59 for clinical response, p = 0.90 for clinical remission). The rate of sustained remission at 48 weeks was 44% in the DD group, 54% in the SI group and 33% in the SA group (p = 0.88). CONCLUSION: The short- and long-term efficacy of doubling the dose of IFX, shortening the interval of IFX or switching to ADA is similar for CD patients who no longer respond to IFX.

Lycopene inhibits ischemia/reperfusion-induced neuronal apoptosis in gerbil hippocampal tissue.

Plant lycopene exhibits antioxidant activity in animal tissues. Transient cerebral ischemia/reperfusion in Mongolian gerbils resulted in delayed neuronal death in hippocampal regions. We examined the antioxidant effects of lycopene because we expected lycopene to attenuate ischemia-related neuronal damage by controlling apoptosis at the gene level. The gerbils were divided into two groups: the normal feeding (control) group that received normal market food (MF) and the lycopene group that received MF containing lycopene (5 mg in 100 g MF food). After 1.5-2.0 months (when body weight were 60-65 g), the lycopene level was 38.2 ± 17.6 ng/ml in serum and 11.9 ± 4.0 µg/g-wet weight tissue in the liver. Levels of B cell leukemia-2, an apoptosis-suppressing protein, decreased in control animal brains 1, 3, and 7 days after surgery, whereas the levels increased in lycopene-treated animal brains. Moreover, cysteinyl aspartate-specific protease-3 activity increased gradually after ischemia, but was suppressed in the lycopene-treated animal brains 7 days after surgery. Finally, hippocampal superoxide dismutase (SOD) activity decreased in the control group 3 h after ischemia and, gradually increased thereafter, whereas it was significantly elevated in the lycopene group. Thus, orally administered lycopene is accumulated in the body, and provided protections against ischemia/reperfusion-induced brain injury by inducing an increase in SOD activity and inhibiting apoptosis.

Effect of keishibukuryogan on endothelial function in patients with at least one component of the diagnostic criteria for metabolic syndrome: a controlled clinical trial with crossover design.

We evaluated the effect of keishibukuryogan (KBG; Guizhi-Fuling-Wan), a traditional Japanese (Kampo) formula, on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (Endo-PAT2000) in patients with metabolic syndrome-related factors by controlled clinical trial with crossover design. Ninety-two patients were assigned to group A (first KBG-treatment period, then control period; each lasting 4 weeks, with about one-year interval) or group B (first control, then KBG-treatment). In forty-nine (27, group A; 22, group B) patients completing all tests, the mean value of the natural logarithmic-scaled reactive hyperemia index (L_RHI) increased and those of serum nonesterified fatty acid (NEFA), malondialdehyde, and soluble vascular cell adhesion molecule 1 decreased significantly during the KBG-treatment period, but not during the control period, and 4-week changes of L_RHI, NEFA, and malondialdehyde between the 2 periods showed significance. These results suggest that KBG has beneficial effect on endothelial function in patients with metabolic syndrome-related factors.

[Clinicopathological features of serrated lesions of the colorectum].

We reviewed 428 subjects with colorectal serrated lesions resected endoscopically or surgically at our institution. Colorectal serrated lesions were pathologically divided into 3 groups: hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA). SSA/P was detected frequently in the right colon and SSA/P was mainly flat-elevated. Cancers occurring in SSA/P were found more frequently than HP or TSA. The incidence of cancer in SSA/P was equivalent to that of cancer in traditional adenoma. Further studies are warranted to clarify clinicopathological features of serrated lesions of the colorectum.

Optical properties and Faraday effect of ceramic terbium gallium garnet for a room temperature Faraday rotator.

The optical properties, Faraday effect and Verdet constant of ceramic terbium gallium garnet (TGG) have been measured at 1064 nm, and were found to be similar to those of single crystal TGG at room temperature. Observed optical characteristics, laser induced bulk-damage threshold and optical scattering properties of ceramic TGG were compared with those of single crystal TGG. Ceramic TGG is a promising Faraday material for high-average-power YAG lasers, Yb fiber lasers and high-peak power glass lasers for inertial fusion energy drivers.

A chinese herbal medicine, tokishakuyakusan, reduces the worsening of impairments and independence after stroke: a 1-year randomized, controlled trial.

In post-stroke patients, the recurrence of stroke and progression of impairments lead to a bedridden state and dementia. As for their treatments, only anti-hypertension and anti-coagulation therapies to prevent the recurrence of stroke are available. In Asia, post-stroke patients with impairments are often treated with herbal medicine. The present study evaluated the effectiveness of tokishakuyakusan (TS) in improving the impairment and independence in post-stroke patients. Thirty-one post-stroke patients (mean age = 81.4 years) were recruited and enrolled. Participants were randomly assigned to the TS group (n = 16) or non-treatment (control) group (n = 15) and treated for 12 months. Impairments were assessed using the Stroke Impairment Assessment Set (SIAS). Independence was evaluated using the functional independence measure (FIM). For each outcome measure, mean change was calculated every 3 months. The results were that impairments according to SIAS did not significantly change in the TS group. In contrast, SIAS significantly worsened in the control group. There was a significant difference between the two groups. In each term of SIAS, affected lower extremity scores, abdominal muscle strength, function of visuospatial perception, and so forth. in the TS group were better than those in the control group. Independence according to FIM did not change significantly in the TS group. In contrast, FIM significantly worsened in the control group. There was also a significant difference between the two groups. In conclusion, TS was considered to suppress the impairments of lower limbs and to exert a favorable effect on cerebral function for post-stroke patients.

[A case of steroid-dependent ulcerative colitis complicated by skin infection of Mycobacterium szulgai].

We describe a case of a 47-year old Japanese man with steroid-dependent, refractory ulcerative colitis complicated by non-tuberculous mycobacterial skin infection. The patient remained in remission by combination therapy of 100mg azathioprine and 27.5mg prednisolone (total dose over 25g for three years), but developed a deep genital ulcer. Mycobacterium szulgai was confirmed by skin culture, and the ulcer became turned into a scar after oral administration of isoniazid, rifampicin, and ethanbutol.

Anti-tumor necrosis factor therapy decreases the risk of initial intestinal surgery after diagnosis of Crohn's disease of inflammatory type.

BACKGROUND: Anti-tumor necrosis factor (TNF) therapy induces and maintains clinical remission in patients with Crohn's disease (CD). However, the effect of anti-TNF therapy on the natural course of CD remains controversial. We aimed to investigate the effect of anti-TNF therapy on the initial intestinal surgery for CD. METHODS: In this single-center retrospective cohort study, clinical course of 199 CD patients of inflammatory type at the initial diagnosis (the period between 1973 and 2014) was precisely reviewed until the end of 2016. Patients were divided into TNF and non-TNF groups based on anti-TNF agent use. After comparisons of clinical characteristics and medical treatments, propensity scores were calculated for covariates. Risk of intestinal surgery was compared by a Cox proportional hazards model using the propensity scores. The effect of immunomodulators on initial intestinal surgery was assessed in the TNF group. RESULTS: During the study period, 108 patients received anti-TNF therapy. The patients in the TNF group were diagnosed more recently, and more frequently had isolated colonic involvement, and perianal disease. Immunomodulators were more frequently used in the TNF group. Cumulative probability of initial intestinal surgery was significantly lower in the TNF group (P < 0.0001). The hazard ratio in the TNF group was 0.32 (95% CI 0.13-0.74). Immunomodulators did not decrease the risk of initial intestinal surgery. CONCLUSIONS: Anti-TNF therapy can decrease the risk of intestinal surgery among patients with inflammatory-type CD at the initial diagnosis. Further studies should be necessary to determine the additive effect of immunomodulators on the risk of intestinal surgery.

Risk of surgery in patients with stricturing type of Crohn's disease at the initial diagnosis: a single center experience.

BACKGROUND/AIMS: It remains uncertain which patients with stricturing-type Crohn's disease (CD) require early small bowel surgery after the initial diagnosis. We aimed to clarify clinical characteristics associated with the intervention in such condition of CD. METHODS: We retrospectively evaluated the clinical course of 53 patients with CD and small bowel strictures who were initially treated with medications after the initial diagnosis. We investigated possible associations between small bowel surgery and the following: clinical factors and radiologic findings at initial diagnosis and the types of medications administered during follow-up. RESULTS: Twenty-eight patients (53%) required small bowel resection during a median follow-up period of 5.0 years (range, 0.5-14.3 years). The cumulative incidence rates of small bowel surgery at 2, 5, and 10 years were 26.4%, 41.0%, and 63.2%, respectively. Univariate analysis indicated that obstructive symptoms (P=0.036), long-segment stricture (P<0.0001), and prestenotic dilation (P<0.0001) on radiography were associated with small bowel surgery, and immunomodulatory (P=0.037) and biological therapy (P=0.008) were significant factors during follow-up. Multivariate analysis revealed that long-segment stricture (hazard ratio [HR], 4.25; 95% confidence interval [CI], 1.78-10.53; P=0.001) and prestenotic dilation (HR, 3.41; 95% CI, 1.24-9.62; P=0.018) on radiography showed a positive correlation with small bowel surgery, and biological therapy (HR, 0.40; 95% CI, 0.15-0.99; P=0.048) showed a negative correlation. CONCLUSIONS: CD patients with long-segment stricture and prestenotic dilation on radiography seem to be at a higher risk of needing small bowel surgery. For such patients, early surgical intervention might be appropriate, even at initial diagnosis.

Clinical Search for Undiagnosed Mesenteric Phlebosclerosis at Outpatient Departments Specializing in Herbal (Kampo) Medicine.

OBJECTIVE: Mesenteric phlebosclerosis (MP) is a disease characterized by calcification of the mesenteric vein, which causes chronic mesenteric ischemia. Recently, the long-term intake of gardenia fruit ('Sanshishi' in Japanese) has been attracting attention as a possible cause. Usually, only advanced, severe MP cases get reported. However, we suspected that some latent cases of this disease may exist. We performed this study in order to determine the prediagnostic cases at our outpatient departments of herbal (Kampo) medicine, with particular attention paid to the initial changes, such as any slight color change of the colon, as shown in colonoscopy. METHODS: We recommend colonoscopy and computed tomography (CT) scans for patients with a long-term history of taking herbal medicines containing gardenia fruit. Clinical examinations were performed upon receiving patients' consent from December 2013 to November 2014. RESULTS: Of the 103 patients who took gardenia fruit long-term, 29 agreed to be checked for MP. 14 patients underwent colonoscopy. Four patients were confirmed to have MP due to the presence of fibrotic deposition of the colonic membrane on histological inspection. Twenty-one patients underwent abdominal CT screening. Characteristic calcification of the mesenteric vein was observed on CT scans in 2 patients. All 4 MP patients took Kampo formulas containing gardenia fruit for more than 6.8 years. The other patients did not develop MP, despite long-term gardenia fruit intake. CONCLUSION: We detected the latent and undiagnosed MP cases. All diagnoses were made while paying careful attention to any slight changes in colonoscopy and CT scans.

Single-shot spatial-coherence measurement of 13 nm high-order harmonic beam by a Young's double-slit measurement.

The interference pattern produced by a single 13 nm high-order harmonic pulse is captured by an extreme-ultraviolet CCD camera. A beam divergence of 0.35 mrad and a high fringe visibility of 0.96 are obtained with an optimal phase-matching condition for the 13 nm harmonics. The spatial coherence length of the 13 nm harmonics selected by Mo/Si multilayer mirrors is larger than the beam diameter. This result shows that the 13 nm harmonic beam is useful for applications in interferometry, time-resolved studies of ultrafast dynamics.

Development of high-throughput, high-damage-threshold beam separator for 13 nm high-order harmonics.

We demonstrate a high-throughput, high-damage-threshold beam separator for wavelengths shorter than 30 nm, which uses a 10 nm thick niobium nitrogen film prepared on a Si substrate, set at the Brewster angle relative to the pump wavelength. The film was deposited by rf reactive magnetron sputtering on a Si substrate. The beam separator has an attenuation ratio of 0.01 and a damage-threshold intensity of at least 0.8 TW/cm2 for a 26 fs pump pulse. The measured reflectivity of the beam separator exceeded 70% in a wavelength range of 13-18 nm. This broadband beam separator may be used to eliminate energetic laser pulses from longitudinally pumped x ray lasers as well as from high-order harmonics.

Nanophase-separated synchronizing structure with parallel double periodicity from an undecablock terpolymer.

A new nanophase-separated structure with parallel double periodicity has been identified for an undecablock terpolymer in bulk. The polymer includes two long poly(2-vinypyridine) (P) chains on each end, with five short polyisoprene (I) and four short polystyrene (S) chains at the center. This polymer exhibits a hierarchical lamellar structure with two crystallographic periods: 88 nm and 16 nm. The 88 nm period includes one thick P lamella and five thin I-S-I-S-I lamellae, of extremely high orientation.

Diblock-type supramacromolecule via biocomplementary hydrogen bonding.

Control of nanostructure formation by a diblock-type supramacromolecule via biocomplementary hydrogen bonding has been achieved. Two different homopolymers, poly(4-trimethylsilylstyrene) and poly(styrene-d8), that are end-decorated with complementary oligonucleotides, i.e., thymidine phosphates and deoxyadenosine phosphates, were prepared by using the phosphoramidite method and blended successively. Association behavior in a blend solution was examined with NMR, and a cast bulk film obtained from the solution has been confirmed to show a nanophase-separated structure by transmission electron microscopy and X-ray scattering. Suppression of this nanostructure formation of a block-type supramacromolecule was also attained by adding a smaller agent as an inhibitor.

Novel synthesis and characterization of bioconjugate block copolymers having oligonucleotides.

Novel and efficient synthesis of polymers terminated with nucleotides via the phosphoramidite method has been developed. A hydroxyl-terminated polymer was converted into a polymer capped with a nucleotide in three steps, where the conversion of the reactions was very high, almost 100%. By repetition of this synthetic method, a block copolymer composed of a synthetic polymer, polystyrene, and biological oligonucleotides with thymidine units has been successfully synthesized. A microphase-separated structure of this block copolymer was observed by both transmission electron microscopy and small-angle X-ray scattering, and a cylindrical structure was confirmed.