4569 research outputs found
Sort by
De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
A Pilot Study Investigating the Use of Regional Oxygen Saturation as a Predictor of Ischemic Wound Healing Outcome after Endovascular Treatment in Patients with Chronic Limb-Threatening Ischemia
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Objective: To determine the prognostic value of regional tissue oxygenation saturation (rSO2) for ulcer healing after endovascular treatment (EVT) of peripheral arterial disease (PAD).
Materials and Methods: Among PAD patients, 34 patients with chronic limb-threatening ischemia underwent EVT for limb salvage. We retrospectively analyzed the cutoff rSO2 values on postoperative day 1 to predict ulcer healing and patient prognosis. Skin perfusion pressure (SPP) and transcutaneous oxygen pressure (TcPO2) were also used to assess wound healing.
Results: A finger-mounted tissue oximeter can easily measure rSO2 on the dorsal foot. Among the 34 patients, the ulcer healed in 25, and no changes were observed in 2 patients at 1 month after EVT. However, 7 patients needed major amputation at the same time. Wound healing was achieved in all patients with rSO2 ≥50%. With this cutoff, the sensitivity and specificity of the new device for wound healing were 100% and 64%, respectively. In all the wound healing cases, SPP was ≥45mmHg, and TcPO2 was ≥40mmHg.
Conclusion: To assess limb ischemia, rSO2 can be measured quickly and easily using this device. We suggest that an rSO2 >50% shows good prognosis for ulcer healing.doctoral thesi
Mesalazine granule formulation improves clinical data in Crohn’s disease compared with tablet formulation
Get PDF浜松医科大学博士（医学）doctoral医学系研究科The efficacy of sustained-release preparations of mesalazine as a remission maintenance treatment for Crohn’s disease remains to be established. We aimed to examine the changes in compliance rate and clinical data 2 years after switching from mesalazine tablet to granule formulation at our facility among patients with Crohn’s disease in remission. We investigated the rate of continuous treatment of mesalazine granules and examined the changes in Crohn’s Disease Activity Index (CDAI) and serum C-reactive protein (CRP), albumin, and hemoglobin (Hb) levels 2 years after the switch. Compliance rate (continuous treatment vs. additional treatment) and continuous treatment rate [good (rate of ≥70%) vs. poor (rate<70%)] were investigated. Of 46 patients, 12 (27.3%) received additional treatment and 32 (72.7%) did not require additional treatment in 2 years. No significant change in CDAI after switching to granule modification was noted in 32 patients in the continuous treatment group. Nevertheless, clinical remission was maintained for 2 years, and serum CRP levels decreased significantly (P=0.023) and Hb levels increased significantly (P=0.002). No change in the compliance rate was found. Our results suggest that mesalazine granule formulation may have a remission maintenance effect that is superior to that of mesalazine tablets.doctoral thesi
Simple LC-MS/MS Methods for the Quantitation of Total and Free Aprepitant and its Active N-Dealkylated Metabolites in Human Plasma
Get PDF雑誌掲載タイトル：Simple Liquid Chromatography?Tandem Mass Spectrometry Method for Quantitation of Total and Free Aprepitant and Its Active N-Dealkylated Metabolites in Human PlasmaBackground: Aprepitant, an antiemetic selective neurokinin-1 receptor antagonist, is primarily metabolized to active N-dealkylated form (ND-AP) and then converted to its carbonyl form (ND-CAP) in humans. This study developed simple liquid chromatography-tandem mass spectrometry methods using electrospray ionization (ESI) for the quantitation of plasma total and free aprepitant and its N-dealkylated metabolites and applied it to patient plasma.
Methods: Free aprepitant and ND-AP in plasma were fractionated by centrifugal ultrafiltration. The analytes in plasma or its ultrafiltrated specimen treated by triethylamine/acetonitrile were isocratically separated on a 3-μm octadecylsilyl column with a total run time of 10 minutes and scanned with positive ion ESI.
Results: The calibration curves of total aprepitant, ND-AP, and ND-CAP ranged from 50?2500, 20?1000, and 5?250 ng/mL, respectively, while that of free aprepitant and ND-AP ranged from 2?150 ng/mL. Their intra- and inter-assay accuracy and imprecision values were 93.5 107.7% and 94.6?103.3%, and 2.1?7.5% and 1.0?8.9%, respectively. Aprepitant and its metabolites did not exhibit any matrix effects or instabilities in plasma specimens. In cancer patients receiving oral aprepitant, the plasma concentration ranges of total aprepitant, ND-AP, and ND-CAP, and of free aprepitant and ND-AP were 137?2170, 104?928, 22.4?97.6, 8.11?60.0, and 3.53?56.0 ng/mL, respectively. The median plasma free fraction rates of aprepitant and ND-AP were 4.14% and 4.90%, respectively.
Conclusions: The present methods with acceptable analytical performance can be used to evaluate total and free aprepitant and its N-dealkylated metabolites in patient plasma.journal articl
Green nut oil or DHA supplementation restored decreased distribution levels of DHA containing phosphatidylcholines in the brain of a mouse model of dementia
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies
Get PDFCorpus callosum anomalies (CCA) is a common congenital brain anomaly with various etiologies. Although one of the most important etiologies is genetic factors, the genetic background of CCA is heterogenous and diverse types of variants are likely to be causative. In this study, we analyzed 16 Japanese patients with corpus callosum anomalies to delineate clinical features and the genetic background of CCAs. We observed the common phenotypes accompanied by CCAs: intellectual disability (100%), motor developmental delay (93.8%), seizures (60%), and facial dysmorphisms (50%). Brain magnetic resonance imaging showed colpocephaly (enlarged posterior horn of the lateral ventricles, 84.6%) and enlarged supracerebellar cistern (41.7%). Whole exome sequencing revealed genetic alterations in 9 of the 16 patients (56.3%), including 8 de novo alterations (2 copy number variants and variants in ARID1B, CDK8, HIVEP2, and TCF4) and a recessive variant of TBCK. De novo ARID1B variants were identified in three unrelated individuals, suggesting that ARID1B variants are major genetic causes of CCAs. A de novo TCF4 variant and somatic mosaic deletion at 18q21.31-qter encompassing TCF4 suggest an association of TCF4 abnormalities with CCAs. This study to analyze CCA patients using whole exome sequencing, demonstrating that comprehensive genetic analysis would be useful for investigating various causal variants of CCAs.journal articl
PD-1 expression defines epidermal CD8+CD103+ T cells preferentially producing IL-17A and using skewed TCR repertoire in psoriasis
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Correlations between serum cetuximab and EGFR-related markers, and skin disorders in head and neck cancer patients
Get PDFPurpose: Cetuximab inhibits epidermal growth factor receptor (EGFR) signaling in cancer and skin cells, thereby inducing anti-cancer effects and skin disorders. The present study aimed to evaluate the relationships between serum cetuximab and EGFR-related markers, and adverse effects in head and neck cancer patients.
Methods: Thirty-four head and neck cancer patients receiving weekly intravenous cetuximab were enrolled. Serum cetuximab levels were determined just before dosing. Blood samples for determination of serum EGFR-related markers including soluble epidermal growth factor receptor (sEGFR) and interleukin-6 (IL-6) were obtained. The severities of skin disorders, their medications, and hypomagnesemia treatment were also assessed.
Results: Serum levels of cetuximab and sEGFR were negatively and positively correlated with that of IL-6, respectively. The serum cetuximab level was 2-fold higher in the patients with a grade 2–3 skin rash than with a grade 0–1 rash. The serum cetuximab cut-off value related to severe skin rash was 71 μg/mL (sensitivity, 59%; and specificity, 94%). The use of a strong topical corticosteroid for skin rash was also associated with a higher serum cetuximab level. Serum levels of sEGFR and IL-6 had no correlations with the skin disorder severities or their medications. Hypomagnesemia treatment using intravenous magnesium sulfate was not related to serum cetuximab and EGFR-related markers.
Conclusions: Head and neck cancer patients with a higher serum IL-6 level tended to have a lower serum cetuximab level. Serum cetuximab had positive correlations to skin rash severity and its medication in the study population.journal articl
Clinical outcome of condoliase injection treatment for lumbar disc herniation: Indications for condoliase therapy
Get PDFBackground
Condoliase is a novel, potent chemonucleolytic drug available for clinical use for lumbar disc herniation (LDH) in Japan. The aim of this study was to assess the clinical outcome of condoliase therapy in patients with LDH, as well as factors affecting the clinical outcome.
Methods
We enrolled patients with LDH who were receiving condoliase injection. The following baseline data were collected: symptom duration; herniation level and type; T2 signal intensity of herniation; adverse events; rates of spondylolisthesis, posterior intervertebral angle of ≥5°, and vertebral body translation of ≥3 mm. Change in disc height, disc degeneration, herniation size, visual analogue scale (VAS) for leg and back pain, and Oswestry Disability Index (ODI) were evaluated at the baseline, and 3-month follow-up. These data were compared between patients with efficacious (VAS improvement of ≥20 mm; group E) and inefficacious (VAS improvement <20 mm or required operation; group I) for condoliase treatment.
Results
Forty-seven patients (20 women, 27 men; mean age 48 years) were included. The herniation level was L2/3 in one patient, L3/4 in two, L4/5 in 23, and L5/S1 in 21. Median symptom duration was 8 months. The mean VAS and ODI improved significantly from the baseline to 3-month follow-up (p<0.01). Group E included 33 patients (70.2%) and group I included 14, three of whom had a history of discectomy. The rates of spondylolisthesis and posterior intervertebral angle ≥5° were significantly higher in group I than in group E. However, the rates of trans-ligamentous type and herniation with high signal intensity on T2-weighted images (highT2) were significantly higher in group E. Reduction of disc herniation was more frequently observed in group E.
Conclusions
Condoliase injection resulted in significantly improved symptoms in patients with LDH. Condoliase therapy was less effective for patients with a history of discectomy, spondylolisthesis, or those with a posterior intervertebral angle ≥5°, while trans-ligamentous type and high T2 herniation were associated with increased efficacy.journal articl
