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Objectives The association of preoperative RV function with hemodynamics during OPCAB or emergency conversion is not clear. The aim of this study was to investigate the association of vasoactive-inotropic score with tricuspid annular plane systolic excursion and tricuspid regurgitation in off-pump coronary artery bypass grafting, and to calculate the optimal cut-off value of tricuspid annular plane systolic excursion to predict emergency conversion to cardiopulmonary bypass. Methods Patients over 20 years of age who had undergone off-pump coronary artery bypass grafting between April 2015 and March 2020 were enrolled in this study. We retrospectively assessed the association of intraoperative maximum “vasoactive-inotropic score”, a weighted sum of various inotropes and vasoconstrictors, with tricuspid annular plane systolic excursion and tricuspid regurgitation. A receiver operating characteristic curve of conversion on tricuspid annular plane systolic excursion was also constructed. Results 135 patients were included in final analysis. Conversion was performed in 10 cases. Multiple regression analysis showed that tricuspid annular plane systolic excursion, mild or more tricuspid regurgitation and experienced surgeon were significantly related to vasoactive-inotropic score. The receiver operating characteristic curve to predict conversion by tricuspid annular plane systolic excursion showed an optimal cut-off value of 15.0 mm and area under the curve of 0.808. Conclusions Tricuspid annular plane systolic excursion and tricuspid regurgitation were associated with vasoactive-inotropic score in off-pump coronary artery bypass grafting. The optimal cut-off value of tricuspid annular plane systolic excursion to predict emergency conversion was 15 mm.

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1–3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer. In patients with ulcerative colitis, chronic inflammation can lead to remodelling of the colorectal epithelium through positive selection of clones with mutations in genes related to IL-17 signalling, which, however, might be negatively selected during colitis-associated carcinogenesis.

Background Myxedema coma, which occurs due to hypothyroidism, is a rare and life-threatening condition. Some patients have hemodynamic dysfunction, which consequently leads to cardiac arrest. The rarity of this condition makes it difficult to determine the cause of cardiac arrest. It is important to diagnose myxedema coma based on clinical findings, including physical examination and laboratory parameters. We present a case of undiagnosed and untreated hypothyroidism that initially caused myxedema coma and then led to cardiac arrest. Case presentation A 56-year-old woman who had no medical history was transferred to our hospital for the management of return of spontaneous circulation due to sudden cardiac arrest. Findings of laboratory tests revealed that she had hypothyroidism. On physical examination, she was found to have a puffy face, thin eyebrows, and severe systemic non-pitting edema. Therefore, the patient was clinically diagnosed with myxedema coma, which was the cause of cardiac arrest. She was treated with thyroid hormone and hydrocortisone, resulting in improvement in her general condition, except for the neurological dysfunction. Conclusions This case suggests that myxedema coma is caused by undiagnosed and untreated hypothyroidism, leading to sudden cardiac arrest. Our findings are useful in the differential diagnosis of hypothyroidism based on characteristic physical examination findings. Clinicians should be aware of the differential diagnosis of myxedema coma based on findings from physical examination and laboratory testing of thyroid function, and the treatment should be started immediately.

Immune-related adverse events (irAEs) are commonly observed in patients treated with immune checkpoint inhibitors (ICI), and prompt diagnosis and treatment of irAEs is of utmost importance. Gastrointestinal (GI) events are among the most frequent irAEs and the hallmark symptom is diarrhea. Intestinal hypomotility as irAEs is exceedingly rare, and needs wider recognition given that the presentation is insidious.Here, we report a case of 79-year-old woman with metastatic melanoma under nivolumab and ipilimumab combination therapy. She developed ileus symptom, and was diagnosed with acute colonic pseudo-obstruction. The symptom relieved soon after administering high-dose prednisolone five days after the onset. ICI therapy was discontinued.Intestinal hypomotility as GI irAEs is exceedingly rare and there have been five reported cases to our knowledge. In reviewing past cases, we speculate that the prompt initiation of corticosteroids resulted in a favorable outcome. Our case illustrates that early recognition of these rare irAEs is essential in order to ensure prompt treatment.

A 56-year-old man with COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation, was transferred to our hospital. He was successfully treated with dexamethasone and remdesivir, followed by favipiravir, and he was extubated on day 30. Eighteen days after admission, he developed severe watery diarrhoea (passing more than 7000 mL/day). Subsequently, he went into shock due to hypovolaemia and hypoalbuminaemia (2.3 g/dL), and norepinephrine and albumin administration were commenced. Contrast-enhanced CT showed thickening of the small and large intestinal walls without findings suggesting intestinal ischaemia, such as decreased bowel wall enhancement and mesenteric thrombosis (figure 1A). Sigmoidoscopy on day 32 (figure 1B) showed prominent detachment of the colonic mucosa, and peroral enteroscopy …

Monoclonal antibodies have accelerated the availability of treatment options for many diseases in which the molecular mechanism has been elucidated in detail. Therefore, an assay that can universally analyze antibodies for clinical pharmacokinetics and cross-sectional studies would be indispensable. We have developed a universal antibody bioanalysis with a Fab-selective tryptic reaction, named nano-surface and molecular-orientation limited (nSMOL) proteolysis, that collects the specific antibody signature peptides in biological samples. Using the nSMOL method, we have fully validated the bioanalysis of many antibodies, Fc-fusion proteins, and their biosimilars. Inflammatory immune diseases often require long-term clinical management because of the remission and relapse observed. Accurate antibody monitoring in systemic circulation could contribute to the improvement of clinical outcomes. Because several biopharmaceuticals can be selected as practical treatment options, the assay development that quantitates many antibodies simultaneously would be applicable in many theraprutic monitoring. In this study, we have validated the LC-MS bioanalysis method for seven-mixed antibodies (Infliximab, Adalimumab, Ustekinumab, Golimumab, Eculizumab, Etanercept, and Abatacept) using the nSMOL normal reaction condition and two-mixed antibodies (Tocilizumab and Mepolizumab) using the acidified reduction acceleration condition, as reported in our previous papers. Moreover, this multiplexed assay has been verified using clinical patient samples. The nSMOL approach enables the quantitation of several immunosuppressive antibodies simultaneously in human serum, and nSMOL can potentially be applicable to the drug-drug interaction assays or therapeutic antibody monitoring of several inflammatory immune diseases to optimize administration.

Background: Healthcare workers must be protected during extubation of patients with coronavirus disease 2019 (COVID-19) owing to the presence of aerosolized droplets. Herein, we report a technique for extubating a patient with COVID-19 while minimizing aerosol dispersion. Case Report: We retrospectively identified a total of 79 patients admitted to our hospital from February 2020 to January 2021. Six of these patients were intubated for mechanical ventilation, 2 of whom had to be extubated. We prepared a clear vinyl sheet in the shape of a tent to place over the patient, and 2 staff members, both well experienced in airway management, stood outside the tent on either side of the patient. Before extubation, we confirmed that the patient’s consciousness level was good and the patient had no distress by adjusting the dose of sedative drugs. After extubation, a surgical mask was placed on the patient’s face. Conclusion: Our experience indicates that this method of extubation in a patient with COVID-19 could be safely implemented to protect healthcare workers.

Background and Aims: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Methods: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Results: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti–integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti–integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6–fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. Conclusions: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity., 指定難病「潰瘍性大腸炎」の自己抗体発見 --新たな診断や治療開発へ--. 京都大学プレスリリース. 2021-03-09.

Purpose The authors previously revealed the association of the follicular fluid (FF) volume with oolemma stretchability following the gonadotropin‐releasing hormone (GnRH) antagonist protocol during intracytoplasmic sperm injection (ICSI). However, the impact of the GnRH agonist protocol on oolemma stretchability remains unclear. Methods Data that were obtained from 74 ICSI cycles were reviewed retrospectively. Controlled ovarian stimulation was performed in accordance with the short GnRH agonist protocol. Each follicle was individually aspirated and assigned to one of six groups, according to the FF volume. The oolemma stretchability during ICSI was evaluated by using a mechanical stimulus for oolemma penetration; that is, oolemma penetration with or without aspiration (high vs low stretchability, respectively). Results The incidence of low oolemma stretchability was significantly higher in the

Background Serratus plane block is a thoracic truncal block that has been proposed as alternatives for analgesia such as epidural anesthesia and paravertebral block for the anterolateral chest wall. Previously, we performed the clinical study about optimal volume of the local anesthetic in serratus plane block. The primary aim of this study was to assess the pattern of distribution of dye into the serratus plane of cadavers after ultrasound-guided serratus plane injection. Findings Ultrasound-guided serratus plane injection was performed at the level of the fourth rib on the mid-axillary line in nine adult Thiel-embalmed cadavers. In each cadaver, one side was injected with 20 ml of methylene blue dye and the contralateral side with 40 ml. Dissections of the thoracic walls were performed 20 min after the injection. The spread of the dye to intercostal nerves, lateral and medial pectoral nerves, long thoracic nerve, and thoracodorsal nerves was assessed. All T2–T5 intercostal nerves in the 40-ml group and all T3–T4 nerves in the 20-ml group were stained with the dye. A larger number of intercostal nerves was stained in the 40-ml group than that in the 20-ml group. Medial and lateral pectoral nerves were not frequently stained in either group. Conclusions The range of craniocaudal spread of the injectate was wider in the 40-ml group than that in the 20-ml group after ultrasound-guided serratus plane injection in Thiel-embalmed cadavers.

Background/Aims: Our physicians work to expand the possibilities to treat female patients with inflammatory bowel disease (IBD) who wish to become pregnant. Although many drugs, including 5-aminosalicylate (5-ASA), corticosteroids, immunomodulators, and biologics, are used safely during pregnancy, few reports have described the therapeutic regimen throughout pregnancy and the management of patients who relapse during pregnancy precisely. The aim of this study was to assess the management of patients with IBD during pregnancy.Methods: We identified 19 patients (five with Crohn's disease and 14 with ulcerative colitis [UC]) who became pregnant with a total of 23 pregnancies between May 2005 and May 2015 by reviewing the medical records of Kyoto University Hospital. The following data were collected: the maternal variables, the IBD treatment type, the disease activity, the pregnancy outcome, and the mode of delivery.Results: Among the 19 patients, 18 had become pregnant after being diagnosed with IBD, while one had developed UC newly after pregnancy. Throughout the gestation, all patients were treated with probiotics, 5-ASA, prednisolone, cytapheresis, or infliximab. The relapse rate during pregnancy was 21.7% (5/23 cases). The five patients who experienced a relapse were able to pursue their pregnancy after intensification of their treatments. There were no adverse fetal or neonatal problems, except in one case that required an emergency Caesarean section because of placental dysfunction and in which a very low-birth-weight infant was born preterm.Conclusions: Our present data confirmed that even if the disease flares up during pregnancy, good pregnancy outcomes can be achieved with an optimal intensification of the patient's treatment.

Background and study aims Diaphragm disease (DD) is a rare gastrointestinal disease featuring multiple thin, circumferential strictures in the intestine, related to prolonged intake of nonsteroidal anti-inflammatory drugs (NSAIDs). Here, we report a case of DD associated with cytomegalovirus (CMV) infection in a patient not taking NSAIDs. A 72-year-old man was referred to our hospital due to persistent epigastric pain. Push enteroscopy showed extensive mucosal detachment in the upper jejunum. Immunohistochemistry examination of biopsy specimens revealed CMV positivity. In addition, CMV antigenemia was positive. Antiviral treatment with ganciclovir improved his symptoms and the CMV antigenemia became negative. Wireless capsule enteroscopy performed 1 month after antiviral treatment showed regenerated mucosa and multiple diaphragm-like strictures in the jejunum, resulting in capsule retention. Balloon dilatation using double balloon enteroscopy (DBE) was performed and the capsule was retrieved endoscopically. DBE 6 months after antiviral therapy confirmed no recurrence of stenosis or inflammation. The patient had no history of long-term NSAID use. In a case of DD unassociated with NSAIDs, CMV infection should be considered in the differential diagnosis.

To present the characteristics and pathology of a patient with congenital achromatopsia. The patient was a 22-year-old Japanese woman who was 8 years old when she first visited our clinic. Comprehensive ophthalmic examinations including visual acuity measurements, perimetry, optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, electroretinography (ERG), and color vision tests were performed. Her genomic DNA was used as the template for the amplification of exons of five candidate genes for achromatopsia; CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H, and the amplified products were sequenced. A missense mutation, found in the CNGA3, was studied both electrophysiologically and biochemically. Her phenotype was typical of congenital complete achromatopsia. She was followed for 14 years, and her vision and fundus findings were stable. However, the scotopic ERG b-waves at age 22 were smaller than those at age 8, and her FAF images showed increased autofluorescence in both maculae. Genetic examinations revealed combined heterozygous mutations of c.997_998delGA and p.M424V in the CNGA3 gene. The homomeric channel consisting of the CNGA3 subunit with the p.M424V mutation had a weak cGMP-activated current in patch-clamp recordings. In heterologous expression analyses, the expression at the cell surface of the mutant CNGA3 subunit was about 28 % of the wild type. The two novel mutations found in the CNGA3 gene, c.997_998delGA and p.M424V, can cause complete achromatopsia. The vision of the patient was stationary until the third decade of life although the FAF was altered at the age of 22 years.

We previously identified 3-chloro-N-{(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-piperidine-2-yl]methyl}-4-(trifluoromethyl)pyridine-2-carboxamide (5, TP0439150) as a potent and orally available glycine transporter 1 (GlyT1) inhibitor. In this article, we describe our identification of 1-methyl-N-(propan-2-yl)-N-({2-[4-(trifluoromethoxy)phenyl]pyridin-4-yl}methyl)-1H-imidazole-4-carboxamide (7n) as a structurally diverse back-up compound of 5, using central nervous system multiparameter optimization (CNS MPO) as a drug-likeness guideline. Compound 7n showed a higher CNS MPO score and different physicochemical properties as compared to 5. Compound 7n exhibited potent GlyT1 inhibitory activity, a favorable pharmacokinetics profile, and elicited an increase in the cerebrospinal fluid (CSF) concentration of glycine in rats.

A novel glycine transporter 1 (GlyT1) inhibitor was designed by the superposition of different chemotypes to enhance its inhibitory activity. Starting from 2-chloro-N-{(S)-phenyl[(2S)-piperidin-2-yl]methyl}-3-(trifluoromethyl)benzamide (2, SSR504734), the introduction of heteroaromatic rings enabled an increase in the GlyT1 inhibitory activity. Subsequent optimization led to the identification of 3-chloro-N-{(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-piperidine-2-yl]methyl}-4-(trifluoromethyl)pyridine-2-carboxamide (7w), which showed a powerful GlyT1 inhibitory activity (IC50=1.8 nM), good plasma exposure and a plasma to brain penetration in rats that was sufficient to evaluate the compound's pharmacological properties. Compound 7w showed significant effects in several rodent models for schizophrenia without causing any undesirable central nervous system side effects.

Since the hypofunction of the N-methyl-D-aspartate (NMDA) receptor is known to be involved in the pathophysiology of schizophrenia, the enhancement of NMDA receptor function through glycine modulatory sites is expected to be a useful approach for the treatment of schizophrenia.We investigated the efficacy of a glycine transporter 1 (GlyT1) inhibitor that potentiates NMDA receptor function by increasing synaptic glycine levels in animal models for cognitive dysfunction and negative symptoms, both of which are poorly managed by current antipsychotics.A newly synthesized GlyT1 inhibitor, 3-chloro-N-{(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-piperidin-2-yl]methyl}-4-(trifluoromethyl)pyridine-2-carboxamide (TASP0315003) significantly improved cognitive deficit induced by MK-801 in the object recognition test in rats. Likewise, TASP0315003 significantly improved MK-801 impaired cognition in the social recognition test in rats and also enhanced social memory in treatment-naïve rats. In addition, repeated phencyclidine (PCP) treatment reduced the social interaction of paired mice, which may reflect negative symptoms such as social withdrawal, and both acute and sub-chronic treatment with TASP0315003 reversed the reduction in social interaction induced by PCP. Moreover, TASP0315003 additionally exhibited an antidepressant effect in the forced swimming test in rats. In contrast, TASP0315003 did not affect spontaneous locomotor activity or rotarod performance and did not induce catalepsy, indicating that TASP0315003 does not cause sedation or motor dysfunction, which is sometimes observed with the use of current antipsychotics.These results suggest that GlyT1 inhibitors including TASP0315003 may be useful for the treatment of cognitive dysfunction and the negative symptoms of schizophrenia without having undesirable central nervous system side effects.

Background and Objectives Serratus plane block is performed for analgesia of the anterior chest wall. However, there has been no study concerning the appropriate volume for this block. This prospective randomized controlled study assesses the dermatomal spread and analgesic effects of serratus plane block. Methods Ultrasound-guided serratus plane block was performed for breast cancer surgery. The patients were randomly assigned to receive 20 or 40 mL of 0.375% ropivacaine. The primary end point was the number of affected dermatomes as assessed by cold test and pinprick test 20 minutes after the block procedure. Secondary end points were the time until the first postoperative analgesic rescue, adverse effects, and complications. Results The number of affected dermatomes assessed by the cold test for patients receiving 40 mL of 0.375% ropivacaine was significantly larger than that for patients receiving 20 mL (P = 0.002; 6 [5–7] vs 4 [3–4] dermatomes). Similarly, with the pinprick test, the affected area was larger for the 40 mL group than for the 20 mL group (P = 0.009; 4 [2–6] vs 2 [1–3] dermatomes). There were no differences between the 2 groups in secondary end points. Conclusions Ultrasound-guided serratus plane block spread in the craniocaudal direction is more widespread with 40 mL than with 20 mL of 0.375% ropivacaine. The time until the first postoperative analgesic rescue dose was not extended by a larger volume of injection. Clinical Trials Registration UMIN Clinical Trials Registry (identifier UMIN000016549).

Brassinolide (BL) and castasterone (CS) are the representative members of brassinosteroid class of plant steroid hormone having plant growth promoting activity. In this study, eleven CS analogs bearing a variety of side chains were synthesized to determine the effect of the side chain structures on the BL-like activity. The plant hormonal activity was evaluated in a dwarf rice lamina inclination assay, and the potency was determined as the reciprocal logarithm of the 50% effective dose (ED50) from each dose-response curve. The reciprocal logarithm of ED50 (pED50) was decreased dramatically upon deletion of the C-28 methyl group of CS. The introduction of oxygen-containing groups such as hydroxy, methoxy, and ethoxycarbonyl was also unfavorable to the activity. The pED50 was influenced by the geometry of carbon-carbon double bond between C-24 and C-25 (cis and trans), but the introduction of a fluorine atom at the C-25 position of the double bond did not significantly change the activity. The binding free energy (ΔG) was calculated for all ligand-receptor binding interactions using molecular dynamics, resulting that ΔG is linearly correlated with the pED50.

OBJECTIVE Oocyte degeneration often occurs after intracytoplasmic sperm injection (ICSI), and the risk factor is low-quality oocytes. The follicular fluid (FF) provides a crucial microenvironment for oocyte development. We investigated the relationships between the FF volume aspirated from individual follicles and oocyte retrieval, oocyte maturity, oolemma stretchability, fertilization, and development. METHODS This retrospective study included data obtained from 229 ICSI cycles. Ovarian stimulation was performed according to a gonadotropin-releasing hormone antagonist protocol. Each follicle was individually aspirated and divided into six groups according to FF volume (

Although the efficacy of tacrolimus for inducing remission of refractory ulcerative colitis (UC) is established, its efficacy for maintaining remission of UC has not been evaluated.The aim of this study was to evaluate the efficacy of tacrolimus compared with thiopurines for maintaining remission in patients with refractory UC.Twenty-four UC patients treated with tacrolimus and 34 treated with thiopurines to maintain remission were enrolled as the tacrolimus group and the thiopurine group, respectively. In the tacrolimus group, 82.8% of the patients were treated with tacrolimus for induction of the remission, whereas 70% of the patients in the thiopurine group were induced remission with either corticosteroid or cytapheresis. Proportions of patients who kept steroid-free remission between the tacrolimus and the thiopurine groups were compared. Maintenance of remission using tacrolimus or thiopurines was defined as no need for other therapies other than aminosalicylates without relapse for at least 3 months. Secondarily, to determine whether the response to thiopurines affects the long-term efficacy of tacrolimus maintenance therapy, the overall cumulative relapse-free survival based on the Kaplan-Meier method was estimated in thiopurine-naive or thiopurine-intolerant patients and thiopurine-refractory ones in the tacrolimus group.Remission was successfully maintained in 17 patients (70.8%) of the tacrolimus group, and 28 patients (82.4%) of the thiopurine group. The overall cumulative relapse-free survival of thiopurine-naive or thiopurine-intolerant patients in the tacrolimus group was similar to that in the thiopurine group, and significantly higher than that of thiopurine-refractory patients in the tacrolimus group.Maintenance therapy with tacrolimus for patients with UC could be considered an alternative to thiopurine therapy.

An intraoperative fluorescence imaging (IFI) system, which can provide visual images, could be the common method for assessing graft patency intraoperatively. We conducted a prospective comparison of the diagnostic accuracy of both the fast Fourier transformation (FFT) analysis of transit-time flowmetry (TTFM) waveform and the IFI system to determine graft failure.The study included 10 saphenous vein grafts (SVGs), all of which were aortocoronary grafts. Each patient underwent isolated coronary artery bypass grafting (CABG), including conventional CABG or off-pump CABG, and then underwent X-ray angiography after CABG. When intraoperative hemodynamics had stabilized, the grafts were evaluated with both the IFI system and TTFM. Based on the obtained flow profile of TTFM, certain variables were calculated. The waveforms of TTFM were analyzed with the FFT series. Harmonic distortion (HD) was calculated from the amplitudes, and the fundamental frequency was thus determined using the FFT series.The IFI system demonstrated a satisfactory flow of all grafts. X-ray angiography demonstrated that one SVG was 75% stenosed, and the others were patent. The mean graft flow (MGF) and the pulsatility index (PI) of the patent SVGs were not significantly different from those of the stenosed SVG. The HD of the patent SVGs was significantly different from that of the stenosed SVG.The HD of the TTFM waveform can provide better diagnostic accuracy for detecting clinically significant grafts than MGF and PI of TTFM and the IFI system.

Background and Aim: Little is known about the efficacy and safety of infliximab for ulcerative colitis refractory to tacrolimus. The aim of this study was to evaluate the efficacy and safety of infliximab in the induction of remission in ulcerative colitis patients with persistent symptoms despite tacrolimus therapy. Methods: We report a retrospective, observational, single-center case series of 12 consecutively enrolled patients with ulcerative colitis refractory to tacrolimus that received infliximab therapy for the induction of remission. Eight patients received a single infusion of infliximab, and four received two or more infusions. Median follow-up duration was 16.0 months (range, 1.6–41.4 months). The clinical response was evaluated based on a modified Truelove-Witts severity index. Results: Six patients (50.0%) achieved clinical remission within 30 days. Overall cumulative colectomy-free survival was estimated to be 58.3% at 41.4 months. Adverse events included an elevation of liver enzymes (1/12; 8.3%) and a mild infusion reaction (1/12; 8.3%). No mortality occurred. Conclusions: Infliximab can induce remission in patients with ulcerative colitis who do not tolerate or respond to tacrolimus therapy.

Objective: The aim of this study was to determine the computed tomography (CT) values of various pulmonary abnormalities in cubic region of interest (ROI) and square ROI and evaluate the CT findings by histogram analysis in the ROI. Methods: The study included 89 patients with the following 8 pulmonary CT patterns: normal lung, ground-glass attenuation, fine reticular opacity, coarse reticular opacity, honeycombing, airspace consolidation, nodular opacity, and emphysema. Cubic and square ROIs were selected in each CT pattern, and 5 values (contrast, variance, entropy, skewness, and kurtosis) were calculated. Results: In the histogram of ground-glass attenuation, fine reticular opacity, and coarse reticular opacity, peaks had moved to the right compared with the normal lung. Only emphysema had higher contrast and lower entropy than the normal lung (P < 0.001). The other abnormalities had lower contrast and higher entropy than the normal lung. Conclusions: In conclusion, the shapes of histograms were characteristic of various abnormalities of the lung, and the values reflected the histogram quantitatively.

Patient dose reduction in computed tomography (CT) always results in a trade off between radiation exposure and image quality. There are few reports that estimate the relationship between image quality and X-ray exposure in CT examinations as one optimal index. The purpose of this study was to determine the optimal parameter settings enabling a low radiation exposure without compromising image quality using a particular 4-row multislice CT (MSCT) scanner (Aquilion VZ 4-slice CT scanner, Toshiba Medical Systems Corporation, Otawara, Tochigi, Japan). Normalized dose divided by image noise for helical pitches (nDNR: normalized dose to noise ratio) were calculated in consideration of beam collimation and tube current-time product. Optimal tube current-time product was calculated using the nDNR for the helical pitches based on user-defined standards of quality of the CT image. As a result, the nDNR proved to be well-supported to decrease the patient exposure in various exposure conditions of MSCT scans; however, the dose and image noise did not show a linear relation to the helical pitch. In conclusion, nDNR can be applied to patient dose reduction while keeping an acceptable image quality using a particular 4-row MSCT scanner.

The aim of this study was to evaluate the decreasing of cardiac motion artifact and whether the extent of ground-glass attenuation of idiopathic pulmonary fibrosis (IPF) was accurately assessed by electrocardiography (ECG)-triggered high-resolution computed tomography (HRCT) by 0.5-s/rotation multidetector-row CT (MDCT).ECG-triggered HRCT were scanned at the end-diastolic phase by a MDCT scanner with the following scan parameters; axial four-slice mode, 0.5 mm collimation, 0.5-s/rotation, 120 kVp, 200 mA/rotation, high-frequency algorithm, and half reconstruction. In 42 patients with IPF, both conventional HRCT (ECG gating(-), full reconstruction) and ECG-triggered HRCT were performed at the same levels (10-mm intervals) with the above scan parameters. The correlation between percent diffusion of carbon monoxide of the lung (%DLCO) and the mean extent of ground-glass attenuation on both conventional HRCT and ECG-triggered HRCT was evaluated with the Spearman rank correlation coefficient test.The correlation between %DLCO and the mean extent of ground-glass attenuation on ECG-triggered HRCT (observer A: r = -0.790, P0.0001; observer B: r = -0.710, P0.0001) was superior to that on conventional HRCT (observer A: r = -0.395, P0.05; observer B: r = -0.577, P = 0.002) for both observers.ECG-triggered HRCT by 0.5 s/rotation MDCT can reduce the cardiac motion artifact and is useful for evaluating the extent of ground-glass attenuation of IPF.

Objective: The aim of this study was to evaluate volume histogram analysis between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Methods: Sixty cases (UIP, n = 22; NSIP, n = 38) were evaluated retrospectively. Three parameters (contrast, variance, and entropy) were calculated in 3 types of regions of interest (ROIs): (a) whole lung, (b) right lower lobe, and (c) cubic ROIs. To evaluate the influence of extent of abnormal findings, the numbers of voxels with low or high density in whole lung were compared with the 3 parameters. Result: No significant differences were observed between the ROIs of whole lung and the right lower lobe. In all cubic ROIs, entropy in UIP was larger than that in NSIP (P < 0.001). The numbers of voxels with low-density areas significantly correlated with the values of contrast and entropy, whereas those with high-density areas significantly correlated with all 3 parameters. Conclusion: Volume histogram analysis for cubic ROIs may be feasible for differentiating between UIP and NSIP.

Purpose: To determine the effects of detector configuration, as well as vessel orientation, on the depiction accuracy of arterial stenosis using four-channel multidetector-row helical computed tomography (MDCT) angiography in vitro. Material and Methods: Five acrylic vessel phantoms (3 mm in diameter with 25 or 50% stenosis, or 5 mm with 25, 50, or 75% stenosis) were scanned with a four-channel MDCT scanner at five vessel orientations (0, 30, 45, 60, and 90° to the z-axis) using 4×1.25, 2.5, 3.75, and 5.0-mm detector configurations at beam pitches of 0.75 and 1.5. The percentage of stenosis was calculated by the ratio of the full width at half maximum for stenotic and non-stenotic portions of the phantom, and compared to the actual known values. Results: A detector configuration of 4×1.25 mm provided good reproducibility, as well as high accuracy for assessing vessel stenosis, while a 4×2.5-mm or wider detector configuration caused underestimations of stenosis. Although the phantoms perpendicular to the z-axis were underestimated, the errors were kept in clinically acceptable ranges using the 4×1.25-mm detector configuration. Conclusion: Four-channel MDCT accurately discerns stenosis for vessel phantoms of 3 or 5 mm in diameter at any orientation when using a detector configuration of 4×1.25 mm.

During the past decade, there has been a notable worldwide increase in the number of computed tomographic (CT) examinations. Since the radiation exposure to the patient during CT examinations is relatively high, it is important to optimize the dose so that it is set as low as possible but remains consistent with the required diagnostic image quality. Therefore we have developed a Digital Imaging and Communications in Medicine (DICOM) image-based program that calculates organ dose and effective dose values corresponding to tube current modulation. The values for primary radiation were derived from manufacturer specifications with international recommendations and from reference values (ICRP publication 60). Based on these values, organ doses can be computed by the program for arbitrary scan protocols in conventional and in spiral CT. In contrast to similar programs for CT dose assessment, our developed program can perform automatic extraction of the scan protocols from the DICOM tag. Users can easily reproduce and recalculate values by loading DICOM data without the requirement for time-consuming work. Additionally, further extensions are planned to our developed software.

The combination of cytarabine (ara-C) with fludarabine is a common approach to treating resistant acute myeloid leukemia. Success depends on a fludarabine triphosphate (F-ara-ATP)-mediated increase in the active intracellular metabolite of ara-C, ara-C 5'-triphosphate (ara-CTP). Therapy-resistant leukemia may exhibit ara-C resistance, the mechanisms of which might induce cross-resistance to fludarabine with reduced F-ara-ATP formation. The present study evaluated the effect of combining ara-C and fludarabine on ara-C-resistant leukemic cells in vitro. Two variant cell lines (R1 and R2) were 8-fold and 10-fold more ara-C resistant, respectively, than the parental HL-60 cells. Reduced deoxycytidine kinase activity was demonstrated in R1 and R2 cells, and R2 cells also showed an increase in cytosolic 5'-nucleotidase II activity. Compared with HL-60 cells, R1 and R2 cells produced smaller amounts of ara-CTP. Both variants accumulated less F-ara-ATP than HL-60 cells and showed cross-resistance to fludarabine nucleoside (F-ara-A). R2 cells, however, accumulated much smaller amounts of F-ara-ATP and were more F-ara-A resistant than R1 cells. In HL-60 and R1 cells, F-ara-A pretreatment followed by ara-C incubation produced F-ara-ATP concentrations sufficient for augmenting ara-CTP production, thereby enhancing ara-C cytotoxicity. No potentiation was observed in R2 cells. Nucleotidase might preferentially degrade F-ara-A monophosphate over ara-C monophosphate, leading to reduced F-ara-ATP production and thereby compromising the F-ara-A-mediated potentiation of ara-C cytotoxicity in R2 cells. Thus, F-ara-A-mediated enhancement of ara-C cytotoxicity depended on F-ara-ATP accumulation in ara-C-resistant leukemic cells but ultimately was associated with the mechanism of ara-C resistance.

Three castasterone (CS) derivatives with varied side-chain moieties, 26,27-bisnorcastasterone (20S-bisnorCS), 20-epi-26,27-bisnorcastasterone (20R-bisnorCS), and 21,26,27-trisnorcastasterone (trisnorCS), were synthesized stereoselectively from either stigmasterol or dehydroisoandrosterone. The 50% effective doses (ED50, nmol/plant) in the concentration–response curve for brassinolide-like activity in the rice lamina inclination assay were determined to be 0.020 nmol (pED50 = 10.7) for 20S-bisnorCS, 3.2 nmol (pED50 = 8.5) for 20R-bisnorCS, and 2.0 nmol (pED50 = 8.7) for trisnorCS. An analog containing an ester linkage between the steroid and the side-chain moiety of 20S-bisnorCS was also synthesized and its activity was evaluated to be 3.2 nmol (pED50 = 8.5), being equipotent to 20R-bisnorCS and trisnorCS. The activity of 20S-bisnorCS was 1/40 that of CS. The conformation analysis was conducted using a systematic search, showing that the activity decreases with an increase in the degree of freedom of the side chain of the steroidal skeleton.

OBJECTIVES : The aim of this study was to achieve the quantitative analysis of the characteristic computed tomography (CT) findings and course of interstitial pneumonia using the volume histogram method. METHODS : Contrast (CNT), variance (VAR), and entropy (EPY) values from whole-lung volume data were compared between normal lungs and 5 diseases that have characteristic CT findings. Thirteen cases with nonspecific interstitial pneumonia (NSIP) were evaluated before and after treatment. RESULTS : In cases with thickening of the bronchovascular bundles and interlobular thickening, ground-glass attenuation, airspace consolidation, and honeycombing, the values of VAR and EPY were greater than those in the normal cases (P < 0.05). In the cases with NSIP, the CNT value after treatment was significantly greater and the values of VAR and EPY after treatment were significantly lower than those before treatment (P < 0.05). CONCLUSIONS : Volume histogram analysis is a promising method for the evaluation of diffuse lung diseases and the effectiveness of treatment.

During the past decade, there has been a notable increase in the number of computed tomographic (CT) examinations be across the world. In CT angiography, the vessels are imaged by using thin-collimation multislice CT scanning while a bolus of contrast medium is intravenously injected at a high rate to achieve a high degree of vascular enhancement. For acquisition of constant density of cardiovascular organs, we developed a mathematic algorithm for a multiphasic injection method that would provide uniform, prolonged vascular contrast enhancement for spiral CT angiography. Additionally, we applied the computer fluid dynamics (CFD) to the patient specific model of abdominal aortic aneurysm. In these studies, optimal results are obtained with good quality of CT image and the patient specific cardiovascular modeling in CFD.

北海道・十勝医療圏における過去4年間(平成13年1月～平成16年12月)の院外心停止症例について,ウツタイン様式に基づいて解析・検討した。4年間に圏内で発生した院外心停止症例の総数は952例で,そのうちウツタイン様式で患者情報を収集できたのは757例であった。757例中,心原性心停止,非心原性心停止,外因性心停止の数はそれぞれ400例(52.8%), 127例(16.8%), 230例(30.4%)で,心原性心停止の割合は国内他報告と同様であった。目撃された心原性心停止は165例で,社会復帰できたのは4例(2.4%)であった。初回心電図が心室細動であった症例は43例(5.7%)で,その割合は国内他報告と同等であるが,海外の報告と比較すると低い値であった。十勝医療圏における課題として,初回心電図が心室細動である症例がこの4年間で増えていないこと,医療圏面積が広いため,国内他地域の報告と比較して覚知～救急隊現着(平均8分)や病院搬送(平均27分)に時間がかかること,bystander CPR施行率が32.1%と低いこと,救急救命士の特定行為指示要請体制の整備不足などが示唆された。社会復帰率を向上させるために,これらの課題を改善していく必要があると思われた。

Isolated traumatic tricuspid valve regurgitation is an uncommon complication of blunt chest trauma. Tricuspid valve replacement has been ordinarily managed for this lesion. Herein, we report two cases of successful repair for traumatic tricuspid valve regurgitation, 11 and 40 years following blunt chest trauma, respectively. Tricuspid valve repairs were performed using an artificial chordae implantation with expanded polytetrafluoroethylene (CV-5) sutures and ring annuloplasty. Postoperative echocardiography revealed that the tricuspid valve regurgitation improved to mild and trivial respectively in two patients. They are presently doing well, 4 and 2 years after the repair, respectively.

Purpose Only 2 mutations in the arrestin gene have been previously reported to be associated with Oguchi's disease, a homozygous Asn309(1-bp del) mutation in Japanese families and a homozygous Arg193stop mutation in an Indian family. The aim of this article is to report 2 novel mutations in the arrestin gene in 2 Japanese patients with Oguchi's disease and to describe the clinical features with the mutations. Design Molecular genetic study and observational case report. Participants Two unrelated Japanese patients with Oguchi's disease associated with novel arrestin mutations. Methods Genomic DNA was extracted from leukocytes of the peripheral blood, and exons 2 through 16 of the arrestin gene were amplified by polymerase chain reaction and directly sequenced. A complete ophthalmologic examination was performed, including best-corrected visual acuity, slit-lamp and fundus examinations, fundus photography, and electroretinography (ERG). Main outcome measures Direct sequencing of the arrestin gene, evaluation of visual acuity, refraction, and ERG. Results Three arrestin gene mutations were identified in 2 patients. A compound heterozygous mutation, Arg175stop and Asn309(1-bp del), was identified in 1 patient with Oguchi's disease. The former mutation has not been reported, whereas the latter is known to be a frequent mutation in Oguchi's disease in Japanese families. In a second patient, another novel mutation was detected in the gene, a homozygous Arg292stop mutation. Both patients demonstrated characteristic features of Oguchi's disease, including night blindness, golden-yellow discoloration of the retina, absent rod ERG response, and "negative" type bright-flash ERG after 30 minutes of dark adaptation. Conclusions The existence of 2 novel mutations of the arrestin gene in 2 unrelated Japanese patients strongly supports the previous data that arrestin gene mutations are associated with Oguchi's disease. All of the mutations in the arrestin gene that have been identified in Oguchi's disease are null mutations, indicating that only critical gene defects in the arrestin gene are associated with Oguchi's disease.