[Early Detection of and Initial Response to Oxaliplatin-Related Hypersensitivity Reactions].

Oxaliplatin(L-OHP)-related hypersensitivity reactions(HSRs)may be fatal due to bronchospasm, dyspnea, and hypotension. Therefore, management of HSRs is extremely important, and a prompt and appropriate response is required when HSRs develop. To clarify the importance of early detection and an appropriate initial response to HSRs, we retrospectively investigated the expression of HSRs and subsequent response in patients using L-OHP from April 2016 to December 2017 at the outpatient chemotherapy center of Nagasaki Medical Center. HSRs were observed in 14/155 cases(one case of Grade 1 HSRs and 13 cases of Grade 2 HSRs). No significant risk factors were identified in individuals with and without HSRs. HSRs devel- oped following a median of 7.9(2-11)courses of chemotherapy and a median 687.8(75.4-960.2)mg/m2 cumulative dose. Half of the patients were able to recognize the hypersensitivity early by themselves. Furthermore, nurses were able to implement an appropriate initial response. Early detection and an appropriate early response to HSRs can possibly prevent the severity of symptoms.

A prospective, observational, multicenter study on risk factors and prophylaxis for low emetic risk chemotherapy-induced nausea and vomiting.

PURPOSE: The incidence of and the risk factors for nausea and vomiting in patients undergoing low emetic risk chemotherapy (LEC) are unclear. The aim of the study was to provide information on these topics by performing a multicenter, observational, prospective study. METHODS: The study consisted of patients who were administered first-time LEC that was consistent or inconsistent with current guidelines. Using the visual analog scale, patients recorded their daily food intake and the occurrence and severity of nausea over a 5-day treatment period. RESULTS: The overall incidence of chemotherapy-induced nausea and vomiting did not differ significantly between patients undergoing guideline-consistent (n = 89) or guideline-inconsistent (n = 121) prophylaxis (30.3 vs. 22.3%, respectively; P = 0.19). Logistic regression analysis identified a history of nausea and LEC other than taxanes as independent risk factors associated with nausea and vomiting in patients undergoing LEC. The mean daily visual analog scale scores for nausea severity and a decrease in food intake were <25 mm throughout the entire observation period. CONCLUSIONS: Guideline-consistent prophylaxis appeared to control nausea and vomiting effectively in patients undergoing LEC. However, patients with a history of nausea and receiving LEC other than taxanes should be carefully observed and treatment should be adjusted according to their symptoms.

Large-Scale Moth-Eye-Structured Roll Mold Fabrication Using Sputtered Glassy Carbon Layer and Transferred Moth-Eye Film Characterization.

Currently, there is high demand for the development of a highly mass-producible technology for manufacturing moth-eye-structured films with an antireflection function. Conventional moth-eye-structured films have been produced by roll-to-roll (RTR) ultraviolet nanoimprint lithography (UV-NIL) using porous alumina, but the process of manufacturing the roll mold with aluminum is both complicated and time-consuming. To solve this problem, we proposed a sputtering process for forming a thin film of glassy carbon on a roll substrate and fabricated a moth-eye structure through the irradiation of oxygen plasma. A glassy carbon (GC) moth-eye-structure roll mold with a uniform reflectance of less than 0.1% over a length of 1560 mm was fabricated following this method. In addition, a superhydrophobic moth-eye-structured film was produced by RTR UV-NIL using the proposed roll mold, which exhibited a reflectance of 0.1%. In this study, a moth-eye-structure roll using porous alumina was compared with a film transferred from it. The GC moth-eye-structure roll mold was found to be superior in terms of antireflection, water repellency, and productivity. When the proposed large-area GC moth-eye-structured film was applied to window glass, significant anti-reflection and water-repellent functionalities were obtained.

Control of swelling height of Si crystal by irradiating Ar beam.

It has been found that ion implantation can induce a swelling (step-height) phenomenon on crystal surface. In this paper, we studied about the control of swelling height of Si crystal by irradiating Ar beam under various parameters (fluence, charge and energy). These irradiation parameters were regulated by an irradiation facility that enables to achieve the multiple ionization. For both charges, the swelling height was studied with the various fluencies of two different charges Ar(1+) and Ar(4+). The swelling height increased with increasing the fluence. The swelling height was also studied by changing energy of Ar(4+) beam. The swelling height increased by increasing the energy. The obtained swelling heights are understood base on the contribution of ion-beam induced defect, which is evaluated by SRIM. By comparing with the previous results, it was found that the expansion phenomena also depend on irradiated ion. The swelling structures were found to be stable more than two months. The present results have shown that this method of producing swelling structure indicates the potential application to fabricate 3-D nanostructure.

Transfer Durability of Line-Patterned Replica Mold Made of High-Hardness UV-Curable Resin.

Ultraviolet nanoimprint lithography (UV-NIL) requires high durability of the mold for the mass production of nanostructures. To evaluate the durability of a line-patterned replica mold made of high-hardness UV curable resin, repetitive transfer and contact angle measurements of the replica mold were carried out. In the line patterns, as the contact angle decreases due to repeated transfer, capillary action occurs, and water flows along them. Therefore, it can be said that a mold with a line pattern exhibits an anisotropic contact angle because these values vary depending on the direction of the contact angle measurement. Subsequently, these anisotropic characteristics were investigated. It was determined that it was possible to predict the lifetime of line-and-space molds over repeated transfers. As the transcription was repeated, the contact angle along the line patterns decreased significantly before becoming constant. Moreover, the contact angle across the line pattern decreased slowly while maintaining a high contact angle with respect to the contact angle along the line pattern. The contact angle then decreased linearly from approximately 90°. The mold was found to be macroscopically defect when the values of the contact angle along the line pattern and the contact angle across the line pattern were close. Predicting the mold's lifetime could potentially lead to a shortened durability evaluation time and the avoidance of pattern defects.

Influence of proton pump inhibitors and H2-receptor antagonists on the efficacy and safety of dasatinib in chronic myeloid leukemia patients.

We evaluated the effect of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) on the efficacy and safety of dasatinib for chronic-phase chronic myeloid leukemia (CP-CML). Retrospective analyses were performed for patients with CP-CML who received dasatinib at seven hospitals between April 2009 and December 2016. Seventy-three patients were identified, 16 of whom received PPIs or H2RAs concurrently with dasatinib. Major molecular response at 12 months was observed in 13 of 13 patients (100%) with concurrent PPIs or H2RAs (combination group), and in 23 of 51 patients (45.1%) who received only dasatinib (dasatinib-alone group; P < 0.001). Deep molecular response at 12 months was observed in four of six patients (66.7%) in the combination group, and seven of 38 patients (18.4%) in the dasatinib-alone group (P = 0.027). Dasatinib chemotherapy was stopped after 18 months for 25 patients (43.9%) from the dasatinib-alone group, but for none from the combination group. Combination treatment with PPIs or H2RAs did not reduce the efficacy of dasatinib. PPIs and H2RAs reduce the incidence of dasatinib discontinuation due to adverse events and increase the efficacy of dasatinib chemotherapy for patients.

Fabrication of non reflective structure on glassy carbon surface using oxygen ion beam irradiation.

Oxygen ion beam irradiation of glassy carbon (GC) surface is used to fabricate anti-reflection (AR) structures. Ion beam energy of 500 eV has been used to fabricate the finest pitch of AR structures in an irradiation time of 24 min or more. It has been used to fabricate conical AR structures of more than 250 nm in height, and has non-reflective (less than 0.1% reflection) property over the range of visible light. Furthermore, with this method, oblique incident angle reflection has been suppressed. This method is very simple. However, fabrication of AR structures with high throughput is needed, that is now considered achievable.

Effect of post exposure bake in inorganic electron beam resist and utilizing for nanoimprint mold.

A high-aspect-ratio structural mold has been fabricated using a simple process that comprises of electron beam lithography (EBL) and post exposure bake (PEB) of inorganic resist. Using developed inorganic resist for mold, pattern transfer to a photo-curable polymer was carried out by ultraviolet nanoimprint lithography (UV-NIL). The developed inorganic resist has enough hardness to be used for mold because this resist structure is almost equivalent to that of quartz. The aspect ratio of the fabricated mold with PEB was 2.59; this value is twice the size of aspect ratio of fabricated mold without PEB (1.16). Thus, PEB is very effective in fabricating high-aspect ratio pattern in inorganic resist. The size of the fabricated mold with PEB was 1004 nm developed depth and 388 nm line and 252 nm space. Using the mold, UV-NIL was carried out. The size of replicated pattern was 942 nm height and 278 nm line and 241 nm space. The replicated height and line width were slightly smaller than mold depth and line width because of volume shrinkage of photo-curable polymer by UV irradiation. The aspect ratio of the replicated pattern using the mold with PEB was 3.39; thus, high-aspect-ratio transfer was also possible. This process is useful for rapid fabrication of quarter wavelength plates.

Comparative Study of Performance using Five Different Gamma-ray Spectrometers for Thyroid Monitoring under Nuclear Emergency Situations.

A performance test was carried out using five different gamma-ray spectrometers applicable to thyroid monitoring. The energy resolution and efficiency for 7.6-cm × 7.6-cm NaI(Tl), 5.1-cm × 5.1-cm CeBr3, 3.8-cm × 3.8-cm SrI2(Eu), and 2.5-cm × 2.5-cm SrI2(Eu) gamma-ray scintillation spectrometers and a CdTe gamma-ray semiconductor spectrometer were evaluated using the Oak Ridge Institute for Nuclear Studies thyroid-neck phantom with a mock I source for prompt thyroid monitoring after a nuclear emergency. The respective energy resolutions of the full-energy peak for ~0.360 MeV of 3.8-cm × 3.8-cm SrI2(Eu) and 2.5-cm × 2.5-cm SrI2(Eu) scintillation spectrometers were 4.2% and 4.3%, and these values were very close to the value obtained by the CdTe semiconductor spectrometer. The efficiencies of four of the gamma-ray spectrometers were compared based on the efficiency of the 7.6-cm × 7.6-cm NaI(Tl) scintillation spectrometer at 0 cm from the phantom surface, and these values were ~70% for 5.1-cm × 5.1-cm CeBr3, ~30% for 3.8-cm × 3.8-cm SrI2(Eu), 10% for 2.5-cm × 2.5-cm SrI2(Eu) and 2% for 1-cm × 0.1-cm CdTe. Furthermore, the detection limits at various dose rates for the four gamma-ray scintillation spectrometers were evaluated using the method based on International Organization for Standardization publication ISO 11929:2010.

Highly charged ion beam applied to lithography technique.

In various fields of nanotechnology, the importance of nanoscale three-dimensional (3D) structures is increasing. In order to develop an efficient process to fabricate nanoscale 3D structures, we have applied highly charged ion (HCI) beams to the ion-beam lithography (IBL) technique. Ar-ion beams with various charge states (1+ to 9+) were applied to fabricate spin on glass (SOG) and Si by means of the IBL technique. The Ar ions were prepared by a facility built at Kochi University of Technology, which includes an electron cyclotron resonance ion source (NANOGAN, 10 GHz). IBL fabrication was performed as a function of not only the charge state but also the energy and the dose of Ar ions. The present results show that the application of an Ar(9+) beam reduces the etching time for SOG and enhances the etching depth compared with those observed with Ar ions in lower charged states. Considering the high-energy deposition of HCI at a surface, the former phenomena can be understood consistently. Also, the latter phenomena can be understood based on anomalously deep structural changes, which are remarkable for glasses. Furthermore, it has also been shown that the etching depth can be easily controlled with the kinetic energy of the Ar ions. These results show the possibilities of the IBL technique with HCI beams in the field of nanoscale 3D fabrication.

Clinical training: a simulation program for phlebotomy.

BACKGROUND: Basic clinical skills training in the Japanese medical education system has traditionally incorporated on-the-job training with patients. Recently, the complementary use of simulation techniques as part of this training has gained popularity. It is not known, however, whether the participants view this new type of education program favorably; nor is the impact of this program known. In this study we developed a new simulation-based training program in phlebotomy for new medical residents and assessed their satisfaction with the program METHODS: The education program comprised two main components: simulator exercise sessions and the actual drawing of blood from other trainees. At the end of the session, we surveyed participant sentiment regarding the program. RESULTS: There were 43 participants in total. In general, they were highly satisfied with the education program, with all survey questions receiving scores of 3 or more on a scale of 1-5 (mean range: 4.3 - 4.8), with 5 indicating the highest level of satisfaction. Additionally, their participation as a 'patient' for their co-trainees was undertaken willingly and was deemed to be a valuable experience. CONCLUSION: We developed and tested an education program using a simulator for blood collection. We demonstrated a high satisfaction level among the participants for this unique educational program and expect that it will improve medical training, patient safety, and quality of care. The development and dissemination of similar educational programs involving simulation for other basic clinical skills will be undertaken in the future.

Two cases of numb chin syndrome diagnosed as malignant disease.

Numb chin syndrome (NCS) is defined as reduced or absent sensation in an area of the chin and lower lip within the distribution of the mental or inferior alveolar nerves. The causes of NCS may be neoplastic, traumatic, dental, toxic, drug-induced, inflammatory, autoimmune or infectious. NCS may be the preliminary symptom of malignancy or recurrence/metastasis in patients with cancer. Therefore, the occurrence of NCS warrants careful examination and monitoring of such patients. This article presents two cases of NCS reported in a patient with prostate cancer and in a patient with Burkitt lymphoma/leukaemia.

Risk factors for delayed chemotherapy-induced nausea and vomiting with low-emetic-risk chemotherapy: a prospective, observational, multicenter study.

PURPOSE: Improvement in the control of delayed chemotherapy-induced nausea and vomiting (CINV) is needed. There is limited information on antiemetic prophylaxis for patients undergoing low-emetic-risk chemotherapy (LEC), and the optimal antiemetic treatment is not well understood. Therefore, we analyzed the risk factors for delayed CINV to aid in the development of individualized treatments. PATIENTS AND METHODS: This prospective multicenter study was conducted in 13 hospitals and included patients with solid cancers undergoing LEC. A total of 222 patients were enrolled between September 2013 and November 2014. The participants completed a daily diary for 5 days after the commencement of the first cycle of LEC to describe the daily incidence of CINV (yes/no). Furthermore, the participants described the severity of nausea and the amount of food intake with the help of VAS. RESULTS: Two hundred and ten patients provided their data that were analyzed using multivariate logistic regression to examine the risk factors for delayed CINV. History of CINV, Eastern Cooperative Oncology Group performance status score ≥1, acute CINV, and single-day antiemetic prophylaxis were identified as independent risk factors for delayed CINV. CONCLUSION: The current use of antiemetic prophylaxis according to the recommended guideline appears to effectively control delayed CINV in patients undergoing LEC. Therefore, patients with the abovementioned risk factors should be carefully observed, and their treatment should be adjusted according to their symptoms. The use of multiple-day dexamethasone may be beneficial for those patients who develop acute CINV, especially when it is accompanied by anorexia.

How Different Respiratory Rate Patterns affect Cardiorespiratory Variables and Performance.

This study aims to elucidate how respiratory rate (RR) patterns may affect respiratory gas exchange variables and performance during incremental intensity- exercise. 10 healthy young men (mean ± SD, age: 20.7 ± 0.5 years, height: 174.3 ± 5.7 cm, and body mass: 72.6 ± 10.4 kg) performed three incremental tests on a cycle ergometer at three different RR (60, 45 and 30 breaths per min) in each trial. During the tests, tidal volume (TV), minute ventilation (VE), fractional content of oxygen (FeO2), fractional content of carbon dioxide (FeCO2), oxygen uptake (VO2), expiratory carbon dioxide (VCO2), equivalent of oxygen (EqO2), VE/VCO2, and respiratory exchange ratio (RER) were determinate breath-by-breath. Additionally, exercise time (as a performance marker) was measured. Statistical analyses for the results were carried out to determine significant differences between the three trials. VCO2, VO2, and exercise time did not show statistical differences in the three trials. Therefore, we concluded that RR affects some respiratory gas exchange variables but does not influence the VO2max and endurance performance.

High glycated albumin (GA) levels and the GA/HbA1c ratio in patients with insulin autoimmune syndrome.

Insulin autoimmune syndrome (IAS) involves not only fasting hypoglycemia, but also postprandial hyperglycemia. In the present study, we hypothesized that glycated albumin (GA) levels and the GA/HbA1c ratio, which reflect fluctuations in plasma glucose levels, are elevated in IAS patients. Four IAS patients were enrolled in the present study. Thirty-two non-diabetic subjects matched for gender, age, and BMI were used as the control group. The fasting plasma glucose levels in the IAS patients were significantly lower than in the control group. However, the oral glucose tolerance test (OGTT) revealed impaired glucose tolerance or diabetes mellitus in all the IAS patients, and thus the OGTT 2-h plasma glucose levels were significantly higher than in the control group. The GA levels and the GA/HbA1c ratio in the IAS patients were significantly higher than in the control group, despite no significant difference in the HbA1c levels between the two groups. In one case in which IAS spontaneously went into remission, there was a significant correlation between anti-insulin antibodies and GA, but not HbA1c. Improvement in glucose fluctuations was observed by continuous glucose monitoring in another patient along with improvement in the clinical symptoms. Furthermore, anti-insulin antibodies, GA, and the GA/HbA1c ratio decreased, but HbA1c did not change significantly in three IAS patients along with the improvement in clinical symptoms. These results suggest that GA and the GA/HbA1c ratio are useful indicators for determining the level of disease activity in IAS patients.

Hypothyroidism changes adrenoceptor- and muscarinic receptor-mediated blood pressure responses.

Hypothyroidism was induced by the administration of 0.03% methimazole to drinking water for 1, 2 or 6 weeks to study whether there is a change in adrenoceptor- and muscarinic receptor-mediated blood pressure responses in hypothyroid rats. After 1, 2 and 6 weeks of treatment, the pressor response to norepinephrine was progressively suppressed, and after 6 weeks a significant suppression was observed as compared to control. The depressor response induced by isoprenaline, acetylcholine or sodium nitroprusside was not significantly different between control and hypothyroid rats at any time. The pressor response induced by N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide (NO) synthase, was significantly reduced in hypothyroid rats after 1, 2 or 6 weeks of treatment, and the magnitude of the reduction was almost the same for three groups. These results indicated that hypothyroidism causes a time-dependent decrease in pressor responses mediated by alpha-adrenoceptors, but a time-independent decrease in those induced by L-NOARG, and suggest that a progressive decrease in alpha-adrenoceptor-mediated pressor responses occurs in hypothyroidism; however, the decrease in basal NO production and/or release in the peripheral vasculature already occurs in hypothyroid rats at an early stage of the disease.

Alteration in endothelial function and modulation by treatment with pioglitazone in rabbit renal artery from short-term hypercholesterolemia.

The present study was undertaken to investigate endothelial function and epoxyeicosatrienoic acids (EETs), which is a cytochrome P-450 monooxygenase (CYP) metabolite and one of the candidates as an endothelium-derived hyperpolarizing factor (EDHF) in the renal artery isolated from short-term hypercholesterolemic rabbits, and also to characterize the effects of pioglitazone on it. Rabbits were fed normal, 0.5% cholesterol chow, or 0.5% cholesterol chow plus 300 ppm pioglitazone for 5 weeks. The tension of isolated renal artery rings was measured isometrically. Serum lipid levels were measured and morphometric analysis was performed. EET contents in the renal artery were also determined. The cholesterol chow diet for 5 weeks increased serum lipid levels, and pioglitazone had no influence on it. In the phenylephrine precontracted renal artery, the cholesterol chow did not affect acetylcholine-induced relaxation. The N(G)-nitro-l-arginine- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine was significantly enhanced in rabbits receiving the cholesterol chow as compared to rabbits receiving the control diet, and pioglitazone normalized it. The resistant part of acetylcholine-induced relaxation was significantly inhibited when the renal artery was treated with charybdotoxin, an inhibitor of large- and intermediate-conductance Ca(2+)-activated K(+) channels, or N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a nonselective CYP inhibitor, and it was significantly inhibited by sulfaphenazole, a selective CYP2C9 inhibitor in rabbits receiving only the cholesterol chow. In KCl-precontracted renal artery, the cholesterol chow inhibited acetylcholine-induced relaxation and pioglitazone normalized it. The cholesterol chow increased the production of EETs and reduced nitrate/nitrite contents in the renal artery, and pioglitazone strongly suppressed them. These results suggest that the EETs may be one of the EDHFs in the rabbit renal artery and beneficial effects of pioglitazone on alterations in endothelial function induced by cholesterol feeding are due, in part, to the protective action on the nitric oxide system and/or the suppression of increased production of EETs.

Rapid and simple determination of epoxyeicosatrienoic acids in rabbit renal artery by reversed-phase HPLC with fluorescence detection.

A liquid chromatographic method with fluorescence detection coupled with a solid-phase extraction was applied to the rapid determination of epoxyeicosatrienoic acids (EETs) in the rabbit renal artery. The EETs were extracted with an acetonitrile from renal artery homogenate and concentrated by a solid-phase extraction method. The concentrated EETs were reacted directly with a 6, 7-dimethoxy-1-methyl-2 (1H)-quinoxalinone-3-propionyl-carboxylic acid (DMEQ) hydrazide and separated by a reversed-phase HPLC with eluting a combination of a step-wise and a gradient of a mixture of methanol and water. The content of EETs in the renal arteries was significantly greater in the 0.5% cholesterol fed rabbits than in control rabbits. It is suggested that hyperchlesterolemia increases the production of EETs in the rabbit renal artery.

Fabricating a high-resolution mask with improved line-edge roughness by using a nonchemically amplified resist and a postexposure bake.

The authors have developed a high-resolution technique for fabricating photomasks at the 10-nm half-pitch logic nodes and beyond. Current mask-manufacturing techniques use a chemically amplified resist (CAR) that has a complex mechanism of acid generation, complicating the criteria for selecting the polymer and the quencher for industrial purposes. Thus, it is important to study fabricating masks with non-CARs. The authors exposed a non-CAR, diluted ZEP520A, to variable-shaped electron-beam lithography and used a postexposure bake (PEB) to modify the resist. Studying how the PEB temperature affected the non-CAR and resultant masks, the authors demonstrate that their technique can produce high-resolution structures. By measuring the critical dimensions (CDs), the authors show that the PEB shrunk, enlarged, and retained the size of 1:1 line-and-space, isolated space, and isolated line patterns, respectively. By optimizing the PEB temperature, the authors improved the line-edge roughness (LER) of the 1:1 line-and-space and isolated space CDs by ∼40%. To understand how the PEB affected the resultant structures, the authors measured the hardness of cured resists with and without a PEB at various temperatures. Optimizing the PEB temperature of the non-CAR increased the resist contrast, annealing the resist and improving the LER. As such, their technique is capable of high resolutions on the order of 20 nm. The insights the authors gained from optimizing the PEB might be useful when fabricating next-generation masks.

Remitting seronegative symmetrical synovitis with pitting edema syndrome in individuals with type 2 diabetes mellitus or impaired glucose tolerance.

An association between remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and insulin or dipeptidyl peptidase-4 (DPP4) inhibitor therapy were previously reported. We encountered four cases of RS3PE syndrome with type 2 diabetes mellitus or impaired glucose tolerance (IGT) without insulin or DPP4 inhibitor medication.