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Suvorexant (Belsomra(R)), a dual orexin receptor antagonist widely used in the treatment of insomnia, inhibits the arousal system in the brain. However, the drug’s ventilatory effects have not been fully explored. This study aims to investigate the expression of orexin receptors in respiratory neurons and the effects of suvorexant on ventilation. Immunohistology of brainstem orexin receptor OX2R expression was performed in adult mice (n = 4) in (1) rostral ventral respiratory group (rVRG) neurons projecting to the phrenic nucleus (PhN) retrogradely labeled by Fluoro-Gold (FG) tracer, (2) neurons immunoreactive for paired like homeobox 2b (Phox2b) in the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN), and (3) neurons immunoreactive for neurokinin 1 receptor (NK1R) and somatostatin (SST) in the preBötzinger complex (preBötC). Additionally, we measured in vivo ventilatory responses to hyperoxic hypercapnia (5% CO2) and hypoxia (10% O2) before and after suvorexant pretreatment (10 and cumulative 100 mg/kg) in unrestrained mice (n = 10) in a body plethysmograph. We found the OX2R immunoreactive materials in pFRG/RTN Phox2b and preBötC NK1R/SST immunoreactive neurons but not in FG-labeled rVRG neurons, which suggests the involvement of orexin in respiratory control. Further, suvorexant expressly suppressed the hypercapnic ventilatory augmentation, otherwise unaffecting ventilation. Central orexin is involved in shaping the hypercapnic ventilatory chemosensitivity. Suppression of hypercapnic ventilatory augmentation by the orexin receptor antagonist suvorexant calls for caution in its use in pathologies that may progress to hypercapnic respiratory failure, or sleep-disordered breathing. Clinical trials are required to explore the role of targeted pharmacological inhibition of orexin in ventilatory pathologies.

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., 「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.

In the field of respiratory clinical practice, the importance of measuring carbon dioxide (CO2) concentrations cannot be overemphasized. Within the body, assessment of the arterial partial pressure of CO2 (PaCO2) has been the gold standard for many decades. Non-invasive assessments are usually predicated on the measurement of CO2 concentrations in the air, usually using an infrared analyzer, and these data are clearly important regarding climate changes as well as regulations of air quality in buildings to ascertain adequate ventilation. Measurements of CO2 production with oxygen consumption yield important indices such as the respiratory quotient and estimates of energy expenditure, which may be used for further investigation in the various fields of metabolism, obesity, sleep disorders, and lifestyle-related issues. Measures of PaCO2 are nowadays performed using the Severinghaus electrode in arterial blood or in arterialized capillary blood, while the same electrode system has been modified to enable relatively accurate non-invasive monitoring of the transcutaneous partial pressure of CO2 (PtcCO2). PtcCO2 monitoring during sleep can be helpful for evaluating sleep apnea syndrome, particularly in children. End-tidal PCO2 is inferior to PtcCO2 as far as accuracy, but it provides breath-by-breath estimates of respiratory gas exchange, while PtcCO2 reflects temporal trends in alveolar ventilation. The frequency of monitoring end-tidal PCO2 has markedly increased in light of its multiple applications (e.g., verify endotracheal intubation, anesthesia or mechanical ventilation, exercise testing, respiratory patterning during sleep, etc.).

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

Obstructive sleep apnea (OSA) patients are at risk for increased blood pressure and carotid intima-media thickness (IMT), with pulmonary hypertension and right-sided heart failure potentially developing as well. Chronic intermittent hypoxia (IH) has been used as an OSA model in animals, but its effects on vascular beds have not been evaluated using objective unbiased tools. Previously published and current experimental data in mice exposed to IH were evaluated for IMT in aorta and pulmonary artery (PA) after IH with or without normoxic recovery using software for meta-analysis, Review Manager 5. Because IMT data reports on PA were extremely scarce, atherosclerotic area percentage from lumen data was also evaluated. IH significantly increased IMT parameters in both aorta and PA as illustrated by Forest plots (P < 0.01), which also confirmed that IMT values after normoxic recovery were within the normal range in both vascular beds. One-sided scarce lower areas in Funnel Plots were seen for both aorta and PA indicating the likelihood of significant publication bias. Forest and Funnel plots, which provide unbiased assessments of published and current data, suggest that IH exposures may induce IMT thickening that may be reversed by normoxic recovery in both aorta and PA. In light of the potential likelihood of publication bias, future studies are needed to confirm or refute the findings. In conclusion, OSA may induce IMT thickening (e.g., aorta and/or PA), but the treatment (e.g., nasal continuous positive airway pressure) will likely lead to improvements in such findings.

ATP-sensitive potassium (KATP) channels consist of two structurally different subunits: a pore-forming subunit of the Kir6.0-family (Kir6.1 or Kir6.2) and a regulatory sulfonylurea receptor subunit (SUR1, SUR2A or SUR2B). Although Kir6.2 is widely distributed in the brain, the mechanisms that underlie the impact of Kir6.2 on emotional behavior are not yet fully understood. To clarify the role of Kir6.2 in emotional behavior, in the present study, we investigated the behavioral characteristics of Kir6.2-knockout (Kir6.2-/-) mice. Kir6.2-/- mice showed impaired general behavior in a locomotor activity test and open field test. In addition, anxiety-like behavior was observed in the open field test, elevated plus-maze test and light-dark test. In particular, excessive anxiety-like behavior was observed in female Kir6.2-/- mice. Moreover, we investigated whether Kir6.2 is expressed on monoamine neurons in the brain. Immunohistochemical studies showed that Kir6.2 was co-localized with tryptophan hydroxylase (TPH), a marker of serotonergic neurons, in dorsal raphe nuclei. Kir6.2 was also co-localized with tyrosine hydroxylase (TH), a marker of dopaminergic/noradrenergic neurons, in the ventral tegmental area and locus coeruleus. Next, we checked the protein levels of TH and TPH in the midbrain. Interestingly, TPH expression was significantly elevated in female Kir6.2-/- mice. These results suggest that Kir6.2 in monoamine neurons, especially serotonergic neurons, could play a key role in emotional behavior.

IntroductionThe rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by using existing international scales. Further, evidence of socioeconomic consequences among patients with COVID-19 is scarce. To address the multidimensional issues from sequelae of COVID-19, evidence from comprehensive surveys beyond clinical perspectives is critical that investigates health, and social determinants of disease progression as well as socioeconomic consequences at a large scale.Methods and analysisIn this study, we plan to conduct a nationwide and comprehensive survey for the sequelae of COVID-19 in a total of 1000 patients diagnosed at 27 hospitals throughout Japan. This study will evaluate not only the health-related status of patients from clinical perspectives but also the Health-related Quality of Life (HRQoL) scores, socioeconomic status and consequences to discuss the sequelae of the disease and the related risk factors. The primary endpoint is the frequency of long-term complications of COVID-19 infection. The secondary endpoints are risk factors for progression to sequelae of COVID-19 infection. The study will provide robust and important evidence as a resource to tackle the issues from the sequelae of COVID-19 from the multi-dimensional perspectives.Ethics and disseminationThis trial was approved by the Keio University School of Medicine Ethics Committee (20200243, UMIN000042299). The results of this study will be reported at a society meeting or published in a peer-reviewed journal.

Some patients with severe asthma also have fungal sensitization and are considered to have severe asthma with fungal sensitization. However, there is limited information on the clinical features of SAFS.To investigate the clinical characteristics of severe asthma with fungal sensitization.The present study enrolled 124 patients with severe asthma. We evaluated clinical aspects, such as various serum cytokines, fractional exhaled nitric oxide, pulmonary function, and serum immunoglobulin E (IgE). Fungal sensitization was assessed by determining serum levels of IgE specific to fungal allergens (Aspergillus, Alternaria, Candida, Cladosporium, Penicillium, and Trichophyton species and Schizophyllum commune). The protocol was registered at a clinical trial registry (www.umin.ac.jp/ctr/index-j.htm; UMIN 000002980).Thirty-six patients (29%) showed sensitization to at least 1 fungal allergen. The most common species were Candida (16%), Aspergillus (11%), and Trichophyton (11%). The rate of early-onset asthma (16 years of age) was higher in patients with fungal sensitization than in those without fungal sensitization (45% vs 25%; P = .02). Interleukin-33 levels were higher in patients with fungal sensitization than in those without fungal sensitization. Of patients with atopic asthma, Asthma Control Test scores were worse in patients with multiple fungal sensitizations than in patients with a single fungal sensitization or those without fungal sensitization.Severe asthma with fungal sensitization is characterized by early onset of disease and high serum levels of interleukin-33. Multiple fungal sensitizations are associated with poor asthma control.UMIN Clinical Trials Registry (UMIN-CTR; www.umin.ac.jp/ctr/index-j.htm): UMIN 000002980.

Although the incidence of postbulbar duodenal ulcers is low, many complications occur, such as hemorrhage, stenosis and perforation, and there are many points to be paid attention to with regard to its pathology. A high acid level has been pointed out as a cause, but this is not conclusive, and its association with Helicobacter pylori (Hp) infection is also unclear. We investigated chronic cases excluding acute cases such as acute duodenal mucosal lesion we encountered between 2001 and 2015. Five cases corresponded, accounting for 1.4% of all chronic duodenal ulcer cases, and there were more male patients (four patients were male), as previously reported. All cases were solitary punched-out ulcer on the medial side near the superior duodenal flexure, and many complications were observed such as melena in all patients, narrowing in 2, and penetration in 1. No specific pathology, such as Crohn’s disease, vasculitis, or Zollinger-Ellison syndrome, was noted, no patient was previously medicated with NSAIDs or low dose aspirin, and 3 patients were infected with Hp. All cases were healed by proton pump inhibitor administration or gastric acid secretion-suppressing treatment with selective proximal vagotomy. Recurrence after Hp eradication occurred in all of the 3 Hp-infected patients, suggesting that involvement of Hp in the cause of disease is unlikely.

Background and objective Body weight of patients with obstructive sleep apnea after initiation of nasal continuous positive airway pressure appears to increase. We hypothesized that intermittent hypoxia (IH) will decrease energy expenditure (EE), and that normoxic recovery will lead to body weight gains. Methods C57BL/6 J male mice were exposed to either 12 h/day of mild IH (alternating FIO2-10-11% and 21%; 640 s cycle), or severe IH (FIO2-6-7%-21%; 180 s cycle) or sham IH daily for 4 or 8 weeks. After exposures, EE was evaluated while mice were kept under normoxia for 5 weeks and organ histology was evaluated. Results EE was not decreased by IH. However, visceral white adipocyte size after normoxic recovery was significantly increased in severe IH in an intensity-dependent manner. Conclusion Our hypothesis that IH would decrease EE was not corroborated. However, IH and normoxic recovery seem to promote severity-dependent enlargement of visceral adipocytes, likely reflecting altered energy preservation mechanisms induced by IH.

BackgroundUsual clinical practice for arterial blood gas analysis (BGA) in conscious patients involves a one-time arterial puncture to be performed after a resting period of 20–30 min. The aim of this study was to evaluate the use of transcutaneous BGA for estimating this gold standard arterial BGA.MethodsSpontaneously breathing Asian adults (healthy volunteers and respiratory patients) were enrolled (n = 295). Transcutaneous PO2(PtcO2) and PCO2(PtcCO2) were monitored using a transcutaneous monitor (TCM4, Radiometer Medical AsP, Denmark) with sensors placed on the chest, forearm, earlobe or forehead. Transcutaneous BGA at 1-min intervals was compared with arterial BGA at 30 min. Reasonable steps to find severe hypercapnia with PaCO2 > 50 mmHg were evaluated.ResultsSensors on the chest and forearm were equally preferred and used because of small biases (n = 272). The average PCO2bias was close to 0 mmHg at 4 min, and was almost constant (4–5 mmHg) with PtcCO2being higher than PaCO2at ≥8 min. The limit of agreement for PCO2narrowed over time: ± 13.6 mmHg at 4 min, ± 7.5 mmHg at 12–13 min, and ± 6.3 mmHg at 30 min. The limit of agreement for PO2also narrowed over time (± 23.1 mmHg at 30 min). Subgroup analyses showed that the PaCO2and PaO2levels, gender, and younger age significantly affected the biases. All hypercapnia subjects with PaCO2 > 50 mmHg (n = 13) showed PtcCO2 ≥ 50 mmHg for until 12 min.ConclusionsAlthough PtcCO2is useful, it cannot completely replace PaCO2because PCO2occasionally showed large bias. On the other hand, the prediction of PaO2using PtcO2was unrealistic in Asian adults. PtcCO2 ≥ 50 mmHg for until 12 min can be used as a screening tool for severe hypercapnia with PaCO2 > 50 mmHg.

A 42-year-old Japanese man developed Churg–Strauss syndrome 7 years after being diagnosed with chronic eosinophilic pneumonia. Prominent eosinophilia, subcutaneous nodules, and neuropathy in the left leg were seen. A pathological diagnosis of necrotizing vasculitis was determined by a biopsy of a subcutaneous nodule. The leg pain was severe and there was prominent atrophy of the thigh and calf, but the muscle weakness was mild. Serum anti-myeloperoxidase anti-neutrophil cytoplasmic antibody was positive. Because the initial treatment with an intravenous methylprednisolone pulse at 1 g/day for 3 days was not sufficient, a onetime treatment with intravenous cyclophosphamide at 15 mg/kg and intravenous immunoglobulin therapy (IVIG) at 400 mg/kg/day for 5 days were administered. Peripheral eosinophilia improved and the leg pain significantly improved. IVIG was repeated 1 month later and symptoms gradually improved further. The early diagnosis of Churg–Strauss syndrome and the early initiation of IVIG with cyclophosphamide were thought to be important.

Objectives: Recent reports on venous blood gas analysis have shown that venous bicarbonate concentration is useful in the evaluation of the body acid-base status. Most of these reports have been based on the Bland-Altman analysis comparing arterial and venous blood gas values. We intended to elucidate any factors that decrease the agreement between venous and arterial bicarbonate concentrations, which might impair the usefulness of venous blood gas analysis. Methods: Healthy volunteers and patients with various diseases (n = 141) were evaluated by simultaneous arterial and venous blood sampling and Bland-Altman analysis. The venous-arterial bicarbonate concentration difference was compared between healthy volunteers and untreated respiratory alkalosis patients. Intentional hyperventilation (30 or 60 breaths/min, for 3 min) was also performed on 6 healthy volunteers and the venous-arterial bicarbonate concentration difference was evaluated. Results: The relative average bias in bicarbonate concentration was 2.00 mEq/l with venous bicarbonate higher than arterial bicarbonate with 95% limits of agreement of ±4.15 mEq/l. Hyperventilation challenges increased the venous-arterial bicarbonate concentration difference in an intensity-dependent manner. The venous-arterial bicarbonate concentration difference was higher in untreated respiratory alkalosis patients than in healthy volunteers (P Conclusion: Although venous bicarbonate may be useful to evaluate the body acid-base status, hyperventilation increases the venous-arterial bicarbonate concentration difference. Physicians should keep this phenomenon in mind.

Objective: The Japanese drug use system allowed the “once-daily use” of inhaled corticosteroid (ICS) fluticasone furoate (FF) combined with a long acting beta-2 agonist (LABA) vilanterol (VI) against asthma for the first time in 2013. Until then, patients with asthma had to use ICS at least twice-daily. We investigated the real-world efficacy and problems of this drug (FF/VI). Methods: This was an open-label, uncontrolled, within-group time-series (before-after) design. Prior treatments of asthma (twice-daily use of ICS with or without LABA) were switched to once-daily use of FF/VI (200 μg/25 μg). Subjects were evaluated by lung function tests prior to, and 2–3 months after, the initiation of FF/VI. Questions on the asthma control test (ACT) and preference of drugs were asked to patients. Results: One hundred and twenty-eight Japanese asthma outpatients were enrolled from 2014–2018 and 107 subjects completed the study. Peak flow, instantaneous flow at 75% of the forced vital capacity (V75), V50, maximum mid-expiratory flow rate, forced expiratory volume in 1 s, and ACT score in FF/VI-using subjects were significantly increased (all p

A 55-year-old man visited our department because of epigastric pain. Upper gastrointestinal endoscopy revealed a small, undermined ulcer in the gastric cardia. He had no history of taking NSAIDs, and was positive for Helicobacter pylori (Hp) infection. After Hp eradication therapy followed by 8 weeks of proton pump inhibitor (PPI) administration, re-endoscopy showed that the ulcer had slightly shrunk without scarring, and the surrounding mucosa was markedly elevated, like in a submucosal tumor. Endoscopic ultrasonography, performed at the same time, showed thickening of the submucosal and muscular layers around the ulcer. After continuous PPI administration, the mucosal elevation disappeared, and the ulcer shrunk and later scarred. However, when the dose of PPI was reduced with the aim of discontinuing it after the confirmation of successful Hp eradication, the ulcer recurred. We report this case of gastric ulcer because of its peculiar clinical presentation.

A man taking antithrombotic agents was admitted because of melena. Upper gastrointestinal endoscopy revealed a large, pedunculated polyp bleeding from erosions on its top. The polyp was endoscopically resected, and histopathologically diagnosed as Brunner ’ s gland hyperplasia. It is commonly encountered as a small, raised lesion, but may enlarge or bleed. We report this case, with a review of the Japanese literature and discussion of the mechanism of bleeding. doi: http://dx.doi.org/10.4021/gr532e

Microplasma technology was used in many applications from biomedical to surface treatment of polymers. A new application could be the surface treatment of glass panels for the electronic industry in order to improve the surface wettability. The remote microplasma method is proposed for the surface treatment of glass. It can be easily applied as an industrial process due to the relatively low discharge voltage around 1 kV and small size of the reactor. This paper presents the surface treatment of glass by microplasma using Ar and mixtures of Ar with N2 and O2. A microplasma process was analyzed by the emission spectroscopy method. A Marx generator with MOSFET switches, a neon transformer, and a pulsed power supply were used to energize the electrodes. The emission spectrum was measured by an intensified charge-coupled device camera and a spectrometer. An optic fiber was used to have an accurate measurement of a small part of the microplasma discharge. Surface wettability of glass was confirmed, measuring the contact angle before and after the microplasma treatment. The surface of glass was modified due to the action of the radicals and active species generated by microplasma. The emission spectrum of the microplasma discharge in Ar and mixtures of Ar with and showed ArI peaks, OH peaks, second positive band system peaks, and first positive band system peaks.

A 60-year-old male presented with cough and fever (case 1), and a 77-year-old female patient with hemoptysis (case 2) were admitted to IUHW Shioya Hospital. Interferon gamma release assay (IGRA: QFT-3G and T-SPOT. TB) were both performed on each patient; the QFT-3G was positive and T-SPOT.TB was negative in both cases despite different final diagnosis. While case 1 was determined to have active tuberculosis, in case 2 active tuberculosis was eliminated as the diagnosis. The contradictory results in these patients should serve as a reminder to clinicians that they should not rely on the results of IGRA testing for the diagnosis of active tuberculosis. Keywords: Interferon Gamma Release Assay; Negative; Tuberculosis; T-SPOT; QFT

A middle-aged man with no symptom or history visited our hospital due to duodenal abnormality and fecal occult blood detected by health screening. Upper gastrointestinal endoscopy showed marked enlargement of the papilla of Vater surrounded by nodules, and biopsy disclosed non-caseating granuloma. Colonoscopy yielded findings suggestive of intestinal tuberculosis such as annular ulcers. Examination of the biopsy samples failed to make a diagnosis of tuberculosis, and no pulmonary lesion was found, but whole-blood interferon gamma release assay was positive. The duodenal lesion was also suspected to be tubercular, so antitubercular drugs were administered. As this resulted in the resolution of both lesions, a definite diagnosis of tubercular papillitis of Vater was made. Duodenal tuberculosis is rare, and a localized lesion of the major duodenal papilla is extremely rare. However, this case suggests that tuberculosis must be considered in the differential diagnosis of lesions of the papilla of Vater.

Microplasma can be found in many applications. The technology is also used for surface treatment of polymers. The process of surface treatment by microplasma is environmental friendly, and it could be realized at low cost due to the relatively low discharge voltage (around 1 kV) even under atmospheric pressure and the small size of the power supply and reactor. This paper presents the surface treatment by microplasma of polyethylene naphthalate (PEN) film using Ar gas and mixtures of Ar with N2 and O2. The microplasma process was analyzed by the emission spectroscopy method. An experimental Marx generator with MOSFET switches was used as a pulsed high-voltage power supply. The emission spectra were measured by an intensified charge coupled device camera, a spectrometer, and a photomultiplier tube. Surface wettability of the PEN film was confirmed by measuring the contact angle before and after the microplasma surface treatment. It was observed that the contact angle of the PEN film decreased, especially with the O2/Ar mixture. The analysis using an X-ray photoelectron spectrometer showed the decrease of C1s, which correspond to the C-H bond. The emission spectrum of the microplasma discharge in the N2/Ar mixture showed Ar peaks, OH peaks, N2 second positive band system peaks (N2 SPS), N2 first positive band system peaks ( N2 FPS), and decrease in the peak intensities of ArI and OH for microplasma discharge in the O2/Ar mixture. The lifetime emission signals for the N2 SPS for the microplasma discharge in 0.25% N2 in Ar were around 1 μs. The calculation of the microplasma rotational and electron temperatures shows low rotational and high electron temperatures.

Introduction Since the invention of the pulse oximeter, physicians often or even routinely perform venous blood gas analysis (VBGA). However, it has not been generally agreed that the application of VBGA is practically meaningful in routine clinical situations such as in an ED. Methods We measured venous-arterial P co 2 difference ((v-a)P co 2) and arterial-venous pH difference ((a-v)pH), and analyzed the physiological factors that affect these differences in healthy volunteers and hyperventilation patients. Results In healthy volunteers, both (v-a)P co 2 and (a-v)pH increased during finger exercise or hyperventilation in an intensity-dependent manner. Doppler echography indicated that increases in (v-a)P co 2 and (a-v)pH during hyperventilation are induced by reduction of peripheral blood flow. Approximately 40% of patients with untreated respiratory alkalosis were found to be incorrectly diagnosed if based only on VBGA. Conclusions It must be noted that VBGA may lead to overestimation of acidosis and to underestimation of respiratory alkalosis when extremities muscles are active or patients are hyperventilating. Physicians should keep these limitations in mind when conducting VBGA.

Hepatopulmonary syndrome (HPS) (hypoxaemia due to intrapulmonary vasodilation and a right-to-left shunt associated with liver disease) resolves after liver transplantation. The authors describe a case of spontaneous resolution of HPS prior to liver transplantation. This patient was diagnosed with HPS associated with extra-hepatic biliary atresia when she was 10 years old. She exhibited digital clubbing, facial vascular dilation, cyanosis, and suffered from dyspnoea during exercise. The patient's PaO(2) at rest was 53.8 mm Hg in room air and a Technetium-99m macro-aggregated albumin lung perfusion scan demonstrated a right-to-left shunt. Although her symptoms and laboratory data supported a diagnosis of HPS, she nevertheless showed spontaneous resolution within 2 years. When she was 14 years old, pulmonary hypertension was evident upon examination of her echocardiogram. HPS may be improved or masked by an accidental overlap with pulmonary hypertension in the terminal stage of liver disease.

This report describes a novel technique for the calibration of accelerometers. The theory is based on acceleration as a vector quantity and the fact that the mathematical function of accelerometers is the projection of a real motion vector space to a signal vector space. The sensitivity should be therefore be defined as a matrix. The definition of the calibration shall be to derive all of the components in the sensitivity matrix. The transverse sensitivity value in the conventional definition can be derived using sensitivities in the sensitivity matrix. Cross sensitivity makes a large influence on the measurement error.

This report describes the calibration of accelerometers. The theory for the calibration is based on acceleration as a vector quantity, and the sensitivity derived by the theory is defined as a matrix. The experiment was conducted using a three-dimensional vibration generator and three one-channel laser interferometers. The accelerometer used in the experiment is a three-axis type. Comparison with the conventional calibration method places an importance on the transverse sensitivities, because their influence on the acceleration measurement is impossible to disregard. The relation between the transverse sensitivities derived by the matrix concept and the conventional transverse sensitivities defined by ISO-5347 Part 11 is stated. Importance of the dimension of the motion space created by the vibration generator is stated in terms of the calibration.

This paper describes the system for the calibration of accelerometers using a three-dimensional vibration generator and laser interferometers. The vibration generator is an electrodynamic type, IMV TS-1030 S, which can generate motion with the arbitrary direction in the three-dimensional coordinate system under sinusoidal, random and shock operation mode. It has five actuators in total, two actuators each for X-axis and Y-axis and one for Z-axis motion. Motion of the table is monitored during the operation by the three piezoelectric-accelerometers, BK 4393. The signal from them is used for the control of the table, feed forward and feed back. Motion of the table in three-dimensional space is measured by three laser interferometers, Neoark MLD 301 K. The sensitivity of an accelerometer is defined in the form of a matrix including the cross sensitivity. Size of the matrix is 1×3, 2×3 and 3×3 for one-axis accelerometer, two-axis accelerometer and three-axis accelerometer, respectively. Since acceleration is a vector quantity, input signals and output signals of an accelerometer make a vector space. An accelerometer is mathematically a device executing a projection between two vector spaces. This system is the realization of this concept.

A 61-year-old man took loxoprofen sodium hydrate, a prodrug NSAID, for acute upper respiratory infection for 5 days, developed melena 2 days later, and was admitted to our hospital. Upper gastrointestinal endoscopy revealed a giant and deeply undermined ulcer mainly in the greater curvature of the antrum, which occupied halfway around the lumen. His medical history was unremarkable. He was negative for Helicobacter pylori infection, and was diagnosed with NSAID-induced acute gastric ulcer in the absence of other causes of gastric ulcer. Giant gastric ulcers, as in this patient, are rare. Moreover, deeply undermined or huge gastric ulcers sometimes develop during the long-term administration of NSAIDs, but very rarely after their short-term administration, which prompted us to report this case.

A trend in sintered machine parts is the production of net shaped objects and comprex shaped parts. Correspondingly the machinability of green compacts with a lathe was investigated experimentally. In this regard, the compactibility of a raw powder was also discussed. Beside Fe-40% Cu plated powder with excellent compactibility, Fe-40%Cu, Fe-3%Cu, Fe-3%Cu-1%C and Fe-1%C as mixed powders and Fe powder were used. All these green strengths increase in proportion to the compacting pressure in the range of 98MPa to 686MPa. As the results of cutting test, satisfactory cutting surfaces were obtained for the green compacts with the radial crushing strength above about 60 MPa. Furthermore, the graphite as one of the alloying elements serves to provide lubrication on cutting. Conseqently, both Fe-3%Cu-1%C and Fe-1%C compacts exhibit good machinability in spite of low green strength in comparison with the others.