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The perinatal resuscitation history in Japan is short, with the earliest efforts in the field of neonatology. In contrast, the standardization and dissemination of maternal resuscitation is lagging. With the establishment of the Maternal Death Reporting Project and the Maternal Death Case Review and Evaluation Committee in 2010, with the aim of reducing maternal deaths, the true situation of maternal deaths came to light. Subsequently, in 2015, the Japan Council for the Dissemination of Maternal Emergency Life Support Systems (J-CIMELS) was established to educate and disseminate simulations in maternal emergency care; training sessions on maternal resuscitation are now conducted in all prefectures. Since the launch of the project and council, the maternal mortality rate in Japan (especially due to obstetric critical hemorrhage) has gradually decreased. This has been probably achieved due to the tireless efforts of medical personnel involved in perinatal care, as well as the various activities conducted so far. However, there are no standardized guidelines for maternal resuscitation yet. Therefore, a committee was set up within the Japan Resuscitation Council to develop a maternal resuscitation protocol, and the Guidelines for Maternal Resuscitation 2020 was created in 2021. These guidelines are expected to make the use of high-quality resuscitation methods more widespread than ever before. This presentation will provide an overview of the Guidelines for Maternal Resuscitation 2020.

The majority of women undergoing cesarean delivery in the United States receive neuraxial morphine, the most effective form of postoperative analgesia for this surgery. Current American Society of Anesthesiologists (ASA) and American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend respiratory monitoring standards following neuraxial morphine administration in the general surgical population that may be too frequent and intensive when applied to the healthy obstetric population receiving a single dose of neuraxial morphine at the time of surgery. There is limited evidence to support or guide the optimal modality, frequency, and duration of respiratory monitoring in the postoperative cesarean delivery patient receiving a single dose of neuraxial morphine. Consistent with the mission of the Society for Obstetric Anesthesia and Perinatology (SOAP) to improve outcomes in pregnancy for women and neonates, the purpose of this consensus statement is to encourage the use of this highly effective analgesic technique while promoting safe practice and patient-centered care. The document aims to reduce unnecessary interruptions from respiratory monitoring in healthy mothers while focusing vigilance on monitoring in those women at highest risk for respiratory depression following neuraxial morphine administration. This consensus statement promotes the use of low-dose neuraxial morphine and multimodal analgesia after cesarean delivery, gives perspective on the safety of this analgesic technique in healthy women, and promotes patient risk stratification and perioperative risk assessment to determine and adjust the intensity, frequency, and duration of respiratory monitoring.

Objective To elucidate the novel biological functions of heparan sulfate (HS) by clinic-pathologically studying a patient with paroxysmal atrioventricular (AV) block. Patient A long-surviving male patient with Sanfilippo syndrome type A presented with paroxysmal AV block at age 33 years. He then survived another 2.5 years after the onset of paroxysmal AV block and pacemaker implantation. Methods and results His cardiac histopathological examination at autopsy showed HS storage in the cardiac conduction system (CCS), especially in the atrioventricular node (AVN)-His bundle branches. Conclusion HS storage in the CCS might trigger AV block, arising from below the AVN-His bundle branches. This is the first description to indicate that HS might be an essential constituent of life-long CCS plasticity and that its storage in the CCS results in AV block.

Background Following the increase in the number of children with food allergies, support systems are now required for school lunches, but a large-scale factual investigation has not been carried out. Objective We evaluated the features of elimination diet due to food allergy and the support system in kindergartens and schools. Methods A prefecture-based questionnaire survey regarding measures for food allergies in school lunches of all kindergartens, public elementary schools, and public junior high schools (631 facilities) was conducted in Oita Prefecture, Japan. Results The recovery rate of the questionnaire was 99.5%, which included 106,008 students in total. A total of 1,562 children (1.5%) required elimination diets. The rate of children on elimination diets in kindergartens and elementary/junior high schools that required medical certification by a physician was 1.2% (324 among 27,761 children), which was significantly lower than the 1.8% of children (1,227 among 68,576 students) on elimination diets at the request of guardians without the need for medical certification (p < 0.0001). A total of 43.9% of the kindergartens and schools said that they would contact guardians if symptoms were observed after accidental ingestion, while a low 8.1% stated that they provided support to children themselves, including the administration of adrenaline auto-injectors. Conclusion Medical certification reduces the number of children requiring elimination diets, but it has not been adequately implemented. Furthermore, waiting to contact guardians after symptoms are observed may lead to the delayed treatment of anaphylaxis. Cooperation between physicians and teachers is desired to avoid the overdiagnosis and undertreatment of children with food allergies.

Cough headache can be a primary benign condition or secondary to underlying etiologies. We herein describe a case of a 52-year-old woman with cough headache that presented as reversible cerebral vasoconstriction syndrome (RCVS). Some cases of RCVS are caused by an aberrant sympathetic response to activities that cause an intracranial pressure surge. Therefore, cough headache should be recognized as a possible presentation of RCVS, even without thunderclap headache or neurological deficits.

Background: The accurate identification of an intervertebral lumbar level is essential to avoid neuraxial anesthesia and analgesia-related spinal cord injury. It has been shown that estimation of L...

Various degrees of left ventricular outflow tract (LVOT) obstruction have been seen in patients with subvalvular aortic stenosis (SAS). Regional analgesia during labor for parturients with SAS is relatively contraindicated because it has a potential risk for hemodynamic instability due to sympathetic blockade as a result of vasodilation by local anesthetics. We thought continuous spinal analgesia (CSA) using an opioid and minimal doses of local anesthetic could provide more stable hemodynamic status. We demonstrate the management of a 28-year-old pregnant patient with SAS who received CSA for her two deliveries. For her first delivery (peak pressure gradient (∆P) between LV and aorta was approximately 55 mmHg), intrathecal fentanyl was used as a basal infusion, but we needed a small amount of bupivacaine to provide supplemental intrathecal analgesia as labor progressed. Although there were mild fluctuations in hemodynamics, she was asymptomatic. For her second delivery (∆P between LV and aorta was approximately 90 mmHg), minimal doses of continuous bupivacaine were used as a basal infusion. For her additional analgesic requests, bolus co-administration of fentanyl was effective. There were no fluctuations in her hemodynamics. Although her SAS in her second pregnancy was more severe than in the first, her hemodynamics exhibited less fluctuation during the second delivery with this method. In conclusion, CSA using fentanyl combined with minimal doses of bupivacaine provided satisfactory analgesia and stable hemodynamics in parturient with severe SAS.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a rare inherited disease which begins with migraine and later develops repeated cerebral subcortical infarction and dementia. We present an anesthetic experience of an undiagnosed CADASIL woman complicated with preeclampsia. She developed headache, slurred speech, cognitive dysfunction and restlessness at 35 weeks' gestation and was diagnosed as hypertensive encepha- lopathy. Urgent cesarean section was decided. After ruling out meningitis by physical examination, and intracranial hemorrhage, cerebral swelling and hydro- cephalus by brain CT, spinal anesthesia was chosen. Mild sedation was necessary because the patient became restless and uncooperative during surgery. The anesthetic course was uneventful otherwise. She was either restless or lethargy and had hallucinatory episodes on 1st post-operative day. The neurologist suspected CADASIL because of multiple lacunar infarct lesions on MRI and her family history. The diagnosis was confirmed by skin biopsy and a genetic test.

Moyamoya disease (MD) is an occlu- sive cerebrovascular disease with risks of cerebral ischemia or hemorrhage. Although cesarean section (CS) is the prevailing delivery mode for these parturi- ents to stabilize cerebral circulation, the preferable mode remains controversial. We have conducted vagi- nal delivery with neuraxial analgesia (NA) because safety with the procedure is equivalent to that with CS. The aim of this study is to investigate peripartum outcomes, particularly delivery mode and occurrence of cerebrovascular events, in women with MD.We retrospectively analyzed the data of parturients with MD for the previous 8 years.Among 13 pregnancies during this period, eight were vaginal deliveries with NA, while CS was executed in five cases according to obstetric indica- tions. Instrumental deliveries were conducted in five among eight vaginal delivery cases. No cerebrovascular event occurred during delivery. A transient ischemic attack in one case of vaginal delivery and cerebral ischemia in CS were noted in the postpartum period.We successfully managed vaginal deliveries in the eight patients with MD using NA. NA provides pain relief and assures maternal hemody- namic and respiratory stability during delivery. Instru- mental delivery plays a key role in reducing the dura- tion of the second stage of labor.

Autoimmune disorders are common in women at their childbearing age. This chapter discusses systemic lupus erythematosus, antiphospholipid syndrome, Sjogren’s syndrome, and rheumatoid arthritis. All of them affect pregnancy outcome, and therefore careful management should be started before conception. Anesthetic considerations are also important depending on the clinical pathology of an individual parturient. These disorders may deteriorate during pregnancy and can result in cardiac, pulmonary, and renal dysfunction. Platelet count in systemic lupus erythematosus and anticoagulation therapy in antiphospholipid syndrome should be checked. Airway assessment is crucial particularly in rheumatoid arthritis.

It has been suggested that the combined effect of natural products may improve the effect of treatment against the proliferation of cancer cells. In this study, we evaluated the combination of 1'-acetoxychavicol acetate (ACA), obtained from Alpinia galangal, and sodium butyrate, a major short chain fatty acid, on the growth of HepG2 human hepatocellular carcinoma cells and found that treatment had a synergistic inhibitory effect. The number of HepG2 cells was synergistically decreased via apoptosis induction when cells were treated with both ACA and sodium butyrate. In ACA- and sodium butyrate-treated cells, intracellular reactive oxygen species (ROS) levels and NADPH oxidase activities were increased significantly. The decrease in cell number after combined treatment of ACA and sodium butyrate was diminished when cells were pretreated with catalase. These results suggest that an increase in intracellular ROS levels is involved in cancer cell death. AMP-activated protein kinase (AMPK), a cellular energy sensor, plays an essential role in controlling processes related to tumor development. In ACA- and sodium butyrate-treated cells, AMPK phosphorylation was induced significantly, and this induction improved when cells were pretreated with catalase. These results suggest that the increase in intracellular ROS is involved in the increase of AMPK phosphorylation. In normal hepatocyte cells, treatment with ACA and sodium butyrate did not decrease cell numbers or increase ROS levels. In conclusion, combined treatment with ACA and sodium butyrate synergistically induced apoptotic cell death via an increase in intracellular ROS and phosphorylation of AMPK. Our findings may provide new insight into the development of novel combination therapies against hepatocellular carcinoma.

Delayed respiratory depression is a feared complication of intrathecal morphine in patients undergoing cesarean delivery. The incidence, timing and risk factors for hypoxia in this population are not known.Patients undergoing cesarean delivery under spinal anesthesia at a tertiary care center from October 2012 to March 2016 were included in the study. The Berlin sleep apnea Questionnaire was completed before surgery. Oxygen saturation was recorded every second for 24hours after the initiation of spinal anesthesia. Desaturation events were defined as a median saturation of90% (mild) or85% (severe) across a 30-s period. Multivariable logistic regression was used to determine predictors of a desaturation event.A total of 721 patients were included in the analysis. Within this cohort, 169 women (23%) experienced at least one mild desaturation event, 91 (13%) experienced two or more mild desaturations, and 26 (4%) suffered a severe desaturation event. After the administration of intrathecal morphine, the median times to first mild or first severe desaturation were 7.4 (IQR 4.1-13.5)h and 12.0 (IQR 5.4-19.6)h, respectively. Patients who screened positive for sleep apnea had increased odds of having a mild desaturation event (OR 2.31, 95% CI 1.40 to 3.79, P=0.001), as did patients who were obese (OR 1.80, 95% CI 1.05 to 3.09, P=0.033).Mild hypoxemia occurred frequently in women receiving intrathecal morphine 150μg for post-cesarean analgesia. Desaturations were observed most frequently 4-8hours after administration of intrathecal morphine. Obesity and a positive Berlin Questionnaire were risk factors for hypoxemic events.

Aim The aim of our study was: (i) to investigate whether transversus abdominis plane (TAP) block confers additional analgesic effects to epidural morphine alone; and (ii) to determine plasma levels of local anesthetics after TAP block in post-cesarean women. Material and Methods The subjects were parturients undergoing cesarean section under combined spinal-epidural anesthesia. Morphine (2 mg) was administered to the epidural space close to the end of surgery. Women who desired TAP block were allocated to the TAP group. Women who did not undergo TAP block were allocated to the control group. In the TAP group, 20 mL of either 0.375% ropivacaine or 0.3% levobupivacaine was infused to both sides of the transversus abdominis plane after surgery. All patients were placed on a patient-controlled i.v. analgesia regimen with morphine after surgery. Time to the first morphine request and amount of morphine consumption within 24 h after surgery were compared in patients with and without TAP block. Plasma concentrations of local anesthetics were determined at 15, 30 and 60 min after TAP block. Results Forty and 54 patients were allocated to the control and TAP group, respectively. The median time to the first morphine request was longer (555 vs 215 min), and the median cumulative morphine consumption within 24 h was lower (5.3 vs 7.7 mg) in the TAP group than in the control group. The maximum median concentrations of ropivacaine and bupivacaine after TAP block were 784 and 553 ng/mL, respectively. Conclusion TAP block had additional analgesic effects to epidural morphine alone.

Degradation of maternally stored mRNAs after fertilization is an essential process for mammalian embryogenesis. Maternal mRNA degradation depending on deadenylases in mammalian early embryos has been mostly speculated, rather than directly demonstrated. Previously, we found that gene expression of nocturnin, which functions as a circadian clock-controlled deadenylase in mammalian cells, was clearly changed during the maternal-to-zygotic transition (MZT). Here, we investigated the possible role of nocturnin during mouse MZT. First, we examined the expression profile and localization of nocturnin in mouse oocytes and early embryos. The abundance of Nocturnin mRNA level was significantly decreased from the MII to 4-cell stages and slightly increased from the 8-cell to blastocyst stages, whereas the Nocturnin protein level was almost stable in all examined cells including GV and MII oocytes and early embryos. Nocturnin was localized in both the cytoplasm and the nucleus of all examined cells. We then examined the effect of loss or gain of Nocturnin function on early embryonic development. Knockdown of Nocturnin by injection of Nocturnin antisense expression vector into 1-cell embryos resulted in the delay of early embryonic development to the early blastocyst stage. Moreover, Nocturnin-overexpressed embryos by injection of Nocturnin expression vector impaired their development from the 1-cell to 2-cell or 4-cell stages. These results suggest that precise expression of nocturnin is critical to proper development of early mouse embryos. Functional analysis of nocturnin may contribute to the understanding of the possible role of the deadenylase at mouse MZT.

【目的】延髄外側症候群患者における摂食・嚥下リハビリテーションが，脳卒中急性期のリスクとなる再発/進行や誤嚥性肺炎に対してどのような影響を及ぼすか検討した．【対象と方法】延髄外側症候群の連続症例を対象として，2004年9月の摂食・嚥下リハビリテーション立ち上げ以前の2年間の10例（未介入群）と立ち上げ後2年間の10例（介入群）をそれぞれの年齢，入院期間，絶食期間，リスク（再発/進行率・誤嚥性肺炎発生率）及び転帰を比較検討した．【結果】未介入群は平均年齢64歳（男9例，女1例；梗塞8例，出血2例）であった．介入群は平均年齢60歳（男8例，女2；梗塞10例）であった．発症から経口摂食（直接訓練）開始までの期間は，未介入群10.9日に対して介入群2.3日（p=0.005）であった．嚥下造影は介入群9例に施行した．転帰では自宅退院が未介入群4例，介入群6例で，機能ゴールでは，歩行自律が両群とも7例であり有意差を認めなかった．未介入は転院が多かった．退院時の食事形態（藤島の嚥下食1））は未介入群で嚥下III 3例・移行食5例・普通食2例で，介入群は移行食3例・刻み粥食2例，普通食4例と回復がやや早かった．退院時フォロー時の最終摂食能力は普通食が両群とも7例で有意差がなかった．誤嚥性肺炎は未介入群6例，介入群3例であり有意差（p=0.04）を認めた．脳卒中の再発/進行は，6例（両群ともに3例）で，発症3∼8日目に座位開始などの安静を変更した時に再発/進行していた（p>0.05）．【考察】最終的摂食・嚥下機能には有意差がないが，発症2日目より摂食・嚥下リハビリテーションが関わることで，誤嚥性肺炎予防と早期機能回復を促していると考えられた．また摂食・嚥下リハビリテーションを早期に開始することは，脳卒中の再発/進行リスクにならないと考えられた．

Background & Aims: Activins belong to the transforming growth factor-β superfamily. Recent studies have shown that activin and its natural antagonist, follistatin, are involved in tissue repair and inflammatory processes. The aim of this study was to determine whether neutralization of activins with follistatin would have an in vivo anti-inflammatory effect in several murine models of colitis. Methods: We assessed activin levels in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS). We subsequently tested the effects of an intraperitoneal injection of follistatin before or after induction of TNBS colitis. We also examined the established colitis induced by oral dextran sulfate sodium (DSS) as well as the spontaneous colitis that develops in interleukin (IL)-10 gene-deficient (IL-10−/−) mice. Results: Levels of activin transcripts in the colon during the acute phase of TNBS colitis were up-regulated. Epithelial cells, infiltrating macrophages (Mϕ), and endothelial cells produced excess activin βA. Pretreatment with follistatin increased the survival rate of mice with TNBS colitis from 33% to 82% and decreased the plasma levels of IL-6 and amyloid A. Administration of follistatin also reduced the histologic score and tissue myeloperoxidase activity in established TNBS and DSS colitis and reduced the severity of the colitis in IL-10−/− mice. Based on results obtained from 3 mouse models and from in vitro experiments, follistatin promoted the proliferation of colonic epithelial cells. Conclusions: Neutralization of activins by follistatin promoted epithelial cell division and tissue repair, clearly suggesting a treatment modality for intestinal inflammation.

Rainwater collected during the period of February-April, 2003 in Kanazawa University and Hakui, Ishikawa Prefecture, Japan, was investigated by ion chromatography of the dissolved ions, and Scanning electron microscopy equipped with energy dispersive analyzer (SEM-EDX), electron microprobe analyzer (EPMA), transmission electron microscopy, and X-ray powder diffraction (XRD) analyses of the filtered samples. The pH, Eh, EC, dissolved oxygen (DO) and depleted U (DU) of the rainwater were also measured. The results show a rare case with low pH value of rain and high value of electrical conductivity (EC) in the rainwater during certain period. The NO 3 -, SO 4 2- and NH 4 + concentrations on 26th March, show quite high values after oil field fires on 21st March 2003. The powdery dust and carbon-bearing nm sized particles contained in the rainwater have characteristics different from that of the Asian dust (Kosa). Since 21 March, 2003 the Iraq plunged into the war, the 9 oil field fires were reported on 25 March, 2003 in Rumaylah oil field near the borderline of Kuwait. The first precipitation was caught in Kanazawa on 24 March, 2003. The pH value of the rainwater indicated a strong acid rain (pH 3.6) with black powdery dusts. The acid rain on 27th March to 2nd April (pH 3.4-4.3; 5-17mm) associated with WNW wind (2.7-4.1m/s) has continued to the first 10 days of April in Kanazawa, during the 9 oil fields were burning in Iraq. The EC in rainwater collected from 24 March to 15 April, 2003, shows high concentrations of ions, suggesting high contents of water soluble-carbon particles and soot. In the meantime, it was the highest season of sandstorms at bare dried land in Iraq from the end of March to the beginning of April. Westerly wind blew around 5500m high, and the sandstorm with 2000m wide was transported by strong wind to Zagros 3000m high mountains. The hot wind hit the Zagros Mountains and easily to join and rise to Westerly wind high by a rising air current. The 234U/ 238U activity (around 0.2) in typical depleted uranium (DU) is quite low compared with that (around 1.0) in natural uranium. The contamination of DU from the Iraq conflict may be, if any, negligibly small on undetectable level. On the other hand, the powdery dusts and carbon-bearing particles of rainwater have been produced by combustion of oil field in Iraq and they are directly cycling in our planet by Westerly wind. Black carbon particles are a product of incomplete combustion, and are the principal light-absorbing atmospheric aerosol. The result reminds us of the scientific values of short-term atmospheric environment records during Iraq's War. This has consequences for primary production of powdery dusts coming from Iraq to the atmosphere over half the globe away. © 2004 Elsevier Ltd. All rights reserved.

Background When oral or nasal fiberoptic laryngoscopy is attempted, mandibular advancement has been reported to improve the laryngeal view. The authors hypothesized that mandibular advancement may also improve the laryngeal view during direct laryngoscopy. Methods Forty patients undergoing elective surgery under general anesthesia were included in this study. After establishment of an adequate level of anesthesia and muscle relaxation, direct laryngoscopy was performed by inexperienced physicians. Four different maneuvers--simple direct laryngoscopy without any assistance (C), simple direct laryngoscopy with mandibular advancement (M), simple direct laryngoscopy with the BURP maneuver (backward, upward, rightward pressure maneuver of the larynx; B), and simple direct laryngoscopy with both mandibular advancement and the BURP maneuver (BM)--were attempted in each subject, and the laryngeal aperture was videotaped with each procedure. An instructor in anesthesiology who was blinded to the procedure evaluated the visualization by reviewing videotape off-line, using the Cormack-Lehane classification system (grades I-IV) and a rating score within each subject (1 = best view; 4 = poorest view). The Friedman test followed by the Student-Newman-Keuls test was performed for statistical comparison. P < 0.05 was considered significant. Results The laryngeal view was improved with M and B when compared with C (P < 0.05 by both rating and Cormack-Lehane evaluation). BM was the most effective method to visualize the laryngeal aperture (P < 0.05, vs. B and M by rating evaluation), whereas B and M were the second and the third most effective methods, respectively. No statistical difference was observed between B and M with the Cormack-Lehane classification. Conclusion Mandibular advancement improves the laryngeal view during direct laryngoscopy performed by inexperienced physicians.

本稿は、逆接を表す「ところで」の意味について考察をし、「ところで」は話者が因果関係と比較した結果、「ところで」に先行する事態が最終段階にまで発展しても必ずしも予測された関係になるわけではないことを表すことを述べた。その「ところで」の意味については、「ところで」の従属節中の表現に注目し、「ても」と比較することによって検証した。その結果、「ても」には「も」の「並列・累加」が、「ところで」には直前の動詞の示す「事態の段階」が反映されており、「ても」と「ところで」が置き換え可能なのは、次の場合に限られるという違いも明らかになった。それは、「ても」が「ところで」の直前の動詞が表す一つの事態内での開始・終了といった段階を並列・累加する場合である。そして明らかに別の事態を並列・累加しているような場合には、「ところで」と置き換えはできないのである。さらに「ところで」の従属節中に不定語が現れやすいこと、複数句が表せないこと、主節に否定表現が現れやすいこと、文末に意志や希望の表現が来にくいというこれまで先行研究で記述されていた構文的特徴と本稿での「ところで」の意味の関係を考察し、それらを関連づけた。, This paper aims to analyze tokorode. It shows that tokorode is a concessive expression that reflects the aspect of the verb preceding it and relates this meaning to other structural characters of this expression. For example, negation tends to be used in the main clause and the subordinate clause cannot be repeated. This paper also shows differences between temo and tokorode. They cannot replaced each other when the event of the subordinate clause is compared with other events.

Background & Aims: T helper (Th) 1 and Th2 cell subsets significantly influence the pathological features of inflammation in the gastrointestinal tract in a distinct manner. It is now established that the transfer of CD4 + CD45RB Hi (RB Hi ) T cells to either severe combined immunodeficient (SCID) or recombinase activation gene 2–deficient (RAG −/− ) mice results in a severe granulomatous hypertrophic colitis mediated by Th1 cells. We have modified this approach to address the role of Th2 cells. Methods: RB Hi T cells from wild-type (Wt) mice or mice genetically predisposed to Th2 responses (interferon-γ–defective [IFN-γ −/− ]) with or without B cells were transferred to T cell receptor (TCR)-β and δ-chain–defective (TCR −/− ) or SCID mice. Results: Transfer of Wt RB Hi T cells induced wasting disease with severe colitis in the TCR −/− mice. In contrast, IFN-γ −/− RB Hi T cells induced severe weight loss and hypoalbuminemia without significant inflammation in the colon. The small intestine of these mice exhibited villus atrophy, a decrease in brush-border enzymes, reduced enterocyte proliferation, and an increased number of goblet cells. The presence of B cells was necessary for these changes, because SCID recipients required cotransfer of B cells, together with IFN-γ −/− RB Hi T cells for ileal lesions to develop. Treatment of TCR −/− recipients of IFN-γ −/− RB Hi T cells with anti–IL-4 mAb abrogated both the wasting disease and the villus atrophy. Conclusions: Dysregulated Th2 cells cause atrophic changes and goblet cell transformation in the small intestinal epithelium and wasting disease mediated by excess interleukin-4 and B cells. GASTROENTEROLOGY 2003;124:672-682

Our past studies showed that Peyer's patches were required for the induction of oral tolerance to the protein antigen ovalbumin (OVA), but not to the hapten 2,4,6-trinitrobenzene sulfonic acid (TNBS). In the present study, the effects of immunosenescence on oral tolerance induction were assessed with these two toleragens. Significant reductions in OVA-specific serum IgG antibody and CD4(+) T cell responses to subsequent challenge were observed in OVA-fed, young adult mice. Importantly, these reduced anti-OVA antibody responses were associated with delayed-type hypersensitivity, and antigen-induced CD4(+) T(h)1- and T(h)2-type cytokine responses. On the other hand, aged mice fed OVA failed to develop oral tolerance. Thus, CD4(+) T cells from Peyer's patches produced selected T(h)2- but no T(h)1-type cytokines. The TNP-specific serum IgG antibody and T cell responses were significantly diminished by prior TNBS feeding in young adult, 6- to 8-month-old and 12- to 14-month-old, but not in senescent, 2-year-old mice. Finally, we have directly assessed dendritic cell subsets and T cell responses in Peyer's patches, and their function in tolerance induction was impaired at an earlier stage of life. These results suggest that lack of oral tolerance to the protein OVA during aging is the result of dysfunctional Peyer's patches.

The aim of this review of the literature was to evaluate the effectiveness of anesthetics in protecting the heart against myocardial ischemia-reperfusion injury.Articles were obtained from the Medline database (1980-, search terms included heart, myocardium, coronary, ischemia, reperfusion injury, infarction, stunning, halothane, enflurane, desflurane, isoflurane, sevoflurane, opioid, morphine, fentanyl, alfentanil sufentanil, pentazocine, buprenorphine, barbiturate, thiopental, ketamine, propofol, preconditioning, neutrophil adhesion, free radical, antioxidant and calcium).Protection by volatile anesthetics, morphine and propofol is relatively well investigated. It is generally agreed that these agents reduce the myocardial damage caused by ischemia and reperfusion. Other anesthetics which are often used in clinical practice, such as fentanyl, ketamine, barbiturates and benzodiazepines have been much less studied, and their potential as cardioprotectors is currently unknown. There are some proposed mechanisms for protection by anesthetic agents: ischemic preconditioning-like effect, interference in the neutrophil/platelet-endothelium interaction, blockade of Ca2+ overload to the cytosolic space and antioxidant-like effect. Different anesthetics appear to have different mechanisms by which protection is exerted. Clinical applicability of anesthetic agent-induced protection has yet to be explored.There is increasing evidence of anesthetic agent-induced protection. At present, isoflurane, sevoflurane and morphine appear to be most promising as preconditioning-inducing agents. After the onset of ischemia, propofol could be selected to reduce ischemia-reperfusion injury. Future clinical application depends on the full elucidation of the underlying mechanisms and on clinical outcome trials.

Near-infrared spectrophotometry (NIRS) is a new technique that allows continuous non-invasive monitoring of tissue oxygenation and haemodynamics in the brain. We used NIRS in various types of paediatric epileptic seizures in order to understand the pathophysiology of epileptic seizures in childhood epilepsy. This study examined 15 children ranging in age from 1.5 months to 16 years (nine males and six females), with different types of epilepsy. Six series of tonic spasms and 67 isolated seizures were recorded. The results demonstrated that several pathophysiological processes exist during epileptic seizures in childhood. (i) Convulsive seizures were associated with a remarkable increase in cerebral blood volume (CBV), while absence seizures were associated with a mild decrease or no change in CBV of the frontal cortex. (ii) An initial transient decrease in CBV was observed in some types of convulsive seizures. (iii) An ictal increase in CBV changed to an ictal decrease in the course of tonic status epilepticus. (iv) There was definite heterogeneity in the CBV changes during tonic spasms in patients with West syndrome. NIRS is easily applicable to paediatric patients with epilepsy and may provide new insights into the pathophysiology of various types of epileptic seizure.

Background Moyamoya disease more commonly occurs in young people and women, so patients with this disease may experience pregnancy and delivery. Cesarean section (CS) is often chosen as the mode of delivery for these patients in Japan. No appropriate mode of delivery has yet been established for pregnant women with moyamoya disease in terms of stroke prevention. We have used vaginal delivery under epidural analgesia (EA) in such patients unless CS has been indicated for the maternal or fetal reasons. This study retrospectively analyzed our patients with moyamoya disease who gave birth to confirm the safety of vaginal delivery under EA. Methods Twelve consecutive patients diagnosed with moyamoya disease had 14 deliveries at our hospital between September 2004 and January 2013. The incidences of intrapartum stroke were compared between cases of vaginal delivery under EA and CS cases. Results Ten vaginal deliveries under EA and 4 elective CSs were performed. No intrapartum stroke was observed during either vaginal delivery under EA or CS. Among the patients who underwent vaginal delivery under EA, 1 parturient who experienced 2 deliveries suffered transient ischemic attack during both postpartum periods. All 14 infants were healthy without sequelae. Conclusions Vaginal delivery under EA is an option for patients with moyamoya disease, provided that close cooperation with neurosurgeons, obstetricians, and anesthesiologists is assured.

Amniotic fluid embolism (AFE) is a disorder with a high mortarity rate, because it often causes sudden respiratory failure, circulatory collapse and disseminated intravascular coagulation (DIC). We present a case of AFE in which an obstetric anesthesiologist promptly initiated resuscitation of a parturient and saved her without any sequelae. Her fetus was diagnosed as intrauterine fetal demise on 25th gestational week and vaginal delivery under epidural analgesia was planned. One hundred and five minutes after induction of labor with prostaglandine E1, sudden tetanic convulsion occurred with a loss of consciousness. An obstetric anesthesiologist immediately started to resuscitate her and her consciousness was restored. However, noncoagulable vaginal bleeding followed. As the hemorrhage persisted, AFE was suspected. Anesthesiologists gave effective massive transfusion therapy, and she recovered from coagulopathy. Total blood loss was 5,524 g. This case was diagnosed as AFE with high serum sialyl-Tn antigen and zinc-coproporphyrin. The obstetric anesthesiologists are one of the best groups of physicans for resuscitation because they have skills in managing obstetric emergencies such as AFE. In this case, the crucial points for successful resuscitation were prompt obstetric anesthesiologist involvement and good communications with obstetricians and midwives.

To clarify the pathophysiology of tonic spasms, 21 patients with West syndrome were analyzed using ictal and interictal single photon emission computed tomography (SPECT). We focused on whether ictal perfusion changes were observed in the focal cortical region. Eight of the patients studied showed definite focal cortical ictal hyperperfusion, indicating that there is a unique subset of West syndrome that can be classified as infantile localization-related epilepsy. Of those eight patients, only two showed asymmetric spasms, suggesting that seizure symptomatology in infants gives only limited information on the localization-related nature of epilepsy. Furthermore, the activation of subcortical structures by focal cortical regions might be attributable to the symmetric seizure phenomena. Thirteen patients showed a diffuse pattern in their ictal SPECTs; this probably included patients with diffuse hyperperfusion and those with no changes. The following have yet to be determined: (1) whether West syndrome is divided into subgroups based on the origin of spasms, in that some patients have the origin in the cortical hemisphere and some have the origin in structures other than the cortical hemisphere, such as the brain stem; (2) whether differences in ictal SPECT patterns reflect a unique nature of tonic spasms in West syndrome, where tonic spasms appear in clusters and the interval of each spasm is different among each patient.

Oral delivery of a large dose or prolonged feeding of protein Ags induce systemic unresponsiveness most often characterized as reduced IgG and IgE Ab- and Ag-specific CD4+ T cell responses. It remains controversial whether oral tolerance extends to diminished mucosal IgA responses in the gastrointestinal tract. To address this issue, mice were given a high oral dose of OVA or PBS and then orally immunized with OVA and cholera toxin as mucosal adjuvant, and both systemic and mucosal immune responses were assessed. OVA-specific serum IgG and IgA and mucosal IgA Ab levels were markedly reduced in mice given OVA orally compared with mice fed PBS. Furthermore, when OVA-specific Ab-forming cells (AFCs) in both systemic and mucosa-associated tissues were examined, IgG AFCs in the spleen and IgA AFCs in the gastrointestinal tract lamina propria of mice given OVA orally were dramatically decreased. Furthermore, marked reductions in OVA-specific CD4+ T cell proliferative and cytokine responses in spleen and Peyer’s patches were seen in mice given oral OVA but were unaffected in PBS-fed mice. We conclude that high oral doses of protein induce both mucosal and systemic unresponsiveness and that use of mucosal adjuvants that induce both parenteral and mucosal immunity may be a better way to assess oral tolerance.

Induction of mucosal immunity by oral immunization with protein antigen alone is difficult: potent mucosal adjuvants, vectors, or other special delivery systems are required. Cholera toxin (CT) has been shown to be an effective adjuvant for the development of mucosal vaccines and, when given with vaccine, induces both mucosal and systemic immune responses via a Th2 cell-dependent pathway. However, and in addition to potential type-I hypersensitivity, a major concern for use of mucosal adjuvants such as CT is that this molecule is not suitable for use in humans because of its inherent toxicity. When we examined the potential toxicity of CT for the central nervous system, both CT and CT-B accumulated in the olfactory nerves/epithelium and olfactory bulbs of mice when given by the nasal route. The development of effective mucosal vaccines for the elderly is also an important issue; however, only limited information is available. When mucosal adjuvanticity of CT was evaluated in aged mice, an early immune dysregulation was evident in the mucosal immune system. The present review discusses these potential problems for effective mucosal vaccine development. Tolerance represents the most common and important response of the host to environmental antigens, including food and commensal bacterial components, for the maintenance of an appropriate immunological homeostasis. We have examined whether Peyer patches could play a more important role for the maintenance of oral tolerance. Using Peyer patch-null mice, we found that mice lacking this gut-associated lymphoid tissue retained their capability to produce secretory IgA antibodies but did not develop normal oral tolerance to protein antigens.

Despite recent advances in the cellular and molecular analysis of induction and regulation of mucosal immune responses, little is yet known about differences which occur in aging. To address this important issue, we have compared the mucosal and systemic immune responses of aged (12- to 14-mo- or 2-year-old) and young adult (6- to 8-wk-old) C57BL/6 mice. Both aged and young mice were immunized weekly with three oral doses of 1 mg of OVA and 10 μg of cholera toxin (CT) as mucosal adjuvant. Both groups of mice over 1 or 2 years of age showed reduced levels of Ag-specific mucosal or systemic immune responses at day 21. An Ag-specific B cell enzyme-linked immunospot assay confirmed these results at the cellular level. When the Ag-induced cytokine responses were examined at both protein and mRNA levels, CD4+ T cells from spleen and Peyer’s patches of young adult mice revealed elevated levels of IL-4 production; however, these cytokine responses were significantly diminished in aged mice. In contrast to mucosal immunization, mice s.c. immunized with OVA plus CT resulted in impaired OVA-specific but intact CT B subunit-specific immune responses in 12- to 14-mo-old mice although the responses to both Ags were depressed in 2-year-old mice. These results provide the first evidence that the development of age-associated alterations possibly occurs earlier in the mucosal immune system than in the systemic immune compartment.

Two children with influenza A-related encephalopathy were treated with a combination of mild hypothermia (deep body temperature of the forehead: 35 degrees C) and anticytokine agents (high-dose methylprednisolone and ulinastatin), while receiving amantadine. One of the cases exhibited acute necrotizing encephalopathy on computed tomography (CT). Although no severe complications occurred, correctable hypokalemia and hyperglycemia occurred in both cases. Both patients recovered without any neurological sequelae. Our therapeutic protocol appears to be effective for managing influenza A-related encephalopathy.

We used interictal single photon emission computed tomography (SPECT) on 40 patients with West syndrome to determine whether cortical perfusion abnormalities are closely related to the development of West syndrome and whether they are correlated with the long-term seizure prognosis or the developmental outcome. Localized cortical perfusion abnormalities were seen in 24 patients (60%), while 15 patients (38%) were classified as normal. The remaining patient showed hyperperfusion of the basal ganglia bilaterally. Of 24 patients with localized perfusion abnormalities, unifocal cortical hypoperfusion was present in 11, multifocal hypoperfusion in 10, multiple cortical hypo- and hyperperfusion in one, hyperperfusion of the bilateral frontal cortices and brain stem in one, and focal hyperperfusion in the residual frontal cortex in one. For statistical analysis, we focused on 26 patients (cryptogenic; 10, symptomatic; 16), who were followed for more than 2 years after the onset of tonic spasms (mean 5.0 years). The results showed that focal cortical perfusion abnormalities were not correlated with the long-term seizure prognosis, the developmental outcome, or the response to ACTH therapy. In agreement with previous reports, the results of interictal SPECT suggested that focal cortical lesions play an important role in the development of West syndrome. However, statistical analysis showed that the existence of cortical dysfunction as defined by SPECT did not predict the seizure prognosis or the developmental outcome.

Purpose. The plethysmographic wave of pulse oximetry reflects arterial pulsation at the fingertip. Since arterial pressure and the pulsatile component of the arterial cross section represent the input and output of the fingertip arterial system, respectively, arterial wall mechanics may be delineated from their relationship. We aimed to construct a mathematical model of the fingertip arterial wall from the relationship between the plethysmographic wave and arterial pressure. Methods. The pulse oximetric plethysmograpic signal at the forefinger and pressure at the ipsilateral radial artery were measured. Employing the data, simple mathematical models with one to four mechanical elements were tested in terms of the goodness of fit and the physiological implications. The determined model was applied to the data obtained during administration of vasoactive agents in anesthetized patients. Results. The mathematical model suited for describing arterial wall mechanics was a four-element, two-compartment model. The two compartments represent passive mechanical and active contractile properties, respectively. In the application of the model to the anesthetized patients, the vasoactive agents produced changes in the model parameters that implied mechanical alterations in the arterial wall. Conclusion. These findings suggest the benefit of the four-element, two-compartment model in analyzing peripheral vascular wall mechanics influenced by various stimuli in intensive care and anesthesia.

We evaluated the ictal and interictal single photon emission computed tomography (SPECT) of 9 patients with West syndrome (WS). In this group, we noted two clear patterns of cortical hyperperfusion and subcortical hyperperfusion in the ictal SPECT. Both patterns were different from the previously documented ictal patterns for complex partial seizures (CPS) or secondarily generalized seizures. Our results suggest that the tonic spasms of WS do not always have a single neurophysiological basis; e.g., patients with hemihypsarrhythmia and focal hypsarrhythmia did not show ictal hyperperfusion of the lesion with hypsarrhythmia. These findings indicate that the origin of hypsarrhythmia as an EEG feature and the origin of tonic spasms may be different in such patients. In particular, hypsarrhythmia appears to originate from cortical lesions, whereas the subcortical structures may be primarily responsible for the tonic spasms. Our report is the first published study of ictal SPECT in patients with WS.