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Background Postural tachycardia syndrome (POTS), a subset of orthostatic dysregulation, has been reported to be associated with anxiety. POTS can be classified into two forms based on the degree of tachycardia during orthostasis. Reportedly, POTS with decreased orthostatic heart rate increase is associated with suppressed cardiac parasympathetic activity and increased sympathetic activity in the supine position. In this study, the relationship between the two types of POTS and anxiety was evaluated in terms of autonomic function. Methods Fifty-two patients (23 males, aged 10–15 years) who were diagnosed with POTS at the Department of Pediatrics, Osaka Medical and Pharmaceutical University from 2019 to 2021, provided completed the State-Trait Anxiety Scale for Children (STAIC) questionnaire. They then completed a standing test and were accordingly classified into the two groups of POTS, the Su group, with tachycardia from the supine position and a low heart rate increase on standing, and the SI group, with a high heart rate increase during standing. Autonomic function was assessed by frequency analysis (MemCalc method) based on heart rate, blood pressure changes, heart rate, and blood pressure variability during the orthostatic test. Results Patients in the Su group had higher characteristic anxiety, lower cardiac parasympathetic activity (RR-HF) in the supine position, and greater variability in cardiac parasympathetic activity during orthostasis than those of patients in the SI group. The Su group had a greater decrease in cardiac index on standing than that of the SI group. Conclusions The Su group results may be partly attributed to chronically low venous return. We also found that patients in the Su group had low parasympathetic activity in the supine position, which may interact with the anxiety-prone characteristics of these patients. Therefore, it seems necessary to consider both physical and psychosomatic treatment approaches for patients with POTS. Trial registration The clinical trial registry of Osaka Medical and Pharmaceutical University, Clinical Trial Registration No. 2662-2. Registered 5 March 2019. https://ompu.bvits.com/rinri/Common/print_approve.aspx?ID=3479

ObjectiveInnate lymphoid cells (ILCs), including natural killer (NK) cells, ILC1, ILC2, lymphoid tissue-inducer (LTi) cells, and ILC3 cell, play a key role in various immune responses. Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by chronic inflammation of exocrine glands, such as the lacrimal and salivary glands (SGs). The role of NK cells among ILCs in the pathogenesis of pSS is still unclear. In this study, the characteristics and subsets of NK cells in the salivary gland (SG) tissue were analyzed using a murine model of pSS.MethodsMultiple phenotypes and cytotoxic signature of the SG NK cells in control and pSS model mice were evaluated by flow cytometric analysis. Intracellular expression of interferon-γ (IFN-γ) among T cells and NK cells from the SG tissues was compared byin vitroexperiments. In addition, pathological analysis was performed using anti-asialo-GM1 (ASGM1) antibody (Ab)-injected pSS model mice.ResultsThe number of conventional NK (cNK) cells in the SG of pSS model mice significantly increased compared with that in control mice at 6 weeks of age. The production level of IFN-γ was significantly higher in SG NK cells than in SG T cells. The depletion of NK cells by ASGM1 Ab altered the ratio of tissue resident NK (rNK) cells to cNK cells, which inhibited the injury to SG cells with the recovery of saliva secretion in pSS model mice.ConclusionThe results indicate that SG cNK cells may enhance the autoreactive response in the target organ by upregulating of IFN-γ, whereas SG rNK cells protect target cells against T cell cytotoxicity. Therefore, the activation process and multiple functions of NK cells in the target organ could be helpful to develop potential markers for determining autoimmune disease activity and target molecules for incurable immune disorders.

Background Postural tachycardia syndrome (POTS) manifests as marked tachycardia while standing. We noticed two forms of circulatory response to orthostatic stress in POTS. We investigated cardiovascular and autonomic nervous response to orthostatic stress in the two forms. Methods We studied 79 patients with POTS and 38 healthy control subjects (Ct). Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. Autonomic nervous function was evaluated on power spectral analysis of HR variability and diastolic BP variability. We divided the subjects into two groups: standing-induced tachycardia (SI group; increase in HR ≥35 beats/min) and supine tachycardia (Su group; standing HR ≥115 beats/min with standing-induced HR increase

Background Migraine is a common and disabling neurological disorder. Studies attempting to determine a relationship between migraine and the autonomic nervous system (ANS) have been inconclusive. Moreover, pediatric studies are extremely limited. Therefore, the present study investigated interictal ANS function in adolescent migraineurs. Methods We studied 21 patients with migraine and 26 healthy controls. Beat-to-beat blood pressure (BP) and heart rate (HR) were noninvasively and continuously measured in the supine and standing positions. ANS function was evaluated by power spectral analysis of HR variability and diastolic BP (DBP) variability. Results HR and systolic BP were not different between the two groups in either the supine or standing position. DBP did not differ between groups in the standing position, but was significantly higher in migraineurs in the supine position. The vasoconstrictor index was significantly higher in migraineurs. High-frequency (HF) RR interval variability (RR-HF) and the ratio of the low-frequency (LF) to HF component of RR interval variability (RR-LF/HF) were not different between the two groups in both position. The LF component of DBP variability (DBP-LF) in the supine position was significantly lower in migraineurs, while DBP- LF during standing in migraineurs was significantly higher than that in controls. Conclusion We found that migraineurs have significantly lower sympathetic vasomotor activity in the supine position and sympathetic vasomotor activity was hyperresponsive during standing. This article is protected by copyright. All rights reserved.

Aim Postural tachycardia syndrome (POTS) is one of the most frequent forms of chronic orthostatic intolerance in children and adolescents. The aim of the present study was to examine the influence of a genetic background on POTS. Methods A total of 96 children and adolescents with orthostatic dysregulation were studied. The polymorphism of the G protein β3 subunit (GNB3) C825T and G protein α subunit (GNAS1) T131C of genes encoding components of the autonomic nervous system were determined and compared with circulatory responses to active standing. Results In the GNB3 gene C825T polymorphism, the CT and TT genotype had a significant lower supine heart rate and a larger increase of heart rate by standing than the CC, associated with evaluated power of the high-frequency component of heart rate variability. According to the criteria of the Japanese clinical guidelines, 48 children were diagnosed as POTS and 30 were as normal responder with somatoform disorder (SD). In GNB3 C825T polymorphism, the TT genotype was more frequently found in the POTS group (45.8%) than in the SD group (25.0%; P = 0.036). In the GNAS1 T393C, the genotype frequencies for the T393C polymorphisms of GNA1 did not differ significantly between the groups. Conclusion The gene polymorphisms GNB3 C825T might be a risk factor for POTS through the enhanced vagal withdrawal of the heart in children and adolescents.

Chronic pain is a common problem in pediatric practice. The prevalence of chronic pain in children is >30%. Because pain indicates emotional expression as well as the physiological reaction toward infection, injury, and inflammation, both physiological and psychological assessments are essential to determine primary interventions for chronic pain. The Japanese Society of Psychosomatic Pediatrics Task Force of clinical practice guidelines for chronic pain in children and adolescents compiled clinical evidence and opinions of specialists associated with the primary care of pediatric chronic pain in the Japanese 'clinical guidelines for chronic pain in children and adolescents' in 2009, which are presented herein. The guidelines consist of three domains: general introduction to chronic pain; chronic abdominal pain; and chronic headache. Each section contains information on the physiological mechanism, psychological aspects, assessment methods, and primary interventions for pediatric chronic pain. These guidelines are expected to help disseminate knowledge on primary interventions for chronic pain in children and adolescents.

Microgravity due to prolonged bed rest may cause changes in cerebral circulation, which is related to brain function. We evaluate the effect of simulated microgravity due to a 6° head-down tilt bed rest experiment on executive function among 12 healthy young men. Four kinds of psychoneurological tests—the table tapping test, the trail making test, the pointing test and losing at rock–paper–scissors—were performed on the baseline and on day 16 of the experiment. There was no significant difference in the results between the baseline and day 16 on all tests, which indicated that executive function was not impaired by the 16-day 6° head-down tilting bed rest. However, we cannot conclude that microgravity did not affect executive function because of the possible contribution of the following factors: (1) the timing of tests, (2) the learning effect, or (3) changes in psychophysiology that were too small to affect higher brain function.

AIM: To investigate changes in cerebral blood volume during standing in healthy children with or without abnormal cardiovascular responses. METHODS: We studied 53 children (age, 10-15 years). Cerebral oxygenated haemoglobin (oxy-Hb) and deoxygenated Hb (deoxy-Hb) were non-invasively and continuously measured using near-infrared spectroscopy (NIRS) (NIRO 300, Hamamatsu Photomedics, Shizuoka, Japan) during active standing. Beat-to-beat arterial pressure was monitored by Portapres. RESULTS: Of 49 children with complete data acquisition, 33 had a normal cardiovascular response to the test (Group I) and 16 showed an abnormal response (Group II); nine with instantaneous orthostatic hypotension, three with postural tachycardia syndrome, three with neutrally mediated syncope and one with delayed orthostatic hypotension. At the onset of standing, Group II showed a significantly larger fall of oxy-Hb than Group I did (-2.9 +/- 2.8 micromol/L vs. -6.4 +/- 7.2 micromol/L, respectively, p < 0.05). During min 1 to 7 of standing, with one exception, changes in oxy-Hb were normally distributed over the level of -4 micromol/L in Group I. Group II also showed a significantly marked decrease in oxy-Hb compared to Group I. Decreases in oxy-Hb were not correlated with blood pressure changes. CONCLUSION: This study shows that precise change in cerebral blood volume caused by orthostatic stress can be determined by NIRS in children in a quantitative manner of NIRS. Children with abnormal circulatory responses to standing showed a significant reduction of oxy-Hb compared with normal counterparts, suggesting impairment of cerebral autoregulation in these children.

This clinical practice guideline provides recommendations for the assessment, diagnosis and treatment of school-aged children and juveniles with orthostatic dysregulation (OD), usually named orthostatic intolerance in USA and Europe. This guideline is intended for use by primary care clinicians working in primary care settings. The guideline contains the following recommendations for diagnosis of OD: (i) initial evaluation composed of including and excluding criteria, the assessment of no evidence of other disease including cardiac disease and so on; (ii) a new orthostatic test to determine four different subsets: instantaneous orthostatic hypotension, postural tachycardia syndrome, neurally mediated syncope and delayed orthostatic hypotension; (iii) evaluation of severity; and (iv) judgment of psychosocial background with the use of rating scales. The guideline also contains the following recommendations for treatment of OD on the basis of the result of an orthostatic test in addition to psychosocial assessment: (i) guidance and education for parents and children; (ii) non-pharmacological treatments; (iii) contact with school personnel; (iv) use of adrenoceptor stimulants and other medications; (v) strategies of psychosocial intervention; and (vi) psychotherapy. This clinical practice guideline is not intended as a sole source of guidance in the evaluation of children with OD. Rather, it is designed to assist primary care clinicians by providing a framework for decision making of diagnosis and treatments.

Tanaka H, Thulesius O, Yamaguchi H, Mino M, Konishi K. Continuous non-invasive finger blood pressure monitoring in children. Acta Padiatr 1994;83:646–52. Stockholm. ISSN 0803–5253 We evaluated the performance of continuous non-invasive finger arterial pressure measurement using the volume-clamp technique (Finapres). The study was designed to compare finger arterial pressure with brachial blood pressure estimated by the auscultatory method in 217 children (90 boys and 127 girls) aged 4–16 years and in 38 adults (aged 18–45 years). Finger and brachial artery pressure readings were obtained consecutively from the ipsilateral side in the supine position. Fingcr arterial pressure waveforms were recorded in all children except 4 with small and thin fingers. There was good agreement for systolic pressure with only a slight underestimation of 1.9 mmHg and 5.1 mmHg lower for diastolic pressure. This difference most probably reflects inaccuracy of the auscultatory cuff method rather than an error in the Finapres. There was large inter-individual variability in Finapres recordings which might be due to diffcrences in vasomotor tone, as demonstrated by systolic amplification in 5 patients with anorexia. However, Finapres showed a small within-subject variability (3.8 mmHg for systolic and 4.1 mmHg for diastolic pressure) dctermined in 5 patients during phenylephrine infusion, and as good reproducibility as the auscultatory method. These results suggest that finger arterial pressure measurement in children older than 6 years of age has similar accuracy as that in adults, and that this method is useful for clinical applications in children, especially for the non-invasive evaluation of autonomic control and cardiovascular reflexes involving transient and rapid blood pressure changes.

Lymphoma of the mucosa-associated lymphoid tissue (MALT) is the distinct clinicopathologic entity belonging to the subset of marginal zone Bcell lymphomas. Although primary laryngeal involvement of the MALT lymphoma is rare, several cases have been reported. This is the first report of MALT lymphoma of the larynx with MR imaging features.

This is a case story of a 14-year-old girl with severe anorexia nervosa (AN) (158 cm, 28 kg, –44.1% ideal body mass index), admitted with purpura, edema, and general fatigue. We treated her carefully and paid particular attention to prevent development of refeeding syndrome (RS), and her body weight increased satisfactorily. However, RS (edema, hypoalbuminemia, and heart failure) occurred despite careful treatment. We used albumin and diuretics for treatment of RS, but severe liver damage resulted. RS was aggravated by the medical treatment. More attention should have been paid to her weight gain and medical treatment should have been initiated more slowly to prevent dramatic changes in the patient's fluid and electrolyte status.

The objective of this study was to investigate the incidence and risk factors of pharyngocutaneous fistula following total laryngectomy. Patients: The study subjects included 45 patients who had received total laryngectomy at Jichi Medical University Hospital, between July 1, 1998 and June 30, 2006. Results: Pharyngocutaneous fistulae developed in 8 patients (18%). Two patients bled from the common carotid artery. There was no significant association between the following items and the incidence of fistula: the surgeon performing the operation, age, laryngectomy etiology, history of smoking, presence of diabetes, preoperative tracheostomy, preoperative partial laryngectomy, combined neck dissection, combined thyroidectomy, low serum albumin level and anemia. The incidence of fistula was significantly higher in patients undergoing concomitant radio chemotherapy. Postoperative hospitalization was significantly longer in the patients who developed fistula. Conclusion: The development of a pharyngocutaneous fistula represents a troublesome complication that often results in increased morbidity and hospitalization time. Following laryngectomy, it is necessary to perform a detailed check of local and systemic conditions and to give postoperative care. When a fistula forms, early and appropriate care is necessary.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have recently published, in both the Journal of the American College of Cardiology (JACC) and Circulation, a Scientific Statement on the Evaluation of Syncope ('Statement'). This Scientific Statement was commissioned to provide guidance for clinicians regarding the evaluation of patients who present with 'syncope'. The Statement was not intended to be a formal set of practice guidelines. However, in the absence of generally accepted practice guidelines in North America, the Statement's potential impact on clinical care may be more far-reaching than expected; it may erroneously be considered to be the authoritative 'de-facto' guideline document. This commentary, submitted by a multidisciplinary consortium of more than 60 physicians with expertise in the management of transient loss of consciousness (TLOC), points out that in many respects the ACCF/AHA Syncope Statement fails to address long-standing clinical errors associated with the evaluation of episodes of apparent TLOC, including syncope. If not appropriately revised, the current Statement may lead to both inadequate patient care as well as a potentially damaging legal environment for physicians undertaking evaluation of patients who present with transient loss of consciousness.

In this paper, quasi-static loading tests and fatigue tests are carried out on spot welded joints of mild steel (270MPa class) and ultra-high strength steel (980MPa class) sheets in order to investigate the influence of strength level of base steels on fatigue strength and fracture mechanism of spot welded joints. Under quasi-static loading, a spot welded part is more liable to be a fracture-initiation site in the ultra-high strength steel than in the mild steel, and as a result fracture behavior of the ultra-high strength steel is considerably affected by a spot welded part as compared with that of the mild steel. Although the fatigue strength of spot welded joints is higher in the ultra-high strength steel than in the mild steel in low cycle fatigue regime, the difference in fatigue strength decreases in high cycle fatigue regime and the fatigue limit is almost the same in both steels. Fracture morphology of spot welded joints under cyclic loading depends on the load level in the ultra-high strength steel, but not in the mild steel. From the comparison between S-N curves for spot welded joints and notched base steels, the dependency of fatigue strength of spot welded joints on base steels is attributed to the notch-sensitivity to fatigue strength of the base steels.

Background: Physical symptoms are an increasing problem among Japanese children and adolescents, and the symptoms seem to be related to their school situation. These symptoms are prevalent in Sweden, and a comparison with Japan is of interest due to the differences in the educational system and school climate. Objective and methods: To compare physical symptoms and psychiatric complaints in school pupils from Japan and Sweden, using a questionnaire that also addressed life satisfaction and stressful life events. The study population comprised 742 Japanese children and 1120 Swedish children attending public compulsory schools, grades 4–9 (10–15 y). Physical symptom and psychiatric complaint scores were calculated for each pupil. Results: The Japanese children had significantly higher physical symptom and psychiatric complaint scores than did the Swedish children. Both the physical symptom and psychiatric complaint scores were significantly higher in adolescents than in preadolescents in Japan; this trend was less apparent in Swedish children. In addition, Japanese children were found to have considerably lower life satisfaction. Loss of appetite was the only physical symptom more prevalent in the Swedish population compared to the Japanese population. Conclusion: We conclude that Japanese schoolchildren have more physical symptoms and psychiatric complaints and less life satisfaction than Swedish schoolchildren of corresponding ages.

1979年以降, 一時治療として本治療方法を受けた症例は98例 (男性63人, 女性35人) であり, 平均年齢は61歳 (36～86歳) であった。平均観察期間は78カ月 (4～230カ月) である。症例全体の死因特異的生存率は5年および10年ともに77%であった。T分類別の5年局所制御率はT2 : 89%, T3 : 91%, T4a : 66%, T4b : 62%であった。5年局所制御率は扁平上皮癌以外の病理型では扁平上皮癌に比べ有意に悪かった。そこで80例の扁平上皮癌でのT分類別5年局所制御率ではT2 : 100%, T3 : 93%, T4a : 78%, T4b : 69%であった。眼窩先端部に進展を認めた症例では有意に局所制御が悪かった。89例のT3T4症例で72例の症例が治療後に適切な視機能を呈していた。本治療方法は上顎洞悪性腫瘍に対し有効な治療方法と考えられるが, 扁平上皮癌以外の病理型と眼窩先端部に進展を認める症例では適応に慎重を要する。

近年放射線治療単独と比較し化学放射線治療の有効性を示す報告がある。docetaxel (DOC) はチューブリンの合成を阻害し, 放射線に感受性を有するG2/M期に細胞周期を停止させる作用がある。よって放射線照射と併用することより有効な放射線増感効果が期待される。Stage III/IV頭頸部癌19症例を対象にDOC併用加速多分割放射線治療をおこなった。17例が治療を完遂できた。症例に対する治療効果は complete response (CR) 10例, partial response (PR) 7例であり, 奏功率100%, CR率58%であった。T分類別の効果ではCRをT1T2では11例中10例に認めたのに対し, T3T4では6例中0例であった。有害事象では全例に Grade 3以上の粘膜炎を認めた。疼痛管理に9例に麻薬の投与が必要であった。補助療法として末梢補液が8例, 経管栄養が2例, 中心静脈栄養が1例に必要であった。PR例では後治療として化学療法をおこないCRを得られた症例を認めた。

Objectives: To measure postural changes in cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance. Study design: We studied 28 patients (age, 10 to 22 years) and 20 healthy control subjects (age, 6 to 27 years). Cerebral oxygenated hemoglobin (oxy-Hb) and deoxygenated Hb were noninvasively and continuously measured with near infrared spectroscopy during active standing. Beat-to-beat arterial pressure was monitored by Finapres. Results: Orthostatic intolerance determined by cardiovascular responses to standing was observed in 16 of 28 patients: instantaneous orthostatic hypotension in 8, delayed orthostatic hypotension in 2, and postural orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared spectroscopy at the onset of active standing was not found in 15 of 16 patients with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with chronic fatigue without orthostatic intolerance but only in 2 of 20 control subjects. Thirteen of 16 patients with orthostatic intolerance showed prolonged reduction in oxy-Hb during standing. Conclusions: Impaired cerebral hemodynamics in patients with chronic fatigue syndrome and postural orthostatic tachycardia suggest a link between impaired cerebral oxygenation and chronic fatigue. However, this cannot explain the symptoms in patients meeting the criteria of chronic fatigue without orthostatic intolerance. (J Pediatr 2002;140:412-7)

We report the case of a 14-year-old boy with instantaneous orthostatic hypotension (INOH) with symptoms of orthostatic intolerance. We investigated the effect of high sodium intake on hemodynamics and circulatory responses to orthostatic stress using Portapres. Moreover, a multifrequency bioelectrical impedance method was used to confirm increased plasma volume. Although we began treatment with an alpha-adrenoceptor agonist after his admission into our hospital, the effect was not sufficient. We, therefore, began a regimen of high sodium intake (NaCl 3 g two times a day per os in addition to regular diet, NaCl 5-6 g /day) to increase plasma volume. As a result, 48 hours after sodium intake, orthostatic tolerance was markedly improved with a concomitant increase in blood pressure in the orthostatic test. By measuring the patient's body water before and after the high sodium intake, we were able to document the increase in plasma volume. We conclude that high sodium intake is an effective treatment for orthostatic hypotension in combination with vasoactive drugs.

1987年1月から2001年12月までに手術を施行した stage III/IV舌癌は36例 (stage III 18例, stage IV18例) であった。無病生存率 (Kaplan-Meier 法) は1年: 80%, 2年: 76%, 5年: 76%であった。再発は11例に認め, いずれも stage IV であった。再発および転移の部位は局所2例, 頸部リンパ節4例, 頸動脈間隙4例, 肺1例であった。頸部リンパ節再発と頸動脈間隙再発は術後1年以内の早期に認めた。頸部リンパ節再発に対し頸部郭清術を施行したが制御できず全例原病死した。また患側の頸動脈間隙再発を切除・再建18例中4例 (20%) に認めた。全例切除不能であり3例に化学放射線治療をおこなったが制御できず, 未治療の1例とともに原病死した。表在性の病変でも原発部位が正中にかかる場合や切除・再建術の対象となる場合には対側頸部リンパ節転移を認めなくても supraomohyoid neck dissection が必要と考えられた。切除・再建術の場合では頸動脈間隙再発を防ぐ切除方法や術後照射などの術後治療が必要と考えられた。

Cricoarytenoid arthritis is a frequent complication of rheumatoid arthritis. 17% to 33% patients with rheumatoid arthritis suffering from arthritis of the cricoarytenoid joints have been reported. In association with an upper respiratory infection, this can become life-threatening upper airway obstruction. We report a case of severely symptomatic cricoarytenoid arthritis in a 48-year old woman with rheumatoid arthritis. Dyspnea and stridor had appeared, and the cricoarytenoid joint was swollen. The vocal cord was fixed in the midline. The dyspnea and stridor had not reduced with conservative treatment, and tracheotomy was performed. After CO2 laser arytenoidectomy was performed, the patient was free of dyspnea for 7 months, and phonatory function was as good as before the surgery.

The outcome of radiation therapy or surgery was studied retrospectively in 30 previously untreated patients with squamous cell carcinoma (SCC) of the lateral wall of the oropharynx. Twenty-two patients with tonsillar SCC and 8 patients with tonsillar pillar SCC were treated between 1978 and 1997 at the Jichi Medical School Hospital. The group consisted of 25 men and 5 women, aged 34 to 82 years (average, 63 years). In the tonsillar SCC group, lesions were T1 in 2 cases, T2 in 2, T3 in 13, and T4 in 5; 5, 3, 12 and 2 patients had NO, N1, N2, and N3 disease, respectively. In the tonsillar pillar SCC group, lesions were T2 in 5 cases, T3 in 2, and T4 in 1; 6 patients had NO, 1 had N1, and 1 had N2 disease. Fourteen patients were treated with radiation and 16 were treated with surgery, 14 of whom also received preoperative irradiation. Eleven patients in the surgery group underwent resection by a transoral approach and 5 underwent extended surgery with reconstruction. Disease-free survival rate at 3 years by the Kaplan-Meier method was 64% in the radiation group and 78% in the surgery group (not significantly different) in those with tonsillar SCC, and 67% and 82%, respectively, (not significantly different) in those with tonsillar pillar SCC. The surgical approach was transoral in patients with noninvasive T2 or T3 primary lesions. No local recurrence was observed. Transoral resection appears to be useful for treating noninvasive lateral wall SCC of the oropharynx.

Recent advances in computer technology have made it possible to noninvasively determine fast and dynamic changes in autonomic nervous activity in humans. Power spectral analysis of heart rate variation, beat-to-beat blood pressure analysis, skin blood flow by the laser Doppler technique, sensitive sudorometry and direct measurement of sympathetic nervous discharge have been successfully applied in adults, but there are still only few studies reported in children and adolescents. This article reviews the usefulness of these autonomic function tests in the pediatric field including reliability and methodological limits. Power spectral analysis of heart rate variability seems to be a new potential method, but there have been only few studies in children. Orthostatic maneuvers with noninvasive beat-to-beat measurement of finger arterial pressure, especially during active standing, is useful for the evaluation of orthostatic intolerance in children as well as adults with autonomic failure. A new pharmacological method using multiple autonomic agents might indicate a more precise information including alpha- and beta-adrenoceptor sensitivity. It should be realized that a single test cannot identify impaired autonomic functions, and a combination of several autonomic tests should be employed. Moreover, age-related changes and racial differences in autonomic function should be considered when interpreting obtained results.

Postural tachycardia syndrome (POTS) manifests as marked tachycardia while standing. We noticed two forms of circulatory response to orthostatic stress in POTS. We investigated cardiovascular and autonomic nervous response to orthostatic stress in the two forms.We studied 79 patients with POTS and 38 healthy control subjects (Ct). Beat-to-beat blood pressure (BP) and heart rate (HR) were non-invasively and continuously measured in the supine and standing positions. Autonomic nervous function was evaluated on power spectral analysis of HR variability and diastolic BP variability. We divided the subjects into two groups: standing-induced tachycardia (SI group; increase in HR ≥35 beats/min) and supine tachycardia (Su group; standing HR ≥115 beats/min with standing-induced HR increase35 beats/min).The Su group had higher supine BP and HR compared with the other groups, indicating dominant sympathetic control of the heart in the supine position. While rising, the SI group had a higher increase in HR than the Ct group, indicating excessive withdrawal of vagal tone. The Su group had a smaller increase in HR and a greater decrease of systolic BP and cardiac index by standing compared with the SI group. These results suggest that compensatory mechanisms of sympathetic function during standing failed in the Su group, probably because of exhaustion by the nearly maximum effort to generate sympathetic drive even in the supine position with low central blood volume.There is a difference between the two types of POTS, in the balance of resting autonomic function and hemodynamic response to standing.

我々は, 超音波振動時に発生するキャビテーション効果を口腔内のプラークコントロールに応用する目的で一連の実験を行っている。今回は, 人工プラークの除去効果が高い2種類のチップを使用し, 顎模型を水中に浸漬した状態で, キャビテーション効果による歯間部隣接面の人工プラークの除去効果について検討を行った。近心隣接面, 4近心隣接面, 6遠心隣接面を被験面とし, プラーク除去用チップ1 側面より発生するキャビテーションを, 口蓋側あるいは頬側のどちらか片側から照射した場合と両側から照射した場合の経時的な人工プラークの除去率を測定した。また, 各チップによる人工プラークの除去率と各歯種ごとの歯間空隙の形態との関係についても検討を加えた。その結果, 片側から照射した場合の人工プラークの除去率は歯種別では1において最も高い除去率を示すことがわかった。また, 1, 4については口蓋側方向から高い除去効果が得られたが, については照射方向での除去率に差は認められなかった。さらに, 両側から照射した場合は, 短時間で隣6接面のほとんど全ての人工プラークが除去されることが確認された。しかし, チップの振動振幅の相違による人工プラークの除去率に差は認められなかった。これらの結果より, キャビテーション効果による隣接面の人工プラークの除去に関しては歯種および歯間空隙の形態学的な要因が関与することが伺われた。

An A to G transition at nucleotide 3, 243 in the tRNALeu (UUR) gene of mitochondrial DNA has recently been identified as a pathogenic point mutation which is associated with diabetes mellitus and sensorineural deafness in several pedigrees. We have also reported a family showing the association of deafness and diabetes mellitus as the predominant clinical features with this mutation. Audiologic data from two patients in this family are presented. Both had a bilaterally symmetrical sensorineural hearing loss at all frequencies. As is often the case with deafness associated with a mitochondrial disorder, the pure-tone threshold values were maximal at high frequencies in both patients. The audiologic work-up presented not only cochlear characteristics but also signs suggestive of retrocochlear disturbance with poor speech discrimination scores as compared to pure-tone thresholds, although auditory brain-stem responses showed neither wave delay nor prolonged interpeak latencies. Caloric excitability was not impaired.

Wilms' tumor (WT1) protein is one of the most promising target antigens for cancer immunotherapy. In fact, clinical responses, such as growth stabilization or shrinkage of tumor with immunological responses, have been reported in patients vaccinated with WT1 peptide. Here, we performed WT1 peptide-based immunotherapy for a patient with chemotherapy-resistant salivary gland cancer, whose histologic type was carcinoma ex pleomorphic adenoma. The patient with its pulmonary metastasis, refractory to chemotherapy, was intradermally injected with 3 mg of WT1 peptide emulsified with Montanide ISA51 adjuvant at one-week intervals for 12 weeks. The considerably rapid growth of tumor was inhibited after WT1 vaccination, and stable disease, lasting three months, was achieved. Concomitantly, immunological responses, i.e. an increase in frequencies of WT1 tetramer(+) CD8(+)T cells and delayed type hypersensitivity response, were detected after the vaccination. These results indicate the potential of WT1 peptide-based immunotherapy for the treatment of chemotherapy-resistant salivery gland cancer.

Psychosomatic and developmental behavioral medicine in pediatrics has been the subject of significant recent attention, with infants, school-age children, and adolescents frequently presenting with psychosomatic, behavioral, and psychiatric symptoms. These may be a consequence of insecurity of attachment, reduced self-confidence, and peer -relationship conflicts during their developmental stages. Developmental cognitive neuroscience has revealed significant associations between specific brain lesions and particular cognitive dysfunctions. Thus, identifying the biological deficits underlying such cognitive dysfunction may provide new insights into therapeutic prospects for the management of those symptoms in children. Recent advances in noninvasive neuroimaging techniques, and especially functional near-infrared spectroscopy (NIRS), have contributed significant findings to the field of developmental cognitive neuroscience in pediatrics. We present here a comprehensive review of functional NIRS studies of children who have developed normally and of children with psychosomatic and behavioral disorders.

In Japan there are a number of children and adolescents with emotion-related disorders including psychosomatic diseases (orthostatic dysregulation, anorexia nervosa, recurrent pains), behavior problems and school absenteeism. According to our previous report, the Japanese children had significantly higher score of physical symptoms and psychiatric complaints than did the Swedish children, and these were more strongly influenced by school-related stress than by home-related stress. To enforce countermeasures for psychosomatic problems in children, the Japanese Society of Psychosomatic Pediatrics (established in 1982) have started several new projects including multi-center psychosomatic researches and society-based activities. In this article, we present an outline of our study on mental health in Japanese children in comparison with Swedish children. Countermeasures including clinical guidelines for child psychosomatic diseases are reviewed and discussed.

Cardiovascular responses on active standing in children with unexplained syncope were investigated with continuous non-invasive finger artery pressure monitoring (Finapres). We examined 34 symptomatic patients (13 boys and 21 girls), aged 8-16 years, and 24 age-matched controls. Finger blood pressure and heart rate were monitored continuously for 5 min in the supine position and for 10 min while standing. Ten of 34 patients developed fainting symptoms with hypotension during upright posture (fainters). In the initial standing phase (0-30 s), two prominent abnormal blood pressure responses were found in patients: a marked decrease 45 +/- 18/23 +/- 8 mmHg and a prolonged recovery time (16.5 +/- 2.9 versus 27.7 +/- 13.6 s), which appeared to be based on impaired vasoconstriction. Either or both abnormalities were observed in 21 (62%) of the 34 patients and in 2 (8%) of the controls. In addition, fainters also had a more marked increase in heart rate during standing compared with non-fainters. Our findings suggested that more than half of children with syncope had abnormal cardiovascular reflexes in the initial phase which appeared to be associated with vasodepressor syncope. The active standing test with a continuous beat-to-beat blood pressure recording has a high sensitivity in detecting abnormalities of autonomic function in patients with unexplained syncope.

本研究は超音波振動時に発生するキャビテーション効果をプラークコントロールに応用することを目的として行った。すなわち超音波発生装置として市販の超音波スケーラー本体と, 水中で超音波振動によりキャビテーションを発生する試作チップ20種類を用い, チップの形態および人工歯面との距離と人工プラークの除去効果について基礎的実験を行った。プラーク除去用チップの屈曲位置と屈曲角度を変えることにより人工プラークの除去面積と振動振幅の大きさは変化することがわかった。しかし, チップの屈曲角度と人工プラークの除去面積の間には一定の関係は認められなかった。また, 振動振幅の大きさがある一定値 (約30μm) までは人工プラークの除去面積は増加するが, その値を超えるとほとんど増加しないことがわかった。さらに, チップと人工歯面との距離と人工プラークの除去面積の関係をみると, その距離が2～3mmのとき最も高い除去効果が認められ, それ以上の距離になると除去面積は減少するが, 約6mmまでは除去可能なチップも存在することが確認された。以上のことから, 今回20種類の試作チップについてプラーク除去効果を調べた結果, キャビテーション効果をプラークコントロールに応用できる可能性が示唆された。

Chronic pain is a common problem in pediatric practice. The prevalence of chronic pain in children is30%. Because pain indicates emotional expression as well as the physiological reaction toward infection, injury, and inflammation, both physiological and psychological assessments are essential to determine primary interventions for chronic pain. The Japanese Society of Psychosomatic Pediatrics Task Force of clinical practice guidelines for chronic pain in children and adolescents compiled clinical evidence and opinions of specialists associated with the primary care of pediatric chronic pain in the Japanese 'clinical guidelines for chronic pain in children and adolescents' in 2009, which are presented herein. The guidelines consist of three domains: general introduction to chronic pain; chronic abdominal pain; and chronic headache. Each section contains information on the physiological mechanism, psychological aspects, assessment methods, and primary interventions for pediatric chronic pain. These guidelines are expected to help disseminate knowledge on primary interventions for chronic pain in children and adolescents.

Postural tachycardia syndrome (POTS) is one of the most frequent forms of chronic orthostatic intolerance in children and adolescents. The aim of the present study was to examine the influence of a genetic background on POTS.A total of 96 children and adolescents with orthostatic dysregulation were studied. The polymorphism of the G protein β3 subunit (GNB3) C825T and G protein α subunit (GNAS1) T131C of genes encoding components of the autonomic nervous system were determined and compared with circulatory responses to active standing.In the GNB3 gene C825T polymorphism, the CT and TT genotype had a significant lower supine heart rate and a larger increase of heart rate by standing than the CC, associated with evaluated power of the high-frequency component of heart rate variability. According to the criteria of the Japanese clinical guidelines, 48 children were diagnosed as POTS and 30 were as normal responder with somatoform disorder (SD). In GNB3 C825T polymorphism, the TT genotype was more frequently found in the POTS group (45.8%) than in the SD group (20.0%; P = 0.036) [corrected]. In the GNAS1 T393C, the genotype frequencies for the T393C polymorphisms of GNA1 did not differ significantly between the groups.The gene polymorphisms GNB3 C825T might be a risk factor for POTS through the enhanced vagal withdrawal of the heart in children and adolescents.

The purpose of the present study was to determine the levels of osteocalcin, a bone specific matrix protein, in gingival crevicular fluid (GCF) from periodontal disease patients and to investigate the relationship between GCF osteocalcin levels and clinical parameters. Nineteen initial visit patients, 5 patients with gingivitis and 14 patients with adult periodontitis, participated in this study. The clinical parameters including probing depth, attachment level, gingival index, and tooth mobility were recorded following careful sampling of GCF with a filter paper strip harvested for 3 minutes. Osteocalcin adsorbed on a strip was extracted in a plastic tube containing 150 microliters of 10 mM sodium phosphate buffer (pH 6.5). GCF osteocalcin was determined by a newly-developed, high sensitive enzyme immunoassay which could recognize the N-terminal 20 residue peptide. In gingivitis patients, no significant amounts of osteocalcin were detected. In periodontitis patients, on the other hand, osteocalcin levels were detected, ranging between 0 and 540 pg/tube and positively correlated with these clinical parameters (P < 0.01). Moreover, in several sites in GI = 3 group, extremely higher levels of GCF osteocalcin were detected. These results strongly suggest that in addition to the presence of GCF osteocalcin the levels of osteocalcin may reflect the degree of the periodontal inflammation at the sampled sites.

歯周疾患における歯肉溝滲出液 (GCF) のタンパク濃度の臨床パラメーターとしての有用性を検討した。対象は成人型歯周炎患者 (23名) で, 平均年齢は52.7歳であった。被検部位はレントゲン写真上で明らかな歯槽骨破壊の認められる歯周ポケット93ヵ所を任意に選択した。本研究に用いたパラメーターは, Plaque Index (PlI), GCF量, probing depth (PD), attachment level (AL), Gingival Index (GI) および動揺度 (Mo) の6種類であった。GCFは, ペリオペーパー ®を 歯肉縁下約1mmに3分間保持, 採取し, ペリオトロン (®6) 0 00にて液量を測定した後, Lowry法を用いてタンパク濃度を算出した。その結果, タンパク濃度と6種のパラメーターとの相関係数は, 上記の記載順に0.41, 0.70, 0.31, 0.29, 0.60および0.39であり, Spearmanの順位相関ですべて有意であった (p

The present investigation is about cardiovascular responses and relevant autonomic function in Swedish and Japanese pubertal children on active standing using non-invasive continuous beat-to-beat finger arterial pressure (FAP) monitoring and power spectral analysis. Examined were 54 Swedish and 57 Japanese children (13-15 years). FAP and heart rate (HR) was continuously recorded in the supine position and during standing. Supine FAP was significantly higher in Swedish compared with Japanese children (121/62 versus 103/53 mmHg, P < 0.001). Swedish children showed a higher increase in arterial pressure and HR upon uprising, resulting in a higher vasoconstrictor index (5.04 ± 0.22 versus 2.31 ± 0.11 mmHgs-1, P < 0.001, respectively). There were also higher increases in arterial pressure and HR in the following steady state period (1-7min) between the two groups. These differences were also found after adjustment of body weight and height. Frequency domain analysis of HR and arterial pressure variability indicated significantly higher low/high frequency power of HR and low frequency power of arterial pressure. These results suggest that Swedish pubertal children have higher basal blood pressure and enhanced cardiovascular sympathetic responses. These differences in the two cohorts might be caused by genetic factors. © 2008 The Authors Journal compilation © 2008 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

障害者の歯周疾患に関する実態を知る目的で, 長崎県内の障害者144名の歯周組織の状態について診査を行った。代表歯6歯 (6 14 41 6) の近心頬側部のProbing Pocket Depth (PDD), Gingival Index (GI), Plaque Index PII), Calculus Index (CI) を調べた。また, アタッチメントレベルとX線写真により, 歯肉炎と歯周炎に分類 (し各々の罹患率を調べ, また歯肉増殖についても調査した。その結果, 全体の99%が歯周疾患に罹患しており, そのうち, 歯周炎は約58%であった。歯周炎の罹患率は10歳代で22%, 20歳代で43%と若年層においても高率であった。PPD, GI, PII, CIの各平均値は健常者より高く, また, 知能程度や在宅と施設の障害者について比較すると, 歯周炎罹患率や歯周組織の状態に差が認められた。抗てんかん剤服用者のうち約31%に歯肉増殖が認められ, これらの者の多くに歯列不正が認められた。

It is postulated that child chronic fatigue syndrome (CFS) involves the autonomic nervous system, although the precise mechanism has not been clearly indicated. This paper reviews recent reports focusing the role of the autonomic nervous system which plays in CFS. Many of the method for measuring autonomic function have appeared in the clinical setting in parallel with advancing computer technology, but these are limited when applied in children. In these blood pressure and heart rate changes during orthostatic stress and these variability are favorably used. As a result, one third of children with CFS showed abnormal cardiovascular adjustment during posture change (orthostatic dysregulation: OD) which is characterized by instantaneous orhthostatic hypotension, postural tachycardia or neurally-mediated syncope. Most of the studies using power spectral analysis of heart rate variability showed sympathetic activation, however no consistent finding has been obtained. In conclusion, autonomic function might be partly involved in CFS such as OD, but its priority in causing CFS is unclear.

Objective While generally considered an effective treatment for moderate to severe epistaxis in hereditary hemorrhagic telangiectasia (HHT), nasal dermoplasty (ND) has not been well established in Japan. This prompted the present Japanese assessment of clinical efficacy and patient satisfaction following this procedure. Methods Retrospective analysis of clinical records of 15 patients with HHT undergoing ND between August 1991 and May 2004 and survey of these patients as to postsurgical conditions. Main outcome measures were skin graft “take” frequency after surgery (all patients), reported patient satisfaction (eight recent patients), and reported volume and frequency of epistaxis after versus before surgery (eight recent patients). Results Graft take rate was 100%. Most patients experienced reduced frequency and volume of bleeding. One patient required an additional operation, total closure of the external nares, 2 years later. Overall patients felt satisfied with ND, experiencing less nasal obstruction than expected. Conclusions ND is effective in Japanese patients with moderate and severe nasal bleeding from HHT, reducing their risk of bleeding.

A 19-year-old Japanese man exhibiting acute right sensorineural hearing loss and vertigo was referred to the Jichi Medical School Hospital in June 1994. Although he had no history of recurrent thrombosis and no family history of thrombosis, he had undergone reconstruction of a right foot joint fracture 4 months earlier. Screening studies for plasminogen activity demonstrated 10% of normal plasminogen activity and his plasminogen was diagnosed as "plasminogen Tochigi" by the gene analysis using restriction enzyme Fnu4HI. The patient's hearing returned to normal with administration of heparin, and he was prescribed warfarin for the prevention of thrombosis until October 1995. There was no recurrence of hearing loss during seven years of follow-up. The cause of this patient's hearing loss is believed to be associated with consumption of the already low levels of plasminogen as a result of his surgery as well as congenital plasminogen disorder.

Background: The number of children with psychosomatic and psychosocial disorders has been increasing in Japan. There are, however, few trained pediatricians who have adequate knowledge of the treatment needed. The Research Group on the Promotion of Management of Children with Psychosomatic and Psychosocial Disorders carried out the present study to (i) disseminate knowledge about psychosomatic and psychosocial disorders of children; and (ii) establish a community-based network model to ensure effective communication among relevant institutions. Methods: To disseminate knowledge of the psychosocial and psychosomatic disorders, the Research Group compiled the Handbook for Psychosomatic Disorders of Children and distributed it to pediatricians throughout Japan. A follow-up questionnaire survey was then carried out. Also, in order to examine the current status of the communication network between pediatricians and the related institutions, the Research Group conducted a questionnaire survey on general pediatricians. Results: Sixty-five percent of the respondents indicated that they were actually using the Handbook. The topics in the Handbook that were most frequently referred to by the respondents were attention deficit hyperactivity disorders, school refusal, eating disorders, and orthostatic dysregulation. Thirty-seven percent of the participants indicated changes in their behavior towards psychosomatic and psychosocial problems. The results of the survey on communication networks found that the pediatricians generally collaborated with different institutions depending on the nature of the problems, such as school refusal and bullying, developmental disorders, child abuse and maltreatment, and others. Conclusion: Promotion of the Handbook would greatly contribute to improving the management of children with psychosomatic and psychosocial disorders, together with the construction of the basic network model for management of these children.