鈴木 猛司

頭頸部癌に対する化学放射線療法は広く行われている治療であるが,稀に合併症として仮性動脈瘤が形成されることがあり,破裂すると致死的な転機をとる。下咽頭癌の化学放射線療法後に総頸動脈の仮性動脈瘤破裂を生じた3症例を経験した。全例で総頸動脈の温存はできず,2例は脳梗塞を発症し寝たきりとなった。1例は初期治療として血管内治療を行い,その後喉頭壊死の治療と再出血予防のため遊離空腸再建を用いた咽頭喉頭食道摘出術と総頸動脈の合併切除を施行した。事前に脳梗塞リスク評価を行い,脳梗塞を発症することなく独歩で退院した。治療は初期止血だけでなく,再出血予防と脳梗塞のリスクを考慮することが重要である。(著者抄録)

37歳男性(脳性麻痺)。繰り返す誤嚥性肺炎に対し喉頭気管分離術を施行する方針となった。しかし術後、気道閉塞をきたし、術後10日に気管支内視鏡検査で気管軟化症と診断された。対処として人工呼吸器による陽圧管理を継続した結果、良好にて在宅人工呼吸器管理による保存的治療の方針となり、術後49日に自宅退院となった。退院後はかかりつけ医で経過観察され、退院から1ヵ月半経過で人工呼吸器装着は夜間のみとなった。

Healthcare providers are vulnerable to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their close proximity to patients with coronavirus disease 2019. SARS-CoV-2 is mainly transmitted via direct and indirect contact with respiratory droplets, and its airborne transmission has also been identified. However, evidence for environmental factors is scarce, and evidence-based measures to minimize the risk of infection in clinical settings are insufficient. Using computational fluid dynamics, we simulated exhalation of large and small aerosol particles by patients in an otolaryngology examination room, where medical procedures require the removal of a face mask. The effects of coughing were analyzed, as well as those of humidity as a controllable environmental factor and of a suction device as an effective control method. Our results show that a suction device can minimize aerosol exposure of healthcare workers by efficiently removing both large (11.6-98.2%) and small (39.3-99.9%) aerosol particles. However, for coughing patients, the removal efficiency varies inversely with the particle size, and the humidity notably affects the aerosol behavior, indicating the need for countermeasures against smaller aerosols. Overall, these results highlight the potential and limitation of using a suction device to protect against SARS-CoV-2 and future respiratory infections.

BACKGROUND COVID-19 is treated using antiviral and immunosuppressive drugs. Therefore, patients treated for COVID-19 may have an increased risk of secondary infection and a masked inflammatory response. We present a case of a deep neck abscess caused by pyogenic sternoclavicular arthritis during treatment for COVID-19. CASE REPORT A 55-year-old man with COVID-19 was admitted to the hospital with hypoxemia. He was then treated with remdesivir, tocilizumab, and dexamethasone and was placed in the prone position. When his condition stabilized, pain in the left shoulder appeared. There was no fever or elevation in inflammation markers, and he was administered analgesics. However, the pain worsened and redness of the left neck appeared. Plain computed tomography (CT) showed swelling of the left neck muscles. Because cellulitis was suspected, he was treated with antibiotics, but his symptoms did not improve. Three days after the plain CT, contrast-enhanced CT showed sternoclavicular arthritis, deep neck abscess, and mediastinal abscess. Therefore, an emergency incisional drainage was performed under general anesthesia. Wound cleaning and drainage were continued after surgery, and after drainage tubes were removed, the patient was discharged on postoperative day 17. CONCLUSIONS Cervical infections after COVID-19 treatment have been reported in a few cases. Particularly, deep neck abscesses require more attention since they could be fatal if not treated immediately. If a secondary infection is suspected in a patient treated with immunosuppressive drugs for COVID-19, a thorough physical examination should be performed to avoid misdiagnosis.

Background/Aims: The Lyon Consensus defined parameters based on upper endoscopy and 24-hour combined multichannel intraluminal impedance-pH (MII-pH), that conclusively establish the presence of gastroesophageal reflux disease (GERD). However, the true role of upper endoscopy and MII-pH to evaluate patients with extraesophageal symptoms (EES) has not been well established. Hypopharyngeal MII (HMII), which directly measures laryngopharyngeal reflux (LPR) events, has been utilized to evaluate patients with EES suggestive of LPR. Methods: This was a retrospective study involving patients with EES for > 12 weeks despite proton pump inhibitor therapy, and had no endoscopic confirmatory evidence for GERD and negative MII-pH. All patients were subsequently referred for further evaluation of EES with "unknown" etiology and underwent laryngoscopy and HMII. Based on HMII, abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (reflux 2 cm distal to the upper esophageal sphincter) > 4/day. Patients with APE were offered antireflux surgery (ARS) and the outcome of ARS was objectively assessed using Reflux Symptom Index. Results: Of 21 patients with EES which was thought to be GERD-unrelated based on endoscopy and MII-pH, 17 patients (81%) had APE. Eight patients with APE who had undergone ARS had significant symptomatic improvement in the Reflux Symptom Index score (19.6 ± 4.9 pre-ARS to 5.8 ± 1.4 post-ARS, P = 0.008). Conclusions: A conventional diagnostic approach using endoscopy and MII-pH may not be sufficient to evaluate patients with EES suggestive of LPR. HMII is essential to evaluate patients with EES, and APE could be a reliable indicator for successful treatment outcomes.

This report is the first to document TEN caused by nivolumab treatment in head and neck cancer. We believe this article can contribute significantly in understanding the principles of nivolumab treatment in patients with head and neck cancer.

良性対称性脂肪腫症(Madelung病)は頸部や躯幹,四肢などに対称性,多発性に脂肪が蓄積する疾患である。Madelung病の3例を経験したので考察を加えて報告する。症例1は76歳男性で,嗄声や嚥下障害,喉頭周囲の脂肪沈着を認めた。手術後の嚥下機能の悪化を懸念して経過観察の方針とした。症例2は61歳男性で,咽頭後間隙に脂肪組織を認め腫瘍摘出術を行った。症例3は72歳男性で,咽頭後および傍咽頭間隙に脂肪沈着を認め,腫瘍摘出術を行い整容的に高い満足度が得られた。本疾患では患者に整容的な改善の希望がある場合や気道閉塞,嚥下障害などの機能異常を認めた際には積極的に外科的治療を検討することが重要である。(著者抄録)

BACKGROUND: Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis. METHODS: One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups. RESULTS: The median salivary pepsin concentration in patients with AET > 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0-469.3] ng/mL vs. 120.0 [97.0-290.1] ng/mL, p < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test (> 109 ng/mL) to diagnose patients with AET > 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group. CONCLUSIONS: In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.

Hypopharyngeal multichannel intraluminal impedance (HMII) that can measure laryngopharyngeal reflux (LPR) events has supported the causal relationship between chronic cough (CC) and LPR containing liquid. However the role of "gas" LPR associated with CC has been poorly understood. We present two cases of patients with CC who had negative LPR containing liquid but had multiple episodes of "gas" LPR on HMII. The majority of "gas" LPR events had a minor pH drop at hypopharynx. Since any etiology of CC was excluded and medical therapy failed, both patients underwent laparoscopic antireflux surgery (LARS). Both of the patients had complete resolution of cough postoperatively. The present cases demonstrated successful outcome of LARS to treat the patients with CC who had documented "gas" LPR on HMII, thus suggesting the causal relationship between CC and "gas" LPR. The number of "gas" LPR events may need to be considered as an important diagnostic parameter.

保存的治療抵抗性の咽喉頭逆流症(LPRD)28例(男性16例、女性12例、年齢中央値51歳)に対し腹腔鏡下逆流防止術(LARS)を施行し、治療効果について検討した。術後経過観察期間12ヵ月(中央値)の結果、LPRD主症状は26例(93%)で改善が認められ、うち16例(57%)は症状の完全な消失が得られていた。LARS後3ヵ月の時点でFSSG、RSIスコアは有意に低下するも、RSIスコアは正常値であった。一方、2例は症状不変であった。また、2例で症状再発が認められたが、いずれもwrapの縦隔内逸脱を腹腔鏡下に整復し、再手術後は症状の改善が得られた。尚、LARSの有害事象である3ヵ月以上継続する食事時の心窩部のつまり感は5例(18%)で確認された。

慢性咳嗽の原因としてGERDは鑑別の一つとなりうるが、本邦では欧米に比較し、その割合は低いと考えられている。しかし、PPI抵抗性のGERDや食道粘膜障害を伴わないNERDの存在、また、日本人の肥満率は欧米のそれと比べ低いことから日本人のGERD罹患率が低く見積もられている可能性がある。近年、24時間下咽頭食道多チャンネルpHインピーダンス検査(HMII)が開発され、確定診断が難しかった咽喉頭逆流(LPR)を測定することができるようになった。本研究は、本邦で初めてHMIIを用い、日本人の原因不明慢性咳嗽患者における咽喉頭逆流症(LPRD)の関与を検討する目的で行った。日本人原因不明慢性咳嗽患者の73%にabnormal proximal exposure(APE)を認め、難治性慢性咳嗽はLPRを含めた胃内容物の高位逆流が原因である可能性が示唆された。また、DeMeester scoreは63%が正常であり、約40%のLPRまたは食道高位への逆流は非酸性の逆流であり、24時間pHモニタリングでは診断が難しく、難治性慢性咳嗽の診断にはHMIIが必要であると考えられた。(著者抄録)

Background: Clinical characteristics of laryngopharyngeal reflux (LPR) in Japanese population remain unclear, and its treatment outcome is suboptimal. The objectives of this study were to evaluate Japanese patients with LPR symptoms using hypopharyngeal multichannel intraluminal impedance (HMII) and to assess the outcome of antireflux surgery (ARS). Methods: Subjects included patients who had LPR symptoms for &gt 12 weeks or laryngoscopic findings suggestive of LPR and underwent laryngoscopy and esophageal testing including HMII. Abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (FCR) (reflux 2 cm distal to the upper esophageal sphincter) ≥ 5/day on HMII. Patients with APE were offered ARS and the outcome of ARS was objectively assessed using Reflux Symptom Index (RSI). Results: From July 2015 to September 2016, 52 patients with LPR symptoms (28 men, 24 women, median BMI 22.3) underwent HMII, and 38 patients (73%) had APE. Of them, 29 (76%) patients were not obese (BMI &lt 25) and 19 (50%) patients had a negative DeMeester score. Approximately one-third of LPR and FCR events were non-acid in the distal esophagus. A positive symptom-association probability was seen only in 18 patients (35%). Mild esophagitis and hiatal hernia were found in 5 (10%) and 23 (48%) patients, respectively. All 12 patients (100%) who had undergone ARS were able to discontinue PPI and had a significant improvement in the RSI scores postoperatively (22.9 ± 10.0 vs. 6.8 ± 6.8, p &lt  .001). Conclusions: APE was frequently observed in Japanese patients with LPR symptoms. Obesity and esophagitis were uncommon in this population. Since a large number of patients with APE had negative DeMeester score and proximal reflux events were often non-acid, a conventional pH monitoring is insufficient. HMII is crucial to evaluate patients with LPR symptoms as the documentation of APE is a key for successful outcome of ARS.

OBJECTIVES: A novel catheter that can measure mucosal admittance (MA), the inverse of impedance, was developed recently. In this pilot study, we aimed to clarify the usefulness of measuring MA for diagnosing gastroesophageal reflux disease (GERD). METHODS: We conducted two prospective studies. In the first study, esophageal MA was evaluated in 120 participants (24 with erosive esophagitis, 82 with heartburn but non-erosive esophagitis, and 14 healthy volunteers) and compared with the endoscopic findings. In the second study, multichannel intraluminal impedance combined with pH (MII-pH) tests was conducted followed by an MA measurement in 33 patients with non-erosive esophagitis and proton pump inhibitor (PPI)-refractory heartburn. Based on the MII-pH test results, patients were divided into GERD or functional heartburn (FH). MA was compared between the GERD and FH groups and also compared with the baseline impedance (BI) and acid exposure time (AET). RESULTS: Median MA at the distal esophagus was significantly higher in patients with erosive esophagitis compared with that in patients with non-erosive esophagitis and healthy volunteers (46.8, 13.1 and 6.5, respectively, P&lt;0.01). In patients with PPI-refractory heartburn, the median MA at the distal esophagus was significantly higher in patients with GERD than those with FH (19.3 vs. 7.2, P&lt;0.05). There was a negative correlation between MA and BI, and a positive correlation between MA and AET at the distal esophagus (r=-0.46 and r=0.53, P&lt;0.05). CONCLUSIONS: Real-time measurement of MA is useful to distinguish GERD from non-GERD.

73歳男。右頸部腫脹を主訴とした。高血圧と慢性心房細動の既往があり、スピロノラクトン、ファモチジン、ワルファリンカリウムを服用していた。生検にてsquamous cell carcinomaを認め、頸部造影CT所見にて、右側口蓋扁桃に30mmの腫瘤および同側のLevel II頸部リンパ節に複数の腫大を認めた。以上より、中咽頭右側壁扁平上皮癌cT2N2bM0と診断した。初診1ヵ月後からセツキシマブ投与を開始し、第5病日から放射線治療2Gy/日を開始した。第24病日に下血を訴え、PT-INR 4.88と凝固の過延長を認めたため、ワルファリンカリウムを中止し、絶食、補液による保存的加療を行った。加療後、下血は自然軽快したため、第35病日よりワルファリンカリウム内服を再開した。頸部造影CTにて中咽頭原発巣およびリンパ節の著明な縮小を認め、第41病日にはセツキシマブ投与を再開し、第61病日には放射線治療を完遂した。第77病日に40.2℃の発熱と呼吸苦の訴えがあり、急性呼吸促迫症候群を疑い、メロペネムとステロイドパルスによる治療を開始した。呼吸状態は改善したが、第102病日に、胸部単純X線にて右横隔膜下にfree airを認め、腹部造影CTでは、横隔膜と肝臓の間隙に大量のfree airを認め、腸管内容物の増加と麻痺性イレウス様の所見も認めた。緊急開腹術を行い、S状結腸を中心に、骨盤内・結腸全体にベラークが付着し、S状結腸・下行結腸には憩室の多発と移行部付近に穿孔を認めた。ドレナージおよび同部位を用いて人工肛門を造設した。術後経過は良好で、プレドニゾロンは約1ヵ月で漸減終了し、中咽頭癌の完全寛解を認めた。消化管症状の再燃はなく、1年後に人工肛門閉鎖術を施行した。中咽頭癌の再発も認めなかった。

Background: People with allergic rhinitis often have laryngeal symptoms (LSs) in addition to nasal symptoms during the pollen-scattering season. Objective: To clarify the characteristics of the LSs induced by pollen exposure using an environmental challenge chamber. Methods: Cypress pollen exposure using an environmental challenge chamber for 25 participants with cypress polleneinduced allergic rhinitis was performed for 3 hours for 2 consecutive days in 3 study courses: namely, pollen exposure under normal nasal breathing and pollen or sham pollen exposure with nasal blockage, which eliminated any allergic reactions in the nasal mucosa. The nasal and LSs scores and the levels of serum inflammatory mediators, including eosinophil cationic protein (ECP), were monitored. Laryngeal examinations and physiologic lung tests were also conducted. Results: Various LSs were reported, and these LSs were significantly elevated during pollen exposure and even under sham exposure with artificial nasal blockage. The pollen exposure with artificial nasal blockage exaggerated the LSs in 32% of the participants and also increased the serum ECP levels. The serum ECP levels did not change after sham exposure. The findings of both laryngeal examinations and lung tests failed to reveal any significant changes. Conclusion: Nasal obstruction could induce significant LSs even without pollen exposure. LSs were enhanced by pollen exposure and allergic reactions in the larynx could thus be involved in this enhancement. Trial Registration: clinicaltrials.gov Identifier: UMIN000015667. (C) 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A 73 year-old male was referred to our hospital complaining of swelling of his right neck, and was diagnosed as having oropharyngeal squamous cell carcinoma, clinical stage T2N2bM0. He had received concurrent radiotherapy with cetuximab treatment and achieved complete remission by the time he had received a total of 70 Gy of radiation to the neck and 7 courses of intravenous cetuximab treatment. However, he developed perforation of the sigmoid colon 1 month after completion of the cetuximab treatment. Cetuximab is a monoclonal antibody directed against epidermal growth factor receptor (EGFR), which binds to EGFR and inhibits cell proliferation. We searched PubMed and the Japan Medical Abstracts Society for cases of bowel perforation associated with cetuximab treatment, and identified 3 other cases of bowel perforation. All developed bowel perforation a couple of months after the completion of cetuximab treatment and had a history of gastrointestinal diseases like colon cancer, stoma creation and colonic diverticular disease. Only a few cases of severe gastrointestinal complications related to cetuximab treatment for head and neck cancer have been reported until now, and this is the first case of a patient with oropharyngeal carcinoma developing bowel perforation requiring urgent surgery. However, we suspect that EGFR inhibitors could exert toxic effects on the bowel mucosa in the same way as VEGF receptor inhibitors, the toxicity of which to the bowel mucosa came to be widely recognized during the post-marketing surveillance. Close observation with an index of suspicion for bowel perforation is thought to be necessary when treating head and neck cancer patients with cetuximab, especially in patients with a history of gastrointestinal diseases like diverticular disease.

声帯ポリープや声帯結節の診断・治療方針の決定には大きさなどの形態的特徴が関与することが多い。初診時から音声治療を行った声帯ポリープ36例、声帯結節35例について、手術の効果および手術の際に測定した病変の大きさと術前音声検査値との相関、病変の大きさとその術後改善率との相関を検討した。手術後の音声機能は、声帯ポリープ・声帯結節の両群で最長発声持続時間・声域・平均呼気流率・Jitter%値(基本周期の変動性の相対的評価)・Shimmer%値(ピーク振幅の変動性の相対的評価)のすべての項目で術前に比べ有意な改善を認めた。病変の大きさとの相関では、ポリープ症例は術前の声域・Jitter%で相関を認め、術後改善率では、声域・平均呼気流率・Jitter%・Shimmer%で相関を認めた。一方、結節症例では術前の声域のみ相関を認めた。Elite vocal performer(EVP)(職業歌手や舞台俳優など自身の「声」が芸術的、商業的価値を持ち、わずかな声の障害が職業に影響を与える)群とEVP以外群で検討を行い、声帯ポリープ症例のEVP群ではEVP以外群と比較して病変の大きさと音声検査値との相関は低かった。結節では両群とも病変の大きさと音声検査値との相関は低かった。両疾患において手術治療は有効で、形態的評価は治療方針決定のために必要であり、音声治療も両疾患の治療に不可欠であると思われた。(著者抄録)

Stimulation of vestibular receptors elicits distinct changes in blood flow to the forelimb and hindlimb, showing that the nervous system has the capacity to produce changes in sympathetic outflow which are specific for a particular region of the body. However, it is unclear whether the rostral ventrolateral medulla (RVLM), the primary region of the brainstem that regulates sympathetic outflow to vascular smooth muscle, has the appropriate connectivity with sympathetic preganglionic neurons to generate anatomically patterned responses. To make this determination, the retrograde fluorescent tracer Fast Blue was injected into the T-4 spinal cord segment of cats, which regulates upper body blood flow, whereas Fluoro-Ruby was injected into the T-10 segment to label projections to a region of the spinal cord that regulates lower body blood flow. More neurons were single-labeled by a particular tracer (92 %) than were double labeled by both tracers (8 %), supporting the notion that the RVLM can regulate sympathetic outflow from a limited number of spinal cord segments. Since a large fraction of RVLM neurons that control sympathetic outflow in rodents contain epinephrine, we additionally determined whether the tracer-labeled cells were immunopositive for the enzyme tyrosine hydroxylase (TH), which participates in the synthesis of catecholamines. Double labeling by the two tracers injected into the spinal cord was more common for TH-immunopositive neurons than for the general population of RVLM neurons: 19 % of the TH-positive cells contained both Fast Blue and Fluoro-Ruby, 30 % contained one of the tracers, and 51 % were not labeled by either tracer. Furthermore, many spinally projecting neurons in close proximity to the RVLM catecholaminergic neurons (41 % of the population) were not immunopositive for TH, suggesting that feline RVLM is neurochemically heterogeneous.

Suzuki T, Sugiyama Y, Yates BJ. Integrative responses of neurons in parabrachial nuclei to a nauseogenic gastrointestinal stimulus and vestibular stimulation in vertical planes. Am J Physiol Regul Integr Comp Physiol 302: R965-R975, 2012. First published January 25, 2012; doi: 10.1152/ajpregu.00680.2011.-The parabrachial and adjacent Kolliker-Fuse (PBN/KF) nuclei play a key role in relaying visceral afferent inputs to the hypothalamus and limbic system and are, thus, believed to participate in generating nausea and affective responses elicited by gastrointestinal (GI) signals. In addition, the PBN/KF region receives inputs from the vestibular system and likely mediates the malaise associated with motion sickness. However, previous studies have not considered whether GI and vestibular inputs converge on the same PBN/KF neurons, and if so, whether the GI signals alter the responses of the cells to body motion. The present study, conducted in decerebrate cats, tested the hypothesis that intragastric injection of copper sulfate, which elicits emesis by irritating the stomach lining, modifies the sensitivity of PBN/KF neurons to vertical plane rotations that activate vestibular receptors. Intragastric copper sulfate produced a 70% median change in the gain of responses to vertical plane rotations of PBN/KF units, whose firing rate was modified by the administration of the compound; the response gains for 16 units increased and those for 17 units decreased. The effects were often dramatic: out of 51 neurons tested, 13 responded to the rotations only after copper sulfate was injected, whereas 10 others responded only before drug delivery. These data show that a subset of PBN/KF neurons, whose activity is altered by a nauseogenic stimulus also respond to body motion and that irritation of the stomach lining can either cause an amplification or reduction in the sensitivity of the units to vestibular inputs. The findings imply that nausea and affective responses to vestibular stimuli may be modified by the presence of emetic signals from the GI system.

Sugiyama Y, Suzuki T, DeStefino VJ, Yates BJ. Integrative responses of neurons in nucleus tractus solitarius to visceral afferent stimulation and vestibular stimulation in vertical planes. Am J Physiol Regul Integr Comp Physiol 301: R1380-R1390, 2011. First published August 10, 2011; doi:10.1152/ajpregu.00361.2011.-Anatomical studies have demonstrated that the vestibular nuclei project to nucleus tractus solitarius (NTS), but little is known about the effects of vestibular inputs on NTS neuronal activity. Furthermore, lesions of NTS abolish vomiting elicited by a variety of different triggering mechanisms, including vestibular stimulation, suggesting that emetic inputs may converge on the same NTS neurons. As such, an emetic stimulus that activates gastrointestinal (GI) receptors could alter the responses of NTS neurons to vestibular inputs. In the present study, we examined in decerebrate cats the responses of NTS neurons to rotations of the body in vertical planes before and after the intragastric administration of the emetic compound copper sulfate. The activity of more than one-third of NTS neurons was modulated by vertical vestibular stimulation, with most of the responsive cells having their firing rate altered by rotations in the head-up or head-down directions. These responses were aligned with head position in space, as opposed to the velocity of head movements. The activity of NTS neurons with baroreceptor, pulmonary, and GI inputs could be modulated by vertical plane rotations. However, injection of copper sulfate into the stomach did not alter the responses to vestibular stimulation of NTS neurons that received GI inputs, suggesting that the stimuli did not have additive effects. These findings show that the detection and processing of visceral inputs by NTS neurons can be altered in accordance with the direction of ongoing movements.

Barman SM, Sugiyama Y, Suzuki T, Cotter LA, DeStefino VJ, Reighard DA, Cass SP, Yates BJ. Rhythmic activity of neurons in the rostral ventrolateral medulla of conscious cats: effect of removal of vestibular inputs. Am J Physiol Regul Integr Comp Physiol 301: R937-R946, 2011. First published July 6, 2011; doi:10.1152/ajpregu.00265.2011.-Although it is well established that bulbospinal neurons located in the rostral ventrolateral medulla (RVLM) play a pivotal role in regulating sympathetic nerve activity and blood pressure, virtually all neurophysiological studies of this region have been conducted in anesthetized or decerebrate animals. In the present study, we used time- and frequency-domain analyses to characterize the naturally occurring discharges of RVLM neurons in conscious cats. Specifically, we compared their activity to fluctuations in carotid artery blood flow to identify neurons with cardiac-related (CR) activity; we then considered whether neurons with CR activity also had a higher-frequency rhythmic firing pattern. In addition, we ascertained whether the surgical removal of vestibular inputs altered the rhythmic discharge properties of RVLM neurons. Less than 10% of RVLM neurons expressed CR activity, although the likelihood of observing a neuron with CR activity in the RVLM varied between recording sessions, even when tracking occurred in a very limited area and was higher after vestibular inputs were surgically removed. Either a 10-Hz or a 20- to 30-Hz rhythmic discharge pattern coexisted with the CR discharges in some of the RVLM neurons. Additionally, the firing rate of RVLM neurons, including those with CR activity, decreased after vestibular lesions. These findings raise the prospect that RVLM neurons may or may not express rhythmic firing patterns at a particular time due to a variety of influences, including descending projections from higher brain centers and sensory inputs, such as those from the vestibular system.

A central pattern generator (CPG) for swallowing in the medulla oblongata generates spatially and temporally coordinated movements of the upper airway and alimentary tract. To reveal the medullary neuronal network of the swallowing CPG, we examined the cytoarchitecture of the swallowing CPG and axonal projections of its individual neurons by extracellular recording and juxtacellular labeling of swallowing-related neurons (SRNs) in the medulla in urethane-anesthetized and paralyzed guinea pigs. Three major types of neuronal discharge patterns were identified during fictive swallowing induced by stimulation of the superior laryngeal nerve: early (burst-like activation during the pharyngeal stage), late (activation after the pharyngeal stage), and inhibited (inhibition during the pharyngeal stage) types. Sixteen neurons were successfully labeled in the nucleus tractus solitarii (NTS) and in the medullary reticular formation (RF). No motoneuron was labeled. The SRNs in the NTS had axons projecting to the NTS, RF, nucleus ambiguus, nucleus hypoglossus, and dorsal motor nucleus of the vagus on the ipsilateral side. Some NTS SRNs projected only within the NTS. The axons of SRNs in the RF projected also to the NTS, RF, motor nuclei on the ipsilateral side, and to the other side RF. These findings show anatomic substrates for the neuronal network of the CPG for swallowing, which consists of complex neuronal connections among SRNs in the NTS, RF, and motor nuclei. J. Comp. Neurol. 519: 2193-2211, 2011. (C) 2011 Wiley-Liss, Inc.

Objective It is important to identify and save the normal parathyroid glands during head and neck surgery because of their role in regulating the blood calcium level, yet it is often difficult to localize normal parathyroid glands during surgery. Fluorescence-guided parathyroidectomy in patients with hyperparathyroidism has already proved useful. However, there are few reports of fluorescence-guided localization of normal parathyroid glands in humans. We investigated the utility of fluorescence-guided localization of normal parathyroid glands during thyroidectomy and completed a spectral fluorescence analysis of the accumulation of 5-aminolevulinic acid metabolites in the parathyroid glands. Methods Eight patients with benign thyroid disease and five with malignant thyroid tumors were given 20 mg/kg body weight of 5-aminolevulinic acid orally 5 hours before surgery. After the posterior surface of the thyroid gland was exposed and the recurrent laryngeal nerve was identified, we illuminated the area with a violet-blue light of 405 nm. Tissues showing red fluorescence were biopsied to analyze the spectral fluorescence. Results Under the violet-blue light, normal parathyroid glands showed red fluorescence, while the surrounding structures such as the thyroid gland, muscles, and fat remained nonfluorescent. The spectral peak was observed at 635 nm indicating 5-aminolevulinic acid metabolites. Histopathologically, the biopsied tissue corresponded to normal parathyroid glands. Conclusions 5-Aminolevulinic acid is useful to localize the normal parathyroid glands during thyroid surgery in humans.

Research on animal models as well as human subjects has demonstrated that the vestibular system contributes to regulating the distribution of blood in the body through effects on the sympathetic nervous system. Elimination of vestibular inputs results in increased blood flow to the hindlimbs during vestibular stimulation, because it attenuates the increase in vascular resistance that ordinarily occurs in the lower body during head-up tilts. Additionally, the changes in vascular resistance produced by vestibular stimulation differ between body regions. Electrical stimulation of vestibular afferents produces an inhibition of most hindlimb vasoconstrictor fibers and a decrease in hindlimb vascular resistance, but an initial excitation of most upper body vasoconstrictor fibers accompanied by an increase in upper body vascular resistance. The present study tested the hypothesis that neurons in the principal vasomotor region of the brainstem, the rostral ventrolateral medulla (RVLM), whose projections extended past the T10 segment, to spinal levels containing sympathetic preganglionic neurons regulating lower body blood flow, respond differently to electrical stimulation of the vestibular nerve than RVLM neurons whose axons terminate rostral to T10. Contrary to our hypothesis, the majority of RVLM neurons were excited by vestibular stimulation, despite their level of projection in the spinal cord. These findings indicate that the RVLM is not solely responsible for establishing the patterning of vestibular-sympathetic responses. This patterning apparently requires the integration by spinal circuitry of labyrinthine signals transmitted from the brainstem, likely from regions in addition to the RVLM.

甲状腺腫瘍などの手術において正常副甲状腺を同定し確実に温存することは、術後の血中カルシウム維持のために重要である。これまで、病的副甲状腺の染色方法の報告はあるものの、正常副甲状腺の術中同定法の報告は少ない。今回、アミノレブリン酸(5-ALA)を用い、正常副甲状腺の術中光線力学的同定を行った。甲状腺良性腫瘍患者9例において、副甲状腺を露出する約5時間前に5-ALA20mg/kgを経口投与した。甲状腺裏面露出後、周囲組織を波長405nmの青紫色光で励起させ、赤色発光し副甲状腺と考えられる組織を一部生検し病理組織検査を行った。全例が赤色蛍光発光し容易に確認でき、病理組織学的にも正常副甲状腺と確認された。(著者抄録)

Inhibitory postsynaptic potentials (IPSPs) of laryngeal motoneurons (LMs) are essential for narrowing the glottis at just the right time during swallowing, which prevents aspiration. To examine the property of IPSPs of LMs during swallowing, we monitored the effects of intracellular application of chloride ion and extracellular application of inhibitory neurotransmitter antagonists on the membrane potential trajectories of LMs during fictive swallowing in decerebrate, paralyzed cat. Adductor LMs hyperpolarized briefly at the beginning of the pharyngeal stage of swallowing (PS) and then depolarized explosively during the remaining part of the PS. Abductor LMs exhibited various patterns during swallowing; hyperpolarization during the PS followed by depolarization at the offset of the PS, slight depolarization, or plateau potentials. Chloride-dependent IPSPs were revealed during the initial part of PS in adductor LMs and during the whole PS in abductor LMs. The swallow-related IPSPs were depressed by iontophoretic extracellular application of bicuculline in both adductor and abductor LMs, but they were not modified by strychnine application. It is concluded that the swallow-related inhibition of both adductor and abductor LMs is chloride-dependent IPSPs mediated through GABA(A) receptors, not through glycine receptors. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

The purpose of the present study was to determine whether murines could be substituted for traditional experimental mammals to study the brainstem mechanism of vocalization. We conducted systematic electrical and chemical stimulation of the brainstem in guinea pigs to identify the similarities in the call sites between murines and other mammals. We further examined whether or not fictive vocalization could be induced in paralyzed guinea pigs, an experimental model which facilitates neuronal recording in the brainstem. The sites where electrical stimulation evoked vocalization were distributed continuously from the periaqueductal grey (PAG) to the lower brainstem. This call area usually ended at the most caudal part of the inferior olive and thus did not continuously extend to the nucleus retroambiguus. Microinjections of D,L-homocysteic acid and bicuculline induced vocalization at the PAG, parabrachial nucleus, and the most dorsal part of the pontine reticular formation. The brainstem call areas and vocal motor patterns induced from these areas were approximately consistent with those in other mammals. Fictive vocalization induced by PAG stimulation could be identified from activities of the phrenic, abdominal, and superior laryngeal nerves in paralyzed guinea pigs. We thus concluded that guinea pigs can be utilized in studies of brainstem vocal mechanism. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.