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Background: Maximum bite force (MBF) is a common and useful index of masticatory function; it correlates with physical strength in elderly people. Palpation of stiffness in the masseter muscle during forceful biting has been considered to be associated with MBF. However, this assessment method relies on subjective judgments; no study has verified the relationship between MBF and quantitative measurements of masseter muscle stiffness (MMS)., Objective: We aimed to verify the association between masseter muscle myotonometric assessment results and MBF., Methods: In total, 117 community-dwelling >65-year-old individuals from the Tokyo metropolitan area were assessed. MMS on the dominant side during forceful biting was measured with a MyotonPRO device. Masseter muscle thickness (MMT) during rest and forceful biting was measured with an ultrasonic diagnostic apparatus, and the difference in MMT (DMMT) between the rest and forceful biting conditions was determined. MBF data were obtained with a pressure-sensitive sheet and an associated device. To determine the independent variables affecting MBF and MMS, multivariate linear regression analyses with adjustments for age, sex and number of teeth were performed., Results: The multivariate analysis revealed that MBF correlated with the number of teeth (β = .489, P < .001) and MMS (β = .259, P = .003) (R 2  = .433). MMS correlated with MBF (β = .308, P = .003) and DMMT (β = .430, P < .001) (R 2  = .326)., Conclusion: Masseter muscle stiffness possibly reflects a force generated by the masseter muscle during forceful biting. Therefore, MMS is effective to assess tooth loss as well as an index of masseter muscle strength when evaluating MBF., (© 2020 John Wiley & Sons Ltd.)

Background: Although age-related changes in muscle quality influence muscle strength, the relationship between masseter muscle (MM) quality and maximum biting force (MBF) has never been studied., Objective: The aims of the study were to verify the relationship among MM quality, MBF, and the displacement of the MM while biting forcefully (MMD) and to clarify the age-related decline in MBF in healthy elderly persons., Methods: Seventy-four healthy community-dwelling individuals (mean age, >65 years) from Tokyo metropolis were recruited. The thickness (index of muscle quantity), echo intensity (index of muscle quality) and displacement of the MM while biting forcefully (MMT, MMEI and MMD, respectively) were measured by ultrasonography. MBF was measured using a pressure-sensitive sheet. Independent predictors of MBF and MMD were determined using multivariate linear regression analyses adjusted for age, sex and the number of present teeth., Results: MBF was significantly correlated with the number of teeth (β = 0.577, P < .001) and MMD (β = 0.302, P = .015), but not with MMT (β = 0.019, P = .868) or MMEI (β = 0.054 P = .703). MMD was significantly correlated with MMEI (β = -0.606, P < .001), but not with MMT (β = 0.048, P = .681) or the number of teeth (β = 0.065, P = .613)., Conclusions: MMEI was associated with MMD, an index of MBF, regardless of tooth number. The age-related quality change in the MM might cause a decrease in its contraction, resulting in age-related decline in MBF., (© 2019 John Wiley & Sons Ltd.)

Stroke is associated with multiple forms of disability, including dysphagia. Post-stroke dysphagia increases the risks of pneumonia and mortality and often results in cessation of oral feeding. However, appropriate rehabilitation methods can eventually lead to resumption of oral food intake. This study tried to clarify that re-initiating oral food intake could modify the composition of oral/gut microbial communities in patients with dysphagia. From 78 patients with sub-acute stage of stroke, 11 complete tube feeding subjects without taking antibiotics were enrolled and received rehabilitation for re-initiation of oral food intake, and 8 subjects were brought back to complete oral feeding. Oral and gut microbiota community profiles were evaluated using 16S rRNA sequencing of the saliva and feces samples before and after re-initiation of oral food intake in patients recovering from enteral nutrition under the same nutrient condition. Standard nutrition in the hospital was 1,840 kcal, including protein = 75 g, fat = 45 g, and carbohydrates = 280 g both for tube and oral feeding subjects. Oral food intake increased oral and gut microbiome diversity and altered the composition of the microbiome. Oral and gut microbiome compositions were drastically different; however, the abundance of family Carnobacteriaceae and genus Granulicatella was increased in both the oral and gut microbiome after re-initiation of oral food intake. Although oral microbiota showed more significant changes than the gut microbiota, metagenome prediction revealed the presence of more differentially enriched pathways in the gut. In addition, simpler co-occurrence networks of oral and gut microbiomes, indicating improved dysbiosis of the microbiome, were observed during oral feeding as compared to that during tube feeding. Oral food intake affects oral and gut microbiomes in patients recovering from enteral nutrition. Rehabilitation for dysphagia can modify systemic health by increasing the diversity and altering the composition and co-occurrence network structure of oral and gut microbial communities., (Copyright © 2019 Katagiri, Shiba, Tohara, Yamaguchi, Hara, Nakagawa, Komatsu, Watanabe, Ohsugi, Maekawa and Iwata.)

Liposarcomas are most commonly found in the extremities, in the retroperitoneum and, less often, in the head and neck area. The spermatic cord is a rare site of origin, accounting for about 4-7% of all liposarcomas. We report a case of dedifferentiated liposarcoma of the spermatic cord. A 51-year-old man was referred to our hospital for a painless hard mass in the left inguinal region. Abdominal computed tomography showed a left spermatic cord mass measuring 70 mm in diameter. We performed left high orchiectomy with resection of the mass. Immunohistochemical analysis revealed positive for murine double minute 2 (MDM 2) and cyclin dependent kinase 4 (CDK 4). Therefore, this sarcoma was diagnosed to be dedifferentiated liposarcoma. Since the surgical margin was positive, an additional wide resection including the surrounding normal tissue was performed. Complete excision was achieved after re-resection. He was alive 12 months postoperatively without any signs of recurrence. Dedifferentiated liposarcoma of the spermatic cord is a rare neoplasm. To the best of our knowledge, the present case is the 14th reported case in Japan.

Dysphagia is a common problem among older adults, causing aspiration pneumonia and malnutrition. It has been reported that calf circumference (CC), an index of nutritional status and physical activity, correlated with dysphagia in acute care hospitals, suggesting that CC can be a useful index for assessing dysphagia. We therefore aimed to explore the association between dysphagia and CC among community elderly people who require long-term care and determined the optimal CC cut-off value for patients with dysphagia. Our cross-sectional study, conducted at Tokyo Metropolis, included 154 participants (65 men) aged > 65 years (mean age: 80.1 ± 7.1) who required long-term care and were examined for dental disease and dysphagia during home visiting treatment. Age, body mass index (BMI), mini-nutritional assessment short-form (MNA-SF) score, Barthel index (BI), CC, functional oral intake scale (FOIS), and dysphagia severity scale (DSS) were evaluated. A DSS score < 5 was defined as dysphagia. To determine the association between CC and dysphagia, we performed logistic regression analysis and calculated the CC cut-off value for dysphagia. Thirty-seven participants (24.0%) were diagnosed with dysphagia. The logistic regression analysis showed that the presence of dysphagia was independently associated with CC after adjusting for age and sex. The CC cut-off value for the presence of dysphagia was 31.0 cm in men (sensitivity, 0.818; specificity, 0.868) and 29.3 cm in women (sensitivity, 0.760; specificity, 0.859). CC is a useful index for assessing dysphagia among community dwelling individuals who require long-term care.

Potentially curative treatments for early-stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of radiotherapy and radiofrequency ablation (RFA) for early-stage HCC. Consecutive patients with ≤3 early-stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3-year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval [CI], 2.7-9.2; versus 12.9%, 95% CI, 9.9-16.2) (P < 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3-year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2-77.7; and 70.4%; 95% CI, 58.5-79.4, respectively; P = 0.86). Conclusion: Radiotherapy has excellent local control and comparable overall survival in patients with well-compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA., (© 2019 by the American Association for the Study of Liver Diseases.)

Purpose: Producing tongue pressure (TP) by pushing the tongue against the palate consists of lifting the tongue muscles and elevating the floor of the mouth via suprahyoid muscle contraction. Though studies have shown that tongue-pressure resistance training (TPRT) increases tongue function, none have focused on suprahyoid muscle function enhancements. Our study aimed to verify whether TPRT improves both tongue function and hyoid movement during swallowing., Materials and Methods: Eighteen patients (mean age: 76.8±6.2 years) with presbyphagia presenting with symptoms such as coughing and choking were enrolled. All patients performed daily living activities independently. None of the participants had diseases causing dysphagia or previous oral or pharyngeal surgery. Participants were instructed to push their tongues against the palate as hard as possible with their mouths closed for 10 seconds, and then resting for 10 seconds. A set consisted of five consecutive exercise and resting periods; two sets per day were performed for a month. TP and the oral diadochokinetic rate (ODKR), measured by repetitions of the syllables /ta/ and /ka/, assessed tongue function. The extent of anterior and superior hyoid movement and parameters related to swallowing, including the penetration aspiration scale (PAS) and the normalized residue ratio scale (NRRS) in the valleculae (NRRSv) and piriform sinus (NRRSp), were evaluated based on videofluoroscopic data., Results: The anterior ( P =0.031) and superior hyoid movement ( P =0.012), TP ( P =0.002), ODKR/ta/ ( P =0.034), ODKR/ka/ ( P =0.009), and the width of the upper esophageal sphincter ( P =0.001) were larger at follow-up than at baseline. NRRSp ( P =0.022), PAS ( P =0.016), and pharyngeal transit times ( P =0.004) were smaller at follow-up than at baseline., Conclusion: TPRT improved tongue strength, dexterity, both anterior and superior hyoid elevation, and swallowing functions. Therefore, TPRT could improve tongue function and suprahyoid muscle function simultaneously and contribute to prevention of sarcopenic dysphagia., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background and Objective: A decrease of swallowing muscle strength causes dysphagia, and a relationship between swallowing muscle strength and appendicular muscle mass has been reported. Moreover, the effect of trunk retention function on swallowing function has been clinically recognized. However, the relationship between trunk muscle mass and swallowing muscle strength is unclear. We aimed to clarify the association between these variables in elderly individuals., Methods: Subjects were 118 healthy community-dwelling individuals aged ≥65 years (men: 37, women: 81). We measured total muscle mass, grip strength, jaw-opening force, tongue pressure, cross-sectional area (CSA) of the geniohyoid muscle, and tongue muscle thickness. The appendicular skeletal muscle mass index (ASMI) and trunk muscle mass index (TMI) were calculated based on the appendicular skeletal muscle mass and trunk muscle mass, and corrected by height squared. Multiple regression analysis was performed with jaw-opening force and tongue pressure as dependent variables and with age, sex, grip strength, ASMI, TMI, CSA of the geniohyoid muscle, and tongue muscle thickness as independent variables., Results: Significant explanatory factors for jaw-opening force were sex (p = 0.002) and TMI (p = 0.003). Significant explanatory factors for tongue pressure were aging (p = 0.001), tongue muscle thickness (p = 0.027), and TMI (p = 0.033)., Conclusions: Until now, the relationship between swallowing muscles and whole body muscle mass has been reported using ASMI as the indicator of whole body muscle mass. This study suggests that TMI may be used as a highly relevant indicator of swallowing muscles rather than ASMI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In our aging society, the number of patients with dysphagia, which is associated with disease and aging, is rapidly increasing. The swallowing reflex is a complex process that involves coordinated contractions of swallowing muscles. Many researchers have reported that age-related changes, such as frailty and sarcopenia, affect swallowing muscles and contribute to the decline in the swallowing function. Thus, simple, non-invasive evaluation methods and exercises for swallowing muscles in elderly patients with dysphagia are important. Anterior-superior hyolaryngeal elevation during swallowing results from contractions of the suprahyoid muscle, which plays a primary role in opening the upper esophageal sphincter, along with relaxation of the cricopharyngeal muscle and laryngeal closure. Thus, many researchers have studied methods for evaluating and augmenting suprahyoid muscles. On the other hand, some researchers have reported on dysphagia rehabilitation focused on jaw-opening actions, because hyolaryngeal elevation muscles correspond with jaw-opening muscles. In this study, we describe a new dysphagia evaluation method and an exercise that focuses on suprahyoid muscles with application of jaw-opening actions.

Introduction: The geographical inequity of physicians is a serious problem in Japan. However, there is little evidence of inequity in the future geographical distribution of physicians, even though the future physician supply at the national level has been estimated. In addition, possible changes in the age and sex distribution of future physicians are unclear. Thus, the purpose of this study is to project the future geographical distribution of physicians and their demographics., Methods: We used a cohort-component model with the following assumptions: basic population, future mortality rate, future new registration rate, and future in-migration and out-migration rates. We examined changes in the number of physicians from 2005 to 2035 in secondary medical areas (SMAs) in Japan. To clarify the trends by regional characteristics, SMAs were divided into four groups based on urban or rural status and initial physician supply (lower/higher). The number of physicians was calculated separately by sex and age strata., Results: From 2005 to 2035, the absolute number of physicians aged 25-64 will decline by 6.1% in rural areas with an initially lower physician supply, but it will increase by 37.0% in urban areas with an initially lower supply. The proportion of aged physicians will increase in all areas, especially in rural ones with an initially lower supply, where it will change from 14.4% to 31.3%. The inequity in the geographical distribution of physicians will expand despite an increase in the number of physicians in rural areas., Conclusions: We found that the geographical disparity of physicians will worsen from 2005 to 2035. Furthermore, physicians aged 25-64 will be more concentrated in urban areas, and physicians will age more rapidly in rural places than urban ones. The regional disparity in the physician supply will worsen in the future if new and drastic measures are not taken., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Swallowing muscle strength weakens with aging. Although numerous studies have investigated tongue pressure (TP) changes with age, studies on jaw-opening force (JOF), an indicator of suprahyoid muscle strength, are lacking. We investigated differences between age-related declines in TP and JOF in a cross-sectional study of 980 healthy and independent participants (379 men, 601 women) without dysphagia. Hand grip strength (HGS), TP, and JOF were compared among decade-based age groups in multiple comparison analyses with post-hoc tests and effect size calculated. Participants were divided into adult (20 s-50 s) and elderly groups (60 s-80 s); within each group, Pearson correlations between age and muscle strength indices were evaluated. TP started to significantly decline in the 60 s and 50 s for men and women (p < .01, medium effect size and p < .05, small effect size, respectively); HGS also declined at these ages (men: p < .01, women: p < .01, medium effect size). JOF started to significantly decline in men in their 80 s (p < .01, large effect size), but remained unchanged in women. In the elderly group, all measurements declined with age more sharply in men (HGS: r = -0.56, TP: r = -0.63, JOF: r = -0.13) than in women (HGS: r = -0.38, TP: r = -0.49, JOF: r = -0.003). TP declined more steeply than did JOF. Thus, the age related-decline in TP was similar to that of the HGS, but not the JOF. The results reveal that different patterns exist in the age-related decline in swallowing muscle strength, and suggest that maintenance of JOF might contribute to safe swallowing in healthy elderly individuals., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: This study was aimed to examine the effectiveness of a high-speed jaw-opening exercise, which targets the contraction of fast-twitch muscle fibers, in improving swallowing function., Subjects and Methods: Twenty-one subjects (mean age 74.0±5.7 years) with dysphagia-related symptoms, such as coughing or choking during eating, performed the exercise. None of the included subjects had neurological symptoms or history of surgery that could cause significant dysphagia. All subjects took regular meals, and maintained independent activities of daily life. The exercise schedule consisted of 3 sets of 20 repetitions each of rapid and maximum jaw-opening movement with a 10-second interval between sets. The exercise was performed twice daily for 4 weeks., Results: Following the intervention, there was a significant increase in the vertical position of the hyoid bone at rest. Furthermore, during swallowing, the elevation of the hyoid bone and the velocity of its movement and esophageal sphincter opening increased significantly while the duration of the hyoid elevation and the pharyngeal transit time reduced significantly., Conclusions: Our results demonstrated that high-speed jaw-opening exercise resulted in increased elevation velocity of the hyoid bone during swallowing, indicating its role in effectively strengthening the fast-twitch muscle fibers of suprahyoid muscles. Furthermore, since the rest position of the hyoid bone appeared to have improved, this exercise may be especially useful in elderly individuals with a lower position of the hyoid bone at rest and those with decreased elevation of the hyoid bone during swallowing, which are known to be associated with an increased risk of aspiration., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: This study aimed to determine whether excessive neck muscle tone affects hyoid bone kinetics during swallowing using videofluorography (VF) in an unnatural posture in adults., Subjects and Methods: Subjects were 28 adults (12 men, 16 women; mean age, 39.75±9.50 years) who were suspected to have some symptom of swallowing disorders but did not have swallowing dysfunctional from the result of videofluorography. We first established the participant's posture a reclining wheelchair that was adjusted to a 30-degree angle with the headrest (without excessive neck muscle tone) or without headrest (with excessive neck muscle tone), used an electromyogram above the mylohyoid muscle to represent the suprahyoid muscles and above the sternohyoid muscle to represent the infrahyoid muscles to confirm neck muscle tone, and then conducted VF of swallowing measurements. Videofluorographic images were obtained when 5 mL of 50% (w/v) barium sulfate was being swallowed, and hyoid bone coordinate (the resting position and the elevated position), extent of horizontal and vertical hyoid bone elevation, as well as duration and velocity of hyoid bone elevation were evaluated (x-axis and y-axis coordinates for the resting position of hyoid bone are referred to as Xr and Yr, respectively; those for the elevated hyoid bone position induced during swallowing are referred to as Xs and Ys, respectively)., Results: In the resting position of the hyoid bone, the Yr coordinates in those with excessive neck muscle tone were significantly lower than in those without excessive neck muscle tone. Vertical hyoid bone elevation and hyoid bone elevation velocity were significantly higher with excessive neck muscle tone than without excessive neck muscle tone, whereas horizontal elevation showed no significant differences., Conclusion: Our findings suggest that the generation of neck muscle tone due to inappropriate posture may encourage hyoid depression and increase the extent of hyoid bone elevation, thereby increasing the risk of aspiration., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Patients receiving methotrexate (MTX) for the treatment of autoimmune disease are at a high risk of developing lymphoproliferative disorders (LPD), the so-called methotrexate-associated lymphoproliferative disorders (MTX-LPD). We recently performed abdominal ultrasonography (US) in a patient with rheumatoid arthritis (RA) who had developed hepatic dysfunction during the course of MTX therapy; the examination revealed multiple well-demarcated hepatic tumors with slightly irregular borders, the largest one measuring 9 cm in diameter. In view of the finding of portal and hepatic veins perforating the tumor, we suspected a diagnosis of malignant lymphoma and performed a hepatic tumor biopsy. Histopathological examination of the biopsy specimens revealed a diagnosis of diffuse large B-cell lymphoma, and we made a final diagnosis of MTX-LPD. MTX treatment was discontinued, which resulted in rapid resolution of the lesions. Resolution of MTX-LPD can be obtained just by discontinuation of MTX treatment. In patients receiving MTX therapy who are found to have hepatic tumors perforated by the portal vein and/or hepatic vein on abdominal US, it is advisable to perform hepatic tumor biopsy to facilitate differential diagnosis of MTX-LPD and enable a definite diagnosis.

We report a successful management of anesthesia in a 55-year-old male patient with spinal and bulbar muscular atrophy (SBMA). His respiratory and swallowing functions were preserved preoperatively. He underwent an osteosynthesis for a femoral neck fracture under general anesthesia using nondepolarizing muscle relaxant. The anesthetic concerns in patients with SBMA are the possibility of postoperative respiratory dysfunction due to anesthetics or muscle relaxants and that of postoperative neurological deterioration due to spinal or epidural anesthesia. In this case, the effect of an intubating dose of rocuronium (0.5 mg · kg(-1)) was markedly prolonged, but it was completely reversed by sugammadex (2 mg · kg(-1)). Postoperative course was uneventful and clinical symptoms of SBMA did not become exacerbated.

We report the successful management of anesthesia in a 46-year-old male dialysis patient with chronic inflammatory demyelinating polyneuropathy (CIDP). He underwent an osteosynthesis of the ankle joint using general anesthesia combined with epidural anesthesia. The anesthetic concerns in patients with CIDP are the possibility of postoperative respiratory dysfunction due to anesthetics or muscle relaxants and that of postoperative neurological deterioration due to spinal or epidural anesthesia. In this case, sevoflurane (1.5-2%) did not cause respiratory dysfunction postoperatively and muscle relaxant effect of rocuronium was effectively reversed by sugammadex. Epidural anesthesia using ropivacaine (0.2-0.375%) and fentanyl did not worsen the neurological symptoms of CIDP post-operatively.

Glycinergic transmission has an important role in regulating nociception in the spinal cord. The glycine transporter-2 (GlyT2) is localized at presynaptic terminals of glycinergic neurons and eliminates glycine from the synaptic cleft to terminate glycinergic transmission. Systemic and intrathecal administration of GlyT2 inhibitors alleviate various types of pain. Although the GlyT2s and glycine receptors are widely distributed in the central nervous system, little is known about the role of glycinergic transmission in pain perception at supraspinal regions. The present study examined the antinociceptive effect of intracerebroventricular (i.c.v.) administration of the selective GlyT2 inhibitor ALX1393 on inflammatory and neuropathic pain in experimental models. For i.c.v. administration, a guide cannula was implanted into the right lateral ventricle of male Sprague-Dawley rats. Normal rats were used to assess inflammatory nociception using the formalin test and motor function using the rotarod test. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats. The CCI rats were then used to assess mechanical, cold, and thermal hyperalgesia using the electronic von Frey test, cold plate test, and the plantar test, respectively. ALX1393 (25, 50, and 100 μg) was administered i.c.v. to examine its effects on supraspinal antinociception. Supraspinal ALX1393 in normal rats suppressed the late-phase response in the formalin test but did not affect motor performance. In the CCI rats, ALX1393 inhibited mechanical and cold hyperalgesia in a dose-dependent manner. The antihyperalgesic effects of ALX1393 (100 μg) were reversed completely by i.c.v. pretreatment with a glycine receptor antagonist strychnine (10 μg). These results suggest that GlyT2 contributes to nociceptive transmission at supraspinal level and that the selective GlyT2 inhibitor is a promising candidate for the treatment of inflammatory and neuropathic pain without causing motor dysfunction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Luteolin, a major component of flavones, is known to have various physiological properties. Although luteolin reportedly has an antinociceptive effect on acute and inflammatory pain, little is known about its effect on neuropathic pain. The aim of the present study was to determine whether luteolin could ameliorate hyperalgesia in the central nervous system using a neuropathic pain model. Chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. Luteolin (0.1-1.5 mg) was administered intrathecally or intracerebroventricularly to examine the central effects on mechanical, thermal, and cold hyperalgesia using the electronic von Frey test, plantar test, and cold plate test, respectively. A rotarod test was also performed to assess motor function in normal rats. Spinally applied luteolin dose-dependently attenuated mechanical and cold hyperalgesia, but it had no effect on thermal hyperalgesia. At the highest dose, luteolin affected motor performance. The spinal action of luteolin on mechanical hyperalgesia was inhibited by intrathecal pretreatment with the γ-aminobutyric acidA (GABAA) receptor antagonist bicuculline and μ-opioid receptor antagonist naloxone, but not by intrathecal pretreatment with either the benzodiazepine receptor antagonist flumazenil or glycine receptor antagonist strychnine. Supraspinal application of luteolin had no antihyperalgesic effects in any test. These findings suggest that luteolin ameliorates mechanical and cold hyperalgesia at least in part by activating GABAA receptors in a flumazenil-insensitive manner and μ-opioid receptors in the spinal cord, but that the supraspinal regions are unlikely to contribute to the antihyperalgesic action of luteolin. Luteolin could be a candidate therapeutic agent for neuropathic pain., (Copyright © 2014. Published by Elsevier Inc.)

A 78-year-old man, weighing 74 kg and 172 cm in height suddenly developed asystole during direct laryngoscopy. His heart started beating soon after chest compressions. Direct larygoscopy can stimulate the vagal nerve of the larynx. Although a gradual decrease in heart rate ordinarily occurs prior to asystole, few reports describe the sudden asystole during direct laryngoscopy. Intravenous injection of atropine could avoid the adverse event. Anesthesiologists should pay attention to the occurence of asystole and prepare for resuscitation.

Objective: To assess the jaw-opening force test (JOFT) for dysphagia screening., Design: Criterion standard., Setting: University dental hospital., Participants: Patients complaining of dysphagia (N=95) and with symptoms of dysphagia with chronic underlying causes (mean age ± SD, 79.3±9.61y; range, 50-94y; men: n=49; mean age ± SD, 77.03±9.81y; range, 50-94y; women: n=46; mean age ± SD, 75.42±9.73y; range, 51-93y) admitted for treatment between May 2011 and December 2012 were included., Interventions: None., Main Outcome Measures: All patients were administered the JOFT and underwent fiberoptic endoscopic evaluation of swallowing (FEES). The mean jaw-opening strength was compared with aspiration (ASP) and pharyngeal residue observations of the FEES, which was used as the criterion standard., Results: A receiver operating characteristic (ROC) curve analysis was performed. Forces of ≤3.2kg for men and ≤4kg for women were appropriate cutoff values for predicting ASP with a sensitivity and specificity of .57 and .79 for men and .93 and .52 for women, respectively. Based on the ROC analyses for predicting pharyngeal residue, forces of ≤5.3kg in men and ≤3.9kg in women were appropriate cutoff values, with a sensitivity and specificity of .80 and .88 for men and .83 and .81 for women, respectively., Conclusions: The JOFT could be a useful screening tool for predicting pharyngeal residue and could provide useful information to aid in the referral of patients for further diagnostic imaging testing. However, given its low sensitivity to ASP the JOFT should be paired with other screening tests that predict ASP., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Chlorogenic acid (CGA), one of the most abundant dietary polyphenols, is known to have various physiological properties. Although CGA is reported to have an antinociceptive effect on acute and inflammatory pain, little is known about its effect on neuropathic pain or its action site. The aim of the present study was to determine whether intrathecally administered CGA can ameliorate hyperalgesia in a neuropathic pain model. Chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. CGA (0.5, 1, or 2mg) was administered intrathecally to examine the effects on mechanical, thermal, and cold hyperalgesia using the electronic von Frey test, plantar test, and cold plate test, respectively. A rotarod test was also performed to assess motor function. To identify the neurotransmitter pathway involved in the spinal action of CGA, the present study examined the effect of intrathecal pretreatment with several antagonists of spinal pain processing receptors on the action of CGA in the electronic von Frey test and cold plate test. Spinally applied CGA dose-dependently alleviated mechanical and cold hyperalgesia. Conversely, CGA had no effect on thermal hyperalgesia. At the highest dose, CGA affected motor performance. The antihyperalgesic action of CGA was partially reversed by bicuculline, an γ-aminobutyric acidA (GABAA) receptor antagonist, at a dose that did not affect baseline behavioral responses. These findings suggest that CGA ameliorates mechanical and cold hyperalgesia partly by activating GABAergic transmission in the spinal cord, and that CGA may be useful for novel treatments for neuropathic pain., (© 2013 Published by Elsevier B.V.)

Background: A sustained virological response (SVR) is the major end point of therapy for chronic hepatitis C virus (HCV) infection. Late relapse of infection is rare and poorly characterized. Three of 103 patients with a SVR treated at the National Institutes of Health had late relapse. We evaluated HCV RNA sequences in serum and liver tissue to distinguish relapse from reinfection., Methods: Per patient, 10-22 clones of amplified 5' untranslated region were evaluated in pretreatment and relapse serum specimens and in liver biopsy specimens obtained during SVR. Genotypes and sequence diversity were evaluated. Four patients whose infection relapsed before they reached a SVR (ie, the early relapse group) were used as a comparison., Results: Results of tests for detection of serum HCV RNA in all patients with late relapse were repeatedly negative during the first 24 weeks after therapy but became positive 8, 75, and 78 months after SVR. Reinfection risk factors were absent in 2 of 3 patients. In all patients with early or late relapse, apart from minor variations, the original HCV sequence was present before treatment and after relapse. All liver biopsy specimens from patients with late relapse were HCV RNA positive at SVR, with sequences nearly identical to those of specimens obtained at other time points., Conclusions: Sequence comparisons suggest that reappearance of HCV RNA years after a SVR can be from relapse of the initial viral infection rather than reinfection from a different virus.

General anesthesia was successfully performed in a 9-year-old boy with FOP. FOP is a very rare inherited disease of the connective tissue, characterized by progressive heterotopic ossification of skeletal muscles, tendons, and ligaments. Trauma and invasive medical procedures can induce heterotopic ossification. Anesthetic concerns for FOP patients include particular attention to airway management and susceptibility to respiratory complications. Regarding the airway management in general anesthesia, excessive stretching of the jaw and extension of the head may lead to the ankylosis of the temporo-mandibular joint and the neck stiffness. Ankylosis of the costvertebral joints induces restrictive ventilatory impairment, which causes atelectasis and lung infection in the perioperative period. Relating to anesthetic management for a child with FOP, anesthesiologists should keep in mind the prevention of exacerbation of the symptoms and subsequent impairment of activities of daily living postoperatively.

A 38-year-old pregnant woman underwent cesarean section with combined spinal epidural anesthesia. Immediately after intravenous administration of oxytocin, she developed chest and bilateral shoulder pain. Simultaneously, face flushing and ST segment depression on electrocardiogram were observed. Her blood pressure decreased and heart rate increased. She was treated with bolus injection of phenylephrine and continuous infusion of nicorandil and noradrenaline. At the end of surgery, all the symptoms disappeared. Because oxytocin may induce myocardial ischemia probably due to coronary vasoconstriction and peripheral vasodilation, it is important for anesthesiologists to note that oxytocin should be given to patients as slowly as possible. Alternative agents such as mythylergometrine may be used safely for an individual who is susceptive to oxytocin.

We report 6 cases with facial flushing, decreased arterial blood pressure and increased heart rate during thoracic surgery. These symptoms appeared 28 +/- 9 minutes (mean +/- SD) after the beginning of the surgery. Arterial blood pressure decreased significantly from 92/48 mmHg to 72/40 mmHg. While heart rate increased significantly from 66 to 83 beats x min(-1). Arterial blood pressure returned to the original values 22 +/- 9 minutes from the appearance of the symptoms. When facial flushing concomitant with circulatory instability occurs during lung surgery, it is important to rule out immediately anaphylactic reaction to the drugs administered and to maintain circulation appropriately.

A 93-year-old woman with a vulvar cancer was scheduled for resection of the tumor and sentinel lymph node biopsy under general anesthesia. At the beginning of the operation, a total of 20 ml of 2.5% patent blue was injected into the tumor and the surroundings to identify sentinel lymph node. After the injection, arterial oxygen saturation measured by pulse oximetry gradually dropped to 80%. The oxygen saturation recovered to the original level at 300 min post-injection, but blue pigmentation distributed throughout her body persisted until the following day. Her perioperative course was uneventful. In case of desaturation after dye injection, it is important to rule out true hypoxemia immediately by performing arterial blood gas analysis. Conversely, CO-oximetry is not necessarily useful for accurate diagnosis.

A 36-year-old woman with systemic lupus erythematous secondary to diabetes underwent right total hip arthroplasty in the left lateral position. An epidural catheter was inserted at the L1-2 interspace and placed cephalad prior to induction of general anesthesia. After the operation, she complained of numbness on the dorsum and plantar of the left foot and was unable to dorsiflex and plantarflex the ankle. The symptoms persisted after discontinuation of the epidural infusion of a local anesthetic, and they became exacerbated after the second operation in the left lateral position. Electromyography and nerve conduction study revealed palsies of the left common peroneal nerve and the tibial nerve due to local compression and also showed mononeuritis multiplex. Fortunately, the symptoms disappeared completely eight months post-operation. It should be noted that lateral positioning may be at a substantial risk of perioperative peripheral neuropathy in patients with diseases causing neural disorder.

Hypotaurine is an intermediate in taurine biosynthesis from cysteine in astrocytes. Although hypotaurine functions as an antioxidant and organic osmolyte, its physiological role in the central nervous system remains unclear. This study used behavioral assessments to determine whether hypotaurine influenced nociceptive transmission in acute, inflammatory, and neuropathic pain. The tail flick, paw pressure, and formalin tests were performed in male Sprague-Dawley rats to examine the effects of the intrathecal administration of hypotaurine (100, 200, 400, 600 μg) on thermal, mechanical, and chemical nociception. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats, and the electronic von Frey test and plantar test were performed to assess the effects on neuropathic pain. To determine which neurotransmitter pathway(s) was involved in the action of hypotaurine, in this study, we examined how the antagonists of spinal pain processing receptors altered the effect of 600 μg hypotaurine. To explore whether hypotaurine affected motor performance, the Rotarod test was conducted. Hypotaurine had antinociceptive effects on thermal, mechanical, and chemical nociception in the spinal cord. In CCI rats, hypotaurine alleviated mechanical allodynia and thermal hyperalgesia. These effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist. Conversely, hypotaurine did not affect motor performance. This study demonstrated that intrathecal hypotaurine suppressed acute, inflammatory, and neuropathic pain. Hypotaurine may regulate nociceptive transmission physiologically by activating glycinergic neurons in the spinal cord, and it is a promising candidate for treating various pain states.

General anesthesia was given twice to a 9-year-old girl with Lennox-Gastaut syndrome (LGS). LGS is one of the catastrophic forms of childhood epilepsy, and very few reports describe its anesthetic management. The anesthetic concern in LGS patients is a possibility of perioperative epilepsy due to proconvulsive effects of anesthesia-related drugs and due to the interaction between anesthetics and therapeutic drugs. Fortunately, her perioperative course was uneventful. The patients having LGS should be placed under careful observation postoperatively.

Background: Performing epidural anesthesia is accompanied by pain. The aim of this study is to examine whether intravenous administration of a sedative, an opioid, or an anesthetic eliminates pain score during the epidural procedure., Methods: Two-hundred and fifty-nine patients undergoing epidural anesthesia were randomly allocated into six groups. Prior to the epidural anesthesia, midazolam, fentanyl, ketamine, midazolam plus fentanyl or midazolam plus ketamine was given intravenously to the patients in each group. After the procedure, the effects of these drugs on pain relief in the patients were assessed by visual analogue scale(VAS)., Results: VAS was significantly decreased in all drug-treated groups to a similar extent, as compared with drug-free group. There was no significant difference between the drug-treated groups. Serious side effects including persistent respiratory suppression were not observed in this study., Conclusions: The findings obtained from this study suggest that the analgesic action of the drug is not essential to the pain relief and the anxiolytic action is important for the epidural procedure.

An 81-year-old female patient underwent arthroscopic repair of rotator cuff and provided cervical epidural catheterization for postoperative analgesia. On postoperative day (POD) 4 she developed fever and complained of neck pain and numbness in her fingers. Magnetic resonance imaging showed cervical epidural abscess at C6-7. Surgical decompression was performed and antibiotics were given to the patient on POD 5. Fortunately, she recovered fully from the symptoms after the surgery and no neurological deficit remained at discharge.

A patient having an anti-acetylcholine receptor (AChR) antibody without myasthenia gravis was scheduled for thymectomy. Neuromuscular blockade monitoring showed a normal response to vecuronium in the patient. This finding suggests that sensitivities to neuromuscular blocking agents in the patients depend not on the titers of the antibody but also on the presence or absence of the preoperative symptoms such as muscle weakness. It is, however, recommended that neuromuscular blocking agents should be administered carefully under monitoring the neuromuscular function, as is the case for myasthenia gravis, because little is understood about the effect of neuromuscular blocking agent on the neuromuscular function in the asymptomatic patients having anti-AChR antibody.

There is little report describing the effect of remifentanil on cardiac conduction system. We present a successful anesthetic management with remifentanil in a patient with sick sinus syndrome. A 66-year-old woman (31-kg, 121-cm) having sinoatrial (SA) block was diagnosed as having hepatic cell carcinoma, and radiofrequency ablation (RFA) was scheduled. She was also suffering from kyphosis due to the past history of tuberculous spondylitis. Preoperative examination of her respiratory function indicated a severe constrictive pulmonary disorder. Anesthesia was induced with propofol (30 mg), and maintained with sevoflurane (1-2%) and oxygen/air in combination with remifentanil (0.5 microg x kg(-1) x min(-1)). Temporary pacemaker was prepared during anesthesia. Neither remifentanil nor sevoflurane deteriorated SA block and her heart rate was well controlled. Respiratory dysfunction was not seen in the postoperative course. Our case suggests that remifentanil may be a suitable analgesic for patients with cardiac conduction abnormalities.

Background: The voltage-dependent sodium channel is the primary site of action for local anesthetics (LAs). Although systemically administered low-dose LAs have been shown to exert antihyperalgesic effects, the molecular targets responsible for these effects are not fully known and their functional effects on inhibitory neurotransmitter receptors associated with antinociception have not been sufficiently studied., Methods: We examined the effects of lidocaine and procaine (0.1 microM to 3 or 10 mM) on recombinant human alpha1 glycine, alpha1beta2gamma2S gamma-aminobutyric acid type A (GABA(A)), and rho1 GABA(C) receptors expressed in Xenopus laevis oocytes, using a two-electrode voltage-clamp system. We also evaluated the effects of LAs on two mutant glycine receptors, alpha1(S267C) and alpha1(S267Q), in an effort to clarify the interaction between LAs and glycine receptors., Results: Low concentrations of both lidocaine and procaine enhanced glycine receptor function, whereas high concentrations of lidocaine and procaine inhibited glycine receptor function. Lidocaine (10 microM) produced a significant leftward shift in the glycine concentration-response curve, indicating an increase in the apparent affinity for glycine. This enhancement was not altered in the mutant receptors. Both lidocaine and procaine at high concentrations inhibited GABA(A) receptor currents, whereas neither lidocaine nor procaine affected GABA(C) receptor function., Conclusions: Lidocaine and procaine enhanced glycine receptor function at low concentrations and inhibited the functions of glycine and GABA(A) receptors at high concentrations. The mechanism of the LA-induced enhancement of glycine receptor function probably differs from that of general anesthetics. These findings may explain the pharmacological effects of LAs, such as antinociception and convulsion.

We present a case of unintentional total spinal anesthesia, which occurred during cervical epidural block. A 34-year-old man with complex regional pain syndrome of the right upper arm was treated with epidural block at C7-T1 interspace. Immediately after test-dose injection of ropivacaine 1.5 ml, he complained of paresthesia of his upper extremities. He developed difficulty talking and breathing. Subsequently he showed a complete paralysis with the loss of consciousness, respiratory arrest, and bilateral midriasis. Mandatory ventilation was started and endotracheal tube was placed. Eighty minutes after the injection of ropivacaine, he recovered consciousness and spontaneous respiration resumed. Checking adequate ventilation, his trachea was extubated. Neurological dysfunction was not seen thereafter. Although test-dose injection is recommended especially in high-risk patients and case of difficulty of epidural space identification, it does not fully prevent complications. For cervical epidural block, local anesthetics should either be given at small doses or not be given as long as a possibility of spinal injection is remaining.

A wide range of physiological effects are mediated by alpha2-adrenoceptors (ARs) through their association with G protein-coupled inwardly rectifying potassium (GIRK) channels. Although alpha2-ARs are divided into three subtypes (alpha2A-C), a pharmacological distinction among the subtypes is difficult to establish because of the lack of a selective agonist and antagonist; therefore, little is known about the effects of anesthetics on the alpha2-AR subtypes. We expressed each subtype together with GIRK1/GIRK2 subunits in Xenopus oocytes and observed alpha2-AR-mediated GIRK1/GIRK2 currents to test the effects of ethanol, halothane, and several IV anesthetics at clinical concentrations. UK 14,304, a selective alpha2-AR agonist, evoked GIRK1/GIRK2 currents in every subtype. None of the IV anesthetics, which included pentobarbital, propofol, ketamine, and alphaxalone, influenced UK 14,304-evoked potassium currents in any of the receptor subtypes. Ethanol enhanced the UK 14,304-evoked potassium currents, whereas halothane inhibited the currents. However, these effects were not significantly different from those on the baseline-GIRK1/GIRK2 current, suggesting that neither ethanol nor halothane acts directly on the alpha2-AR subtypes. Although none of the drugs examined had any effect on the alpha2-ARs, the physiological actions of the alpha2-ARs mediated by the GIRK1/GIRK2 channels may be affected by ethanol and halothane.

CT-colonography (CT-C), a new diagnostic imaging technique for cancer of the large intestine--which is increasing rapidly owing to westernized eating habits--has advanced from the developmental stage to the stage of practical application, thanks to progress in MSCT and workstation development. Therefore, based on the results of CT-C application using 16 lines of MSCT to a screening test, we reviewed the usefulness of CT-C in our clinic. We supplemented defective depiction, and found that change of position was effective for virtual image exclusion. We consider that CT-C can support diagnosis if the target of screening tests is a polypoid lesion of more than 6 mm. In addition, it is expected that the number of examinations performed during office visits will increase because of the decreased invasiveness of the procedure, its lack of pain, and its ability to provide early lesion detection.

We assessed the effects of tramadol, a centrally acting analgesic, and its major metabolite, on neurotransmitter-gated ion channels. Tramadol binds to mu-opioid receptors with low affinity and inhibits reuptake of monoamines in the central nervous system. These actions are believed to primarily contribute to its antinociceptive effects. However, little is known about other sites of tramadol's action. We tested the effects of tramadol and its M1 metabolite (0.1-100 microM) on human recombinant neurotransmitter-gated ion channels, including glycine, gamma-aminobutyric acid(A) (GABA(A)), and N-methyl-D-aspartate (NMDA) receptors, expressed in Xenopus oocytes. Tramadol and M1 metabolite did not have any effects on glycine receptors. GABA(A) receptors were significantly inhibited only at large concentrations (100 microM). NMDA receptors were inhibited in a concentration-dependent manner. Tramadol and M1 metabolite inhibited the glutamate-concentration response curve without changing the half-maximal effective concentration or the Hill coefficient, indicating a noncompetitive inhibition. This study suggests that glycine receptors do not provide the antinociceptive effect of tramadol and that the inhibition of GABA(A) receptors at large concentration might correlate with convulsions. The inhibitory effect on NMDA receptors may contribute to the antinociceptive effect of tramadol at relatively large concentrations.

There have been several reports on anesthesia for a patient with a history of multiple drug allergies. We present here anesthesia for a 33-year-old woman with histories of multiple drug allergies. She was scheduled to undergo total abdominal hysterectomy. We could not perform preoperative screening of the drugs using a dermal test because of a high risk of anaphylactic shock. Anesthesia was induced and maintained with sevoflurane and nitric oxide. The operation was finished without complications and her postoperative course was uneventful. It is important preoperatively to obtain histories of allergies adequately for recognition of allergens.