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1.
Br J Anaesth ; 132(6): 1211-1218, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677950

RESUMO

BACKGROUND: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001). CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.


Assuntos
Antifibrinolíticos , Procedimentos Cirúrgicos Cardíacos , Fibrinólise , Testes Imediatos , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/farmacologia , Ácido Tranexâmico/uso terapêutico , Antifibrinolíticos/uso terapêutico , Antifibrinolíticos/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fibrinólise/efeitos dos fármacos , Estudo de Prova de Conceito , Ponte Cardiopulmonar , Ativador de Plasminogênio Tecidual/farmacologia , Adulto , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga
2.
Surg Today ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913156

RESUMO

PURPOSE: To evaluate the usefulness of robotic subxiphoid-optical thymectomy (RST). METHODS: Thirty-seven procedures (thymoma, n = 19; thymic carcinoma, n = 1; myasthenia gravis, n = 3; and others, n = 14) performed between October 2020 and December 2023 were included. The right and left 6th intercostal midclavicular lines and subxiphoid, with an assistant port placed in the right third intercostal anterior axillary line, were adapted. Postoperative pain was assessed using a numerical rating scale (NRS). RESULTS: A good view of the surgical field is obtained. The median console time was 113 min and the time to roll-in was 30 min. The body mass index (BMI) was 21.6. One patient with thymic carcinoma required combined resection of the left phrenic nerve and left brachiocephalic vein without conversion to thoracotomy, and 1 patient had post-pericardiotomy syndrome with bilateral pleural effusion. There was a correlation between the prolonged time to roll-in and BMI (ρ = 0.439; p = 0.007). Pain was controlled with oral medication on postoperative day 1 and significantly decreased at discharge and at the first outpatient visit without epidural anesthesia (median NRS scores: 4, 1, and 1, respectively). CONCLUSION: RST is a safe procedure that provides surgeons with a sufficient view of the anterior mediastinum and causes minimal postoperative pain.

3.
Int J Mol Sci ; 25(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38999942

RESUMO

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of SCN11A, SCN10A, and SCN9A, which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for SCN11A, SCN10A, and SCN9A. In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of SCN11A, SCN10A, and SCN9A, respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.


Assuntos
Testes Genéticos , Canal de Sódio Disparado por Voltagem NAV1.7 , Canal de Sódio Disparado por Voltagem NAV1.8 , Canal de Sódio Disparado por Voltagem NAV1.9 , Humanos , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Canal de Sódio Disparado por Voltagem NAV1.9/genética , Japão/epidemiologia , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Masculino , Feminino , Testes Genéticos/métodos , Adulto , Adolescente , Criança , Predisposição Genética para Doença , Adulto Jovem , Pré-Escolar , Mutação , Dor , Reto/anormalidades
4.
J Anesth ; 38(1): 98-104, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38150014

RESUMO

PURPOSE: The reduced effects of allogeneic transfusion with acute normovolemic hemodilution (ANH) have been reported. Harvesting a large volume of blood may maximize the effect in patients with low body weight, and the prevention of hypotension is important. Remimazolam is an anesthetic with few circulatory responses. Our aim was to evaluate whether high-volume ANH reduces the need for transfusion in cardiac patients under remimazolam anesthesia. METHODS: In this retrospective single-center study, we enrolled cardiopulmonary bypass (CPB) patients who received remimazolam anesthesia. Changes in hemodynamic parameters were assessed. The numbers of blood transfusions and chest tube outputs were also evaluated. RESULTS: In a total of 51 patients, ANH was performed in 27 patients with a mean body mass index of 23.2 (ANH volume: 740 ± 222 mL). No significant differences were observed in mean blood pressure during blood collection. The intraoperative amount of red blood cell (RBC) transfusion was significantly lower in the ANH group than in the control group (431 ± 678 and 1260 ± 572 mL, p < 0.001). The avoidance rates of RBC were 66.7 and 4.2%, respectively. The multivariate analysis result revealed that ANH correlated with RBC, with an odds ratio of 0.067 (95% confidence interval 0.005-0.84, p < 0.05). The postoperative bleeding at 24 h was significantly lower in the ANH group (455 ± 228 and 797 ± 535 mL, p < 0.01). CONCLUSION: In patients undergoing CPB, ANH reduced intraoperative transfusion amount and postoperative bleeding. Hemodynamic changes during blood collection were minimal under remimazolam anesthesia and high-volume ANH was feasible.


Assuntos
Anestesia , Benzodiazepinas , Procedimentos Cirúrgicos Cardíacos , Humanos , Hemodiluição , Estudos Retrospectivos
5.
J Anesth ; 38(2): 254-260, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38289493

RESUMO

To explore the current status of anesthesia research activity in Japan, we analyzed the number of abstracts presented at the Japanese Society of Anesthesiologists (JSA) annual meetings by several factors including gender, society branches, and subspecialty categories. The number of abstracts at JSA annual meetings has declined sharply since 2016 with no gender gap. A decrease in the neurological field predated the overall decline, but other subspecialty categories showed a similar decline. Although the Tokyo, Tokai-Hokuriku, and Kyushu branches were responsible for more than half of the reduction, the trend was similar among all branches. In a survey regarding academic activities of university hospital residents and faculty, Ph.D. aspirants' rate was only 20-30%. Residents had never presented an abstract at scientific conferences and never published any papers at nearly 40% and 30% of the university hospitals, respectively. Our survey suggests that junior anesthetists are losing interest in research. Senior faculty and mentors must redouble efforts to embed and encourage research in departments and by anesthetists in training. If a revival of anesthesia research in Japan does not occur then a service only specialty awaits.


Assuntos
Anestesia , Anestesiologia , Humanos , Japão , Anestesiologia/educação , Hospitais Universitários , Anestesiologistas
6.
Mol Pain ; : 17448069231181973, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254240

RESUMO

Activation of neurons and glial cells in the dorsal root ganglion is one of the key mechanisms for the development of hyperalgesia. The aim of the present study was to examine the role of neuroglial activity in the development of opioid-induced hyperalgesia. Male rats were treated with morphine daily for 3 days. The resultant phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in the dorsal root ganglion was analyzed by immunohistochemistry and Western blotting. Pain hypersensitivity was analyzed using behavioral studies. The amount of cytokine expression in the dorsal root ganglion was also analyzed. Repeated morphine treatment induced hyperalgesia and marked induction of phosphorylated ERK1/2 in the neurons and satellite glial cells on day 3. An opioid receptor antagonist, toll like receptor-4 inhibitor, MAP/ERK kinase (MEK) inhibitor and gap junction inhibitor inhibited morphine-induced hyperalgesia and ERK1/2 phosphorylation. Morphine treatment induced alteration of cytokine expression, which was inhibited by the opioid receptor antagonist, toll like receptor-4 inhibitor, MEK inhibitor and gap junction inhibitor. Dexamethasone inhibited morphine-induced hyperalgesia and ERK1/2 phosphorylation after morphine treatment. The peripherally restricted opioid receptor antagonist, methylnaltrexone, inhibited hyperalgesia and ERK1/2 phosphorylation. Morphine activates ERK1/2 in neurons and satellite glial cells in the dorsal root ganglion via the opioid receptor and toll like receptor-4. ERK1/2 phosphorylation is gap junction-dependent and is associated with the alteration of cytokine expression. Inhibition of neuroinflammation by activation of neurons and glia might be a promising target to prevent opioid-induced hyperalgesia.

7.
Mol Biol Rep ; 50(7): 6005-6017, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37273064

RESUMO

BACKGROUND: Family with sequence similarity 134, member B (FAM134B), also known as Reticulophagy regulator 1 (RETREG1), is an ER-phagy receptor involved in ER homeostasis. Congenital mutations in the FAM134B gene have been reported to be associated with hereditary sensory and autonomic neuropathy type 2B (HSAN2B); however, the molecular differences between wild-type and HSAN2B-linked FAM134B are not fully understood. METHODS AND RESULTS: We prepared several human FAM134B constructs, such as the HSAN2B-linked mutant, and compared their features with those of wild-type FAM134B by transfecting these constructs into FAM134B-deficient Neuro2a cells. Although intrinsic FAM134B protein expression in wild-type Neuro2a cells was affected by the supply of amino acids in the culture medium, the expression of each HSAN2B-linked mutant FAM134B protein was hardly affected by serum and amino acid deprivation. On the other hand, the intracellular localization of GFP-tagged HSAN2B-linked mutants, except for P7Gfs133X, overlapped well with ER-localized SP-RFPKDEL and did not differ from that of GFP-tagged wild-type FAM134B. However, analysis of protein‒protein interactions using the NanoBiT reporter assay revealed the difference between wild-type and C-terminal truncated mutant FAM134B. Furthermore, this NanoBiT assay demonstrated that both wild-type and G216R FAM134B interacted with LC3/GABARAPL1 to the same extent, but the FAM134B construct with mutations near the LC3-interacting region (LIR) did not. Similar to the NanoBiT assay, the C-terminal-truncated FAM134B showed lower ER-phagy activities, as assessed by the cotransfection of GFP-tagged reporters. CONCLUSIONS: We showed that wild-type and HSAN2B-linked FAM134B have different molecular characteristics by transfecting cells with various types of constructs. Thus, this study provides new insights into the molecular mechanisms underlying HSAN2B as well as the regulation of ER-phagy.


Assuntos
Neuropatias Hereditárias Sensoriais e Autônomas , Peptídeos e Proteínas de Sinalização Intracelular , Humanos , Autofagia/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
8.
J Anesth ; 37(4): 532-538, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37160444

RESUMO

PURPOSE: Preoperative opioid treatment increases postoperative adverse events. This study was aimed to analyze preoperative opioid prevalence in countries with low opioid consumption. Additionally, the effect of low opioid usage on postoperative outcomes was also investigated. METHODS: We conducted this single center retrospective cohort analysis in a Japanese university-affiliated hospital to investigate opioid usage and its impact on the duration of postoperative hospitalization and in-hospital mortality. Adult patients who underwent general anesthesia between 2015 and 2020 were included. We extracted the patients' characteristics, surgical information and postoperative outcomes. Subgroup analysis to address opioid dose effect was performed in high and low dose opioid subgroups. RESULTS: Among 20,306 inpatients, 535 (2.63%) patients used opioids preoperatively. Tramadol was the most frequently used opioid. The median morphine equivalent (MME) dose was 15 mg/day. Median duration of hospitalization was 18 and 9 days in the opioid and non-opioid groups, and in-hospital mortality was 2.06% and 0.42%. Multivariable regression analysis demonstrated that preoperative opioid use was associated with a longer duration of hospitalization and in-hospital mortality. Subgroup analysis demonstrated longer durations of hospitalization in both high (> 30 mg/day MME) and low (≤ 30 mg/day MME) dose opioid groups, while higher in-hospital mortality was seen only in the high dose opioid group. CONCLUSIONS: Preoperative opioid usage was one-tenth of the United States average. Despite its low prevalence and small dosage, preoperative opioid usage was associated with poor postoperative outcomes. Dedicated perioperative interventions to prevent opioid-associated adverse events should be developed even in countries with low opioid consumption.


Assuntos
Analgésicos Opioides , Dor Pós-Operatória , Adulto , Humanos , Analgésicos Opioides/efeitos adversos , Morfina , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/induzido quimicamente , Prevalência , Estudos Retrospectivos , Estados Unidos , Período Pré-Operatório
9.
Ann Plast Surg ; 88(5): 490-495, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443265

RESUMO

BACKGROUND: After breast surgery with or without immediate reconstruction, chronic pain can be a major problem for patients. However, few studies have examined the details of the sites of long-lasting postoperative pain. In this study, we specified the postoperative pain location after breast surgery, including reconstruction, to find ways to improve surgical procedures or provide effective pain relief. METHODS: The subjects were 205 Japanese women undergoing mastectomy or breast reconstruction with a tissue expander (TE)/implant or a deep inferior epigastric perforator (DIEP) flap. Patients were asked whether they had pain in different parts of the body at 1 year after surgery. Differences were assessed by cross-tabulation and χ2 statistics. RESULTS: Surveys were completed by 157 subjects. Deep inferior epigastric perforator flap cases had significantly more pain and TE/Imp cases had significantly less pain in the medial breast, upper breast, breast upper medial quadrant, and abdomen (P = 0.006, P = 0.006, P < 0.001, P < 0.001, respectively). In the neck area, pain in TE/Imp cases was significantly worse than that in all other patients (P = 0.025). There was no significant difference in chronic pain in any other body regions among the mastectomy only, TE/Imp, and DIEP flap groups. CONCLUSIONS: The results of the present study revealed that the localization of prolonged postoperative pain after breast surgery differs depending on the surgical procedure. In DIEP flap reconstruction, there was a marked tendency for pain in the inner and upper chest and in the abdomen, whereas TE/IMP surgery resulted in pain around the neck of the affected side. These findings may help improve surgical methods and establish effective pain relief that focuses on the identified pain areas.


Assuntos
Neoplasias da Mama , Dor Crônica , Mamoplastia , Retalho Perfurante , Feminino , Humanos , Neoplasias da Mama/cirurgia , Dor Crônica/etiologia , Dor Crônica/cirurgia , Artérias Epigástricas/cirurgia , Mamoplastia/métodos , Mastectomia/efeitos adversos , Mastectomia/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/cirurgia , Retalho Perfurante/cirurgia , Estudos Prospectivos , Estudos Retrospectivos
10.
Acta Anaesthesiol Scand ; 63(6): 745-750, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30869169

RESUMO

BACKGROUND: Advances in medical technology have resulted in an increased life expectancy in pediatric patients with congenital heart diseases. Assessment of health-related quality of life is crucial to improving their healthcare status. We aimed to assess post-surgical pain prevalence and its impact on health-related quality of life in pediatric patients who underwent cardiac surgery during childhood. METHODS: This cross-sectional study recruited patients aged 4 years or older who underwent cardiac surgery for congenital heart disease at least 1 year prior, during the age of 0-10 years, and were admitted for post-surgical follow-up at our institute. The prevalence, intensity, and location of pain and health-related quality of life were assessed in an interview. Perioperative information was collected from the patients' medical records. Health-related quality of life was assessed using the Pediatric quality of life inventory 4.0 (PedsQL). RESULTS: Pain was reported by 24 (17%) of the 141 participants. One-third of them reported moderate to severe pain that required medical intervention. After adjustment for several confounding factors, multivariable linear regression analysis demonstrated that the presence of pain and the number of surgeries were associated with lower total PedsQL scores. CONCLUSIONS: Pain was present in 17% of the patients who underwent cardiac surgery during childhood. Presence of pain had a negative impact on long-term health-related quality of life after pediatric cardiac surgery.


Assuntos
Dor Crônica/epidemiologia , Cardiopatias Congênitas/cirurgia , Dor Pós-Operatória/epidemiologia , Qualidade de Vida , Adolescente , Criança , Estudos Transversais , Feminino , Cardiopatias Congênitas/psicologia , Humanos , Masculino , Medição da Dor
11.
Mol Pain ; 14: 1744806918767508, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29592783

RESUMO

Background Intense nociceptive signaling arising from ongoing injury activates primary afferent nociceptive systems to generate peripheral sensitization. ERK1/2 phosphorylation in dorsal root ganglion can be used to visualize intracellular signal activity immediately after noxious stimulation. The aim of this study was to investigate spatiotemporal characteristics of ERK1/2 phosphorylation against tissue injury in the primary afferent neurons. Methods Plantar incisions were made in the hind paws of Sprague-Dawley rats (n =150). Levobupivacaine was injected into the plantar aspect of the paws and ankles, Mitogen-activated protein kinase kinase (MEK) inhibitor was injected into the paw, and carbenoxolone, dual inhibitor of the gap junction and pannexin channel, was intraperitoneally injected. Pain hypersensitivity was investigated by a behavioral study, while phosphorylated ERK1/2 was detected in dorsal root ganglion and hind paw using immunohistochemistry and Western blot. Results Phosphorylated ERK1/2 was induced in dorsal root ganglion (26.8 ± 2.9% at baseline, 65.6 ± 3.6% at 2 min, and 26.3 ± 3.4% at 2 h) after the incision. NF-200 positive A-fiber neurons and satellite glial cells were positive for phosphorylated ERK1/2. Injury-induced pain hypersensitivity was abolished by MEK inhibitor. Levobupivacaine treatment inhibited phosphorylated ERK1/2 induction, carbenoxolone treatment inhibited glial phosphorylated ERK1/2 at 2 min after the injury, and carbenoxolone inhibited pain hypersensitivity and neuronal phosphorylated ERK1/2 at 1 h after the injury. Conclusion ERK1/2 phosphorylation in A-fiber neurons and satellite glial cells immediately after injury contributes to the generation of pain hypersensitivity. Signal communication between neurons and satellite glial cells expands the duration of neuronal ERK1/2 phosphorylation and pain hypersensitivity at 1 h after tissue injury.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Extremidades/patologia , Gânglios Espinais/enzimologia , Gânglios Espinais/patologia , Neuroglia/enzimologia , Neurônios/enzimologia , Dor/enzimologia , Analgésicos/farmacologia , Animais , Bupivacaína/farmacologia , Bupivacaína/uso terapêutico , Ativação Enzimática , Extremidades/cirurgia , Hipersensibilidade/enzimologia , Hipersensibilidade/patologia , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Dor/tratamento farmacológico , Dor/patologia , Inibidores de Proteínas Quinases/farmacologia , Ratos Sprague-Dawley
12.
Mol Cell Biochem ; 440(1-2): 65-75, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28825160

RESUMO

Activating transcription factor 4 (ATF4), which is ubiquitously expressed, plays a crucial role in regulating various stress-responsive genes under pathophysiological conditions. Further, growth arrest and DNA damage-inducible gene 34 (GADD34), a downstream target of ATF4, has been reported to negatively regulate ATF4 expression. To understand the relationship between intrinsic ATF4 and GADD34 under resting and ER stress conditions, we used a novel gene editing approach, CRISPR/Cas9, to integrate antibiotic-resistant genes into the target genes, ATF4 and GADD34. First, we manipulated the ATF4 gene in the mouse neuroblastoma cell line, Neuro2a, and compared the ER stress responses between parental and ATF4-edited Neuro2a cells. Next, we established Neuro2a cells with edited GADD34 and ATF4/GADD34 genes and found that ATF4 acts as a proapoptotic factor, but GADD34 depletion did not attenuate the expression of cleaved caspase-3 induced by tunicamycin treatment. These findings provide new insights into the ATF4 signaling cascades. Additionally, the rapid establishment of cells lacking multiple genes using this CRISPR/Cas9 system will be a powerful tool for exploring various cellular issues under pathophysiological conditions.


Assuntos
Fator 4 Ativador da Transcrição , Sistemas CRISPR-Cas , Edição de Genes , Regulação da Expressão Gênica/genética , Proteína Fosfatase 1 , Transdução de Sinais/genética , Fator 4 Ativador da Transcrição/biossíntese , Fator 4 Ativador da Transcrição/genética , Animais , Linhagem Celular , Humanos , Camundongos , Proteína Fosfatase 1/biossíntese , Proteína Fosfatase 1/genética
13.
J Anesth ; 32(3): 434-438, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29523994

RESUMO

We performed a multicenter observational study to assess the prevalence and risk factors of persistent pain after lung cancer surgery and total knee arthroplasty (TKA) in the Japanese population. After receiving Ethics Committee approval, a retrospective chart review was performed for patients who underwent surgery at seven university hospitals in Japan in 2013. A total of 511 patients who underwent lung cancer surgery and 298 patients who underwent TKA were included. The prevalence of chronic postsurgical pain (CPSP) at 3 and 6 months was 18 and 12% after lung surgery and 49 and 33% after TKA, respectively. The prevalence of analgesic use at 3 and 6 months was 16 and 9% after lung surgery and 34 and 22% after TKA, respectively. In both groups, preoperative analgesic use was associated with CPSP. Anesthetic methods or techniques during both types of surgery did not significantly affect the prevalence of CPSP. This is the first study in which the prevalence of CPSP after lung surgery and TKA in Japanese population was extensively evaluated in a multicenter trial. Further prospective studies are needed to confirm the prevalence of CPSP in the Japanese population and to identify risk factors and prevention methods.


Assuntos
Artroplastia do Joelho/métodos , Dor Crônica/epidemiologia , Dor Pós-Operatória/epidemiologia , Toracotomia/métodos , Idoso , Idoso de 80 Anos ou mais , Analgésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Anestesia/efeitos adversos , Anestesia/métodos , Artroplastia do Joelho/efeitos adversos , Dor Crônica/etiologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pregabalina/administração & dosagem , Prevalência , Estudos Retrospectivos , Fatores de Risco
14.
Genes Cells ; 21(10): 1137-1143, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27515429

RESUMO

In this study, we applied a highly sensitive small luciferase, NanoLuc, to establish a knock-in cell line using the CRISPR/Cas9 system and characterized the endogenous promoter activity of the glucose-regulated protein 78 (GRP78) gene. The N-terminal region of the human GRP78 gene was fused to the NanoLuc gene and aligned with the puromycin-resistant gene through the 2A peptide sequence and used as a knock-in vector. The selected cells responded to both pharmacological and genetic ER stress and show NanoLuc-based CRISPR/Cas9 system is a very useful tool to isolate gene-edited cells and to characterize the endogenous promoter activity for genes of interest.


Assuntos
Sistemas CRISPR-Cas , Proteínas de Choque Térmico/genética , Substâncias Luminescentes , Regiões Promotoras Genéticas , Fator 6 Ativador da Transcrição/genética , Animais , Linhagem Celular , Chaperona BiP do Retículo Endoplasmático , Técnicas de Introdução de Genes , Células HEK293 , Humanos , Camundongos , RNA Guia de Cinetoplastídeos , Proteínas Recombinantes de Fusão/genética
15.
Anesthesiology ; 126(1): 150-162, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27984207

RESUMO

BACKGROUND: The molecular mechanisms responsible for sustained pain after tissue injury are largely unknown. The aim of this study was to clarify the role of exchange protein directly activated by cyclic adenosine monophosphate (EPAC) in sustained postincisional nociception, using tissue injury-induced nociceptor priming, and involvement of p38 mitogen-activated protein kinase (p38MAPK) in EPAC-mediated nociceptor priming. METHODS: Plantar incisions were made in the hind paws of Sprague-Dawley rats (n = 144). Nociceptor priming was confirmed by behavior testing followed by prostaglandin E2 injection 14 to 21 days after the incision. ESI-09, a selective EPAC inhibitor, was administered to assess its effects on nociceptor priming. Expression of two isoforms of EPAC (EPAC1/EPAC2) in dorsal root ganglions from naive rats and those 14 days after the incision was detected by immunohistochemistry and Western blotting. Separately, FR167653, a selective p38MAPK inhibitor, was administered to assess its effect on EPAC1/EPAC2 expression and the development of nociceptor priming. RESULTS: Prostaglandin E2 injection 14 to 21 days after the plantar incision induced persistent mechanical hyperalgesia for 7 days. EPAC1/EPAC2 expression in dorsal root ganglion neurons was trivial in naive rats (7.7 ± 4.8% for EPAC1; 6.3 ± 4.1% for EPAC2) but markedly increased 14 days after the incision (21.0 ± 9.4% and 20.1 ± 3.8%, respectively). ESI-09 treatment inhibited prostaglandin E2-induced persistent mechanical hypersensitivity but had no effect on incision-induced acute nociceptive hypersensitivity. Treatment with FR167653 before the incision inhibited the development of nociceptor priming and incision-induced EPAC1/EPAC2 expression (8.5 ± 5.4% and 7.6 ± 3.3%, respectively). CONCLUSIONS: Transient inflammatory stimulation causes long-lasting nociceptive hypersensitivity via nociceptor priming during the subacute period after incision. Acquired EPAC activity by p38MAPK in the dorsal root ganglion neurons is a key for this event.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/metabolismo , Neurônios Aferentes/metabolismo , Nociceptividade/fisiologia , Nociceptores/metabolismo , Dor/fisiopatologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Fatores de Troca do Nucleotídeo Guanina/genética , Hiperalgesia/fisiopatologia , Masculino , Dor/metabolismo , Ratos , Ratos Sprague-Dawley
16.
J Clin Monit Comput ; 31(5): 927-941, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27492429

RESUMO

Arterial pulse waveform analysis (APWA) with a semi-invasive cardiac output monitoring device is popular in perioperative hemodynamic and fluid management. However, in APWA, evaluation of hemodynamic data is not well discussed. In this study, we analyzed how we visually interpret hemodynamic data, including stroke volume variation (SVV) and stroke volume (SV) derived from APWA. We performed arithmetic estimation of the SVV-SV relationship and applied measured values to this estimation. We then collected measured values in six anesthesia cases, including three liver transplantations and three other types of surgeries, to apply them to this SVV-SVI (stroke volume variation index) plot. Arithmetic analysis showed that the relationship between SVV and SV can be drawn as hyperbolic curves. Plotting SVV-SV values in the semi-logarithmic scale showed linear correlations, and the slopes of the linear regression lines theoretically represented average mean cardiac contractility. In clinical measurements in APWA, plotting SVV and SVI values in the linear scale and the semi-logarithmic scale showed the correlations represented by hyperbolic curves and linear regression lines. The plots approximately shifted on the rectangular hyperbolic curves, depending on blood loss and blood transfusion. Arithmetic estimation is close to real measurement of the SVV-SV interaction in hyperbolic curves. In APWA, using SVV as an index of preload and the cardiac index or SVI derived from arterial pressure-based cardiac output as an index of cardiac function, is likely to be appropriate for categorizing hemodynamic stages as a substitute for Forrester subsets.


Assuntos
Hidratação , Hemodinâmica , Monitorização Fisiológica/métodos , Volume Sistólico , Adulto , Idoso , Anestesia , Pressão Arterial , Artérias , Pressão Sanguínea , Débito Cardíaco , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Curva ROC , Respiração Artificial , Processamento de Sinais Assistido por Computador , Volume de Ventilação Pulmonar , Sinais Vitais , Adulto Jovem
17.
Masui ; 66(4): 383-386, 2017 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-30382636

RESUMO

BACKGROUND: Postsurgical hoarseness is one of the major postoperative complications. METHODS: Risk factors associated with the postsur- gical hoarseness were investigated from medical records of 579 adult patients undergoing general anes- thesia with tracheal intubation. Postsurgical hoarseness was judged if a patient developed hoarseness at PODO or PODI by postanesthesia round. Multivariate logistic regression was performed to identify the parameters associated with postsurgical hoarseness. RESULTS: Postsurgical hoarseness developed in 16.1% of patients. None of the patients suffered hoarseness continuing more than 4 days. Multivariate logistic regression revealed increased BMI (odds ratio (OR) 1.06 [95% confidence interval (CI):1.00-1.131], depth of tracheal tube (OR 0.71 [95% CI : 0.57-0.86]), intu- bation performed by doctors in training (OR 4.07 [95% CI : 2.42-7.10]) and intubation with Airway Scope® (OR 2.03 [95% CI : 1.10-3.66]). CONCLUSIONS: Increased BMI, depth of tracheal tube, intubation performed by doctors in training and intu- bation with Airway Scope® are risk factors of postsur- gical hoarseness.


Assuntos
Rouquidão/etiologia , Intubação Intratraqueal/efeitos adversos , Complicações Pós-Operatórias , Adulto , Idoso , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Fatores de Risco
18.
J Anesth ; 35(2): 165-167, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33687548
19.
Gan To Kagaku Ryoho ; 43(3): 345-8, 2016 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-27067852

RESUMO

Various effective strategies have recently been described in the treatment of breast cancer, including endocrine therapy, chemotherapy, and molecular-targeted therapy, providing long-term survival benefits even after cancer recurrence. However, terminal-stage patients experience side effects and worse quality of life (QOL), in addition to deterioration of their general condition caused by the progression of the disease itself. When providing the best supportive care, use of anti-cancer drugs is not taboo and can represent a good option as long as physical, social, psychological, and spiritual supports are provided to both the patients and their families. Medroxyprogesterone acetate (MPA) is an endocrine therapeutic drug. In Japan, MPA is used only as a late-line endocrine therapy for breast cancer recurrence because many other endocrine therapy drugs are much more effective and MPA increases the risk of thrombosis and obesity. Here, we report 2 patients with breast cancer who reached terminal stage more than 10 years after the first diagnosis. MPA was administered as the final-line treatment. During that time, their appetite and QOL improved and the patients became more active than when they had been undergoing aggressive anticancer treatment. Both patients spent quality time with their families until their death. MPA may be a good option as part of palliative care of breast cancer patients in terminal stage.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Acetato de Medroxiprogesterona/uso terapêutico , Cuidados Paliativos , Idoso , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Doente Terminal
20.
J Anesth ; 29(2): 175-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25262474

RESUMO

PURPOSE: In order to investigate the current practice of preoperative anesthesia assessment in Japan, we conducted a nationwide survey of the preoperative anesthesia clinic (PAC). METHODS: A written questionnaire was sent to anesthesia teaching hospitals certified by the Japanese Society of Anesthesiologists. RESULTS: Completed questionnaires were received from 789 hospitals (response rate 62.5 %). PACs were conducted in 52.0 % of these hospitals and were more frequently implemented in large hospitals. Services covered by the PAC included medical history taking, physical examination, review of laboratory data, and obtaining informed consent. Majority of the anesthesiologists at hospitals that did not have a PAC responded that although they acknowledged that a PAC is necessary, they were unable to set one up. The main obstacle preventing establishment of the PAC was shortage of human resources. CONCLUSIONS: Half the anesthesia teaching hospitals in Japan use a PAC for preoperative assessment. At such hospitals, all the procedures required before anesthesia are performed in the clinic. Lack of human resources is the major obstacle preventing establishment of PACs in all hospitals.


Assuntos
Anestesia/normas , Cuidados Pré-Operatórios/normas , Pesquisas sobre Atenção à Saúde , Tamanho das Instituições de Saúde , Hospitais de Ensino/estatística & dados numéricos , Humanos , Consentimento Livre e Esclarecido , Japão , Anamnese , Exame Físico , Médicos/estatística & dados numéricos , Cuidados Pré-Operatórios/estatística & dados numéricos , Inquéritos e Questionários
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