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1.
BMC Anesthesiol ; 24(1): 209, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38907200

RÉSUMÉ

BACKGROUND: We used transcatheter aortic valve implantation (TAVI) procedure time to investigate the association between surgical team maturity and outcome. METHODS: Among patients who underwent TAVI between October 2015 and November 2019, those who had Sapien™ implanted with the transfemoral artery approach were included in the analysis. We used TAVI procedure time and surgery number to draw a learning curve. Then, we divided the patients into two groups before and after the number of cases where the sigmoid curve reaches a plateau. We compared the two groups regarding the surveyed factors and investigated the correlation between the TAVI procedure time and survey factors. RESULTS: Ninety-nine of 149 patients were analysed. The sigmoid curve had an inflection point in 23.2 cases and reached a plateau in 43.0 cases. Patients in the Late group had a shorter operating time, less contrast media, less radiation exposure, and less myocardial escape enzymes than the Early group. Surgical procedure time showed the strongest correlation with the surgical case number. CONCLUSION: The number of cases required for surgeon proficiency for isolated Sapien™ valve implantation was 43. This number may serve as a guideline for switching the anesthesia management of TAVI from general to local anesthesia.


Sujet(s)
Courbe d'apprentissage , Durée opératoire , Remplacement valvulaire aortique par cathéter , Humains , Remplacement valvulaire aortique par cathéter/méthodes , Études rétrospectives , Mâle , Femelle , Sujet âgé de 80 ans ou plus , Sujet âgé , Compétence clinique , Résultat thérapeutique , Sténose aortique/chirurgie
2.
Cureus ; 16(5): e60564, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38887347

RÉSUMÉ

Transnasal humidified rapid-insufflation ventilator exchange (THRIVE) has been reported to have better efficacy during anesthesia induction compared to conventional mask ventilation, including improved oxygenation and prolonged safe apnea time. This study reports on the effectiveness of the THRIVE system during modified electroconvulsive therapy (mECT) for a patient experiencing severe hypoxia. A 78-year-old female patient with bipolar disorder received maintenance mECT every four weeks. She previously experienced a significant hypoxic event, with oxygen saturation (SpO2) dropping to 50% following electrical stimulation. In response, we employed the THRIVE system, designed to deliver high-flow, 100% oxygen, thereby extending apnea tolerance. The implementation of THRIVE ensured a stable oxygen supply, maintaining oxygen saturation levels above 95% throughout the mECT procedure. THRIVE is useful for treating hypoxia that occurs due to the unavoidable lack of ventilation during mECT.

3.
J Med Invest ; 71(1.2): 184-186, 2024.
Article de Anglais | MEDLINE | ID: mdl-38735719

RÉSUMÉ

BACKGROUND: Hereditary angioedema (HAE), a genetic disorder caused by C1-inhibitor deficiency or dysfunction, may cause mucosal edema in the upper airway during tracheal intubation and extubation. CASE REPORT: A 57-year-old man with HAE and a history of laryngeal edema, scheduled to undergo cervical laminoplasty under general anesthesia. General anesthesia was induced by continuous injection of remimazolam and remifentanil, during which manual mask ventilation and intubation were performed without difficulty. The patient was extubated under deep anesthesia. After emergence from general anesthesia, he had no significant upper airway edema and was treated with a C1-inhibitor seven hours post-surgery because of slight tongue swelling. No additional airway edema was observed, and the patient was discharged from the intensive care unit the following day. CONCLUSIONS: Deep anesthesia tracheal extubation with remimazolam may be effective in preventing upper airway edema during anesthetic management in patients with HAE. J. Med. Invest. 71 : 184-186, February, 2024.


Sujet(s)
Anesthésie générale , Angio-oedèmes héréditaires , Humains , Mâle , Adulte d'âge moyen , Angio-oedèmes héréditaires/traitement médicamenteux , Benzodiazépines/usage thérapeutique
4.
JA Clin Rep ; 10(1): 26, 2024 Apr 22.
Article de Anglais | MEDLINE | ID: mdl-38647904

RÉSUMÉ

BACKGROUND: Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and succinylcholine, leading to a hypermetabolic reaction. The pathogenic ryanodine receptor 1 (RYR1) gene variant is critical. Patients susceptible to MH should avoid triggering agents, and total intravenous anesthesia (TIVA) is preferred. Remimazolam is safe in patients with suspected MH. CASE PRESENTATION: We present the first case of remimazolam treatment in a genetically confirmed patient with MH without MH development. A 72-year-old man with a family history of MH underwent remimazolam-based TIVA. After informed consent was obtained, a muscle biopsy and genetic testing were performed. Intraoperatively and postoperatively, the patient exhibited no signs of MH. An enhanced function of the RYR1 channel into releasing calcium was indicated, and the genetic testing revealed a pathogenic variant of RYR1. CONCLUSIONS: Remimazolam-based TIVA is safe in patients confirming the diagnosis of MH.

5.
Cureus ; 16(2): e54156, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38496151

RÉSUMÉ

Klippel-Trenaunay syndrome (KTS) is also associated with venous thrombosis originating from varicose veins in the lower extremities, pulmonary embolism, and pulmonary hypertension. This study describes the anesthetic management of laparoscopic cholecystectomy in a 54-year-old male KTS patient with orthostatic hypotension due to massive varicose veins in the lower extremities and pulmonary thromboembolism. Compressing the varicosities with an elastic bandage can maintain stable circulatory dynamics even under general anesthesia management to prevent position and insufflation-induced changes that can occur spontaneously.

6.
Nutrients ; 16(6)2024 Mar 15.
Article de Anglais | MEDLINE | ID: mdl-38542761

RÉSUMÉ

Patients undergoing gastrectomy for gastric cancer may experience alterations in olfaction, yet the association between olfactory changes and postoperative weight loss remains uncertain. This study aimed to elucidate the relationship between olfactory changes and postoperative weight loss in patients with gastric cancer. Patients who underwent radical gastrectomy for gastric cancer between February 2022 and August 2022 were included in the study. Those experiencing a higher Visual Analog Scale (VAS) score postoperatively compared to preoperatively were deemed to have undergone olfactory changes. Postoperative weight loss was determined using the 75th percentile as a cutoff value, designating patients surpassing this threshold as experiencing significant weight loss. Multivariate logistic regression analysis was employed to identify risk factors for postoperative weight loss, with statistical significance set at p < 0.05. Out of 58 patients, 10 (17.2%) exhibited olfactory changes. The rate of postoperative weight loss at one month was markedly higher in the group with olfactory changes compared to those without (9.6% versus 6.2%, respectively; p = 0.002). In addition, the group experiencing olfactory changes demonstrated significantly lower energy intake compared to the group without such changes (1050 kcal versus 1250 kcal, respectively; p = 0.029). Logistic regression analysis revealed olfactory changes as an independent risk factor for significant weight loss at one month postoperatively (odds ratio: 7.64, 95% confidence interval: 1.09-71.85, p = 0.048). In conclusion, olfactory changes emerged as an independent risk factor for postoperative weight loss at one month in patients with gastric cancer following gastrectomy.


Sujet(s)
Troubles de l'olfaction , Tumeurs de l'estomac , Humains , Tumeurs de l'estomac/complications , Complications postopératoires/étiologie , Gastrectomie/effets indésirables , Perte de poids , Études rétrospectives
7.
Medicina (Kaunas) ; 60(3)2024 Feb 21.
Article de Anglais | MEDLINE | ID: mdl-38541085

RÉSUMÉ

Refractory peripheral neuropathy can occur as a side effect in 60-70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw. This was carried out before the Paclitaxel administration and during the first, second, third, and fourth weeks. Using a rat model of PTX-induced neuropathic pain (PTX rat), we injected PTX (intraperitoneally, 2 mg/kg) five times every 2 days. Using the dynamic plantar test, we evaluated the anti-allodynic effect of YKS (orally administered, 1 g/kg). YKS administration on a daily basis significantly enhanced the withdrawal threshold in PTX rats and reduced the expression level of activated microglia immunostaining with Iba1, a specific marker for microglia. The intrathecal administration of WAY-100635 (5-hydroxytryptamine [5-HT]1A receptor antagonist) and Ketanserin (5-HT2A/2C receptor antagonist) inhibited the protective effects of YKS. YKS exhibited an anti-allodynic effect in a rodent model of PTX-induced neuropathic pain by reducing the sensitivity to pain stimuli. These results suggest that Yokukansan may activate 5-HT receptors in the spinal cord, mediating Paclitaxel-induced neuropathic pain.


Sujet(s)
Médicaments issus de plantes chinoises , Hyperalgésie , Névralgie , Humains , Rats , Mâle , Animaux , Hyperalgésie/induit chimiquement , Hyperalgésie/traitement médicamenteux , Hyperalgésie/métabolisme , Sérotonine , Paclitaxel/effets indésirables , Rat Sprague-Dawley , Névralgie/induit chimiquement , Névralgie/traitement médicamenteux , Modèles animaux de maladie humaine
9.
Sci Rep ; 13(1): 20486, 2023 11 22.
Article de Anglais | MEDLINE | ID: mdl-37993532

RÉSUMÉ

Necessary and sufficient opioids should be administered for safe and stable anesthesia. However, opioid sensitivity varies among individuals. We previously reported that sympathetic responses to nociceptive stimuli under propofol anesthesia could be predicted by measuring the minimum evoked current of the vascular stiffness value (MECK). However, this result has only been proven under propofol anesthesia. We propose that MECK could be used under anesthesia with a volatile anesthetic. Thirty patients undergoing laparotomy with sevoflurane anesthesia received 0.7 minimum alveolar concentration (MAC) sevoflurane and intravenous remifentanil at a constant concentration of 2 ng/mL, followed by tetanic stimulation, to measure MECK. After tetanic stimulation, the same anesthetic conditions were maintained, and the rate of change in systolic blood pressure (ROCBP) during the skin incision was measured. The correlation coefficient between the MECK and ROCBP during skin incision under sevoflurane anesthesia was R = - 0.735 (P < 0.01), similar to that in a previous study with propofol (R = - 0.723). Thus, a high correlation was observed. The slope of the linear regression equation was - 0.27, similar to that obtained in the study on propofol (- 0.28). These results suggest that, as with propofol anesthesia, MECK can be used as a predictive index for ROCBP under 0.7 MAC sevoflurane anesthesia.Clinical trial registration: Registry, University hospital Medical Information Network; registration number, UMIN000047425; principal investigator's name, Noboru Saeki; date of registration, April 8, 2022.


Sujet(s)
Anesthésie , Anesthésiques par inhalation , Éthers méthyliques , Propofol , Plaie opératoire , Rigidité vasculaire , Humains , Analgésiques morphiniques/pharmacologie , Anesthésiques par inhalation/pharmacologie , Anesthésiques intraveineux/pharmacologie , Pression sanguine , Éthers méthyliques/pharmacologie , Propofol/pharmacologie , Sévoflurane/pharmacologie
10.
A A Pract ; 17(11): e01727, 2023 Nov 01.
Article de Anglais | MEDLINE | ID: mdl-37948548

RÉSUMÉ

Ropivacaine is an amide local anesthetic with rare reports of anaphylaxis. To our knowledge, this is the first report of delayed nonimmune anaphylaxis induced by ropivacaine. A 70-year-old man underwent general anesthesia with a nerve block for a total knee arthroplasty. The patient developed symptoms of anaphylaxis 3.5 hours after receiving ropivacaine for femoral and tibial nerve blocks. A basophil activation test (BAT) revealed ropivacaine as the causative agent. Notably, anaphylaxis can be caused by medications even hours after their administration, and all administered drugs should be suspected of potentially causing anaphylaxis.


Sujet(s)
Anaphylaxie , Bloc nerveux , Mâle , Humains , Sujet âgé , Ropivacaïne/effets indésirables , Anesthésiques locaux/effets indésirables , Anaphylaxie/induit chimiquement , Amides/effets indésirables , Bloc nerveux/effets indésirables
11.
J Med Invest ; 70(3.4): 430-435, 2023.
Article de Anglais | MEDLINE | ID: mdl-37940528

RÉSUMÉ

Monitored anesthesia care (MAC) often causes airway complications, particularly posing an elevated risk of aspiration and airway obstruction in obese patients. This study aimed to quantify the levels of aspiration and airway obstruction using an artificial intelligence (AI)-based acoustic analysis algorithm, assessing its utility in identifying airway complications in obese patients. To verify the correlation between the stridor quantitative value (STQV) calculated by acoustic analysis and body weight, and to further evaluate fluid retention and airway obstruction, STQV calculated exhaled breath sounds collected at the neck region, was compared before and after injection of 3 ml of water in the oral cavity and at the start and end of the MAC procedures. STQV measured immediately following the initiation of MAC exhibited a weak correlation with body mass index. Furhtermore, STQV values before and after water injection increased predominantly after injection, further increased at the end of MAC. AI-based analysis of cervical respiratory sounds can enhance the safety of airway management during MAC by quantifying airway obstruction and fluid retention in obese patients. J. Med. Invest. 70 : 430-435, August, 2023.


Sujet(s)
Obstruction des voies aériennes , Anesthésie , Humains , Bruits respiratoires , Intelligence artificielle , Obstruction des voies aériennes/diagnostic , Obstruction des voies aériennes/complications , Acoustique , Obésité/complications , Eau
12.
Genes (Basel) ; 14(11)2023 Oct 27.
Article de Anglais | MEDLINE | ID: mdl-38002952

RÉSUMÉ

Remimazolam is a novel general anesthetic and its safety in patients with malignant hyperthermia (MH) is unknown. We used myotubes derived from the skeletal muscle of patients with MH to examine the response to ryanodine receptor 1 (RYR1) agonist and remimazolam in MH-susceptible patients. Patients underwent muscle biopsy for the Ca2+-induced Ca2+ release (CICR) rate test, a diagnostic tool for MH in Japan. Ten patients had myotubes obtained from skeletal muscle cultures, and the genes associated with malignant hyperthermia in these patients were analyzed. The EC50 of caffeine, cresol, and remimazolam to induce intracellular calcium concentration change were compared between myotubes from CICR-negative genetic test patients and myotubes from other patients. Eight of the ten were CICR-positive, five of whom had RYR1 causative gene mutations or variants. Two patients had CICR-negative genetic tests, and as expected had the highest EC50 (the concentration of a drug that gives a half-maximal response) in response to caffeine, 4CmC and remimazolam. Three patients had a positive CICR but no known variants in RYR1 or CACNA1S (voltage-gated calcium channel subunit alpha1S). Myotubes in these patients had significantly lower EC50s for all agents than myotubes in CICR-negative patients. When myotubes from a patient who was CICR-negative and had no gene variant were used as a control, myotubes from CICR-positive patients were more hyper-responsive than controls to all stimulants used. The EC50 for remimazolam was lowest for myotubes from CICR-positive, RYR1-mutant patients, at 206 µM (corresponding to 123 µg/mL). The concentration was more than 80-times higher than the clinical concentration. RYR1 gene variants in R4645Q and W5020G were shown to be causative gene mutations for MH. Intracellular calcium in myotubes from MH patients are elevated at high concentrations of remimazolam but not at clinically used concentrations of remimazolam. Remimazolam appears to be safe to use in patients with MH.


Sujet(s)
Hyperthermie maligne , Canal de libération du calcium du récepteur à la ryanodine , Humains , Canal de libération du calcium du récepteur à la ryanodine/génétique , Hyperthermie maligne/traitement médicamenteux , Hyperthermie maligne/génétique , Calcium/métabolisme , Caféine/pharmacologie , Fibres musculaires squelettiques/métabolisme
13.
Medicine (Baltimore) ; 102(46): e36081, 2023 Nov 17.
Article de Anglais | MEDLINE | ID: mdl-37986333

RÉSUMÉ

BACKGROUND: Remimazolam is a novel, ultrashort-acting benzodiazepine that can be antagonized by flumazenil. This study aimed to determine whether remimazolam-based anesthesia with flumazenil provides a more rapid emergence than propofol-based anesthesia in older patients undergoing spinal surgery. METHODS: This was a prospective, single-blind, randomized controlled trial. Forty-four patients > 75 years old who had undergone spinal surgery were enrolled in this study. They were randomly assigned to the remimazolam or propofol group (1:1) using a computer randomization system stratified by age and body weight. For anesthesia induction and maintenance, remifentanil was administered at a defined dose in both groups, and remimazolam or propofol was adjusted to maintain the bispectral index or state entropy monitoring within 40-60. All anesthetics were discontinued simultaneously after the postoperative X-ray and 0.5 mg flumazenil was administered to the remimazolam group. The primary outcome was extubation time after discontinuing anesthesia, and the secondary outcomes were time to eye opening, obeying commands, and achieving a white fast-track score (WFTS) of 12. RESULTS: Thirty-nine patients were finally analyzed: remimazolam group (n = 20), propofol group (n = 19). There were no significant differences in intraoperative variables, such as operative time, anesthesia time, and patient background, between the 2 groups. Extubation times were significantly shorter in the remimazolam group than in the propofol group (4 vs 8 minutes, P < .001). The time to eye opening, obeying commands, and achieving a WFTS of 12 were significantly shorter in the remimazolam group (P < .001, for all comparisons). CONCLUSION: Remimazolam-based anesthesia with flumazenil resulted in a faster emergence than propofol-based anesthesia in older patients undergoing spinal surgery.


Sujet(s)
Propofol , Humains , Sujet âgé , Flumazénil , Anesthésiques intraveineux , Études prospectives , Méthode en simple aveugle , Benzodiazépines , Anesthésie générale
14.
Sci Rep ; 13(1): 20196, 2023 11 18.
Article de Anglais | MEDLINE | ID: mdl-37980396

RÉSUMÉ

Respiratory monitoring is crucial during monitored anaesthesia care (MAC) to ensure patient safety. Patients undergoing procedures like gastrointestinal endoscopy and dental interventions under MAC have a heightened risk of aspiration. Despite the risks, no current system or device can evaluate aspiration risk. This study presents a novel acoustic monitoring system designed to detect fluid retention in the upper airway during MAC. We conducted a prospective observational study with 60 participants undergoing dental treatment under MAC. We utilized a prototype acoustic monitoring system to assess fluid retention in the upper airway by analysing inspiratory sounds. Water was introduced intraorally in participants to simulate fluid retention; artificial intelligence (AI) analysed respiratory sounds pre and post-injection. We also compared respiratory sounds pre-treatment and during coughing events. Coughing was observed in 14 patients during MAC, and 31 instances of apnoea were detected by capnography. However, 27 of these cases had breath sounds. Notably, with intraoral water injection, the Stridor Quantitative Value (STQV) significantly increased; furthermore, the STQV was substantially higher immediately post-coughing in patients who coughed during MAC. In summary, the innovative acoustic monitoring system using AI provides accurate evaluations of fluid retention in the upper airway, offering potential to mitigate aspiration risks during MAC.Clinical trial number: jRCTs 062220054.


Sujet(s)
Anesthésie , Bruits respiratoires , Humains , Intelligence artificielle , Anesthésie/effets indésirables , Acoustique , Eau
15.
Front Pharmacol ; 14: 1284586, 2023.
Article de Anglais | MEDLINE | ID: mdl-38026993

RÉSUMÉ

Background and purpose: In this study, we aimed to elucidate the action mechanisms of propofol, particularly those underlying propofol-induced protein kinase C (PKC) translocation. Experimental approach: Various PKCs fused with green fluorescent protein (PKC-GFP) or other GFP-fused proteins were expressed in HeLa cells, and their propofol-induced dynamics were observed using confocal laser scanning microscopy. Propofol-induced PKC activation in cells was estimated using the C kinase activity receptor (CKAR), an indicator of intracellular PKC activation. We also examined PKC translocation using isomers and derivatives of propofol to identify the crucial structural motifs involved in this process. Key results: Propofol persistently translocated PKCα conventional PKCs and PKCδ from novel PKCs (nPKCs) to the plasma membrane (PM). Propofol translocated PKCδ and PKCη of nPKCs to the Golgi apparatus and endoplasmic reticulum, respectively. Propofol also induced the nuclear translocation of PKCζ of atypical PKCs or proteins other than PKCs, such that the protein concentration inside and outside the nucleus became uniform. CKAR analysis revealed that propofol activated PKC in the PM and Golgi apparatus. Moreover, tests using isomers and derivatives of propofol predicted that the structural motifs important for the induction of PKC and nuclear translocation are different. Conclusion and implications: Propofol induced the subtype-specific intracellular translocation of PKCs and activated PKCs. Additionally, propofol induced the nuclear translocation of PKCs and other proteins, probably by altering the permeability of the nuclear envelope. Interestingly, propofol-induced PKC and nuclear translocation may occur via different mechanisms. Our findings provide insights into the action mechanisms of propofol.

16.
Nutrients ; 15(19)2023 Oct 03.
Article de Anglais | MEDLINE | ID: mdl-37836536

RÉSUMÉ

Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber that is effective for defecation control. It influences the gut microbiota, by which it is metabolized to yield short-chain fatty acids (SCFAs), and it was also recently shown to protect against influenza infection in humans. We here investigated the effects of PHGG in a mouse model of influenza H1N1 virus infection. Eight-week-old C57BL/6 mice were fed normal chow with or without PHGG (500 mg/kg per day) for 4 weeks, infected with H1N1 at 10 weeks of age, and analyzed at 12 weeks of age. Administration of PHGG attenuated the decline in body weight induced by H1N1 infection without affecting food intake. It also ameliorated intestinal atrophy and increased the production of SCFAs including acetic acid, propionic acid, and butyric acid in the cecum, thereby preventing the inhibitory effect of H1N1 infection on SCFA production. The H1N1-induced increases in the serum concentrations of inflammatory cytokines including interferon-γ and interleukin-6 and anti-inflammatory cytokine such as interleukin-10 were all inhibited by PHGG intake. In addition, PHGG administration attenuated inflammatory gene expression in the lung and promoted both natural killer cell activity and regulatory T-cell differentiation in the spleen. Our findings suggest that the consumption of PHGG may improve the gut environment and thereby limit the inflammatory response to H1N1 infection. They may thus provide the basis for novel dietary intervention strategies to suppress the excessive inflammation associated with virus infection.


Sujet(s)
Maladies transmissibles , Microbiome gastro-intestinal , Sous-type H1N1 du virus de la grippe A , Grippe humaine , Infections à Orthomyxoviridae , Humains , Souris , Animaux , Souris de lignée C57BL , Inflammation/traitement médicamenteux , Inflammation/métabolisme , Galactanes/pharmacologie , Mannanes/pharmacologie , Gommes végétales/pharmacologie , Acides gras volatils/métabolisme , Fibre alimentaire/pharmacologie
17.
J Clin Med ; 12(16)2023 Aug 20.
Article de Anglais | MEDLINE | ID: mdl-37629444

RÉSUMÉ

(1) Background: Remimazolam is a novel benzodiazepine that prevents postoperative nausea and vomiting (PONV), is more effective than volatile anesthetics, and was recently approved for use in Japan. (2) Methods: This prospective, double-blind, randomized controlled trial study aimed to compare the efficacy of remimazolam and propofol as general anesthetics in terms of the incidence of PONV after laparoscopic gynecological surgery (UMIN000046237). High-risk female patients who underwent general anesthesia with either remimazolam or propofol for the maintenance of anesthesia were enrolled. The primary outcome was the incidence of PONV in the two groups (i.e., REM versus PROP) 2 h and 24 h after surgery. The incidence of vomiting without nausea, rescue antiemetic use, and the severity of nausea were also evaluated. (3) Results: No significant differences in PONV were identified between the REM and PROP groups at 2 h or 24 h. Furthermore, no differences were observed in any of the measured parameters, and no adverse events were reported. (4) Conclusions: The results of the present study suggest that remimazolam may be as effective as propofol in preventing PONV; however, further investigation is necessary to identify possible differences between these two agents.

18.
Eur J Pharmacol ; 955: 175806, 2023 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-37230321

RÉSUMÉ

Propofol is widely used for general anesthesia and sedation; however, the mechanisms of its anesthetic and adverse effects are not fully understood. We have previously shown that propofol activates protein kinase C (PKC) and induces its translocation in a subtype-specific manner. The purpose of this study was to identify the PKC domains involved in propofol-induced PKC translocation. The regulatory domains of PKC consist of C1 and C2 domains, and the C1 domain is subdivided into the C1A and C1B subdomains. Mutant PKCα and PKCδ with each domain deleted were fused with green fluorescent protein (GFP) and expressed in HeLa cells. Propofol-induced PKC translocation was observed by time-lapse imaging using a fluorescence microscope. The results showed that persistent propofol-induced PKC translocation to the plasma membrane was abolished by the deletion of both C1 and C2 domains in PKCα and by the deletion of the C1B domain in PKCδ. Therefore, propofol-induced PKC translocation involves the C1 and C2 domains of PKCα and the C1B domain of PKCδ. We also found that treatment with calphostin C, a C1 domain inhibitor, abolished propofol-induced PKCδ translocation. In addition, calphostin C inhibited the propofol-induced phosphorylation of endothelial nitric oxide synthase (eNOS). These results suggest that it may be possible to modulate the exertion of propofol effects by regulating the PKC domains involved in propofol-induced PKC translocation.


Sujet(s)
Propofol , Protéine kinase C , Humains , Protéine kinase C/métabolisme , Protein kinase C-alpha/métabolisme , Propofol/pharmacologie , Cellules HeLa , Isoenzymes/métabolisme , Transport des protéines
19.
Biomed Res Int ; 2023: 8340209, 2023.
Article de Anglais | MEDLINE | ID: mdl-36874927

RÉSUMÉ

Purpose: Malignant hyperthermia (MH) is a rare genetic disorder but one of the most severe complications of general anesthesia. The mortality rate of MH has dropped from 70% in the 1960s to 15% because of dantrolene, the only currently accepted specific treatment for MH. In this study, we retrospectively identified the optimal dantrolene administration conditions to reduce MH mortality further. Methods: Our database performed a retrospective analysis of patients with MH clinical grading scale (CGS) grade 5 (very likely) or 6 (almost certain) between 1995 and 2020. We examined whether dantrolene administration affected mortality and compared the clinical variables associated with improved prognosis. Furthermore, a multivariable logistic regression analysis was used to identify specific variables associated with improved prognosis. Results: 128 patients met the inclusion criteria. 115 patients were administered dantrolene; 104 survived, and 11 died. The mortality rate of patients who were not administered dantrolene was 30.8%, which was significantly higher than those of patients who were administered dantrolene (P = 0.047). Among patients administered dantrolene, the interval from the first sign of MH to the start of dantrolene administration was significantly longer in the deceased than in the survivors (100 min vs. 45.0 min, P < 0.001), and the temperature at the start of dantrolene administration was also significantly higher in the deceased (41.6°C vs. 39.1°C, P < 0.001). There was no significant difference in the rate of increase in temperature between the two, but there was a substantial difference in the maximum temperature (P < 0.001). The multivariable analysis also showed that the patient's temperature at dantrolene administration and interval from the first MH sign to dantrolene administration was significantly associated with improved prognosis. Conclusions: Dantrolene should be given as rapidly as possible once MH has been diagnosed. Beginning treatment at a more normal body temperature can prevent critical elevations associated with a worse prognosis.


Sujet(s)
Dantrolène , Hyperthermie maligne , Humains , Études rétrospectives , Température du corps , Peuples d'Asie de l'Est , Maladies rares
20.
Am J Case Rep ; 24: e939369, 2023 Mar 21.
Article de Anglais | MEDLINE | ID: mdl-36944584

RÉSUMÉ

BACKGROUND Hemophagocytic syndrome (HPS) is a rare syndrome characterized by abnormal activation of histiocytes and hemophagocytosis. We report the clinical management of recurrent HPS following 2 cesarean sections in the same patient. CASE REPORT A 33-year-old primiparous mother presented during her second trimester of pregnancy, and HPS was diagnosed based on pancytopenia, hyperferritinemia (13 170 ng/ml), and hemophagocytosis in bone marrow examination. Despite steroid therapy, her HPS did not improve. Following the delivery of a healthy premature infant, there was no improvement in HPS, and immunochemotherapy was started 4 days postoperatively. Thrombocytopenia and hyperferritinemia persisted but normalized over the next 2 months, and immunochemotherapy was discontinued after 6 months. About 1 year after chemotherapy, the patient became pregnant with her second child. At 35 weeks of gestation, recurrence of HPS was suspected, and a C-section was performed at 36 weeks of gestation. The surgery was complicated by placenta previa, and general anesthesia was initiated after successful delivery of the infant. Epidural anesthesia was not performed due to concerns for postoperative thrombocytopenia. CONCLUSIONS Interestingly, HPS was likely triggered twice by pregnancy in this patient. Although reports of HPS during pregnancy are rare, there have been reports of rapid deterioration and death. Early diagnosis and therapeutic intervention are essential.


Sujet(s)
Hyperferritinémie , Lymphohistiocytose hémophagocytaire , Pancytopénie , Thrombopénie , Femelle , Nourrisson , Enfant , Grossesse , Humains , Adulte , Lymphohistiocytose hémophagocytaire/diagnostic , Lymphohistiocytose hémophagocytaire/thérapie , Lymphohistiocytose hémophagocytaire/complications , Femmes enceintes , Hyperferritinémie/complications , Pancytopénie/étiologie , Thrombopénie/complications
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