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2.
Thyroid ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38666696

RESUMEN

Background: The density of tumor-associated macrophages in the tumor microenvironment of anaplastic thyroid cancer (ATC) is associated with poor prognosis. However, the crosstalk between macrophages and ATC cells is poorly understood. This study aimed to examine the impact of macrophages on cancer cell phenotypes. We found a new mediator between M2 macrophages and ATC cells through proteomics analysis. Methods: The role of macrophages in proliferation, migration, and invasion of ATC cells was evaluated using coculture assay and conditioned medium (CM). Secretory factors in the CM from single or coculture were identified using liquid chromatography-tandem mass spectrometry proteomics analysis. We evaluated the role of the secretory factor in proliferation, migration, and invasion of cancer cells. In vivo xenograft model was used to evaluate the effect of the factor. Results: M2 macrophages significantly increased the proliferation, migration, and invasion of ATC cells, whereas M1 macrophages decreased the proliferation, migration, and invasion of ATC cells. Based on proteomic analysis of CM, we identify carboxypeptidase A4 (CPA4) as a mediator of the crosstalk between macrophages and ATC cells. CPA4 was only detected in the coculture media of M2 macrophage/8505C, and its expression in cancer cells increased by M2 macrophage. The expression of CPA4 protein was significantly higher in human thyroid cancers, particularly in ATCs, than normal and benign tissues. A bioinformatics analysis of public data revealed that CPA4 expression was associated with poor prognosis and dedifferentiation of thyroid cancer. Knockdown of CPA4 suppressed proliferation, colony formation, migration, and invasion of ATC cells, consistent with the decrease of STAT3, ERK, and AKT/mTOR phosphorylation and epithelial-mesenchymal transition (EMT) marker expression. In addition, the increased expression of CPA4 in cancer cells by M2 macrophage stimulation induced the polarization of macrophages to the M2 phenotype, which formed a positive feedback loop. Xenograft tumors did not develop after CPA4 knockdown. Conclusions: Our data suggest that CPA4 stimulates the progression of thyroid cancer by mediating between M2 macrophages and ATC cells. CPA4 can be a new therapeutic target for the treatment of patients with ATC.

3.
Thyroid ; 34(4): 484-495, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38115586

RESUMEN

Background: Anaplastic thyroid cancer (ATC) is highly aggressive and has very limited treatment options. Recent studies suggest that cancer stem cell (CSC) activity in ATC could underlie this recurrence and resistance to treatment. The recent approval by the U.S. Food and Drug Administration of the combined treatment of BRAF and MEK inhibitors for ATC patients has shown some efficacy in patients harboring the BRAFV600E mutation. However, it was unknown whether the combined treatment could affect the CSC activity. This study explores the effects of the BRAF and MEK inhibitors on CSC activity in human ATC cells. Methods: Using three human ATC cells, THJ-11T, THJ-16T, and 8505C cells, we evaluated the effects of dabrafenib (a BRAF kinase inhibitor), trametinib (an MEK inhibitor), or a combined treatment of the two drugs on the CSC activity by tumorsphere formation, Aldefluor assays, expression profiles of key CSC markers, immunohistochemistry, and in vivo xenograft mouse models. Furthermore, we also used confocal imaging to directly visualize the effects on drugs on CSCs by the SORE6-mCherry reporter in cultured cells and xenograft tumor cells. Results: The BRAF inhibitor, dabrafenib, had weak efficacy, while the MEK inhibitor, trametinib, showed strong efficacy in attenuating the CSC activity, as evidenced by suppression of CSC marker expression, tumorsphere formation, and Aldefluor assays. Using ATC cells expressing a fluorescent CSC SORE6 reporter, we showed reduction of CSC activity in the rank order of combined > trametinib > dabrafenib through in vitro and in vivo xenograft models. Molecular analyses showed that suppression of CSC activity by these drugs was, in part, mediated by attenuation of the transcription by dampening the RNA polymerase II activity. Conclusions: Our analyses demonstrated the presence of CSCs in ATC cells. The inhibition of CSC activity by the MEK signaling could partially account for the efficacy of the combined treatment shown in ATC patients. However, our studies also showed that not all CSC activity was totally abolished, which may account for the recurrence observed in ATC patients. Our findings have provided new insights into the molecular basis of efficacy and limitations of these drugs in ATC patients.


Asunto(s)
Imidazoles , Oximas , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Ratones , Animales , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/genética , Proteínas Proto-Oncogénicas B-raf/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/uso terapéutico , Células Madre Neoplásicas/patología , Línea Celular Tumoral , Mutación
4.
Oncogene ; 42(41): 3075-3086, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37634007

RESUMEN

Thyroid hormone receptor α1 (TRα1) mediates the genomic actions of thyroid hormone (T3). The biology of TRα1 in growth and development has been well studied, but the functional role of TRα1 in cancers remains to be elucidated. Analysis of the human thyroid cancer database of The Cancer Genome Atlas (TCGA) showed that THRA gene expression is lost in highly dedifferentiated anaplastic thyroid cancer (ATC). We, therefore, explored the effects of TRα1 on the progression of ATC. We stably expressed TRα1 in two human ATC cell lines, THJ-11T (11T-TRα1 #2, #7, and #8) and THJ-16T (16T-TRα1 #3, #4, and #8) cells. We found that the expressed TRα1 inhibited ATC cell proliferation and induced apoptosis. TCGA data showed that THRA gene expression was best correlated with the paired box gene 8 (PAX8). Consistently, we found that the PAX8 expression was barely detectable in parental 11T and 16T cells. However, PAX8 gene expression was elevated in 11T- and 16T-TRα1-expressing cells at the mRNA and protein levels. Using various molecular analyses, we found that TRα1 directly regulated the expression of the PAX8 gene. Single-cell transcriptomic analyses (scRNA-seq) demonstrated that TRα1 functions as a transcription factor through multiple signaling pathways to suppress tumor growth. Importantly, scRNA-seq analysis showed that TRα1-induced PAX8, via its transcription program, shifts the cell landscape of ATC toward a differentiated state. The present studies suggest that TRα1 is a newly identified regulator of thyroid differentiation and could be considered as a potential therapeutic target to improve the outcome of ATC patients.


Asunto(s)
Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Receptores alfa de Hormona Tiroidea/genética , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/metabolismo , Neoplasias de la Tiroides/metabolismo , Factores de Transcripción , Diferenciación Celular/genética
5.
Endocr Relat Cancer ; 30(6)2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36939877

RESUMEN

Anaplastic thyroid cancer (ATC) is one of the most aggressive solid cancers in humans, with limited treatment options. Recent studies suggest that cancer stem cell (CSC) activity contributes to therapeutic resistance and recurrence of ATC. We show that the expression of the endogenous thyroid hormone receptor ß gene (THRB) is silenced in ATC and demonstrate that the exogenously expressed TRß suppresses CSC activity. Decitabine is one of the demethylation agents to treat myelodysplastic syndrome and acute myeloid leukemia patients and is currently in clinical trials for hematopoietic malignancies and solid tumors. We aim to show that the re-expression of the endogenous THRB gene by decitabine can attenuate CSC activity to block ATC tumor growth. We treated ATC cell lines derived from human ATC tumors (11T and 16T cells) with decitabine and evaluated the effects of the reactivated endogenous TRß on CSC activity in vitro and in vivo xenograft models. We found that treatment of 11T and 16T cells with decitabine reactivated the expression of endogenous TRß, as evidenced by western blot and immunohistochemical analyses. The expressed TRß inhibited cell proliferation by arresting cells at the S phase, increased apoptotic cell death by upregulation of cleaved caspase-3, and markedly suppressed the expression of CSC regulators, including cMYC, ALDH, SOX2, CD44, and ß-catenin. Decitabine also inhibited xenograft tumor growth by suppressing CSC activity, inhibiting cancer cell proliferation, and increasing apoptosis. Our findings suggest that re-expression of the endogenous TRß is a novel therapeutic approach for ATC via suppression of CSC activity.


Asunto(s)
Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Receptores beta de Hormona Tiroidea/metabolismo , Genes erbA , Decitabina/metabolismo , Decitabina/farmacología , Decitabina/uso terapéutico , Línea Celular Tumoral , Células Madre Neoplásicas/metabolismo , Apoptosis , Proliferación Celular
6.
Thyroid ; 33(2): 239-250, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36103385

RESUMEN

Background: Mutations of thyroid hormone receptor α (TRα1) result in resistance to thyroid hormone (RTHα), exhibiting symptoms of retarded growth, delayed bone maturation, anemia, and severe constipation. Using a mouse model of RTHα (Thra1PV/+ mouse), we aimed at understanding the molecular basis underlying the severe constipation observed in patients. Methods: The Thra1PV/+ mouse expresses a strong dominant negative mutant, PV, which has lost T3 binding and transcription activity. Thra1PV/+ mouse faithfully reproduces growth abnormalities and anemia as shown in RTHα patients and therefore is a valid model to examine causes of severe constipation in patients. We used histopathological analysis, confocal fluorescence imaging, transmission electron microscopy (TEM), and gene expression profiles to comprehensively analyze the colonic abnormalities of Thra1PV/+ mouse. Results: We found a significant increase in colonic transit time and decrease stool water content in Thra1PV/+ mouse, mimicking constipation as found in patients. Histopathological analysis showed expanded lamina propria filled with interstitium fluid between crypt columns, enlarged muscularis mucosa, and increased content of collagen in expanded submucosa. The TEM analysis revealed shorter muscle fibers with wider gap junctions between muscle cells, fewer caveolae, and hypoplastic interstitial cells of Cajal (ICC) in the rectal smooth muscles of Thra1PV/+ mice. These abnormal histological manifestations suggested defective intercellular transfer of small molecules, electrolytes, and signals for communication among muscles cells, validated by Lucifer Yellow transferring assays. Expression of key smooth muscle contractility regulators, such as calmodulin, myosin light-chain kinase, and phosphorylated myosin light chain, was markedly lower, and c-KIT signaling in ICC was attenuated, resulting in decreased contractility of the rectal smooth muscles of Thra1PV/+ mice. Collectively, these abnormal histopathological alterations and diminished contractility regulators led to the constipation exhibited in patients. Conclusions: This is the first demonstration that TRα1 mutants could act to cause abnormal rectum smooth muscle organization, defects in intercellular exchange of small molecules, and decreased expression of contractility regulators to weaken the contractility of rectal smooth muscles. These findings provide new insights into the molecular basis underlying constipation found in RTHα patients.


Asunto(s)
Anemia , Receptores alfa de Hormona Tiroidea , Humanos , Receptores alfa de Hormona Tiroidea/genética , Receptores alfa de Hormona Tiroidea/metabolismo , Hormonas Tiroideas , Mutación , Estreñimiento/genética
7.
Oncogene ; 41(44): 4893-4904, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36195659

RESUMEN

Cancer progression is associated with metabolic reprogramming and causes significant intracellular stress; however, the mechanisms that link cellular stress and growth signalling are not fully understood. Here, we identified a mechanism that couples the mitochondrial stress response (MSR) with tumour progression. We demonstrated that the MSR is activated in a significant proportion of human thyroid cancers via the upregulation of heat shock protein D family members and the mitokine, growth differentiation factor 15. Our study also revealed that MSR triggered AKT/S6K signalling by activating mTORC2 via activating transcription factor 4/sestrin 2 activation whilst promoting leucine transporter and nutrient-induced mTORC1 activation. Importantly, we found that an increase in mtDNA played an essential role in MSR-induced mTOR activation and that crosstalk between MYC and MSR potentiated mTOR activation. Together, these findings suggest that the MSR could be a predictive marker for aggressive human thyroid cancer as well as a useful therapeutic target.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Neoplasias de la Tiroides , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/genética , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología
8.
Thyroid ; 32(8): 937-948, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35822558

RESUMEN

Background: Anaplastic thyroid cancer (ATC) is an aggressive solid cancer in humans with few treatment options. Recent studies suggest that aberrant gene transcription could contribute to aggressive ATC progression. To test this hypothesis, we assessed if blocking cyclin-dependent protein 7 (CDK7) activity could impede ATC progression through attenuation of cancer stem cell (CSC) activity. Methods: We treated cell lines isolated from human ATC (THJ-11T and -16T) and xenograft mice induced by these cells with the CDK7 inhibitor THZ1. Through integrative transcriptome analyses we found that the NOTCH1-cMYC signaling axis was a potential target of CDK7 inhibition in ATC. To determine the regulatory action of NOTCH1-cMYC signaling in CSC maintenance, we evaluated the effect of a selective NOTCH1 inhibitor, crenigacestat, on CSC capacities in ATC. Results: THZ1 markedly inhibited proliferation of ATC cells and xenograft tumor growth by blocking cell cycle progression and inducing apoptosis. NOTCH1 was sensitive to suppressive transcription mediated by CDK7 inhibition and was highly enriched in tumorspheres from ATC cells. Treatment of ATC cells with either crenigacestat or THZ1 blocked formation of tumorspheres, decreased aldehyde dehydrogenase activity, and suppressed in vivo initiation and growth of tumors induced by ATC cells, indicating that NOTCH1 was a critical regulator of CSC activity in ATC. Furthermore, we demonstrated that cMYC was a downstream target of NOTCH1 signaling that collaboratively maintained CSC activity in ATC. Of note, genomic analysis showed that low CDK7 expression contributed to longer disease-free survival of thyroid cancer patients. Conclusions: NOTCH1 is a newly identified CSC regulator. Targeting NOTCH1-cMYC signaling is a promising therapeutic strategy for ATC.


Asunto(s)
Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Ratones , Células Madre Neoplásicas/patología , Receptor Notch1/genética , Receptor Notch1/metabolismo , Receptor Notch1/uso terapéutico , Transducción de Señal , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo
9.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-718414

RESUMEN

A 34-year-old man who previously underwent a craniotomy due to oligodendroglioma was admitted with a diagnosis of recurrent brain tumor. An awake craniotomy was planned. Approximately 15 minutes after completing the scalp nerve block, his upper torso suddenly moved and trembled for 10 seconds, suggesting a generalized clonic seizure. He recovered gradually and fully in 55 minutes without any neurological sequelae. The emergency computed tomography scan revealed a localized fluid collection and small intracerebral hemorrhage nearby in the temporoparietal cortex beneath the skull defect. He underwent surgery under general anesthesia at 8 hours after the seizure and was discharged from the hospital after 10 days. This report documents the first case of generalized seizure that was caused by the accidental intracerebral injection of local anesthetics. Although the patient recovered completely, the clinical implications regarding the scalp infiltration technique in a patient with skull defects are discussed.


Asunto(s)
Adulto , Humanos , Anestesia General , Anestésicos Locales , Neoplasias Encefálicas , Hemorragia Cerebral , Craneotomía , Diagnóstico , Urgencias Médicas , Bloqueo Nervioso , Oligodendroglioma , Cuero Cabelludo , Convulsiones , Cráneo , Torso
10.
Yonsei Medical Journal ; : 980-986, 2016.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-63322

RESUMEN

PURPOSE: During emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy. MATERIALS AND METHODS: Seventy-four patients undergoing clipping of unruptured cerebral aneurysm were recruited. In the dexmedetomidine group, patients were administered dexmedetomidine (0.5 µg/kg) for 5 minutes, while the patients of the remifentanil group were administered remifentanil with an effect site concentration of 1.5 ng/mL until endotracheal extubation. The incidence and severity of cough and hemodynamic variables were measured during the recovery period. Hemodynamic variables, respiration rate, and sedation scale were measured after extubation and in the post-anesthetic care unit (PACU). RESULTS: The incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation. CONCLUSION: We concluded that a single bolus of dexmedetomidine (0.5 µg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration.


Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Extubación Traqueal , Periodo de Recuperación de la Anestesia , Tos/tratamiento farmacológico , Craneotomía/efectos adversos , Dexmedetomidina/farmacología , Método Doble Ciego , Hemodinámica/efectos de los fármacos , Piperidinas/farmacología , Estudios Prospectivos , Reflejo/efectos de los fármacos , Sistema Respiratorio/irrigación sanguínea
11.
Yonsei Medical Journal ; : 1260-1270, 2016.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-79765

RESUMEN

PURPOSE: Owing to the recommendations of the Surviving Sepsis Campaign guidelines, protocol-based resuscitation or goal-directed therapy (GDT) is broadly advocated for the treatment of septic shock. However, the most recently published trials showed no survival benefit from protocol-based resuscitation in septic shock patients. Hence, we aimed to assess the effect of GDT on clinical outcomes in such patients. MATERIALS AND METHODS: We performed a systematic review that included a meta-analysis. We used electronic search engines including PubMed, Embase, and the Cochrane database to find studies comparing protocol-based GDT to common or standard care in patients with septic shock and severe sepsis. RESULTS: A total of 13269 septic shock patients in 24 studies were included [12 randomized controlled trials (RCTs) and 12 observational studies]. The overall mortality odds ratio (OR) [95% confidence interval (CI)] for GDT versus conventional care was 0.746 (0.631-0.883). In RCTs only, the mortality OR (95% CI) for GDT versus conventional care in the meta-analysis was 0.93 (0.75-1.16). The beneficial effect of GDT decreased as more recent studies were added in an alternative, cumulative meta-analysis. No significant publication bias was found. CONCLUSION: The result of this meta-analysis suggests that GDT reduces mortality in patients with severe sepsis or septic shock. However, our cumulative meta-analysis revealed that the reduction of mortality risk was diminished as more recent studies were added.


Asunto(s)
Humanos , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resucitación/métodos , Choque Séptico/mortalidad
12.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-175781

RESUMEN

Remote cerebellar hemorrhage (RCH) occurring distant to the site of original surgery, such as supratentorial or spinal surgery, is rare but potentially fatal. Because the pathophysiology of RCH is thought to be excessive cerebrospinal fluid drainage during the perioperative periods, its diagnosis usually depends on the occurrence of unexpected neurologic disturbances and/or postoperative brain computerized tomography imaging. Because of its rarity, RCH-associated neurologic disturbances such as delayed awakening or nausea and vomiting may often be misdiagnosed as the effects of residual anesthetics or the effect of postoperative analgesic agents unless radiologic images are taken. Treatment for RCH ranges from conservative treatment to decompressive craniectomy, with prognoses ranging from complete resolution to fatality. Here, we report two cases of RCH after surgical clipping of an unruptured cerebral aneurysm of the anterior communicating artery and review anesthetic considerations.


Asunto(s)
Analgésicos , Anestésicos , Arterias , Encéfalo , Cerebelo , Líquido Cefalorraquídeo , Craniectomía Descompresiva , Diagnóstico , Drenaje , Hemorragia , Aneurisma Intracraneal , Hemorragias Intracraneales , Náusea , Periodo Perioperatorio , Pronóstico , Instrumentos Quirúrgicos , Vómitos
13.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-74417

RESUMEN

Light chain systemic amyloidosis is rare but may accompany laryngeal or pulmonary involvement, which may increase the risk in airway management. We present a case of a patient planned for resection of cervical epidural mass. The patient had face and neck ecchymoses and purpuras with an unknown cause. Mask ventilation and intubation were successful, but the operation was cancelled to evaluate bleeding from facial skin lesions. A diagnosis of light chain systemic amyloidosis prompted evaluation of involvement of other organs and treatment. This case shows the importance of preoperative evaluation and careful airway management in patients with systemic amyloidosis.


Asunto(s)
Humanos , Manejo de la Vía Aérea , Amiloidosis , Anestesia , Diagnóstico , Equimosis , Hemorragia , Intubación , Máscaras , Cuello , Púrpura , Piel , Ventilación
14.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-83305

RESUMEN

BACKGROUND: We determined the protective effects of a high dose of ulinastatin on myocardial and renal function in patients undergoing aortic valve replacement with cardiopulmonary bypass (CPB). METHODS: Sixty patients were assigned randomly to either the ulinastatin group (n = 30) or the control group (n = 30). In the ulinastatin group, ulinastatin (300,000 U) was given after the induction of anesthesia, ulinastatin (400,000 U) was added to the CPB pump prime, and then ulinastatin (300,000 U) was administered after weaning from CPB. In the control group, the same volume of saline was administered at the same time points. Creatine kinase-MB levels were assessed 1 day before surgery, and on the first and second postoperative day (POD 1 and 2). Serum creatinine and cystatin C levels were assessed 1 day before surgery, upon intensive care unit arrival, and on POD 1 and 2. The level of plasma neutrophil gelatinase-associated lipocalin was assessed before induction of anesthesia, upon ICU arrival, and on POD 1. RESULTS: No significant differences were observed in serum levels of creatine kinase-MB and biomarkers of renal injury between the two groups at any point during the study period. CONCLUSIONS: Ulinastatin showed no cardiac or renal protective effects after CPB in patients undergoing aortic valve replacement.


Asunto(s)
Humanos , Anestesia , Válvula Aórtica , Biomarcadores , Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Creatina , Creatinina , Cistatina C , Glicoproteínas , Unidades de Cuidados Intensivos , Lipocalinas , Neutrófilos , Plasma , Destete
15.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-41599

RESUMEN

BACKGROUND: The objective of this study was to investigate the association between A118G single nucleotide polymorphism (SNP) of human micro-opioid receptor (OPRM1) gene and the postoperative pain response in Korean patients undergoing thyroidectomy. METHODS: Fifty two adult patients undergoing thyroidectomy were enrolled in this study. Their blood samples were genotyped for the A118G polymorphism. Pain intensity was assessed by a verbal numerical rating scale (VNRS) at postanesthesia care unit, postoperative 6, 24, and 48 hours. Mechanical pain threshold was assessed using electronic von Frey preoperatively and repeated at postoperative 24 and 48 hours on the forearm and periincisional regions. RESULTS: Of the 50 patients, 23 patients were A118 homozygous (AA), 19 patients were heterozygous (AG), and 8 patients were 118G homozygous (GG). The VNRS score was higher in patients with GG genotype than other genotypes at PACU (P < 0.05). Mechanical pain thresholds on the forearm and periincisional area were decreased at postoperative 24 and 48 hours from the preoperative values in all genotypes (P < 0.05). However, the changes in pain thresholds were similar among the genotypes. CONCLUSIONS: A118G SNP of OPRM1 gene is associated with inter-individual difference in immediate postoperative pain score in Korean population.


Asunto(s)
Adulto , Humanos , Electrónica , Electrones , Antebrazo , Genotipo , Umbral del Dolor , Dolor Postoperatorio , Polimorfismo de Nucleótido Simple , Receptores Opioides , Tiroidectomía
16.
Artículo en Coreano | WPRIM (Pacífico Occidental) | ID: wpr-69753

RESUMEN

BACKGROUND: The aim of this prospective, double-blind randomized study was to compare the recovery characteristics of desflurane-remifentanil and propofol-remifentanil anesthesia in patients undergoing a laparoscopic cholecystectomy under BIS monitoring. METHODS: Eight patients (ASA I-II, 20-65 yr) undergoing laparoscopic cholecystectomy were randomly assigned to receive propofol-remifentanil anaesthesia or desflurane-remifentanil. The BIS was monitored and maintained between 45-55. At the end of surgery all anesthetics were discontinued. Time to eye opening and time to extubation was recorded. Subsequently, the patients were transported to the post-anesthetic care unit (PACU) and the modified aldrete score, visual analogue scale (VAS), blood pressure, heart rate, and postoperative nausea and vomiting (PONV) were recorded upon arrival at the PACU, as well as at 15 min, 30 min, 1 hr, 2 hr, and 24 hr. RESULTS: There were no significant differences in the incidence of PONV between the two groups. Modified aldrete scores were significantly higher in the propofol group at 15 min postoperative period (P = 0.013, Propofol = 9.87, Desflurane = 9.62). Further, VAS scores were significantly higher in the desflurane group at 30 min (P = 0.037, Propofol = 4.26, Desflurane = 5.0), and the number of antiemetic injections were significantly higher in the desflurane group at arrival to the PACU (P = 0.035, Propofol = 0, Desflurane = 0.11 +/- 0.052) and at 24 hr (P = 0.03, Propofol = 0.41 +/- 0.562, Desfluarane = 0.62 +/- 0.157). CONCLUSIONS: In patients undergoing laparoscopic cholecystectomy with BIS monitoring, there is no significant differences in the incidence of PONV. The use of propofol is associated with less postoperative pain.


Asunto(s)
Humanos , Anestesia , Periodo de Recuperación de la Anestesia , Anestésicos , Presión Sanguínea , Colecistectomía Laparoscópica , Monitores de Conciencia , Ojo , Frecuencia Cardíaca , Incidencia , Isoflurano , Dolor Postoperatorio , Piperidinas , Náusea y Vómito Posoperatorios , Periodo Posoperatorio , Propofol , Estudios Prospectivos
17.
Artículo en Coreano | WPRIM (Pacífico Occidental) | ID: wpr-24572

RESUMEN

BACKGROUND/AIMS: Thyrotropin (TSH)-secreting pituitary adenoma (TSHoma) is rare and represents 1~2% of all pituitary adenomas. TSHoma should be distinguished from the thyroid hormone resistance syndrome. Patients with TSHoma may be misdiagnosed with primary hyperthyroidism and often receive inappropriate thyroid gland treatment. METHODS: We assessed the clinical characteristics of patients with TSHoma who presented to Severance Hospital at the Yonsei University College of Medicine, Seoul, Korea between 2005 and 2009. RESULTS: Of 484 patients who underwent pituitary tumor resection, eight (1.65%; five women and three men) were found to have TSHoma. The mean age was 40.6+/-8.9 years at diagnosis (range, 28~55 years). The median duration from onset of symptoms to diagnosis was 17 months (range, 4~60 months). Four patients had overt symptoms of hyperthyroidism and two had visual field defect. Six patients had elevated free thyroxine (FT4) levels with elevated or inappropriately normal TSH levels, and two patients had symptoms associated with Hashimoto's thyroiditis. The serum levels of free alpha-subunit measured in two patients were elevated. Six of the tumors were macroadenomas (>10 mm) and two were microadenomas. Complete tumor removal was achieved in all patients. Five patients had preoperative anterior pituitary dysfunction; three patients recovered from this after surgery. Three patients were lost to follow up and five patients showed no evidence of recurrence or hyperthyroidism in the follow-up period (mean, 30.8 months, range, 3~57). CONCLUSIONS: Early diagnosis and complete removal of the tumor mass may improve the neurological and endocrine deficits.


Asunto(s)
Femenino , Humanos , Diagnóstico Precoz , Estudios de Seguimiento , Hipertiroidismo , Corea (Geográfico) , Perdida de Seguimiento , Neoplasias Hipofisarias , Recurrencia , Glándula Tiroides , Síndrome de Resistencia a Hormonas Tiroideas , Tiroiditis , Tirotropina , Tiroxina , Campos Visuales
18.
Artículo en Coreano | WPRIM (Pacífico Occidental) | ID: wpr-114361

RESUMEN

We report a case of Caplan's Syndrome, which presented as multiple pulmonary nodules. A 58-year-old male was admitted to hospital due to multiple pulmonary nodules. In addition, the patient presented with multiple arthritis, and dyspnea on exertion. Rheumatoid arthritis had been diagnosed 35 years ago. The patient had worked as a stonemason for 20 years. Computed Tomography (CT) revealed numerous well-defined tiny nodules scattered in both lungs, which was suspicious of miliary tuberculosis or malignancy. The patient was started on antituberculous medications and referred to our hospital. First, a transbronchial lung biopsy was performed, which showed no evidence of granuloma. It was our opinion that the biopsy was insufficient, and a follow-up video-associated thoracoscopy was performed. The pathological report determined necrotizing granulomatous inflammation and silicosis on background. According to imaging studies, pathologic reports, and clinical symptoms, we concluded that the patient had Caplan's syndrome. We controlled his rheumatic medications, and instructed him to avoid exposure to hazardous dust.


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Artritis , Artritis Reumatoide , Biopsia , Síndrome de Caplan , Polvo , Disnea , Estudios de Seguimiento , Granuloma , Inflamación , Pulmón , Nódulos Pulmonares Múltiples , Silicosis , Toracoscopía , Tuberculosis Miliar
19.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-219324

RESUMEN

BACKGROUND: Experimental and clinical studies have suggested that remifentanil probably causes acute tolerance or postinfusion hyperalgesia. This study was designed to confirm whether remifentanil given during propofol anesthesia induced postoperative pain sensitization, and we wanted to investigate whether pregabalin could prevent this pronociceptive effect. METHODS: Sixty patients who were scheduled for total abdominal hysterectomy were randomly allocated to receive (1) a placebo as premedication and an intraoperative saline infusion (control group), (2) a placebo as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (remifentanil group), or (3) pregabalin 150 mg as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (pregabalin-remifentanil group). Postoperative pain was controlled by titration of fentanyl in the postanesthetic care unit (PACU), followed by patient-controlled analgesia (PCA) with fentanyl. The patients were evaluated using the visual analogue scale (VAS) for pain scores at rest and after cough, consumption of fentanyl, sedation score and any side effects that were noted over the 48 h postoperative period. RESULTS: The fentanyl titration dose given in the PACU was significantly larger in the remifentanil group as compared with those of the other two groups. At rest, the VAS pain score in the remifentanil group at 2 h after arrival in the PACU was significantly higher than those in the other two groups. CONCLUSIONS: The results of this study show that remifentanil added to propofol anesthesia causes pain sensitization in the immediate postoperative period. Pretreatment with pregabalin prevents this pronociceptive effect and so this may be useful for the management of acute postoperative pain when remifentanil and propofol are used as anesthetics.


Asunto(s)
Humanos , Analgesia Controlada por el Paciente , Anestesia , Anestésicos , Tos , Fentanilo , Ácido gamma-Aminobutírico , Hiperalgesia , Histerectomía , Dolor Postoperatorio , Piperidinas , Periodo Posoperatorio , Premedicación , Propofol , Pregabalina
20.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-113125

RESUMEN

Pneumothorax during laparoscopic surgery is a potentially fatal complication.We present a case of left-sided pneumothorax complicating laparoscopic anterior resection of the sigmoid colon cancer.After signs suggestive of pneumothorax were recognized during carbon dioxide pneumoperitoneum, chest X-ray confirmed the diagnosis.Oxygen saturation and vital signs were maintained by increasing the inspired oxygen fraction and deflating the pneumoperitoneum.The pneumothorax resolved spontaneously after surgery and there were no complications.This case shows the importance of vigilance on the part of the anesthesiologist during laparoscopic surgery.


Asunto(s)
Dióxido de Carbono , Colon Sigmoide , Laparoscopía , Oxígeno , Neumoperitoneo , Neumotórax , Tórax , Signos Vitales
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