RESUMO
CatSper is a voltage dependent calcium ion channel present in the principal piece of sperm tail. It plays a crucial role in sperm hyperactivated motility and so in fertilization. Extracellular loops of mouse sperm CatSper were used to develop a vaccine to achieve protection from pregnancy. These loops were inserted at one of the three hypervariable regions of Human Papilloma Virus (HPV) capsid protein (L1). Recombinant vaccines were expressed in E.coli as inclusion body (IB), purified, refolded and assembled into virus-like particles (VLP) in vitro, and adsorbed on alum. Four vaccine candidates were tested in Balb/C mice. All the constructs proved immunogenic, one showed contraceptive efficacy. This recombinant contraceptive vaccine is a non-hormonal intervention and is expected to give long-acting protection from undesired pregnancies.
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Unanticipated difficult laryngoscopy is associated with serious airway-related complications. We aimed to develop and test a convolutional neural network-based deep-learning model that uses lateral cervical spine radiographs to predict Cormack-Lehane grade 3 or 4 direct laryngoscopy views of the glottis. We analysed the radiographs of 5939 thyroid surgery patients at our hospital, 253 (4%) of whom had grade 3 or 4 glottic views. We used 10 randomly sampled datasets to train a model. We compared the new model with six similar models (VGG, ResNet, Xception, ResNext, DenseNet and SENet). The Brier score (95%CI) of the new model, 0.023 (0.021-0.025), was lower ('better') than the other models: VGG, 0.034 (0.034-0.035); ResNet, 0.033 (0.033-0.035); Xception, 0.032 (0.031-0.033); ResNext, 0.033 (0.032-0.033); DenseNet, 0.030 (0.029-0.032); SENet, 0.031 (0.029-0.032), all p < 0.001. We calculated mean (95%CI) of the new model for: R2 , 0.428 (0.388-0.468); mean squared error, 0.023 (0.021-0.025); mean absolute error, 0.048 (0.046-0.049); balanced accuracy, 0.713 (0.684-0.742); and area under the receiver operating characteristic curve, 0.965 (0.962-0.969). Radiographic features around the hyoid bone, pharynx and cervical spine were associated with grade 3 and 4 glottic views.
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Aprendizado Profundo , HumanosRESUMO
The aim of this study was to evaluate the effectiveness of cricoid and paralaryngeal force for oesophageal entrance occlusion during induction of anaesthesia. Seventy-four patients were included in this randomised, crossover study. The relative position of the glottis and outer anteroposterior diameter of the upper oesophageal entrance were assessed at baseline, after the application of 30 N cricoid and paralaryngeal force, and after induction of anaesthesia. The occlusion rate of the oesophageal entrance with cricoid and paralaryngeal force was assessed during direct laryngoscopy. The relative position of the upper oesophageal entrance to the glottis changed in 45 out of 74 patients after induction of anaesthesia and during direct laryngoscopy compared with the awake state. The application of cricoid and paralaryngeal force decreased the mean (SD) diameter of the upper oesophageal entrance to a similar degree in awake (8.5 (2.1) mm to 6.4 (1.7) mm and 6.5 (1.6) mm, respectively; p < 0.001) and anaesthetised (8.7 (2.2) mm to 6.5 (1.7) mm and (6.7 (1.9) mm, respectively; p < 0.001) states. During direct laryngoscopy, the occlusion rate of the oesophageal entrance was greater with cricoid compared with paralaryngeal force (46/74 vs. 26/74, respectively; p = 0.002). The relative position of the upper oesophageal entrance to the glottis may change after induction of anaesthesia and during direct laryngoscopy. Cricoid and paralaryngeal force both decrease the diameter of the upper oesophageal entrance in awake and anaesthetised states. Occlusion of the oesophageal entrance is achieved more frequently with cricoid force compared with paralaryngeal force during direct laryngoscopy.
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Anestesia/métodos , Cartilagem Cricoide/anatomia & histologia , Esôfago/anatomia & histologia , Laringoscopia/métodos , Laringe/anatomia & histologia , Ultrassonografia/métodos , Estudos Cross-Over , Feminino , Humanos , Intubação Intratraqueal/métodos , Masculino , Pessoa de Meia-Idade , PressãoRESUMO
PURPOSE: The purpose of this study was to evaluate the feasibility, safety, and clinical effectiveness of ultrasound and fluoroscopy-guided percutaneous nephrostomy (PCN) placement in infants and young children. MATERIALS AND METHODS: Between January 2000 and December 2015, 57 patients had a total of 66 fluoroscopically guided PCN placement procedures. There were 37 boys and 20 girls with a mean age 8.6±15.3 (SD) months (range: 1 day-75.5months). The most common underlying disease was upper-urinary-tract obstruction, including ureteropelvic-junction stenosis (27/66, 40.9%) and ureterovesical-junction stenosis (16/66, 24.2%). Technical success, complications, clinical effectiveness, and radiation exposure were retrospectively analyzed. Technical success was defined as completion of PCN catheter in the renal calyx or proximal ureter. Complications were graded in severity using the Common Terminology Criteria for Adverse Event (version 4.03). Clinical effectiveness was evaluated with presence of decompression of the hydronephrosis on follow-up ultrasonography. RESULTS: All PCN placement procedures were technically successful. A total of 37 complications were identified in 33/37 procedures (89.2%), with transient gross hematuria (n=28) being most common (mean hematuria duration 2.2±1.4 [range: 1-6] days), which were grade 1 Postprocedural fever occurred after eight procedures; four and three patients were graded 1 and 2, respectively. Complete hydronephrosis decompression was achieved in 35/53 kidneys (66%), incomplete hydronephrosis decompression in 17/55 kidneys (32.1%), and progression of hydronephrosis was noted in 1/55 kidney (1.9%). Dose-area-product (DAP) was 44.86±89 (SD) (range: 3.7-464) µGycm2 and cumulative dose was 10.3±20.4 (SD) (range: 0.3-97.9) mGy. CONCLUSION: PCN is a feasible and effective treatment option to relieve urinary obstruction, and can serve as a bridging procedure until definitive corrective surgery in pediatric patients.
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Nefrostomia Percutânea/métodos , Doenças Urológicas/terapia , Feminino , Fluoroscopia , Humanos , Lactente , Recém-Nascido , Masculino , Nefrostomia Percutânea/efeitos adversos , Radiografia Intervencionista , Estudos Retrospectivos , Ultrassonografia de IntervençãoRESUMO
Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP(+)) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP(+) reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP(+)-induced decrease of cdr2 was primarily caused by calpain- and ubiquitin proteasome system-mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP(+)-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP(+)-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration.
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Degeneração Neural/metabolismo , Degeneração Neural/patologia , Proteínas do Tecido Nervoso/metabolismo , Proteólise , 1-Metil-4-fenilpiridínio , Envelhecimento/metabolismo , Animais , Calpaína/metabolismo , Morte Celular , Linhagem Celular , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Regulação para Baixo , Mesencéfalo/metabolismo , Neuroproteção , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Mudanças Depois da Morte , Ratos Sprague-Dawley , Substância Negra/metabolismo , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/metabolismo , Ubiquitina/metabolismoRESUMO
Sulfuretin, one of the major flavonoid glycosides found in the stem bark of Albizzia julibrissin and heartwood of Rhus verniciflua, is a known anti-oxidant. We previously demonstrated that sulfuretin inhibits neuronal death via reactive oxygen species (ROS)-dependent mechanisms in human SH-SY5Y cells, although other relevant mechanisms of action of this compound remain largely uncharacterized. As part of our ongoing exploration of the pharmacological actions of sulfuretin, we studied the neuroprotective effects of sulfuretin against amyloid beta (Aß)-induced neurotoxicity in human SH-SY5Y and primary hippocampal neuron cells and investigated the possible mechanisms involved. Specifically, we found in the present study that sulfuretin significantly attenuates the decrease in cell viability, release of lactate dehydrogenase, and accumulation of ROS associated with Aß25-35-induced neurotoxicity in neuronal cells. Furthermore, sulfuretin stimulated the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a downstream target of phosphatidylinositol 3-kinases (PI3K)/Akt. We demonstrated that sulfuretin induces the expression of heme oxygenase-1 (HO-1), an anti-oxidant response gene. Notably, we found that the neuroprotective effects of sulfuretin were diminished by an Nrf2 small interfering RNA (siRNA), the HO-1 inhibitor zinc protoporphyrin IX (ZnPP), as well as the PI3K/Akt inhibitor LY294002. Taken together, these results indicated that sulfuretin protects neuronal cells from Aß25-35-induced neurotoxicity through activation of Nrf/HO-1 and PI3K/Akt signaling pathways. Our results also indicate that sulfuretin-induced induction of Nrf2-dependent HO-1 expression via the PI3K/Akt signaling pathway has preventive and/or therapeutic potential for the management of Alzheimer's disease.
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Peptídeos beta-Amiloides/toxicidade , Benzofuranos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Técnicas de Silenciamento de Genes , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/antagonistas & inibidores , Heme Oxigenase-1/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity in allogeneic hematopoietic cell transplant (alloHCT) recipients. Little is known about the epidemiology of antiviral resistance in the pediatric population. We performed the prospective study to assess the impact of drug-resistant CMV infections in pediatric alloHCT recipients. METHODS: Pediatric alloHCT recipients who developed CMV infection were consecutively enrolled from May 2009 to April 2012. CMV polymerase chain reaction amplification and sequencing analysis for UL97 and UL54 genes were performed at enrollment and during follow-up. RESULTS: In total, 208 sequence data from viruses in 49 recipients were eligible for the final analysis. Resistant CMV infection caused by UL97 and UL54 mutations occurred in 4.1% (2/49) and 2.0% (1/49), respectively. Known UL97 mutations, M460V and C592G, were observed in each of 2 patients. One patient with the M460V UL97 mutation had an additional T700A UL54 mutation. Drug-resistant CMV attributable mortality was 2.0% (1/49). One or more known sequence variants (drug-sensitive) were observed in all 49 patients. Thirty-one (63.3%) and 28 patients (60.9%) already had known UL97 and UL54 sequence variants before antiviral therapy, respectively. CONCLUSION: This study provides comprehensive information on the epidemiology of both UL97 and UL54 variants and mutations in alloHCT recipients.
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Antivirais/farmacologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/efeitos dos fármacos , Farmacorresistência Viral , Transplante de Células-Tronco Hematopoéticas , Adolescente , Criança , Pré-Escolar , Citomegalovirus/genética , Feminino , Genótipo , Humanos , Lactente , Masculino , MutaçãoRESUMO
During nasotracheal intubation, the tracheal tube passes through either the upper or lower pathway in the nasal cavity, and it has been reported to be safer that the tracheal tube passes though the lower pathway, just below the inferior turbinate. We evaluated the use of a nasogastric tube as a guide to facilitate tracheal tube passage through the lower pathway, compared with the 'conventional' technique (blind insertion of the tracheal tube into the nasal cavity). A total of 60 adult patients undergoing oral and maxillofacial surgery were included in the study. In 20 out of 30 patients (66.7%) with the nasogastric tube-guided technique, the tracheal tube passed through the lower pathway, compared with 8 out of 30 patients (26.7%) with the 'conventional' technique (p = 0.004). Use of the nasogastric tube-guided technique reduced the incidence and severity of epistaxis (p = 0.027), improved navigability (p = 0.034) and required fewer manipulations (p = 0.001) than the 'conventional' technique.
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Intubação Intratraqueal/instrumentação , Adulto , Idoso , Epistaxe/prevenção & controle , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Masculino , Pessoa de Meia-Idade , Cavidade NasalAssuntos
Ablação por Cateter/métodos , Endossonografia/métodos , Etanol/administração & dosagem , Insulinoma/diagnóstico por imagem , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Feminino , Humanos , Insulinoma/complicações , Insulinoma/cirurgia , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgiaAssuntos
Hidrocarboneto de Aril Hidroxilases/genética , Intervenção Coronária Percutânea , Farmacogenética , Ticlopidina/análogos & derivados , Difosfato de Adenosina/química , Adulto , Idoso , Alelos , Povo Asiático , Clopidogrel , Estudos de Coortes , Citocromo P-450 CYP2C19 , Feminino , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Projetos Piloto , Inibidores da Agregação Plaquetária/uso terapêutico , Testes de Função Plaquetária , Polimorfismo de Nucleotídeo Único , Ticlopidina/uso terapêuticoRESUMO
AIM: To evaluate the magnetic resonance imaging features of desmoplastic fibroma (DF) of bone. MATERIALS AND METHODS: Two radiologists retrospectively evaluated imaging findings of pathologically confirmed DFs in eight patients. Involved sites and longitudinal location in long bones were evaluated using radiography and computed tomography (CT). At MRI, the presence of low signal areas on T2-weighted images (low-T2), enhancement, cystic changes, and locations of the mass were evaluated. The location of masses was evaluated, based on cortical disruption and adjacent soft-tissue extension. RESULTS: Involved sites were the femur in three patients, the tibia in two, and the humerus, fibula, and pubic bone in one each. Of the seven masses in the long bones, three were located in the epi- and metaphysis, two in the meta- and diaphysis, one in the diaphysis, and one in the epiphysis. Seven masses had areas of low T2-weighted or heterogeneous enhancement, and three (38%) showed cystic changes. cortical disruption was seen at MRI in six of eight patients (88%). CONCLUSION: DFs contained cystic change. Cortical disruption may also occur, which may cause confusion with malignant lesions.
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Neoplasias Ósseas/patologia , Fibroma Desmoplásico/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Fibroma Desmoplásico/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: propofol is an excellent sedative agent for use in patients undergoing bronchoscopy. The addition of an opioid to propofol can be advantageous because of the antitussive effect of the opioid and the possible improvement in sedation quality. However, it may increase the risk of hypoxaemia. To investigate the effect of the addition of alfentanil to propofol, we performed a prospective study to compare propofol-only sedation with propofol-alfentanil combination sedation in patients undergoing bronchoscopy. METHODS: patients were randomly assigned either to the propofol-only (group P, n=32) or to the propofol-alfentanil combination group (group PA, n=32). The average peripheral oxygen saturation (SpO(2) ) and the lowest SpO(2) during the sedation were compared. Patient and bronchoscopist satisfaction as well as the degree of coughing were compared using a 100 mm visual analogue scale, where 0 indicated the least and 100 indicated the most satisfied. RESULTS: group P had the higher average SpO(2) (%) during the procedure than group PA (97.8 ± 1.6 and 96.4 ± 1.1, P<0.01) as well as the lowest SpO(2) (%) (95.4 ± 2.7 and 94.0 ± 2.4, P<0.05). Patient satisfaction (92.2 ± 13.5 and 92.3 ± 18.2), bronchoscopist satisfaction (76.6 ± 18.1 and 72.8 ± 19.1), and degree of cough (73.4 ± 22.7 and 72.2 ± 18.5; group P and group PA, respectively) were not different between the groups. CONCLUSIONS: the combination of propofol and alfentanil resulted in a greater respiratory depression than propofol alone; furthermore, the addition of an opioid did not improve the quality of sedation. In conclusion, we do not recommend sedation with propofol and alfentanil during bronchoscopy.
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Alfentanil , Anestésicos Intravenosos , Broncoscopia/métodos , Propofol , Administração Tópica , Idoso , Anestésicos Locais/administração & dosagem , Sedação Consciente , Tosse/prevenção & controle , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Hipóxia/induzido quimicamente , Hipóxia/epidemiologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Satisfação do Paciente , Resultado do TratamentoRESUMO
BACKGROUND: In this double-blind, randomized, placebo-controlled study, we evaluated the effects of magnesium sulphate on neuromuscular blocking agent requirements and analgesia in children with cerebral palsy (CP). METHODS: We randomly divided 61 children with CP undergoing orthopaedic surgery into two groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and 15 mg kg(-1) h(-1) by continuous infusion during the operation. The control group (Group S) received the same amount of isotonic saline. Rocuronium was administered 0.6 mg kg(-1) before intubation and 0.1 mg kg(-1) additionally when train-of-four counts were 2 or more. I.V. fentanyl and ketorolac were used to control postoperative pain. Total infused analgesic volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and 48 h. RESULTS: The rocuronium requirement of Group M was significantly less than that of Group S [0.29 (0.12) vs 0.42 (0.16) mg kg(-1) h(-1), P<0.05]. Cumulative analgesic consumption in Group M was significantly less after operation at 24 and 48 h (P<0.05), and pain scores in Group M were lower than in Group S during the entire postoperative period (P<0.05). Serum magnesium concentrations in Group M were higher until 24 h after operation (P<0.05). The incidence of postoperative nausea and vomiting and rescue drug injections was similar in the two groups. No shivering or adverse effects related to hypermagnesaemia were encountered. CONCLUSIONS: I.V. magnesium sulphate reduces rocuronium requirements and postoperative analgesic consumption in children with CP.
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Analgésicos/farmacologia , Paralisia Cerebral/complicações , Sulfato de Magnésio/farmacologia , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Adolescente , Analgésicos/sangue , Analgésicos/uso terapêutico , Analgésicos Opioides/administração & dosagem , Androstanóis/administração & dosagem , Paralisia Cerebral/cirurgia , Criança , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Sinergismo Farmacológico , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Sulfato de Magnésio/sangue , Sulfato de Magnésio/uso terapêutico , Masculino , Osteotomia , Medição da Dor/métodos , RocurônioRESUMO
BACKGROUND: In a randomized, double-blind, prospective study, we have evaluated the effect of i.v. infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements. METHODS: Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included. After the induction of spinal anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) for 15 min and then 15 mg kg(-1) h(-1) by continuous i.v. infusion until the end of surgery. The saline group (Group S) received the same volume of isotonic saline over the same period. After surgery, a patient-controlled analgesia (PCA) device containing morphine and ketorolac was provided for the patients. Postoperative pain scores, PCA consumption, and the incidences of shivering, postoperative nausea, and vomiting were evaluated immediately after surgery, and at 30 min, 4, 24, and 48 h after surgery. Serum magnesium concentrations were checked before the induction of anaesthesia, immediately after surgery, and at 1 and 24 h after surgery. RESULTS: Postoperative pain scores were significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Postoperative magnesium concentrations were higher in Group M (P<0.05 at 4, 24, and 48 h after surgery), but no side-effects associated with hypermagnesemia were observed. Haemodynamic variables and the incidences of shivering, nausea, and vomiting were similar in the two groups. CONCLUSIONS: I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia.
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Analgésicos não Narcóticos/administração & dosagem , Raquianestesia/métodos , Sulfato de Magnésio/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Adulto , Idoso , Analgesia Controlada pelo Paciente/métodos , Analgésicos não Narcóticos/sangue , Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Artroplastia de Quadril , Pressão Sanguínea/efeitos dos fármacos , Esquema de Medicação , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Cetorolaco/administração & dosagem , Sulfato de Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Medição da Dor/métodos , Dor Pós-Operatória/sangueRESUMO
BACKGROUND: Only a few clinical trials have been conducted in patients with advanced pancreatic cancer after failure of first-line gemcitabine-based chemotherapy. Therefore, there is no current consensus on the treatment of these patients. We conducted a randomised phase II study of the modified FOLFIRI.3 (mFOLFIRI.3; a regimen combining 5-fluorouracil (5-FU), folinic acid, and irinotecan) and modified FOLFOX (mFOLFOX; a regimen combining folinic acid, 5-FU, and oxaliplatin) regimens as second-line treatments in patients with gemcitabine-refractory pancreatic cancer. METHODS: The primary end point was the 6-month overall survival rate. The mFOlFIRI.3 regimen consisted of irinotecan (70 mg m(-2); days 1 and 3), leucovorin (400 mg m(-2); day 1), and 5-FU (2000 mg m(-2); days 1 and 2) every 2 weeks. The mFOLFOX regimen was composed of oxaliplatin (85 mg m(-2); day 1), leucovorin (400 mg m(-2); day 1), and 5-FU (2000 mg m(-2); days 1 and 2) every 2 weeks. RESULTS: Sixty-one patients were randomised to mFOLFIRI.3 (n=31) or mFOLFOX (n=30) regimen. The six-month survival rates were 27% (95% confidence interval (CI)=13-46%) and 30% (95% CI=15-49%), respectively. The median overall survival periods were 16.6 and 14.9 weeks, respectively. Disease control was achieved in 23% (95% CI=10-42%) and 17% patients (95% CI=6-35%), respectively. The number of patients with at least one grade 3/4 toxicity was identical (11 patients, 38%) in both groups: neutropenia (7 patients under mFOLFIRI.3 regimen vs 6 patients under mFOLFOX regimen), asthaenia (1 vs 4), vomiting (3 in both), diarrhoea (2 vs 0), and mucositis (1 vs 2). CONCLUSION: Both mFOLFIRI.3 and mFOLFOX regimens were tolerated with manageable toxicity, offering modest activities as second-line treatments for patients with advanced pancreatic cancer, previously treated with gemcitabine.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: Cancerous stem-like cells (CSCs) have been implicated as cancer-initiating cells in a range of malignant tumours. Diverse genetic programs regulate CSC behaviours, and CSCs from glioblastoma patients are qualitatively distinct from each other. The intrinsic connection between the presence of CSCs and malignancy is unclear. We set out to test whether tumour stem-like cells can be identified from benign tumours. METHODS: Tumour sphere cultures were derived from hormone-positive and -negative pituitary adenomas. Characterisation of tumour stem-like cells in vitro was performed using self-renewal assays, stem cell-associated marker expression analysis, differentiation, and stimulated hormone production assays. The tumour-initiating capability of these tumour stem-like cells was tested in serial brain tumour transplantation experiments using SCID mice. RESULTS: In this study, we isolated sphere-forming, self-renewable, and multipotent stem-like cells from pituitary adenomas, which are benign tumours. We found that pituitary adenoma stem-like cells (PASCs), compared with their differentiated daughter cells, expressed increased levels of stem cell-associated gene products, antiapoptotic proteins, and pituitary progenitor cell markers. Similar to CSCs isolated from glioblastomas, PASCs are more resistant to chemotherapeutics than their differentiated daughter cells. Furthermore, differentiated PASCs responded to stimulation with hypothalamic hormones and produced corresponding pituitary hormones that are reflective of the phenotypes of the primary pituitary tumours. Finally, we demonstrated that PASCs are pituitary tumour-initiating cells in serial transplantation animal experiments. CONCLUSION: This study for the first time indicates that stem-like cells are present in benign tumours. The conclusions from this study may have applications to understanding pituitary tumour biology and therapies, as well as implications for the notion of tumour-initiating cells in general.
Assuntos
Adenoma/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Hipofisárias/patologia , Adenoma/genética , Adenoma/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Hormônios Hipotalâmicos/biossíntese , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Multipotentes/metabolismo , Células-Tronco Multipotentes/patologia , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Hormônios Hipofisários/biossíntese , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Células Tumorais CultivadasRESUMO
Etomidate is a popular anaesthetic induction agent, but it frequently causes myoclonic movements. Although both benzodiazepines and opioids reduce myoclonus, there has been no comparative study between these agents. Thus, we conducted a prospective, randomized study to compare midazolam and remifentanil as pre-treatment agents for reducing etomidate-induced myoclonus in 90 adults undergoing surgery. Patients were pre-treated before the etomidate injection, either with saline (Group C), midazolam 0.5 mg/kg (Group M) or remifentanil 1 microg/kg (Group R). Both Groups M and R showed a significantly lower incidence of myoclonus compared with Group C (17%, 17% and 77%, respectively). The incidence of myoclonus was not significantly different between Groups M and R, but 10% (n = 10) of the patients in Group R experienced remifentanil-related side-effects. We conclude that midazolam is probably a better choice than remifentanil for reducing etomidate-induced myoclonus during anaesthesia induction.
Assuntos
Anestésicos Intravenosos/antagonistas & inibidores , Etomidato/agonistas , Midazolam/uso terapêutico , Mioclonia/prevenção & controle , Piperidinas/uso terapêutico , Anestésicos Intravenosos/efeitos adversos , Método Duplo-Cego , Etomidato/efeitos adversos , Humanos , Incidência , Pessoa de Meia-Idade , Mioclonia/induzido quimicamente , Mioclonia/epidemiologia , Remifentanil , Resultado do TratamentoRESUMO
Accidental endobronchial intubation is reported frequently during laparoscopic gynaecological surgery. We performed a prospective randomised study to compare three different methods of endotracheal tube placement in terms of susceptibility of accidental endobronchial intubation in patients undergoing laparoscopic gynaecologic surgery. The endotracheal tube was positioned by one of three methods: it was secured by palpating at the suprasternal notch while holding the pilot balloon (Group(Cuff)); by placing the 21 cm mark at the upper incisors (Group(21cm)); or by placing a guide mark, which was made on the surface of the tube 2 cm above the proximal end of the cuff at the level of the vocal cords (Group(VC)). The distance from the tip of endotracheal tube to the carina was measured with the patient in a neutral position (D(TC0)) and after the formation of pneumoperitoneum in the Trendelenburg position (D(TC1)). Eighty-eight patients were enrolled. Pneumoperitoneum and Trendelenburg position caused inward movement of the endotracheal tube toward the carina in 99%. In each group, the mean value of D(TC1) was significantly shorter than D(TC0) (Group(Cuff) 3.0 +/- 1.1 vs. 1.7 +/- 1.0, Group(21cm) 2.5 +/- 0.8 vs. 1.1 +/- 0.9, Group(VC) 3.5 +/- 0.7 vs. 2.3 +/- 0.8, D(TC0) vs. D(TC1) respectively) (all P < 0.01). Accidental endobronchial intubation occurred in 14%, with the lowest frequency in Group(VC) (2.6 %, P < 0.01) and the highest in Group(21cm), although this was not significantly (P = 0.09) different from Group(Cuff) (26.7% vs. 10.0%). The incidence of endobronchial intubation was lowest in Group(VC) but endobrochial intubation could not be avoided using any of these methods.
Assuntos
Anestesia Obstétrica/métodos , Intubação Intratraqueal/métodos , Laparoscopia , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Intubação Intratraqueal/efeitos adversos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Endometriosis is considered a frequent, benign disease with the ability to undergo neoplastic processes. The aim of this study was to evaluate the limitless replication potential of the endometrium in patients with endometriosis by examining human telomerase reverse transcriptase (hTERT) mRNA expression and telomerase activity. METHODS: Endometrium samples from 30 endometriosis patients and 30 patients without endometriosis were obtained via endometrial biopsy. The expression of hTERT mRNA was determined by real-time RT-PCR assay, and telomerase activity was measured by telomerase repeat amplification protocol (TRAP) assay. RESULTS: The mean normalized hTERT (N hTERT) mRNA level was significantly higher in the endometriosis than in the control group (P = 0.013). The mean hTERT mRNA levels during the proliferative phase and during the secretory phase were higher in the endometriosis group than in the control group, although the difference was only significant for the secretory phase (P = 0.036). We found a prominent difference in endometrial telomerase activity between moderate-to-severe endometriosis and the control group (P = 0.048). The levels of hTERT mRNA and telomerase activity increased as the disease became more severe (P = 0.038, P = 0.016). CONCLUSIONS: This study showed the overexpression of hTERT mRNA and telomerase activity in the endometrium of endometriosis patients. These finding suggest that replication potential of endometrial cells may have an important role in the pathogenesis of endometriosis.
Assuntos
Endometriose/enzimologia , Endométrio/enzimologia , Telomerase/metabolismo , Adulto , Feminino , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Telomerase/genéticaRESUMO
During gynaecological laparoscopic surgery, alterations in cerebral blood flow and intracranial pressure are frequently reported. These changes affect cerebral perfusion pressure and thus may affect cerebral oxygenation. In this prospective study, the effect of gynaecological laparoscopic surgery on cerebral oxygenation was examined by following the changes in regional cerebral oxygen saturation (rSo2). Twenty-four female patients were enrolled. The mean rSo2 was 65.5 +/- 5.4% at baseline before surgery, 60.8 +/- 5.6% when the patient was placed in the Trendelenburg position, 57.1 +/- 9.3% after creation of pneumoperitoneum, and 64.0 +/- 7.3% after the completion of surgery. During the period of pneumoperitoneum, rSo2 fell below 50% in two hypercapnic patients. In comparison with baseline, rSo2 declined significantly in the Trendelenburg position. The creation of pneumoperitoneum itself did not decrease the average rSo2 value further unless the patients were hypercapnic.