RESUMO
Hydrodynamics-based gene delivery (HGD) is a widely recognized technique for delivering exogenous DNA with high efficiency to murine hepatocytes. In this study, we investigated stimulation of exogenous DNA uptake and expression using a commercially available reagent for HGD. We also examined which mouse strain and mouse liver lobe would achieve the best gene delivery performance. Mice were injected with a solution containing reporter plasmid DNA or DNA and a gene delivery reagent. One day after the HGD procedure, liver samples were isolated and subjected to biochemical and histochemical analyses. The reporter plasmid DNA showed the strongest signal when the DNA was dissolved in TransIT-EE Hydrodynamic Delivery Solution (Takara Bio Inc., Shiga, Japan). Evaluation of transgene expression in each hepatic lobe in ICR, C57BL/6N, Balb/cA, and B6C3F1 mice showed that ICR mice exhibited the best gene transfer and that the right median lobe had the highest level of transgene expression. These findings suggest the importance of choice in mouse strains and liver lobes when performing gene-based manipulations of the liver.
Assuntos
Técnicas de Transferência de Genes , Fígado/fisiologia , Animais , Expressão Gênica , Fígado/química , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Especificidade da EspécieRESUMO
BACKGROUND: Crush syndrome (CS) has been reported in disasters, terrorist incidents, and accidents, and the clinical and pathologic picture has gradually been clarified. Few lethal and reproducible animal models of CS with use of a quantitative load are available. A new model is needed to investigate pathologic and therapeutic aspects of this injury. MATERIALS AND METHODS: Using a device built from commercially available components, both hindlimbs of anesthetized rats were respectively compressed for 6 h using 3.6-kg blocks. The effects of trunk warming alone without compressed hindlimbs (Group A), non-warming at room temperature (Group B), whole-body warming including compressed hindlimbs (Group C), or warming of compressed hindlimbs alone (Group D) during compression were examined. Survival rates were compared and hematological and histologic analyses were performed at specific time points after compression release. RESULTS: Limb or whole-body warming significantly worsened the survival of rats. We found a much lower survival rate of 0%-10% in animals, in which the hindlimbs were warmed during compression (Groups C and D) at 12 h after compression release, compared with 90%-100% in animals without warming of the hindlimbs (Groups A and B). Groups C and D showed significantly enhanced hyperkalemia at ≥4 h after compression release and all blood samples from dead cases showed hyperkalemia (>10 mEq/L). CONCLUSIONS: We developed a new lethal and reproducible rat CS model with a quantitative load. This study found that warming of compressed limbs worsened the survival rate and significantly enhanced hyperkalemia, apparently leading to cardiac arrest.
Assuntos
Síndrome de Esmagamento/etiologia , Modelos Animais de Doenças , Temperatura , Animais , Temperatura Corporal , Síndrome de Esmagamento/sangue , Síndrome de Esmagamento/patologia , Membro Posterior/fisiologia , Masculino , Músculo Esquelético/patologia , Potássio/sangue , Ratos , Ratos Sprague-Dawley , Análise de SobrevidaRESUMO
PURPOSE: The aim of this study was to achieve improvements in the work environment of Japanese surgeons and shortage of surgeons. METHODS: Questionnaires were distributed to selected Japanese surgical Society (JSS) members. Retrospective analysis was conducted comparing the current 2011 survey with previous 2007 survey. To examine the influence of 2010 revision of the fee for medical services performed by surgeons, we distributed a second questionnaire to directors of hospitals and administrators of clerks belonging to official institutes in JSS. Collective data were analyzed retrospectively. RESULTS: The main potential causes for the shortage of surgeons in Japan were long hours (72.8 %), excessive emergency surgeries (69.4 %), and high risk of lawsuit (67.7 %). Mean weekly working hours of surgeons in national or public university hospitals and private university hospitals were 96.2 and 85.6, respectively. Approximately 70 % of surgeons were forced to do hardworking tasks, possibly leading to death from overwork. Of note, approximately 25 % of surgeons had over time of more than 100 h a week, coinciding to the number of hours that might lead to death from fatigue, described in the Japanese labor law. Although the total medical service fee in hospitals, especially in large-scale hospitals with more than 500 beds, increased markedly after 2010 revision of the fee for medical services performed by surgeons, few hospitals gave perquisites and/or incentives to surgeons. CONCLUSION: To prevent and avoid collapse of the surgical specialty in Japan, an improvement in the work environment of surgeons by initiation of the JSS would be required as soon as possible.
Assuntos
Planos de Pagamento por Serviço Prestado/tendências , Cirurgia Geral , Saúde Ocupacional , Planos de Incentivos Médicos/tendências , Médicos/psicologia , Médicos/estatística & dados numéricos , Tolerância ao Trabalho Programado , Humanos , Japão , Estudos Retrospectivos , Inquéritos e Questionários , Tolerância ao Trabalho Programado/psicologia , Recursos HumanosRESUMO
BACKGROUND: Hypertonic saline solution (HS) as a submucosal fluid cushion (SFC) for endoscopic submucosal dissection (ESD) has several disadvantages, including a short effect duration and increased risk of bleeding and perforation. Photocrosslinkable chitosan hydrogel in DMEM/F12 medium (PCH) can be converted into an insoluble hydrogel by UV irradiation for 30 seconds. OBJECTIVE: To evaluate the feasibility, usefulness, and safety of PCH as an SFC for ESD of esophagi, compared with HS and sodium hyaluronate (SH). DESIGN: Survival animal study. SETTINGS: Research laboratory study of 24 pig models in vivo. INTERVENTIONS: Twenty-four pigs were used in the 2 steps: First, ESD of the esophagus was performed with PCH, SH, or HS (each n = 6) as an SFC, and the effects of these agents on wound healing were examined endoscopically and histologically. Second, in vivo degradation of PCH (n = 3) and HS (n = 3) was examined in independent pig esophagi. MAIN OUTCOME MEASUREMENTS: Outcome measurements included feasibility and safety of PCH-assisted ESD of esophagus, gross and histologic evidence of the treated esophagus, biodegradation of injected PCH, and clinical tolerance by the animals. RESULT: PCH injection led to a longer-lasting elevation with clearer margins compared with SH and HS, thus enabling precise ESD along the margins of the elevated mucosa without complications such as bleeding and perforation. The aspects of wound repair after PCH-assisted ESD were similar to those of SH- and HS-assisted ESDs. Biodegradation of PCH was confirmed to be almost completed within 8 weeks on the basis of endoscopic and histologic observations. LIMITATIONS: In vivo animal model study. CONCLUSION: PCH permits more reliable ESD of the esophagus without complications than do SH and HS. Furthermore, the applied PCH appeared to be completely biodegraded within 8 weeks. Thus, PCH is a promising agent as an SFC in ESD of the esophagus.
Assuntos
Quitosana/uso terapêutico , Esôfago/cirurgia , Hidrogel de Polietilenoglicol-Dimetacrilato/uso terapêutico , Mucosa/cirurgia , Animais , Quitosana/efeitos adversos , Dissecação , Esofagoscopia , Esôfago/patologia , Ácido Hialurônico/uso terapêutico , Hidrogel de Polietilenoglicol-Dimetacrilato/efeitos adversos , Masculino , Processos Fotoquímicos , Cloreto de Sódio/uso terapêutico , Suínos , Viscossuplementos/uso terapêuticoRESUMO
Frozen and thawed platelet-rich plasma (PRP) contains high concentrations of various growth factors, such as fibroblast growth factor (FGF)-2, vascular endothelial growth factor, and hepatocyte growth factor. We previously reported that low-molecular-weight heparin/protamine microparticles (LH/P MPs) are useful as biodegradable carriers for the controlled release of FGF-2. In this study, we examined the ability of PRP/LH/P MPs to prevent limb loss in an induced ischemic hind-limb model that used adult BALB/c-nu/nu male mice. One day after inducing ischemia, intramuscular injections of a PRP/LH/P MPs solution were administered into several sites of the ischemic hind limb. Seven days and onward after the injections, the PRP/LH/P MPs-treated and PRP-treated groups recovered from ischemia, as reflected by the improved oxygen saturation. In the PRP-treated group, however, the level of recovery of oxygen saturation after ischemia decreased after 14 days. From the 21st day onward, there was a significant difference between those two groups. In the LH/P MPs-treated group, a partial recovery occurred only in the early period. The saline-treated group (i.e., the control) and the noninjection group (i.e., ischemia only) exhibited no recovery. The limb survival rate at 1 year in the ischemia-induced mice injected with PRP/LH/P MPs was approximately 25 % (two of eight mice) but was absent in the other groups.
Assuntos
Anticoagulantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Antagonistas de Heparina/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Membro Posterior/irrigação sanguínea , Isquemia/tratamento farmacológico , Salvamento de Membro , Protaminas/administração & dosagem , Animais , Isquemia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Fisiológica/efeitos dos fármacosRESUMO
Esophageal cancers usually exhibit lymph-node metastases. Although a solitary lymph-node metastasis is occasionally found, the involvement of an intrathoracic paraaortic node is rare. We present here an intrathoracic mid-esophageal cancer case in which an accompanying solitary retroaortic mass was found within the posterior mediastinum by integrated positron emission tomography/computed tomography. For diagnosis, thoracoscopic resection of the mass was performed from a left thoracic approach, and histology revealed it to be a squamous cell carcinoma metastasized from the esophageal cancer. Upon radical esophagectomy after neoadjuvant therapy as a T3N1M0 Stage IIIa (AJCC/UICC) cancer, the esophageal cancer was found to have invaded unexpectedly deeply in the vicinity of the descending aorta. Another lymph node within the paraaortic region was also involved (T4N1M0 Stage IIIc). The present case and other cases we review here inform our understanding of metastasis to intrathoracic paraaortic nodes as follows:1) its existence may indicate extensive lymph-node metastasis or direct tumor invasion nearby, and 2) it may be accompanied by other lymph-node involvements in this region, even if it appears solitary upon preoperative investigation. Thus, for radical esophagectomy, sufficient lymph-node dissection is required, even at locations not reached by the usual right thoracic approach. Definitive chemoradiotherapy may be a better choice for preoperatively recognized T3 esophageal cancer when the cancer is accompanied by paraaortic lymph node metastasis.
Assuntos
Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/patologia , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Metástase Linfática , Masculino , Imagem Multimodal , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: The localized delivery of exogenous, angiogenic growth factors such as fibroblast growth factor (FGF)-2 has become a promising alternative treatment of peripheral artery disease (PAD) and critical limb ischemia (CLI). The present study describes the efficacy of fragmin/protamine microparticles containing FGF-2 (F/P-MPs/FGF-2) to promote vessel growth in a rabbit model of hindlimb ischemia. METHODS: A total of 24 rabbits were used to construct a model of hindlimb ischemia by resection of the left femoral artery. The rabbits were randomly divided into four groups 10 days after surgery (day 0); group A: control (non-treated; 1 mL of phosphate-buffered saline [PBS]); group B: FGF-2 (100 µg FGF-2 in 1 mL PBS)-treated; group C: F/P-MPs (12 mg dried F/P MPs in 1 mL PBS)-treated; and group D; F/P MPs/FGF-2 (100 µg FGF-2 and 12 mg dried F/P MPs in 1 mL PBS)-treated (n = 6 each). The drugs were administered intramuscularly to each group. Blood flow and blood pressure were measured in each group on days 0, 14, and 28. Angiography was performed to assess arteriogenesis on day 28. The number of capillaries on day 28 was determined by direct counting CD31(-) and α-smooth muscle antibody (α-SMA)-positive vessels. RESULTS: Neither death nor wound infection was observed throughout the experiment. The F/P MPs/FGF-2-treated group showed marked improvement in the blood flow ratio, blood pressure ratio, and capillary number in comparison to the control group, FGF-2-treated group, and F/P MPs-treated group. The F/P MPs-treated group showed intermediate improvement in blood flow ratio and capillary number in comparison to the control group and FGF-2-treated group. CONCLUSIONS: The F/P MPs/FGF-2-treated group strongly induced functional collateral vessels in the rabbit model of hindlimb ischemia, indicating a possible therapy for PAD.
Assuntos
Indutores da Angiogênese/administração & dosagem , Anticoagulantes/química , Circulação Colateral/efeitos dos fármacos , Dalteparina/química , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Antagonistas de Heparina/química , Isquemia/tratamento farmacológico , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Protaminas/química , Actinas/metabolismo , Análise de Variância , Indutores da Angiogênese/química , Animais , Pressão Sanguínea/efeitos dos fármacos , Capilares/efeitos dos fármacos , Capilares/metabolismo , Capilares/fisiopatologia , Química Farmacêutica , Modelos Animais de Doenças , Portadores de Fármacos , Composição de Medicamentos , Fator 2 de Crescimento de Fibroblastos/química , Membro Posterior , Imuno-Histoquímica , Injeções Intramusculares , Isquemia/diagnóstico por imagem , Isquemia/metabolismo , Isquemia/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Tamanho da Partícula , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Coelhos , Radiografia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fatores de TempoRESUMO
This study examined the hemostatic efficacy of photocrosslinkable chitosan hydrogel-mixed photocrosslinked chitosan sponges (PCM-S) after hepatic injury in rats. The left lobe of the liver was penetrated with a dermal punch to produce a penetrating wound in heparinized and nonheparinized rats. Treated rats either had PCM-S applied into the wound and then were immediately ultraviolet irradiated, or they had TachoComb (TC) inserted into the wound. Blood loss, hemostasis, and survival were quantified after the hepatic injury. Measurements on serum alanine aminotransferase in nonheparinized rats and hemoglobin concentrations and histologic examinations in heparinized rats were performed to assess hepatic function. Although the hemostatic effect in the PCM-S-treated nonheparinized rats was identical to that of the TC-treated group, PCM-S-treatment has higher hemostatic effect in heparinized rats. No adverse events related to the use of PCM-S were detected in blood and histologic examinations.
Assuntos
Quitosana/uso terapêutico , Hemorragia/terapia , Técnicas Hemostáticas/instrumentação , Hidrogéis/uso terapêutico , Fígado/lesões , Animais , Modelos Animais de Doenças , Hemostáticos/uso terapêutico , Hepatopatias/terapia , Masculino , Poríferos , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: Supplemental oxygenation is essentially important in critically ill patients with potentially reversible pulmonary insufficiency. An extracorporeal membrane oxygenator and percutaneous cardiopulmonary support have been used for these patients. However, these techniques are associated with so many complications that an additional new therapeutic modality is required. The purpose is to investigate if the peritoneal cavity can be used as "extrapulmonary respiration" that is analogous to peritoneal dialysis and utilizes the efficacy of liposome-encapsulated hemoglobin (artificial oxygen carrier; TRM-645). METHODS: Rats weighing an average of 300 g (n = 18) received an incision in the right chest to generate pneumothorax, which resulted in severe and lethal hypoxia. Oxygenated TRM-645 and human red blood cells (MAP group) were administered into the peritoneum in the experimental rats' pneumothorax model. No treatment except the right pneumothorax was administered to the sham group. RESULTS: Survival times from the pneumothorax were significantly longer in the TRM-645 and MAP groups than in the sham group (32.0 +/- 6.9 and 22.0 +/- 4.9 min vs 9.2 +/- 1.9 min, P < 0.01). In addition, an arterial blood gas analysis showed that the oxygenation in levels significantly improved. CONCLUSIONS: The abdomen (peritoneum) can potentially become an "artificial lung" that can be employed in critical care settings. TRM-645 provides an alternative to the use of washed human red blood cells.
Assuntos
Substitutos Sanguíneos/farmacologia , Hemoglobinas/farmacologia , Lipossomos/farmacologia , Oxigênio/metabolismo , Peritônio/metabolismo , Insuficiência Respiratória/terapia , Animais , Gasometria , Modelos Animais de Doenças , Transfusão de Eritrócitos , Humanos , Pneumotórax Artificial , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Insuficiência Respiratória/fisiopatologia , Taxa de SobrevidaRESUMO
A case of hyponatremia following the first course of systemic adjuvant chemotherapy with cisplatin (CDDP) and 5-FU in a previously treated patient with esophageal cancer is reported. A 61-year-old man was admitted to our hospital for adjuvant chemotherapy after transthoracic esophagectomy and 3-field lymphadenectomy for esophageal cancer. Six days following chemotherapy, his serum sodium concentration was found to be 118 mEq/L, without edema or dehydration. This hyponatremic state was diagnosed as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) induced by CDDP, based on the hypo-osmolality of his serum and urine, and an inappropriate level of plasma vasopressin.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/efeitos adversos , Síndrome de Secreção Inadequada de HAD/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The healthcare system surrounding surgeons is collapsing due to Japan's policy of limiting health expenditure, market fundamentalism, shortage of healthcare providers, unfavorable working environment for surgeons, increasing risk of malpractice suits, and decreasing number of those who desire to pursue the surgery specialty. In the USA, nonphysician and mid-level clinicians such as nurse practitioners (NPs) and physician assistants (PAs) have been working since the 1960s, and the team approach to medicine which benefits patients is functioning well. One strategy to avoid the collapse of the Japanese surgical healthcare system is introducing the NP/PA system. The division of labor in medicine can provide high-quality, safe healthcare and increase the confidence of the public by contributing to: reduced postoperative complications; increased patient satisfaction; decreased length of postoperative hospital stay: and economic benefits. We have requested that the Ministry of Health, Labor and Welfare establish a Japanese NP/PA system to care for patients more efficiently perioperatively. The ministry has decided to launch a trial profession called "tokutei (specifically qualified) nurse" in February 2010. These nurses will be trained and educated at the Master's degree level and allowed to practice several predetermined skill sets under physician supervision. We hope that all healthcare providers will assist in transforming the tokutei nurse system into a Japanese NP/PA system.
Assuntos
Profissionais de Enfermagem/estatística & dados numéricos , Papel do Profissional de Enfermagem , Equipe de Assistência ao Paciente , Assistentes Médicos/estatística & dados numéricos , Cirurgia Geral , JapãoRESUMO
It is difficult to treat patients with acquired airway stenosis, and the quality of life of such patients is therefore lowered. We have suggested the application of photodynamic therapy (PDT) as a new treatment for airway stenosis and have determined the efficacy of PDT in animal disease models using a second-generation photosensitizer with reduced photosensitivity. An airway stenosis rabbit model induced by scraping of the tracheal mucosa was administered NPe6 (5 mg kg(-1)), and the stenotic lesion was irradiated with 670 nm light emitted from a cylindrical diffuser tip at 60 J cm(-2) under bronchoscopic monitoring. PDT using NPe6 improved airway stenosis (P = 0.043) and respiratory stridor. A significant prolongation of survival time was seen in the PDT-treated animals compared to that in the untreated animals (P = 0.025) and 44% of the treated animals achieved long-term survival (>60 days). In conclusion, PDT using NPe6 is effective for improvement in airway stenosis.
Assuntos
Constrição Patológica/tratamento farmacológico , Fotoquimioterapia , Porfirinas/uso terapêutico , Traqueia/patologia , Animais , Modelos Animais de Doenças , Masculino , CoelhosRESUMO
BACKGROUND AND AIMS: Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry. METHODS: A total of 210 cases with gastric cancer were selected. These consisted of 105 cases with regional LN metastasis (LN[+] group) and 105 cases without LN metastasis (LN[-] group). Both groups exhibited the same depth of invasion. Cancer tissues were subjected to immunohistochemistry with antibodies against claudin-3, claudin-4, beta-catenin, matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for the objective discrimination between lymphatics and blood vessels. The expression of each protein as well as the histopathological parameters were compared between LN(+) and LN(-) groups. RESULTS: Along with lymphatic invasion by cancer cells and gross tumor size, MMP-1 expression in cancer cells at the invasive front of the primary tumor was a significant, independent predictor of LN metastasis. The expression of claudins and beta-catenin was associated with the histopathological type of cancer, but not with LN status. CONCLUSION: Among the cancer invasion-related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive front were the predictive factors of LN metastasis of gastric cancer.
Assuntos
Biomarcadores Tumorais/análise , Vasos Linfáticos/patologia , Metaloproteinase 1 da Matriz/análise , Neoplasias Gástricas/secundário , Neoplasias Gástricas/cirurgia , Idoso , Estudos de Casos e Controles , Claudina-3 , Claudina-4 , Feminino , Gastrectomia , Humanos , Imuno-Histoquímica , Metástase Linfática , Vasos Linfáticos/química , Masculino , Metaloproteinase 2 da Matriz/análise , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Gástricas/química , Resultado do Tratamento , Proteínas de Transporte Vesicular/análise , beta Catenina/análise , Fator de von Willebrand/análiseRESUMO
Fragmin/protamine microparticles (F/P MPs) have been shown to bind to culture plates, thereby retaining heparin-binding cytokines. Most protocols for in vitro cultures of human microvascular endothelial cells (hMVECs), human dermal fibroblast cells (hDFCs), and hematopoietic cell line (TF-1) include high fetal bovine serum (FBS) (10%) medium as a nutritional supplement. Growth rates of those cells on the F/P MP-coated plates were higher in low FBS (1%) medium containing fibroblast growth factor (FGF)-2 (for hMVECs and hDFCs) and interleukin (IL)-3/granulocyte-macrophage colony-stimulating factor (for TF-1 cells) than without coating. The cytokines in low FBS medium were shown to be immobilized on the F/P MP-coated plate and released into the culture medium with a half releasing time of 4-5 days. Furthermore, those cells grew well on each cytokine-preimmobilized F/P MP-coated plate in low FBS medium. Thus, the F/P MP-coated matrix with adequate heparin-binding cytokines may provide biomaterials for controlling cellular growth and differentiation.
Assuntos
Técnicas de Cultura de Células/métodos , Citocinas/metabolismo , Citocinas/farmacologia , Dalteparina/metabolismo , Nanopartículas/química , Protaminas/metabolismo , Animais , Bovinos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Meios de Cultura/química , Dalteparina/química , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Interleucina-3/metabolismo , Interleucina-3/farmacologia , Protaminas/química , Ligação Proteica , Soro/químicaRESUMO
We anesthetized three patients with refractory atrial fibrillation undergoing the new thoracoscopic mini Maze procedure. This minimally invasive surgical procedure provides isolation and ablation of the bilateral pulmonary vein without thoracotomy or cardiopulmonary bypass, which was performed first in the United States in 2003. General anesthesia was administrated with a double lumen tracheal tube for bilateral single lung ventilation, and epidural anesthesia was also administrated. We prepared transesophageal echocardiography, a pulmonary artery catheter with pacing wires, and a 20 G arterial line connected to continuous cardiac output monitor. We also prepared a 14 G peripheral intravenous line and two 4 Fr sheaths on the left femoral artery and vein for bleeding and conversion to cardiopulmonary bypass. One patient required massive transfusion and conversion to open procedure with thoracotomy and cardiopulmonary bypass to control sudden and massive bleeding from the pulmonary vein. Another patient was complicated with dextrocardia, but the procedure was successful. One other patient had no complications and the procedure was performed as planned. Certain anesthetic management is essential for this new procedure and we have to prepare for any predictable events.
Assuntos
Anestesia Epidural , Anestesia Geral , Fibrilação Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Ablação por Cateter/métodos , Toracoscopia/métodos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Assistência PerioperatóriaRESUMO
OBJECTIVE: To investigate the efficacy of liposome-encapsulated hemoglobin (LHb) transfusion in rats undergoing lethal progressive hemodilution. SUMMARY BACKGROUND DATA: Unlike other acellular hemoglobin-based oxygen carriers, LHb has lipid bilayer membranes that are similar to mammalian red blood cells (RBCs), which prevent hemoglobin from having any direct contact with the blood components and the endothelium. Acellular hemoglobin has a high affinity for nitric oxide (NO), and because they are reported to behave as NO scavengers, acellular hemoglobin-based oxygen carriers could have pressor effects on the peripheral vessels. During a massive hemorrhage, acellular hemoglobin caused vasoconstriction could decrease peripheral perfusion, thereby leading to diminished oxygen delivery. METHODS: Rats were subjected to blood withdrawal (0.2 mL/min) with a simultaneous resuscitation using an isovolemic fluid transfusion that contained LHb, 5% albumin, or washed rat RBCs for 150 minutes (n = 15 in each group). RESULTS: All rats transfused with LHb or RBCs were rescued from lethal progressive hemodilution, whereas none of the albumin-transfused rats survived. LHb did not affect the plasma NO metabolite levels, suggesting it was not a potent NO scavenger. LHb also improved hemodilution-induced metabolic acidosis, and reduced exaggerated neuroendocrine responses and injuries to the heart, liver, and kidney. It suppressed expression of hypoxia-inducible factor-1alpha in the liver and kidney, suggesting improvement of hypoxia at molecular response levels. However, neither transfused LHb nor RBCs improved the acute lung injury that occurs after progressive hemodilution. CONCLUSION: LHb transfusion is effective in rescuing rats undergoing progressive hemodilution from lethal organ hypoxia without scavenging NO.
Assuntos
Hemoglobinas/administração & dosagem , Hipóxia/terapia , Rim/irrigação sanguínea , Fígado/irrigação sanguínea , Pulmão/irrigação sanguínea , Óxido Nítrico/metabolismo , Choque Hemorrágico/terapia , Animais , Transfusão de Componentes Sanguíneos/métodos , Líquido da Lavagem Broncoalveolar/química , Cápsulas , Modelos Animais de Doenças , Hidratação/métodos , Hemodiluição , Hipóxia/complicações , Hipóxia/metabolismo , Rim/patologia , Lipossomos , Fígado/patologia , Pulmão/patologia , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Óxido Nítrico/sangue , Tamanho do Órgão , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ressuscitação/métodos , Choque Hemorrágico/complicações , Choque Hemorrágico/metabolismo , Estatísticas não Paramétricas , Volume Sistólico , Análise de SobrevidaRESUMO
BACKGROUND: Acquired airway stenosis in childhood is resistant to conventional treatment. We examined whether endoscope-assisted photodynamic therapy (PDT) is effective for airway stenosis in animal models of which the pathophysiologic progressions are similar to those of clinical cases showing rapid deterioration. METHODS: Tracheal mucosa-scraped rabbits were administered IV porfimer sodium (Photofrin; Wyeth K.K., Tokyo, Japan) [2 mg/kg], and the tracheal lesions were irradiated with 630 nm of light emitted from a cylindrical diffuser tip via a transtracheal approach. RESULTS: Rabbits without PDT (untreated animals) showed dense granulation tissue in the scraped lesion, resulting in airway stenosis complicated with respiratory stridor. PDT ameliorated the degree of airway stenosis (p = 0.008) and reduced respiratory stridor; rabbits that received PDT showed patchy granulation tissue that was only 20 to 30% of the volume of that seen in the untreated animals. Survival time of rabbits that received PDT was significantly prolonged compared with that of untreated animals (p = 0.03). CONCLUSIONS: PDT was effective for airway stenosis in rabbit models. This suggests that PDT has the potential as a new therapeutic method for airway stenosis originating from granulation tissue.
Assuntos
Fotoquimioterapia , Estenose Traqueal/tratamento farmacológico , Animais , Modelos Animais de Doenças , Masculino , CoelhosRESUMO
Attempts to image reporter gene expression driven by weak promoters are often hampered by the poor transcriptional activity of such promoters. Most tissue-specific promoters are weak compared with stronger but constitutively expressing viral promoters. In this study, we validated methods of enhancing the transcriptional activity of weak promoters using a Cre-loxP system in vitro and in vivo. We constructed a tester vector, pCTL, which carries a strong systemic cytomegalovirus enhancer/chicken beta-actin promoter (CAG), loxP-flanked CAT, and firefly luciferase (luc) cDNAs. Herpes simplex virus-thymidine kinase (HSV-tk) promoter was used as a weak and systemic promoter and ligated to Cre for construction of pTC. Luc activity was higher (about 10-fold enhancement) in co-transfected (with pCTL and pTC) than in singly (with HSV-tk promoter-driven luc expression vector pTL) transfected NIH3T3 cells. In vivo electroporation-mediated gene delivery of both pCTL and pTC into murine oviductal epithelium yielded results (about 16-fold enhancement) similar to those obtained with in vitro-transfected NIH3T3 cells. To evaluate tissue-specific enhancement of gene expression, podocyte (glomerular visceral epithelial cell)-specific nephrin promoter was ligated to the Cre gene or luc cDNA to create pNC and pNL, respectively. We achieved 2.4-fold improvement of luc gene expression in the mouse kidney in vivo when pCTL and pNC were co-transfected via the tail vein via the lipoplex method. The combination of a weak tissue-specific promoter with the Cre-loxP system could thus be used to enhance the strength of tissue-specific promoters in vitro and in vivo.