RESUMO
INTRODUCTION: Military surgeons must be prepared to care for severe and complex life-threatening injuries rarely seen in the civilian setting. Typical civilian training and practice do not provide adequate exposure to the broad set of surgical skills required. The German Bundeswehr Medical Service has developed and refined the War Surgery Course (WSC) to meet this training gap. This article describes the recent experience with this readiness curriculum. METHODS: Run annually since 1998, WSC consists nowadays of 5â days with 20 theoretical modules. Four sessions with standardised practical skills training use a live tissue porcine model, and the recently added cadaver-based Advanced Surgical Skills for Exposure in Trauma course. Sixteen military surgeons who participated in the WSC in January 2016 completed a survey of their self-rated readiness for 114 predefined emergency skills before and after completion, and provided an overall evaluation of the course. RESULTS: Self-assessed readiness improved significantly over baseline for all areas covered in both the practical skills and theoretical knowledge portions of the WSC curriculum. Additionally, all participants rated the course as important and universally recommended it to other military surgeons preparing for missions. CONCLUSIONS: The WSC course format was well received and perceived by learners as a valuable readiness platform. Ongoing evaluation of this course will enable data-driven evolution to ensure a maximum learning benefit for participants. With the increasing multinational nature of modern military missions, surgeons' training should follow international standards. Continuing evolution of military surgical training courses should further encourage the sharing and adoption of best educational practices.
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Currículo , Cirurgia Geral/educação , Medicina Militar/educação , Treinamento por Simulação , Traumatologia/educação , Animais , Cadáver , Competência Clínica , Alemanha , Humanos , Modelos Anatômicos , SuínosRESUMO
This study examined the ability of l-arginine, l-cysteine and l-methionine, to inhibit postharvest senescence of broccoli. Florets were dipped in aqueous solutions of the amino acids at concentrations from 1.0 to 100 mM and stored at 10 °C. A 5 mM dip was found to be optimal in delaying senescence as measured by retention of green colour, vitamin C and antioxidant activity, and a lower level of ethylene production, respiration, weight loss, phenylalanine ammonia lyase (PAL) activity and ion leakage with the benefits being similar for all three amino acids. Arginine, cysteine and methionine have Generally Recognised As Safe (GRAS) status and should have few impediments in obtaining regulatory approval for commercial use if similar effects were found for other leafy vegetables.
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Arginina/farmacologia , Brassica/efeitos dos fármacos , Cisteína/farmacologia , Metionina/farmacologia , Proteínas de Plantas/metabolismo , Amônia-Liases/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Brassica/metabolismo , Etilenos/metabolismo , Fatores de TempoRESUMO
BACKGROUND: Early hemorrhage control using resuscitative endovascular balloon occlusion of the aorta (REBOA) can save lives. This study was designed to evaluate the ability to train Quick Response Team Fire Fighters (QRT-FF) to gain percutaneous femoral artery access and place a REBOA catheter in a model, using a comprehensive theoretical and practical training program. METHODS: Six QRT-FF participated in the training. SOF medics from a previous training served as the control group. A formalized training curriculum included basic anatomy and endovascular materials for percutaneous access and REBOA placement. Key skills included (1) preparation of an endovascular toolkit, (2) achieving vascular access in the model, and (3) placement and positioning of REBOA. RESULTS: QRT-FF had significantly better scores compared with medics using endovascular materials (P = .003) and performing the procedure without unnecessary attempts (P = .032). Basic surgical anatomy scores for QRT-FF were significantly better than SOF medics (P = .048). QRT-FF subjects demonstrated a significantly higher overall technical skills point score than medics (P = .030). QRT-FF had a median total time from start of the procedure to REBOA inflation of 3:23 minutes, and medics, 5:05 minutes. All six QRT-FF subjects improved their procedure times-as did four of the five medics. CONCLUSIONS: Our training program using a task training model can be utilized for percutaneous femoral access and REBOA placement training of QRT-FF without prior ultrasound or endovascular experience. Training the use of advanced bleeding control options such as REBOA, as a secondary occupational task, has the potential to improve outcomes for severely bleeding casualties in the field.
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Bombeiros/educação , Hemorragia/prevenção & controle , Aorta , Oclusão com Balão , Cateterismo Periférico , Procedimentos Endovasculares , Estudos de Viabilidade , Artéria Femoral , Humanos , Avaliação de Programas e Projetos de Saúde , RessuscitaçãoRESUMO
BACKGROUND: The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) in patients with severe haemorrhagic shock is increasing. Obtaining vascular access is a necessary prerequisite for REBOA placement in these situations. METHODS: During the EVTM workshop (September 2017, Örebro, Sweden), 21 individuals participated in this study, 16 participants and five instructors. A formalised curriculum was constructed including basic anatomy of the femoral region and basic training in access materials for REBOA placement in zone 1. Key skills: (1) preparation of endovascular toolkit, (2) achieving vascular access in the model and (3) bleeding control with REBOA. Scoring ranged from 0 to 5 for non-anatomical skills. Identification of anatomical structures was either sufficient (score=1) or insufficient (score=0). Five consultants performed a second identical procedure as a post test. RESULTS: Consultants had significantly better overall technical skills in comparison with residents (p=0.005), while understanding of surgical anatomy showed no difference. Procedure times differed significantly (p<0.01), with residents having a median procedure time of 3 min and 24 s, consultants 2:33 and instructors 1:09. CONCLUSION: This comprehensive training model using a live tissue-simulator hybrid porcine model can be used for femoral access and REBOA placement training in medical personnel with different prior training levels. Higher levels of training are associated with faster procedure times. Further research in open and percutaneous access training is necessary to simulate real-life situations. This training method can be used in a multistep training programme, in combination with realistic moulage and perfused cadaver models.
Assuntos
Oclusão com Balão/métodos , Procedimentos Endovasculares/educação , Modelos Cardiovasculares , Animais , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Estudos de Viabilidade , Humanos , SuínosRESUMO
BACKGROUND: Vascular access is a necessary prerequisite for REBOA placement in patients with severe hemorrhagic shock. METHODS: During an EVTM workshop, 10 Special Forces (SOF) medics, five combat nurses, four military nonsurgeon physicians, and four military surgeons participated in our training program. The military surgeons functioned as the control group. A formalized curriculum was constructed including basic anatomy and training in access materials for resuscitative endovascular balloon occlusion of the aorta (REBOA) placement. Key skills were (1) preparation of endovascular toolkit, (2) achieving vascular access in the model, and (3) bleeding control with REBOA. RESULTS: The baseline knowledge of anatomy for SOF medics was significantly less than that for nurses and physicians. Medics had a median time of 3:59 minutes to sheath insertion; nurses, 2:47; physicians, 2:34; and surgeons, 1:39. Military surgeons were significantly faster than medics and military nurses (ρ = .037 resp. 0.034). Medics had a median total time from start to REBOA inflation of 5:05 minutes; nurses, 4:06; military physicians, 3:36; and surgeons, 2:36. CONCLUSION: This study showed that a comprehensive theoretical and practical training program using a task training model can be used for percutaneous femoral access and REBOA placement training of military medical personnel without prior ultrasound or endovascular experience. Higher levels of training reduce procedure times.
Assuntos
Aorta , Oclusão com Balão , Procedimentos Endovasculares/educação , Medicina Militar/educação , Militares/educação , Ressuscitação/educação , Choque Hemorrágico/terapia , Estudos de Viabilidade , Humanos , Militares/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Ressuscitação/métodos , Análise e Desempenho de TarefasRESUMO
OBJECTIVE: Current skills assessment in the Fundamentals of Laparoscopic Surgery (FLS) program is labor intensive, requiring one proctor for every 1-2 subjects. The ProMIS Augmented Reality (AR) simulator (Haptica, Dublin IR) allows for objective assessment of physical tasks through instrument tracking technology. We hypothesized that the ProMIS metrics could differentiate between ability groups as well as standard FLS scoring with fewer personnel requirements METHODS: We recruited 60 volunteer subjects. Subjects were stratified based on their laparoscopic surgical experience. Those who had performed more than 100 laparoscopic procedures were considered experienced (n = 8). Those with fewer than 10 laparoscopic procedures were considered novices (n = 44). The rest were intermediates (n = 8). All subjects performed up to five trials of the peg transfer task from FLS in the ProMIS simulator. The FLS score, instrument path length, and instrument smoothness assessment were generated for each trial. RESULTS: For each of the five trials, experienced surgeons outperformed intermediates, who in turn outperformed novices. Statistically significant differences were seen between the groups across all trials for FLS score (p < 0.001), ProMIS path length (p < 0.001), and ProMIS smoothness (p < 0.001). When the FLS score was compared to the path length and smoothness metrics, a strong relationship between the scores was apparent for novices (r = 0.78, r = 0.94, p < 0.001) respectively), intermediates (r = 0.5, p = 0.2, r = 0.98, p < 0.001), and experienced surgeons (r = 0.86, p = 0.006, r = 0.99, p < 0.001). CONCLUSIONS: The construct that the standard scoring of the FLS peg transfer task can discriminate between experienced, intermediate, and novice surgeons is validated. The same construct is valid when the task is assessed using the metrics of the ProMIS. The high correlation between these scores establishes the concurrent validity of the ProMIS metrics. The use of AR for objective assessment of FLS tasks could reduce the personnel requirements of assessing these skills while maintaining the objectivity.
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Competência Clínica , Simulação por Computador , Cirurgia Geral/educação , Laparoscopia , Interface Usuário-Computador , Adulto , Avaliação Educacional , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Opportunities to improve emergency surgery outcomes exist through guided better practice and reduced variability. Few attempts have been made to define optimal care in emergency surgery, and few clinically derived key performance indicators (KPIs) have been published. A summit was therefore convened to look at resources for optimal care of emergency surgery. The aim of the Donegal Summit was to set a platform in place to develop guidelines and KPIs in emergency surgery. METHODS: The project had multidisciplinary global involvement in producing consensus statements regarding emergency surgery care in key areas, and to assess feasibility of producing KPIs that could be used to monitor process and outcome of care in the future. RESULTS: Forty-four key opinion leaders in emergency surgery, across 7 disciplines from 17 countries, composed evidence-based position papers on 14 key areas of emergency surgery and 112 KPIs in 20 acute conditions or emergency systems. CONCLUSIONS: The summit was successful in achieving position papers and KPIs in emergency surgery. While position papers were limited by non-graded evidence and non-validated KPIs, the process set a foundation for the future advancement of emergency surgery.
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Lesões Encefálicas Traumáticas/cirurgia , Pediatria/métodos , Acidentes por Quedas/mortalidade , Acidentes por Quedas/estatística & dados numéricos , Acidentes de Trânsito/mortalidade , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Mundo Árabe , Lesões Encefálicas Traumáticas/epidemiologia , Criança , Pré-Escolar , Técnica Delphi , Feminino , Humanos , Lactente , Masculino , Oriente Médio/epidemiologia , Pediatria/tendências , Estudos Retrospectivos , Centros de Traumatologia/organização & administração , Centros de Traumatologia/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Major surgery is known to suppress T-cell function; however, its differential effects on the production of helper T-cell type 1 (T(H)1) and type 2 (T(H)2) cytokines remains unknown. OBJECTIVE: To measure the production patterns of T(H)1 (interleukin 2 [IL-2] and interferon gamma) and T(H)2 (IL-4 and IL-10) cytokines following major surgery. DESIGN, SETTING, AND PATIENTS: A cohort study of patients (both active and former members of the armed forces) at a military hospital. INTERVENTION: Aortic surgery or carotid endarterectomy and measurement of serum IL-6 levels by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Unstimulated and stimulated intracellular levels of IL-2, IL-4, IL-10, and interferon gamma in CD4+, CD8+, and gammadelta+ T cells and serum IL-6 levels immediately before and for 2 days after aortic surgery or carotid endarterectomy. RESULTS: No unstimulated production of T(H) or T(H)2 cytokines was detected. Stimulated intracellular levels of IL-2 and interferon gamma were significantly depressed during the postoperative period in all T-cell subsets in both patient groups. There were no postoperative increases in stimulated IL-4 or IL-10 levels. CONCLUSION: Major surgery suppresses the potential responses of T(H)1 cytokines without enhancing production of T(H)2 cytokines.
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Aorta/cirurgia , Endarterectomia das Carótidas , Interferon gama/biossíntese , Interleucinas/biossíntese , Células Th1/imunologia , Células Th2/imunologia , Idoso , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: The selectin glycoproteins are involved in the pathogenesis of renal ischemia-reperfusion injury. We investigated the ability of glycyrrhizin, a known selectin inhibitor, to attenuate renal ischemia-reperfusion injury. METHODS: Eighteen New Zealand white rabbits underwent midline laparotomy with renal artery cross-clamping. After 30 minutes of reperfusion, group 1 (control, n = 10) animals received a saline infusion, while group 2 (GLY, n = 8) animals received a glycyrrhizin infusion. Renal function was compared between the two groups after 72 hours of reperfusion. A t test was utilized, with alpha set at P<0.05. RESULTS: Group 1 and group 2 animals had similar baseline renal function. However, after 72 hours of reperfusion, group 1 animals had a significantly higher mean blood urea nitrogen creatinine ratio than group 2 animals (P<0.01), indicating preserved renal function in rabbits treated with glycyrrhizin. CONCLUSIONS: Selectin blockade using glycyrrhizin attenuates renal ischemia-reperfusion injury when given 30 minutes after the onset of reperfusion in a rabbit model.
Assuntos
Ácido Glicirrízico/farmacologia , Rim/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Selectinas/fisiologia , Animais , Nitrogênio da Ureia Sanguínea , Rim/fisiopatologia , Coelhos , Traumatismo por Reperfusão/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: The purpose of this study was to determine whether imbrication of native fascia versus excision and closure of new raw fascia forms a stronger union. METHODS: We utilized the anterior rectus sheath fascia of Sprague-Dawley rats as the model. Sixty rats underwent fascial tightening procedures. Each rat had the anterior rectus sheath shortened by 1 cm, 30 by imbrication and 30 by excision and closure. Ten of each group were harvested at 7 days' healing, 10 at 14 days, and 10 of each group at 28 days' healing. The anterior rectus sheath was removed, a "dumbbell" shape constructed, and the cross sectional area at the point of interest determined. The fascia was placed on an Instron tensiometer to determine the breaking strength. Tensile strength was calculated and the data analyzed by ANOVA and the Kruskall-Wallis test. Tissue samples of the closures were histologically analyzed for fibroblast counts, degree of inflammation, and presence of dense fibrous connective tissue. Tissue samples were also analyzed for enzymatic collagen crosslinking. RESULTS: There was a statistically significant difference in tensile strength between the two groups at 7, 14, and 28 days. Results show that at 7 days the mean tensile strength of excision was 0.133 kg/mm2 +/- 0.056 and the mean tensile strength of imbrication was 0.083 kg/mm2 +/- .048 (P < 0.05); at 14 days the mean tensile strength of excision was 0.105 kg/mm2 +/- 0.033 and the mean tensile strength of imbrication was 0.057 kg/mm2 +/- 0.014 (P < 0.002), and at 28 days the mean tensile strength of excision was 0.279 kg/mm2 +/- 0.143 and the mean tensile strength of imbrication was 0.145 kg/mm2 +/- 0.061 (P < 0.03). Histologic findings showed no statistical significance between the two closure methods when comparing degree of inflammation or the number of fibroblasts present. However, at 7 and 14 days there is a significantly greater presence of dense fibrous connective tissue in the excision group (P < 0.03 at 7 days and P < 0.044 at 14 days by ANOVA). Collagen crosslink analysis showed that by day 28 there is a significantly greater amount (P < 0.05 by ANOVA) of the difunctional crosslink dihydroxylysinonorleucine (DHLNL) and a greater ratio between DHLNL and the difunctional crosslink hydroxylysinonorleucine (HLNL) in the excision and closure group. CONCLUSION: We conclude that at 7, 14, and 28 days healing, excision provides a significantly stronger closure than imbrication. According to the crosslinking analysis, it is likely that this strength advantage may continue to increase over time. These findings suggest that excision and closure may be the preferred method for fascial tightening procedures.
Assuntos
Fasciotomia , Cicatrização , Animais , Tecido Conjuntivo/patologia , Fáscia/imunologia , Fáscia/patologia , Fáscia/fisiologia , Inflamação , Masculino , Ratos , Ratos Sprague-Dawley , Procedimentos Cirúrgicos Operatórios/métodos , Resistência à Tração , Cicatrização/fisiologiaRESUMO
Major surgery suppresses intracellular T-cell cytokine production. Laparoscopic surgery has been reported to have no effect on in vitro lymphocyte reactivity, but its effects on intracellular cytokine production are unknown. This study measured T-cell intracellular gamma-interferon, interleukin-4 (IL-4), and interleukin-10 (IL-10), along with serum interleukin-6 (IL-6) and cortisol levels, immediately before and 1 day after laparoscopic cholecystectomy in a cohort of six Air Force and veteran patients. Stimulated intracellular levels of gamma-interferon were slightly, but not significantly, elevated during the postoperative period in all T-cell subsets. There were no postoperative changes in stimulated IL-4 or IL-10 levels. Postoperative serum IL-6 levels, but not serum cortisol levels, were significantly elevated compared to preoperative values. In conclusion, laparoscopic surgery causes slight trauma but has no effect on T-cell intracellular interferon, IL-4, and IL-10 responses.
Assuntos
Colecistectomia Laparoscópica , Colecistite/imunologia , Colecistite/cirurgia , Citocinas/sangue , Linfócitos T/imunologia , Adulto , Colelitíase/imunologia , Colelitíase/cirurgia , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Hidrocortisona/sangue , Terapia de Imunossupressão , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-4/sangue , MasculinoRESUMO
BACKGROUND AND OBJECTIVES: Reported complications of retained gallstones following laparoscopic cholecystectomy (LC) are increasing. This study was undertaken to evaluate the effects of retained gallstones following LC in a prairie dog model. METHODS: Twenty-seven prairie dogs with diet-induced gallstones were divided into three groups of nine. Group I (control) had LC with removal of stones. Group II had LC followed by return of native stones intra-abdominally. Group III had LC followed by return of infected stones (stones dipped in Escherichia coli) intra-abdominally. Animals were euthanized at two months and the character and extent of intra-abdominal adhesions were scored. RESULTS: Adhesions were present in 56% of animals in Group I, 89% in Group II, and 100% in Group III. The character and extent of adhesions in groups II & III were significantly greater than the control group (p < 0.03). Group III exhibited the highest degree of adhesions when compared to control (p < 0.007). Histopathology revealed evidence of micro-abscess formation, foreign body giant cell reaction, and fat necrosis adjacent to retained stones. CONCLUSION: Retained intra-abdominal gallstones, especially if infected, are associated with increased adhesions and inflammatory response in this LC model. Further investigation into the long-term consequences of this entity is warranted.
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Colecistectomia Laparoscópica/efeitos adversos , Colelitíase/cirurgia , Infecções por Escherichia coli/etiologia , Peritonite/etiologia , Aderências Teciduais/etiologia , Animais , Colecistectomia Laparoscópica/métodos , Modelos Animais de Doenças , Cães , Infecções por Escherichia coli/patologia , Masculino , Necrose , Peritonite/patologia , Recidiva , Medição de Risco , Sciuridae , Aderências Teciduais/patologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pancreatic cancer is a devastating cancer that presents late, is rapidly progressive and has current therapeutics with only limited efficacy. Bioactive compounds are ubiquitously present in fruits and numerous studies in vitro are addressing the activity of these compounds against pancreatic cancer, thus studies of specific bioactive compounds could lead to new anti-pancreatic cancer strategies. Australian native fruits have been used as foods and medicines by Australian Aboriginals for thousands of years, and preliminary studies have found these fruits to contain rich and diversified bioactive components with high antioxidant activity. Thus, Australian native fruits may possess key components for preventing or delaying the onset of tumorigenesis, or for the treatment of existing cancers, including pancreatic cancer. MATERIALS AND METHODS: Numerous databases including PubMed, SciFinder, Web of Knowledge, Scopus, and Sciencedirect were analysed for correlations between bioactive components from fruits and pancreatic cancer, as well as studies concerning Australian native fruits. RESULTS: In this review, we comprehensively highlight the proposed mechanisms of action of fruit bioactives as anti-cancer agents, update the potential anti-pancreatic cancer activity of various major classes of bioactive compounds derived from fruits, and discuss the existence of bioactive compounds identified from a selection Australian native fruits for future studies. CONCLUSION: Bioactive compounds derived from fruits possess the potential for the discovery of new anti-pancreatic cancer strategies. Further, Australian native fruits are rich in polyphenols including some flora that contain unique phenolic compounds, thereby warranting further investigations into their anti-cancer properties.
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Antineoplásicos Fitogênicos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Fenóis/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Austrália , Frutas , Humanos , Medicina Tradicional , Neoplasias Pancreáticas/patologia , Fenóis/isolamento & purificação , Polifenóis/isolamento & purificação , Polifenóis/farmacologiaRESUMO
Postharvest treatment of fruit and vegetables with a low concentration of nitric oxide gas can extend postharvest life but application of nitric oxide by release from a gas cylinder is not feasible for many horticultural situations. This paper reports on development of a solid mixture to generate nitric oxide gas in the presence of horticultural produce. The solid NO-donor compound, diethylenetriamine/nitric oxide (DETANO) was found to quantitatively liberate nitric oxide in the presence of a range of acidic substances including citric acid. A solid mixture of DETANO and citric acid with wheat starch added as a filler and moisture absorbent in the ratio of 1:10:20 was found to be stable for at least six months when stored in dry air. However, in humid air, absorption of moisture from the atmosphere led to reaction of DETANO with citric acid and the evolution of nitric oxide gas. When the dry mixture was placed in a container with strawberry and mushroom, the moisture given off by produce activated the mixture and resulted in a similar extension in postharvest life as achieved by direct fumigation with nitric oxide gas. Commercial use of such a solid mixture could be through tablets or sachets which are more manageable in a farm or packing house than gas fumigation.
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Manipulação de Alimentos/métodos , Conservação de Alimentos/métodos , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Poliaminas/química , Agaricales , Agricultura/métodos , Fragaria , Gases , Modelos Biológicos , Proteínas de Plantas/química , Temperatura , Fatores de TempoRESUMO
Leiomyosarcoma of the skin and subcutaneous tissues is a rare tumor of smooth muscle origin. A case report of leiomyosarcoma of the hand is presented. The lesion was treated with wide local excision and has shown no recurrence in 2 years of follow-up.
Assuntos
Mãos , Leiomiossarcoma/patologia , Neoplasias Cutâneas/patologia , Neoplasias de Tecidos Moles/patologia , Punho , Seguimentos , Humanos , Leiomiossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/cirurgia , Neoplasias de Tecidos Moles/cirurgiaRESUMO
BACKGROUND: Tension pneumothorax is a reported risk with pneumoperitoneum in the presence of diaphragmatic injuries. A goat model with and without diaphragmatic injury was used to determine if varying levels of intra-abdominal pressure (IAP) result in tension pneumothorax. METHODS: Twenty-four goats were divided equally into four groups: (1) 5 mm Hg IAP control, (2) 15 mm Hg IAP control, (3) 5 mm Hg IAP with diaphragmatic injury, (4) 15 mm Hg IAP with diaphragmatic injury. Chest x-ray films were made and heart rate (HR), mean arterial pressure, central venous pressure (CVP), arterial blood gases, and airway pressure (AP) were measured at 10-minute intervals up to 30 minutes. Significant changes were determined by using the one-way analysis of variance and Mann-Whitney test with alpha set at p < 0.05. RESULTS: In group 4, 100% (all six goats) developed radiographic evidence of tension pneumothorax by 10 minutes. Mean changes from baseline at 20 minutes for the following parameters were all significantly different from controls: HR (p < 0.05), CVP (p < 0.0001), PaO2 (p < 0.001), and AP (p < 0.004). Mortality was 67% (four of six) at 25 minutes. In group 3, 100% (all six goats) of the animals developed radiographic evidence of a simple pneumothorax without mediastinal shift. In this group, there were significant changes in PaO2 (p < 0.003), AP (p < 0.04), and HR (p < 0.05). Mortality was 16% (one of six) at 25 minutes. CONCLUSION: In this goat model of diaphragmatic injury, tension pneumothorax is a significant threat when pneumoperitoneum is maintained at 15 mm Hg IAP. Pneumoperitoneum at 5 mm Hg IAP leads to simple pneumothorax with deleterious effects on oxygenation. Changes in AP, CVP, HR, and PaO2 provide early clues to the development of the problem.
Assuntos
Diafragma/lesões , Laparoscopia , Pneumoperitônio Artificial/efeitos adversos , Pneumotórax/etiologia , Animais , Modelos Animais de Doenças , Cabras , PressãoRESUMO
Two series of anhydride modified cantharidin analogues were synthesised and screened for their phosphatase inhibition (PP1 and PP2A) and cytotoxicity in various cancer cell lines (Ovarian A2780, ADDP; Osteosarcoma 143B; and Colon HCT116 and HT29). One series was synthesised by a novel, high yielding one-pot hydrogenation-ring-opening-esterification procedure, the other by acid catalysed acetal formation. Analogues 5-7 and 9 displayed moderate PP2A selectivity (ca. 5- to 20-fold) and inhibition typically in the low microM range (comparable, in some cases to cantharidin). The anticancer activity of these analogues varied with the cell line under study; however, many of them showed selective cytotoxicity for the colon tumour cell lines.
Assuntos
Anidridos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Cantaridina/análogos & derivados , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Isoenzimas/antagonistas & inibidores , Fosfoproteínas Fosfatases/antagonistas & inibidores , Cantaridina/síntese química , Cantaridina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células Tumorais CultivadasRESUMO
Laparoscopic surgery for cancer has led to the unwelcome occurrence of malignant seeding of port sites. It is hypothesized that this seeding may be a result of aerosolization and forced egress of cells from the peritoneum as a result of pneumoperitoneum. The purpose of this study was to develop a model that would allow for future investigations of cellular aerosolization. Six swine were anesthetized, intubated, and ventilated. A port was placed in the midline and the abdomen insufflated. After insufflation a 14-gauge angiocath was placed in the abdomen through a separate site and attached to a closed system that allowed escaping air to bubble through 3 ml of saline. Intraabdominal pressure was serially increased at 30-min intervals to 8, 10, 12, 14, 16, and 18 mm Hg, and separate saline samples were collected at each interval. Saline samples were centrifuged, and epithelial cells were counted by direct vision and Giemsa staining. Epithelial cells were recovered at all levels of pneumoperitoneum. There was a moderate correlation between the level of pneumoperitoneum and the number of cells collected (r = 0.61, p < 0.19). Results of this study suggest that during pneumoperitoneum there is an ongoing egress of aerosolized cells from the abdomen. Application of this model may aid in future study of aerosolization of cancer cells during laparoscopic surgery.
Assuntos
Aerossóis , Células Epiteliais , Laparoscopia/efeitos adversos , Pneumoperitônio Artificial/efeitos adversos , Animais , Inoculação de Neoplasia , SuínosRESUMO
BACKGROUND: The purpose of this study was to investigate the effects of increasing intraabdominal pressure (IP) on gastric blood flow, as measured by gastric tonometry and traditional hemodynamic measurements. METHODS: Nine swine were anesthetized, intubated, and ventilated. Arterial and pulmonary artery catheters were placed by cutdown, a trocar was placed in the abdomen, and a gastric tonometer was placed in the stomach. Serial measurements of arterial and mixed venous blood gases, cardiac output, wedge pressure, lactic acid, and gastric intramucosal pH (pHi) were collected at intraperitoneal pressures of 0, 8, 10, 12, 14, 16, and 18 mm Hg after 30 min equilibration. Statistical analysis included Pearson correlation and Student's t test. RESULTS: Increasing levels of IP were correlated with decreased arterial pH (p < 0.00003), increased mixed venous CO2 (p < 0.003), decreased intramucosal pH (p < 0.014), and increased arterial CO2 (p < 0.015). Gastric pHi differed significantly from baseline at IP levels of 16 mm Hg (p < 0.004) and 18 mm Hg (p < 0.01). No significant effects were observed on cardiac output or arterial lactate. No significant effects were observed in a control group that had been insufflated to 8 mm Hg and held constant over 3 h. CONCLUSIONS: In this model, gastric blood flow is adversely affected by increasing i.p. with pronounced effects in excess of 15 mm Hg. These results suggest that gastric tonometry may be used to monitor the adverse effects of pneumoperitoneum. Gastric pHi may be an earlier indicator of altered hemodynamic function during laparoscopy than traditional measures.
Assuntos
Abdome/fisiopatologia , Mucosa Gástrica/irrigação sanguínea , Hemodinâmica/fisiologia , Pneumoperitônio Artificial , Animais , Gasometria , Dióxido de Carbono , Concentração de Íons de Hidrogênio , Ácido Láctico/sangue , Laparoscopia , Manometria , Pressão , SuínosRESUMO
Cantharidin and its analogues have been of considerable interest as potent inhibitors of the serine/threonine protein phosphatases 1 and 2A (PP1 and PP2A). However, limited modifications to the parent compounds is tolerated. As part of an on-going study we have developed a new series of cantharidin analogues, the cantharimides. Inhibition studies indicate that cantharimides possessing a D- or L-histidine, are more potent inhibitors of PP1 and PP2A (PP1 IC(50)=3.22+/-0.7 microM; PP2A IC(50)=0.81+/-0.1 microM and PP1 IC(50)=2.82+/-0.6 microM; PP2A IC(50)=1.35+/-0.3 microM, respectively) than norcantharidin (PP1 IC(50)=5.31+/-0.76 microM; PP2A IC(50)=2.9+/-1.04 microM) and essentially equipotent with cantharidin (PP1 IC(50)=3.6+/-0.42 microM; PP2A IC(50)=0.36+/-0.08 microM). Cantharimides with non-polar or acidic amino acid residues are only poor inhibitors of PP1 and PP2A.