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1.
Scand J Surg ; 103(2): 112-119, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24737851

RESUMEN

BACKGROUND: Resuscitative thoracotomy is a heroic procedure that may offer the only survival hope for trauma patients in extremis. However, this operation has been the subject of much debate and its use, feasibility, outcomes, and cost are being continuously re-evaluated. METHODS: This is a review of the most current (after 2000) literature on resuscitative thoracotomy, based on computer database searches for studies on resuscitative thoracotomy, emergency department thoracotomy, and emergency thoracotomy. Studies were selected for inclusion in this review based on their relevance and contribution to our understanding of resuscitative thoracotomy. RESULTS: A total of 37 studies were included, and the following resuscitative thoracotomy-related topics were critically discussed: indications, biochemical profile, long-term outcome, organ donation, pre-hospital use, military use, international aspects, intra-aortic balloon occlusion, suspended animation, and cost and occupational exposure. CONCLUSIONS: This review demonstrates that the indications for resuscitative thoracotomy become clearer and that new information is available regarding its use in the pre-hospital urban environment and military settings. Furthermore, it points to new strategies to supplement resuscitative thoracotomy including intra-aortic balloon occlusion and suspended animation. Finally, it sheds light on the long-term outcomes, organ donation, and cost and occupational exposure following resuscitative thoracotomy.

2.
Scand J Surg ; 103(2): 156-160, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24743726

RESUMEN

BACKGROUND: Resuscitative thoracotomy is a dramatic operation performed in otherwise unsalvageable trauma patients. Analysis of its efficacy is based mostly on institutional series compiling the experience of multiple surgeons. This study aimed to report more consistent information by describing the resuscitative thoracotomy practice of a single surgeon and its evolution during more than two decades. METHODS: A retrospective review of consecutive patients who underwent resuscitative thoracotomy in July 1990 to December 2012. Demographics, mechanism of injury, signs of life, injuries, and outcomes were analyzed. Comparisons were made between penetrating and blunt trauma patients and between pre- and post-introduction of a selective resuscitative thoracotomy protocol. RESULTS: Sixty-seven resuscitative thoracotomies were performed. Most patients were males (84%), and mean age was 38 years. Mechanism of injury was stab wounds (54%, 36), blunt force (25%, 17), and gunshot wounds (21%, 14). Survival was 22% (8/36), 0% (0/17), and 7% (1/14), respectively. All nine survivors had signs of life upon admission, and survival in patients with signs of life on admission was 25% (8/32) in the stab wounds group and 8% (1/12) in the gunshot wounds group. Seven of the nine survivors (78%) were discharged neurologically intact. The most common injury in survivors was cardiac laceration with tamponade (6/9) and lung injury (3/9). Three survivors had a cardiac and lung injury, one had a lung hilum injury, and one had an abdominal inferior vena cava laceration. The switch to resuscitative thoracotomy protocol (2002) improved overall (31 vs 8%, p < 0.05) and penetrating trauma (45 vs 10%, p < 0.05) survival, eliminated resuscitative thoracotomy in patients presenting with no signs of life, and tended to reduce resuscitative thoracotomy utilization in blunt trauma patients. CONCLUSION: This single-surgeon series supports that resuscitative thoracotomy can be lifesaving in selected penetrating trauma patients in extremis. A switch to a selective evidence-based protocol increased overall and penetrating resuscitative thoracotomy survival and limited resuscitative thoracotomy performance to patients arriving with signs of life.

4.
Isr Med Assoc J ; 3(9): 691-7, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11574989

RESUMEN

Red cell substitutes are currently under development for use in a variety of surgery and trauma-related clinical conditions. The need for artificial oxygen-carrying fluids continues to be driven by the shortage of donor blood, the complex logistics of blood banking, the risk of virally transmitted diseases, current transfusion practices, and the projected increased demand for blood products in the future. The effort to develop a replacement for the red cell component has evolved over the last century and has presented a number of significant challenges including safety and efficacy concerns. Recent progress in understanding the fundamental interactions of hemoglobin with the body at the molecular, cellular and tissue levels has led to the production of improved red cell substitutes suitable for clinical testing. Currently, seven products are being tested for a variety of applications including trauma, surgery, sepsis, cancer and anemia. Although some of these trials were unsuccessful, the majority of the available products exert no toxicity or only low level side effects. Encouraging results in early clinical trials with oxygen-carrying fluids support further development of these products and have increased the hope that a usable oxygen-carrying fluid will soon be available in the clinic. The purpose of this review is to provide up-to-date information on the status of these products with special emphasis on pre-clinical and clinical experience.


Asunto(s)
Hemoglobinas/fisiología , Sustitutos del Plasma , Animales , Ensayos Clínicos como Asunto , Semivida , Humanos , Liposomas , Sustitutos del Plasma/efectos adversos , Sustitutos del Plasma/economía , Sustitutos del Plasma/farmacocinética , Sustitutos del Plasma/uso terapéutico
5.
Circ Res ; 88(10): 1066-71, 2001 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-11375277

RESUMEN

Deamination of adenosine on pre-mRNA to inosine is a recently discovered process of posttranscription modification of pre-mRNA, termed A-to-I RNA editing, which results in the production of proteins not inherent in the genome. The present study aimed to identify a role for A-to-I RNA editing in the development of microvascular lung injury. To that end, the pulmonary expression and activity of the RNA editase ADAR1 were evaluated in a mouse model of endotoxin (15 mg/kg IP)-induced microvascular lung injury (n=5) as well as in cultured alveolar macrophages stimulated with endotoxin, live bacteria, or interferon. ADAR1 expression and activity were identified in sham lungs that were upregulated in lungs from endotoxin-treated mice (at 2 hours). Expression was localized to polymorphonuclear and monocytic cells. These events preceded the development of pulmonary edema and leukocyte accumulation in lung tissue and followed the local production of interferon-gamma, a known inducer of ADAR1 in other cell systems. ADAR1 was found to be upregulated in alveolar macrophages (MH-S cells) stimulated with endotoxin (1 to 100 microg/mL), live Escherichia coli (5x10(7) colony-forming units), or interferon-gamma (1000 U/mL). Taken together, these data suggest that ADAR1 may play a role in the pathogenesis of microvascular lung injury possibly through induction by interferon.


Asunto(s)
Adenosina Desaminasa/metabolismo , Pulmón/metabolismo , Síndrome de Dificultad Respiratoria/metabolismo , Adenosina/metabolismo , Adenosina Desaminasa/genética , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Endotoxinas , Escherichia coli/inmunología , Hibridación in Situ , Inosina/biosíntesis , Interferón gamma/farmacología , Leucocitos/patología , Pulmón/irrigación sanguínea , Pulmón/patología , Macrófagos Alveolares/citología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/fisiología , Ratones , Ratones Endogámicos C57BL , Microcirculación/efectos de los fármacos , Microcirculación/metabolismo , Microcirculación/patología , Circulación Pulmonar/efectos de los fármacos , Edema Pulmonar/inducido químicamente , Edema Pulmonar/patología , Edición de ARN/fisiología , ARN Mensajero/metabolismo , Proteínas de Unión al ARN , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/patología , Regulación hacia Arriba/efectos de los fármacos
6.
J Trauma ; 50(4): 674-7, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11303163

RESUMEN

BACKGROUND: Recurrent pneumothorax is the most significant complication after discontinuation of thoracostomy tubes. The primary objective of the present study was to determine which method of tube removal, at the end of inspiration or at the end of expiration, is associated with a lesser risk of developing a recurrent pneumothorax. A secondary objective was to identify potential risk factors for developing recurrence. METHODS: A prospective study of 102 chest tubes in 69 trauma patients (1.5 tubes per patient) randomly assigned to removal at the end of inspiration (n = 52) or the end of expiration (n = 50). RESULTS: Recurrent pneumothorax or enlargement of a small but stable pneumothorax was observed after the removal of four chest tubes in the end-inspiration group (8%) and after discontinuation of three chest tubes (6%) in the end-expiration group (p = 1.0). Of those, only two tubes in the end-inspiration group and 1 tube in the end-expiration group required repeat closed thoracostomy. Multiple factors were analyzed that did not adversely affect outcome. These included patient age, Injury Severity Score, Revised Trauma Score, mechanism of injury, hemothorax, thoracotomy, thoracostomy, previous lung disease, chest tube duration, the presence of more than one thoracostomy tube in the same hemithorax, or a small (but stable) pneumothorax at the time of tube removal. CONCLUSIONS: Discontinuation of chest tubes at the end of inspiration or at the end of expiration has a similar rate of post-removal pneumothorax. Both methods are equally safe.


Asunto(s)
Tubos Torácicos/efectos adversos , Neumotórax/etiología , Neumotórax/terapia , Mecánica Respiratoria , Toracostomía/instrumentación , Toracostomía/métodos , Toracotomía/instrumentación , Toracotomía/métodos , Adolescente , Adulto , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Respiración Artificial , Factores de Riesgo , Traumatismos Torácicos/clasificación , Traumatismos Torácicos/complicaciones , Factores de Tiempo , Índices de Gravedad del Trauma
7.
Ann Pharmacother ; 35(1): 41-4, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11197584

RESUMEN

OBJECTIVE: To report a case of trovafloxacin-associated leukopenia, which occurred in a trauma patient shortly after administration and resolved following discontinuation of the drug. CASE SUMMARY: A 79-year-old white man was admitted to Yale New Haven Hospital after sustaining partial amputation of his right lower leg by an industrial lawn mower. After successful resuscitation, he underwent complete right lower amputation and was treated with intravenous alatrofloxacin mesylate. He developed leukopenia that resolved after discontinuation of the drug. DISCUSSION: Trovafloxacin is a broad-spectrum synthetic fluoroquinolone used for a wide variety of bacterial infections. We report, for the first time in the English-language literature, a case of trovafloxacin-associated leukopenia. The leukopenia resolved promptly after discontinuation of the drug. This association is further supported by the exclusion of other potential causes for this adverse effect. CONCLUSIONS: Leukopenia is a well-recognized adverse effect of several drugs. We report a case of trovafloxacin-associated leukopenia during treatment of a trauma patient. Healthcare personnel should be aware of this possible adverse reaction in patients treated with trovafloxacin.


Asunto(s)
Antiinfecciosos/efectos adversos , Fluoroquinolonas , Leucopenia/inducido químicamente , Naftiridinas/efectos adversos , Anciano , Humanos , Recuento de Leucocitos , Leucopenia/sangre , Masculino
8.
Crit Care Med ; 28(6): 1924-30, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10890643

RESUMEN

OBJECTIVE: To test the hypothesis that liposome encapsulated hemoglobin (LEH), an experimental oxygen-carrying fluid, exacerbates endotoxin-induced lung injury in the rat. DESIGN: Prospective, randomized animal study. SETTING: University animal laboratory. METHODS: Anesthetized Sprague-Dawley rats (n = 8-13) were infused with LEH (10% of estimated total blood volume) or vehicle (0.9% NaCl). Thirty minutes later, Escherichia coli endotoxin (3.6 mg/kg, i.v.) or vehicle (0.9% NaCl) was administered, and skeletal muscle oxygen tension as well as lung injury were assessed at 2, 4, and 8 hrs. Oxygen tension was measured using a miniaturized thin film oxygen sensor placed in the rectus abdominis muscle, and lung injury was evaluated by determining lung weights, lung myeloperoxidase activity, lung tissue tumor necrosis factor-alpha level, and protein concentration in bronchoalveolar lavage fluid. RESULTS: The intravenous bolus injection of E. coli endotoxin elevated lung water content (33% +/- 5%; p < .01 vs. sham controls), myeloperoxidase activity (56% +/- 6%; p < .01), and tumor necrosis factor-alpha production (1320 +/- 154 pg/g lung tissue; p < .05 vs. undetected levels in sham controls), as well as induced protein accumulation in bronchoalveolar lavage fluid (258% +/- 38%; p < .01) and skeletal muscle hypoxia (52 +/- 8 mm Hg; p < .05). Pretreatment with LEH, which when infused alone did not induce lung injury, had no effect on these responses. CONCLUSION: In this specific model of endotoxin-induced lung injury, LEH does not exacerbate microvascular leakage and leukosequestration, the hallmarks of adult respiratory distress syndrome.


Asunto(s)
Hemoglobinas/administración & dosificación , Síndrome de Dificultad Respiratoria/etiología , Sepsis/complicaciones , Animales , Líquido del Lavado Bronquioalveolar , Edema , Endotoxinas , Liposomas , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
9.
Crit Care Med ; 28(6): 1947-52, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10890646

RESUMEN

OBJECTIVE: To develop an improved small animal experimental paradigm that more closely mimics human sepsis. DESIGN: Prospective, randomized, controlled animal study. SETTING: Medical school research laboratory. SUBJECTS: Male Sprague-Dawley rats (280-320 g). INTERVENTIONS: We monitored the hemodynamic, hematologic, and biochemical consequences of abdominal sepsis produced by intraperitoneal implantation of a fibrin clot containing Escherichia coli in conscious, antibiotic-treated, rats. MEASUREMENTS AND MAIN RESULTS: Similar to human sepsis, the implanted, infected clot (LD50 = 5-7 x 10(8) colony forming units/mL, n = 6) elevated cardiac index (>7% vs. sterile clot, p < .05, at 4 hrs), whereas mean arterial pressure and heart rate remained unaffected. The total peripheral resistance index and stroke volume index tended to decrease and increase, respectively. In contrast, an intravenous bolus injection of endotoxin (LD50 of E. coli lipopolysaccharide = 5.6 mg/kg, n = 7), the most commonly used sepsis model, induced profound hypodynamic responses manifested by a 27% decrease (vs. endotoxin vehicle, p < .01) in cardiac index, a 28% increase in the total peripheral resistance index (p < .01), and a 33% decrease in the stroke volume index (P < .01). The infectious peritonitis model also displayed dose-dependent thrombocytopenia (<61%, p < .05), leukopenia (<60%, p < .05), and mortality rate (50% at 5-7 x 10(8) colony forming units/mL, p < .05) with a minimally elevated serum tumor necrosis factor-alpha level (145 vs. 12 +/- 6 pg/mL in controls, p < .05). CONCLUSION: This rodent model of antibiotic-treated, intra-abdominal infection features key characteristics of clinical sepsis. Although the hyperdynamic response observed in septic patients undergoing resuscitation was not clearly elicited, this paradigm better mimics clinical sepsis compared with the commonly used endotoxin model. Thus, utilization of this paradigm may provide additional opportunities to explore mechanisms of sepsis and to examine novel therapeutics.


Asunto(s)
Modelos Animales de Enfermedad , Sepsis/complicaciones , Sepsis/fisiopatología , Animales , Estado de Conciencia , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
10.
Am J Med Qual ; 15(1): 9-15, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10680220

RESUMEN

Because trauma admission and hospitalization patterns have profound effects on the organization and utilization of urban trauma-care systems, the objective of this study was to identify and analyze these patterns. As an example, admissions to an urban Level I trauma center were reviewed. Retrospective review of all 2029 trauma admissions to a Level I trauma center was conducted from 1993 to 1996. The result was that most trauma patients were young (40% < 30 years of age) and male (74%). Mechanisms of injury were motor vehicle accident (36%), fall (27%), gunshot (17%), stab (7%), assault (6%), and swimming or diving accident (3%). Half of the patients were directly admitted from the scene. Injury Severity Score, length of stay, and mortality were 14.1 +/- 0.3, 10.5 +/- 0.3 days, and 5.1%, respectively. Admissions tended to occur more frequently between 4:00 PM and midnight (46%), between Friday and Sunday (52%), and between July and October (41%). The following patterns were identified: admissions per year decreased (-21%) because of reduced penetrating trauma (-43%, P < .01); pediatric patients (< 15 years) had similar incidence of penetrating trauma as adults (ages 15-45). Length of stay for all mechanisms of injury was not statistically different; most mortalities occurred within the first day (33%, P < .01) or after 6 days (36%, P < .01); early mortality was mainly due to penetrating injury (74%, P < .01), whereas late mortality was related to blunt trauma (92%, P < .01). The conclusion was that admission and demographic patterns were identified, which may be useful in the utilization, modification, and future design of trauma systems.


Asunto(s)
Admisión del Paciente/estadística & datos numéricos , Centros Traumatológicos/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Interpretación Estadística de Datos , Femenino , Hospitales Universitarios , Hospitales Urbanos , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Masculino , Persona de Mediana Edad , Philadelphia/epidemiología , Estudios Retrospectivos , Estaciones del Año , Factores Sexuales , Factores de Tiempo , Heridas y Lesiones/mortalidad , Heridas y Lesiones/terapia , Heridas no Penetrantes/epidemiología , Heridas Penetrantes/epidemiología
12.
Injury ; 30(7): 471-4, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10707214

RESUMEN

BACKGROUND: Specific analysis of the relationship between abdominal injuries and lumbar spine fractures has not yet been reported. METHODS: A retrospective review of 258 blunt trauma patients with lumbar spine fractures treated between 1991 and 1996. RESULTS: 26 patients sustained concomitant lumbar spine fractures and abdominal injuries. The mechanism of injury was motor vehicle collision (73%), pedestrian-struck (11%), fall (8%) and assault (8%) resulting in ISS, RTS and mortality of 27 +/- 4, 6.5 +/- 0.4 and 8%, respectively. Forty-four lumbar spine fractures were identified (1.7/pt) in association with splenic (54%), renal (41%), hepatic (32%) and small bowel (23%) injuries and no retroperitoneal involvement. Multilevel lumbar spine fractures were associated with a higher organ injury/fracture ratio compared with single level fractures (p < 0.01) including a twofold higher incidence of solid organ (spleen, liver and kidney) injury (p < 0.01). The level and type of fracture did not affect the incidence of total and individual organ injury. Patients with abdominal injuries were more severely injured mainly due to increased incidence of associated thoracic injuries although no significant difference in mortality was observed. CONCLUSION: Abdominal injuries occurred only in the minority of blunt trauma patients with lumbar spine fractures. These injuries, which followed a similar distribution pattern as in blunt trauma in general, occurred most commonly due to motor vehicle collisions and in association with multilevel vertebral fractures. No correlation with fracture type or level was identified.


Asunto(s)
Traumatismos Abdominales/epidemiología , Vértebras Lumbares/lesiones , Traumatismo Múltiple/epidemiología , Traumatismos de la Médula Espinal/epidemiología , Fracturas de la Columna Vertebral/epidemiología , Adulto , Femenino , Humanos , Masculino , Philadelphia/epidemiología , Estudios Retrospectivos , Heridas no Penetrantes
13.
Shock ; 9(6): 428-33, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9645495

RESUMEN

Liposome-encapsulated hemoglobin (LEH) is an experimental oxygen-carrying resuscitation fluid. Because LEH is cleared from the circulation primarily by the reticuloendothelial system, its effect on the development of sepsis remains a major concern. Thus, the present study aimed to evaluate whether LEH modifies consequences of endotoxemia in the conscious normovolemic rat. LEH infusion at 10% of estimated blood volume (n = 10) did not affect mortality (30%, p < .05) and serum tumor necrosis factor-alpha levels (6204 +/- 414, p < .05) induced by 3.6 mg/kg Escherichia coli endotoxin administered (intravenous bolus) 22 h later. In contrast, when a shorter LEH-endotoxin time interval (<12 h, n = 10) or a higher dose of endotoxin (14.4 mg/kg, n = 20) was tested, LEH enhanced endotoxin-induced mortality (90% and 100%, respectively, p < .05) and broadened serum tumor necrosis factor-alpha response without modifying its peak levels. LEH (n = 20) did not exacerbate the endotoxin-induced tachycardia, leukopenia, and thrombocytopenia. Therefore, in this model, the effect of LEH on endotoxin-induced responses was dependent on the time interval between LEH and endotoxin administration as well as the endotoxin dose. The clinical relevance of these results should be further investigated.


Asunto(s)
Sustitutos Sanguíneos/administración & dosificación , Sustitutos Sanguíneos/uso terapéutico , Hemoglobinas/administración & dosificación , Hemoglobinas/uso terapéutico , Choque Séptico/tratamiento farmacológico , Animales , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Frecuencia Cardíaca , Lipopolisacáridos , Liposomas , Masculino , Ratas , Ratas Sprague-Dawley , Choque Séptico/sangre , Tromboxano B2/sangre , Factor de Necrosis Tumoral alfa/metabolismo
15.
Surgery ; 122(2): 303-12, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9288136

RESUMEN

BACKGROUND: Using differential display reverse transcriptase-polymerase chain reaction we have recently identified mob-1, the novel rat homologue of the human alpha-chemokine IP-10, as a highly inducible gene in adult respiratory distress syndrome (ARDS) lungs. The present study aimed to further implicate mob-1 in the pathogenesis of ARDS. METHODS: Pulmonary mob-1 mRNA up-regulation was confirmed by Northern blot analysis in three different rat models of ARDS-like lung injury and localized to pulmonary macrophages by using in situ hybridization. Also, Escherichia coli-derived recombinant mob-1 (rmob-1) was tested for its properties in relationship to lung injury. RESULTS: In vivo, intratracheal injection of rmob-1 (50 micrograms/rat) induced pulmonary leukosequestration (myeloperoxidase +93% +/- 8% versus control, p < 0.05) with preferential accumulation of neutrophils in bronchoalveolar lavage fluid (36.0% +/- 1.0% versus 0.1% +/- 0.1% in controls, p < 0.01). In vitro, transwell migration studies demonstrated chemotactic activity of rmob-1 (50 to 100 ng/ml) toward human monocytes (+151% +/- 34% versus rmob-1 vehicle, p < 0.01) and only weak chemotaxis for human neutrophils (+15% +/- 0% versus rmob-1 vehicle, p < 0.01). Utilizing a rat aortic ring model ex vivo, rmob-1 at 100 ng/ml exerted a very potent inhibitory effect on angiogenesis (-78.7% +/- 6.3% versus rmob-1 vehicle, p < 0.01), a major component of the resolution phase of ARDS. CONCLUSIONS: Taken together, these data support the involvement of mob-1 in the pathogenic mechanisms of ARDS possibly through chemotaclic actions on inflammatory cells and modulation of angiogenesis in the recovery phase of the disease.


Asunto(s)
Quimiocinas CXC , Quimiocinas/biosíntesis , Citocinas/biosíntesis , Pulmón/inmunología , Síndrome de Dificultad Respiratoria/inmunología , Transcripción Genética , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiología , Secuencia de Bases , Líquido del Lavado Bronquioalveolar/citología , Quimiocina CXCL10 , Quimiotaxis de Leucocito/efectos de los fármacos , Quimiotaxis de Leucocito/fisiología , Clonación Molecular , Citocinas/toxicidad , Cartilla de ADN , Modelos Animales de Enfermedad , Escherichia coli , Factor 2 de Crecimiento de Fibroblastos/farmacología , Humanos , Técnicas In Vitro , Pulmón/patología , Datos de Secuencia Molecular , Monocitos/efectos de los fármacos , Monocitos/fisiología , Neovascularización Fisiológica/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/fisiología , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/biosíntesis , Ratas , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/toxicidad , Síndrome de Dificultad Respiratoria/patología
17.
Shock ; 7(6): 391-404, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9185238

RESUMEN

Despite considerable progress in understanding the pathogenic mechanisms of Gram-negative sepsis, the outcome of septic patients has not significantly improved. There are ample data that support a role for inflammatory mediators in sepsis that act in synergy with infectious agents to initiate and propagate the disease process. One such mediator is the glycerophospholipid platelet-activating factor (PAF). The objective of the present review is to summarize experimental and clinical evidence implicating PAF as a mediator in the pathomechanism of sepsis. This review is timely because many potent and selective PAF antagonists have matured for clinical development and a careful analysis of the data that support or refute the merit of clinical trials with such compounds may be important for both academic and pharmaceutical applications.


Asunto(s)
Factor de Activación Plaquetaria/fisiología , Sepsis/metabolismo , Animales , Infecciones por Bacterias Gramnegativas/metabolismo , Humanos
18.
Lipids ; 32(4): 377-81, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9113625

RESUMEN

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol measurements. In vivo, the intravenous infusion of LEH (5.6 mL/kg, n = 6) elevated serum triglycerides (+92% vs. baseline, P < .05), total cholesterol (+25% vs. baseline, P < .01), LDL cholesterol (+72% vs. baseline, P < .01) and had no effect on serum HDL cholesterol. In addition, LEH did not alter the elevation in serum triglycerides (+302% vs. baseline, P < .01) and LDL cholesterol (+86% vs. baseline, P < .01) induced by lipopolysaccharide (3.6 mg/kg, i.v., n = 6. Ex vivo, measurements of triglycerides and total cholesterol as well as LDL and HDL cholesterol in whole blood from naive rats were not changed by the addition of LEH (0-50%, n = 6). In vitro, the addition of a fixed concentration of LEH (50%, n = 6) to varying concentrations of cholesterol solution (0-50%), or vice versa, had no effect on cholesterol determination. It is therefore concluded that LEH only minimally affects serum levels of triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and does not interfere with their measurement.


Asunto(s)
Sustitutos Sanguíneos/farmacología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Colesterol/sangre , Hemoglobinas/farmacología , Liposomas , Triglicéridos/sangre , Animales , Sustitutos Sanguíneos/administración & dosificación , Hemoglobinas/administración & dosificación , Técnicas In Vitro , Infusiones Intravenosas , Lipopolisacáridos/farmacología , Masculino , Ratas , Ratas Sprague-Dawley
19.
Ann Thorac Surg ; 63(4): 1200-4, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9124944

RESUMEN

BACKGROUND: Candida pericarditis is a rare medical and surgical emergency which, unless treated, leads to impaired cardiac function and death. To facilitate early diagnosis, the clinical features of this condition should be identified. METHODS: Twenty-five cases of Candida pericarditis reported in the last 30 years along with 1 new case were reviewed with regard to demographics, precipitating factors, diagnosis, treatment, and outcome. RESULTS: The syndrome occurred in immunocompromised (73%), antibiotic-treated (62%), or postpericardiotomy (54%) patients. The clinical presentation was frequently subtle and nonspecific. Nevertheless, unexplained fever, an increasing cardiac shadow on chest roentgenogram, or the development of cardiac tamponade may be suggestive. Positive culture for Candida in pericardial fluid or histologic evidence of yeast forms in pericardial tissue establishes the diagnosis. A combination of pericardiocentesis followed by operative drainage and antifungal agents is the usual treatment. Untreated, Candida pericarditis is 100% lethal, whereas prompt diagnosis and treatment lead to cure (mean follow-up, 19 months). CONCLUSIONS: Fever and evolving cardiac tamponade in immunocompromised or postpericardiotomy patients may be suggestive of Candida pericarditis; the presence of organisms in pericardial fluid is diagnostic. Pericardiocentesis followed by operative drainage and antifungal agents appears to be the treatment that is most likely to be curative.


Asunto(s)
Candidiasis , Pericarditis/microbiología , Adenocarcinoma/cirugía , Candida albicans/aislamiento & purificación , Taponamiento Cardíaco/etiología , Drenaje , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Huésped Inmunocomprometido , Persona de Mediana Edad , Pericarditis/complicaciones , Pericarditis/terapia , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/terapia
20.
J Lipid Mediat Cell Signal ; 15(3): 255-84, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9041476

RESUMEN

Platelet-activating factor (PAF) is a potent phospholipid mediator released from inflammatory cells in response to diverse immunologic and non-immunologic stimuli. Animal studies have implicated PAF as a major mediator involved in coronary artery constriction, modulation of myocardial contractility and the generation of arrhythmias which may bear on cardiac disorders such as ischemia, infarction and sudden cardiac death. PAF effects are induced by direct actions of PAF on cardiac tissue to modify chronotropic and inotropic activity, or indirectly via the release of eicosanoids such as thromboxane A2 (TXA2), leukotrienes (LT) or cytokines (TNF alpha). The development of selective, high affinity PAF receptor antagonists has permitted investigations on the role of PAF in experimental animal models of cardiac injury. In vivo and in vitro studies strongly suggest that PAF receptor antagonists might convey therapeutic benefits in ischemic conditions and certain arrhythmias. In addition, PAF antagonists might have a cardiac allograft-preservation effect. Although clinical studies with PAF receptor antagonists in patients with cardiac diseases have not yet been reported, the experimental results to date suggest that PAF receptor antagonists might be useful in some specific cardiac disorders in humans.


Asunto(s)
Cardiopatías/tratamiento farmacológico , Factor de Activación Plaquetaria/metabolismo , Glicoproteínas de Membrana Plaquetaria/antagonistas & inhibidores , Receptores de Superficie Celular , Receptores Acoplados a Proteínas G , Animales , Células Cultivadas , Vasos Coronarios/efectos de los fármacos , Corazón/efectos de los fármacos , Cardiopatías/metabolismo , Trasplante de Corazón , Humanos , Estructura Molecular , Contracción Miocárdica/efectos de los fármacos , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Factor de Activación Plaquetaria/antagonistas & inhibidores , Factor de Activación Plaquetaria/biosíntesis , Factor de Activación Plaquetaria/farmacología
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