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1.
Vet Pathol ; 53(2): 456-67, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26936752

RESUMEN

Inbred mice are a unique model system for studying aging because of the genetic homogeneity within inbred strains, the short life span of mice relative to humans, and the rich array of analytic tools that are available. A large-scale aging study was conducted on 28 inbred strains representing great genetic diversity to determine, via histopathology, the type and diversity of spontaneous diseases that aging mice develop. A total of 20 885 different diagnoses were made, with an average of 12 diagnoses per mouse in the study. Eighteen inbred strains have had their genomes sequenced, and many others have been partially sequenced to provide large repositories of data on genetic variation among the strains. This vast amount of genomic information can be utilized in genome-wide association studies to find candidate genes that are involved in the pathogenesis of spontaneous diseases. As an illustration, this article presents a genome-wide association study of the genetic associations of age-related intestinal amyloidosis, which implicated 3 candidate genes: translocating chain-associated membrane protein 1 (Tram1); splicing factor 3b, subunit 5 (Sf3b5); and syntaxin 11 (Stx11). Representative photomicrographs are available on the Mouse Tumor Biology Database and Pathbase to serve as a reference when evaluating inbred mice used in other genetic or experimental studies to rule out strain background lesions. Many of the age-related mouse diseases are similar, if not identical, to human diseases; therefore, the genetic discoveries have direct translational benefit.


Asunto(s)
Envejecimiento/genética , Amiloidosis/genética , Variación Genética , Estudio de Asociación del Genoma Completo/métodos , Genoma/genética , Ratones Endogámicos , Animales , Causas de Muerte , Estudios de Cohortes , Estudios Transversales , Modelos Animales de Enfermedad , Femenino , Estudios Longitudinales , Masculino , Ratones , Ratones Endogámicos/genética , Fenotipo , Análisis de Secuencia de ADN
2.
Eur J Trauma Emerg Surg ; 39(6): 561-7, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26815540

RESUMEN

Trauma surgeons frequently encounter injured limbs at risk for compartment syndrome. This article reviews data regarding the pathophysiology of compartment syndrome, factors in measuring compartment pressures, thresholds for performing fasciotomies, and outcomes from the development of compartment syndromes and performing fasciotomies.

3.
Scand J Surg ; 91(1): 67-71, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12075839

RESUMEN

Laparoscopy and thoracoscopy have been used in the evaluation of injured patients for over 30 years. Despite this long history, indications for use of these techniques remains controversial. The widespread availability of videoscopic equipment which followed the introduction of laparoscopic cholecystectomy increased interest and utilization of minimally invasive techniques in evaluation of trauma patients. Laparoscopy has been most beneficial in the evaluation of hemodynamically stable victims of stabbings and gunshots. This technique has primarily been used to detect peritoneal penetration in tangential wounds of the abdominal wall and for evaluation of the diaphragm in patients with thoracoabdominal wounds. Laparoscopic evaluation in blunt trauma patients is of unproven utility, but has been used in the assessment of patients with documented solid organ injury and in the evaluation of patients with suspected hollow viscus injury. Small subsets of patients are candidates for therapeutic laparoscopic interventions, i.e., suture repair of diaphragmatic lacerations. Thoracoscopy or videoassisted thoracic surgery (VATS) is useful for evaluation of the diaphragm, early evacuation of clotted hemothorax, and assessment of ongoing bleeding.


Asunto(s)
Servicios Médicos de Urgencia/normas , Laparoscopía/normas , Toracoscopía/normas , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/cirugía , Humanos , Laparoscopía/métodos , Selección de Paciente , Cirugía Torácica Asistida por Video , Toracoscopía/métodos
4.
South Med J ; 94(8): 825-9, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11549196

RESUMEN

Advances in technology have made it possible for telemedicine to be used in multiple areas of medicine, including trauma care. Teleradiology and teleconsultation are becoming standard operating procedure for many rural facilities. Future uses of telemedicine include teleproctoring and telepresence surgery. The medicolegal and financial impact of telemedicine remains to be determined. The potential influence of telemedicine in the care of future trauma patients will likely be important and may alter patterns of referral, consultation, and treatment.


Asunto(s)
Servicios Médicos de Urgencia/tendencias , Telemedicina , Heridas y Lesiones/terapia , Humanos , Telemedicina/economía , Telemedicina/métodos , Telemedicina/estadística & datos numéricos , Telemedicina/tendencias , Reino Unido , Estados Unidos
5.
J Immunol ; 167(1): 366-74, 2001 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-11418672

RESUMEN

The destructive pulmonary inflammation associated with Pseudomonas aeruginosa colonization is caused, in part, by the production of the chemokine IL-8, which recruits neutrophils into the lung. The Pseudomonas autoinducer, N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL), is a small lipid-soluble molecule that is essential in the regulation of many P. aeruginosa virulence factors, but little is known about how it affects eukaryotic cells. In this report we demonstrate that 3-O-C12-HSL is a potent stimulator of both IL-8 mRNA and protein from human fibroblasts and epithelial cells in vitro. The IL-8 produced from these 3-O-C12-HSL-stimulated cells was found to be functionally active by inducing the chemotaxis of neutrophils. To determine a mechanism for this IL-8 induction, deletion constructs of the IL-8 promoter were examined. It was found that the DNA region between nucleotides -1481 and -546 and the transcription factor NF-kappaB were essential for the maximal induction of IL-8 by 3-O-C12-HSL. This was confirmed by EMSAs, where 3-O-C12-HSL induced a shift with both AP-2 and NF-kappaB consensus DNA. The activation of NF-kappaB and subsequent production of IL-8 were found to be regulated by a mitogen-activated protein kinase pathway. These findings support the concept that the severe lung damage that accompanies P. aeruginosa infections is caused by an exuberant neutrophil response stimulated by 3-O-C12-HSL-induced IL-8. Understanding the mechanisms of 3-O-C12-HSL activation of lung structural cells may provide a means to help control lung damage during infections with P. aeruginosa.


Asunto(s)
4-Butirolactona/fisiología , Proteínas de Unión al ADN/fisiología , Células Epiteliales/metabolismo , Fibroblastos/metabolismo , Homoserina/fisiología , Interleucina-8/biosíntesis , Pulmón/metabolismo , FN-kappa B/fisiología , Pseudomonas aeruginosa/fisiología , Factores de Transcripción/fisiología , Transcripción Genética , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , Regiones no Traducidas 5'/fisiología , Línea Celular , Sistema Libre de Células/fisiología , Células Cultivadas , Quimiotaxis de Leucocito/inmunología , Proteínas de Unión al ADN/biosíntesis , Electroforesis en Gel de Poliacrilamida , Activación Enzimática/efectos de los fármacos , Activación Enzimática/inmunología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Fibroblastos/efectos de los fármacos , Fibroblastos/inmunología , Homoserina/análogos & derivados , Homoserina/farmacología , Humanos , Interleucina-8/genética , Interleucina-8/fisiología , Pulmón/citología , Pulmón/inmunología , FN-kappa B/biosíntesis , Neutrófilos/inmunología , Regiones Promotoras Genéticas/inmunología , Pseudomonas aeruginosa/patogenicidad , Factor de Transcripción AP-1/biosíntesis , Factor de Transcripción AP-2 , Factores de Transcripción/biosíntesis , Transcripción Genética/inmunología
6.
Am Surg ; 67(3): 243-8, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11270882

RESUMEN

The causes and effects of increased intra-abdominal pressure and abdominal compartment syndrome have been well documented. However, there have been no large series to determine normal intra-abdominal pressure in hospitalized patients. The purpose of this study was to determine normal intra-abdominal pressure in randomly selected hospitalized patients and to identify factors that predict variation in normal intra-abdominal pressure. A total of 77 patients were prospectively enrolled between September 1998 and July 1999. Data obtained included patient demographics (i.e., age, gender, height, weight, and body mass index), reason for hospitalization and bladder catheterization, previous and current surgical status, comorbidities, and intra-abdominal pressures. Intra-abdominal pressure readings were obtained through an indwelling transurethral bladder (Foley) catheter. Data were analyzed by analysis of variance and multiple regression analysis. There were 36 females and 41 males with a mean age of 67.7 years. Average weight, height, and body mass index were 79.6 kg, 1.70 m, and 27.6 kg/m2, respectively. Mean intraabdominal pressure was 6.5 mm Hg (range 0.2-16.2 mm Hg). Body mass index was positively related to intra-abdominal pressure (P < 0.0004). Gender, age, and medical and surgical histories did not significantly affect intra-abdominal pressure. However, using multiple regression analysis, a relationship between intra-abdominal pressure, body mass index, and abdominal surgery was discovered. Intra-abdominal pressure is related to a patient's body mass index and influenced by recent abdominal surgery. Thus, the normal intra-abdominal pressure can be estimated in hospitalized patients by using the derived equation. Knowledge of the expected intra-abdominal pressure can then by used in recognizing when an abnormally high intra-abdominal pressure or abdominal compartment syndrome exists.


Asunto(s)
Abdomen/fisiología , Abdomen/fisiopatología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estatura , Índice de Masa Corporal , Peso Corporal , Comorbilidad , Síndromes Compartimentales/diagnóstico , Síndromes Compartimentales/etiología , Síndromes Compartimentales/fisiopatología , Femenino , Humanos , Masculino , Manometría/instrumentación , Manometría/métodos , Persona de Mediana Edad , Trastornos Nutricionales/fisiopatología , Obesidad/fisiopatología , Valor Predictivo de las Pruebas , Presión , Estudios Prospectivos , Valores de Referencia , Análisis de Regresión , Cateterismo Urinario
7.
Hum Mol Genet ; 10(5): 433-43, 2001 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-11181567

RESUMEN

Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional and/or genetic disruptions in homocysteine metabolism. The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. This variant, with mild enzymatic deficiency, is associated with an increased risk for neural tube defects and pregnancy complications and with a decreased risk for colon cancer and leukemia. Although many studies have reported that this variant is also a risk factor for vascular disease, this area of investigation is still controversial. Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications. To investigate the in vivo pathogenetic mechanisms of MTHFR deficiency, we generated mice with a knockout of MTHFR: Plasma total homocysteine levels in heterozygous and homozygous knockout mice are 1.6- and 10-fold higher than those in wild-type littermates, respectively. Both heterozygous and homozygous knockouts have either significantly decreased S-adenosylmethionine levels or significantly increased S-adenosylhomocysteine levels, or both, with global DNA hypomethylation. The heterozygous knockout mice appear normal, whereas the homozygotes are smaller and show developmental retardation with cerebellar pathology. Abnormal lipid deposition in the proximal portion of the aorta was observed in older heterozygotes and homozygotes, alluding to an atherogenic effect of hyperhomocysteinemia in these mice.


Asunto(s)
Aorta/metabolismo , Hiperhomocisteinemia/genética , Metabolismo de los Lípidos , Sistema Nervioso/patología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/fisiología , Animales , Secuencia de Bases , Metilación de ADN , Cartilla de ADN , Heterocigoto , Homocigoto , Hiperhomocisteinemia/enzimología , Hiperhomocisteinemia/patología , Metilenotetrahidrofolato Reductasa (NADPH2) , Ratones , Ratones Noqueados , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/metabolismo , Fenotipo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
Artículo en Inglés | MEDLINE | ID: mdl-11795630

RESUMEN

A variety of platelet substitutes (e.g., rehydrated, lyophilized (RL) platelets, thromboerythrocytes, plateletsomes, infusible platelet membranes, synthocytes, fibrinogen-coated microcapules) are potentially useful as hemostatic agents in transfusion medicine. However, as "foreign" particles, platelet substitutes interact to varying extents with elements of the reticulo-endothelial system for clearance, reducing hemostatic efficacy. Experiments were performed to better understand the interaction of RL platelets with elements of the innate and acquired immune systems. The infusion of heterologous RL platelets into rats resulted in rapid clearance from the free circulation with half-life values of minutes. The clearance of RL platelets was inhibited when macrophages were rendered apoptotic with gadolinium. Transmission EM analysis of splenic tissue after infusion of lyophilized cells, as well as in vitro mixing studies with splenic macrophages and RL platelets, indicated that macrophage-mediated phagocytosis mechanisms were operant in RL platelet clearance by the reticulo-endothelial system. Studies with IV IgG, as a competitive inhibitor of the macrophage Fc receptor, provides evidence that RL platelet destruction is in part mediated by platelet surface bound IgG. This hypothesis was further supported by the finding that RL platelets react with IgG class antibodies that are pre-existing in naïve animals. These studies provide a rational basis for prolonging the circulation time of RL platelets and other platelet substitutes.


Asunto(s)
Plaquetas/citología , Conservación de la Sangre/métodos , Transfusión de Plaquetas , Bazo/citología , Animales , Plaquetas/inmunología , Liofilización , Inmunoglobulina G/análisis , Inmunoglobulinas Intravenosas , Macrófagos/inmunología , Fagocitosis , Ratas , Ratas Sprague-Dawley , Bazo/inmunología
9.
Blood ; 96(13): 4227-35, 2000 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-11110696

RESUMEN

Defects in a triad of organelles (melanosomes, platelet granules, and lysosomes) result in albinism, prolonged bleeding, and lysosome abnormalities in Hermansky-Pudlak syndrome (HPS). Defects in HPS1, a protein of unknown function, and in components of the AP-3 complex cause some, but not all, cases of HPS in humans. There have been 15 inherited models of HPS described in the mouse, underscoring its marked genetic heterogeneity. Here we characterize a new spontaneous mutation in the mouse, cappuccino (cno), that maps to mouse chromosome 5 in a region conserved with human 4p15-p16. Melanosomes of cno/cno mice are immature and dramatically decreased in number in the eye and skin, resulting in severe oculocutaneous albinism. Platelet dense body contents (adenosine triphosphate, serotonin) are markedly deficient, leading to defective aggregation and prolonged bleeding. Lysosomal enzyme concentrations are significantly elevated in the kidney and liver. Genetic, immunofluorescence microscopy, and lysosomal protein trafficking studies indicate that the AP-3 complex is intact in cno/cno mice. It was concluded that the cappuccino gene encodes a product involved in an AP-3-independent mechanism critical to the biogenesis of lysosome-related organelles. (Blood. 2000;96:4227-4235)


Asunto(s)
Modelos Animales de Enfermedad , Síndrome de Hermanski-Pudlak/genética , Proteínas de la Membrana/genética , Ratones Mutantes/genética , Proteínas de Ensamble de Clatrina Monoméricas , Subunidades alfa de Complejo de Proteína Adaptadora , Proteínas Adaptadoras del Transporte Vesicular , Adenosina Difosfato/sangre , Animales , Plaquetas/química , Plaquetas/patología , Mapeo Cromosómico , Ojo/patología , Genes , Genes Recesivos , Heterogeneidad Genética , Color del Cabello/genética , Síndrome de Hermanski-Pudlak/epidemiología , Síndrome de Hermanski-Pudlak/patología , Humanos , Riñón/enzimología , Riñón/ultraestructura , Lipofuscina/metabolismo , Hígado/enzimología , Hígado/ultraestructura , Lisosomas/enzimología , Melanosomas/patología , Ratones , Ratones Endogámicos C3H , Modelos Animales , Fenotipo , Puerto Rico/epidemiología , Serotonina/sangre , Piel/patología , Especificidad de la Especie
10.
Int J Radiat Oncol Biol Phys ; 48(3): 767-78, 2000 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-11020574

RESUMEN

PURPOSE: To evaluate the treatment outcomes in patients with optimally debulked Stage III and IV endometrial adenocarcinoma (ACA) or Stages I-IV uterine papillary serous (UPSC) or clear cell (CCC) carcinoma of the uterus, treated postoperatively with whole abdominopelvic irradiation (WAPI). METHODS AND MATERIALS: Between 1979 and 1998, 48 patients received postoperative WAPI at our institution. Twenty-two patients had FIGO Stage III or Stage IV ACA and 26 patients had FIGO Stages I-IV UPSC or CCC. The median dose was 30 Gy to the upper abdomen and 49.8 Gy to the pelvis. Mean follow-up was 37 months (2.4-135 months). RESULTS: The 3-year estimated disease-free survival (DFS) and overall survival (OS) rates for the entire group were 60% and 77%, respectively. Patients with ACA had 3-year DFS and OS of 79% and 89%, respectively, compared with 47% and 68% in the UPSC/CCC group. Early-stage patients (I and II) with UPSC/CCC had 3-year DFS and OS of 87% compared with 32% and 61% in those with advanced (Stage III and IV) disease. The 3-year actuarial major complication rate was 7%, with no treatment-related deaths. All 4 failures in the ACA group were extra-abdominal and 6 of the 11 in the UPSC/CCC group had an extra-abdominal component. Age and UPSC/CCC histology were significant prognostic factors for DFS and OS. In addition, stage and number of extrauterine sites of disease were significant predictors for DFS in UPSC/CCC. CONCLUSION: WAPI is a safe, effective treatment for patients with optimally debulked advanced-stage uterine ACA or early-stage UPSC/CCC. Survival was significantly worse in advanced-stage UPSC/CCC patients. We recommend future trials of WAPI with concurrent, or subsequent systemic therapy in patients with advanced-stage UPSC or CCC.


Asunto(s)
Neoplasias Endometriales/radioterapia , Neoplasias Uterinas/radioterapia , Abdomen , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/radioterapia , Análisis de Varianza , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/radioterapia , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Irradiación de Hemicuerpo/métodos , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pelvis , Dosificación Radioterapéutica , Insuficiencia del Tratamiento , Neoplasias Uterinas/patología
11.
J Trauma ; 48(6): 1015-22; discussion 1023-4, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10866245

RESUMEN

BACKGROUND: The Emergency Nurses Association (ENA) has formally resolved that family presence (FP) during resuscitation and invasive procedures (TR) is the right of the patient and is beneficial for both patients and family members. Furthermore, FP during TR has been implemented at several trauma centers. Because this policy is controversial, a survey was conducted to assess the opinions of members of the American Association for the Surgery of Trauma (AAST) and ENA in regard to FP. METHODS: A survey instrument regarding FP during TR was mailed to the AAST membership (n = 813) and a random sampling (10%) of ENA members (n = 2,988). Questions regarding membership (AAST vs. ENA), age, gender, years in practice, trauma experience, the patient's right to FP during the primary survey, secondary survey, and invasive procedures, the potential effects of FP on trauma team function, and medicolegal implications were included in the survey. Qualitative and quantitative variables were analyzed by analysis of variance and chi2 analysis, respectively. Responses to questions by using a Likert Scale for degree of agreement were analyzed by using the Kruskal-Wallis test. RESULTS: A total of 1,629 (AAST, n = 368; ENA, n = 1,261) surveys were returned (43.4% response). There were 44 surveys returned as undeliverable (1.2%). The members of the AAST were older, more likely to be male, had been in practice longer, and had greater trauma experience when compared with ENA members (p < 0.001). More AAST than ENA members (97.8% vs. 80.2%) believed that FP during all phases of TR was inappropriate (p < 0.001). Fewer AAST members believed that FP was a patient right when compared with ENA members (p < 0.0001). The AAST members were more likely to believe FP interfered with patient care and increased the stress of trauma team members (p < 0.0001). The majority of AAST and ENA members had experience with FP during TR (55.3 vs. 67.8%; p < 0.001). However, the impressions of their experiences were widely disparate, with 63.6% of ENA and only 17.5% of AAST members, indicating that the experience was beneficial (p < 0.001). CONCLUSION: Attitudes toward FP during TR are significantly different between AAST and ENA members. Because of these differences in opinion, implementation of an FP policy may create conflicts between trauma team members and may interfere with the effectiveness of the trauma team.


Asunto(s)
Actitud del Personal de Salud , Medicina de Emergencia/estadística & datos numéricos , Enfermería de Urgencia/estadística & datos numéricos , Familia , Resucitación , Heridas y Lesiones/terapia , Adulto , Análisis de Varianza , Distribución de Chi-Cuadrado , Recolección de Datos , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sociedades Médicas , Sociedades de Enfermería , Encuestas y Cuestionarios , Estados Unidos
12.
Arch Surg ; 135(6): 682-6; discussion 686-7, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10843364

RESUMEN

HYPOTHESIS: Ogilvie syndrome is a postoperative complication. DESIGN: Case series. SETTING: University-affiliated tertiary-care hospital. PATIENTS AND METHODS: The medical records of patients diagnosed as having Ogilvie syndrome after trauma or operation between 1989 and 1998 were reviewed. Medical charts were examined for history, treatment, cecal diameter, and outcome. MAIN OUTCOME MEASURES: Data were summarized in an attempt to identify patient populations at risk for Ogilvie syndrome. RESULTS: Ogilvie syndrome was diagnosed in 36 patients, 24 of whom were men. Average age at diagnosis was 68.9 years. Abdominal radiographs were obtained at time of diagnosis (mean cecal diameter, 13.4 cm; range, 8-20 cm). Operations preceding Ogilvie syndrome were orthopedic or spinal (n= 14), cardiothoracic (n= 12), abdominal (n= 5), and vascular (n= 2). Nonoperative trauma accounted for 3 cases. Coronary artery bypass grafting was the single most frequent procedure leading to Ogilvie syndrome (n=9 [25%]). Conservative treatment was successful in 52.8% of cases (n = 19). Twenty colonoscopic decompressions were performed on 13 patients, with an overall success rate of 77% (n= 10). Of the 3 patients in whom colonoscopic decompression failed, 2 died and 1 required operation. Five of the 36 patients required surgical intervention, with a mortality rate of 60% (n= 3). CONCLUSIONS: Previous studies have shown Ogilvie syndrome to occur most commonly after obstetrical/ gynecologic, abdominal/pelvic, and orthopedic procedures. Our data confirm that patients undergoing orthopedic and spinal procedures are at higher risk, but that the surgical procedure most commonly leading to Ogilvie syndrome was coronary artery bypass grafting. Cardiothoracic surgeons, orthopedic surgeons, and neurosurgeons should be cognizant of this complication in the patient whose abdomen becomes distended postoperatively. If recognized early and treated appropriately, pseudo-obstruction will resolve in most patients. If surgical intervention is required, the subsequent mortality rate is high.


Asunto(s)
Seudoobstrucción Colónica , Complicaciones Posoperatorias , Anciano , Seudoobstrucción Colónica/diagnóstico por imagen , Seudoobstrucción Colónica/fisiopatología , Seudoobstrucción Colónica/terapia , Colonoscopía , Descompresión Quirúrgica , Femenino , Humanos , Masculino , Registros Médicos/estadística & datos numéricos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/fisiopatología , Radiografía , Estudios Retrospectivos , Factores de Riesgo
13.
Am Surg ; 65(8): 715-9, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10432079

RESUMEN

Intestinal ischemia is a common condition in critically ill patients and has been postulated to play a role in the development of organ failure and death. This has resulted in the recent interest in monitoring gastric intramucosal pH (pHi) in critically ill patients to provide earlier evidence of inadequate resuscitation, cardiogenic dysfunction, or sepsis. Several reports have indicated that low pHi values obtained during the initial 24 to 48 hours of intensive care unit (ICU) admission were associated with the development of organ failure and death. The purpose of this study was to assess the predictive value of serial pHi measurements obtained throughout the entire ICU admission. A retrospective analysis of critically ill trauma, burn, and surgical patients who had frequent pHi determinations during ICU treatment was performed. When stratified by pHi values, there were no significant differences in length of stay, organ dysfunction, or mortality. Our findings suggest that serial pHi determinations obtained beyond the early critical care period are less reliable predictors of poor outcome.


Asunto(s)
Enfermedad Crítica , Mucosa Intestinal/metabolismo , Intestinos/irrigación sanguínea , Isquemia/metabolismo , Isquemia/mortalidad , Insuficiencia Multiorgánica/etiología , Procedimientos Quirúrgicos Operativos/efectos adversos , Heridas y Lesiones/complicaciones , Adulto , Anciano , Quemaduras/complicaciones , Femenino , Humanos , Concentración de Iones de Hidrógeno , Isquemia/complicaciones , Isquemia/etiología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/metabolismo , Valor Predictivo de las Pruebas , Estudios Retrospectivos
14.
Invest Ophthalmol Vis Sci ; 40(8): 1874-8, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10393064

RESUMEN

PURPOSE: To demonstrate the importance of genetic background interaction on the development of ocular phenotypes in p53-deficient mice. METHODS: Eyes of adult mice, homozygous and heterozygous for the p53 gene disruption in the 129/SvJ and C57BL/6J (B6) genetic backgrounds, and their F1 progeny were examined by indirect ophthalmoscopy and by light microscopy. RESULTS: Indirect ophthalmoscopy revealed unilateral or bilateral vitreal opacities, fibrous retrolental tissue, and retinal folds in adult B6 mice but not in 129/Sv mice homozygous for a p53 null mutation. In B6 p53-/- mice, blood vessels extended from the peripapillary inner retina through the posterior vitreous and into the retrolental membrane. Optic nerves were hypoplastic. CONCLUSIONS: These findings indicate that alleles from the B6 background contribute to the aberrant ocular phenotypes observed in p53 deficiency. They also suggest that p53 or the pathway in which it functions may be important for normal eye development.


Asunto(s)
Anomalías Múltiples/genética , Anomalías del Ojo/genética , Genes p53/genética , Retina/anomalías , Proteína p53 Supresora de Tumor/deficiencia , Cuerpo Vítreo/anomalías , Anomalías Múltiples/patología , Animales , Catarata/genética , Catarata/patología , Cartilla de ADN/química , Anomalías del Ojo/patología , Oftalmopatías/genética , Oftalmopatías/patología , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Nervio Óptico/anomalías , Nervio Óptico/patología , Fenotipo , Retina/patología , Displasia Retiniana/genética , Displasia Retiniana/patología , Proteína p53 Supresora de Tumor/genética , Cuerpo Vítreo/patología
15.
Bioorg Med Chem Lett ; 9(7): 985-90, 1999 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-10230625

RESUMEN

The ability of the naturally occurring tumoricidal ellagitannin coriariin A to stimulate secretion of both IL-1beta and TNF-alpha from human peripheral blood mononuclear cells has been demonstrated. Companion studies with the monomeric gallotannin beta-D-pentagalloylglucose and a synthesized dimeric gallotannin-ellagitannin hybrid suggest that TNF-alpha rather than IL-1beta is the causative agent in tannin-mediated antitumor action in vivo, in contrast to an ealier proposal.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Flavonoides , Fenoles/farmacología , Plantas/química , Polímeros/farmacología , Taninos/química , Factor de Necrosis Tumoral alfa/biosíntesis , Humanos , Cinética , Estructura Molecular , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Polifenoles
16.
J Bacteriol ; 181(5): 1623-9, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10049396

RESUMEN

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important human pathogen. The production of several virulence factors by P. aeruginosa is controlled through two quorum-sensing systems, las and rhl. We have obtained evidence that both the las and rhl quorum-sensing systems are also required for type 4 pilus-dependent twitching motility and infection by the pilus-specific phage D3112cts. Mutants which lack the ability to synthesize PAI-1, PAI-2, or both autoinducers were significantly or greatly impaired in twitching motility and in susceptibility to D3112cts. Twitching motility and phage susceptibility in the autoinducer-deficient mutants were partially restored by exposure to exogenous PAI-1 and PAI-2. Both twitching motility and infection by pilus-specific phage are believed to be dependent on the extension and retraction of polar type 4 pili. Western blot analysis of whole-cell lysates and enzyme-linked immunosorbent assays of intact cells were used to measure the amounts of pilin on the cell surfaces of las and rhl mutants relative to that of the wild type. It appears that PAI-2 plays a crucial role in twitching motility and phage infection by affecting the export and assembly of surface type 4 pili. The ability of P. aeruginosa cells to adhere to human bronchial epithelial cells was also found to be dependent on the rhl quorum-sensing system. Microscopic analysis of twitching motility indicated that mutants which were unable to synthesize PAI-1 were defective in the maintenance of cellular monolayers and migrating packs of cells. Thus, PAI-1 appears to have an essential role in maintaining cell-cell spacing and associations required for effective twitching motility.


Asunto(s)
Proteínas Bacterianas/fisiología , Proteínas de Unión al ADN/fisiología , Pseudomonas aeruginosa/fisiología , Transactivadores/fisiología , Factores de Transcripción/fisiología , Adhesión Bacteriana , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/fisiología , Proteínas Bacterianas/genética , Bronquios/microbiología , Membrana Celular/fisiología , Células Cultivadas , Proteínas de Unión al ADN/genética , Células Epiteliales/microbiología , Proteínas Fimbrias , Fimbrias Bacterianas/fisiología , Humanos , Ligasas , Movimiento , Inhibidor 1 de Activador Plasminogénico/genética , Inhibidor 1 de Activador Plasminogénico/fisiología , Inhibidor 2 de Activador Plasminogénico/genética , Inhibidor 2 de Activador Plasminogénico/fisiología , Fagos Pseudomonas/fisiología , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/virología , Transducción de Señal , Transactivadores/genética , Factores de Transcripción/genética
17.
Mamm Genome ; 10(2): 102-6, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9922387

RESUMEN

A dominant induced mutation in the mouse, tightly associated with a reciprocal chromosomal translocation between Chrs 4 and 17, causes abnormal head tossing and circling behavior (the translocation induced circling mutation, Tim). Affected mice develop an unusual anterior subcapsular cataract that appears after birth and is progressive. The most likely explanation for the phenotypic observations is that the translocation breakpoint disrupted a gene or its regulation. Although the Mos protooncogene is located close to the translocation breakpoint and transgenic mice that overexpress Mos demonstrate cataracts and circling behavior, there were no gross changes in the Mos gene or in its level of expression. The morphological changes observed in the lens resemble those seen in some human congenital cataract syndromes.


Asunto(s)
Catarata/genética , Cromosomas/genética , Células Epiteliales/citología , Cristalino/metabolismo , Trisomía , Animales , Animales Recién Nacidos , Northern Blotting , Southern Blotting , División Celular , Aberraciones Cromosómicas , Trastornos de los Cromosomas , ADN/análisis , ADN/genética , Femenino , Cristalino/patología , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Endogámicos DBA
18.
Cytokine ; 10(4): 313-8, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9617578

RESUMEN

There is some evidence that, in humans and experimental animals, psychological stress may suppress or enhance immune functions, depending on the nature of the stressor and the immune variables under consideration. The possibility that psychological stress may affect the production of pro-inflammatory and immunoregulatory cytokines was investigated in 38 medical students, who had blood samplings a few weeks before and after as well as one day before an academic examination. Psychological stress significantly increased the stimulated production of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-1 receptor antagonist (IL-1Ra), interferon gamma (IFN-gamma) and IL-10. Students with high stress perception during the stressful condition had a significantly higher production of TNF-alpha, IL-6, IL-1Ra and IFN-gamma than students with a low-stress perception. Students with a high anxiety response had a significantly higher production of IFN-gamma and a lower production of the negative immunoregulatory cytokines, IL-10 and IL-4, than students without anxiety. These findings suggest that, in humans, changes in the production of the pro-inflammatory cytokines, TNF-alpha, IL-6 and IFN-gamma, and negative immunoregulatory cytokines, IL-10 and IL-4, take part in the homeostatic responses to psychological stress and that stress-induced anxiety is related to a T-helper-1-like response.


Asunto(s)
Ansiedad/sangre , Citocinas/sangre , Estrés Fisiológico/sangre , Adulto , Ansiedad/inmunología , Femenino , Humanos , Masculino , Estrés Fisiológico/inmunología , Células TH1/inmunología
19.
Arch Surg ; 133(5): 530-5; discussion 535-6, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9605916

RESUMEN

BACKGROUND: Sonography has become the primary mode for the initial evaluation of abdominal injury in many trauma centers. However, the rate at which nonradiologists become proficient in this technique remains controversial. OBJECTIVE: To assess the learning curve for this technique in a single institution. DESIGN: Retrospective review of sonographic examinations for trauma performed by senior surgical residents during a 24-month period at an American College of Surgeons-verified level I trauma center. SETTING: University-affiliated private hospital. PATIENTS AND METHODS: Before the initiation of a program of surgeon-performed trauma ultrasound, senior surgical residents (postgraduate years 4 and 5) received 11.5 hours of hands-on and didactic instruction in the focused ultrasound examination for trauma. This examination then became a standard component of the evaluation of injured patients. Subsequent groups of senior residents received 8 hours of instruction at the onset of new academic years, 6 and 18 months, respectively, after the initial course. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were then calculated for each 6-month period after the introduction of trauma sonography. RESULTS: During the 24-month study period, 902 sonographic examinations were performed. No statistically significant differences were noted in sensitivity, specificity, accuracy, positive predictive value, or negative predictive value for any 6-month period of study when compared with the other 6-month periods or with the values calculated for the entire study period. CONCLUSIONS: Senior surgical residents are capable of performing the focused ultrasound examination for trauma with a high level of skill after a concise introductory course. A learning curve was not apparent in our series. Criteria for being permitted to perform trauma sonography that include the requirement of a large number of examinations or extensive proctoring should be reassessed.


Asunto(s)
Traumatismos Abdominales/diagnóstico por imagen , Educación Médica Continua , Ultrasonografía Intervencional , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad
20.
J Trauma ; 44(4): 604-6; discussion 607-8, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9555830

RESUMEN

BACKGROUND: It has been demonstrated that surgeons and surgery residents, trained in the focused abdominal sonographic examination, are able to accurately and reliably evaluate trauma patients. Despite this, radiologists have objected to surgeon-performed sonography for several reasons. We set out to compare the accuracy of sonographic examinations performed by surgery residents and radiologists. METHODS: A retrospective review of medical records of all trauma patients who received focused ultrasound examinations from January 1, 1995, through June 30, 1996, at one of two American College of Surgeons-verified Level I trauma centers in the same city was undertaken. Ultrasound examinations were performed by surgery residents at trauma center A (TCA) and by radiologists or radiology residents at trauma center B (TCB). Findings for each patient were compared with the results of computed tomography, diagnostic peritoneal lavage, operative exploration, or observation. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for each group of patients. Comparison of patient charges for the trauma ultrasound examinations at each of the trauma centers was also made. RESULTS: Patient populations at the two centers were similar except that the mean Injury Severity Score at TCB was higher than at TCA (11.74 vs. 9.6). Sensitivity, specificity, accuracy, or negative predictive value were not significantly different between the two cohorts. A significantly lower positive predictive value for examinations performed by surgery residents was noted and attributed to a lower threshold of the surgery residents to confirm their findings by computed tomography. Billing data revealed that the average charge for trauma sonography by radiologists (TCB) was $406.30. At TCA, trauma sonography did not generate a specific charge; however, a $20.00 sum was added to the trauma activation fee to cover ultrasound machine maintenance and supplies. CONCLUSION: Focused ultrasound examination in the trauma suite can be as safely and accurately performed by surgery residents as by radiologists and radiology residents and should be a routine part of the initial trauma evaluation process.


Asunto(s)
Competencia Clínica/normas , Cirugía General/educación , Internado y Residencia/normas , Cuerpo Médico de Hospitales/normas , Traumatismo Múltiple/diagnóstico por imagen , Radiología/educación , Adolescente , Adulto , Ahorro de Costo , Femenino , Cirugía General/normas , Precios de Hospital , Humanos , Kansas , Masculino , Persona de Mediana Edad , Radiología/normas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Centros Traumatológicos , Ultrasonografía/economía , Ultrasonografía/normas
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