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1.
Children (Basel) ; 7(6)2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32492791

RESUMEN

Although gastrostomy placement is one of the most common procedures performed in children, the optimal technique remains unclear. The purpose of this study was to evaluate variability in the method of gastrostomy tube placement in children in the United States. Patients <18 years old undergoing percutaneous endoscopic gastrostomy (PEG) or surgical gastrostomy (SG) (including open or laparoscopic) from 1997 to 2012 were identified using the Kids' Inpatient Database. Method of gastrostomy placement was evaluated using a multivariable mixed-effects logistic regression model with a random intercept term and a patient-age random-effect term. A total of 67,811 gastrostomy placements were performed during the study period. PEG was used in 36.6% of entries overall and was generally consistent over time. PEG placement was less commonly performed in infants (adjusted odds ratio [aOR] 0.30, 95%CI 0.26-0.33), children at urban hospitals (aOR: 0.38, 95%CI 0.18-0.82), and children cared for at children's hospitals (aOR 0.57, 95%CI 0.48-0.69) and was more commonly performed in children with private insurance (aOR 1.17, 95%CI 1.09-1.25). Dramatic variability in PEG use was identified between centers, ranging from 0% to 100%. The random intercept and slope terms significantly improved the model, confirming significant center-level variability and increased variability among patients <1 year old. These findings emphasize the need to further evaluate the safest method of gastrostomy placement in children, in particular among the youngest patients in whom practice varies the most.

2.
J Pediatr Surg ; 55(11): 2387-2392, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32145975

RESUMEN

BACKGROUND/PURPOSE: Children with inflammatory bowel disease (IBD) have increased risk for venous thromboembolism (VTE). We sought to determine incidence and risk factors for postoperative VTE in a multicenter cohort of pediatric patients undergoing colorectal resection for IBD. METHODS: Retrospective review of children ≤18 years who underwent colorectal resection for IBD from 2010 to 2016 was performed at four children's hospitals. Primary outcome was VTE that occurred between surgery and last follow-up. Factors associated with VTE were determined using univariable and multivariable analyses. RESULTS: Two hundred seventy-six patients were included with median age 15 years [13,17]. Forty-two children (15%) received perioperative VTE chemoprophylaxis, and 88 (32%) received mechanical prophylaxis. DVT occurred in 12 patients (4.3%) at a median of 14 days postoperatively [8,147]. Most were portomesenteric (n = 9, 75%) with the remaining catheter-associated DVTs in extremities (n = 3, 25%). There was no association with chemoprophylaxis (p > 0.99). On Cox regression, emergent procedure [HR 18.8, 95%CI: 3.18-111], perioperative plasma transfusion [HR 25.1, 95%CI: 2.4-259], and postoperative infectious complication [HR 10.5, 95%CI: 2.63-41.8] remained predictive of DVT. CONCLUSION: Less than 5% of pediatric IBD patients developed postoperative VTE. Chemoprophylaxis was not protective but rarely used. Patients with risk factors identified in this study should be monitored or given prophylaxis for VTE. LEVEL OF EVIDENCE: Treatment Study, Level III.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Complicaciones Posoperatorias/epidemiología , Proctocolectomía Restauradora/efectos adversos , Tromboembolia Venosa , Adolescente , Transfusión de Componentes Sanguíneos , Niño , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/cirugía , Plasma , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
3.
Clin Perinatol ; 47(1): 183-196, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32000925

RESUMEN

Neonatal appendicitis is a rare disease with a high mortality rate. Appendicitis is difficult to diagnose in neonatal and infant populations because it mimics other more common conditions in these age groups. Furthermore, signs and symptoms of appendicitis are often nonspecific in nonverbal patients and a high index of suspicion is necessary to initiate the appropriate diagnostic work-up. The keys to successful management of appendicitis in infants include keeping the diagnosis on the differential in the setting of unexplained intra-abdominal sepsis, following a diagnostic algorithm in the work-up of infant abdominal pathology, and performing appendectomy once the diagnosis is confirmed.


Asunto(s)
Apendicitis/congénito , Apendicitis/diagnóstico , Enfermedades Raras/congénito , Enfermedades Raras/diagnóstico , Apendicectomía , Apendicitis/cirugía , Diagnóstico Diferencial , Humanos , Lactante , Recién Nacido , Perforación Intestinal/congénito , Perforación Intestinal/diagnóstico , Perforación Intestinal/cirugía , Enfermedades Raras/cirugía , Factores de Riesgo
4.
J Laparoendosc Adv Surg Tech A ; 29(10): 1311-1314, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31549898

RESUMEN

Background: Esophagojejunostomy is facilitated by use of a circular stapler, particularly when performed laparoscopically. The minimum patient size that will allow use of circular staplers in the small intestine is unknown. Materials and Methods: Retrospective review of esophagogastric dissociations performed at a single tertiary care institution for 48 months. This was combined with a geometric derivation of a size-estimation formula. Results: From the 7 cases identified, patients weighing >16 kg easily accommodated the 21 mm stapler. There was a narrow fit in the patient weighing 13.6 kg, and the 6 kg patient was too small for the stapler. Conclusions: Through a combination of clinical observation and physical reasoning, circular stapler applicability in small intestine is predicted by patient weight or intestinal measurement. Patients weighing >16 kg will accept the stapler, whereas patients <13 kg are likely too small. Alternately, on the basis of a geometric derivation, if the width of the flat intestine is >1.6 × the device diameter, the device will fit. This calculation can be applied broadly (e.g., incision length for laparoscopic ports or single-port access devices).


Asunto(s)
Anastomosis Quirúrgica/instrumentación , Esófago/cirugía , Gastrectomía/métodos , Yeyuno/cirugía , Neoplasias Gástricas/cirugía , Engrapadoras Quirúrgicas , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos , Adulto Joven
5.
J Pediatr Surg ; 54(12): 2539-2545, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31519359

RESUMEN

BACKGROUND/PURPOSE: Surgical management of appendicitis accounts for ~30% of total expenditure in the practice of pediatric surgery and is associated with high cost variation. We hypothesize that incorporating single-incision laparoscopy (SILS) and the resultant by-product dual-incision laparoscopy (DILS) into a historically three-incision laparoscopic (TILS) appendectomy practice affords equal outcomes at lower cost. METHODS: Appendectomies performed at a large-volume tertiary care children's hospital from 1/2015-12/2017 were retrospectively reviewed. Appendectomy technique and appendicitis severity were stratified against operative and admission direct variable (DV) costs. Secondary outcomes included perioperative time course and 30-day postoperative outcomes. RESULTS: A total of 970 appendectomies were analyzed during the study period (61% acute, 39% complex appendicitis). SILS and DILS had significantly lower mean DV costs and OR times compared to TILS for both acute and complex appendicitis while maintaining equivalent outcomes. CONCLUSIONS: SILS and DILS appendectomy techniques can be incorporated into pediatric surgical practice at lower cost than TILS appendectomy while maintaining equivalent outcomes. Further, the introduction of a tiered approach to laparoscopic appendectomy, in which all cases are started as SILS with additional incisions added based on operative difficulty, is estimated to save $74,580 annually in operative DV costs at a pediatric surgical center averaging 314 laparoscopic appendectomies per year. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Apendicectomía/métodos , Apendicitis/cirugía , Costos Directos de Servicios/estadística & datos numéricos , Laparoscopía/métodos , Enfermedad Aguda , Adolescente , Apendicectomía/economía , Apendicitis/economía , Niño , Preescolar , Femenino , Humanos , Lactante , Laparoscopía/economía , Masculino , Tempo Operativo , Periodo Posoperatorio , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
6.
A A Case Rep ; 9(11): 311-318, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-28719384

RESUMEN

A term infant born cyanotic failed multiple intubation attempts and tracheostomy placement. After esophageal intubation resulted in the ability to ventilate, he was presumed to have tracheal agenesis and distal bronchoesophageal fistula. He was transferred to our institution where he was diagnosed with Floyd Type II tracheal agenesis. He underwent staged tracheal reconstruction. He was discharged to home at 4 months of age with a tracheostomy collar, cervical spit fistula, and gastrostomy tube. He represents the sole survivor-to-discharge of tracheal agenesis in the United States. We describe the anesthetic considerations for a patient with tracheal agenesis undergoing reconstruction.


Asunto(s)
Anestesia/métodos , Constricción Patológica/cirugía , Procedimientos de Cirugía Plástica/métodos , Tráquea/anomalías , Tráquea/cirugía , Humanos , Recién Nacido , Intubación Intratraqueal , Masculino , Respiración con Presión Positiva , Traqueostomía
8.
Exp Lung Res ; 43(1): 38-48, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28266889

RESUMEN

Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. MATERIALS AND METHODS: Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. RESULTS: Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. CONCLUSION: Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury.


Asunto(s)
Neumonía en Organización Criptogénica/prevención & control , Lesión Pulmonar/metabolismo , Receptor de Adenosina A2B/fisiología , Transducción de Señal/fisiología , Adenosina/farmacología , Animales , Isquemia , ARN Mensajero/análisis , Ratas , Receptor de Adenosina A2A/análisis , Receptor de Adenosina A2A/genética , Receptor de Adenosina A2B/análisis , Receptor de Adenosina A2B/genética
9.
Am J Physiol Heart Circ Physiol ; 312(5): H1096-H1104, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28213406

RESUMEN

To examine the effect of endothelium-derived extracellular vesicles (eEVs) on the mediator of flow-induced dilation (FID), composition, formation, and functional effects on the mediator of FID were examined from two different eEV subtypes, one produced from ceramide, while the other was produced from plasminogen-activator inhibitor 1 (PAI-1). Using video microscopy, we measured internal-diameter changes in response to increases in flow in human adipose resistance arteries acutely exposed (30 min) to eEVs derived from cultured endothelial cells exposed to ceramide or PAI-1. FID was significantly impaired following exposure to 500K/ml (K = 1,000) of ceramide-induced eEVs (Cer-eEVs) but unaffected by 250K/ml. FID was reduced in the presence of PEG-catalase following administration of 250K/ml of Cer-eEVs and PAI-1 eEVs, whereas Nω-nitro-l-arginine methyl ester (l-NAME) had no effect. Pathway analysis following protein composition examination using liquid chromatography tandem mass spectrometry (LC-MS/MS) demonstrated that both subtypes were strongly linked to similar biological functions, primarily, mitochondrial dysfunction. Flow cytometry was used to quantify eEVs in the presence or absence of l-phenylalanine-4'-boronic acid (PBA) and mitochondria-targeted [93-boronophenyl)methyl]triphenyl-phosphonium (mito-PBA), cytosolic and mitochondrial-targeted antioxidants, respectively. eEV formation was significantly and dramatically reduced with mito-PBA treatment. In conclusion, eEVs have a biphasic effect, with higher doses impairing and lower doses shifting the mediator of FID from nitric oxide (NO) to hydrogen peroxide (H2O2). Despite differences in protein content, eEVs may alter vascular function in similar directions, regardless of the stimulus used for their formation. Furthermore, mitochondrial ROS production is required for the generation of these vesicles.NEW & NOTEWORTHY The vascular effect of endothelium-derived extracellular vesicles (eEVs) is biphasic, with higher doses decreasing the magnitude of flow-induced dilation (FID) compared with lower doses that shift the mediator of FID from nitric oxide to H2O2 eEVs may cause vascular dysfunction via similar pathways despite being formed from different stimuli, although both require mitochondrial reactive oxygen species for their formation.


Asunto(s)
Arteriolas/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Endotelio Vascular/fisiología , Vesículas Extracelulares/fisiología , Mitocondrias/fisiología , Vasodilatación/fisiología , Tejido Adiposo/irrigación sanguínea , Tejido Adiposo/fisiología , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad
10.
J Pediatr Surg ; 51(12): 1976-1982, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27678507

RESUMEN

PURPOSE: Comparative outcomes of enhanced percutaneous endoscopic gastrostomy (PEG) and laparoscopic gastrostomy (LG) have not been elucidated in infants. We describe the outcomes and procedural episodic expenditures of PEG versus LG in this high-risk population. METHODS: One hundred eighty-three gastrostomies in children under 1year were reviewed from our institution spanning 1/2011-6/2015. Pertinent demographics and 3-month complications (mortality, gastrocolic fistula, reoperation, cellulitis, granulation, pneumonia, and tube dislodgement <6weeks) were collected. Facility and professional administrative data was used to conduct a charge and cost analysis of PEG and LG procedures as well as their statistically significant complications. RESULTS: Seventy-eight PEG and 105 LG infants were compared. LG infants were significantly younger, had higher ASA class, and increased frequency of cardiopulmonary disease. Significant major complications included a 3.8% incidence of gastrocolic fistula among PEGs (3.8% vs 0%, p=0.04) and 7.6% early tube dislodgements among LG infants (0 vs. 7.6%, p=0.01), resulting in $86,896 of additional charges with PEG complication. Incorporating complication frequency, average charges and variable cost per case were $8964 and $253 greater using PEG. CONCLUSIONS: Despite a healthier cohort, infants undergoing enhanced PEG have more morbid and costly complications. LG may be the less burdensome approach to gastrostomy in infants. LEVEL OF EVIDENCE: Case-Control Study/Retrospective Comparative Study - Level III.


Asunto(s)
Gastroscopía/economía , Gastrostomía/métodos , Precios de Hospital/estadística & datos numéricos , Costos de Hospital/estadística & datos numéricos , Laparoscopía/economía , Complicaciones Posoperatorias/economía , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Gastrostomía/economía , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Complicaciones Posoperatorias/epidemiología , Reoperación/economía , Estudios Retrospectivos , Wisconsin
11.
Shock ; 46(4): 420-30, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26974426

RESUMEN

Tc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a preclinical marker of lung injury in two well-established rat models of human acute lung injury (ALI).Rats were exposed to >95% O2 (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 h later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart rates, oxygen saturation, bronchoalveolar lavage (BAL) cell counts and protein, lung homogenate glutathione (GSH) content, and pulmonary vascular endothelial filtration coefficient (Kf).For hyperoxia rats, HMPAO lung uptake increased after 24 h (134%) and 48 h (172%) of exposure. For LPS-treated rats, HMPAO lung uptake increased (188%) 24 h after injury and fell with resolution of injury. DEM reduced HMPAO uptake in hyperoxia and LPS rats by a greater fraction than in normoxia rats. Both hyperoxia exposure (18%) and LPS treatment (26%) increased lung homogenate GSH content, which correlated strongly with HMPAO uptake. Neither of the treatments had an effect on Kf at 24 h. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL, and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury.


Asunto(s)
Lesión Pulmonar Aguda/diagnóstico por imagen , Lesión Pulmonar Aguda/diagnóstico , Hiperoxia/complicaciones , Lipopolisacáridos/farmacología , Oximas/análisis , Lesión Pulmonar Aguda/inducido químicamente , Animales , Peso Corporal/fisiología , Lavado Broncoalveolar , Glutatión/metabolismo , Frecuencia Cardíaca/fisiología , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratas , Ratas Sprague-Dawley
12.
Blood ; 124(26): 3978-81, 2014 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-25339362

RESUMEN

High mobility group box 1 (HMGB1) is a chromatin-binding protein that maintains DNA structure. On cellular activation or injury, HMGB1 is released from activated immune cells or necrotic tissues and acts as a damage-associated molecular pattern to activate Toll-like receptor 4 (TLR4). Little is known concerning HMGB1 release and TLR4 activity and their role in the pathology of inflammation of sickle cell disease (SCD). Circulating HMGB1 levels were increased in both humans and mice with SCD compared with controls. Furthermore, sickle plasma increased HMGB1-dependent TLR4 activity compared with control plasma. HMGB1 levels were further increased during acute sickling events (vasoocclusive crises in humans or hypoxia/reoxygenation injury in mice). Anti-HMGB1 neutralizing antibodies reduced the majority of sickle plasma-induced TLR4 activity both in vitro and in vivo. These findings show that HMGB1 is the major TLR4 ligand in SCD and likely plays a critical role in SCD-mediated inflammation.


Asunto(s)
Anemia de Células Falciformes/metabolismo , Proteína HMGB1/metabolismo , Inflamación/metabolismo , Receptor Toll-Like 4/metabolismo , Anemia de Células Falciformes/inmunología , Animales , Regulación de la Expresión Génica , Humanos , Hipoxia/patología , Ligandos , Ratones , Ratones Endogámicos C57BL , Oxígeno/metabolismo , Transducción de Señal
13.
J Pediatr Surg ; 49(7): 1083-6, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24952793

RESUMEN

BACKGROUND: Despite randomized controlled trials and meta-analyses, it remains unclear whether laparoscopic pyloromyotomy (LP) carries a higher risk of incomplete pyloromyotomy and mucosal perforation compared with open pyloromyotomy (OP). METHODS: Multicenter study of all pyloromyotomies (May 2007-December 2010) at nine high-volume institutions. The effect of laparoscopy on the procedure-related complications of incomplete pyloromyotomy and mucosal perforation was determined using binomial logistic regression adjusting for differences among centers. RESULTS: Data relating to 2830 pyloromyotomies (1802 [64%] LP) were analyzed. There were 24 cases of incomplete pyloromyotomy; 3 in the open group (0.29%) and 21 in the laparoscopic group (1.16%). There were 18 cases of mucosal perforation; 3 in the open group (0.29%) and 15 in the laparoscopic group (0.83%). The regression model demonstrated that LP was a marginally significant predictor of incomplete pyloromyotomy (adjusted difference 0.87% [95% CI 0.006-4.083]; P=0.046) but not of mucosal perforation (adjusted difference 0.56% [95% CI -0.096 to 3.365]; P=0.153). Trainees performed a similar proportion of each procedure (laparoscopic 82.6% vs. open 80.3%; P=0.2) and grade of primary operator did not affect the rate of either complication. CONCLUSIONS: This is one of the largest series of pyloromyotomy ever reported. Although laparoscopy is associated with a statistically significant increase in the risk of incomplete pyloromyotomy, the effect size is small and of questionable clinical relevance. Both OP and LP are associated with low rates of mucosal perforation and incomplete pyloromyotomy in specialist centers, whether trainee or consultant surgeons perform the procedure.


Asunto(s)
Mucosa Intestinal/lesiones , Perforación Intestinal/etiología , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/etiología , Estenosis Pilórica/cirugía , Píloro/cirugía , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos
14.
Artículo en Inglés | MEDLINE | ID: mdl-24596654

RESUMEN

BACKGROUND: Endothelium-derived microparticles (EMPs) are submicron vesicles released from the plasma membrane of endothelial cells in response to injury, apoptosis or activation. We have previously demonstrated EMP-induced acute lung injury (ALI) in animal models and endothelial barrier dysfunction in vitro. Current treatment options for ALI are limited and consist of supportive therapies. We hypothesize that standard clinical continuous venovenous hemofiltration (CVVH) reduces serum EMP levels and may be adapted as a potential therapeutic intervention. MATERIALS AND METHODS: EMPs were generated from plasminogen activation inhibitor-1 (PAI-1)-stimulated human umbilical vein endothelial cells (HUVECs). Flow cytometric analysis was used to characterize EMPs as CD31- and annexin V-positive events in a submicron size gate. Enumeration was completed against a known concentration of latex beads. Ultimately, a concentration of ~650,000 EMP/mL perfusate fluid (total 470 mL) was circulated through a standard CVVH filter (pore size 200 µm, flow rate 250 mL/hr) for a period of 70 minutes. 0.5 mL aliquots were removed at 5- to 10-minute intervals for flow cytometric analysis. EMP concentration in the dialysate was measured at the end of 4 hours to better understand the fate of EMPs. RESULTS: A progressive decrease in circulating EMP concentration was noted using standard CVVH at 250 mL/hr (a clinical standard rate) from a 470 mL volume modelling a patient's circulation. A 50% reduction was noted within the first 30 minutes. EMPs entering the dialysate after 4 hours were 5.7% of the EMP original concentration. CONCLUSION: These data demonstrate that standard CVVH can remove EMPs from circulation in a circuit modelling a patient. An animal model of hemofiltration with induction of EMP release is required to test the therapeutic potential of this finding and potential of application in early treatment of ALI.

15.
Shock ; 39(3): 271-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23364425

RESUMEN

Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of technetium Tc 99m macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase 3. Pulmonary artery blood flow to left lungs was less than 0.1% of the cardiac output, and bronchial artery circulation was ∼2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation, and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. In quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP.


Asunto(s)
Neumonía en Organización Criptogénica/etiología , Modelos Animales de Enfermedad , Isquemia/complicaciones , Pulmón/irrigación sanguínea , Animales , Caspasa 3/metabolismo , Neumonía en Organización Criptogénica/diagnóstico por imagen , Neumonía en Organización Criptogénica/metabolismo , Neumonía en Organización Criptogénica/patología , Isquemia/diagnóstico por imagen , Isquemia/metabolismo , Isquemia/patología , Pulmón/diagnóstico por imagen , Pulmón/metabolismo , Pulmón/patología , Masculino , Cintigrafía , Radiofármacos , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Compuestos de Sulfhidrilo , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Receptor Toll-Like 4/metabolismo
16.
Pulm Circ ; 3(3): 578-88, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24618542

RESUMEN

Abstract Pulmonary or systemic infections and hypoxemic respiratory failure are among the leading causes of admission to intensive care units, and these conditions frequently exist in sequence or in tandem. Inflammatory responses to infections are reproduced by lipopolysaccharide (LPS) engaging Toll-like receptor 4 (TLR4). Apoptosis is a hallmark of lung injury in sepsis. This study was conducted to determine whether preexposure to LPS or hypoxia modulated the survival of pulmonary artery endothelial cells (PAECs). We also investigated the role TLR4 receptor expression plays in apoptosis due to these conditions. Bovine PAECs were cultured in hypoxic or normoxic environments and treated with LPS. TLR4 antagonist TAK-242 was used to probe the role played by TLR4 receptors in cell survival. Cell apoptosis and survival were measured by caspase 3 activity and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) incorporation. TLR4 expression and tumor necrosis factor α (TNF-α) production were also determined. LPS increased caspase 3 activity in a TAK-242-sensitive manner and decreased MTT incorporation. Apoptosis was decreased in PAECs preconditioned with hypoxia prior to LPS exposure. LPS increased TNF-α production, and hypoxic preconditioning blunted it. Hypoxic preconditioning reduced LPS-induced TLR4 messenger RNA and TLR4 protein. TAK-242 decreased to baseline the LPS-stimulated expression of TLR4 messenger RNA regardless of environmental conditions. In contrast, LPS followed by hypoxia substantially increased apoptosis and cell death. In conclusion, protection from LPS-stimulated PAEC apoptosis by hypoxic preconditioning is attributable in part to reduction in TLR4 expression. If these signaling pathways apply to septic patients, they may account for differing sensitivities of individuals to acute lung injury depending on oxygen tensions in PAECs in vivo.

17.
J Surg Res ; 166(1): 32-9, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20828748

RESUMEN

BACKGROUND: Previously, we have shown that endothelial microparticles (EMPs) injected into mice induce acute lung injury (ALI) [1]. In this study, we hypothesize that EMPs induce ALI by initiating cytokine release in the lung, leading to recruitment and activation of neutrophils. MATERIALS AND METHODS: C57BL/6J male mice (8-10 wk old) were intravenously injected with EMPs (200,000/mL), LPS (2 mg/kg), or both. Bronchoalveolar lavage (BAL) and serum levels of IL-1ß and TNF-α were analyzed by enzyme-linked immunoassay (ELISA). Morphometric analysis was performed on H and E stained lung sections. Myeloperoxidase (MPO) levels were determined via an enzymatic assay and immunofluorescence of stained sections. RESULTS: EMPs led to significantly increased pulmonary and systemic IL-1ß and TNF-α levels, which correlated with increased neutrophil recruitment to the lung. MPO levels in the lungs were increased significantly following injection of EMPs or LPS, compared to PBS. In mice treated with EMPs and LPS either simultaneously or successively, the cytokine and MPO levels were significantly increased over that of either treatment alone. CONCLUSION: EMPs contribute to lung injury through the initiation of a cytokine cascade that increases recruitment of neutrophils and subsequent release of MPO. Furthermore, treatment of mice with both EMPs and LPS induced greater lung injury than either treatment alone, suggesting that EMPs prime the lung for increased injury by other pathogens. Therapies aimed at reducing or blocking EMPs may be a useful strategy for attenuating lung injury.


Asunto(s)
Lesión Pulmonar Aguda/inmunología , Micropartículas Derivadas de Células/inmunología , Células Endoteliales/inmunología , Neumonía/inmunología , Lesión Pulmonar Aguda/patología , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Micropartículas Derivadas de Células/patología , Células Endoteliales/patología , Humanos , Interleucina-1beta/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Neutrófilos/metabolismo , Neutrófilos/patología , Peroxidasa/metabolismo , Neumonía/patología , Factor de Necrosis Tumoral alfa/sangre , Venas Umbilicales/citología
18.
J Pediatr Surg ; 45(9): 1767-71, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20850618

RESUMEN

PURPOSE: The purpose of this article was to report surgical and pain management outcomes of the initial Nuss procedure experience at the Children's Hospital of Wisconsin (Milwaukee) and to place this experience in the context of the published literature. METHODS: The initial 118 consecutive Nuss procedures in 117 patients were retrospectively reviewed with approval of the Children's Hospital of Wisconsin human rights review board. Patient, surgical, complication, and pain descriptors were collected for each case. Statistical methods for comparison of pain strategies included the Kolmogorov-Smirnov test for normality, 1-way repeated measures analysis of variance, and paired t tests. RESULTS: Patient, surgical, and complication descriptors were comparable to other large series. Complication rates were 7% early and 25% late. Epidural success rate was 96.4%. There was 1 episode of recurrence 2 years postbar removal (n = 114). CONCLUSIONS: The institution of the Nuss procedure provides a highly desired result with significant complication rates. The ideal approach would deliver this result with lower risk. A pain service-driven epidural administration of morphine or hydromorphone with local anesthetic provides excellent analgesia for patients after Nuss procedure. The success of epidural analgesia is independent of catheter site and adjunctive medications. Ketorolac was an effective breakthrough medication.


Asunto(s)
Analgesia Epidural , Tórax en Embudo/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Procedimientos Quirúrgicos Torácicos/efectos adversos , Adolescente , Niño , Femenino , Humanos , Masculino , Dolor Postoperatorio/etiología , Estudios Retrospectivos
19.
J Pediatr Surg ; 45(7): 1534-7, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20638539

RESUMEN

Previous reports describing laparoscopic-assisted transhiatal gastric transposition for long gap esophageal atresia (LGEA) have focused on older infants (median age of 11 months). By performing this operation at an earlier age, patients may avoid esophagostomies or prolonged hospitalizations with nasoesophageal tubes. An additional benefit is the earlier introduction of oral feeds, which is likely to decrease the incidence of oral aversion and feeding difficulties. In this report, we describe our surgical technique for performing a laparoscopic-assisted gastric transposition in a 56-day-old former 36-week premature infant with LGEA.


Asunto(s)
Atresia Esofágica/cirugía , Esofagoplastia/métodos , Laparoscopía/métodos , Estómago/cirugía , Anastomosis Quirúrgica , Humanos , Lactante , Masculino
20.
Shock ; 29(4): 504-11, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18598005

RESUMEN

Endothelial microparticles (EMPs) are small vesicles released from the plasma membrane of endothelial cells in response to cell injury, apoptosis, or activation. Low levels of MPs are shed into the blood from the endothelium, but in some pathologic states, the number of EMPs is elevated. The mechanism of MP formation and the wide-ranging effects of elevated EMPs are poorly understood. Here, we report the protein composition of EMPs derived from human umbilical cord endothelial cells stimulated with plasminogen activator inhibitor type 1 (PAI-1). Two-dimensional gel electrophoresis followed by mass spectrometry identified 58 proteins, of which some were verified by Western blot analysis. Gene Ontology database searches revealed that proteins identified on PAI-1-derived EMPs are highly diverse. Endothelial microparticles are composed of proteins from different cellular components that exhibit multiple molecular functions and are involved in a variety of biological processes. Important insight is provided into the generation and protein composition of PAI-1-derived EMPs.


Asunto(s)
Células Endoteliales/efectos de los fármacos , Inhibidor 1 de Activador Plasminogénico/farmacología , Proteínas/análisis , Western Blotting , Línea Celular , Electroforesis en Gel Bidimensional , Células Endoteliales/citología , Células Endoteliales/metabolismo , Humanos , Focalización Isoeléctrica , Proteínas/química , Proteínas/metabolismo , Proteómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
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