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1.
Pediatr Surg Int ; 30(3): 333-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24292371

RESUMEN

BACKGROUND/PURPOSE: Although physician-reported complications following circumcision are very low, parental satisfaction is not well documented. This study examined parental opinions and compared these with those of the medical professional. METHODS: Physicians independently assessed complications and cosmetic outcome following the circumcision. Six weeks post-circumcision, parental report of complications, cosmetic outcome, and overall satisfaction were assessed. RESULTS: Newborn infants (n = 710) were prospectively recruited and underwent either a Gomco [n = 552 (78 %)] or Plastibell(®) [n = 158 (22 %)] circumcision. Physician assessed complication rates were equivalent (Gomco 4.3 % versus Plastibell 5.1 %; p = 0.67), however, parental assessment found a much lower complication rate for Gomco 5.6 % versus Plastibell 12.0 % (p < 0.001). There was no difference between who performed the procedure nor between the techniques in regards to parental rating of overall satisfaction (excellent/good: Gomco 96.9 % versus Plastibell 95.6 %, p = 0.45). However, perceived post-operative pain as scored by parents was significantly higher in patients undergoing Plastibell procedure (6.4 % too much pain) versus Gomco (2.7 %; p = 0.05). Gomco accounted for 72.7 % of parental cosmetically unsatisfactory cases. CONCLUSIONS: Clinicians and parents differed considerably in terms of opinion of cosmetic outcome and occurrence of post-operative complications. This study emphasizes the need for clinicians to better understand and address parental concerns before and after circumcision.


Asunto(s)
Circuncisión Masculina/métodos , Evaluación de Procesos y Resultados en Atención de Salud/estadística & datos numéricos , Padres , Satisfacción del Paciente/estadística & datos numéricos , Circuncisión Masculina/estadística & datos numéricos , Humanos , Recién Nacido , Masculino , Michigan/epidemiología , Evaluación de Procesos y Resultados en Atención de Salud/métodos , Dolor Postoperatorio/epidemiología , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos
2.
Surgery ; 140(2): 212-20, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16904972

RESUMEN

BACKGROUND: Recent work indicates that mechanical force induces small-bowel growth, although methods reported do not have direct clinical application. We report a clinically feasible technique of enterogenesis and describe intestinal function in this model. METHODS: Using a pig model (n = 11), we stretched isolated small intestinal segments mechanically for 7 days in vivo with an intraluminal device. Control segments were not stretched. Morphology, histology, and epithelial proliferation were assessed. Absorption and epithelial barrier function were examined in an Ussing chamber. RESULTS: Stretch segments were significantly longer than Control segments and had nearly 2-fold greater surface area (P < .001). Mucosal thickness was much greater in Stretch than Control segments (772 +/- 134 vs. 647 +/- 75 microm, P = .02). Although villus height was reduced in Stretch and Control segments (353 +/- 76 vs. 324 +/- 76 microm, P = .6) versus native jejunum (522 +/- 87, P < .0005), crypt depth was increased dramatically in Stretch (450 +/- 95 microm) versus Control segments (341 +/- 64, P = .005). This observation was accompanied by a 2-fold increase in cellular proliferation (26.3 +/- 3.8 vs 12.1 +/- 6.6 % bromodeoxyuridine+, P < .05). Barrier function was intact ([3H]-mannitol permeation, 0.16 +/- 0.08%, vs native jejunum, 0.17 +/- 0.08%, P = .81). Glucose-mediated sodium transport was similar in Stretch versus native jejunum segments (60.0 +/- 23.5 vs 82.3 +/- 47.3 microA/cm2, P = .31), as was carbachol-induced chloride transport (82.4 +/- 72.2 vs 57.2 +/- 33.4 microA/cm2, P = .54) and alanine absorption (16.46 +/- 12.94 vs 23.53 +/- 21.31 microA/cm2, P = .53). CONCLUSIONS: Mechanical stretching induces small intestinal growth, while maintaining function. Epithelial architecture does change, such that a decrease in villus height is offset by a marked increase in crypt depth and a 2-fold increase in epithelial proliferation. Epithelial barrier and absorptive functions remain intact. The device described may have direct clinical applicability.


Asunto(s)
Yeyuno/crecimiento & desarrollo , Estrés Mecánico , Dispositivos de Expansión Tisular , Animales , Diseño de Equipo , Estudios de Factibilidad , Femenino , Absorción Intestinal/fisiología , Yeyuno/patología , Yeyuno/fisiopatología , Modelos Animales , Porcinos , Resistencia a la Tracción
3.
JPEN J Parenter Enteral Nutr ; 30(6): 474-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17047170

RESUMEN

BACKGROUND: Parenteral nutrition (PN) is known to induce villus atrophy, epithelial cell (EC) apoptosis, and increase mucosal permeability. The study hypothesized that increasing amounts of energy delivery to mice would result in the best outcome, with the least effects on the mucosa. METHODS: Mice were randomized to enteral controls (saline infusion with ad libitum enteral food) or to 1 of 3 PN groups (with no enteral nutrition): full (100% of daily average energy intake for the mouse), reduced (75% of energy intake) or very low (50% of energy intake). Mice received PN for 7 days. Mucosal morphology, EC apoptosis, and bacterial translocation were assessed. RESULTS: Villus height decreased significantly with decreasing levels of caloric intake and was significantly lower in all PN groups compared with controls. Body weight loss was significantly greater in PN groups vs controls and was greatest in mice with the lowest caloric delivery. A consistent trend toward a higher EC apoptotic index with decreasing caloric intake was observed, and apoptosis in all PN groups exceeded controls (2-fold). All PN groups demonstrated greater bacterial translocation than controls. CONCLUSIONS: PN induces intestinal EC apoptosis and villus and crypt atrophy, even at 100% of predicted energy needs, and such changes increased with greater reduction of energy intake. This study supports a concept that lack of enteral nutrition, rather than absolute caloric levels, is responsible for many of the adverse effects of PN. The study also allows the investigators to better optimize a mouse model of PN delivery.


Asunto(s)
Apoptosis/efectos de los fármacos , Traslocación Bacteriana/efectos de los fármacos , Ingestión de Energía/fisiología , Mucosa Intestinal , Nutrición Parenteral/efectos adversos , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Nutrición Enteral , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Organismos Libres de Patógenos Específicos , Aumento de Peso
4.
J Am Coll Surg ; 200(5): 670-6, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15848356

RESUMEN

BACKGROUND: Whether the 80 hours per week limit on surgical residents' work hours has reduced the number or variety of cases performed by residents is unknown. STUDY DESIGN: We quantified residents' operative experience, by case category, on a pediatric surgical service. The number of senior and junior residents' cases were compared between residents from the year before (n = 47) and after (n = 44) the 80-hour limit. Residents also completed a questionnaire about their operative and educational experience. As an additional dimension of the educational experience, resident participation in clinic was assessed. Student's t-test was used. RESULTS: Total number of cases performed either by senior (before, 1.58 +/- 0.42 versus after, 1.84 +/- 0.82 cases/day) or junior (before, 0.70 +/- 0.21 versus after, 0.71 +/- 0.15) residents has not changed (p = NS). Senior residents' vascular access and endoscopy rate increased; other categories remained stable. Residents' perception of their experience was unchanged. But residents' participation in outpatient clinic was significantly decreased (before, 66.0% +/- 14.7% versus after, 17.0% +/- 19.9% of clinics covered, p < 0.005). CONCLUSIONS: The 80-hour limit has had minimal impact on residents' operative experience, in case number and variety, and residents' perceptions of their educational experience. Residents' reduction in duty hours may have been achieved at the expense of outpatient clinic experiences.


Asunto(s)
Internado y Residencia , Pediatría/organización & administración , Servicio de Cirugía en Hospital/organización & administración , Carga de Trabajo/estadística & datos numéricos , Adulto , Femenino , Humanos , Masculino , Medicina/estadística & datos numéricos , Admisión y Programación de Personal , Especialización , Encuestas y Cuestionarios
5.
JPEN J Parenter Enteral Nutr ; 29(5): 337-43; discussion 343-4, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16107596

RESUMEN

BACKGROUND: Neonates receiving parenteral nutrition (PN) are at risk for PN-associated cholestasis (PNAC); however, no preventive factors for PNAC have been clearly identified. Despite reports suggesting that taurine may prevent PNAC in neonates, such an effect of taurine has not yet been definitively demonstrated. We determined whether taurine supplementation reduces the incidence of PNAC in premature or critically ill neonates. METHODS: This study was part of a prospective, randomized, multi-institutional trial designed to assess cholecystokinin vs placebo as a potential preventive therapy of PNAC. Taurine supplementation of PN varied between institutions. The presence or absence of taurine in PN was analyzed by multivariate analysis, with a primary outcome measure of serum conjugated bilirubin (CB) as a measure of PNAC. RESULTS: Taurine reduced PNAC in premature infants (estimated maximum CB [95% confidence interval] 0.50 mg/dL [-0.17 to 1.18] for those receiving taurine, vs 3.45 mg/dL [1.79-5.11] for neonates not receiving taurine, approaching significance, p = .07). Taurine significantly reduced PNAC in infants with necrotizing enterocolitis (NEC; estimated maximum CB 4.04 mg/dL [2.85-5.23], NEC infants receiving taurine, vs 8.29 mg/dL [5.61-10.96], NEC infants not receiving taurine, p < .01). There were too few neonates with surgical anomalies to evaluate the effect of taurine in this group. CONCLUSIONS: Within specific subgroups of neonatal patients, taurine supplementation does offer a very significant degree of protection against PNAC. Patients with NEC or severe prematurity are most likely to benefit substantially from taurine supplementation.


Asunto(s)
Colestasis/prevención & control , Enfermedades del Prematuro/prevención & control , Nutrición Parenteral/efectos adversos , Taurina/uso terapéutico , Bilirrubina/sangre , Colagogos y Coleréticos/metabolismo , Colagogos y Coleréticos/farmacología , Colecistoquinina/metabolismo , Colecistoquinina/farmacología , Colestasis/etiología , Enfermedad Crítica , Método Doble Ciego , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/etiología , Análisis Multivariante , Estudios Prospectivos , Taurina/fisiología
6.
J Heart Lung Transplant ; 22(8): 937-45, 2003 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12909476

RESUMEN

OBJECTIVES: Use of the heterotopic rat cardiac isograft model is limited by ventricular atrophy attributable to the left ventricle's non-working state. Previous studies indicate that increased left ventricular pressure-volume work minimizes atrophy. We used a simpler approach to increase ventricular work, imposing aortic regurgitation on the transplant. We hypothesized that this would prevent atrophy and preserve left ventricular compliance. METHODS: We analyzed heterotopic transplants with aortic valvotomy and without aortic valvotomy (controls). Recipient native hearts served as separate controls. After 15 to 25 days, we measured cardiac wet weight, dry weight, and water content of all groups and measured echocardiographic left ventricular wall thickness and end-diastolic and end-systolic diameters in both transplant groups. Left ventricular volume infusions yielded pressure-volume data that we analyzed using regression methods. RESULTS: Aortic regurgitant transplants weighed more than control transplants (dry weight, 0.109 +/- 0.013 g vs 0.097 +/- 0.016 g; p = 0.020, 2-way analysis of variance), but all transplants weighed less than native hearts weighed (p = 0.001). Control transplants were less compliant than regurgitant transplants (p = 0.002), but the latter were similar to their own native hearts (p = 0.34). Wall thickness decreased in regurgitant vs control transplants (p = 0.020, Student's t-test), but end-diastolic and end-systolic diameters increased (p < or = 0.001). CONCLUSIONS: Aortic regurgitation in heterotopic transplants improves left ventricular compliance through chamber dilatation without preventing atrophy. Moderate acute aortic regurgitation affects ventricular remodeling more than it stimulates myocardial hypertrophy. Smaller end-diastolic diameter, greater wall thickness, and myocardial edema may explain decreased compliance in non-working transplants.


Asunto(s)
Insuficiencia de la Válvula Aórtica/fisiopatología , Diástole/fisiología , Trasplante de Corazón/efectos adversos , Trasplante Heterotópico/efectos adversos , Disfunción Ventricular Izquierda/prevención & control , Remodelación Ventricular/fisiología , Animales , Atrofia/diagnóstico por imagen , Atrofia/etiología , Atrofia/prevención & control , Presión Sanguínea/fisiología , Modelos Animales de Enfermedad , Masculino , Miocardio/patología , Ratas , Ratas Sprague-Dawley , Ultrasonografía , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología
8.
J Pediatr Surg ; 44(7): 1410-7, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19573671

RESUMEN

BACKGROUND: Outcomes remain controversial for patients undergoing straight (SIAA) vs J pouch (JPAA) ileoanal anastomosis, particularly in children where fewer such cases are performed. Our 3 centers have had extensive experience with both techniques. Thus, we had the unique opportunity to compare outcomes within the same centers. METHODS: We retrospectively analyzed 250 children after proctocolectomy with either SIAA or JPAA, for the first 3 years after pull-through. A functional stooling score was developed to further assess outcomes. Data were analyzed using chi(2) tests and generalized linear mixed models for repeated measures. RESULTS: Two hundred three patients had sufficient data for complete analysis (42% males; mean surgery age, 15 +/- 7years). Surgical indications were ulcerative colitis (168) and familial adenomatoid polyposis (35). Surgical procedures included SIAA (112) and JPAA (91). Daytime and nighttime stooling frequencies were significantly higher (P < .013) for SIAA patients at 1 to 24 months after pull-through; however, stooling frequencies began approximating each other by this time. Symptomatic pouchitis (compared to enteritis after SIAA) was significantly higher in JPAA patients (odds ratio, 4.5; confidence interval, 2.32-8.72). Frequency of pouchitis declined with time. There was no significant difference in the incidence of surgical complications between the 2 groups. Finally, continence rates were strikingly good in both groups compared to previously reported series. CONCLUSION: Straight ileoanal anastomosis and JPAA are associated with considerable morbidity; SIAA has higher stool frequency and JPAA has increased pouchitis. Over time, we found that problems improved, and functional stooling scores became similar. JPAA had consistently lower stool frequency and better continence rates; however, these differences were small and may have minimal clinical significance. In addition, such differences need to be balanced against the high rate of pouchitis with JPAA. Continence was excellent regardless of the technique.


Asunto(s)
Poliposis Adenomatosa del Colon/cirugía , Canal Anal/cirugía , Colitis Ulcerosa/cirugía , Reservorios Cólicos/fisiología , Íleon/cirugía , Reservoritis/epidemiología , Proctocolectomía Restauradora/métodos , Adolescente , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Defecación/fisiología , Femenino , Finlandia/epidemiología , Estudios de Seguimiento , Humanos , Masculino , Morbilidad , Complicaciones Posoperatorias , Reservoritis/etiología , Proctocolectomía Restauradora/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Estados Unidos/epidemiología
9.
Am J Clin Nutr ; 88(6): 1552-9, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19064515

RESUMEN

BACKGROUND: Little information is available about the financial charges incurred by patients with short-bowel syndrome (SBS). This is particularly true for pediatric SBS patients who receive some of the most complex medical care. OBJECTIVES: The aims of this study were to determine the total cost of care for these patients and to analyze their utilization of home and hospital-based health care services. DESIGN: This was a retrospective review of the total charges incurred by 41 children with SBS over the past decade, encompassing both inpatient and home-care charges. RESULTS: The mean (+/- SD) total cost of care for pediatric SBS was US$505 250 +/- US$248 398 (corrected for inflation to the year 2005) for the first year of care alone. Inpatient hospitalization accounted for most of these expenses (US$416 818 +/- US$242 689, or 82% of the total), and this was attributable to prolonged requirements for intensive care resources, numerous surgical procedures, and multiple readmissions during the first year of diagnosis. Hospital-based costs steadily declined in subsequent years, but home-care services, in stark contrast, unexpectedly increased every year for the first 5 y of diagnosis-a trend that was highly significant (P < 0.005), reaching US$184 520 +/- US$111 075 for the fifth year of home care. This increasing cost was attributable to increasing complications of parenteral nutrition, especially infectious complications. Although per-patient charges varied widely, the mean total cost of care per child over a 5-y period was US$1 619 851 +/- US$1 028 985. A strong correlation was found between higher charges and infants with <10% of predicted small-bowel length. CONCLUSIONS: This study was the first to calculate the total costs for pediatric SBS patients and to provide an in-depth analysis of these patients' actual utilization of health care services. This information may help guide health care providers and families who have children with SBS. The comprehensive care of pediatric SBS patients costs significantly more than has previously been estimated. Contrary to previous views, home care significantly increases each year after diagnosis.


Asunto(s)
Costos de la Atención en Salud/estadística & datos numéricos , Servicios de Atención de Salud a Domicilio/economía , Costos de Hospital , Hospitales Pediátricos/economía , Servicio Ambulatorio en Hospital/economía , Síndrome del Intestino Corto/economía , Adolescente , Análisis de Varianza , Niño , Preescolar , Costos y Análisis de Costo , Femenino , Estudios de Seguimiento , Gastos en Salud , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Masculino , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Nutrición Parenteral/efectos adversos , Nutrición Parenteral/economía , Estudios Retrospectivos , Síndrome del Intestino Corto/mortalidad , Síndrome del Intestino Corto/terapia , Análisis de Supervivencia , Estados Unidos
10.
Am J Physiol Gastrointest Liver Physiol ; 295(1): G88-G98, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18483182

RESUMEN

Angiotensin converting enzyme (ACE) has been shown to be involved in regulation of apoptosis in nonintestinal tissues. This study examined the role of ACE in the modulation of intestinal adaptation utilizing ACE knockout mice (ACE-/-). A 60% small bowel resection (SBR) was used, since this model results in a significant increase in intestinal epithelial cell (EC) apoptosis as well as proliferation. Baseline villus height, crypt depth, and intestinal EC proliferation were higher, and EC apoptosis rates were lower in ACE-/- compared with ACE+/+ mice. After SBR, EC apoptosis rates remained significantly lower in ACE-/- compared with ACE+/+ mice. Furthermore, villus height and crypt depth after SBR continued to be higher in ACE-/- mice. The finding of a lower bax-to-bcl-2 protein ratio in ACE-/- mice may account for reduced EC apoptotic rates after SBR in ACE-/- compared with ACE+/+ mice. The baseline higher rate of EC proliferation in ACE-/- compared with ACE+/+ mice may be due to an increase in the expression of several EC growth factor receptors. In conclusion, ACE appears to have an important role in the modulation of intestinal EC apoptosis and proliferation and suggests that the presence of ACE in the intestinal epithelium has a critical role in guiding epithelial cell adaptive response.


Asunto(s)
Células Epiteliales/citología , Mucosa Intestinal/citología , Peptidil-Dipeptidasa A/genética , Animales , Apoptosis/fisiología , Proliferación Celular , Regulación de la Expresión Génica , Íleon/citología , Íleon/enzimología , Mucosa Intestinal/enzimología , Yeyuno/citología , Yeyuno/enzimología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Electrónica de Transmisión , Peptidil-Dipeptidasa A/metabolismo
11.
Pediatr Surg Int ; 23(5): 379-90, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17205293

RESUMEN

Early intestinal adaptation after massive small bowel resection (SBR) is driven by increased epithelial cell (EC) proliferation. There is a clear clinical difference in the post-operative course of patients after the loss of proximal (P) compared to distal (D) small bowel. This study examined the effects of the site of SBR on post-resectional intestinal adaptation, and investigated the potential mechanisms involved. C57BL/6J mice (n = 7/group) underwent: (1) 60% P-SBR, (2) 60% D-SBR, (3) 60% mid (M)-SBR and (4) SHAM-operation (transection/reanastomosis). Mice were sacrificed at 7 days after surgery and ECs and adjacent mucosal lymphocytes (IELs) isolated. Adaptation was assessed in both jejunum and ileum by quantification of villus height, crypt depth, villus cell size, crypt cell size (microns), goblet cell number, and EC proliferation (%BrdU incorporation). Proliferation signalling pathways including keratinocyte growth factor (KGF)/KGFR(1), IL-7/IL-7R, and epidermal growth factor receptor (EGFR) were measured by RT-PCR. Expression of IL-7 was further analysed by immunofluorescence. Data were analyzed using ANOVA. All three SBR models led to significant increases in villus height, crypt depth, goblet cell numbers and EC proliferation rate when compared to respective SHAM groups. The strongest morphometric changes were found for jejunal segments after M-SBR and for ileal segments after P-SBR. Furthermore, morphometric analysis showed that at 1-week post-resection a tremendous increase in EC numbers occurred in jejunal villi (cell hyperplasia), whereas a significant increase in EC size predominated in ileal villi (cell hypertrophy). mRNA expression of KGF, KGFR(1), IL-7R, and EGFR showed a significant increase only after D-SBR, whereas IL-7 increased significantly after SBR in all investigated models, and this was confirmed by immunofluorescence studies. Early intestinal adaptation shows distinct differences depending on the site of SBR, and is predominately driven by cell hyperplasia in jejunal villi and cell hypertrophy in ileal villi. However, the exact mechanisms, which guide these signalling pathways are still unclear.


Asunto(s)
Adaptación Fisiológica/fisiología , Proliferación Celular , Células Epiteliales/fisiología , Intestino Delgado/fisiología , Intestino Delgado/cirugía , Animales , Tamaño de la Célula , Células Epiteliales/ultraestructura , Técnica del Anticuerpo Fluorescente/métodos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Interleucina-7/metabolismo , Intestino Delgado/ultraestructura , Linfocitos/fisiología , Linfocitos/ultraestructura , Masculino , Ratones , Ratones Endogámicos C57BL , Periodo Posoperatorio , Receptores de Factores de Crecimiento/metabolismo , Receptores de Interleucina-7/metabolismo , Recuperación de la Función , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Transducción de Señal/fisiología , Organismos Libres de Patógenos Específicos
12.
Dig Dis Sci ; 52(4): 1060-70, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17342403

RESUMEN

Ulcerative colitis is characterized by elevated rates of epithelial cell apoptosis, and an up-regulation of pro-apoptotic cytokines including tumor necrosis factor alpha (TNF-alpha). Recently, angiotensin converting enzyme (ACE) has been shown to promote apoptosis. In addition, pharmacologic ACE inhibition (ACE-I) both prevents apoptosis and reduces TNF-alpha expression in vitro. We hypothesized that ACE-I, using enalaprilat, would decrease colonic epithelial cell apoptosis and reduce colitis severity in the dextran sulfate sodium (DSS)-induced colitis model in mice. We assessed the severity of colitis, and colonic epithelial cell apoptosis, after administration of DSS. Mice were given either daily ACE-I treatment or daily placebo. ACE-I treatment markedly improved clinical outcomes. In addition, ACE-I treatment significantly reduced the maximum histopathologic colitis grade. ACE-I also dramatically reduced the epithelial apoptotic rate. To investigate the mechanism by which ACE-I reduced apoptosis; we measured TNF-alpha, Bcl-2, and Bax expression. TNF-alpha mRNA was significantly lower with ACE-I treatment compared to placebo at every time point, as was the ratio of Bax to Bcl-2. We conclude that ACE-I reduces the severity of DSS-induced colitis and reduces epithelial cell apoptosis.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Colitis/patología , Enalaprilato/farmacología , Animales , Apoptosis/efectos de los fármacos , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/fisiopatología , Colon/irrigación sanguínea , Colon/metabolismo , Colon/patología , Sulfato de Dextran , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Citometría de Flujo , Mucosa Intestinal/irrigación sanguínea , Mucosa Intestinal/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Peptidil-Dipeptidasa A/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Flujo Sanguíneo Regional/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2/metabolismo
13.
Pediatr Surg Int ; 22(1): 37-42, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16307277

RESUMEN

Massive small bowel resection (SBR) results in a significant increase in intestinal epithelial cell (EC) proliferation as well as apoptosis. Because the site of SBR (proximal (P) vs. distal (D)) affects the degree of intestinal adaptation, we hypothesized that different rates of EC apoptosis would also be found between P-SBR and D-SBR models. Wild-type C57BL/6J mice underwent: (1) 60% P-SBR, (2) 60% D-SBR, or (3) SHAM-operation (transaction-reanastomosis) at the mid-gut point. Mice were sacrificed after 7 days. EC apoptosis was measured by TUNEL staining. EC-related apoptotic gene expression including intrinsic and extrinsic pathways was measured with reverse transcriptase-polymerase chain reaction. Bcl-2 and bax protein expression were analyzed by Western immunoblotting. Both models of SBR led to significant increases in villus height and crypt depth; however, the morphologic adaptation was significantly higher after P-SBR compared to D-SBR (P<0.01). Both models of SBR led to significant increases in enterocyte apoptotic rates compared to respective sham levels; however, apoptotic rates were 2.5-fold higher in ileal compared to jejunal segments (P<0.01). P-SBR led to significant increases in bax (pro-apoptotic) and Fas expression, whereas D-SBR resulted in a significant increase in TNF-alpha expression (P<0.01). EC apoptosis seems to be an important component of intestinal adaptation. The significant difference in EC apoptotic rates between proximal and distal intestinal segments appeared to be due to utilization of different mechanisms of action.


Asunto(s)
Adaptación Fisiológica , Apoptosis/fisiología , Enterocitos/metabolismo , Íleon/fisiología , Yeyuno/fisiología , Síndrome del Intestino Corto/fisiopatología , Análisis de Varianza , Animales , Apoptosis/genética , Expresión Génica , Íleon/citología , Íleon/cirugía , Yeyuno/citología , Yeyuno/cirugía , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
14.
Cytokine ; 31(6): 419-28, 2005 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-16102972

RESUMEN

BACKGROUND: Interleukin-7 (IL-7) plays a crucial role in controlling T-cell development and homeostasis. IL-7 knock out and IL-7 receptor knock out mice show distinct declines in absolute numbers of the intestinal intraepithelial lymphocytes (IEL). Therefore, we hypothesized that exogenous administration of IL-7 would alter IEL phenotype and function. METHODS: Adult C57BL/6J mice were treated with IL-7 or saline. Mice were euthanized at day 7. Cytokine and keratinocyte growth factor (KGF) expressions were measured with RT-PCR. IEL phenotype was studied with flow cytometry. Finally, to address the association of endogenous epithelial cell (EC)-derived IL-7 and IEL, confocal microscopy was used to observe co-localization of IL-7 to IEL subpopulations. RESULTS: IL-7 administration significantly increased IEL numbers. CD8alphabeta+ IEL increased 3.2-fold, CD8+CD44+ IEL increased 1.3-fold, and alphabeta-T-cell receptor (TCR)+ IEL increased 1.3-fold. IL-7 administration also significantly changed both alphabeta-TCR+ IEL- and gammadelta-TCR+ IEL-derived cytokine expressions. Interestingly, IL-7 administration also led to a significant increase in KGF expression. Confocal microscopy showed a high level of co-localization between the alphabeta-TCR+ IEL and EC-derived IL-7. gammadelta-TCR+ IEL showed a lower level, but still significant, co-localization. CONCLUSION: IL-7 administration significantly affected IEL phenotype and function. The observed co-localization suggests that there is a close IEL-EC cross-communication mediated by EC-derived IL-7 expression.


Asunto(s)
Interleucina-7/farmacología , Mucosa Intestinal/inmunología , Linfocitos T/efectos de los fármacos , Animales , Comunicación Celular , Ciclo Celular/fisiología , Citocinas/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Citometría de Flujo , Interleucina-7/fisiología , Mucosa Intestinal/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Fenotipo , ARN Mensajero/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/fisiología
15.
J Surg Res ; 123(1): 8-16, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15652945

RESUMEN

BACKGROUND: Total parenteral nutrition (TPN) results in a loss of mucosal immune function by alterations in both phenotype and function of intraepithelial lymphocytes (IEL). We hypothesized that the observed changes with TPN administration are caused by the lack of enteral feeding, and not to the TPN solution itself. METHODS: Mice received oral feeding (Control), TPN alone (TPN), or TPN plus oral feeding (TPN+Food). Mice were killed after 7 days, and bacteriological cultures from spleen, liver, and mesenteric lymph nodes obtained, with bacterial translocation (BT) being defined as a positive culture. IEL phenotype was analyzed by flow cytometry. IEL messenger RNA (mRNA) cytokine expression used reverse transcriptase polymerase chain reaction (RT-PCR). Apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining. RESULTS: BT significantly (P < 0.05, with analysis of variance [ANOVA]) increased in the TPN group (53%) compared with Control (9%) and TPN+Food (14%) groups. TPN also resulted in a significant (P < 0.01) increase in epithelial cell apoptosis: TPN 7.6 +/- 1.1% versus Control 2.9 +/- 1.1% and TPN+Food 2.1 +/- 0.3% (mean +/- SD). Height of the villus-crypt complex was significantly decreased in TPN mice (315 +/- 16 microm) compared with Control (431 +/- 27 microm) and TPN+Food (421 +/- 26 microm) groups. IEL phenotypes significantly changed with TPN administration: CD4+ CD8- as well as CD4+ CD8+ subpopulations were reduced compared with Control or TPN+Food mice; as were the CD8alphabeta+ thymus-dependent, and CD8+ CD44+ mature IEL. IEL cytokine mRNA expression was also significantly altered with TPN: IL-2 and IL-10 expression declined, and IL-4 IL-6, interferon gamma (IFN-gamma), transforming growth factor beta-1 (TGF-beta1), and tumor necrosis factor-alpha (TNF-alpha) were increased, when compared with Control or TPN+Food mice. CONCLUSIONS: This study demonstrates that the major factor responsible for TPN-induced BT and IEL-changes is the lack of enteral feeding and not the administration of the TPN solution itself.


Asunto(s)
Mucosa Intestinal/inmunología , Linfocitos/inmunología , Nutrición Parenteral Total , Animales , Apoptosis , Traslocación Bacteriana , Citocinesis/genética , Inmunofenotipificación , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/análisis
16.
Ann Surg ; 242(3): 403-9; discussion 409-12, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16135926

RESUMEN

OBJECTIVE: To determine predictors of survival and of weaning off parenteral nutrition (PN) in pediatric short bowel syndrome (SBS) patients. SUMMARY BACKGROUND DATA: Pediatric SBS carries extensive morbidity and high mortality, but factors believed to predict survival or weaning from PN have been based on limited studies. This study reviews outcomes of a large number of SBS infants and identifies predictors of success. METHODS: Multivariate Cox proportional hazards analysis was conducted on 80 pediatric SBS patients. Primary outcome was survival; secondary outcome was ability to wean off PN. Nonsignificant covariates were eliminated. P < 0.05 was considered significant. RESULTS: Over a mean of 5.1 years of follow-up, survival was 58 of 80 (72.5%) and 51 weaned off PN (63.8%). Cholestasis (conjugated bilirubin > or =2.5 mg/dL) was the strongest predictor of mortality (relative risk [RR] 22.7, P = 0.005). Although absolute small bowel length was only slightly predictive, percentage of normal bowel length (for a given infant's gestational age) was strongly predictive of mortality (if <10% of normal length, RR of death was 5.7, P = 0.003) and of weaning PN (if > or =10% of normal, RR of weaning PN was 11.8, P = 0.001). Presence of the ileocecal valve (ICV) also strongly predicted weaning PN (RR 3.9, P < 0.0005); however, ICV was not predictive of survival. CONCLUSIONS: Cholestasis and age-adjusted small bowel length are the major predictors of mortality in pediatric SBS. Age-adjusted small bowel length and ICV are the major predictors of weaning from PN. These data permit better prediction of outcomes of pediatric SBS, which may help to direct future management of these challenging patients.


Asunto(s)
Fenómenos Fisiológicos Nutricionales Infantiles , Nutrición Parenteral , Síndrome del Intestino Corto/terapia , Preescolar , Colestasis/etiología , Colestasis/mortalidad , Femenino , Humanos , Lactante , Masculino , Tamaño de los Órganos/efectos de los fármacos , Nutrición Parenteral/efectos adversos , Pronóstico , Estudios Retrospectivos , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/mortalidad , Análisis de Supervivencia
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