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1.
Dis Colon Rectum ; 66(11): e1134-e1137, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37540020

RESUMO

BACKGROUND: Treatment of perineal defects after abdominoperineal resection or salvage surgery for either locally advanced rectal cancer or anal carcinoma can be challenging. Myocutaneous flap reconstruction has proven to reduce perineal morbidity and abscess formation in the pelvis; however, it is associated with significant donor-site morbidity. To our knowledge, this is the first report of a laparoscopic oblique rectus abdominis myocutaneous flap harvesting for perineal reconstruction. This technical note aimed to demonstrate the feasibility of the technique. IMPACT OF INNOVATION: Introduction of a laparoscopic technique in harvesting of this flap can potentially further reduce morbidity associated with this flap creation by minimizing abdominal wall trauma and obviating the need for laparotomy for tunneling of the flap intra-abdominally. TECHNOLOGY, MATERIALS, AND METHODS: This report describes a technique using a 6-port laparoscopy, in which the harvesting of the myocutaneous flap was performed after a standardized abdominoperineal resection. The flap itself is passed through the rectus sheath toward the pelvis with the help of a retractor. PRELIMINARY RESULTS: Two patients successfully underwent a laparoscopic oblique rectus abdominis flap reconstruction after abdominoperineal resection. CONCLUSION AND FUTURE DIRECTIONS: This report describes our initial experience with laparoscopic harvesting of an oblique rectus abdominis flap for perineal reconstruction after abdominoperineal resection. We believe the technique is easy and reproducible for laparoscopic surgeons and can reduce donor-site morbidity. However, further studies will be needed to confirm this observation.

2.
Dis Colon Rectum ; 65(5): 713-720, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34890373

RESUMO

BACKGROUND: Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn's disease. Safety and efficacy outcomes from the clinical trial known as "Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn's disease," or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported. OBJECTIVE: The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn's disease and complex perianal fistulas. DESIGN: This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn's disease. SETTINGS: This study extension was conducted in multiple hospitals across 7 European countries and Israel. PATIENTS: Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group. INTERVENTIONS: Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas. MAIN OUTCOME MEASURES: Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104. RESULTS: Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group. LIMITATIONS: Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point. CONCLUSIONS: Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B812.ClinicalTrials.gov No: NCT01541579. ESTUDIO DE SEGUIMIENTO PARA EVALUAR LA SEGURIDAD Y EFICACIA A LARGO PLAZO DE DARVADSTROCEL TRATAMIENTO CON CLULAS MADRE MESENQUIMALES EN PACIENTES CON ENFERMEDAD DE CROHN PERIANAL FISTULIZANTE ENSAYO CONTROLADO ALEATORIZADO DE FASE ADMIRECD: ANTECEDENTES:Darvadstrocel es una terapia con células madre mesenquimales alogénicas expandidas derivadas de tejido adiposo para el tratamiento de fístulas perianales complejas en pacientes con enfermedad de Crohn. Los resultados del ensayo clínico conocido como "Células madre mesenquimales derivadas de tejido adiposo para la inducción de la remisión en la enfermedad de Crohn fistulizante perianal" o ADMIRE-CD (NCT01541579), en cuanto a la seguridad y eficacia hasta 52 semanas después del tratamiento, fueron previamente informados. Seguidamente, se presentan los resultados de un seguimiento extendido de 104 semanas.OBJETIVO:Evaluar la seguridad y eficacia a largo plazo de darvadstrocel a dos años del tratamiento en pacientes con enfermedad de Crohn y fístulas perianales complejas.DISEÑO:Este fue un estudio de fase 3, aleatorizado, a doble ciego, controlado (ADMIRE-CD) en pacientes con enfermedad de Crohn perianal fistulizante.DESARROLLO:Esta extensión del estudio se realizó en varios hospitales de siete países europeos e Israel.PACIENTES:Cuarenta pacientes participaron en la extensión de seguimiento: tratamiento con darvadstrocel (n = 25); grupo control (n = 15).INTERVENCIONES:Se administró Darvadstrocel o solución salina (grupo control) una vez, localmente, tras el legrado del trayecto fístuloso y cierre del orificio interno (con la colocación previa de setón). A todos los pacientes se les permitió continuar con los tratamientos médicos en curso para las fístulas.PRINCIPALES MEDIDAS DE RESULTADO:Los eventos de efectos adversos graves derivados del tratamiento se registraron hasta la semana 104. La remisión clínica, definida como el cierre de todas las aberturas externas tratadas que drenaban al inicio espontáneamente o por compresión suave de los dedos, fue evaluado en la semana 104.RESULTADOS:Del total de 40 pacientes, 37 completaron la extensión de seguimiento. Hasta la semana 104, se reportaron 7 eventos de efectos adversos graves resultantes del tratamiento, de los cuales 4 ocurrieron entre las semanas 52 y 104. En la semana 104, se reportó remisión clínica en 14/25 (56%) pacientes en el grupo de darvadstrocel y 6/15 (40%) pacientes en el grupo de control.LIMITACIONES:Solo una pequeña cantidad de pacientes participaron en el período de seguimiento extendido y no se realizaron exámenes por técnicas de imagen en la visita a 104 semanas.CONCLUSIONES:Darvadstrocel fue bien tolerado y la remisión clínica después del tratamiento con darvadstrocel puede mantenerse hasta 104 semanas en pacientes con enfermedad de Crohn perianal fistulizante. Consulte Video Resumen en http://links.lww.com/DCR/B812. (Traducción-Dr Osvaldo Gauto and Dr Julian Panés.)ClinicalTrials.gov No. NCT01541579.


Assuntos
Doença de Crohn , Células-Tronco Mesenquimais , Doença de Crohn/complicações , Doença de Crohn/terapia , Europa (Continente) , Seguimentos , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco
3.
Dis Colon Rectum ; 64(9): 1064-1073, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397557

RESUMO

BACKGROUND: Rectal cancer in adolescents and young adults (age ≤39) is increasing. Early diagnosis is a challenge in this subset of patients. OBJECTIVE: This study aims to analyze the presentation pattern and outcomes of sporadic rectal cancer in adolescents and young adults. DESIGN: This is a retrospective study. SETTING: This study was conducted at 3 European tertiary centers. PATIENTS: Data on adolescents and young adults operated on for sporadic rectal cancer (January 2008 through October 2019) were analyzed. To compare outcomes, adolescents and young adults were matched to a group of patients aged ≥40 operated on during the same period. MAIN OUTCOME MEASURES: The primary outcomes measured were clinical presentation and long-term outcomes. RESULTS: Sporadic rectal cancers occurred in 101 adolescents and young adults (2.4%; mean age, 33.5; range, 18-39); 51.5% were male, and a smoking habit was reported by 17.8% of patients. The rate of a family history for colorectal cancer was 25.7%, and of these patients, 24.7% were obese. Diagnosis based on symptoms was reported in 92.1% patients, and the mean time from first symptoms to diagnosis was 13.7 months. The most common symptom at diagnosis was rectal bleeding (68.8%), and 12% and 34% of the adolescents and young adults presented with locally advanced or metastatic disease at diagnosis. Consequently, 68.3% and 62.4% adolescents and young adults received neoadjuvant and adjuvant treatments. The rate of complete pathological response was 24.1%; whereas 38.6% patients had stage IV disease, and 93.1% were microsatellite stable. At a mean follow-up of 5 years, no difference in cancer-specific survival, but a lower disease-free survival was reported in adolescents and young adults (p < 0.0001) vs the matched group. Adolescents and young adults with stages I to II disease had shorter cancer-specific survival and disease-free survival (p = 0.006; p < 0.0001); with stage III disease, they had a shorter disease-free survival (p = 0.01). LIMITATIONS: This study was limited by its observational, retrospective design. CONCLUSIONS: The significantly delayed diagnosis in adolescents and young adults may have contributed to the advanced disease at presentation and lower disease-free survival, even at earlier stages, suggesting a higher metastatic potential than in older patients. See Video Abstract at http://links.lww.com/DCR/B537. CNCER DE RECTO EN PACIENTES ADOLESCENTES Y ADULTOS JVENES CUADRO DE PRESENTACIN CLNICA Y COMPARACIN DE DESENLACES POR CASOS EMPAREJADOS: ANTECEDENTES:El cáncer de recto en adolescentes y adultos jóvenes (edad ≤ 39) está aumentando. El diagnóstico temprano es un desafío en este subgrupo de pacientes.OBJETIVO:Analizar el cuadro de presentación y los desenlaces en adolescentes y adultos jóvenes con cáncer de recto esporádico.DISEÑO:Estudio retrospectivo.ÁMBITO:Tres centros europeos de tercer nivel.PACIENTES:Se analizaron los datos de adolescentes y adultos jóvenes operados de cáncer de recto esporádico (enero de 2008 - octubre de 2019). Para comparar los desenlaces se emparejó a adolescentes y adultos jóvenes con un grupo de pacientes mayores de 40 años operados en el mismo período de tiempo.PRINCIPALES VARIABLES ANALIZADAS:Cuadro clínico, resultados a largo plazo.RESULTADOS:Los cánceres de recto esporádicos en adolescentes y adultos jóvenes fueron 101 (2,4%, edad media: 33,5, rango 18-39). El 51,5% eran hombres, el 17,8% de los pacientes fumaba. El 25,7% tentía antecedentes familiares de cáncer colorrectal. El 24,7% eran obesos. El diagnóstico con base en los síntomas se informó en el 92,1% de los pacientes, el tiempo promedio desde los primeros síntomas hasta el diagnóstico fue de 13,7 meses. El síntoma más común en el momento del diagnóstico fue el sangrado rectal (68,8%). 12% y 34% de adolescentes y adultos jóvenes presentaron enfermedad localmente avanzada o metastásica en el momento del diagnóstico. Por lo tanto, el 68,3% y el 62,4% de adolescentes y adultos jóvenes recibieron neoadyuvancia y adyuvancia. La tasa de respuesta patológica completa fue del 24,1%; mientras que el 38,6% estaban en estadio IV. El 93,1% eran microsatelite estable. Con una media de seguimiento de 5 años, no se observaron diferencias en la sobrevida específica del cáncer, pero se informó una menor sobrevida libre de enfermedad en adolescentes y adultos jóvenes (p <0,0001) frente al grupo emparejado. Los adolescentes y adultos jóvenes en estadios I-II tuvieron una sobrevida específica por cáncer y una sobrevida libre de enfermedad más corta (p = 0,006; p <0,0001); el estadio III tuvo una sobrevida libre de enfermedad más baja (p = 0,01).LIMITACIONES:Diseño observacional y retrospectivo.CONCLUSIONES:El diagnóstico notablemente demorado en adolescentes y adultos jóvenes puede contribuir a la presentación de una enfermedad avanzada y a una menor sobrevida libre de enfermedad, incluso en estadios más tempranas, lo cual implica un mayor potencial metastásico en comparación con pacientes mayores. Consulte Video Resumen en http://links.lww.com/DCR/B537.


Assuntos
Carcinoma/diagnóstico , Carcinoma/terapia , Hemorragia Gastrointestinal/etiologia , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapia , Adolescente , Adulto , Fatores Etários , Carcinoma/complicações , Carcinoma/secundário , Diagnóstico Tardio , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Anamnese , Instabilidade de Microssatélites , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Retais/complicações , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
4.
Lancet Gastroenterol Hepatol ; 4(8): 599-610, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31178342

RESUMO

BACKGROUND: Previous studies have suggested that sigmoidectomy with primary anastomosis is superior to Hartmann's procedure. The likelihood of stoma reversal after primary anastomosis has been reported to be higher and reversal seems to be associated with lower morbidity and mortality. Although promising, results from these previous studies remain uncertain because of potential selection bias. Therefore, this study aimed to assess outcomes after Hartmann's procedure versus sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy, for perforated diverticulitis with purulent or faecal peritonitis (Hinchey III or IV disease) in a randomised trial. METHODS: A multicentre, randomised, open-label, superiority trial was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands. Patients aged between 18 and 85 years who presented with clinical signs of general peritonitis and suspected perforated diverticulitis were eligible for inclusion if plain abdominal radiography or CT scan showed diffuse free air or fluid. Patients with Hinchey I or II diverticulitis were not eligible for inclusion. Patients were allocated (1:1) to Hartmann's procedure or sigmoidectomy with primary anastomosis, with or without defunctioning ileostomy. Patients were enrolled by the surgeon or surgical resident involved, and secure online randomisation software was used in the operating room or by the trial coordinator on the phone. Random and concealed block sizes of two, four, or six were used, and randomisation was stratified by age (<60 and ≥60 years). The primary endpoint was 12-month stoma-free survival. Patients were analysed according to a modified intention-to-treat principle. The trial is registered with the Netherlands Trial Register, number NTR2037, and ClinicalTrials.gov, number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, and June 9, 2013, and trial termination on June 3, 2016, 133 patients (93 with Hinchey III disease and 40 with Hinchey IV disease) were randomly assigned to Hartmann's procedure (68 patients) or primary anastomosis (65 patients). Two patients in the Hartmann's group were excluded, as was one in the primary anastomosis group; the modified intention-to-treat population therefore consisted of 66 patients in the Hartmann's procedure group (46 with Hinchey III disease, 20 with Hinchey IV disease) and 64 in the primary anastomosis group (46 with Hinchey III disease, 18 with Hinchey IV disease). In 17 (27%) of 64 patients assigned to primary anastomosis, no stoma was constructed. 12-month stoma-free survival was significantly better for patients undergoing primary anastomosis compared with Hartmann's procedure (94·6% [95% CI 88·7-100] vs 71·7% [95% CI 60·1-83·3], hazard ratio 2·79 [95% CI 1·86-4·18]; log-rank p<0·0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann's procedure compared with primary anastomosis (morbidity: 29 [44%] of 66 patients vs 25 [39%] of 64, p=0·60; mortality: two [3%] vs four [6%], p=0·44). INTERPRETATION: In haemodynamically stable, immunocompetent patients younger than 85 years, primary anastomosis is preferable to Hartmann's procedure as a treatment for perforated diverticulitis (Hinchey III or Hinchey IV disease). FUNDING: Netherlands Organisation for Health Research and Development.


Assuntos
Colo Sigmoide/cirurgia , Doença Diverticular do Colo/cirurgia , Perfuração Intestinal/cirurgia , Peritonite/etiologia , Protectomia , Reto/cirurgia , Idoso , Anastomose Cirúrgica/efeitos adversos , Colostomia , Doença Diverticular do Colo/complicações , Feminino , Humanos , Ileostomia , Perfuração Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Protectomia/efeitos adversos , Resultado do Tratamento
5.
BMC Surg ; 10: 29, 2010 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-20955571

RESUMO

BACKGROUND: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). METHODS/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs. DISCUSSION: The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis. TRIAL REGISTRATION: Nederlands Trial Register NTR2037.


Assuntos
Diverticulite/complicações , Perfuração Intestinal/cirurgia , Lavagem Peritoneal/métodos , Peritonite/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Colectomia , Colostomia , Feminino , Humanos , Perfuração Intestinal/etiologia , Laparoscopia , Pessoa de Meia-Idade , Peritonite/etiologia , Resultado do Tratamento
6.
Arch Pediatr ; 17(8): 1153-5, 2010 Aug.
Artigo em Francês | MEDLINE | ID: mdl-20541377

RESUMO

Acute renal failure (ARF) following Chlamydia pneumoniae pneumonia is rarely reported in adults. We present an observation in a 10-year-old child, who had C. pneumoniae pneumonia treated with roxithromycin for a period of 10 days, without any other nephrotoxic drug, in particular nonsteroidal anti-inflammatory drugs. At the end of antibiotic treatment, he presented with asthenia, polyuria, polydipsia, increased plasma creatinine, metabolic acidosis, hypokalemia, and markers of tubular damage. The etiological investigations showed positive C. pneumoniae antibodies, increased serum concentrations of C3 and C4 complement, IgA, and IgG. No uveitis was noted. The diagnosis was tubulointerstitial nephropathy after C. pneumoniae pneumonia. C. pneumoniae pneumonia should be considered a differential diagnosis of community-acquired pneumonia, especially in cases of poor response to conventional antibiotic therapy. It may be associated with tubulointerstitial nephropathy and/or rapidly progressive glomerulonephritis whose severity varies in children as in adults. Early and effective treatment of C. pneumoniae infection with macrolide antibiotics usually provides favorable progression of renal function.


Assuntos
Injúria Renal Aguda/etiologia , Infecções por Chlamydophila/complicações , Injúria Renal Aguda/sangue , Injúria Renal Aguda/fisiopatologia , Adulto , Anorexia/etiologia , Anorexia/microbiologia , Antibacterianos/uso terapêutico , Criança , Infecções por Chlamydophila/sangue , Infecções por Chlamydophila/tratamento farmacológico , Chlamydophila pneumoniae , Creatinina/sangue , Diagnóstico Diferencial , Febre/etiologia , Febre/microbiologia , Humanos , Masculino , Resultado do Tratamento
7.
J Magn Reson Imaging ; 31(1): 110-6, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20027578

RESUMO

PURPOSE: To test the ability of MION-47 enhanced MRI to identify tissue macrophage infiltration in a rabbit model of aortic valve sclerosis (AVS). MATERIALS AND METHODS: The aortic valves of control and cholesterol-fed New Zealand White rabbits were imaged in vivo pre- and 48 h post-intravenous administration of MION-47 using a 1.5 Tesla (T) MR clinical scanner and a CINE fSPGR sequence. MION-47 aortic valve cusps were imaged ex vivo on a 3.0T whole-body MR system with a custom gradient insert coil and a three-dimensional (3D) FIESTA sequence and compared with aortic valve cusps from control and cholesterol-fed contrast-free rabbits. Histopathological analysis was performed to determine the site of iron oxide uptake. RESULTS: MION-47 enhanced the visibility of both control and cholesterol-fed rabbit valves in in vivo images. Ex vivo image analysis confirmed the presence of significant signal voids in contrast-administered aortic valves. Signal voids were not observed in contrast-free valve cusps. In MION-47 administered rabbits, histopathological analysis revealed iron staining not only in fibrosal macrophages of cholesterol-fed valves but also in myofibroblasts from control and cholesterol-fed valves. CONCLUSION: Although iron oxide labeling of macrophage infiltration in AVS has the potential to detect the disease process early, a macrophage-specific iron compound rather than passive targeting may be required.


Assuntos
Estenose da Valva Aórtica/diagnóstico , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Meios de Contraste , Óxido Ferroso-Férrico , Masculino , Nanopartículas , Coelhos , Esclerose , Sensibilidade e Especificidade
8.
Circ Cardiovasc Imaging ; 2(3): 226-34, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19808597

RESUMO

BACKGROUND: Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. In this report, we determined the utility of the MR contrast agent gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA. METHODS AND RESULTS: Five control and 7 atherosclerotic rabbits were sequentially imaged after administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T(1)-weighted pulse sequence on a 3-T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values after GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours after injection but not Gd-DTPA at peak enhancement was shown to correlate with a quantitative histological morphology index related to these 2 plaque features. CONCLUSIONS: GdF-enhanced MRI of atherosclerotic plaques allows noninvasive quantitative information about plaque composition to be acquired at multiple time points after injection (within 1 and up to 24 hours after injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events.


Assuntos
Doenças da Aorta/patologia , Ruptura Aórtica/etiologia , Aterosclerose/patologia , Meios de Contraste , Gadolínio DTPA , Angiografia por Ressonância Magnética , Compostos Organometálicos , Animais , Doenças da Aorta/complicações , Ruptura Aórtica/patologia , Aterosclerose/complicações , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Modelos Animais de Doenças , Estudos de Viabilidade , Fluorocarbonos , Gadolínio DTPA/administração & dosagem , Gadolínio DTPA/farmacocinética , Injeções , Masculino , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/farmacocinética , Valor Preditivo dos Testes , Coelhos
9.
Clin Pharmacol Ther ; 86(6): 609-18, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19865079

RESUMO

The aim of this study was to develop a population pharmacokinetic model of tacrolimus in pediatric kidney transplant patients, identify factors that explain variability, and determine dosage regimens. Pharmacokinetic samples were collected from 50 de novo pediatric kidney transplant patients (age 2-18 years) who were on tacrolimus treatment. Population pharmacokinetic analysis of tacrolimus was performed using NONMEM, and the impact of variables (demographic and clinical factors, and CYP3A4-A5, ABCB1, and ABCC2 polymorphisms) was tested. The pharmacokinetic data were described by a two-compartment model that incorporated first-order absorption and lag time. The apparent oral clearance (CL/F) was significantly related to body weight (allometric scaling); in addition, it was higher in patients with low hematocrit levels and lower in patients with CYP3A5*3/*3. The population pharmacokinetic-pharmacogenetic model developed in de novo pediatric kidney transplant patients demonstrated that, in children, tacrolimus dosage should be based on weight, hematocrit levels, and CYP3A5 polymorphism. Individualization of therapy will enable the optimization of tacrolimus exposure, with resultant beneficial effects on kidney function in the initial post-transplantation period.


Assuntos
Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Transplante de Rim , Modelos Biológicos , Polimorfismo Genético , Tacrolimo/farmacocinética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adolescente , Fatores Etários , Peso Corporal , Criança , Pré-Escolar , Citocromo P-450 CYP3A/metabolismo , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , França , Hematócrito , Humanos , Imunossupressores/administração & dosagem , Masculino , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Reprodutibilidade dos Testes , Tacrolimo/administração & dosagem , Resultado do Tratamento
10.
Pediatr Transplant ; 13(6): 725-30, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19691564

RESUMO

OBJECTIVE AND METHODS: To assess patient survival in pediatric renal transplantation, we retrospectively reviewed 573 transplants in 553 patients, registered from 1995 to 2005. RESULTS: Mean age at transplantation was 9.9 years. Patient survival at 1, 5 and 10 years was respectively 99%, 97% and 96%. Death occurred at a median time of 2.6 years after transplantation. Long-term patient survival was significantly lower in recipients younger than 5 years old. Seventeen patients (3.1%) died. Two deaths occurred while under maintenance dialysis. Among the remaining patients, the two main causes of death were infections (33%) and malignancies (27%). Interestingly, initial disease-related complications were a major cause of death (34%). CONCLUSION: A low mortality rate was observed, with the majority of deaths due to malignancies and infections, and with a notable participation of complications related to the initial disease. No impact of cardiovascular disease was noted with the given follow-up period. Improvements in managing immunosuppression may contribute to reducing mortality in pediatric renal transplantation.


Assuntos
Rejeição de Enxerto/mortalidade , Nefropatias/mortalidade , Nefropatias/terapia , Transplante de Rim/métodos , Criança , Pré-Escolar , Bases de Dados Factuais , França , Humanos , Imunossupressores/uso terapêutico , Nefropatias/cirurgia , Transplante de Rim/efeitos adversos , Sistema de Registros , Diálise Renal , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
11.
Nephrol Ther ; 5 Suppl 4: S250-5, 2009 Jun.
Artigo em Francês | MEDLINE | ID: mdl-19596344

RESUMO

AIMS: To assess incidence of chronic kidney disease in general population and to describe baseline characteristics of incident patients. METHODS: Between 1st/01/04 and 30/06/06 all incident cases of chronic kidney disease in the Nancy district were prospectively identified. New cases were identified from all medical laboratories in this area and determined by a persistently increased serum creatinine level (> or = 150micromol/l, or paediatric levels) for 3 months after the 1st/01/04, and by living in Nancy area. RESULTS: The annual incidence rate of detected chronic kidney disease was 1 per thousand inhabitants (1,3 per thousand for men and 0,7 per thousand for women). Incidents patients were old (mean age: 77 years) and with numerous comorbidities (diabetes: 34 %, cardiac failure: 23 %). More than 30% of incident patients were diagnosed at sever stage of chronic kidney disease (<30ml/min/1,73m(2)). CONCLUSIONS: The annual incidence of diagnosed chronic kidney disease is common: 10 times more than end-stage renal disease in France. Most of these patients are diagnosed in a severe stage of chronic kidney disease whereas they could be detected earlier and benefit from adequate, appropriate and multidisciplinary take care.


Assuntos
Nefropatias/diagnóstico , Nefropatias/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Pré-Escolar , Doença Crônica , Creatinina/sangue , Feminino , França/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Nefropatias/sangue , Nefropatias/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
12.
Arch Pediatr ; 16(1): 23-6, 2009 Jan.
Artigo em Francês | MEDLINE | ID: mdl-19038535

RESUMO

Neonatal Bartter syndrome is a rare condition, usually revealed by alkalosis and hypokalemia. Clinical and biological signs of neonatal Bartter syndrome are quite different from those encountered when this disease is diagnosed in older children. Diagnosis of neonatal Bartter syndrome is even more difficult in very preterm infants. The aim of this study was to highlight specific clinical and biological signs that may help direct physicians towards the diagnosis of neonatal Bartter syndrome when premature infants present with an atypical renal tubular disorder. Our case reports focus on excessive diuresis with elevated renal sodium excretion and severe dehydration. Correcting tubular disorders early may help avoid dehydration in the fragile preterm newborn.


Assuntos
Síndrome de Bartter/diagnóstico , Doenças do Prematuro/diagnóstico , Fatores Etários , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Síndrome de Bartter/tratamento farmacológico , Síndrome de Bartter/genética , Suplementos Nutricionais , Feminino , Idade Gestacional , Humanos , Indometacina/administração & dosagem , Lactente , Recém-Nascido , Masculino , Potássio/administração & dosagem , Potássio/uso terapêutico , Fatores de Tempo
13.
Transplant Proc ; 38(7): 2321-3, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16980079

RESUMO

Parvovirus B19 (PV B19) infection is known to cause acute anemia in solid organ transplant recipients. Intravenous immunoglobulin combined with reduction of immunosuppression may be of benefit to clear the infection. However, PV B19-associated anemia can be recurrent. We describe three renal transplant recipients with a PV B19 infection. These patients showed recurrent anemia with episodes separated by as much as several months.


Assuntos
Anemia/virologia , Transplante de Rim/efeitos adversos , Infecções por Parvoviridae/diagnóstico , Parvovirus B19 Humano , Adulto , Transfusão de Sangue , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Terapia de Imunossupressão/métodos , Nefropatias/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Tempo
14.
J Chir (Paris) ; 140(1): 22-32, 2003 Feb.
Artigo em Francês | MEDLINE | ID: mdl-12709649

RESUMO

The global mortality for Fournier's gangrene is one in five. In half the cases, the infection is polymicrobial with either anaerobes or gram negative bacilli. Factors which worsen prognosis include renal insufficiency, streptococcal infection, or need for hospital admission. Diagnosis must be prompt and treatment multidisciplinary involving the surgeon, intensivist, and infectious disease specialist; early and adequate surgical debridement must be accompanied by well-chosen antibiotics and hyperbaric oxygen therapy. Post-debridement therapy requires a long period of dressing changes and skin grafting to achieve final wound closure. This is an aggressive disease with a high mortality, but the depth and extent of invasive infection does not determine prognosis; the first priority is prompt and wide surgical excision/debridement of infected tissues to pre-empt the development of systemic sepsis; this should not be deferred while arranging transfer to a facility with a hyperbaric chamber.


Assuntos
Gangrena de Fournier , Antibacterianos/uso terapêutico , Desbridamento , Gangrena de Fournier/classificação , Gangrena de Fournier/diagnóstico , Gangrena de Fournier/microbiologia , Gangrena de Fournier/mortalidade , Gangrena de Fournier/cirurgia , Gangrena de Fournier/terapia , Humanos , Oxigenoterapia Hiperbárica , Masculino , Períneo , Cuidados Pós-Operatórios , Prognóstico , Fatores de Risco , Tomografia Computadorizada por Raios X
16.
Arch Pediatr ; 9(5): 489-94, 2002 May.
Artigo em Francês | MEDLINE | ID: mdl-12053542

RESUMO

OBJECTIVES: The aim of this study was to describe the intensive care unit neonatologists' attitudes about a neonate with terminal or pre-terminal renal failure. METHODS: A questionnaire was sent to all French neonatal intensive care units. Physicians were asked to describe their attitude about neonatal chronic renal failure (Would you agree with dialysis and graft for these children?). Physicians were also presented with two clinical observations involving neonates with varying degrees of renal insufficiency and a complicating comorbidity, including neurological abnormality or socioeconomic circumstances. RESULTS: Responses were obtained from 92% of the university neonatal care units. The will to take care of a neonate with end-stage renal failure till the renal graft, varied greatly from a centre to another one. Three (9%) university-teams said they had a strong will to bring the baby from the neonatal period to the time of renal graft. Eleven other centres (32%) did not have any will for accompanying the baby till the renal graft. Eight centres (24%) would be rather favourable to the idea of dialysis and graft, and 12 others (35%) would be rather unfavourable. CONCLUSION: The results of this study show great differences between French neonatologists when they are faced to newborns with end stage renal failure. Ethical, medical and organisational difficulties are matters of controversy. The epidemiological impact of the perinatal discussion could be a 20% variation of all the renal grafts in children.


Assuntos
Terapia Intensiva Neonatal , Falência Renal Crônica/terapia , Padrões de Prática Médica/normas , Ética Médica , Humanos , Recém-Nascido , Falência Renal Crônica/complicações , Transplante de Rim , Exame Neurológico , Diálise Renal/métodos , Fatores Socioeconômicos , Inquéritos e Questionários
18.
Pediatr Nephrol ; 16(5): 397-403, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11405112

RESUMO

Growth retardation occurs frequently in renal transplanted children (RTx) and can be improved by growth hormone (GH) treatment. This study retrospectively examines the insulin-like growth factor-1 (IGF-1) and IGF binding protein (IGFBP) profile of ten growth-retarded children previously given renal allografts, after 1 year of GH treatment period. Ten prepubertal patients (nine boys and one girl) were investigated. They had a mean chronological age (CA) of 11.4 +/- 1.1 years and a mean bone age (BA) of 7.3 +/- 0.9 years. Mean height was -3.9 +/- 0.4 SD units below the mean for CA. The mean body mass index (BMI) was 16.9 +/- 0.6 and the mean inulin clearance was 36.5 +/- 4.9 ml/min/1.73 m2. Recombinant hGH was given at 4 IU/m2/day. Plasma GH, total and free IGF-1, IGFBP-2 and -3 were measured by specific radioimmunoassay (RIA). IGFBPs were characterized by SDS PAGE techniques and ligand and immunoblot analyses. Mean velocity was markedly increased (P < 0.01) after 1 year of GH therapy, expressed as SD score for BA. The range of growth response was wide. The total and free plasma IGF-1 increased (P < 0.01) by about 100% (mean values after GH therapy: 95.9 +/- 2.1 nM and 165 +/- 29 pM, respectively). Plasma IGFBP-3 concentrations increased by about 40% (mean value: 148 +/- 18 pM, P < 0.01), with a concomitant increase in both intact IGFBP-3 and its 30-kDa proteolytic fragment. There was no change in plasma IGFBP-2 concentration. Both mean values of inulin clearance and BMI were unchanged during the treatment. In view of the IGF-1/IGFBP concentration changes, there should have been an even better growth response to GH therapy in these patients. This strongly suggests IGF-1 insensitivity, probably as a result of corticosteroid therapy.


Assuntos
Hormônio do Crescimento/farmacologia , Substâncias de Crescimento/metabolismo , Transplante de Rim/fisiologia , Adolescente , Western Blotting , Estatura/efeitos dos fármacos , Índice de Massa Corporal , Criança , Pré-Escolar , Eletroforese em Gel de Poliacrilamida , Feminino , Taxa de Filtração Glomerular , Crescimento/efeitos dos fármacos , Humanos , Indicadores e Reagentes , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Masculino , Somatomedinas/metabolismo
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