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Biomedical subjects

Olivier Goulet

Publications and source records attributed to Olivier Goulet.

At least 19 recordsLinked to original sources
PubMed2006

Microvillous inclusion disease (microvillous atrophy).

Microvillous inclusion disease (MVID) or microvillous atrophy is a congenital disorder of the intestinal epithelial cells that presents with persistent life-threatening watery diarrhea and is characterized by morphological enterocyte abnormalities. MVID manifests either in the first days of life (early-onset form) or in the first two months (late-onset form) of life. MVID is a very rare disorder of unknown origin, probably transmitted as an autosomal recessive trait. To date, no prevalence data are available. Ultrastructural analyses reveal: 1) a partial to total atrophy of microvilli on mature enterocytes with apical accumulation of numerous secretory granules in immature enterocytes; 2) the highly characteristic inclusion bodies containing rudimentary or fully differentiated microvilli in mature enterocytes. Light microscopy shows accumulation of PAS-positive granules at the apical pole of immature enterocytes, together with atrophic band indicating microvillus atrophy and, in parallel, an intracellular PAS or CD10 positive line (marking the microvillous inclusion bodies seen on electron microscopy). Intestinal failure secondary to diarrhea is definitive. To date, no curative therapy exists and children with MVID are totally dependent on parenteral nutrition. Long-term outcome is generally poor, due to metabolic decompensation, repeated states of dehydration, infectious and liver complications related to the parenteral nutrition. As MVID is a very rare disorder, which is extremely difficult to diagnose and manage, children with MVID should be transferred to specialized pediatric gastro-intestinal centers, if possible, a center equipped to perform small bowel transplantation. Early small bowel transplantation resulting in intestinal autonomy gives new hope for disease management and outcome.

Atrophy↗
PubMed2006

Study of the impact of liver transplantation on the outcome of intestinal grafts in children.

BACKGROUND: Successful small bowel transplantation remains a challenge due to the septic and immune content of the gut. The possible beneficial role of the liver was assessed in pediatric recipients of isolated intestinal and liver intestinal combined transplantation, receiving the same immunosuppressive therapy. METHODS: Fifteen children who underwent small bowel transplantation (seven SbTx) or combined liver-small bowel transplantation (eight LSbTx) at a single center between 1994 and 1998 were retrospectively reviewed and compared with fifteen controls (eight normal and seven appendicitis as inflammatory control). Transplant and patient survival, acute rejection episodes were analyzed and compared. Epithelial apoptotic body counts (ABC) and NF-kB (p65), Caspase-3 and Bax intestinal immunostaining from days 0 to 20 after transplantation were assessed. RESULTS: Graft and patient survivals at 5 years were respectively 75% and 75% in LSbTx; 43% and 57% in SbTx (NS). Histological analysis showed higher ABC in LSbTx intestinal mucosa (P = 0.05 on day 5, P < 0.01 thereafter). Immunostaining of biopsies on day 0 after reperfusion showed different expression of NF-kB, Caspase-3 and Bax on endothelial (P < 0.05 for NF-kB and Bax), mononuclear (P < 0.05 for Bax) and epithelial cells in LSbTx and SbTx. CONCLUSIONS: Our results suggest a protective role of the liver toward intestinal transplantation even in absence of significative difference, probably due to the small number of children. Early changes in NF-kB immunostaining in the biopsies sampled on day 0, pointed to a possible beneficial effect of the liver in the very early phase following transplantation, perhaps through the differential control of ischemia-reperfusion.

Biomarkers↗
PubMed2006

Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes.

We describe four unrelated children who were referred to two tertiary referral medical genetics units between 1991 and 2005 and who are affected with juvenile polyposis of infancy. We show that these children are heterozygous for a germline deletion encompassing two contiguous genes, PTEN and BMPR1A. We hypothesize that juvenile polyposis of infancy is caused by the deletion of these two genes and that the severity of the disease reflects cooperation between these two tumor-suppressor genes.

Base Sequence↗
PubMed2006

Causes and management of intestinal failure in children.

Intestinal failure is a condition requiring the use of parenteral nutrition as long as it persists. Causes of severe protracted intestinal failure include short bowel syndrome, congenital diseases of enterocyte development, and severe motility disorders (total or subtotal aganglionosis or chronic intestinal pseudo-obstruction syndrome). Intestinal failure may be irreversible in some patients, thus requiring permanent parenteral nutrition. Liver disease may develop with subsequent end-stage liver cirrhosis in patients with intestinal failure as a consequence of both underlying digestive disease and unadapted parenteral nutrition. Death will occur if combined liver-intestine transplantation is not performed. Catheter-related sepsis and/or extensive vascular thrombosis may impede the continuation of a safe and efficient parenteral nutrition and may also require intestinal transplantation in some selected cases. Thus management of patients with intestinal failure requires an early recognition of the condition and the analysis of its risk of irreversibility. Timing of referral for intestinal transplantation remains a crucial issue. As a consequence, management should include therapies adapted to each stage of intestinal failure based on a multidisciplinary approach in centers involving pediatric gastroenterology, parenteral nutrition expertise, home parenteral nutrition program, pediatric surgery, and liver intestinal transplantation program.

Blind Loop Syndrome↗
PubMed2006

Short bowel syndrome and intestinal transplantation in children.

PURPOSE OF REVIEW: This review summarizes recent knowledge and clinical practice for pediatric patients suffering extensive intestinal resection causing short bowel syndrome. This condition requires the use of parenteral nutrition, as long as intestinal failure persists, and may be, in some selected cases, an indication for intestinal transplantation. RECENT FINDINGS: Biological evaluation of intestinal failure is becoming possible with the use of plasma citrulline as a marker of intestinal mass. Few epidemiological data are available; some indicate an increased incidence of short bowel syndrome-related gastroschisis and persistent high incidence of necrotizing enterocolitis. Morbidity and mortality data in pediatric patients with short bowel syndrome are limited, while long-term outcome is better documented from recently reported cohorts. Non-transplant surgery is one of the best options for patients with unadapted short bowel syndrome. Isolated liver transplantation may be avoided. The use of trophic factors for enhancing mucosal hyperplasia still remains disappointing. SUMMARY: The management should include therapies adapted to each stage of intestinal failure, based on a multidisciplinary approach in centers involving pediatric surgery, pediatric gastroenterology, parenteral nutrition expertise, home-parenteral nutrition program, and liver-intestinal transplantation experience. If managed appropriately, the prognosis of short bowel syndrome is excellent, with limited indications for intestinal and/or liver transplantation. Timing for patient referral in specialized centers remains an issue.

Biomarkers↗
PubMed2006

Soy protein infant formulae and follow-on formulae: a commentary by the ESPGHAN Committee on Nutrition.

This comment by the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Committee on Nutrition summarizes available information on the composition and use of soy protein formulae as substitutes for breastfeeding and cows' milk protein formulae as well as on their suitability and safety for supporting adequate growth and development in infants. Soy is a source of protein that is inferior to cows' milk, with a lower digestibility and bioavailability as well as a lower methionine content. For soy protein infant formulae, only protein isolates can be used, and minimum protein content required in the current European Union legislation is higher than that of cows' milk protein infant formulae (2.25 g/100 kcal vs. 1.8 g/100kcal). Soy protein formulae can be used for feeding term infants, but they have no nutritional advantage over cows' milk protein formulae and contain high concentrations of phytate, aluminum, and phytoestrogens (isoflavones), which might have untoward effects. There are no data to support the use of soy protein formulae in preterm infants. Indications for soy protein formulae include severe persistent lactose intolerance, galactosemia, and ethical considerations (e.g., vegan concepts). Soy protein formulae have no role in the prevention of allergic diseases and should not be used in infants with food allergy during the first 6 months of life. If soy protein formulae are considered for therapeutic use in food allergy after the age of 6 months because of their lower cost and better acceptance, tolerance to soy protein should first be established byclinical challenge. There is no evidence supporting the use of soy protein formulae for the prevention or management of infantile colic, regurgitation, or prolonged crying.

Colic↗
PubMed2006

Feeding preterm infants after hospital discharge: a commentary by the ESPGHAN Committee on Nutrition.

Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding.

Anthropometry↗
PubMed2006

Characteristics of inflammatory bowel disease with onset during the first year of life.

BACKGROUND: Inflammatory bowel disease (IBD) is recognized in young children, however, only rare data on onset and evolution are available in children younger than 1 year. In the present clinical study, we aimed to analyze characteristics and clinical course of children with very early onset IBD. We were particularly interested in the relationship between bacterial infections and the use of antibiotics before the onset of IBD. PATIENTS AND METHODS: The IBD database of Necker-Enfants-Malades-Hospital was screened for patients with IBD with disease onset during the first year of life and a follow-up of at least 2.5 years. Ten patients were identified during the period 1996-2002. RESULTS: All patients presented with rectal bleeding and had colonic involvement. Four patients had definitive diagnosis of Crohn disease; ulcerative or indeterminate colitis was seen in 2 and 4 children, respectively. Five of the patients had a positive history of neonatal or early-onset bacterial infection with use of antibiotics before onset of IBD, 4 patients were still breastfed and 3 just weaned when GI symptoms started. Seven patients had a severe onset of disease requiring bowel rest, parenteral nutrition and steroid medication, followed by azathioprine or cyclosporine medication. Surgery was necessary in 3 of 10 patients. Disease relapses were frequent and observed in 8 of 10 children. DISCUSSION: Very early onset IBD may reflect a subgroup of patients characterized by a particular sensitivity to modifications of the intestinal flora. Neonatal IBD was most often severe in presentation and evolution.

Age of Onset↗
PubMed2006

Candidates for intestinal transplantation: a multicenter survey in Europe.

OBJECTIVES: Epidemiology of candidacy for intestinal transplantation (ITx) and timing for referral for ITx are unknown. Patient candidacy and physician attitudes toward ITx were investigated among centers that participated in previous European surveys on home parenteral nutrition (HPN). METHODS: Patients on HPN for benign intestinal failure (IF) were evaluated by a structured questionnaire. Candidacy was assessed by USA Medicare and American Transplantation Society criteria, categorized as: (1) life-threatening HPN complications; (2) high risk of death because of the gastrointestinal disease; (3) IF with high morbidity or patient HPN refusal. Physicians judged candidacy as immediate or potential. RESULTS: Forty-one centers from nine countries enrolled 688 adults (> 18 yr) and 166 pediatric patients; 70% of patients were from five countries which collected 60-100% of their HPN patients. Candidacy was 15.7% in adults and 34.3% in pediatrics (HPN failure, 62.1% and 28.1%; gastrointestinal disease, 25.9% and 59.6%; high morbidity IF or HPN refusal, 12.0% and 12.3%, respectively). Immediate candidacy was required for 14.8% of adult and 15.8% of pediatric candidates (< 50% of candidates because of HPN-related liver failure). Among centers, the candidacy rate ranged 0-100% and was negatively associated with the number of patients enrolled in the survey (R = -0.463, p = 0.002). Among the major contributing countries, candidacy ranged 0.3-0.8/million inhabitants for adults and 0.9-2/million inhabitants < or = 18 yr for pediatric candidates. CONCLUSIONS: The rate of candidacy and the indications for ITx candidacy differed greatly among age groups and HPN centers; within countries candidacy was more homogeneous; physicians had a generally reserved attitude toward ITx.

Adolescent↗
PubMed2005

Clinical and biological consequences of immunization to infliximab in pediatric Crohn's disease.

Tumor necrosis factor (TNF)-alpha plays a critical role in the initiation and progression of Crohn's disease, a chronic inflammatory disorder of the gastrointestinal tract. Infliximab, a chimeric monoclonal antibody blocking TNF-alpha, has proven effective as an induction and maintenance therapy for refractory Crohn's disease in adult and pediatric patients. However, infliximab therapy induces the appearance of neutralizing anti-infliximab antibodies. In the pediatric cohort, we analyzed (n=28) sensitization occurred in 35.7% patients and was associated with a loss of response to maintenance infusions. In two patients presenting high titers of anti-infliximab antibodies, severe infusion reactions were observed, possibly IgE-mediated, precluding further use of the medication. Serum concentrations of TNF-alpha and infliximab were influenced by the presence of anti-infliximab antibodies. We propose that surveillance of circulating infliximab and/or TNF-alpha concentration during maintenance therapy represents an indirect but reliable method to monitor anti-infliximab immunization.

Adolescent↗
PubMed2005

Successful use of the new immune-suppressor sirolimus in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome).

IPEX (immune-dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is an autoimmune disorder with an often lethal outcome in spite of immunosuppressive therapy. We report the successful use of sirolimus in 3 patients with IPEX. The efficacy of sirolimus is probably due to its different mode of action compared to calcineurin-dependent agents.

Child↗
PubMed2005

The need for nutrition support teams in pediatric units: a commentary by the ESPGHAN committee on nutrition.

The reported prevalence of malnutrition in pediatric hospitals ranges from 15% to 30% of patients, with an impact on growth, morbidity and mortality. Major deficits in nutrition care have been highlighted in European hospitals, and the implementation of nutrition support teams (NSTs) has been suggested as a means to improve malnutrition diagnosis and nutrition care for hospitalized patients. This comment by the ESPGHAN Committee on Nutrition reviews disease related-mechanisms causing malnutrition and consequences of malnutrition and suggests a framework for implementation of NSTs in pediatric units. The recommendations by the Committee on Nutrition include: 1) Implementation of NSTs in hospitals is recommended to improve nutritional management of sick children; 2) The main tasks of the NST should include screening for nutritional risk, identification of patients who require nutritional support, provision of adequate nutritional management, education and training of hospital staff and audit of practice; 3) The NST should be multidisciplinary, with expertise in all aspects of clinical nutrition care; 4) The funds needed to support NSTs should be raised from the health care system; and 5) Further research is needed to evaluate the effects of NSTs in prevention and management of pediatric nutritional disorders, including cost effectiveness in different settings.

Child↗
PubMed2005

2003 report of the intestine transplant registry: a new era has dawned.

SUMMARY BACKGROUND DATA: The intestine has been more difficult to transplant than other solid organs. We analyzed registry data to determine the scope and success of intestine transplantation in the current era. METHODS: All known intestinal-transplant programs participated. Patient- and graft-survival estimates were obtained using the Kaplan-Meier product limit method and were analyzed with the Wilcoxon statistic. RESULTS: Sixty-one programs provided data on 989 grafts in 923 patients. Four patients were lost to follow-up. The short-gut syndrome was the most common primary indication for transplantation. Sixty-one percent of the recipients were < or =18 years. Proportionally more combined intestinal and liver transplants were performed in this group. More than 80% of all current survivors had stopped parenteral nutrition and resumed normal daily activities. A multivariate analysis of cases within the last 5 years revealed that transplantation of patients waiting at home, recipient age, antibody induction immune suppression, and center experience with at least 10 cases were associated with improved patient survival. One-year graft survival rates of 81% were achieved in patients who were induced with antithymocyte globulin and maintained on tacrolimus. CONCLUSIONS: Transplantation is an effective therapy for the treatment of patients with end-stage intestine failure who cannot tolerate parenteral nutrition. With newer immune suppressive protocols, 1-year graft and patient survival rates approach the results of liver transplantation. Further improvement in survival are expected with early referral since suitable donor organs are scarce and survival rates are better when patients are well enough to wait at home for their transplant.

Adult↗