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1.
Allergy ; 72(12): 1916-1924, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28600891

ABSTRACT

BACKGROUND: Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was-/- mice recapitulates the pathology of a conventional disease model and/or human food allergy. METHODS: Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was-/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was-/- Fcer1a-/- mice. RESULTS: Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was-/- model. Oral administration of ovalbumin (OVA) in Was-/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was-/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was-/- mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils. CONCLUSIONS: Was-/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food.


Subject(s)
Food Hypersensitivity/etiology , Food Hypersensitivity/metabolism , Mast Cells/immunology , Mast Cells/metabolism , Receptors, IgE/metabolism , Wiskott-Aldrich Syndrome Protein/genetics , Adult , Allergens/immunology , Anaphylaxis , Animals , Disease Models, Animal , Female , Food Hypersensitivity/diagnosis , Gene Expression , Humans , Immunization , Immunoglobulin E/immunology , Male , Mice , Mice, Knockout , Phenotype , Wiskott-Aldrich Syndrome/diagnosis , Wiskott-Aldrich Syndrome/immunology , Young Adult
2.
Support Care Cancer ; 25(9): 2933-2941, 2017 09.
Article in English | MEDLINE | ID: mdl-28536886

ABSTRACT

Gastrointestinal mucositis is a complex inflammatory reaction of the mucous membranes, a side effect of both chemotherapy and radiotherapy. Currently, assessment scales are used to diagnose mucositis. However, a biomarker which would determine whether there is mucositis and thereby establish the severity objectively would be very useful. This will give the opportunity to evaluate studies, to determine risk factors and incidence, and it will make it possible to compare studies. Moreover, this biomarker might improve clinical management for patients. In this paper, we reviewed studies concerning potential biomarkers in blood samples and fecal samples, and potential tests in breath samples and urine samples. We include biomarkers and tests studied in animal models and/or in clinical trials, and discuss the validity, diagnostic accuracy, and applicability.


Subject(s)
Biomarkers/blood , Gastrointestinal Neoplasms/complications , Mucositis/diagnosis , Animals , Humans , Incidence , Mucositis/etiology , Risk Factors
3.
Pediatr Obes ; 12(4): e33-e36, 2017 08.
Article in English | MEDLINE | ID: mdl-27241878

ABSTRACT

BACKGROUND: Children with obesity show differences in brain structure, executive function and appetitive traits when compared with lean peers. Little is known on the relationship between brain structure and these traits. OBJECTIVES: To investigate the relationship between differences in brain structure and executive function and appetitive traits, in obese and lean adolescents. METHODS: MRI was used to measure cortical thickness and subcortical volumes. Executive function was measured by a Stop Signal-and a Choice Delay Task. Appetitive traits were measured using the Child Eating Behaviour Questionnaire. RESULTS: Adolescents with obesity had greater volumes of the pallidum; 1.78 mL (SE 0.03, p=0.014), when compared with controls; 1.65 mL (SE 0.02). In the group with obesity, greater pallidum volume was positively associated with the ability to delay reward in the Choice Delay Task (p=0.012). CONCLUSION: The association between pallidum volumes and Choice Delay Task in obese adolescents supports the hypothesis that the pallidum plays an important role in executive dysfunction in obese children.


Subject(s)
Brain/physiopathology , Executive Function , Feeding Behavior , Pediatric Obesity/physiopathology , Adolescent , Child , Child Behavior , Female , Humans , Magnetic Resonance Imaging , Male , Surveys and Questionnaires
4.
Best Pract Res Clin Gastroenterol ; 30(2): 249-61, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27086889

ABSTRACT

The ultimate goal in the treatment of short bowel syndrome is to wean patients off parenteral nutrition, by promoting intestinal adaptation. Intestinal adaptation is the natural compensatory process that occurs after small bowel resection. Stimulating the remaining bowel with enteral nutrition can enhance this process. Additionally, medication can be used to either reduce factors that complicate the adaptation process or to stimulate intestinal adaptation, such as antisecretory drugs and several growth factors. The aim of this review was to provide an overview of the best nutritional strategies and medication that best promote intestinal adaptation.


Subject(s)
Adaptation, Physiological , Intestine, Small/physiopathology , Parenteral Nutrition , Short Bowel Syndrome/physiopathology , Enteral Nutrition , Humans , Intestine, Small/surgery , Nutritional Status , Short Bowel Syndrome/surgery
5.
Clin Nutr ; 35(1): 225-229, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25660415

ABSTRACT

BACKGROUND & AIMS: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date prevalence of CIF and characterizing these patients using the specially developed multicenter web-based Dutch Registry of Intestinal Failure and Intestinal Transplantation (DRIFT). METHODS: Cross-sectional study. CIF was defined as type 3 intestinal failure in which >75% of nutritional requirements were given as home parenteral nutrition (HPN) for ≥ 4 weeks in children and >50% for ≥3 months in adults. All patients with CIF receiving HPN care by the three Dutch specialized centers on January 1, 2013 and all ITx patients were registered in DRIFT (https://drift.darmfalen.nl). RESULTS: In total, 195 patients with CIF (158 adults, 37 children) were identified, of whom 184 were registered in DRIFT. The Dutch point prevalence of CIF was 11.62 per million (12.24 for adults, 9.56 for children) on January 1, 2013. Fifty-seven patients (31%) had one or more indications for ITx, while 12 patients actually underwent ITx since its Dutch introduction. Four patients required transplantectomy of their intestinal graft and 3 intestinal transplant patients died. CONCLUSION: The multicenter registry DRIFT revealed an up-to-date prevalence of CIF and provided nationwide insight into the patients with CIF during HPN and after ITx in the Netherlands. DRIFT will facilitate the multicenter monitoring of individual patients, thereby supporting multidisciplinary care and decision-making.


Subject(s)
Intestinal Diseases/epidemiology , Intestines/transplantation , Organ Transplantation , Registries , Adult , Child , Chronic Disease , Cross-Sectional Studies , Female , Humans , Internet , Intestinal Diseases/surgery , Intestines/physiopathology , Male , Netherlands/epidemiology , Nutritional Requirements , Parenteral Nutrition, Home , Postoperative Complications/therapy , Prevalence
6.
Transplant Proc ; 46(6): 2102-8, 2014.
Article in English | MEDLINE | ID: mdl-25131117

ABSTRACT

AIM: In 2001, a multidisciplinary intestinal rehabilitation program, prompted by a nationwide collaboration on intestinal failure (Dutch Registry for Intestinal Failure and Intestinal Transplantation), was started for children who have short bowel syndrome (SBS). This study evaluates this program, focusing on children who have SBS after extensive bowel resection. DESIGN: This is a retrospective cohort study. METHOD: Demographic data, general information on disease status, and outcome of intestinal rehabilitation of patients treated between 2001 and 2009 were collected. Outcome measures were intestinal autonomy, intestinal and/or liver transplantation, and survival. RESULTS: Ten boys and 9 girls, median gestational age 36 weeks, were treated. Eight were referred, 3 times as many as in the period 1991-2000. Causes of SBS were intestinal atresia (3), gastroschisis (2), volvulus (9), necrotising enterocolitis (3), and strangulation (2). The median remaining small-intestinal length was 35 cm (range, 10 to 70 cm). In 14 patients the ileocecal valve was still present. In all patients at least 25% of colon was still present. The median follow-up was 25 months (range, 50 days to 9 years). After a median of 138 days (range, 41 days to 11 years) on total parenteral nutrition, 16 patients (84%) reached intestinal autonomy. Central venous catheter-related complications occurred in all; there were liver function disorders in 68%, and a failure to thrive in 26%. One patient underwent intestinal lengthening. No patient needed intestinal transplantation, but one underwent liver transplantation for intestinal failure-associated liver disease. Overall mortality was 11%: those 2 patients died of abdominal sepsis. CONCLUSION: This specialized intestinal rehabilitation program led to intestinal autonomy in 84% of the patients who had SBS. None of the patients underwent an intestinal transplantation.


Subject(s)
Short Bowel Syndrome/rehabilitation , Child , Child, Preschool , Enteral Nutrition , Female , Follow-Up Studies , Humans , Infant , Intestinal Absorption/physiology , Male , Netherlands , Parenteral Nutrition, Total , Patient Care Team , Retrospective Studies , Short Bowel Syndrome/etiology , Short Bowel Syndrome/pathology , Treatment Outcome
7.
Am J Physiol Gastrointest Liver Physiol ; 300(2): G283-91, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21088238

ABSTRACT

Patients with chemotherapy-induced gastrointestinal mucositis suffer from anorexia, diarrhea, and stomach pain, often causing weight loss and malnutrition. When the intestinal function during mucositis would be known, a rational feeding strategy might improve the nutritional state, accelerate recuperation, and increase survival of mucositis patients. We developed a methotrexate (MTX)-induced mucositis rat model to study nutrient digestion and absorption. To determine lactose digestion and absorption of its derivative glucose during mucositis, we injected Wistar rats intravenously with MTX (60 mg/kg) or 0.9% NaCl (controls). Four days later, we orally administered trace amounts of [1-(13)C]lactose and [U-(13)C]glucose and quantified the appearance of labeled glucose in the blood for 3 h. Finally, we determined plasma citrulline level and harvested the small intestine to assess histology, myeloperoxidase level, glycohydrolase activity, immunohistochemical protein, and mRNA expression. MTX-treated rats showed profound villus atrophy and epithelial damage. During the experimental period, the absorption of lactose-derived [1-(13)C]glucose was 4.2-fold decreased in MTX-treated rats compared with controls (P < 0.01). Lactose-derived [1-(13)C]glucose absorption correlated strongly with villus length (rho = 0.86, P < 0.001) and with plasma citrulline level (rho = 0.81, P < 0.001). MTX treatment decreased jejunal lactase activity (19.5-fold, P < 0.01) and immunohistochemical protein and mRNA expression (39.7-fold, P < 0.01) compared with controls. Interestingly, MTX treatment did not affect the absorption of [U-(13)C]glucose during the experimental period. We conclude that lactose digestion is severely decreased during mucositis while glucose absorption is still intact, when supplied in trace amounts. Plasma citrulline level might be a useful objective, noninvasive marker for lactose maldigestion during mucositis in clinic.


Subject(s)
Digestion , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/metabolism , Lactose/metabolism , Methotrexate/adverse effects , Mucositis/chemically induced , Mucositis/metabolism , Absorption , Animals , Citrulline/blood , Gastrointestinal Diseases/pathology , Gastrointestinal Diseases/physiopathology , Glucose/metabolism , Glycoside Hydrolases/metabolism , Immunohistochemistry , Injections, Intravenous , Intestinal Mucosa/metabolism , Jejunum/enzymology , Lactase/genetics , Lactase/metabolism , Male , Methotrexate/administration & dosage , Microvilli/pathology , Mucositis/pathology , Mucositis/physiopathology , Pilot Projects , RNA, Messenger/metabolism , Rats
9.
Biochim Biophys Acta ; 1801(6): 665-73, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20298808

ABSTRACT

Clinically relevant fat malabsorption is usually due to impaired intestinal fat digestion (lipolysis) and/or to impaired solubilization of the lipolytic metabolites. We hypothesized that Gelucire 44/14 - a semi-solid self-micro-emulsifying excipient - could increase fat absorption. In relevant rat models for impaired lipolysis or for impaired solubilization we tested whether administration of Gelucire 44/14 enhanced fat absorption. Rats with impaired lipolysis (lipase inhibitor Orlistat diet) and rats with reduced solubilization (permanent bile diversion) underwent a 72 h fat balance test to assess fat absorption. The absorption kinetics of a stable isotope-labeled fatty acid was assessed in rats with reduced solubilization, in the presence or absence of Gelucire 44/14. Gelucire 44/14 improved fat absorption in rats with impaired lipolysis (from 70% to 82%, p<0.001). In rats with reduced solubilization, Gelucire 44/14 did not increase fat absorption nor did it reconstitute the absorption kinetics of (13)C-labeled palmitate, compared with control rats administered buffer without Gelucire 44/14. The present data show that Gelucire 44/14 might enhance fat absorption under conditions of impaired lipolysis, but not during impaired solubilization. We speculate that, due to its self-micro-emulsification properties, Gelucire 44/14 stabilizes and improves residual lipolytic enzyme activity in vivo, which could be of therapeutic value in clinical conditions of fat malabsorption due to impaired lipolysis.


Subject(s)
Fats/metabolism , Lipolysis , Polyethylene Glycols , Animals , Intestinal Absorption , Male , Rats , Rats, Wistar
10.
Am J Physiol Gastrointest Liver Physiol ; 297(3): G520-31, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19608735

ABSTRACT

Essential fatty acid (EFA) deficiency in mice has been associated with increased bile production, which is mainly determined by the enterohepatic circulation (EHC) of bile salts. To establish the mechanism underlying the increased bile production, we characterized in detail the EHC of bile salts in EFA-deficient mice using stable isotope technique, without interrupting the normal EHC. Farnesoid X receptor (FXR) has been proposed as an important regulator of bile salt synthesis and homeostasis. In Fxr(-/-) mice we additionally investigated to what extent alterations in bile production during EFA deficiency were FXR dependent. Furthermore, we tested in differentiating Caco-2 cells the effects of EFA deficiency on expression of FXR-target genes relevant for feedback regulation of bile salt synthesis. EFA deficiency-enhanced bile flow and biliary bile salt secretion were associated with elevated bile salt pool size and synthesis rate (+146 and +42%, respectively, P < 0.05), despite increased ileal bile salt reabsorption (+228%, P < 0.05). Cyp7a1 mRNA expression was unaffected in EFA-deficient mice. However, ileal mRNA expression of Fgf15 (inhibitor of bile salt synthesis) was significantly reduced, in agreement with absent inhibition of the hepatic bile salt synthesis. Bile flow and biliary secretion were enhanced to the same extent in EFA-deficient wild-type and Fxr(-/-) mice, indicating contribution of other factors besides FXR in regulation of EHC during EFA deficiency. In vitro experiments show reduced induction of mRNA expression of relevant genes upon chenodeoxycholic acid and a selective FXR agonist GW4064 stimulation in EFA-deficient Caco-2 cells. In conclusion, our data indicate that EFA deficiency is associated with interrupted negative feedback of bile salt synthesis, possibly because of reduced ileal Fgf15 expression.


Subject(s)
Bile Acids and Salts/metabolism , Bile/metabolism , Enterohepatic Circulation , Fatty Acids, Essential/deficiency , Intestine, Small/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Animals , Caco-2 Cells , Chenodeoxycholic Acid/metabolism , Cholesterol 7-alpha-Hydroxylase/metabolism , Enterohepatic Circulation/drug effects , Enterohepatic Circulation/genetics , Feedback, Physiological , Fibroblast Growth Factors/metabolism , Humans , Intestinal Absorption , Intestine, Small/drug effects , Isoxazoles/pharmacology , Kinetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , RNA, Messenger/metabolism , Receptors, Cytoplasmic and Nuclear/deficiency , Receptors, Cytoplasmic and Nuclear/genetics
11.
Am J Physiol Gastrointest Liver Physiol ; 295(3): G605-13, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18653724

ABSTRACT

Essential fatty acid (EFA) deficiency in mice induces fat malabsorption. We previously reported indications that the underlying mechanism is located at the level of the intestinal mucosa. We have investigated the effects of EFA deficiency on small intestinal morphology and function. Mice were fed an EFA-deficient or control diet for 8 wk. A 72-h fat balance, the EFA status, and small intestinal histology were determined. Carbohydrate absorptive and digestive capacities were assessed by stable isotope methodology after administration of [U-(13)C]glucose and [1-(13)C]lactose. The mRNA expression and enzyme activity of lactase, and concentrations of the EFA linoleic acid (LA) were measured in small intestinal mucosa. Mice fed the EFA-deficient diet were markedly EFA-deficient with a profound fat malabsorption. EFA deficiency did not affect the histology or proliferative capacity of the small intestine. Blood [13C6]glucose appearance and disappearance were similar in both groups, indicating unaffected monosaccharide absorption. In contrast, blood appearance of [13C]glucose, originating from [1-(13)C]lactose, was delayed in EFA-deficient mice. EFA deficiency profoundly reduced lactase activity (-58%, P<0.01) and mRNA expression (-55%, P<0.01) in mid-small intestine. Both lactase activity and its mRNA expression strongly correlated with mucosal LA concentrations (r=0.77 and 0.79, respectively, P<0.01). EFA deficiency in mice inhibits the capacity to digest lactose but does not affect small intestinal histology. These data underscore the observation that EFA deficiency functionally impairs the small intestine, which in part may be mediated by low LA levels in the enterocytes.


Subject(s)
Dietary Fats/metabolism , Digestion , Fatty Acids, Essential/deficiency , Glucose/metabolism , Intestinal Absorption , Intestine, Small/metabolism , Lactose Intolerance/metabolism , Lactose/metabolism , Animals , Blood Glucose/metabolism , Carbon Isotopes , Down-Regulation , Glucose/administration & dosage , Intestine, Small/enzymology , Kinetics , Lactase/genetics , Lactase/metabolism , Lactose/administration & dosage , Lactose/blood , Lactose Intolerance/etiology , Lactose Intolerance/physiopathology , Linoleic Acid/metabolism , Male , Mice , RNA, Messenger/metabolism
12.
Ned Tijdschr Geneeskd ; 151(10): 602-6, 2007 Mar 10.
Article in Dutch | MEDLINE | ID: mdl-17402653

ABSTRACT

Two girls aged 12 and 7 years with asthma and peanut and nut allergy developed anaphylactic shock after ingestion of peanuts and nuts from an unreported source. They were both given intramuscular epinephrine. The 12-year-old girl was treated clinically for shock and after two days was discharged from hospital. The 7-year-old girl died. Risk factors for life-threatening anaphylactic reactions are adolescent to young adult age, asthma, previous severe anaphylactic reactions to the food in question, previous reaction to small dose of the food in question and allergy to peanuts or tree nuts. A double-blind, placebo-controlled food challenge should be carried out to document the culprit food. The most important therapeutic intervention is the intramuscular administration of epinephrine. For patients with two or more risk factors the prescription of an epinephrine auto-injector should be considered.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Anaphylaxis/drug therapy , Epinephrine/therapeutic use , Nut Hypersensitivity/drug therapy , Peanut Hypersensitivity/drug therapy , Child , Fatal Outcome , Female , Humans , Injections, Intramuscular , Treatment Outcome
13.
Scand J Gastroenterol Suppl ; (243): 39-45, 2006.
Article in English | MEDLINE | ID: mdl-16782621

ABSTRACT

Intestinal transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients who fail total parenteral nutrition (TPN) therapy. Early referral for evaluation for small bowel transplantation has to be considered in patients with permanent intestinal failure who have occlusion of more than two major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation, and is further improving. Rejection, bacterial, fungal and viral (CMV, EBV) infection, post-transplant lymphoproliferative disease (PTLD) and graft versus host disease (GvHD) are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects of immunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.


Subject(s)
Digestive System Surgical Procedures/trends , Intestine, Small/transplantation , Adult , Digestive System Surgical Procedures/adverse effects , Female , Graft Rejection , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Intestinal Diseases/surgery , Intestine, Small/blood supply , Intestine, Small/pathology , Middle Aged , Netherlands , Parenteral Nutrition, Total
14.
Ned Tijdschr Geneeskd ; 149(8): 385-90, 2005 Feb 19.
Article in Dutch | MEDLINE | ID: mdl-15751316

ABSTRACT

Intestinal failure is characterised by inability of the intestine to absorb sufficient nutrients to maintain the integrity and function of the body. This can be caused by malabsorption due to too short an intestine or an abnormality of the mucosa, or by a severe motility disorder. In addition to dietary measures, the prescription of total parental nutrition (TPN) at home is sometimes necessary. This treatment is a burden on the patient and the risk of complications must be reduced to a minimum. The risks of long-term parenteral nutrition can be limited and the quality of the provision of services can be increased if the co-ordination is in the hands of a centre for home parenteral nutrition. In the Netherlands there are two centres for home-TPN: the St Radboud University Medical Centre in Nijmegen and the University Medical Centre (AMC) in Amsterdam. In both children and adults, the most common indications are the short bowel syndrome and motility disorders. However, the syndromes that cause this are clearly different in the different age groups. Parenteral nutrition can be given for long periods of time. A large variety of complications can occur, related especially to the equipment or the nutrients. When the nutrition is given via a central venous catheter, then sepsis is a serious and possibly life-threatening complication. In case of administration via an arteriovenous shunt, thrombosis of the shunt is the most frequent problem. If the treatment by means of home-TPN fails, then transplantation of the small intestine should be considered.


Subject(s)
Intestinal Diseases/therapy , Parenteral Nutrition, Home Total/methods , Adult , Child , Esophageal Motility Disorders/therapy , Humans , Intestinal Diseases/physiopathology , Intestines/physiopathology , Intestines/transplantation , Parenteral Nutrition, Home Total/adverse effects , Short Bowel Syndrome/therapy , Treatment Outcome
15.
Ned Tijdschr Geneeskd ; 149(8): 391-8, 2005 Feb 19.
Article in Dutch | MEDLINE | ID: mdl-15751317

ABSTRACT

Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients where total parenteral nutrition (TPN) therapy for intestinal failure is unsuccessful. Early referral for screening for small bowel transplantation should be considered in patients with permanent intestinal failure who have occlusion of more than 2 major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies, the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation and is further improving. Rejection, bacterial, fungal and viral (Cytomegalovirus, Epstein-Barr-virus) infections, post-transplant lymphoproliferative disease and graft versus host disease are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects ofimmunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.


Subject(s)
Intestine, Small/transplantation , Short Bowel Syndrome/surgery , Adult , Child , Graft Rejection , Graft Survival , Humans , Liver/physiology , Parenteral Nutrition, Home Total , Postoperative Complications , Quality of Life , Short Bowel Syndrome/therapy , Treatment Outcome
16.
Ned Tijdschr Geneeskd ; 149(8): 413-7, 2005 Feb 19.
Article in Dutch | MEDLINE | ID: mdl-15751321

ABSTRACT

Three children, 2 boys aged 5 and 4 years, and 1 girl aged 2 years, who suffered from intestinal failure as a result of a short bowel syndrome and who were dependent on total parenteral nutrition (TPN), were screened for small bowel transplantation. The girl also had progressive liver failure. Each child had a clear indication for either isolated small bowel or combined small bowel/liver transplantation. All three children were enrolled in an intestinal rehabilitation program because they were referred early. The intestinal rehabilitation consisted of a systematic analysis of the absorptive capacity of the residual intestine, optimizing enteral and parenteral feeding, prevention of catheter sepsis and further deterioration of liver function. The rehabilitation was performed in an in-patient setting. All three children were partially weaned from TPN, while their growth improved. None of the children were consequently listed for small bowel transplantation. When a child is initially referred for small bowel transplantation, intestinal rehabilitation should be considered as part of an intestinal transplantation program.


Subject(s)
Short Bowel Syndrome/rehabilitation , Child, Preschool , Female , Humans , Intestine, Small/transplantation , Liver Transplantation , Male , Parenteral Nutrition, Total , Short Bowel Syndrome/surgery , Short Bowel Syndrome/therapy , Treatment Outcome
17.
Ned Tijdschr Geneeskd ; 148(17): 840-4, 2004 Apr 24.
Article in Dutch | MEDLINE | ID: mdl-15141652

ABSTRACT

A 13-year-old girl presented with rectal bleeding, abdominal pain and a palpable mass in the lower right abdomen. The history mentioned a chronic anaemia since she was 2 years old. Further examination did not give any indications for inflammation as etiological factor and showed a thickening of (apparently) the small intestine. A laparotomy was performed, since the age and presentation made a malignant lymphoma a probable diagnosis. The combination of chronic anaemia and rectal bleeding also suggested a benign vascular malformation. A large cavernous haemangioma of the transverse colon was found. This was resected and the patient fully recovered. Although a haemangioma of the colon is rare, it is important to keep this possibility in mind in the case of rectal bleeding in childhood, especially when other causes of rectal bleeding are excluded. Usually haemangiomas show spontaneous regression, but this is rare in intestinal haemangiomas. Surgical resection is the therapy of choice in the case of a solitary haemangioma.


Subject(s)
Colon/surgery , Colonic Neoplasms/surgery , Hemangioma, Cavernous/surgery , Adolescent , Anemia/etiology , Colonic Neoplasms/diagnosis , Diagnosis, Differential , Female , Gastrointestinal Hemorrhage/etiology , Hemangioma, Cavernous/diagnosis , Humans , Rectum/pathology
18.
Gastroenterology ; 121(6): 1437-50, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11729123

ABSTRACT

BACKGROUND & AIMS: Cdx2 is critical in intestinal proliferation and differentiation. Modulation of Cdx2 function in response to cellular signaling is to be elucidated. We hypothesize that phosphorylation of the Cdx2 activation domain can modulate its function. METHODS: The Cdx2 activation domain was delineated in transient transfections using different portions of Cdx2 fused to the Gal4-DNA binding domain. In vivo phosphorylation was studied by metabolic labeling with (32)P-orthophosphate. To study a potential phosphorylation site, polyclonal antibodies were generated: CNL was raised against amino acids 54-66 of Cdx2 and P-Cdx2-S60 against the same epitope in which serine 60 was phosphorylated. RESULTS: A critical region for transactivation resides within amino acids 60-70. Substitution of serine 60 with alanine reduces incorporation of (32)P-orthophosphate substantially. S60-phosphorylation decreases Cdx2 transactivation. Phosphorylation of serine 60 can be inhibited with the mitogen-activated protein kinase inhibitors PD98059 or UO126. P-Cdx2-S60 recognizes phosphorylated serine 60 mainly in proliferative compartment of the intestinal epithelial layer. In contrast, CNL recognizes Cdx2 predominantly in the differentiated compartment. CONCLUSIONS: The Cdx2 activation domain is phosphorylated at serine 60 via the mitogen-activated protein kinase pathway. S60-phosphorylated and S60-nonphosphorylated Cdx2 have different transcriptional activity, as well as different spatial expression patterns in the intestinal epithelium.


Subject(s)
Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Transcriptional Activation/physiology , Amino Acid Sequence/genetics , Animals , CDX2 Transcription Factor , Cell Division/physiology , Cell Line , Cell Nucleus/metabolism , Colon/cytology , Colon/metabolism , DNA-Binding Proteins/metabolism , Homeodomain Proteins/chemistry , Humans , Immunohistochemistry , Intestine, Small/cytology , Intestine, Small/metabolism , Mice , Mitogen-Activated Protein Kinases/metabolism , Molecular Sequence Data , Phosphorylation , Protein Structure, Tertiary , Serine/metabolism , Trans-Activators
19.
J Pediatr Gastroenterol Nutr ; 27(1): 37-46, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9669724

ABSTRACT

BACKGROUND: In children, lactase and sucrase-isomaltase are essential intestinal glycohydrolases, and insufficiency of either enzyme causes diarrhea and malnutrition. Little is known about the regulation of lactase and sucrase-isomaltase expression in the duodenum during childhood. In this study, the mechanisms of regulation of duodenal expression of both enzymes were examined in a study population with ages ranging from 1 to 18 years. METHODS: Duodenal biopsy specimens from 60 white children were used to analyze tissue morphology and to quantify lactase and sucrase-isomaltase mRNA and protein. RESULTS: Among healthy subjects, high interindividual variability was noted in both mRNA and protein levels for lactase and sucrase-isomaltase. Lactase mRNA level per subject did not correlate with sucrase-isomaltase mRNA level and thus appeared independent. Both lactase and sucrase-isomaltase protein levels correlated significantly with their respective mRNA levels. For each enzyme, a significant inverse correlation was observed between the degree of villus atrophy and mRNA levels. Aging from 1 to 18 years did not result in significant changes in mRNA or protein levels of either enzyme. Immunostaining patterns within the duodenal epithelium for lactase differed from sucrase-isomaltase in adjacent sections, illustrating independent regulation at the cellular level. CONCLUSIONS: In the duodenum of white children, lactase and sucrase-isomaltase seem primarily regulated at the transcriptional level. The expression of each enzyme in the intestinal epithelium is regulated by an independent mechanism. Lactase and sucrase-isomaltase exhibit stable mRNA and protein levels in healthy children as they grow to adulthood. Mucosal damage affected levels of both enzymes negatively.


Subject(s)
Duodenum/enzymology , Gene Expression Regulation, Enzymologic , Sucrase-Isomaltase Complex/genetics , beta-Galactosidase/genetics , Adolescent , Aging , Antibodies, Monoclonal , Atrophy , Biopsy , Child , Child, Preschool , Humans , Immunohistochemistry , Infant , Intestinal Mucosa/enzymology , Intestinal Mucosa/pathology , Lactase , Prospective Studies , RNA, Messenger/metabolism
20.
J Histochem Cytochem ; 46(2): 231-40, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9446830

ABSTRACT

The clinical importance of carbamoyl phosphate synthase I (CPSI) relates to its capacity to metabolize ammonia, because CPSI deficiencies cause lethal serum ammonia levels. Although some metabolic parameters concerning liver and intestinal CPSI have been reported, the extent to which enterocytes contribute to ammonia conversion remains unclear without a detailed description of its developmental and spatial expression patterns. Therefore, we determined the patterns of enterocytic CPSI mRNA and protein expression in human and rat intestine during embryonic and postnatal development, using in situ hybridization and immunohistochemistry. CPSI protein appeared during human embryogenesis in liver at 31-35 e. d. (embryonic days) before intestine (59 e.d.), whereas in rat CPSI detection in intestine (at 16 e.d.) preceded liver (20 e.d.). During all stages of development there was a good correlation between the expression of CPSI protein and mRNA in the intestinal epithelium. Strikingly, duodenal enterocytes in both species exhibited mosaic CPSI protein expression despite uniform CPSI mRNA expression in the epithelium and the presence of functional mitochondria in all epithelial cells. Unlike rat, CPSI in human embryos was expressed in liver before intestine. Although CPSI was primarily regulated at the transcriptional level, CPSI protein appeared mosaic in the duodenum of both species, possibly due to post-transcriptional regulation.


Subject(s)
Carbamoyl-Phosphate Synthase (Ammonia)/analysis , Carbamoyl-Phosphate Synthase (Ammonia)/genetics , Duodenum/enzymology , Intestinal Mucosa/enzymology , Adolescent , Aging/metabolism , Animals , Child , Child, Preschool , Duodenum/embryology , Duodenum/growth & development , Gene Expression , Gene Expression Regulation, Developmental , Humans , Immunohistochemistry , In Situ Hybridization , Infant , Intestinal Mucosa/embryology , Intestinal Mucosa/growth & development , Liver/embryology , Liver/enzymology , Liver/growth & development , Mitochondria/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Species Specificity
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