Search

Background: The vast majority of children will undergo their first exposure to common allergenic foods at home. However, the first exposure may lead to clinical reactions. It has been proposed to introduce allergenic foods gradually into the diets of children at risk for food allergy, but no practical dietary advice has been devised. Objective: The aim of this study was to devise safe introduction schedules for common allergenic foods for use at home, based on the challenge doses as administered in double-blind, placebo-controlled food challenge (DBPCFCs) in children who were never exposed previously to these foods. Methods: Seventy-two DBPCFCs were performed in 63 children as a first known exposure. The incrementing challenge doses were converted into equivalent portions of these foods in their usual household form and incorporated in introduction schedules. The feasibility of the introduction scales was tested in parents of the children attending our clinic. Results: Based on the results of the positive challenges (37) in which severe reactions did not occur, detailed introduction schedules and a reference photograph of the required increasing amounts of food were devised for use at home. Feasibility testing showed that, when using these introduction schedules, parents portioned the initial doses significantly lower than without detailed instructions. Conclusions: The introduction schedules and reference photograph provide information for parents to introduce the required amounts of allergenic foods in initial low doses at home. This is expected to improve the safety of this procedure.

Background: Tyrosinemia type I is associated with an increased risk of liver cancer development. The formation of the pathogenic fumarylacetoacetate is prevented by 2-(2-nitro-4-3 trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC). Still, some patients with NTBC treatment develop liver cancer. A rise of alpha-fetoprotein (AFP) is an indicator of liver cancer.Aim: To study the predictive value of AFP in tyrosinemia type I patients for the discrimination between patients at high and low risk of liver cancer development.Methods: We examined the course of AFP values of 11 Dutch patients with tyrosinemia type I treated by NTBC of whom four were diagnosed with liver cancer.Results: The four patients with liver cancer had a course of AFP different from the other patients in either velocity of the decrease of AFP, achieving normal AFP and/or having a rise of AFP concentrations.Conclusion: Apart from a rise of AFP, a slow AFP decrease, and never normalizing levels of AFP are important predictors of liver cancer development in further life. (c) 2006 Elsevier Inc. All rights reserved.

The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy-resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A-I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 x 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side-effect. In conclusion, MARS may induce a long-term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.

Wij bespreken een aantal psychosociale aspecten, die een specifieke rol spelen in de diverse fasen van het proces van orthotope levertransplantatie bij kinderen. Een psychosociale screening voor de tranplantatie is van groot belang, overigens niet zozeer voor de selectie van kandidaten, als wel voor het optimaliseren van het beloop. Acute psycho-organische stoornissen spelen in de postoperatieve fase frequent een rol. Psycho-organische stoornissen spelen, naast de emotionele verwerking, ook een rol bij de pro-gnose op langere termijn. Voor de middellange termijn zijn er echter aanwijzingen dat deze patientengroep geen verhoogd risico loopt ten opzichte van andere chronisch zieke kinderen. Over de lange termijn zijn onvoldoende gegevens bekend. Therapieontrouw is een belangrijke complicatie. Voor het volgen van deze groep patienten is meer geprotocolleerd en longitudinaal onderzoek essentieel.

The ability of ultrasound to detect biliary obstruction, bile leakage and generalized ductal changes after orthotopic liver transplantation (OLT) was compared to cholangiography. Cholangiography was considered to be the gold standard. Adequate opacification of the biliary tree was achieved in 139 cholangiograms. Biliary obstruction, intermediate or large bile leakage, and generalized ductal changes were diagnosed with cholangiography in 15% (21/139), 14% (20/139), and 16% (22/139), respectively. Normal ultrasound findings could not exclude biliary stricture, generalized ductal changes, or bile leakage, and fluid collections were not correlated with bile leakage. Abnormal ultrasound findings were highly predictive of the cholangiographic diagnosis of biliary obstruction or generalized ductal changes (specificity of 98% and 100%, respectively). An irregular appearance of the bile ducts and increased periductal echogenicity proved to be characteristic features for generalized ductal changes. (C) 1996 John Wiley & Sons, Inc.

Data on the frequency of resolution of anaphylaxis to foods are not available, but such resolution is generally assumed to be rare.To determine whether the frequency of negative challenge tests in children with a history of anaphylaxis to foods is frequent enough to warrant challenge testing to re-evaluate the diagnosis of anaphylaxis, and to document the safety of this procedure.All children (n=441) who underwent a double-blind, placebo-controlled food challenge (DBPCFC) between January 2003 and March 2007 were screened for symptoms of anaphylaxis to food by history. Anaphylaxis was defined as symptoms and signs of cardiovascular instability, occurring within 2 h after ingestion of the suspected food.Twenty-one children were enrolled (median age 6.1 years, range 0.8-14.4). The median time interval between the most recent anaphylactic reaction and the DBPCFC was 4.25 years, range 0.3-12.8. Twenty-one DBPCFCs were performed in 21 children. Eighteen of 21 children were sensitized to the food in question. Six DBPCFCs were negative (29%): three for cows milk, one for egg, one for peanut, and one for wheat. In the positive DBPCFCs, no severe reactions occurred, and epinephrine administration was not required.This is the first study using DBPCFCs in a consecutive series of children with a history of anaphylaxis to foods, and no indications in dietary history that the food allergy had been resolved. Our study shows that in such children having specific IgE levels below established cut-off levels reported in other studies predicting positive challenge outcomes, re-evaluation of clinical reactivity to food by DBPCFC should be considered, even when there are no indications in history that anaphylaxis has resolved. DBPCFCs can be performed safely in these children, although there is a potential risk for severe reactions.Cite this as: B. J. Vlieg-Boerstra, E. J. Duiverman, S. van der Heide, C. M. A. Bijleveld, J. Kukler and A. E. J. Dubois, Clinical and Experimental Allergy, 2008 (38) 1935-1942.

The vast majority of children will undergo their first exposure to common allergenic foods at home. However, the first exposure may lead to clinical reactions. It has been proposed to introduce allergenic foods gradually into the diets of children at risk for food allergy, but no practical dietary advice has been devised.The aim of this study was to devise safe introduction schedules for common allergenic foods for use at home, based on the challenge doses as administered in double-blind, placebo-controlled food challenge (DBPCFCs) in children who were never exposed previously to these foods.Seventy-two DBPCFCs were performed in 63 children as a first known exposure. The incrementing challenge doses were converted into equivalent portions of these foods in their usual household form and incorporated in introduction schedules. The feasibility of the introduction scales was tested in parents of the children attending our clinic.Based on the results of the positive challenges (37) in which severe reactions did not occur, detailed introduction schedules and a reference photograph of the required increasing amounts of food were devised for use at home. Feasibility testing showed that, when using these introduction schedules, parents portioned the initial doses significantly lower than without detailed instructions.The introduction schedules and reference photograph provide information for parents to introduce the required amounts of allergenic foods in initial low doses at home. This is expected to improve the safety of this procedure.

Background: A cardinal feature of the double-blind, placebo-controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented.Objective: To analyse the occurrence and features of placebo events in DBPCFCs and to assess their contribution to the diagnostic accuracy of the DBPCFC in children.Methods: The study population consisted of 132 challenges in 105 sensitized children (age range 0.7-16.6 years, median 5.3 years), who underwent DBPCFCs with cow's milk, egg, peanut, hazelnut and soy. Placebo and active food challenges were performed on different days.Results: A total number of 17 (12.9%) positive placebo events occurred, which could be classified as immediate (9/17), late-onset (8/17), objective (11/17) or subjective (6/17). Four of 74 (5.4%) positive active food challenges were revealed to be false positive by administration of a placebo challenge. This is 3% (4/132) of all challenges. When computed by a statistical model, the false positive rate was 0.129 (12.9% of all challenges).Conclusions: Placebo events with diverse clinical characteristics occur in DBPCFCs in a significant number of children. The diagnostic significance of the administration of a placebo challenge is first, to identify false positive diagnoses in DBPCFCs by refuting false positive tests in individual patients. Secondly, to allow for blinding of the active food challenge. Thirdly, applying a statistical model demonstrates that some positive challenges may be false positive and that the test may need to be repeated in selected cases.

Objective: The purpose of this investigation was to verify if avoidance of allergenic foods in children adhering to a food allergen avoidance diet from birth was complete and feasible, and whether dietary assessment can be used as a tool in predicting the outcome of double-blind, placebo-controlled food challenges (DBPCFCs).Design: Children adhering to an allergen avoidance diet from birth underwent DBPCFCs. The investigator-dietician verified whether the elimination was complete, using food frequency questionnaires for common allergenic foods.Setting: University Medical Centre Groningen, the Netherlands.Subjects: Thiry-eight children aged 1-13 years, who were consecutively referred to the University Medical Centre Groningen for DBPCFC between January 2002 and February 2004.Results: Among the 38 children undergoing DBPCFCs, there were 15 challenges with egg, 15 with peanut, five with hazelnut and three with soy. Fifteen food challenges (39%) were positive. Small quantities of allergenic foods were inadvertently present in the diets of 13 patients (34%), were possibly present in the diets of 14 patients (37%) and could not be identified in the diets of 11 patients (29%). Seven patients (54%) who had inadvertently ingested small quantities of allergenic foods without sequelae had a positive DBPCFC.Conclusion: Dietary avoidance was incomplete and not feasible in most cases. Tolerance of small amounts of allergenic foods does not preclude positive challenge reactions. Dietary assessment does not seem a useful tool in predicting the outcome of DBPCFC in children adhering to an elimination diet.

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.

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.

A few months after birth two sisters aged 5 and 9 years had developed cholestasis and abnormal liver functions with symptoms including itching and jaundice. The younger sister also developed rickets and clotting disorders. On clinical, biochemical and immunohistopathological grounds the diagnosis of 'progressive familial intrahepatic cholestasis (PFIC) type 2' was made. Medical treatment was not succesfull in reducing symptoms. An ileocolonic bypass in the younger child was not effective. Subsequently, both patients underwent partial external biliary diversion (PEBD). Except for a period of intermittent itching in the younger child, both patients remained free of symptoms 2 years after PEBD. In cases where an early diagnosis is made, PEBD could delay or even prevent the necessity of liver transplantation.

A boy suffered from severe recurrent intestinal infections from the age of 8 months onwards; investigation into an immune disorder ultimately resulted in the diagnosis of 'hyper-IgM syndrome'. He was treated successfully with bone marrow transplantation, using an HLA-matched donor. Another boy had severe recurrent respiratory tract infections from the age of 3 months onwards. At the age of 6.5 years, 'hyper-IgM syndrome' was diagnosed. No suitable donor was available. In addition, he developed sclerosing cholangitis and end-stage liver disease, making a combined bone marrow and liver transplantation too risky. He died at 10.5 years of age. X-linked hyper-IgM syndrome is a rare congenital immunodeficiency disorder, characterised by a defect in both humoral and cellular immune responses. Deficiency in the membrane glycoprotein CD40 ligand (expressed on activated T-cells) compromises T-cell interactions with antigen-presenting cells. In a child with severe recurrent infections, and with dysgammaglobulinaemia with a normal or increased IgM level, the diagnosis of 'X-linked hyper-IgM syndrome' should be considered.

The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy-resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A-I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 x 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side-effect. In conclusion, MARS may induce a long-term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.

Background: Selective angiography involves increased risk for children and may cause vascular complications. The aim of this study was to determine whether selective angiography is still necessary for viewing the portal vein and hepatic artery. Methods: Doppler ultrasound, abdominal aortography, and selective angiography were performed and interpreted independently in 62 children (median age = 1 year 3 months), with end-stage liver disease, who were candidates for orthotopic liver transplantation. Results: Selective angiography agreed with the Doppler ultrasound findings of patency, flow direction, and diameter of the extrahepatic portal vein in 84%, 73%, and 79% of the children, respectively. Important additional information was obtained from selective angiography in only five of the 62 children (8%). Selective angiography showed an anomaly of the hepatic artery in 21 of the 62 children (33%). In 18 out of these 21 children (85%), an anomaly of the hepatic artery was already visible on the abdominal aortogram. Conclusion: Selective angiography did not play any significant role in the detection of an anomaly of the hepatic artery and should only be done if the Doppler ultrasound findings of the portal vein are inconclusive or if abdominal aortography cannot provide reliable information about the hepatic artery. For the evaluation of the portal vein and hepatic artery, we recommend Doppler ultrasound and abdominal aortography, a less invasive angiographic procedure.

Dietary treatment cannot prevent a lethal outcome in many patients with hereditary tyrosinaemia type I (van Spronsen et al 1994). Therefore, until the discovery of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) as a potential drug (Lindstedt et al 1992), orthotopic liver transplantation (OLT) was the only definitive treatment in patients with this disease (van Spronsen 1989). We report our experiences with OLT in 9 patients with tyrosinaemia type I.

Vascular manifestations as extraintestinal symptoms of Crohn's disease are rare and only occasionally reported in children. A 14-year-old girl with vascular compromise prior to intestinal manifestations of Crohn's disease is described. The vascular symptoms were due to segmental narrowing of several major arteries as shown by angiography. This kind of vascular involvement in our patient is different from the pattern described in Crohn's disease and resembles Takayasu's disease. Recently, it has been suggested that Crohn's disease could be mediated by multifocal gastrointestinal infarction due to chronic focal mesenteric arteritis at the level of the muscularis propria of the gut. In Takayasu's disease, a granulomatous inflammation of the vasa vasorum of affected vessels is frequently found. An intramural arteritis, granulomatous in nature, could be the common pathway in both Crohn's and Takayasu's diseases. Until the etiologies of both diseases are uncovered, the interrelation between them will remain subject to speculation.

In 45 liver transplant recipients, the value of weekly monitoring of cytomegalovirus (CMV) antigenemia for early diagnosis of active CMV infection was compared with serology and rapid viral isolation. Active CMV infection occurred in 23 patients. The sensitivities of the antigenemia assay and serology (of blood) and rapid viral isolation (from blood or urine) were 96%, 96%, 57%, and 70%, respectively. First diagnostic results of these methods were obtained a median of 25, 36, 31, and 49 days, respectively, after transplant. CMV infection was symptomatic in 20 patients; antigenemia was present at the onset of disease in 13 of these. Maximum CMV antigenemia levels were higher in patients with severe disease than in those with mild or asymptomatic infection. CMV antigenemia is a sensitive, early, quantitative marker of active CMV infection after liver transplantation.

A simple test is described for the diagnosis of monosaccharide malabsorption in infancy caused by a congenital defect of glucose and galactose transport. Increased hydrogen (H2) excretion in expired air after ingestion of sugar was used to diagnose this condition in an infant with severe diarrhoea after breast feeding. Abnormal amounts of H2 were excreted after oral administration of glucose and galactose, but not after fructose. A carbohydrate free diet supplemented with fructose resulted in rapid weight gain and disappearance of diarrhoea. The diagnosis of glucose-galactose malabsorption was confirmed by 14C-glucose transport studies on a jejunal mucosal biopsy specimen. These findings indicate that interval breath H2 estimation in mixed expired air is a non-invasive, reliable procedure for detection of monosaccharide malabsorption in infancy.

Extrahepatic biliary atresia (EHBA) is an infrequent disease confined to early infancy. Its aetiology is not clear, but an infectious agent has been implicated. Demonstration of a time-space clustering would support this hypothesis. Therefore, we investigated the time-space distribution of all 89 cases of EHBA born in a 10-year period in the Netherlands. We carried out a similar study in West Germany and analysed 130 cases of EHBA, born between 1969 and 1986, from 4 paediatric surgical centres. Analysis of these cases did not reveal any evidence for clustering in specific years or in a specific period of the year. The places of birth of the patients also were randomly distributed over rural areas, villages and towns. Neither did a method to reveal time-space interaction give any support for clustering. This random distribution of patients with EHBA suggests that EHBA could be pathogenetically a heterogeneous disease.

Lactulose is often used as a substrate to estimate the mouth-to-caecum transit time (MCTT), but because of osmotic effects the outcome depends on the dose consumed. In this study, barley groats, a complex carbohydrate (CH) that produces a clear breath hydrogen response after consumption, were used. Eight volunteers consumed the same dose of softened barley groats (1.0 g CH/kg body weight) three times. Ten volunteers ate three different doses (0.75, 1.0, and 1.5 g CH/kg body weight). Breath samples were collected every 30 or 60 min for at least 12.5 h and analysed for hydrogen. To study the effect of the particle size of the barley groats or the addition of fat on the MCTT, 11 volunteers consumed barley groats (1.0 g CH/kg body weight) with cream cheese (0.25 g fat/kg body weight) and 5 volunteers ate crushed barley groats (particles of +/- 1 mm, 1.0 g CH/kg body weight). After consumption of 1.0 g CH/kg body weight a mean MCTT of 8.4 +/- 0.4 h was found. After consumption of the high dose, a mean MCTT of 9.0 +/- 0.5 h was found, and after the low dose, 8.5 +/- 0.6 h. Addition of fat resulted in a significantly increased MCTT, presumably caused by retarded stomach emptying (9.2 +/- 0.6 h versus 8.1 +/- 0.5 h in controls). Particle size did not significantly affect the MCTT (7.2 +/- 0.5 h at 1 mm versus 7.8 +/- 0.6 h at normal particle size).(ABSTRACT TRUNCATED AT 250 WORDS)