Search

Copyright of Tijdschrift Voor Kindergeneeskunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An abstract of the conference paper "The effectiviness of an innovative web-based application to monitor HRQOL problems in paediatric rheumatology clinical practice," by L. Haverman and colleagues is presented.

Objective: To determine the relation between intestinal permeability and birth weight, gestational age, postnatal age, and perinatal risk factors in neonates.Study Design: Intestinal permeability was measured by the sugar absorption test within two days of birth and three to six days later in preterm and healthy term infants. In the sugar absorption test, the urinary lactulose/mannitol ratio is measured after oral ingestion of a solution (375 mosm) of lactulose and mannitol.Results: A first sugar absorption test was performed in 116 preterm (26-36 weeks gestation) and 16 term infants. A second test was performed in 102 preterm and nine term infants. In the preterm infants, the lactulose/mannitol ratio was not related to gestational age (r = -0.09, p = 0.32) or birth weight (r = 0.07, p = 0.43). The median lactulose/mannitol ratio was higher if measured less than two days after birth than when measured three to six days later (0.427 and 0.182 respectively, p<0.001). The lactulose/mannitol ratio was higher in preterm infants than term infants if measured within the first 2 days of life (0.404 and 0.170 respectively, p < 0.001), but not different three to six days later (0.182 and 0.123 respectively, p = 0.08). In multiple regression analysis of perinatal risk factors, only umbilical arterial pH correlated with the lactulose/mannitol ratio in preterm infants less than 2 days of age (T = -1.98, p = 0.05).Conclusions: In preterm infants (26-36 weeks gestation), intestinal permeability is not related to gestational age or birth weight but is higher during the first 2 days of life than three to six days later. It is higher in preterm infants than in healthy term infants only if measured within two days of birth. This suggests rapid postnatal adaptation of the small intestine in preterm infants. [ABSTRACT FROM AUTHOR]

Background: Infants with atopic dermatitis (AD) have a high risk of developing asthma. We investigated the effect of early intervention with synbiotics, a combination of probiotics and prebiotics, on the prevalence of asthma-like symptoms in infants with AD. Methods: In a double-blind, placebo-controlled multicentre trial, ninety infants with AD, age <7 months, were randomized to receive an extensively hydrolyzed formula with Bifidobacterium breve M-16V and a galacto/fructooligosaccharide mixture (Immunofortis®), or the same formula without synbiotics during 12 weeks. After 1 year, the prevalence of respiratory symptoms and asthma medication use was evaluated, using a validated questionnaire. Also, total serum IgE and specific IgE against aeroallergens were determined. Findings: Seventy-five children (70.7% male, mean age 17.3 months) completed the 1-year follow-up evaluation. The prevalence of 'frequent wheezing' and 'wheezing and/or noisy breathing apart from colds' was significantly lower in the synbiotic than in the placebo group (13.9% vs 34.2%, absolute risk reduction (ARR) )20.3%, 95% CI )39.2% to )1.5%, and 2.8% vs 30.8%, ARR )28.0%, 95% CI )43.3% to )12.5%, respectively). Significantly less children in the synbiotic than in the placebo group had started to use asthma medication after baseline (5.6% vs 25.6%, ARR )20.1%, 95% CI )35.7% to )4.5%). Total IgE levels did not differ between the two groups. No children in the synbiotic and five children (15.2%) in the placebo group developed elevated IgE levels against cat (ARR )15.2%, 95% CI )27.4% to )2.9%). Conclusion: These results suggest that this synbiotic mixture prevents asthma-like symptoms in infants with AD. [ABSTRACT FROM AUTHOR]

The plasma glucose concentration response to a glucagon bolus is considered an important diagnostic tool in hypoglycemia of unknown origin. The response of plasma glucose concentration to glucagon can however also be misleading in the differential diagnosis. In a 3-week-old male infant suffering recurrent severe preprandial hypoglycemia and dependent on continuous i.v. glucose infusion, extensive diagnostic screening including a liver biopsy did not lead to a diagnosis. Based on an insufficient glycemic response (twice) to a glucagon bolus, a disorder of glycogenolysis was suspected. Glucose production and gluconeogenesis were measured (glycogenolysis calculated) during diminishing i.v. glucose infusion and after a glucagon bolus. Reducing glucose infusion resulted in a steep increase in glycogenolysis and gluconeogenesis, maintaining total glucose turnover (production plus infusion) constant at +/-9 mg x kg(-1) x min(-1) (+/-60% gluconeogenesis, +/-40% glycogenolysis). Plasma glucose concentration however decreased from 4.9 mmol/l to 3.4 mmol/l. Glucagon increased glucose production by 50% but resulted in only a minor increase in glucose concentration. Conclusion. As glucose concentration depends on the balance between glucose production and utilization (uptake), facilitated glucose uptake rather than impaired glycogenolysis explains the hypoglycemic episodes in this patient. A subnormal response of plasma glucose to glucagon therefore does not necessarily imply a disturbance in glycogenolysis. In cases of hypoglycemia of unknown origin, measurement of glucose kinetics with stable isotopes is indicated. [ABSTRACT FROM AUTHOR]

Aims: To determine cognitive and educational attainment in adults with end stage renal disease (ESRD) since childhood. Methods: All Dutch patients with onset of ESRD at age 0-14 years between 1972 and 1992, who were born before 1979, were asked to perform the Wechsler Adult Intelligence Scale (WAIS) test. Educational attainment was assessed by a questionnaire. Determinants of cognitive performance were measured by reviewing medical charts in 37 hospitals. Data on cognition were compared to those of age matched controls who cooperated in the revision of the Dutch WAIS. National Dutch Statistics data were used to compare educational attainment. Results: Data on intelligence and schooling were acquired in 126 of 187 patients (67%) and data on determinants of outcome in all patients. Clinical characteristics of participants and non-participants were comparable. Educational attainment of patients was low compared to the Dutch standard. Patient mean full scale IQ, performal IQ, and verbal IQ were 10.4, 9.2, and 9.7 points lower, respectively, MC compared to those of 36 controls. The lowest scores were observed in tasks which require concentration, memory, and general knowledge. Patients currently on dialysis and transplanted patients had similar IQ scores. Cumulative dialysis duration of more than four years was associated with a 3.4 times higher chance of having a full scale IQ of 1 SD below the mean. Conclusion: ESRD of childhood is associated with an impaired cognitive and educational attainment in adulthood. Long duration of dialysis may enhance intellectual impairment, which may not be reversible after renal transplantation. [ABSTRACT FROM AUTHOR]

Aims: To determine the effect of brief early exposure to cows' milk on the expression of atopy during the first five years of life. Methods: Follow up analysis of a double blind, placebo controlled, randomised feeding intervention trial (BOKAAL study). Subjects were 1108 children from 1533 initially randomised breast fed neonates in the Netherlands. Atopic disease and prevalence of allergic symptoms at age 1, 2, and 5, and specific IgE at age 1 and 5 were determined. Results: Atopic disease in the first year was found in 10.0% (cows' milk) versus 9.3% (placebo) of the children, with a relative risk (RR) of 1 .07. No differences were found in the second year either. At age 5, atopic disease was found in 26.3% (cows' milk) versus 25.0% (placebo), RR 1 .05. There was no difference in the prevalence of allergic symptoms. Specific IgE to cows' milk (RAST positive 2+ or more) was 5.8% (cows' milk) versus 4.1% (placebo) at age 1 (RR 1 .43), and 5.3% versus 3.0% at age 5 (RR 1 .77). There was no difference in sensitisation to other common allergens between the two groups. Conclusion: Early, brief exposure to cows' milk in breast fed children is not associated with atopic disease or allergic symptoms up to age 5. [ABSTRACT FROM AUTHOR]

Aims-To determine frequency, type, determinants, and outcome of malignancies in children with end stage renal failure. Methods-All Dutch patients, aged less than 15 years, who started chronic renal replacement therapy between 1972 and 1992 and who were at least 18 years old on 1 January 1997, were retrospectively studied. Results-Mean follow up from first renal replacement therapy was 15.5 years. Twenty two malignancies were found in 21 of 249 patients. Skin cancer accounted for 59% and non-Hodgkin lymphoma for 23% of malignancies. At 25 years after first renal replacement therapy, the probability of developing a malignancy was 17% (95% CI: 9 to 24%). Compared to the general population the incidence rate for overall cancer was tenfold higher. For non-melanoma skin cancer and non-Hodgkin lymphoma, standardised risks were 222 and 46 respectively. The use of more than 20 mg/kg cyclophosphamide showed an association with increased risk of malignancy. Six patients died as a result of their malignancy, accounting for 9.5% of overall mortality. Whereas four out of five patients with non-Hodgkin lymphoma died, the most frequent malignancy, skin cancer, did not contribute to mortality. Conclusion-The long term risk of certain malignancies is significantly increased in children who have undergone renal replacement therapy. As an important contributor to overall mortality, awareness of this risk of malignancy in these patients is necessary, especially after treatment with cyclophosphamide. [ABSTRACT FROM AUTHOR]

Unlabelled: We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis, and subsequently, a fasting test revealed severe metabolic ketoacidosis with normal blood glucose after 13 h which suggest a defect in ketolysis. In his cultured skin fibroblasts succinyl-CoA:acetoacetate transferase was deficient (residual activity 15%). Treatment in the acute phase consisted of sodium bicarbonate. At the present age of 9 years, psychomotor and physical development are within normal limits.Conclusion: Defects of ketolysis probably are underdiagnosed disorders and should be considered in infants and young children with persistent ketosis. [ABSTRACT FROM AUTHOR]

Regurgitation is a common manifestation in infants below the age of 1 year and a frequent reason of counselling of general practitioners and paediatricians. Current management starts with postural and dietary measures, followed by antacids and prokinetics. Recent issues such as an increased risk of sudden infant death in the prone sleeping position and persistent occult gastro-oesophageal reflux in a subset of infants receiving milk thickeners or thickened "anti-regurgitation formula" challenge the established approach. Therefore, the clinical practices for management of infant regurgitation have been critically evaluated with respect to their efficacy, safety and practical implications. The updated recommendations reached by the working party on the management of infant regurgitation contain five phases: (1 A) parental reassurance; (1 B) milk-thickening agents; (2) prokinetics; (3) positional therapy as an adjuvant therapy; (4 A) H2-blockers; (4 B) proton pump inhibitors; (5) surgery. [ABSTRACT FROM AUTHOR]

Many infants do regurgitate. The recommend-ed therapeutic approach starts with postural and dietary measures, followed by antacids and prokinetics. However, the recent findings regarding the increased risk for sudden infant death (SID) in the prone sleeping position challenge the current recommendations. Management of regurgitation should in the first place aim at reducing parental anxiety. Postural treatment favouring the prone-elevated (30°) position is no longer recommended as a first line treatment of regurgitation, despite its efficacy, because of the unexplained association of SID with the flat prone sleeping position. Favouring the prone elevated position would result in an increased parental anxiousness.Conclusion Positional treatment can only be recom-mended in children beyond the age of SID risk, or as an adjuvant therapy in cases resistant to reassurance, thickeners and prokinetics and in whom other diag-nostic possibilities (infection, etc.) are considered rejected. [ABSTRACT FROM AUTHOR]

Background: Regarding the analysis of RCT data there is a debate going on whether an adjustment for the baseline value of the outcome variable should be made. When an adjustment is made, there is a lot of misunderstanding regarding the way this should be done. Therefore, the aims of this educational paper are: 1) to explain different methods used to estimate treatment effects in RCTs, 2) to illustrate the different methods with a real life example and 3) to give an advise on how to analyse RCT data., Methods: Longitudinal analysis of covariance, repeated measures analysis in which also the baseline value is used as outcome and the analysis of changes were theoretically explained and applied to an example dataset investigating a systolic blood pressure lowering treatment., Results: It was shown that differences at baseline should be taken into account and that regular repeated measures analysis and regular analysis of changes did not adjust for the baseline differences between the groups and therefore lead to biased estimates of the treatment effect. In the real life example, due to the differences at baseline between the treatment and control group, the different methods lead to different estimates of the treatment effect., Conclusion: Regarding the analysis of RCT data, it is advised to use longitudinal analysis of covariance or a repeated measures analysis without the treatment variable, but with the interaction between treatment and time in the model.

Chronically ill children require several hours of additional care per day compared to healthy children. As parents provide most of this care, they have to incorporate it into their daily schedule, which implies a reduction in time for other activities. The study aimed to assess the effect of having a chronically ill child on parental employment and parental leisure activity time, and to explore the role of demographic, social, and disease-related variables in relation to employment and leisure activities. Outcomes of 576 parents of chronically ill children and 441 parents of healthy school children were analyzed with multivariate regression. Having a chronically ill child was negatively related with family employment, maternal labor force participation, and leisure activity time. Use of child care was positively related to family and maternal employment of the total group of parents. Within parents of chronically ill children, most important finding was the negative relation of dependency of the child on daily care and low parental educational level with family and maternal employment. In conclusion, parents of chronically ill children, mothers in particular, are disadvantaged in society probably due to the challenge of combining child care with work and leisure time., (© The Author(s) 2013.)

Background: As the treatment of chronic or life-threatening diseased children has dramatically over recent decades, more and more paediatric patients reach adulthood. Some of these patients are successfully integrating into adult life; leaving home, developing psychosocially, and defining a role for themselves in the community through employment. However, despite careful guidance and support, many others do not succeed. A growing number of adolescents and young adults who have had a somatic disease or disability since childhood apply for disability benefits. The purpose of this study was to assess the health-related quality of life (HRQoL), anxiety and depression of young adults receiving disability benefits because of somatic conditions compared to reference groups from the general Dutch population and to explore factors related to their HRQoL, anxiety and depression., Methods: Young adults (N = 377, 22-31 yrs, 64.3% female) claiming disability benefits completed the RAND-36 and an online version of the HADS. Differences between respondents and both reference groups were tested using analysis of variance and logistic regression analysis by group and age (and gender). Regression analyses were conducted to predict HRQoL (Mental and Physical Component Scale; RAND-36) and Anxiety and Depression (HADS) by demographic and disease-related variables., Results: The respondents reported worse HRQoL than the reference group (-1.76 Physical Component Scale; -0.48 Mental Component Scale), and a higher percentage were at risk for an anxiety (29.7%) and depressive (17.0%) disorder. Better HRQoL and lower levels of anxiety and depression were associated with a positive course of the illness and the use of medical devices., Conclusions: This study has found worse HRQoL and feelings of anxiety and depression experienced by young adults claiming disability benefits. Healthcare providers, including paediatric healthcare providers, should pay systematic attention to the emotional functioning of patients growing up with a somatic condition in order to optimise their emotional well-being and adaptation to society during their transition to adulthood. Future research should focus on emotional functioning in more detail in order to identify those patients that are most likely to develop difficulties in emotional functioning and who would benefit from specific psychosocial support aimed at workforce participation.

Background: In a murine model of allergic inflammation, Bifidobacterium breve M-16V has been shown to reduce IL-4 and IgE by inducing IL-10 and IFN-γ. However, it remains unknown whether this strain has the same effect in humans with allergic disease., Objective: To determine the effects of Bifidobacterium breve M-16V combined with a prebiotic oligosaccharide mixture (synbiotic) on atopic markers, ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) and circulating regulatory T cell percentage in infants with atopic dermatitis., Methods: In a double-blind, placebo-controlled multi-centre trial, 90 infants with atopic dermatitis, age <7 months, were randomized to receive an infant formula with Bifidobacterium breve M-16V and a mixture of short chain galactooligosaccharides and long chain fructooligosaccharides (Immunofortis(®) ), or the same formula without synbiotics during 12 weeks. At week 0 and 12, plasma levels of IL-5, IgG1, IgG4, CTACK and TARC, ex vivo cytokine responses by PBMCs and percentage of regulatory T cells, were determined., Results: There were no significant differences between the synbiotic and the placebo group in IL-5, IgG1, IgG4, CTACK and TARC levels and ex vivo cytokine production by anti-CD3/anti-CD28-stimulated PBMCs. With allergen-specific stimuli, we found a decreased IL-12p40/70 and IL-12p70 production in response to egg allergen (P = 0.04 and P = 0.01, respectively) and decreased IL-12p70 production in response to peanut allergen (P = 0.003) in the synbiotic compared with the placebo group. Circulating regulatory T cell percentage did not significantly differ between the groups., Conclusions and Clinical Relevance: This synbiotic mixture has no detectable effect on plasma levels of the analysed atopic disease markers, ex vivo cytokine production and circulating regulatory T cell percentage in infants with atopic dermatitis, besides down-regulation of IL-12 production in egg- and peanut-stimulated PBMCs. These results do not support the use of this synbiotic in clinical practice., (© 2011 Blackwell Publishing Ltd.)

Aim: A growing number of young adults with somatic diseases/disabilities since childhood apply for disability benefits. The achievement of psychosocial milestones while growing up (course of life) is assumed to be related to job participation. This study assessed the course of life of young adult beneficiaries with somatic limitations compared with peers from the general Dutch population., Methods: Young adult beneficiaries (22-31 years, N = 415) completed the Course of Life Questionnaire assessing the achievement of milestones on autonomy, psychosexual and social development and risk behaviour. Differences between respondents and peers were tested using analysis of variance and logistic regression analysis by group, age and gender. Associations were expressed as odds ratios (OR) with confidence intervals., Results: The beneficiaries achieved fewer milestones or achieved the milestones at a later age than peers. The differences were substantial: most effect sizes were moderate to large and most of the ORs lower than 0.5., Conclusion: Young adult beneficiaries with somatic limitations since childhood are at risk of a delayed course of life. Healthcare providers should pay systematic attention to the psychosocial developmental trajectory of their patients in order to optimize their development to adulthood and, consequently, create conditions for an optimal labour market position., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Background: Evidence-based practice (EBP) is a generally accepted means to improve healthcare quality. However, not all healthcare professionals and managers apply EBP in daily practice. We investigated EBP attitudes, knowledge and the perceived barriers and facilitators to practising EBP , to define tailor-made interventions for improving evidence-based behaviour., Methods: In this cross-sectional survey, doctors and nurses from five major specialities of a university hospital were invited to complete the McColl and Barriers questionnaires., Results: Response rates were 70% (305÷435) for doctors and 74% (396÷537) for nurses. They were welcoming towards EBP, but considered time constraints, knowledge gaps and poor availability of evidence as major barriers to implement EBP . They also mentioned contradicting results (75%) and flawed methodology (69%), while nurses frequently mentioned unawareness of (75%), or difficulty in reading and interpreting research papers (70%). Regarding EBP knowledge, 6/8 common EBP terms could be explained by 54% of doctors but by only 15% of nurses. Facilitating factors among doctors concerned the availability and accessibility of high-level evidence and communication of evidence during various clinical meetings and handovers for clinical decision making. Among nurses, promoting factors involved more teaching and instances to incorporate EBP in clinical practice. Both groups desired more managerial support in terms of motivation and opportunities., Conclusions: Doctors and nurses have embraced the EBP paradigm as an important means to improve quality of clinical patient care, but its application is still cumbersome. This paper offers a tailored programme for implementation and managerial role-models.sustainment of EBP, corroborated by professional and managerial role-models.

Background: Clinical trials investigating the therapeutic effect of probiotics on atopic dermatitis (AD) show inconsistent results. Better results can possibly be achieved by combining probiotics with prebiotics, i.e. synbiotics., Objective: To investigate the therapeutic effect of a synbiotic mixture on the severity of AD in infants., Methods: In a double-blind, placebo-controlled multi-centre trial, 90 infants with AD [SCORing Atopic Dermatitis (SCORAD) score > or =15], aged < 7 months and exclusively formula fed, were randomly assigned to receive either an extensively hydrolysed formula with Bifidobacterium breve M-16V and a galacto-/fructooligosaccharide mixture (Immunofortis), or the same formula without synbiotics for 12 weeks. The primary outcome was severity of AD, assessed using the SCORAD index. A secondary outcome measure was intestinal microbiota composition., Results: There was no difference in SCORAD score improvement between the synbiotic and the placebo group. The synbiotic group did have a significantly higher percentage of bifidobacteria (54.7% vs. 30.1%, P<0.001) and significantly lower percentages of Clostridium lituseburense/Clostridium histolyticum (0.5 vs. 1.8, P=0.02) and Eubacterium rectale/Clostridium coccoides (7.5 vs. 38.1, P<0.001) after intervention than the placebo group. In the subgroup of infants with IgE-associated AD (n=48), SCORAD score improvement was significantly greater in the synbiotic than in the placebo group at week 12 (-18.1 vs. -13.5 points, P=0.04)., Conclusions: This synbiotic mixture does not have a beneficial effect on AD severity in infants, although it does successfully modulate their intestinal microbiota. Further randomized-controlled trials should explore a possible beneficial effect in IgE-associated AD.

Objective: To determine whether the increase in the percentage of stunted growth in Bush Negro infants in the interior of Surinam is related to an absolute food (i.e. energy) shortage or to a shortage of protein., Design: Descriptive., Method: In the villages of Dan and Botopasi, children aged 2-5 years from two schools and their mothers were examined. Growth during the first year of life, duration of breastfeeding, age of introduction of and composition of complementary feeding and current nutritional status of mother and child were determined., Results: Sixteen children and their mothers were included. Compared to the Dutch growth charts, birth weight was significantly lower (p = 0.03). After the age of 6 months there was a significant dropping off in weight gain (p = 0.018). Five of the 16 children received protein-poor complementary feeding, which did not lead to catch-up growth. Between the ages of 2-5, 6 of the 16 children showed stunted growth but none of the children or their mothers was wasted. Five of the 16 mothers had a body mass index > 25., Conclusion: The nutritional status of the mothers showed that there was no absolute shortage of energy. The protein content coming from the complementary food for the Bush Negroes in our research group was below recommended levels. Stunted growth in these children is better explained by a shortage of well-balanced complementary feeding rather than by an absolute shortage of energy. Education about food recommendations for the young child is of great importance in the prevention of chronic malnutrition.

Aim: To assess the quality of life, anxiety and concerns among statin-treated children with familial hypercholesterolaemia (FH) and their parents., Methods: 69 FH children on statin therapy and 87 parents (51 families) participated in this study. Quality of life of the children, and anxiety levels of both the children and their parents, were investigated using self-report questionnaires. In addition, a questionnaire was designed to evaluate FH-specific concerns of these children and their parents on six different topics: 1, knowledge about FH; 2, experience of the disease; 3, family communication; 4, screening; 5, diet; and 6, experience of medication therapy., Results: FH children and their parents reported no problems with regard to quality of life and anxiety. In contrast, the FH survey showed specific FH-related concerns. One-third of the children thought that FH can be cured, and 44% of the children suffered from the fact they have FH, but taking medication makes them feel safer (62%). The majority of the children kept a low cholesterol diet and more than 50% took care not to eat too much fat. Almost 38% of the parents experienced FH as a burden to their family and 79% suffered because their child had FH., Conclusion: These findings show that statin-treated children with FH and their parents did not report affected psychosocial functioning, but did show specific FH-related concerns.

A detailed medical history in combination with a thorough physical examination, including rectal examination, form the cornerstone in the diagnostic work-up for children with functional defecation disorders. Additional investigations are often not informative and have only minor diagnostic or therapeutic implications. Medical therapy in children with functional constipation and solitary encopresis is primarily based on clinical experience. In both patient groups, the role of education, the use of diary cards and toilet training is important. In some patients behaviour interventions are important. Oral laxatives are the basis of treatment of children with functional constipation, whereas they are contra-indicated in children with solitary encopresis. In both groups, biofeedback training appears to be of little additional benefit. Long-term follow-up of children with functional defecation disorders shows that complaints continue far beyond puberty in many children.

The childhood prevalences of constipation and encopresis are 0.3-8% and 1-3% respectively. Following a recent stricter definition and classification, constipation and solitary encopresis are now recognised to be two separate entities. Constipation is characterised by infrequent defecation, often in combination with involuntary loss of faeces. Solitary encopresis most often occurs once a day after school hours. When there is no defecation, the frequency of encopresis increases, the abdominal pain becomes more severe and the appetite becomes less, until a large quantity of faeces is produced (often once per week). The physiology of the defecation and continence mechanism is complex and has only been unravelled in part. The multiple physiological mechanisms involved have a complementary and compensatory effect on each other. This makes it difficult to determine the underlying pathophysiological mechanisms of these functional disorders.

Chronic abdominal pain occurs in 17% of children aged 0-14 years with a peak of 33% at the age of 7 years. According to the Rome II criteria abdominal pain disorders can be classified as functional dyspepsia, irritable bowel syndrome, functional abdominal pain, abdominal migraine, and aerophagia. This new classification will hopefully lead to a more careful diagnosis of functional abdominal pain syndromes and to better treatment strategies. A thorough history taking and physical examination are the cornerstone of diagnostic workup in children with chronic abdominal pain. An extensive explanation and reassurance are the basis of an adequate treatment and in the majority of cases this is successful.

Objective: Early detection of children with sickle cell disease, determination of carriership frequency as well as evaluation of the knowledge regarding this haemoglobinopathy in various ethnic risk groups., Design: Prospective., Methods: From 1 November 1998 through to 31 October 1999, the ethnic background was recorded for consecutive pregnant women under care of the Academic Medical Centre, Amsterdam, the Netherlands, and the presence of carriership for sickle cell disease was evaluated. Carriers were asked about their knowledge of sickle cell disease. A diagnostic blood test of cord blood was also performed using a PCR which could detect both haemoglobin S and C mutations., Results: Fifty-five carriers were detected in a group of 1,016 investigated pregnant women (5.4%). The carriership frequencies in Surinam and African women were 12 and 15.7%, respectively. Knowledge of sickle cell disease, its occurrence in populations at risk, as well as the terms 'inheritance' and 'carriership', differed substantially between Surinam and African women, with awareness being lower in the latter group. In six cases informed consent was not asked. All other 49 carriers consented to a diagnostic test. Two intrauterine deaths occurred. Four children had sickle cell disease: three had HbSS, one had HbSC. Nineteen children proved to be carriers for sickle cell disease, 18 were heterozygotes for HbS, one for HbC., Conclusion: This targeted neonatal screening for sickle cell disease was feasible in a hospital setting. The number of children diagnosed with the disease supports the wider implementation of this method of early detection.

In a recent report by the Society of Integral Cancer Centres in the Netherlands, attention was devoted to the incidence of cancer in children and the mortality arising from this. In recent years the growing diagnostic and therapeutic possibilities have changed the perspective of childhood cancer enormously. Based on a careful classification and clinical staging, national and international investigations have resulted in new and successful therapeutical strategies. Overall prognoses of childhood cancer have improved dramatically from a 5-year survival rate in the 1960s and 1970s of less than 30%, to an 8-year survival rate of more than 70% between 1989 and 1997. However, this success means that more investigations into the long-term effects of childhood cancer and its treatment are needed. In a study at the Amsterdam University Hospital, 700 adult survivors of childhood cancer were reinvestigated of whom over 75% experienced one or more clinically relevant long-term effects. A continuous survey for long-term effects is needed for the development of new therapeutic strategies, which allow children treated for cancer to develop with the same possibilities in life as their healthy peers.

Fabry's disease, deficiency of the enzyme alpha-galactosidase A, is an X-linked lysosomal storage disorder. Clinical symptoms are caused by continuous deposition of specific glycolipids in endothelial cells, neural cells, skin and cornea. These depositions give rise to skin (angiokeratoma) and eye abnormalities (cornea verticillata), acroparaesthesias and anhidrosis and later in life cause renal insufficiency and cardiovascular complications. Hemizygous males suffer from Fabry's disease, whereas female carriers (heterozygotes) are usually asymptomatic. Recently, an atypical presentation of Fabry's disease was described in males who only presented with cardiac involvement. Therefore, the actual number of Fabry patients in the Netherlands could be higher than the predicted 300. Diagnosis in males can be established by measuring alpha-galactosidase enzyme activity in plasma, leukocytes or fibroblasts. Apart from kidney transplantation only symptomatic therapy is available today. Enzyme supplementation therapy (as shown in Gaucher's disease) and substrate deprivation are possible ways of treatment in the future.

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is an autosomal recessive disorder of mitochondrial fatty acid oxidation. Apart from life-threatening metabolic derangement with hypoketotic hypoglycemia, patients often show liver disease, cardiomyopathy, and neuropathy. A common mutation (1528G>C) in the gene coding for the alpha-subunit of the mitochondrial trifunctional protein harboring LCHAD activity is found in 87% of the alleles of patients. LCHAD is considered a rare disorder with only 63 patients reported in the literature. Whether this is due to a truly low prevalence of the disorder or because many patients remain unrecognized as a result of aspecific symptomatology is not clear. A remarkable association between LCHAD deficiency and the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, which is a severe complication of pregnancy, has been reported. Because of this, we studied the frequency of the common LCHAD mutation in the Dutch population by analyzing 2,047 Guthrie cards and 113 women who had suffered from HELLP syndrome. To be able to perform this large-scale study in dried bloodspots, we developed a new sensitive PCR-restriction fragment length polymorphism method. The carrier frequency for the common LCHAD mutation in the Dutch population was found to be low (1:680), consistent with the observed low incidence of the disorder. In the group of women with a history of HELLP syndrome, the prevalence of the common LCHAD mutation was also low (1:113). We conclude that LCHAD deficiency is, indeed, a rare disorder and that heterozygosity for the common mutation is not a major cause of the HELLP syndrome.

Reliability of differential sugar absorption tests is hampered by a lack of standardization of the content and osmolarity of the test solutions. We evaluated the effect of osmolarity of the test solution of the sugar absorption test on the 5 hour urine excretion of orally administered lactulose and mannitol. A group of 28 controls and 14 coeliacs, with villous atrophy grade II to IV, ingested a hyperosmolar sugar absorption test solution and a "low"-osmolar solution, respectively. After an overnight fast, each subject ingested hyperosmolar sugar absorption test solution (2 g mannitol, 5 g lactulose and 40 g sucrose/100 ml (around 1,560 mmol/l)). After two days, this procedure was repeated with low-osmolar solution (2 g mannitol and 5 g lactulose/100 ml (around 375 mmol/l). The influence of the sequence of the tests on the results had previously been excluded. All urine from the 5 h-period following ingestion of the test solution was collected. To calculate the low-osmolar solution ratio, samples were analysed for lactulose and mannitol concentrations by gas chromatography The sensitivity of hyperosmolar SAT solution and low-osmolar solution for the detection of mucosal abnormalities in coeliacs was 64% and 43%, respectively. In conclusion, a hyperosmolar solution discriminates better between normal and damaged mucosa of the small bowel such as villous atrophy due to a relative increase in permeability for lactulose.

Objective: To determine the differences in quality of life between children with sickle cell disease and healthy immigrant children., Design: Descriptive, comparative., Method: The quality of life of children with sickle cell disease between 5 and 15 years old being treated in the Emma Children's Hospital AMC in Amsterdam, the Netherlands, was assessed by using a questionnaire for parents (TNO-AZL Children's Quality of Life Questionnaire (TACQOL) parent form) if the child was between 5 and 11 years old and a questionnaire for children (TACQOL child form) if the child was between 8 and 15 years old. The study period was April-October 1998. The questionnaires were completed by 45 (parents of) patients. The results were compared with a healthy reference group of immigrant children. Statistical analysis was performed using the Student t-Test., Results: Children with sickle cell disease as well as their parents scored significantly lower on the items general physical, motor and independent daily functioning and on occurrence of negative emotions. No significance was observed for the items cognitive functioning and school performance nor for social functioning or occurrence of positive emotions., Conclusion: In children, sickle cell disease leads to compromised physical and possibly also psychological wellbeing, as well as the experience of decreased independence in daily functioning, but not to compromised cognitive or social aspects of the quality of life.

Up to the present, aspecific immunosuppressive medication is still required to prevent rejection of transplanted allogeneic tissues and to treat autoimmune disorders. These drugs are associated with numerous adverse effects. Therefore, alternative forms of immunomodulation are being extensively studied. T-cells play a central role in regulating the immune system. Expanding insight into the cellular mechanisms involved in immune recognition and activation led to the development of new tolerance-inducing strategies. Potential sites for tolerance induction are situated centrally in the thymus as well as in the peripheral T-cell population. Explicitly mentioned tolerance strategies are (a) allogeneic bone marrow transplantation and intrathymic tolerance induction (central tolerance induction), (b) peripheral T-cell clonal deletion, induction of anergy and immune deviation (all three are examples of peripheral tolerance induction).

Background: Cisapride is a gastrointestinal prokinetic agent that is used worldwide in the treatment of gastrointestinal motility-related disorders in premature infants, full-term infants, and children. Efficacy data suggest that it is the most effective commercially available prokinetic drug., Methods: Because of recent concerns about safety, a critical and in-depth analysis of all reported adverse events was performed and resulted in the conclusions and recommendations that follow., Results: Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisapride is given to pediatric patients who can be considered healthy except for their gastrointestinal motility disorder, and the maximum dose does not exceed 0.8 mg/kg per day in 3 to 4 administrations of 0.2 mg/kg (not exceeding 40 mg/d), no special safety procedures regarding potential cardiac adverse events are recommended. However, if cisapride is prescribed for patients who are known to be or are suspected of being at increased risk for drug-associated increases in QTc interval, certain precautions are advisable. Such patients include those:(1) with a previous history of cardiac dysrhythmias, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or disease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc interval should be used before initiation of therapy and after 3 days of treatment to ascertain whether a cisapride-induced cardiac adverse effect is present., Conclusions: With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced doses. If higher doses than this are given, the precautions above are advisable. In any patient in whom a prolonged QTc interval is found, the dose of cisapride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and the administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be restarted at half dose with control of the QTc interval. Unfortunately, at present, normal ranges of QTc interval in children are unknown. However, a critical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater than 470 milliseconds as outside it.

Background: Around birth, myocardial substrate supply changes from carbohydrates before birth to primarily fatty acids after birth. Parallel to these changes, the myocardium is expected to switch from the use of primarily lactate before birth to fatty acids thereafter. However, myocardial lactate uptake and oxidation around birth has not been measured in vivo., Methods and Results: We measured myocardial lactate uptake, oxidation, and release with infusion of [1-13C]lactate and myocardial flux of fatty acids and glucose in chronically instrumented fetal and newborn (1 to 15 days) lambs. Myocardial lactate oxidation was the same in newborn (81.7+/-14.7 micromol. min-1. 100 g-1, n=11) as in fetal lambs (60.7+/-26.7 micromol. min-1. 100 g-1, n=7). Lactate uptake was also the same in newborn as in fetal lambs. Lactate uptake was higher than lactate flux, indicating lactate release simultaneously with uptake. In the newborn lambs, lactate uptake declined with age. Lactate uptake was strongly related to lactate supply, whereas lactate oxidation was not. The supply of fatty acids or glucose did not interfere with lactate uptake, but the flux of fatty acids was inversely related to lactate oxidation., Conclusions: We show that lactate is an important energy source for the myocardium before birth as well as in the first 2 weeks after birth in lambs. We also show that there is release of lactate by the myocardium simultaneously with uptake of lactate. Furthermore, we show that lactate oxidation may be attenuated by fatty acids but not by glucose, probably at the level of pyruvate dehydrogenase.