Lactose and fructose malabsorption in children with recurrent abdominal pain: results of double-blinded testing.

AIM: To investigate malabsorption of lactose and fructose as causes of recurrent abdominal pain (RAP). METHODS: In 220 children (128 girls, mean age 8,8 [4.1-16.0] years) with RAP, hydrogen breath tests (H(2) BT; abnormal if ΔH(2) > 30 ppm) were performed with lactose and fructose. Disappearance of RAP with elimination, recurrence with provocation and disappearance with re-elimination, followed by a 6-month pain-free follow-up, were considered indicative of a causal relation with RAP. For definite proof, a double-blinded placebo-controlled (DBPC) provocation was performed. RESULTS: Malabsorption of lactose was found in 57 of 210, of fructose in 79 of 121 patients. Pain disappeared upon elimination in 24/38 patients with lactose malabsorption, and in 32/49 with fructose malabsorption. Open provocation with lactose and fructose was positive in 7/23 and 13/31 patients. DBPC provocation in 6/7 and 8/13 patients was negative in all. However, several children continued to report abdominal symptoms upon intake of milk or fructose. CONCLUSION: Lactose intolerance nor fructose intolerance could be established as causes of RAP, according to preset criteria including elimination, open provocation and DBPC provocation. However, in clinical practice, persistent feeling of intolerance in some patients should be taken seriously and could warrant extended elimination with repeated challenges.

Recurrent abdominal pain in 200 children: somatic causes and diagnostic criteria.

AIM: To establish to what extent somatic causes can be found in children referred to secondary care with recurrent abdominal pain. METHODS: For 2 years, all consecutive patients (age 4-16 years) fulfilling Apley criteria, referred to secondary care, were included. After a diagnostic work-up, stepwise therapeutic interventions were performed. A diagnosis was considered to be the cause of the pain when the patient became pain free following therapeutic intervention and remained so for at least 6 months. RESULTS: Two hundred and twenty children (128 F, 92 M; mean age 8.8 years) were enrolled, of which 20 were lost to follow-up. Spontaneous recovery was seen in 54 patients, (occult) constipation in 92 patients (of whom 18 also had a somatic cause), gastrointestinal infections in 40, food allergy in five, miscellaneous disorders in seven and uncertain diagnosis in 13. In five patients, stress most likely caused the pain. A total of 198 patients became pain free and remained so during follow-up (mean 18, range 6-60 months). CONCLUSION: In 200 children with recurrent abdominal pain, somatic causes were found in 26%. Laxative therapy was successful in 46%, resulting in nearly all patients with functional abdominal pain to become pain free. Eventually, 99% became pain free using a therapeutic intervention protocol.

Molecular basis of lactase levels in adult humans.

The molecular basis of adult human "lactase deficiency" has long been a subject of controversy. To address this issue, small intestinal biopsies from orienta, black, and white patients were analyzed. Adjacent samples were assayed for lactase and sucrase specific activities and the sucrase/lactase ratio (high ratio signifies lactase deficiency), and the results were compared to lactase steady-state mRNA levels detected in Northern blots probed with a human lactase mDNA. All oriental patients had high ratios and no detectable lactase mRNA. Four black patients had a similar pattern; two with low ratios had detectable mRNA. The group of white patients displayed a range of findings, from high ratio/no mRNA to low ratio/considerable mRNA. Elevated levels of lactase mRNA always correlated with the presence of elevated levels of lactase enzyme activity, suggesting that the difference in levels of adult human intestinal lactase activity among racial groups may be regulated at the level of gene transcription.

Messenger RNA sorting in enterocytes. Co-localization with encoded proteins.

This study describes the intracellular compartmentalization of three different mRNAs in the polarized rat fetal enterocyte. They encode proteins that are known to be localized within different regions of the epithelial cell namely (i) the apical, membrane-bound glycoprotein, lactase-phlorizin hydrolase (lactase), (ii) the mitochondrially localized enzyme, carbamoylphosphate synthetase (CPS), and (iii) the cytoplasmically localized enzyme, phosphoenolpyruvate carboxykinase (PEPCK). These mRNAs are found in close proximity to their respective protein products, i.e. the apical membrane, mitochondria and cytoplasm, respectively. The significance of these observations is twofold; (i) they indicate that mRNAs are sorted into specific domains of the cytosol of intestinal epithelial cells; and (ii) they imply the presence of two distinct pathways of mRNA targeting one that allows transport of mRNAs that are translated on ribosomes associated with the rough endoplasmic reticulum (lactase mRNA), and the other that allows sorting of mRNAs that are translated on free polysomes (CPS and PEPCK mRNA).

Intestinal carbamoyl phosphate synthase I in human and rat. Expression during development shows species differences and mosaic expression in duodenum of both species.

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.

Mechanisms of growth retardation, drug therapy, and nutritional support in pediatric inflammatory bowel disease: a workshop sponsored by the north american and European societies for pediatric gastroenterology and nutrition.

SUMMARY: : Growth retardation is common in children with inflammatory bowel disease (IBD). The most sensitive measure of impaired growth, growth velocity, is abnormal in 65% of children with Crohn's disease. With treatment, growth velocity may return to normal, but catch-up growth is often incomplete and ultimate height lower than predicted. In some patients delayed puberty may compensate for poor growth earlier in life, and there is good evidence that even after menarche, significant growth can occur. Surgery may have a favorable impact on growth in the short term, but final height often remains reduced. The mechanism for growth failure in IBD is thought to be related to both prolonged periods of suboptimal nutritional intake and persistent inflammation. Growth throughout childhood is dependent on growth hormone and insulin-like growth factors (IGF). At puberty, androgens and estrogens also play a significant role in normal growth. Both malnutrition and inflammatory bowel disease result in low levels of IGF-1. With recovery, levels return to normal. Although little work has been done to measure the effects of chronic maintenance drug therapy on growth, it is known that children taking alternate-day prednisone grow normally and can exhibit catch-up growth. Nutritional therapy with tube feeding of elemental diets also improves nutrition and decreases inflammation. Children with either small-bowel Crohn's or Crohn's ileocolitis respond to tube feedings of both elemental or semielemental diets.

Problems in diagnosis of IBD in children.

Children and adolescents with inflammatory bowel disease (IBD) present unique challenges to physicians and all health-care providers. The most important aspect is that children are not small adults. They are characterized by a highly dynamic state of growth and physical change as well as a constant alteration in psychological status. It will not be difficult to recognize IBD, even in children, when it presents with classical symptoms such as bloody diarrhoea, abdominal pain and weight loss. However, some children will present with abdominal pain and depression. Not infrequently these children are diagnosed as being depressed and are seen and treated by psychologists and psychiatrists for different periods of time. In addition, several children will be initially diagnosed as having a bacterial gastroenteritis with a proven positive faecal culture. It seems to be the triggering event in these children, and if adequate therapy fails, colonoscopy is indicated. Recently, Beattie et al. showed that in children seen for chronic abdominal pain simple routine blood tests including full blood count and erythrocyte sedimentation rate are almost always abnormal in children with IBD. But most importantly, growth retardation is common in children with IBD and is more often found in Crohn's disease (CD) than in ulcerative colitis (UC). Faltering growth is a sign of a catabolic situation. Therefore, it is essential to follow the growth of children at the beginning and during treatment of IBD. Growth retardation can be the first symptom of IBD and is often already present before other symptoms of IBD become apparent. Rarely, extra-intestinal manifestations, particularly arthritis, can be the first and sometimes only initial symptom for months to years in children with IBD. About 2% of all patients with IBD present before the age of 10 years, but 30% present between the age of 10 and 19 years. A significant proportion of young patients with IBD will develop the disease just prior to or during puberty. Adolescent growth is characterized by rapid accumulation of lean body mass and any inflammatory disease occurring at this time is likely to have a major impact on nutritional status and growth. This rapid growth requires an appropriate increase in nutritional substrates and failure to achieve catch-up growth may ultimately lead to poor cumulative growth over time. Most of the growth retardation is seen in children with CD, approximately 30%. However, also in UC 15% will show a reduction in growth. The higher percentage in CD could be due to the disease itself or to the relative subtlety of the intestinal manifestations of CD, mainly abdominal pain and general malaise. Not only growth, but also delayed puberty, is a sign of an ongoing disease that most likely needs more intensive treatment. It has been shown that the severity of disease activity plays a more important role in the occurrence of growth retardation than steroid treatment. Therefore in paediatrics it is important to state that growth retardation during medical treatment equals undertreatment. In contrast to adults, the potential benefit of nutritional therapy should be seriously considered in addition to aggressive medical therapy including steroids and other immunosuppressive agents such as azathioprine. The most convincing evidence that malnutrition is primarily responsible for growth failure is based on depletion studies. The malnutrition itself is caused by ongoing inflammation and loss of appetite. Recommendations for nutritional therapy include an increase in energy and protein intake to 150% of recommended daily allowances for height and age. Some studies have shown the benefit of nocturnal nasogastric infusion as supplements of daily intake. Importantly, nutritional support has been shown to be as effective as steroids in achieving remission of disease in children. Furthermore, no significant differences have been shown in studies using elemental versus polymeric diets.

Facilities and equipment in district general hospitals in the Netherlands: are we prepared for the critically ill paediatric patients?

OBJECTIVE: To evaluate the inventory for initial treatment of critically ill children. DESIGN: Prospective study. SETTING: Paediatric emergency settings in 15 major district general hospitals. METHODS: Using an "expert opinion" created by paediatric intensivists, all hospitals were visited twice to check the inventory. Firstly, to examine the initial site of emergency care for children coming from outside the hospital. Secondly, to visit other emergency sites. A total score below 75% of the optimum was considered as not optimally equipped. MAIN RESULTS: Equipment to meet "respiratory problems" was considered by the experts as most essential. Seventy five per cent of all emergency sites scored below 75% (4 of 11 paediatric departments, 1 of 15 emergency rooms. The emergency room was in all aspects significantly better equipped than the paediatric department. Major differences and variations in the inventory were identified between all hospitals. CONCLUSIONS: Emergency rooms are better equipped to meet the needs of critically ill paediatric patients coming from outside the hospital than the paediatric departments. Paediatricians involved in the treatment of children who become critically ill during their stay in the hospital (the "indoor" patients), have less equipment and medication on the paediatric department at their disposal than on their emergency room. Obviously, emergency care on the paediatric wards should be equipped at the same level as in the emergency room because for both locations the "golden hour" is critically important in final outcome.

[Consensus inflammatory intestinal diseases in children: ulcerative colitis and Crohn disease. Work Group Academic Medical Center, Amsterdam]. / Consensus inflammatoire darmziekte bij kinderen: colitis ulcerosa en ziekte van Crohn. Werkgroep Academisch Medisch Centrum, Amsterdam.

Members of different societies, including Paediatrics, Gastroenterology, Clinical Chemistry, Radiology and Pathology, involved in the treatment of children with inflammatory bowel disease (IBD) reached consensus during 12 meetings about definition, clinical and diagnostic work-up as well as initial treatment options in paediatric IBD. On the basis of history and physical examination a distinction is made between colitis-like or Crohn-like appearance. Further laboratory investigations are required in the presence of malnutrition, extraintestinal manifestations or growth retardation. Pathology plays an important part in the final diagnosis. Special attention is given to pubertal staging and height measurements as routine aspects of the treatment of children with IBD.

[Functional childhood gastrointestinal disorders. I. Chronic abdominal pain]. / Functionele gastro-intestinale ziektebeelden op de kinderleeftijd. I. Chronische buikpijn.

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.

[Constipation in childhood; evaluation of a diagnostic-therapeutic protocol]. / Obstipatie op de kinderleeftijd; evaluatie van een diagnostisch-therapeutisch protocol.

In 87 children with constipation an assessment was made of the causes, and of the effect of treatment. Two subdivisions were made, one by age (< 3 years and > or = 3 years) and the second into 'own' or 'referred' patients. For the 59 own children a diagnostic-therapeutic protocol was used, the three-phase protocol. For children over 3 years (n = 29) this policy consists in the first phase of anamnesis, physical examination, diet and oral and/or rectal laxatives. In the second phase, toilet training is administered in combination with diet and oral laxatives. The third phase comprises continuation of the diet and tapering off of the laxatives. If no improvement is seen, supplementary examination is carried out. In the group of own patients younger than 3 years, supplementary examination is already carried out during the first phase. Functional constipation was diagnosed in 69% and 98%, respectively, of the 36 patients under 3 years and the 51 over 3 years. Hirschsprung's disease was diagnosed in 14% and 2%, respectively. In the children > or = 3 years with functional constipation the three-phase policy was successful in 86% with a mean duration of the treatment of 9.5 months. The efficiency of diagnostic examination of children over 3 years appears to be low, justifying the proposed three-phase policy. In children under 3 years, on the other hand, limited laboratory examination is necessary during the first phase. Examination for the presence of Hirschsprung's disease, by means of rectal biopsy or anorectal manometry is indicated if the treatment during the first phase is unsuccessful.

[Chronic constipation in children; good results of biofeedback training as supplementary therapy]. / Chronische obstipatie bij kinderen; gunstige effecten van biofeedback-training als aanvullende therapie.

In two children with refractory constipation biofeedback training was successfully used as a supplementary therapy. In this treatment, a balloon tied to the end of the catheter is inserted into the rectum and inflated with ever-decreasing amounts of air, so as to increase rectal sensibility. In addition, the defaecation pattern is displayed on a monitor. The child learns to control contraction and relaxation of the musculature involved in defaecation.

[Few ethnic differences in acute pediatric problems: 10 years of acute care in the Sophia Children's Hospital in Rotterdam]]. / Geringe etnische verschillen in spoedeisende problemen bij kinderen: 10 jaar acute hulp in het Sophia Kinderziekenhuis te Rotterdam.

OBJECTIVE: To evaluate whether there are differences in acute general paediatric problems and their severity between children with different ethnic backgrounds. DESIGN: Descriptive. METHOD: The following information was registered for patients who visited the paediatric emergency department at the Sophia Children's Hospital in Rotterdam, the Netherlands (1988 through to 1997): demographics, reason for encounter, diagnoses, diagnostics performed and follow-up. Ethnicity was determined by patient's surname. Analyses were performed using the chi 2 test, non-parametric Kruskal-Wallis test and multiple logistic regression. RESULTS: Fifty-one percent of all patients belonged to one of the ethnic minority groups. Infection-related problems were seen more often in Turkish (45%) and Moroccan (46%) children than in Dutch children (41%). Of those children with infection-related problems, the Turkish children were less likely to need X-rays (odds ratio: 0.73), laboratory diagnostics (0.72), an outpatient follow-up (0.79) or hospital admission (0.74). On the other hand, Moroccan paediatric patients were admitted slightly more frequently (to the intensive care department) and were more likely to have a lower respiratory tract infection (1.65). CONCLUSIONS: There were some differences between Dutch children and ethnic minorities in terms of the reasons for encounter and the severity of the problem. Compared with Dutch children, Turkish children presented with less severe infection-related problems, while Moroccan children had more severe infection problems.

[Functional childhood gastrointestinal disorders. II. Constipation and solitary encopresis: physiology and pathophysiology]. / Functionele gastro-intestinale ziektebeelden op de kinderleeftijd. II. Obstipatie en solitaire encopresis; fysiologie en pathofysiologie.

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.

[Functional childhood gastrointestinal disorders. III. Constipation and solitary encopresis; diagnostic work-up and therapy]. / Functionele gastro-intestinale ziektebeelden op de kinderleeftijd. III. Obstipatie en solitaire encopresis; diagnostiek en therapie.

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.

[Pregnancy during residency]. / Zwanger en in opleiding tot specialist.

The number of female residents in the Netherlands has steadily increased in recent years. Due to the increased time on waiting lists to enter residency programmes and to the increased duration of training, female residents will be older during their residencies. This will probably result in an increased number of pregnancies during residencies. A questionnaire regarding pregnancy during residency was sent to 191 residents in two university hospitals in the Netherlands. The response rate was 74.3%. Fifty percent of the male and only 19% of the female residents had children. No negative effects of a pregnancy on their training were experienced or anticipated by the residents. However, a negative effect on the functioning of the department was expected. No formal provisions, like replacements were available and many solutions to replace pregnant colleagues depended on the flexibility of the colleagues. The wish to have children was high and equally distributed among male and female residents, 92% and 96%, resp. Given the difficulty to seek a permanent position and to have children after residency, the choice of many female residents will be to have their children during residency. This increase in number of pregnancies requires anticipation of the residency programme directors. They should take the lead in proposing adequate regulations.

[The relationship between intake of dietary fiber and chronic constipation in children]. / Het verband tussen inname van voedingsvezels en chronische obstipatie bij kinderen.

OBJECTIVE: Evaluation of the feeding patterns of children with chronic constipation, in particular dietary fibres, energy and fluid intake and their influence on colonic transit time. In addition, the effect of dietary recommendations regarding fibres was assessed. DESIGN: Prospective randomized study. SETTING: Department of Paediatric Gastroenterology and Nutrition, Academic Medical Centre, Amsterdam, the Netherlands. METHOD: Children with at least 2 months of complaints related to constipation were enrolled and both dietary intake and colonic transit time were evaluated. After dietary and laxative treatment, in some combined with biofeedback training, and a follow-up of 6 months, a randomized sample were again evaluated regarding their transit times and dietary patterns. RESULTS: In 73 consecutive children mean fibre intake was the same as in healthy controls, although energy and fluid intake were lower. Colonic transit time was increased compared with healthy controls and no relationship was established between fibre intake and transit time. At 6 months no significant increase in mean fibre intake was observed and no relationship was found between either transit time and change in fibre intake or cure and change in fibre intake. In the cured patients no increase of their mean fibre intake could be observed. CONCLUSION: The amount of dietary fibres played no pathogenic part in chronic constipation. Dietary advice did not change the mean fibre content of the diet. In addition, changes in fibre intake had no effect on colonic transit time or cure.

Availability and accuracy of electronic patient data for medical practice assessment.

UNLABELLED: We analyzed availability and accuracy of electronic patient data needed to assess medical practice. A case study was performed in which pediatricians formulated 14 performance indicators that cover aspects of care for children with suspected meningitis. Data items needed to quantify these indicators were listed. Required patient data were gathered from hospital information system and paper medical records. Accuracy of electronically available data was based on comparison with paper data and, when paper data were not available, on how data were recorded at the source, administrative procedures and original goal for which data were recorded. CONCLUSION: Registration of reason for admission and diagnoses gives no reliable basis to select patients with 'suspicion on a disease' as selection criterion. Besides, many performance indicators cannot be reliably quantified because data are not recorded electronically (indication, medication, outpatient diagnosis), are not recorded specific enough (intervention time), are not standardized (radiology report), or cannot be obtained from other hospitals.

Clinical aspects of lactose intolerance in children and adults.

The principal carbohydrate of human milk is the disaccharide lactose. In human and all mammalian species, lactose is hydrolyzed in the small intestine by lactase-phlorizin hydrolase, also abbreviated as lactase. The absence of lactase results in the passage of undigested lactose into the large intestine and is associated with a well-known clinical syndrome: lactose intolerance. Low lactase levels result either from intestinal injury or, as in the majority of world's adult population, from alterations in the genetic expression of lactase. In this review terminology, pathophysiology, symptoms, diagnostic procedures, and therapy of lactose intolerance will be discussed.