Individualized treatment with infliximab therapy in children with Crohn's disease support shorter time intervals between infusions.

OBJECTIVES: To study the effect of an individualized treatment approach with regard to dosage intervals between infliximab infusions on the clinical outcome of pediatric Crohn's disease (CD). PATIENTS AND METHODS: A retrospective analysis of medical records of all pediatric patients with CD who had been treated with infliximab between 1999 and 2007 in two Swedish counties, where an individualized treatment approach had been applied. RESULTS: Twenty-nine patients were included in the study. The number of infusions varied from 2 to 47 (median: 8). Nineteen patients received more than 5 infusions and 13 patients received more than 10 infusions. Most of the patients did not stay in remission when the dosage interval was 8 weeks or longer. CONCLUSIONS: An individualized treatment approach, based on the physician's desire to treat, resulted in shorter dosage intervals than 8 weeks between infliximab infusions in a majority of pediatric patients with CD. The retrospective design of the study must be taken into account when interpreting the results.

Faecal calprotectin in HIV-infected, HAART-naïve Ugandan children.

OBJECTIVES: Calprotectin is a calcium- and zinc-binding protein and a marker in faeces of gastrointestinal inflammation. Reference values have been established in children older than 4 years. The aim of the present study was to determine the concentration of faecal calprotectin (FC) in human immunodeficiency virus (HIV)-infected, highly active antiretroviral therapy-naïve Ugandan children and compare it with the reference value. METHODS: We tested 193 HIV-infected children ages 0 to 12 years in a hospital-based survey for FC. A standardised interview with sociodemographic information and medical history was used to assess risk factors. A cluster of differentiation 4 (CD4) cell percentage was prevalent in all of the children. RESULTS: The median FC concentrations decreased with increasing age, as in healthy children. The median concentration was 208 mg/kg in infants 0 to 1 year, 171 mg/kg among toddlers 1 to 4 years, and 62 mg/kg for children 4 to 12 years. Children with advanced disease and a low CD4 cell percentage had significantly higher FC concentrations than those with a high CD4 cell percentage. Children older than 4 years with diarrhoea had significantly higher FC concentrations compared with those without diarrhoea. CONCLUSIONS: HIV-infected children older than 4 years had a median FC concentration above the reference value, and gut inflammation in the children with elevated values is likely. Children with more advanced disease had increased FC concentrations regardless of age.

Nutritional and clinical status of children admitted to the malnutrition ward, Maputo central hospital: a comparison of data from 2001 and 1983.

Malnutrition is the fourth commonest reason for hospital admission to the paediatric department of the Central Hospital, Maputo and has the second highest death rate (20 per cent). A study from 1995 into mortality at this paediatric department, suggested an increase in severe malnutrition. Recent studies have shown that the global burden of undernutrition in the world is declining; however, data for Eastern Africa shows a deterioration. The current study was aimed at describing and comparing the patients on the malnutrition ward, in 2001 and 1983. The study gathered indices of nutritional status and secondary diagnoses from the notes of all children (aged between 6 months and 5 years) discharged from the malnutrition ward for a period of l year (January-December 2001), and from data (collected in January-December 1983) for the malnutrition ward. Data was entered and analysed using Epi-Info 6 and SPSS statistics package. The ethics committee of the hospital approved the study. Data was collected for 558 children in 2001 and 833 in 1983. There was no gender difference, average age was 21.7 months in 2001 and 23.8 months in 1983 and the average hospital stay was 13.1 and 14.3 days, respectively. In 2001, 33 per cent had kwashiorkor, 26 per cent marasmus, and 28 per cent marasmic kwashiorkor. Three hundred and twenty children (82 per cent) were <2 Z-scores below the median weight-for-age and 252 children (65 per cent) were <3 Z-scores. Forty per cent had malaria, 65 per cent anaemia, 53 per cent bronchopneumonia, 14 per cent TB, 36 per cent diarrhoea, and 12 per cent HIV/AIDS. In 1983, 49 per cent had kwashiorkor, 17 per cent marasmus, and 11 per cent had marasmic kwashiorkor. A total of 494 children (81 per cent) were <2 Z-scores below the median weight-for-age and 335 children (55 per cent) were <3 Z-scores. Eighteen per cent had malaria, 37 per cent anaemia, 28 per cent bronchopneumonia, 6 per cent TB, 8 per cent diarrhoea, and 4.4 per cent measles/post-measles. A comparison between the clinical status of 1983 with that of 2001 shows little difference in age, gender or length of stay. There were fewer admissions in 2001, although a higher percentage of severely underweight children and the 2001 group had more secondary infections, especially malaria, bronchopneumonia and anaemia. Clinical malnutrition at a referral hospital level, in spite of the remarkable Mozambican economic growth, shows signs of following the depressing pattern for much of Eastern Africa. A prospective study including HIV tests and anthropometric data for this and the city's other hospitals is warranted. Discussion needs to be prompted on a local level about malnutrition and the use of guidelines.

Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 1990-2001.

BACKGROUND: An increased incidence of paediatric Crohn's disease was reported recently by our group. AIMS: To assess the incidence and characteristics of inflammatory bowel disease (IBD) in northern Stockholm between 1990 and 2001. METHODS: All records of individuals 0-15 years of age with suspected IBD in the population based catchment area of 180000 individuals were scrutinised using defined diagnostic criteria. Patient files were searched for relatives with IBD, and for concomitant autoimmune diseases. RESULTS: A total of 152 children were diagnosed with IBD, corresponding to an overall incidence (per 100000) of IBD of 7.4. The incidence of Crohn's disease (CD) was 4.9, ulcerative colitis (UC) 2.2, and indeterminate colitis 0.2. Between 1990 and 2001, there was a marked increase in the incidence of CD while the incidence of UC was almost unchanged, leading to a net increase in the overall occurrence of IBD. There was a male dominance of CD. Fourteen per cent and 11% of patients with CD and UC, respectively, had a first or second degree relative with IBD. Eighteen per cent and 10% of patients with CD and UC, respectively, had a concomitant autoimmune disease. Ten patients with CD (10%) underwent surgery. CONCLUSIONS: The incidence of CD has increased in northern Stockholm. The current incidence is higher than that reported from other areas. Our results suggest a shift in presentation and diagnosis from UC towards CD, but also a net increase in IBD. Concomitant autoimmune disorders and family history are common in paediatric IBD.

Regulation of K+ transport in the rat distal colon via angiotensin II subtype receptors and K+ -pathways.

The role of angiotensin subtype-1 (AT1) and -2 (AT2) receptors in mediating the effects of angiotensin II (ANG II) on several K+ transporters was studied in rat distal colon using an Ussing chamber. Angiotensin II induced K+ secretion at two different doses. Secretion occurred at 10-(8) and 10-(4) M, as a result of an increase in serosal-to-mucosal flux (Js-m). The ANG II-induced stimulation of Js-m at a low dose (10-(8) M) was abolished by PD123319 while losartan did not alter the low-dose ANG II-dependent increase in Js-m. In contrast, the increase in Js-m induced by a high-dose of ANG II (10-(4) M) was blocked by losartan, whereas PD123319 partially reduced the stimulatory effect. In the presence of both blockers, high-dose ANG II induced an inhibition of basal Js-m. Low-dose ANG II activated the barium-sensitive K+ channels, whereas the Na+, K+, 2Cl- cotransporter and the Na+, K+ -ATPase pump were unchanged. At the high dose, ANG II activated the barium-sensitive K+ channels and the Na+, K+, 2Cl- cotransporter and inhibited the Na+, K+ -ATPase pump. These data indicate that ANG II stimulates serosal-to-mucosal K+ flux in the rat distal colon at high and low doses via different receptors and K+ transporters.

Early development of human gastric H,K-adenosine triphosphatase.

BACKGROUND: Little is known about the early development of the gastric acid secretion in human neonates. The purpose of this study was to examine the early development of gastric H,K-adenosine triphosphatase (ATPase) by analyzing human gastric biopsy specimens. METHODS: Eighty-eight neonates from week 25 to week 42 of gestation who were treated in a neonatal intensive care unit underwent gastroscopy with biopsy specimens obtained from the corpus. The expression of gastric H,K-ATPase protein in the gastric biopsy specimens was assessed by Western blot analysis, using an antibody directed against the gastric H,K-ATPase. The amount of H,K-ATPase expressed was compared with age, gender, clinical factors, diseases, and the macroscopic and histologic findings at endoscopy. RESULTS: The expression of human gastric H,K-ATPase increased significantly with gestational age. There was a significant increase in the expression of gastric H,K-ATPase during the first 82 days after birth. Boys had a significantly higher expression of gastric H,K-ATPase than girls did, when it was adjusted for gestational and postnatal age. Neither the clinical features nor treatments showed significant correlations with the expression of human gastric H,K-ATPase when controlling for gestational and postnatal age. CONCLUSIONS: This study shows that human gastric H,K-ATPase is expressed from week 25 of gestation, which agrees with earlier findings of gastric pH in preterm infants. The amount of enzyme expressed increases with gestational and postnatal age. The authors speculate that the susceptibility to gastric lesions seen in neonates is not related to the amount of H,K-ATPase. However, studies elucidating the ontogeny of gastric mucosal defense mechanisms are warranted.

Incidence of paediatric Crohn's disease in Stockholm, Sweden.

We report an increase in the incidence of Crohn's disease in northern Stockholm, Sweden.

Potassium homeostasis: ontogenic aspects.

Potassium is the most abundant intracellular cation and plays an important role in a variety of cell functions. Potassium regulation and homeostasis during infancy are, owing to growth and development, different from in later life: infants need to retain more K+ than adults, to avoid growth retardation. Since the K+ requirements are different in infants and in adults, the mechanisms regulating K+ homeostasis also need to be different. This paper includes a review of the literature concerning the regulation of internal and external K+ balances during ontogeny. We examined the role of gastrointestinal tract, kidney and some tissue stores in K+ excretion and distribution during development. We conclude that positive K+ balance in infancy is characterized by higher K+ absorption in gut, lower K+ secretion/excretion in kidney and immaturity of the mechanisms regulating intra/extracellular K+ distribution. Several factors contribute to maintain the positive K+ balance. They include higher expression of absorptive transporters in colon and probably in kidney, lower expression of secretive transporters in colon and kidney, lower renal K+ excretion following K+ loading, immaturity of hepato-renal K+ reflex mechanism, immaturity of tissue K+ binding/releasing capacity and immaturity of the neuro-hormonal control of K+ transport in several organs.

Glucocorticoids stimulate the maturation of H,K-ATPase in the infant rat stomach.

The development of gastric H,K-ATPase from fetal to adult life was studied in the rat. The alpha and beta H,K-ATPase mRNA abundance, the protein abundance, and the enzyme activity increased postnatally. The sharpest increase in mRNA and enzyme activity was observed in the weaning period. Several intestinal enzymes are known to be stimulated by glucocorticoids at the time of weaning. To study the role of glucocorticoids in the maturation of gastric H,K-ATPase, we treated 10-d-old rats with a single injection of betamethasone. Twenty-four hours after betamethasone injection, the enzyme activity was significantly higher than in the control animals (2.6-fold, p < 0.05). The abundance of catalytic alpha H,K-ATPase protein was also increased (2.5-fold, p < 0.01). The time-dependent effect of betamethasone on alpha H,K-ATPase mRNA was determined from 6 to 24 h after treatment. Glucocorticoids did not significantly alter the mRNA abundance within 18 h. Twenty-four hours after injection, the gastric H,K-ATPase mRNA was significantly increased compared with controls (2.8- and 2.2-fold increase for alpha and beta subunits, respectively, P < 0.01 for both). In conclusion this study indicates that glucocorticoids may regulate the long-term maturation of gastric H,K-ATPase by indirectly stimulating enzyme synthesis.

Ontogeny of K+ transport in rat distal colon.

Infants need to retain more K+ than adults to avoid growth retardation. Since the K+ requirements are different in infants (I) and in adults (A), the mechanisms regulating K+ homeostasis should also be different. The colon plays an important role for the regulation of K+ homeostasis. Colonic K+ transport is bidirectional. In this study we have examined the development of colonic K+ transport with special reference to the contribution of different K(+)-transporting pathways. The net colonic K+ uptake, as determined by in vivo perfusion studies and by 86Rb uptake, was significantly higher in I than in A rats. In both I and A colon, approximately 80% of total 86Rb uptake was dependent on vanadate-sensitive P-type adenosinetriphosphatases (ATPases), but the contribution of these different ATPases changes during development. The activity of colonic Na(+)-K(+)-ATPase, measured as ouabain-sensitive Na(+)-dependent ATP hydrolysis and as 86Rb uptake, was lower in I than in A rats. In contrast, the activity of K(+)-ATPases located in apical membrane and measured as ouabain insensitive and SCH-28080 sensitive, as ouabain-sensitive Na(+)-independent ATP hydrolysis, and as 86Rb uptake was significantly higher in I than in A rats. The ratio between apically located K(+)-ATPases and basolateral Na(+)-K(+)-ATPase activities was almost 3.2-fold higher in I than in A colon. We identified with Northern blot the expression of the colonic H(+)-K(+)-ATPase and the Na(+)-K(+)-ATPase alpha-subunits. The alpha-mRNA expression of both ATPases was significantly higher in I than in A rats. The pH and K+ sensitivity of the ouabain-insensitive, SCH-28080-sensitive K(+)-ATPase was the same in I and A colons. In conclusion, the relative activity of apical K+ absorbing ATPases is higher in the I than in the A colon, which should aid infants in retaining K+.

Neonatal Proteus meningoencephalitis. Case report.

Proteus is an uncommon pathogen in neonatal meningitis and has, to our knowledge, not previously been described from Scandinavia. Our case illustrates the typical course of the disease when onset is within the first two weeks of life. The typical patient is a previously healthy, sometimes slightly preterm infant, who develops multiple brain abscesses and has a very poor prognosis. In cases with a later onset, factors predisposing for infection are common and the outcome is less severe. Our patient was a girl born at a gestational age of 36 full weeks, who was a little less alert than normal during the first three days and then became dramatically sick with convulsions and apnoeas. She died at the age of six days with severe brain damage.

Detection of human rotaviruses which do not react with subgroup I- and II-specific monoclonal antibodies.

Of 126 rotavirus-positive specimens, 7 could not be subgrouped (I or II). These strains showed a distinct reaction with a monoclonal antibody recognizing a common region on VP6, but they did not react with VP6 subgroup-specific monoclonal antibodies although they contained as much viral antigen as the subgrouped strains.