A previously healthy 11-year-old girl with behavioural disturbances, desquamation of the skin and loss of teeth.

An 11-year-old girl was admitted with backpain, weight loss, fatigue and behavioural disturbances, starting seven weeks before admission. Physical examination showed acrodynia, tremor, cachexia, hypertension and extensive gingival ulceration. Routine laboratory tests were normal, except for a CRP of 98 mg/l. Screening tests for recreational drugs as well as antibody assays for HIV, hepatitis B and borrelia burgdorferia were negative. Chest X-ray, brain CAT and MRI scan were all normal. Lumbar puncture didn't show any abnormalities. Eventually a 24-hour urine test confirmed the diagnosis that was suspected by further questioning.

[Treatment of neonatal hypoglycaemia: more frequent latching onto the breast versus supplementary feeding with formula; retrospective study of patient files]. / Behandeling van neonatale hypoglykemie: frequenter aanleggen aan de borst versus bijvoeden met flesvoeding; retrospectiefstatusonderzoek.

OBJECTIVE: To evaluate the effects of frequent latching versus supplementary feeding of breastfed infants with hypoglycaemia on blood glucose concentrations and breastfeeding. DESIGN: Retrospective study of patient files. METHOD: All breastfed infants born in the period of investigation (June 1st 2004-April 30th 2005) by artificial or breech delivery were included. In the group with supplementary feeding (June 1st 2004 until December 12th 2004) mild neonatal hypoglycaemia, defined as glucose concentrations between 1.8 and 2.5 mmol/l, with symptoms, or between 1.3 and 1.7 mmol/l, without symptoms, was treated with supplementary feeding with formula. In the group with more frequent latching (December 13th 2004-April 30th 2005) mild neonatal hypoglycaemia (defined as glucose levels of 1.8-2.1 mmol/l) was treated with more frequent latching without supplementary feeding. The change in feeding policy (mid December 2004) was introduced because of excessive numbers of supplementary feedings, which jeopardized breastfeeding. Blood glucose determinations were carried out with the HemoCue B-glucose system. Risk factors for hypoglycaemia were listed, enabling the assessment of data of neonates who did not run an increased risk of hypoglycaemia, a kind of 'control group'. RESULTS: 232 newborn infants were included: 158 in the supplementary feeding group and 74 in the group with more frequent latching. In the supplementary feeding group, 63% (100/158) of the children developed hypoglycaemia, versus 55% (41/77) in the group with more frequent latching. The latter had lower blood glucose concentrations than the supplementary feeding group. This difference was only significant for infants without risk factors: the mean difference in lowest glucose concentration between supplementary feeding and more frequent latching in the group without risk factors was 0.50 mmol/L (SD: 0.69; 95% CI: 0.06-0.93; p = 0.03) versus 0.20 mmol/l (SD: 0.79; 95% CI: -0.05-0.45; p = 0.14) in the group with risk factors. Supplementary feedings decreased by 39% (95% CI: 28-50). The number of infants discharged with breastfeeding only increased by 14% (95% CI: 2-26). Symptomatic hypoglycaemic episodes were not found in the group with supplementary feeding or in the group with more frequent latching. CONCLUSION: Frequent latching instead of supplementary (formula) feeding in infants with mild neonatal hypoglycaemia was associated with lower blood glucose concentrations but with higher percentages of breastfeeding only at discharge.

Vermindering van diagnostiek en overbehandeling bij RS-virus-bronchiolitis na geprotocolleerde behandeling.

PURPOSE: Evaluating the guideline 'Diagnosis and treatment of respiratory syncytial (RS) virus bronchiolitis' on the number of chest X-rays, C-reactive proteïn (CRP) counts, leukocyte counts, and antibiotic prescriptions in infants admitted to hospital with RS bronchiolitis. DESIGN: Retrospective 'before-after' cohort study. LOCATION: Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands. PATIENTS: Infants admitted with proven RS virus infection. METHODS: Guidelines, including sound restriction of performance of X-rays, CRP and leukocytes, were introduced in February 2003. Data from infants admitted with RS virus infection during 1997- 1999 (cohort A) were compared with those admitted from 2003- April 2006 (cohort B)Results: There were 155 infants in cohort A and 170 in cohort B. Implementation of guidelines led to significant reductions of CRP and leukocyte determinations: 49.0% and 48.2%, respectively (both p<0.001) and X-rays: 30.3% (p=0.020). Numbers of antibiotic prescriptions decreased with 55% (p<0.001). The chance of antibiotic prescription increased significantly when X-rays (OR=5.2), CRP (OR=5.4), or leukocytes (OR=4.2) were done. After implementation of the guidelines, the median stay in hospital decreased significantly from 8.0 to 6.0 days (p<0.001; ranges 1-13 days and 2-23 days, respectively). Performing X-ray, CRP or leukocytes, or antibiotic prescription did not significantly alter the total duration of hospital stay. CONCLUSION: Implementation of the guidelines led to significant decreases in numbers of X-rays, CRP and leukocytes determinations, and antibiotic prescriptions. Our data support the restrictive use of chest X-rays, CRP and leukocyte determinations in infants, admitted to hospital with RS virus bronchiolitis.

Evaluation of monitoring strategies for childhood asthma.

INTRODUCTION: The goal of monitoring pediatric asthma is to obtain and maintain asthma control, which is defined as minimizing asthma symptoms, restrictions to daily activities and the use of rescue medication. Long term goals include reducing the risk of fixed airflow limitation, and preventing asthma exacerbations and side effects of treatment. Several monitoring tools are available but no consensus exists on how to monitor patients in the most optimal way. Areas covered: In this review, we provide an overview of different tools and address general considerations on monitoring childhood asthma. Asthma care should be tailored to the individual patient. The health care professional should decide which monitoring strategy and frequency is optimal for the individual patient. Expert commentary: Personalized medicine should be the key issue in monitoring asthma in children. It is crucial to monitor disease activity and deterioration but there is no monitoring strategy that is clearly superior compared to others: The optimal strategy and frequency will vary between patients. Actually, both treatment and monitoring of pediatric asthma probably benefit from a personalized approach.

Reference values for amino acids in cerebrospinal fluid of children determined using ion-exchange chromatography with fluorimetric detection.

One thousand specimens of CSF were collected from subjects ranging in age from newborn to 18 yr, who were undergoing a diagnostic lumbar puncture. Sixty-two samples were judged retrospectively as being suitable for calculating reference age-related values. The analyses were performed by an amino acid analyser using ion-exchange chromatography with fluorimetric detection giving a tenfold increase in sensitivity, thereby enhancing the diagnostic capabilities. As many as 36 known compounds could be detected, additionally 10 we could not identify. In children older than 3 yr nine of the identified compounds showed age-dependency. We found 22 amino acids to be significantly higher in infants younger than 1 yr, with only gamma-aminobutyric acid being significantly lower in infants. Alpha-aminoadipic acid showed a sex difference, being slightly higher in girls.

[Primary meningococcal-monoarthritis (Neisseria meningitidis serotype C) in a child]. / Primaire meningokokkenmonoartritis (Neisseria meningitidis serotype C) bij een kind.

A 26-month-old girl had a painful, swollen right knee, accompanied by fever and vomiting. She had had an upper respiratory tract infection for a number of days. Following a positive culture of synovial fluid, monoarthritis caused by Neisseria meningitidis serotype C without other signs of illness was diagnosed. She recovered completely after one joint aspiration and intravenous and oral antibiotic therapy. N. meningitidis serotype C infections without meningitis or septicaemia are rare, but should form part of the differential diagnosis of septic monoarthritis.

[Childhood hypophosphatasia]. / Hypofosfatasemie op de kinderleeftijd.

Hypophosphatasia was diagnosed in two boys aged four months and two years. This is a rare hereditary bone disease characterized by deficient activity of enzyme alkaline phosphatase. Increased levels of substrates of this enzyme are found: phosphoethanolamine in urine and pyridoxal phosphate in serum. Patients show defective bone mineralization, which results in severe deformities of limbs, thorax and skull and dental abnormalities (loss of teeth and caries). The disease is classified in four age-related forms: perinatal, infantile, childhood and adult hypophosphatasia. The perinatal form is usually lethal. There is no curative therapy. Recognition of the disease is of importance for genetic counselling.

[Optimal breastfeeding to prevent hyperbilirubinaemia in healthy, term newborns]. / Optimale borstvoeding ter preventie van hyperbilirubinemie bij gezonde, voldragen pasgeborenen.

In a newborn infant, frequent bowel movements diminish the enterohepatic circulation of bilirubin, thereby increasing bilirubin excretion. In breastfed newborn infants, the frequency of latching on and administration of supplementary feeds are associated with serum bilirubin concentrations. Frequent breast feeding (at least 8 times a day) and fewer supplementary feeds will result in increased breast milk intake, less weight loss, and lower bilirubin concentrations. In the case of a breastfed infant presenting with neonatal hyperbilirubinaemia, the advice should be to breastfeed more frequently and to withhold supplementary feedings. An icteric newborn infant should be seen and weighed daily. If the infant has lost more than 10% of its birth weight, drinks poorly, or fails to gain weight despite latching onto the breast frequently, it should be referred to the paediatrician for further diagnosis and treatment. To ensure optimal production of breast milk during the first days after birth, early latching on is recommended, preferably within one hour after birth.

[Severe anemia caused by transient erythroblastopenia in young children]. / Ernstige anemie door een tijdelijke erytroblastopenie bij jonge kinderen (TEK).

In the period 1975-1981 seventeen patients aged from 4 to 30 months were seen with transient normochromic, normocytic anemia and reticulocytopenia caused by erythroblastopenia. The majority of the cases (12/17) were seen in autumn and winter. In 16 of the patients bone marrow aspirates were obtained; they showed erythroblastopenia. In 7 cases we observed young lymphoïd cells, which suggested the diagnosis of leukemia. Distinguishing features of congenital hypoplastic anemia and transient erythroblastopenia of childhood are compared. Except for blood transfusion, therapy e.g. corticosteroïds is not necessary in transient erythroblastopenia of childhood. Spontaneous recovery is a diagnostic feature, contrasting with congenital hypoplastic anemia.

Stevens-Johnson syndrome in a child with chronic mercury exposure and 2,3-dimercaptopropane-1-sulfonate (DMPS) therapy.

INTRODUCTION: Stevens-Johnson syndrome (SJS) is an uncommon and potentially serious mucocutaneous disease. The most important step in the management of SJS is early recognition and immediate withdrawal of the causative agent. We present a patient with SJS associated with dimercaptopropane-1-sulfonate (DMPS) therapy. CASE REPORT: An asymptomatic 11-year old boy who had been exposed chronically to mercury vapour had a 24-hour urine mercury concentration of 37 microgram/L (reference value <10 microgram/L). Exposure to the mercury vapour was stopped and treatment with oral DMPS was begun. After two weeks of therapy, he developed a disseminated cutaneous eruption of red pruritic macules on his chest and back, which three days later had spread all over his body with the discrete maculae becoming confluent; erosions and crusts developed on his lips and he had blisters in his mouth. The diagnosis of SJS was made, the DMPS was stopped, and the SJS resolved gradually. DISCUSSION: Chelation agents like DMPS or DMSA are increasingly used and are available over the counter in some countries. These drugs are used in patients with complaints that are attributed to mercury-containing dental amalgams and in children with autism. CONCLUSION: The reported association suggests that SJS may be a potential complication of DMPS therapy, and this should be considered in the risk-benefit analysis of chelation. The reported association suggests that SJS may be a potential complication of DMPS therapy, and this should be considered in the risk-benefit analysis of chelation.

EEG findings in an eleven-year-old girl with mercury intoxication.

An 11-year-old female was seen at our outpatient clinic with a broad variety of symptoms that were due to elemental mercury intoxication. Electromyography and sequential electroencephalography findings obtained at days 2, 36, 88 and 148 are described. The patient was treated with chelation therapy during which she clinically improved considerably. A profound decrease in urinary mercury concentration occurred as well as normalization of the electroencephalogram.

Serum concentrations of cefotaxime and its metabolite desacetyl-cefotaxime in infants and children during continuous infusion.

INTRODUCTION: Continuous infusion of cefotaxime, as opposed to intermittent infusion, seems to be advantageous for a number of reasons. However, few data exist on pharmacokinetics of cefotaxime and its metabolite in infants and children. As part of a quality assessment program, concentrations of cefotaxime and its metabolite desacetyl-cefotaxime were examined. METHODS: Infants and children (age 0-17 years) routinely received cefotaxime by continuous intravenous infusion and had blood samples taken on days 1, 3, and 5 after start of therapy. Measurements were performed by high-performance liquid chromatography (HPLC) of cefotaxime and desacetyl-cefotaxime. RESULTS: Patients receiving a dosage of 100 mg/kg/day had a mean cefotaxime concentration of 24.9 mg/l on day 1, ranging from 0.6 to 182.6 mg/l (N = 222). Cefotaxime concentrations in infants younger than 1 week of age showed the largest variation and significantly decreased on consecutive days (p < 0.001, N = 17), together with a significant drop in the cefotaxime-desacetyl-cefotaxime (cef-des) ratio (p = 0.003, N = 16). Cefotaxime clearance increased significantly during the first days after birth (p = 0.024, N = 16). Patients older than 1 week showed negative and significant correlations of cefotaxime concentrations with calculated glomerular filtration rates (p < 0.0001, N = 73), with no significant change in the cef- des ratio on consecutive days. CONCLUSION: Overall, cefotaxime concentrations varied widely between patients, in particular in those younger than 1 week. Our data suggest that liver metabolism as well as renal excretion contribute to total body clearance of cefotaxime and increase during the first few days of live.

A neonate with an intact congenital umbilical appendix: an alternative theory on the etiology of the appendico-umbilical fistula.

Neonatal umbilical anomalies usually represent remains of the vitelline duct or the allantois. We describe a case of an umbilical appendix in a neonate. The vermiform appendix was found to be positioned in the umbilical cord. In a brief literature review we found eight other reports concerning umbilical appendices. In this article we describe a possible embryological explanation for the development of an umbilical appendix, and discuss whether or not the appendiceal umbilical fistulae reported are congenital or iatrogenic. The possible association between an umbilical appendix and different forms of malpositioning and rotation of the gut is also discussed. Protrusion of the neonatal appendix into the umbilical cord represents a different entity of congenital anomalies. It is important to realize that, in the case of an unrecognized umbilical appendix, medical procedures (e.g., canulation or clamping of the umbilicus) may produce an iatrogenic appendico-umbilical fistula. Careful inspection and palpation of the umbilical cord prior to these procedures may prevent a fistula being created. Furthermore, because the possible association between umbilical appendices and different kinds of malpositioning of the gut is so far not wholly elucidated, we recommend further (radiological) investigation in each case of an umbilical appendix. Correct positioning of the bowel needs to be confirmed in order to rule out possible future complications.

Transient erythroblastopenia of childhood. A review of 22 cases.

In the period 1975-1983 22 patients, aged 4-36 months were seen with severe transient normochromic, normocytic anaemia caused by a transient erythroblastopenia. In 20 patients bone marrow aspirations were obtained; they showed erythroblastopenia. In ten cases we observed young lymphoid cells, suggesting a diagnosis of acute lymphoblastic leukaemia. One patient suspected of a leukaemia, was studied in more detail. All patients showed reticulocytopenia. MCV and HbF were within normal range. During recovery reticulocytosis and higher levels of HbF were found. Except for blood transfusion in most patients, therapy (e.g. corticosteroids) was not necessary. Spontaneous recovery is a feature of this kind of erythroblastopenia, contrasting with congenital hypoplastic anaemia.

Cerebrospinal fluid amino acids, purines and pyrimidines as a tool in the study of metabolic brain diseases.

After establishing more extended reference values for amino acids, purines and pyrimidines in cerebrospinal fluid (CSF) in infancy and childhood, we studied 1250 CSF-aliquots from patients who were undergoing a diagnostic lumbar puncture for diverse clinical indications. Our primary aim was to answer the question whether determination of the concentration of amino acids, purines and pyrimidines in CSF is a useful tool in screening for metabolic disorders in children with unexplained mental retardation. In unexplained mental retardation (95 patients) we observed varying abnormalities of CSF. These were reproducible in only 2 patients (a decrease of homocarnosine in combination with two unidentified compounds). Striking abnormalities in pyrimidine content which are limited to CSF are found in argininosuccinic aciduria and uraemia. In uraemia a general decrease in amino acids in CSF and increase of gamma-aminobutyric acid (GABA) was observed. The results obtained indicate that determination of amino acids, purines and pyrimidines in CSF is only of limited value in the diagnosis of unexplained mental retardation.

Disturbances of cerebral purine and pyrimidine metabolism in young children with chronic renal failure.

Chronic renal failure during childhood may be associated with delayed cognitive development. From 10 children with chronic renal failure, aged 2-59 months, plasma and cerebrospinal fluid (CSF) purines and pyrimidines have been determined. A marked increase of pseudouridine and cytidine was demonstrated in CSF of 10 and 8 children, respectively. The plasma concentration of pseudouridine was increased in a varying degree to a maximal value of more than 10 times the upper limit of normal. The plasma concentration of cytidine showed only moderately elevated values. In 3 children the study of CSF and plasma was repeated 6 weeks after the start of continuous ambulatory peritoneal dialysis. The abnormal concentrations of pseudouridine and cytidine were still present in CSF and plasma. Further studies are necessary to elucidate the cause of this unknown biochemical aberration of the central nervous system.

Cerebrospinal fluid levels of amino acids in infants and young children with chronic renal failure.

Chronic renal failure (CRF) is associated, especially in young children, with delayed cognitive development of unknown origin. As cerebrospinal fluid (CSF) reflects the composition of the extracellular fluid of the brain, not only plasma but also CSF amino acids concentrations were determined in 8 infants (age 2-8 months) and 3 children (age 26, 32 and 56 months) with CRF (creatinine clearance 13 +/- 9 ml/min/ 1.73 m2). In three of these children investigations were repeated after six weeks of CAPD treatment. In the infants, a significant decrease was found in CSF of alpha-aminobutyric acid, valine, isoleucine, leucine, tyrosine, tryptophane, histidine and n-zeta-methyl-1-lysine, whereas there was a significant increase of 3-methylhistidine. In plasma serine, valine, leucine, tyrosine and histidine were significantly decreased, whereas there was a significant increase of aspartic acid, citrulline, and 3-methylhistidine. These abnormalities remained constant after the start of CAPD except for the normalization in CSF and plasma of 3-methylhistidine. These data indicate a generalized disturbance of amino acids in young children with CRF. An abnormal substrate is offered to the neurons and astroglia in children with CRF.

Argininosuccinic aciduria: clinical and biochemical findings in three children with the late onset form, with special emphasis on cerebrospinal fluid findings of amino acids and pyrimidines.

Three children with the late onset form of argininosuccinic aciduria are presented. The first two are sisters. The clinical features are characterized by mild retardation and ataxia, complicated by episodes of hyperammonemia. All patients showed elevated concentrations of argininosuccinic acid and its anhydrides in all body fluids, most pronounced in cerebrospinal fluid (CSF). Moreover, in Cases 1 and 2, we found elevated concentrations of pseudouridine and uridine limited to CSF, which was not reported before. In Case 3, with some residual activity of argininosuccinate lyase (ASL), we found normal values of these compounds. In urine we found elevated concentrations of uracil in Cases 1 and 2, and orotic acid in Case 2. Plasma showed an elevated concentration of orotic acid in all three patients, uracil was elevated in Case 2, cytidine was elevated in Cases 2 and 3. The results are being discussed and indicate that CSF values of pyrimidines reveal new biochemical abnormalities of brain tissue in urea cycle disorders.