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1.  Ethnicity is a strong predictor for Helicobacter pylori infection in young women in a multi-ethnic European city 
Journal of gastroenterology and hepatology  2013;28(11):10.1111/jgh.12315.
BACKGROUND AND AIM
At the same time that H. pylori prevalence is declining in Western countries, immigrants from developing countries with high H. pylori prevalence have settled in Western urban areas. Actual epidemiologic data on H. pylori in a migrant community may help in realizing a more selective approach to assess H. pylori-related diseases. We aimed to define H. pylori prevalence as well as risk groups for H. pylori in a cohort of young women living in a multi-ethnic European city.
METHODS
We measured IgG anti-H. pylori and CagA-antibodies in serum of pregnant women included in a population-based prospective cohort study. Information on demographics, and socio-economic status was collected by questionnaires. Chi-square and logistic regression were used.
RESULTS
In total, 3146 (46%) of the 6837 tested women (mean age 29.7 ± 5.3) were H. pylori-positive and 1110 (35%) of them were CagA-positive. The H. pylori prevalence in Dutch women was 24%, which was significantly lower than in non-Dutch women (64%; p<0.001). In particular, H. pylori positivity was found in 92% of Moroccan (OR 19.2; 95% CI 11.8-32.0), 80% of Cape Verdean (7.6; 5.0-11.5), 81% of Turkish (9.0; 6.7-12.1), 60% of Dutch Antillean (3.3; 2.3-4.7), and 58% of Surinamese women (3.0; 2.3-3.8). Among H. pylori-positive Dutch subjects, 19% were CagA-positive compared with 40% of the non-Dutch subjects (p<0.001).
CONCLUSIONS
Despite a general trend of declining prevalence in Western countries, H. pylori remains highly prevalent in migrant communities, which may constitute target groups for screening and eradication to prevent H. pylori-related diseases.
doi:10.1111/jgh.12315
PMCID: PMC3822168  PMID: 23808840
Helicobacter pylori; cagA protein; epidemiology
2.  Paediatric community-acquired septic shock: results from the REPEM network study 
European Journal of Pediatrics  2013;172(5):667-674.
Introduction and purpose of the study
With this study we aimed to describe a “true world” picture of severe paediatric ‘community-acquired’ septic shock and establish the feasibility of a future prospective trial on early goal-directed therapy in children. During a 6-month to 1-year retrospective screening period in 16 emergency departments (ED) in 12 different countries, all children with severe sepsis and signs of decreased perfusion were included.
Results
A 270,461 paediatric ED consultations were screened, and 176 cases were identified. Significant comorbidity was present in 35.8 % of these cases. Intensive care admission was deemed necessary in 65.7 %, mechanical ventilation in 25.9 % and vasoactive medications in 42.9 %. The median amount of fluid given in the first 6 h was 30 ml/kg. The overall mortality in this sample was 4.5 %. Only 1.2 % of the survivors showed a substantial decrease in Paediatric Overall Performance Category (POPC). ‘Severe’ outcome (death or a decrease ≥2 in POPC) was significantly related (p < 0.01) to: any desaturation below 90 %, the amount of fluid given in the first 6 h, the need for and length of mechanical ventilation or vasoactive support, the use of dobutamine and a higher lactate or lower base excess but not to any variables of predisposition, infection or host response (as in the PIRO (Predisposition, Infection, Response, Organ dysfunction) concept).
Conclusion
The outcome in our sample was very good. Many children received treatment early in their disease course, so avoiding subsequent intensive care. While certain variables predispose children to become septic and shocked, in our sample, only measures of organ dysfunction and concomitant treatment proved to be significantly related with outcome. We argue why future studies should rather be large multinational prospective observational trials and not necessarily randomised controlled trials.
doi:10.1007/s00431-013-1930-x
PMCID: PMC3631515  PMID: 23354787
Paediatric; Child; Emergency medicine; Sepsis; Shock; Outcome
3.  Is there an association between wheezing and constipation in preschool children? Explanations from a longitudinal birth cohort 
BMJ Open  2011;1(2):e000237.
Objective
To assess whether wheezing and atopic dermatitis were associated with constipation in preschool children and to what extent shared risk factors contribute to this relationship.
Methods
A population-based sample of 4651 preschool children was used. At the age of 24, 36 and 48 months, a parental report of functional constipation was available according to the Rome II criteria, and data on atopic dermatitis and wheezing were available using age-adapted questionnaires from the International Study of Asthma and Allergies in Childhood. Stepwise multivariate analyses were performed to assess whether body mass index, infection exposure, food allergy and infant nutrition, and parental stress explained the association between wheezing, atopic dermatitis and constipation.
Results
Out of 4651 children, 12–17% had functional constipation between 24 and 48 months. Symptoms of wheezing decreased from 20% to 12% and atopic dermatitis decreased from 30% to 18% at the age of 24 and 48 months respectively. Between the age of 24 and 48 months, wheezing symptoms were significantly associated with functional constipation (OR 1.17; 1.02 to 1.34) but these results were mainly explained by the child's exposure to infections and use of antibiotics (adjusted odds ratio 1.08; 95% CI 0.95 to 1.24). No significant association was found between symptoms of atopic dermatitis and functional constipation (OR 1.08; 95% CI 0.94 to 1.23).
Conclusions
These findings suggest that functional constipation coexists with wheezing in childhood but is mainly explained by the child's infection exposure and use of antibiotics. Therefore, an independent association between respiratory symptoms and functional bowel disorders as suggested in previous studies is questionable.
Article summary
Article focus
Constipation, wheezing and atopic dermatitis are common symptoms in children.
Functional bowel disorders are linked to asthma and atopy in adults.
Functional bowel disorders, asthma and atopic disease may share common risk-factors that may explain coexistence of these symptoms.
Key messages
Wheezing, but not atopic dermatitis, is associated with functional constipation in preschool children. The association is mainly explained by a history of infection exposure.
Hence, the association between wheezing and functional constipation is not independent. Further research is needed to explore whether this result also applies to the outcome of asthma.
Strengths and limitations of this study
Population-based study population. The study group were not selected according to medical care.
This study addresses a topical area that has not been studied sufficiently and can contribute to the discussion of how asthma or atopy may be associated with functional bowel disorders.
This study took into account multiple shared risk factors of wheezing and constipation to shed light on the suggested association in literature.
Symptoms were available only from parental-reported questionnaires. This may lead to misclassification of the symptoms.
Early wheezing in infancy is not a sufficient predictor of childhood asthma.
No data were available regarding parental concerns of the child's health status. Bias may occur when parents with high concerns are more likely to report symptoms in their child as wheezing, constipation and infectious disease.
No data were available on IgE sensitisation, thus conclusions on the assocation between allergic disease and constipation should be made with caution.
doi:10.1136/bmjopen-2011-000237
PMCID: PMC3191603  PMID: 22021889
4.  Health-related quality of life in preschool children in five health conditions 
Quality of Life Research  2010;20(5):779-786.
Objective
To test the responsiveness of the Infant/Toddler Quality of Life Questionnaire (ITQOL) to five health conditions. In addition, to evaluate the impact of the child’s age and gender on the ITQOL domain scores.
Methods
Observational study of 494 Dutch preschool-aged children with five clinical conditions and 410 healthy preschool children randomly sampled from the general population. The clinical conditions included neurofibromatosis type 1, wheezing illness, bronchiolitis, functional abdominal complaints, and burns. Health-related quality of life (HRQoL) was assessed by a mailed parent-completed ITQOL. Mean ITQOL scale scores for all conditions were compared with scores obtained from the reference sample. The effect of patient’s age and gender on ITQOL scores was assessed using multi-variable regression analysis.
Results
In all health conditions, substantially lower scores were found for several ITQOL scales. The conditions had a variable effect on the type of ITQOL domains and a different magnitude of effect. Scores for ‘physical functioning’, ‘bodily pain’, and ‘general health perceptions’ showed the greatest range. Parental impact scales were equally affected by all conditions. In addition to disease type, the child’s age and gender had an impact on HRQoL.
Conclusions
The five health conditions (each with a distinct clinical profile) affected the ITQOL scales differently. These results indicate that the ITQOL is sensitive to specific characteristics and symptom expression of the childhood health conditions investigated. This insight into the sensitivity of the ITQOL to health conditions with different symptom expression may help in the interpretation of HRQoL results in future applications.
doi:10.1007/s11136-010-9806-2
PMCID: PMC3102208  PMID: 21153564
Health-related quality of life; Preschool children; ITQOL; Variety of diseases
5.  Functional abdominal complaints in pre-school children: parental reports of health-related quality of life 
Quality of Life Research  2010;19(3):363-369.
Purpose
The aim of this study is to assess the influence of functional abdominal complaints (FAC) on health-related quality of life in a group of Dutch pre-school children.
Methods
Parents of children aged up to 6.0  visiting the outpatient pediatric department, Erasmus MC-Sophia, Rotterdam, The Netherlands in the period January 2005–December 2006 for functional abdominal complaints during at least 3 months were asked to complete the Infant/Toddler Quality of life Questionnaire (ITQOL), and questions of the abdominal pain index for use by parents to report pain symptoms in pre-school children. ITQOL scale scores of children with FAC were compared against with Dutch reference values. The abdominal pain index was tested for internal consistency and test–retest reliability. Correlations between ITQOL scale scores and abdominal pain index were assessed by Spearman’s rank test.
Results
Results are based on 81 questionnaires completed by parents of children with FAC (response rate 61%). Children had a median age of 46 months (interquartile range 27–59), 48% girls. A significant impact was observed on most aspects of quality of life, particularly for physical functioning, general development, bodily pain, temperament and moods, general health perceptions and parental emotional impact. Parents of children with functional constipation tended to report lower scores than those of children with other FAC. The abdominal pain index appeared to be valid and was significantly correlated with ITQOL scales bodily pain and general health perceptions.
Conclusions
A substantial lower health-related quality of life is reported in pre-school children with functional abdominal complaints, with effects on physical, emotional and parental domains. The 5-question severity index of abdominal pain appeared a valid tool and may be helpful to quickly assess the severity of abdominal pain in clinical practice.
doi:10.1007/s11136-009-9583-y
PMCID: PMC2836462  PMID: 20069377
Abdominal pain; Pre-school children; Health-related quality of life
6.  Validity of the Manchester Triage System in paediatric emergency care 
Emergency Medicine Journal : EMJ  2006;23(12):906-910.
Objective
To assess the validity of the Manchester Triage System (MTS) in paediatric emergency care, using information on vital signs, resource utilisation and hospitalisation.
Methods
Patients were eligible if they had attended the emergency department of a large inner‐city hospital in The Netherlands from August 2003 to November 2004 and were <16 years of age. A representative sample of 1065 patients was drawn from 18 469 eligible patients. The originally assigned MTS urgency levels were compared with resource utilisation, hospitalisation and a predefined reference classification for true urgency, based on vital signs, resource utilisation and follow‐up. Sensitivity, specificity and percentage of overtriage and undertriage of the MTS were calculated.
Results
The number of patients who used more than two resources increased with a higher level of MTS urgency. The percentage of hospital admissions increased with the increase in level of urgency, from 1% in the non‐urgent patients to 54% in emergent patients. According to the reference classification, the sensitivity of the MTS to detect emergent/very urgent cases was 63%, and the specificity was 78%. Undertriage occurred in 15% of patients, of which 96% were by one urgency category lower than the reference classification. Overtriage occurred in 40%, mostly in lower MTS categories. In 36% of these cases, the MTS classified two or more urgency categories higher than the reference classification.
Conclusions
The MTS has moderate sensitivity and specificity in paediatric emergency care. Specific modifications of the MTS should be considered in paediatric emergency care to reduce overtriage, while maintaining sensitivity in the highest urgency categories.
doi:10.1136/emj.2006.038877
PMCID: PMC2564249  PMID: 17130595
7.  Surgical approaches for cesarean section in cattle 
The Canadian Veterinary Journal  2008;49(6):565-568.
Bovine practitioners are often presented with dystocias that require a cesarean section. Many practitioners perform this surgery using the same approach each time due to their comfort with one specific approach or lack of familiarity of other available options. The goal of this article is to explain the advantages, disadvantages, and indications for each of the different approaches to aid the practitioner in achieving better surgical success rate.
PMCID: PMC2387259  PMID: 18624065
8.  Reliability and validity of health status measurement by the TAPQOL 
Archives of Disease in Childhood  2005;90(4):351-358.
Background: In addition to clinical measures in the evaluation of paediatric interventions, health related quality of life (HRQoL) is an important outcome. The TAPQOL (TNO-AZL Preschool children Quality of Life) was developed to measure HRQoL in preschool children. It is a generic instrument consisting of 12 scales that cover the domains physical, social, cognitive, and emotional functioning.
Aims: To evaluate the feasibility, score distribution, internal consistency, test-retest reliability, and discriminative and concurrent validity of the TAPQOL multi-item scales in preschool children, aged 2–48 months. Also to evaluate the feasibility, reliability, and validity separately for infants (2–12 months old) and toddlers (12–48 months old).
Methods: Parents of a random general population sample of 500 preschool children were sent a questionnaire by mail. A random subgroup of 159 parents who participated received a retest after two weeks.
Results: The response rate was 83% at the test and 75% at the retest. There were few missing answers. Six scales showed ceiling effects. Nine scales had Cronbach's alphas >0.70. In general, score distributions and Cronbach's alphas were comparable for infants and toddlers. Test-retest showed no significant differences in mean scale scores; two scales had intra-class correlations <0.50. Five scales showed significant differences between children with no conditions versus children with two or more parent reported chronic conditions.
Conclusion: Results showed that the TAPQOL is a feasible instrument to measure HRQoL and support the reliability and discriminative validity of the majority of its scales for infants as well as toddlers.
doi:10.1136/adc.2003.048645
PMCID: PMC1720358  PMID: 15781921
9.  Full Structure of the Lipopolysaccharide of Pseudomonas aeruginosa Immunotype 5 
Biochemistry. Biokhimiia  2004;69(2):170-175.
The lipopolysaccharide (LPS) of the opportunistic human pathogen Pseudomonas aeruginosa immunotype 5 was delipidated by mild acid hydrolysis, and the products were separated by high-performance anion-exchange chromatography and analyzed by ESI MS and NMR spectroscopy. LPS species of three types were found, including those with an unsubstituted core and the core substituted with one O-polysaccharide repeating unit or with an O-polysaccharide of a variable number of repeating units. The core region is highly phosphorylated, the major species containing two monophosphate groups and one ethanolamine diphosphate group. Based on these and published data on the O-polysaccharide structure, the full structure of the LPS of P. aeruginosa immunotype 5 was established.
PMCID: PMC1317305  PMID: 15000683
lipopolysaccharide; core oligosaccharide; repeating unit; O-antigen; ethanolamine diphosphate; Pseudomonas aeruginosa; 6dHex) 6-deoxyhexose (rhamnose); 6dHexN) 6-deoxyhexosamine; ESI MS) electrospray ionization mass spectrometry; Hep) L-glycero-D-manno-heptose; Hex) hexose; HexN) hexosamine; HMQC) heteronuclear multi-quantum coherence; GalNAcA) 2-acetamido-2-deoxygalacturonic acid; Kdo) 3-deoxy-D-manno-oct-2-ulosonic acid; LPS) lipopolysaccharide; OS) oligosaccharide; QuiNAc) 2-acetamido-2,6-dideoxyglucose (quinovosamine); Rha) rhamnose
10.  Characteristics of the initial seizure in familial febrile seizures 
Archives of Disease in Childhood  1999;80(2):178-180.
Complex seizure characteristics in patients with a positive family history were studied to define familial phenotype subgroups of febrile seizures. A total of 51 children with one or more affected first degree relatives and 177 without an affected first degree relative were compared for history of complex characteristics of the initial febrile seizure. No difference was found in the frequency of febrile status epilepticus (OR = 1.1 (95% confidence interval (CI) 0.3 to 4.3)), multiple type (OR = 0.6 (CI 0.3 to 1.2)), and focal characteristics (OR = 0.4 (CI 0.2 to 1.2)). The presence of any complex characteristic (OR = 0.5 (CI 0.3 to 1.0)) was higher in those without an affected first degree relative, although differences did not reach significance. The familial type of febrile seizures is not associated with complex characteristics of the initial febrile seizure. Complex seizure characteristics are unlikely to help in discriminating phenotype subgroups for genetic studies of febrile seizures.


PMCID: PMC1717814  PMID: 10325737
11.  Informed consent, parental awareness, and reasons for participating in a randomised controlled study 
Archives of Disease in Childhood  1998;79(2):120-125.
BACKGROUND—The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children.
AIM—To assess the quality of the informed consent process in a paediatric setting.
METHODS—A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures.
RESULTS—181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%).
CONCLUSIONS—Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.


PMCID: PMC1717659  PMID: 9797591
12.  Local variability in respiratory syncytial virus disease severity 
Archives of Disease in Childhood  1997;77(5):410-414.



Respiratory syncytial virus (RSV) lower respiratory tract infections are considered to be a serious disease in centres such as the Sophia Children's Hospital (Rotterdam, the Netherlands), but as more benign infections in others such as the Geneva Children's Hospital (Switzerland). To assess the clinical severity of RSV infections at the two sites, 151 infants primarily admitted with a virologically confirmed RSV infection were studied prospectively (1994-5) and retrospectively (1993-4) (55 infants in Geneva and 96 in Rotterdam). Parameters of RSV morbidity which were more severe in Rotterdam during the two winter seasons were apnoea (1.8 v 23.9%), the rate of admission to the intensive care unit (3.6 v 28.1%), mechanical ventilation (0 v 7.3%), and length of stay in hospital (6.8 v 9.1 days). In Geneva higher respiratory rates (59.2 v 51.2), more wheezing (65.5 v 28.8%), and more retractions (81.8 v 63.3%) were recorded. Fewer infants younger than 4 months (54.9 v 68.7%), but more breast fed infants (94.1 v 38.5%), were admitted in Geneva, although the morbidity parameters remained different after correction for these two variables in multivariate analyses. Thus unidentified local factors influence the pattern and severity of RSV infection and may affect the results of multicentre prophylactic and therapeutic studies.


PMCID: PMC1717370  PMID: 9487963
13.  G Protein Variation in Respiratory Syncytial Virus Group A Does Not Correlate with Clinical Severity 
Journal of Clinical Microbiology  2000;38(10):3849-3852.
Respiratory syncytial virus group A strain variations of 28 isolates from The Netherlands collected during three consecutive seasons were studied by analyzing G protein sequences. Several lineages circulated repeatedly and simultaneously during the respective seasons. No relationships were found between lineages on the one hand and clinical severity or age on the other.
PMCID: PMC87491  PMID: 11015418
14.  Synthesis, stability, and subcellular distribution of major histocompatibility complex class II molecules in Langerhans cells infected with Leishmania major. 
Infection and Immunity  1997;65(8):3444-3450.
Protozoan parasites of the genus Leishmania exist as obligatory intracellular amastigotes and invade macrophages and Langerhans cells, the dendritic cells of the skin. Langerhans cells are much more efficient in presenting Leishmania major antigen to T cells than macrophages are and have the unique ability to retain parasite antigen in immunogenic form for prolonged periods. To analyze the mechanisms that are responsible for this potency, we defined the synthesis, turnover, conformation, and localization of major histocompatibility complex (MHC) class II molecules in Langerhans cells. Hence, Langerhans cells were pulse-labeled; immunoprecipitation of MHC class II molecules and gel electrophoresis followed. In addition, the subcellular distribution of MHC class II molecules in L. major-infected Langerhans cells was analyzed by confocal microscopy. The results show that (i) newly synthesized MHC class II molecules are required for L. major antigen presentation by Langerhans cells, (ii) MHC class II-peptide complexes in Langerhans cells are long-lived, (iii) phagocytosis of L. major modulates MHC class II biosynthesis by reducing its downregulation during Langerhans cell differentiation, and (iv) newly synthesized MHC class II molecules are associated with the parasitophorous vacuole of infected Langerhans cells. These findings support the conclusion that the traits of MHC class II expression correspond to the highly specialized functions of Langerhans cells in the immunoregulation of cutaneous leishmaniasis.
PMCID: PMC175487  PMID: 9234810
16.  Relationship between clinical severity of respiratory syncytial virus infection and subtype. 
Archives of Disease in Childhood  1996;75(2):137-140.
The relationship between clinical severity of respiratory syncytial virus (RSV) infection and distribution of subtype A or B was investigated. The data of 232 children, who were admitted with RSV infection or diagnosed in the outpatient department of the Sophia Children's Hospital, Rotterdam between 1992 and 1995, were studied. The diagnosis of RSV was confirmed by a direct immunofluorescence assay. Subtyping was performed by an indirect immunofluorescence assay using specific monoclonal antibodies. Gender, age at diagnosis, gestational age and birth weight, the presence of underlying diseases, feeding difficulties, the presence of wheezing and retractions, respiratory rate, temperature, clinical diagnosis at presentation, oxygen saturation (SaO2), carbon dioxide tension (PCO2), and pH, characteristics of hospitalisation, and the need for mechanical ventilation were observed. Analysis was performed on data from all patients diagnosed with RSV infection in the period between 1992 and 1995 spanning three RSV seasons, and separately on the RSV season 1993-4. The outcome of the three year analysis (150 (64.7%) subtype A v 82 (35.3%) subtype B) was compared with the outcome of the season 1993-4, a mixed epidemic with 37 (60.7%) subtype A and 24 (39.3%) subtype B isolates. None of the variables observed in the season 1993-4 differed significantly between RSV subtype A and B. Similar results were obtained from the analysis in the period 1992 until 1995, with the exception of PCO2 (a higher PCO2 was found in subtype A, p < 0.001) and retractions (more retractions were noted in patients with subtype A, p = 0.03). After correcting for possible confounders using regression analysis, these differences were not significant anymore. The data indicate that there is no relationship between clinical severity of RSV infection and subtype.
PMCID: PMC1511617  PMID: 8869195
17.  Severity of respiratory syncytial virus infections and immunoglobulin concentrations. 
Archives of Disease in Childhood  1993;69(1):156-157.
In a prospective study in 86 children with respiratory syncytial virus infections, no relation was detected between the severity of infection (based on diagnosis, chest radiography findings, need for mechanical ventilation, and duration of hospitalisation) and serum concentrations of IgG, IgA, IgM, and IgG1-4 on admission.
PMCID: PMC1029437  PMID: 8024304
18.  Expression of T-cell-associated serine proteinase 1 during murine Leishmania major infection correlates with susceptibility to disease. 
Infection and Immunity  1991;59(12):4701-4705.
The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.
Images
PMCID: PMC259102  PMID: 1937831
19.  Excessive secretion of antidiuretic hormone in infections with respiratory syncytial virus. 
Archives of Disease in Childhood  1990;65(11):1237-1239.
The association between infections with respiratory syncytial virus and plasma concentrations of antidiuretic hormone was assessed in 48 patients who had been admitted to hospital. The mean (SEM) concentration of antidiuretic hormone was significantly raised in patients with bronchiolitis (9.3 (1.4) ng/l) compared with non-pulmonary respiratory syncytial virus infections that cause apnoea or upper respiratory tract symptoms (6.1 (1.7) ng/l). The highest concentrations of antidiuretic hormone were seen in patients receiving mechanical ventilation (18.0 (6.7) ng/l). There were no differences in mean serum sodium concentrations among the subgroups. Hypertranslucency on chest radiograph or an arterial carbon dioxide tension above 6.67 kPa were associated with a significantly higher concentration of antidiuretic hormone. Increased or normal maintenance fluid intake in children with pulmonary respiratory syncytial virus infections may cause the same symptoms of fluid overload as the syndrome of inappropriate secretion of antidiuretic hormone. Patients with pulmonary respiratory syncytial virus infection, hypertranslucency in chest radiograph, hypercapnia, or mechanical ventilation are at risk for raised concentrations of antidiuretic hormone. Restricted fluid intake and careful monitoring of fluid balance and plasma electrolyte concentrations are therefore necessary in these patients.
PMCID: PMC1792616  PMID: 2123382
21.  Evidence of T-cell recognition in mice of a purified lipophosphoglycan from Leishmania major. 
Infection and Immunity  1989;57(11):3349-3356.
We have previously reported that a Leishmania major lipophosphoglycan (LPG), given with killed Corynebacterium parvum as an adjuvant, can vaccinate mice against cutaneous leishmaniasis. In order to analyze whether T cells are able to recognize this important parasite antigen, we have studied both humoral and cellular immune responses to L. major LPG that had been isolated from promastigotes by sequential solvent extraction and hydrophobic chromatography. The data show that immunization of mice with highly purified LPG induced an increase in frequency of L. major-reactive T cells and the production of immunoglobulin G antibodies to LPG. Furthermore, genetically resistant mice infected with L. major were able to develop a specific delayed-type hypersensitivity response in the ear to L. major LPG. These findings strongly suggest that T cells can recognize and respond to glycolipid antigens, in this case a host-protective Leishmania LPG, even though such antigens appear not to be potent T-cell stimulators in mice.
PMCID: PMC259819  PMID: 2807527
22.  Childhood leukaemia in The Netherlands, 1973-1986: temporary variation of the incidence of acute lymphocytic leukaemia in young children. 
British Journal of Cancer  1989;59(1):100-105.
The incidence of childhood leukaemia in The Netherlands in the period 1973-1986 was studied by means of the DCLSG nationwide register, which lists all patients according to bone marrow slides classified in the DCLSG central laboratory. Acute lymphocytic leukaemia (ALL) accounted for 81% of cases, acute non-lymphocytic leukaemia (ANLL) for 13%, chronic myelocytic leukaemia (CML) for 2.5%, and acute unclassifiable leukaemia (AUL) for 3%. The peak incidence of ALL was at age 3, common-ALL and pre B-ALL comprising about 95% of the immunophenotypes at this age. Incidence rates for ALL remained stable between 1973 and 1978 at 2.85 cases per 10(5) children per year, exhibited a temporary increase between 1979 and 1984 to 3.60 and dropped back to the lower, previous level in 1985 and 1986. This rise was seen mainly among children in the 1-4 year age group, especially at age 3, and those with common-ALL and an initial WBC less than 5.0 x 10(9) l-1. Cumulative incidence rates per year of birth were fairly homogeneous up to age 6, except for the 1978 birth cohort which exhibited higher rates. Incidence rates for ANLL, CML and AUL remained stable over time. Changes in ascertainment, declining birth rates and a 50% decrease in childhood mortality, e.g. from infectious diseases, could not explain this temporary variation. Moreover, incidence rates in this survey appeared to be similar to those reported in various developed countries for the same period. As far as the aetiology of childhood common-ALL is concerned, therefore, the Dutch data appear to support the hypothesis of 'random mutation' as well as that of a limited role of environmental factors.
PMCID: PMC2246965  PMID: 2788005
23.  Time space distribution of childhood leukaemia in the Netherlands. 
In the western part of the Netherlands during 1973-80 leukaemia was diagnosed in 293 patients aged under 15 years. An overall incidence rate of 2.91 per 100000 person years was calculated. No seasonal influence on months of birth or months of diagnosis of these patients could be traced by the method of Edwards. Time space clustering was looked for by both methods of Mantel and Knox. No significant time space clustering of date and place of diagnosis of childhood leukaemia was found in all types of leukaemia, acute lymphocytic leukaemia (ALL), ALL in boys and girls, ALL in children under 6 years at diagnosis, and in acute non-lymphocytic leukaemia.
PMCID: PMC1052279  PMID: 6577127
24.  Incidence of childhood leukaemia in The Netherlands (1973-1980). 
British Journal of Cancer  1983;47(4):471-475.
The childhood leukaemia incidence rate for the Netherlands was estimated at 3.11 per 100.000 children (aged 0-15 year) per year, based on a complete nation-wide childhood leukaemia registry comprising the period 1973-1980. Acute lymphocytic leukaemia (ALL) accounted for 82.4% of the patients, acute non-lymphocytic leukaemia for 13.6% and chronic myeloid leukaemia for 2.9%. ALL occurred more frequently in boys (sex ratio 1.2). The highest ALL rate was observed in the 3-4 year age group. These figures corresponded with the data of the Manchester Children's Tumour Registry. Neither the incidence rates according to year of diagnosis nor the incidence rates according to year of birth showed a significant trend with time. The total leukaemia incidence rate in urban areas was somewhat higher than in rural areas. While the direct comparison of the incidence rate between these areas is not significant, the trend over the three categories of urbanisation is significant.
PMCID: PMC2011339  PMID: 6573905
25.  Derivation and validation of age and temperature specific reference values and centile charts to predict lower respiratory tract infection in children with fever: prospective observational study 
Objectives To develop reference values and centile charts for respiratory rate based on age and body temperature, and to determine how well these reference values can predict the presence of lower respiratory tract infections (LRTI) in children with fever.
Design Prospective observational study.
Participants Febrile children aged at least 1 month to just under 16 years (derivation population, n=1555; validation population, n=671) selected from patients attending paediatric emergency departments or assessment units in hospitals.
Setting One hospital in the Netherlands in 2006 and 2008 (derivation population); one hospital in the Netherlands in 2003-05 and one hospital in the United Kingdom in 2005-06 (validation population).
Intervention We used the derivation population to produce respiratory rate centile charts, and calculated 50th, 75th, 90th, and 97th centiles of respiratory rate at a specific body temperature. Multivariable regression analysis explored associations between respiratory rate, age, and temperature; results were validated in the validation population by calculating diagnostic performance measures, z scores, and corresponding centiles of children with diagnoses of pneumonic LRTI (as confirmed by chest radiograph), non-pneumonic LRTI, and non-LRTI.
Main outcome measure Age, respiratory rate (breaths/min) and body temperature (°C), presence of LRTI.
Results Respiratory rate increased overall by 2.2 breaths/min per 1°C rise (standard error 0.2) after accounting for age and temperature in the model. We observed no interactions between age, temperature, and respiratory rates. Age and temperature dependent cut-off values at the 97th centile were more useful for ruling in LRTI (specificity 0.94 (95% confidence interval 0.92 to 0.96), positive likelihood ratio 3.66 (2.34 to 5.73)) than existing respiratory rate thresholds such as Advanced Pediatrics Life Support values (0.53 (0.48 to 0.57), 1.59 (1.41 to 1.80)). However, centile cut-offs could not discriminate between pneumonic LRTI and non-pneumonic LRTI.
Conclusions Age specific and temperature dependent centile charts describe new reference values for respiratory rate in children with fever. Cut-off values at the 97th centile were more useful in detecting the presence of LRTI than existing respiratory rate thresholds.
doi:10.1136/bmj.e4224
PMCID: PMC3388747  PMID: 22761088

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