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1.
Int J Obes (Lond) ; 38(7): 1000-4, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24097297

ABSTRACT

BACKGROUND: The transcription factor SIM1 (Single-minded 1) is involved in the control of food intake and in the pathogenesis of obesity. In mice, Sim1 is involved in the development of the paraventricular nucleus, and Sim1 deficiency leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in the SIM1 gene region have been reported in obese individuals. Furthermore, recent data also suggest that loss-of-function point mutations in SIM1 are responsible for SIM1 haplo-insufficiency that is involved in causing human obesity. In this study, we therefore wanted to expand the evidence regarding the involvement of SIM1 mutations in the pathogenesis of severe early-onset obesity. METHODS: We screened 561 severely overweight and obese children and adolescents and 453 lean adults for mutations in the coding region of the SIM1 gene. Mutation screening in all patients and lean individuals was performed by high-resolution melting curve analysis combined with direct sequencing. To evaluate the effect of the mutations on SIM1 transcriptional activity, luciferase reporter assays were performed. RESULTS: Mutation analysis identified four novel nonsynonymous coding variants in SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E. Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also identified. Screening of the lean control population revealed the occurrence of four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For variants p.T481K and p.A517V, which were found in obese individuals, a decrease in SIM1 transcriptional activity was observed, whereas the transcriptional activity of all variants found in lean individuals resembled wild type. CONCLUSIONS: In this study, we have demonstrated the presence of rare SIM1 variants in both an obese pediatric population and a population of lean adult controls. Further, we have shown that functional in vitro analysis of SIM1 variants may help in distinguishing benign variants of no pathogenic significance from variants which contribute to the obesity phenotype.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Genetic Predisposition to Disease , Mutation, Missense , Obesity, Morbid/genetics , Repressor Proteins , Adolescent , Adult , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Child , DNA Mutational Analysis , Genes, Reporter , Genetic Association Studies , Humans , Mice , Phenotype , Repressor Proteins/genetics , Transcriptional Activation
2.
Clin Exp Allergy ; 41(3): 346-56, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21105917

ABSTRACT

BACKGROUND: Asthma is a complex clinical disease characterized by airway inflammation. Recently, various studies reported on the analysis of exhaled breath condensate (EBC) in the search for potential biomarkers for asthma. However, in a complex disease such as asthma, one biomarker might not be enough for early diagnosis or follow-up. OBJECTIVE: The use of proteome analysis may reveal disease-specific proteolytic peptide or protein patterns, and may lead to the identification of novel proteins for the detection of asthma. METHODS: Liquid chromatography and mass spectrometry were used to separate and detect proteins (proteolytic peptides) present in EBC samples from 30 healthy children and 40 children with asthma in the age group of 6-12 years. RESULTS: Support vector machine analysis resulted in differentiating profiles based on asthma status. These proteolytic peptide patterns were not correlated to some well known (spirometry, exhaled nitric oxide) and more recently described exhaled markers (EBC pH, LTB4). The more abundant proteins in EBC were identified as cytokeratins, albumin, actin, haemoglobin, lysozyme, dermcidin, and calgranulin B. CONCLUSION: Although the exact role in the disease development or physiological state of the airways of the proteins described in the presented pattern is not clear at this moment, this is an important step in the search for exhaled biomarkers for asthma. This study shows that EBC contains proteins that are of interest for future non-invasive asthma diagnosis or follow-up.


Subject(s)
Asthma/diagnosis , Biomarkers/analysis , Breath Tests/methods , Proteomics/methods , Child , Chromatography, Liquid , Exhalation , Female , Humans , Male , Mass Spectrometry
3.
Eur Respir J ; 35(4): 865-72, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19926751

ABSTRACT

Persistent wheeze is a common chronic disease in early childhood and later may progress to asthma. However, the association between pre- and post-bronchodilator lung function and the wheezing phenotype in preschool children is not known. Children 4 yrs of age involved in a prospective birth cohort study (in Antwerp, Belgium) concerning perinatal factors and the occurrence of asthma and allergies, were invited to participate in lung function measurements with the forced oscillation technique. The wheezing phenotype was assessed via (bi)annual questionnaires. Wheezing phenotype and baseline respiratory impedance data were available for 325 children, 96% of whom underwent bronchodilation tests. The baseline resistance at 4 Hz was higher in children with early transient (11.0 hPa x s x L(-1), n = 127) or persistent wheeze (11.9 hPa x s x L(-1), n = 54) than in children who never wheezed (10.3 hPa x s x L(-1), n = 144). After bronchodilation, the resistance decreased on average by 22%. The decrease was greater among the persistent wheezers than among those who never wheezed (3.4 versus 2.3 hPa x s x L( -1)). The baseline lung function was poorer and the bronchodilator response was greater in 4-yr-old children with persistent wheeze than in those who never wheeze or who had early transient wheeze, implying a higher bronchomotor tone in the former group.


Subject(s)
Asthma/diagnosis , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Respiratory Function Tests , Surveys and Questionnaires , Adrenal Cortex Hormones/therapeutic use , Asthma/physiopathology , Belgium , Child, Preschool , Electric Impedance , Female , Humans , Male , Phenotype , Respiratory Sounds
4.
Int J Obes (Lond) ; 33(1): 8-13, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18779826

ABSTRACT

Sleep-disordered breathing is highly prevalent in childhood obesity. Two recent cross-sectional studies have demonstrated an independent association between the severity of sleep-disordered breathing and the metabolic syndrome. A limited number of studies have also addressed the correlation between sleep-disordered breathing and insulin resistance, the core factor of the metabolic syndrome. Cross-sectional reports in modestly obese children are in favor of an association between sleep apnea and insulin resistance. However, these findings were not confirmed in studies of normal-weight children and of morbidly obese children. Only one out of three treatment studies before and after adenotonsillectomy confirmed the association between sleep apnea and insulin resistance, but only in obese children. Although statistical power issues and differences in patient characteristics might partially explain these contradicting results, the evidence to date is far from establishing a causal link between sleep-disordered breathing and insulin resistance. Longitudinal studies and randomized control trials are therefore warranted to investigate a possible causal link between sleep-disordered breathing and insulin resistance.


Subject(s)
Metabolic Syndrome/etiology , Obesity/complications , Sleep Apnea Syndromes/complications , Adolescent , Child , Cross-Sectional Studies , Humans , Insulin Resistance , Risk Factors
5.
J Cyst Fibros ; 8(1): 26-30, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18838309

ABSTRACT

BACKGROUND: Published studies concerning the impact of specialist care on lung disease in cystic fibrosis remain limited and most are either biased due to comparison with historical controls and/or underpowered. METHODS: In this retrospective multicentric study, data from all CF children fulfilling the following criteria were collected: 1) Age 6-<18 at the end of 2003; 2) diagnosis before 8 y; 3) follow-up in an accredited CF Belgian centre; 4) at least 1 spirometry and respiratory culture available for 2003. Group A included children referred > or =2 years after the diagnosis. Patients from Group A were then matched with a single early referred patient on the basis of 2 criteria: same centre, as closest age as possible (Group B). RESULTS: Data from 217 children were collected (Group A: 67/217). Late referred patients had a lower FEV(1) (77.2%+/-22.4 vs 86.7% pred.+/-19.4, p=0.01) and a higher prevalence of Pseudomonas aeruginosa (38.6 vs 17.5%, p<0.05). CONCLUSION: In this population of CF children, a delay of 6.1 y (vs 0.1 y) between diagnosis and referral to a specialist clinic resulted in poorer respiratory outcome at age 13.


Subject(s)
Cystic Fibrosis/therapy , Referral and Consultation , Adolescent , Belgium , Child , Cystic Fibrosis/diagnosis , Cystic Fibrosis/microbiology , Disease Progression , Humans , Outcome Assessment, Health Care , Pseudomonas aeruginosa/isolation & purification , Retrospective Studies , Time Factors , Treatment Outcome , Vital Capacity
6.
Horm Res ; 70(4): 224-9, 2008.
Article in English | MEDLINE | ID: mdl-18772595

ABSTRACT

OBJECTIVES: To assess whether sleep-disordered breathing (SDB) in overweight children and adolescents has an additional effect on the spectrum of urinary albumin to protein loss, as markers of early kidney dysfunction. METHODS: Prospective study in a clinical sample of overweight children and adolescents. Each subject underwent anthropometry, blood sampling, oral glucose tolerance test and polysomnography. From a 24-hour urine collection, albumin excretion rate and total urinary protein to creatinine ratio (UPCR) were calculated. RESULTS: 94 nondiabetic subjects were included (mean age = 11.0 +/- 2.5, 42 boys). Average BMI z-score was 2.25 +/- 0.47 (26 overweight subjects and 68 obese subjects). There was no difference in albumin excretion rate or UPCR between subjects with and without SDB. None of the SDB parameters correlated with the transformed albumin excretion rate or UPCR. Albumin excretion rate significantly correlated with fasting insulin and C-peptide and with post-challenge glucose, insulin and C-peptide levels, while UPCR correlated with fasting and post-challenge C-peptide levels. Multiple regression indicated that post-challenge glucose levels were the most important predictors of albumin excretion rate. CONCLUSION: Insulin resistance, and not SDB, was associated with increased levels of albuminuria, indicating early renal dysfunction, in this clinical sample of overweight children and adolescents.


Subject(s)
Albuminuria/urine , Insulin Resistance , Obesity/urine , Sleep Apnea Syndromes/urine , Adolescent , Albuminuria/physiopathology , Biomarkers/urine , Child , Cohort Studies , Creatinine/urine , Female , Glucose Tolerance Test/methods , Humans , Kidney Diseases/etiology , Kidney Diseases/physiopathology , Kidney Diseases/urine , Male , Obesity/complications , Obesity/physiopathology , Polysomnography/methods , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/physiopathology
7.
J Pediatr ; 150(6): 608-12, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17517244

ABSTRACT

OBJECTIVE: To assess whether sleep-disordered breathing (SDB) is a risk factor of the metabolic syndrome (MS) in children and adolescents who are overweight and to examine whether the severity of SDB was independently associated with glucose intolerance, insulin resistance, and/or dyslipidemia. STUDY DESIGN: Consecutive subjects who were overweight or obese underwent polysomnography, fasting blood sample, and oral glucose tolerance test (for calculation of area under the curve [AUC]). SDB was defined as a respiratory disturbance index > or = 2. MS was present when > or = 3 of these factors were present: waist circumference > or = 90th percentile; fasting glucose level > or = 110 mg/dL; triglyceride level > or = 110 mg/dL; high-density lipoprotein cholesterol level < or = 40 mg/dL; blood pressure > or = 90th percentile. RESULTS: A total of 104 subjects were included in the study (44% boys; 58% prepubertal; mean age, 11.1 +/- 2.6 years; 69% obese). Mean SaO2 (odds ratio, 0.54) and SaO2nadir (odds ratio, 0.89) were independent, significant predictors of the presence of MS. Multiple regression showed significant associations between SaO2nadir and high-density lipoprotein cholesterol level, mean SaO2 and both AUC glucose and triglyceride levels, and between the percentage of total sleep time with SaO2 > or = 95% and cholesterol level, while controlling for adiposity and sex, puberty, or both. CONCLUSION: This study supports the hypothesis of an interaction between SDB and metabolic abnormalities, independent of estimates of body fat distribution, in children and adolescents who are overweight and obese.


Subject(s)
Metabolic Syndrome/epidemiology , Overweight , Sleep Apnea Syndromes/epidemiology , Adolescent , Area Under Curve , Blood Glucose/analysis , Child , Comorbidity , Female , Humans , Male , Obesity/epidemiology , Overweight/physiology , Polysomnography , Risk Factors
8.
Pediatr Pulmonol ; 42(2): 159-67, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17186545

ABSTRACT

AIM: Only a limited number of studies, designed to establish normal values for sleep-related respiratory variables in children, have been reported, and all are non-European. The aim of this study was to expand the knowledge on normative data in children. METHODS: Subjects ranging from 6 to 16 years were recruited and underwent full polysomnography. Only subjects without sleep disordered breathing or other sleep problems as assessed by clinical history were included. RESULTS: Sixty subjects were studied ( = 11.7 +/- 2.6 years; 28 boys; = 118.8 +/- 30.6%). was 0.85 +/- 1.06 (range: 0.0-5.5). was 0.06 +/- 0.16 (range: 0.0-0.9); 11 patients had a total of 31 obstructive apneas. Only five obstructive hypopneas were detected with = 0.08 +/- 0.17 (range: 0.0-0.9). was 1.98 +/- 1.39 (range: 0.1-7.2). was 97.0 +/- 0.6% (range: 96.0-98.0); was 91.8 +/- 2.7% (range: 82.0-96.0); <% of total sleep time with SaO2 >or= 95%> was 98.7 +/- 2.1% (range: 90.8-100.0); was 0.8 +/- 0.9 (range: 0.0-4.9) and was 6.1 +/- 1.8 (range: 2.7-10.9). Snoring was detected in 15 patients (4 overweight subjects), with no difference in patient characteristics and sleep-related respiratory variables between snorers and non-snorers. Subjects in the overweight group (n = 22) had a lower SaO2nadir (90.8 +/- 2.7 vs. 92.4 +/- 2.6; P = 0.01) and a higher ODI (1.3 +/- 1.3 vs. 0.4 +/- 0.4; P = 0.0002) than their normal weight peers. CONCLUSION: Our data are in agreement with other non-European studies, designed to establish normal values in children.


Subject(s)
Oximetry , Polysomnography , Sleep Apnea, Central/diagnosis , Sleep Apnea, Obstructive/diagnosis , Sleep/physiology , Adolescent , Body Mass Index , Child , Female , Health Surveys , Humans , Male , Overweight/physiology , Reference Values , Sex Factors , Snoring , White People
9.
Pediatr Pulmonol ; 42(7): 579-83, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17526006

ABSTRACT

AIM: To investigate the association between wheezing and impaired sleep in Sri Lankan children, aged 6-12 years; and, to report the prevalence of asthma-related symptoms in these subjects. METHODS: The International Study of Asthma and Allergies in Childhood questionnaire and a separate sleep questionnaire were completed. RESULTS: Of 800 originally distributed questionnaires, 652 were analyzed. Wheezing was present in 89 children (14%). Within this group, 66% reported wheezing in the last 12 months. Wheezing children had a significantly higher presence of snoring, restless sleep, nocturnal awakenings and daytime tiredness. Wheezing was found to be independently associated with restless sleep (odds ratio (OR) = 2.4). There was no association between wheezing and difficulties falling asleep, nocturnal awakenings, apneas, and daytime sleepiness and tiredness. After adjusting for possible confounders, the following significant associations were present: snoring and apneas (OR = 1.6), chronic rhinitis and apneas (OR = 1.6), snoring and restless sleep (OR = 3.2), chronic rhinitis and restless sleep (OR = 2.1), and hayfever and daytime tiredness (OR = 4.3). Wheezing was related to an increased risk of snoring (OR = 2.8) and subjects with chronic rhinitis had also an increased risk of snoring (OR = 1.7), adjusting for possible confounders. CONCLUSION: The sleep of wheezing children was impaired compared with their non-wheezing peers, resulting in an increased prevalence of daytime tiredness. Upper airway symptoms, such as chronic rhinitis or hayfever, should be carefully considered in these children, as they might be responsible for these sleep problems.


Subject(s)
Respiratory Sounds/physiopathology , Sleep , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Sri Lanka , Surveys and Questionnaires
10.
Respir Med ; 101(6): 1331-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17125983

ABSTRACT

Collection of exhaled breath condensate (EBC) is a simple and noninvasive method to obtain information on the respiratory system. Different mediators can be determined in EBC. However, determinants of variability are not well described. The aim of this study was to evaluate variability of pH, volume and protein concentration of EBC between individuals and between sampling times. Therefore, EBC was collected from 20 healthy volunteers on two different days. Median pH for all samples, measured 5 min after collection without deaeration, was 6.17. Median volume was 1.70 ml and median total protein concentration was 1.02 microg/ml. Coefficients of variation were 5.17%, 21.84% and 37.93%, respectively. No intra- or interday variability could be found, except for the first collection time. Between individuals, significant differences were observed for all three mediators. Age, height and gender can explain part of this variation. In conclusion, no significant difference between sampling times on the same day or on different days was obtained for pH, volume and total protein concentration, provided that subjects are experienced in collecting EBC.


Subject(s)
Breath Tests/methods , Proteins/analysis , Adolescent , Adult , Aging/physiology , Body Height/physiology , Exhalation , Female , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Reference Values , Reproducibility of Results , Specimen Handling/methods
11.
J Appl Physiol (1985) ; 87(3): 902-9, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10484556

ABSTRACT

When input impedance is determined by means of the forced oscillation technique, part of the oscillatory flow measured at the mouth is lost in the motion of the upper airway wall acting as a shunt. This is avoided by applying the oscillations around the subject's head (head generator) rather than at the mouth (conventional technique). In seven wheezing infants, we compared both techniques to estimate the importance of the upper airway wall shunt impedance (Zuaw) for the interpretation of the conventional technique results. Computation of Zuaw required, in addition, estimation of nasal impedance values, which were drawn from previous measurements (K. N. Desager, M. Willemen, H. P. Van Bever, W. De Backer, and P. A. Vermeire. Pediatr. Pulmonol. 11: 1-7, 1991). Upper airway resistance and reactance at 12 Hz ranged from 40 to 120 and from 0 to -150 hPa. l(-1). s, respectively. Varying nasal impedance within the range observed in infants did not result in major changes in the estimates of Zuaw or lung impedance (ZL), the impedance of the respiratory system in parallel with Zuaw. The conventional technique underestimated ZL, depending on the value of Zuaw. The head generator technique slightly overestimated ZL, probably because the pressure gradient across the upper airway was not completely suppressed. Because of the need to enclose the head in a box (which is not required with the conventional technique), the head generator technique is difficult to perform in infants.


Subject(s)
Airway Resistance/physiology , Respiratory System/anatomy & histology , Algorithms , Child, Preschool , Female , Humans , Infant , Male , Models, Biological , Plethysmography , Reproducibility of Results
12.
J Appl Physiol (1985) ; 71(2): 770-6, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1938751

ABSTRACT

The forced oscillation technique according to Làndsér et al. (J. Appl. Physiol. 41:101-106, 1976) was modified for use in infants. Adaptations, including a flexible tube to connect the infant to the measuring system and a bias flow to avoid rebreathing, did not influence impedance values. The linearity of the respiratory system was assessed and confirmed by 1) applying pseudo-random noise oscillations at three different amplitudes to 7 infants and 2) comparing in 12 infants impedance values obtained with pseudo-random noise and with sinusoidal oscillations at 12 and 32 Hz. Intersubject variability, averaged for all frequencies, was 6%. In 17 infants the relative error (+/- SD) between two series of five measurements within a time interval of 15 min was 0.5 +/- 5.7%. No statistically significant difference was found between impedance values before and after repositioning of the infant's head, whereas rotation resulted in a decrease in resistance and no effect on reactance. Our results indicate that the infant-adapted forced pseudo-random noise oscillation technique has the potential to give valuable information about ventilatory lung function in infants.


Subject(s)
Airway Resistance/physiology , Respiratory Function Tests/instrumentation , Asthma/physiopathology , Head , Humans , Infant , Infant, Newborn , Recurrence , Reproducibility of Results
13.
Pediatr Pulmonol ; 17(6): 354-8, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8090605

ABSTRACT

Airways obstruction has been demonstrated in acutely wheezing infants. The aim of the present study was to assess functional abnormalities as detected by measurement of total respiratory system resistance (Rrs) and functional residual capacity (FRC) in infants with a history of recurrent episodes of wheezing, while not acutely ill. In 30 such infants (mean age, 10 months; range, 4-17) and in 10 healthy infants (mean age, 6 months; range, 0-14) four Rrs measurements, performed with the forced pseudo-random noise (PRN) oscillation technique, and three FRC determinations, using the closed-circuit helium dilution technique, were averaged. A lower than predicted FRC was demonstrated in 20/30 (66%) patients. At 16 Hz, Rrs was significantly above predicted in 3/30 (10%) patients. Specific Rrs (Rrs x FRC) at 16 Hz was increased in 5/30 (17%) patients. In conclusion, the PRN oscillation technique combined with FRC measurement by helium dilution detects lung function abnormalities in a minority of wheezing infants during symptom-free intervals.


Subject(s)
Airway Resistance/physiology , Functional Residual Capacity/physiology , Lung/physiology , Tidal Volume/physiology , Case-Control Studies , Chloral Hydrate , Helium , Humans , Infant , Infant, Newborn , Lung/physiopathology , Oscillometry , Peak Expiratory Flow Rate , Plethysmography, Whole Body , Pulmonary Ventilation , Regression Analysis , Reproducibility of Results , Respiratory Sounds , Spirometry
14.
Pediatr Pulmonol ; 11(1): 1-7, 1991.
Article in English | MEDLINE | ID: mdl-1923662

ABSTRACT

By applying oscillations to the respiratory system through a rigid face mask, the infant-adapted Lándsér forced oscillation technique measures impedance of the total respiratory system including the nose, at frequencies from 4 to 52 Hz. The present study was aimed at evaluating nasal impedance in infants from consecutive forced oscillation measurements through both nostrils and each nostril separately, using a simple electrical model. In 30 asthmatic infants with varying degrees of nasal obstruction, aged 1-16 months, calculated nasal resistance (Rn) at 24 Hz ranged from 1 to 16 cm H2O.L-1.s. The ratio of Rn to total respiratory system resistance varied between 1 and 48% (mean: 16%). In seven non-asthmatic infants, aged 0-12 months, Rn was between 1 and 11 cm H2O.L-1.s. Nasal patency (evaluated clinically) was correlated with the calculated Rn (P less than 0.05). Rn showed almost no frequency dependence between 24 and 48 Hz as demonstrated by a mean slope of -0.09 +/- 0.08 cm H2O.s2/L for the asthmatic and of -0.08 +/- 0.07 for the non-asthmatic infants. In seven of the asthmatic infants the differences between two Rn determinations at a 45 min interval ranged from -1.7 to 3.8 cm H2O.L-1.s-1 at 24 Hz and from -3.6 to 1.0 at 48 Hz. Changes in Rn did not correlate with changes in total respiratory system resistance (P greater than 0.05). In conclusion, nasal impedance can be approximated from three consecutive measurements through both nostrils and through each nostril separately.


Subject(s)
Airway Resistance/physiology , Nasal Cavity/physiology , Asthma/physiopathology , Humans , Infant , Infant, Newborn , Models, Biological , Nasal Obstruction/diagnosis , Noise , Oscillometry/methods , Respiratory Physiological Phenomena
15.
Pediatr Pulmonol ; 27(6): 369-75, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10380087

ABSTRACT

In this retrospective study, adult height was assessed in young adult asthmatics who were treated with inhaled corticosteroids (ICs) during childhood (n = 42; 26 boys) and compared to those obtained in asthmatic patients who were never treated with ICs during childhood (n = 43; 23 boys). Standing height of all subjects and their parents was measured. Height data were analyzed using actual length and target height in centimeters, standard deviation scores (SDS), and difference between adult height of the patients and their target height (adult height minus target height). Mean adult height was the same in subjects who took ICs during childhood as compared to those who had never received ICs (boys: 179.3cm+/-6.8 vs. 180.4 cm+/-5.6; girls: 165.8 cm+/-7.5 vs. 167.7 cm+/-7.2). SDS of adult height was also not different between the two groups: in subjects who did not take ICs it was 0.89+/-1.00, while in those who took ICs it was 0.66+/-1.10 (P = 0.31). SDS of target height was also not different between the two groups: in subjects not taking ICs it was 0.95+/-0.86, while in those who took ICs it was 0.28+/-0.76 (P = 0.30). However, subjects who took ICs during childhood showed a statistically significant lower value of adult height minus target height than those who never took ICs (whole group: -0.003+/-5.9 vs. 2.54 +/-4.8, P = 0.03 ; boys: 0.004+/-5.8 vs. 3.09+/-4.5, P = 0.04 ; girls: -0.075+/-6.3 vs. 1.91+/-5.2, P = 0.31). Patients on ICs during childhood who had ever been hospitalized for asthma showed a lower value for adult height minus target height than those who took ICs but were never hospitalized (-3.08+/-7.8 vs. 1.06+/-4.8, P = 0.046). A logistic regression analysis predicting growth impairment showed that the best-fitting model was one that used only ICs as a dependent variable (crude odds ratio, 3.3; 95% CI, 1.3-8.4). Patients who were treated with ICs in combination with intranasal corticosteroids (treatment for rhinitis) tended to have a lower value of adult height minus target height than the other children, but the difference was not statistically significant (P = 0.07). We conclude that although adult height was the same in young adults who were treated with ICs during childhood compared to those who were not treated with ICs during childhood, there was a statistically significant difference between the two groups for adult height minus target height, suggesting mild growth retardation in patients who took ICs during childhood. These findings may be explained by the use of ICs, but it seems more likely that a difference in asthma severity between both groups was responsible for it.


Subject(s)
Anti-Asthmatic Agents/pharmacology , Asthma/physiopathology , Body Height/drug effects , Glucocorticoids/pharmacology , Adolescent , Adult , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Beclomethasone/pharmacology , Beclomethasone/therapeutic use , Female , Glucocorticoids/therapeutic use , Humans , Male , Retrospective Studies , Treatment Outcome
16.
Pediatr Pulmonol ; 20(1): 16-20, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7478776

ABSTRACT

We investigated the effects of 10 mg aerosolized furosemide on clinical score in 28 acutely wheezing infants (Part A) and in a second group of 20 intermittently wheezing babies on airway resistance and functional residual capacity during a symptomfree period (Part B), using a double-blind, placebo-controlled design. In both parts of the study no therapeutic effects were observed during and following aerosol inhalation of 10 mg furosemide.


Subject(s)
Anti-Asthmatic Agents/administration & dosage , Bronchiolitis/drug therapy , Furosemide/administration & dosage , Respiratory Sounds/drug effects , Administration, Inhalation , Aerosols , Airway Resistance/drug effects , Airway Resistance/physiology , Bronchiolitis/physiopathology , Double-Blind Method , Female , Functional Residual Capacity/drug effects , Functional Residual Capacity/physiology , Humans , Infant , Male , Respiratory Sounds/physiopathology , Treatment Failure
17.
Med Biol Eng Comput ; 35(6): 752-6, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9538557

ABSTRACT

The forced oscillation technique is usually calibrated by loading the measuring device with a known impedance. A correction function is calculated, relating the measured and reference impedances at each frequency. However, this one point calibration procedure does not account for transducer asymmetry. A procedure has previously been presented to circumvent this problem: in addition to one known reference impedance, the calibration was repeated with the system occluded (infinite impedance). The aim of the present study was to evaluate a variant of this procedure, in which instead of resorting to an extreme condition imposing high requirements on the flow measuring system, two reference loads of 4 and 50 hPal-1 s were measured, thus covering the range of impedances observed in children and infants (a two-point procedure). The calibration procedure was performed with these two impedances and evaluated with a third impedance of approximately 17 hPal-1 s. The results of three calibration procedures were compared: one-point, two-point and a previously reported calibration procedure. Impedances consisted of sintered glass and mesh wire screens mounted in glass or polyvinyl tubes. For low impedance values, in the range of 4 to 17 hPal-1 s, measured and predicted values were similar for the three calibration procedures at frequencies from 4-52 Hz, although with the one point calibration procedure there was some underestimation above 44 Hz. With the highest load, especially above 32 Hz, marked discrepancies between measured and predicted values were observed with the one-point calibration procedure and the previously reported calibration procedure. Under these circumstances the two-point procedure is preferred.


Subject(s)
Respiratory Function Tests/methods , Respiratory Mechanics , Transducers, Pressure , Calibration , Humans
18.
Pediatr Obes ; 9(1): 36-42, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23325614

ABSTRACT

UNLABELLED: What is already known about this subject BDNF is involved in the regulation of food intake and body weight. BDNF deficient animal models are obese. Chromosomal abnormalities cause obesity in humans. What this study adds Evaluation of point mutations in BDNF. Identification of BDNF mutations in obese children. Point mutations in BDNF are not a common cause of childhood obesity. INTRODUCTION: There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype. METHODS: We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing. RESULTS: Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population. CONCLUSIONS: In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.


Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Genetic Testing , Pediatric Obesity/genetics , Point Mutation , Adolescent , Adult , Child , Child, Preschool , Female , Genetic Variation , Humans , Male , Pediatric Obesity/diagnosis , Phenotype
19.
Obesity (Silver Spring) ; 21(7): 1446-50, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23408643

ABSTRACT

OBJECTIVE: Sleep-disordered breathing (SDB) is prevalent in obesity. Weight loss is one of the most effective treatment options. The aim was to assess the association of SDB and metabolic disruption before and after weight loss. DESIGN AND METHODS: Obese adolescents were included when entering an in-patient weight loss program. Fasting blood analysis was performed at baseline and after 4-6 months. Sleep screening was done at baseline and at follow-up in case of baseline SDB. RESULTS: 224 obese adolescents were included. Median age was 15.5 years (10.1-18.0) and mean BMI z-score was 2.74 ± 0.42. About 30% had SDB at baseline (N = 68). High-density lipoprotein (HDL)-cholesterol was associated with mean nocturnal oxygen saturation () (partial r = 0.21; P = 0.002). Aspartate aminotransferase (ASAT) and alanine aminotransferase were related with oxygen desaturation index (partial r = -0.15; P = 0.03 and partial r = -0.15; P = 0.02), but this became insignificant after correction for sex. After weight loss, 24% had residual SDB. Linear regression showed an association between ASAT and (partial r = -0.34; P = 0.002). There were no significant correlations between improvements in laboratory measurements and sleep parameters. HDL-cholesterol improved in relation with the decrease in BMI z-score. CONCLUSION: SDB at baseline was associated with higher levels of liver enzymes and lower HDL-cholesterol concentration. Improvements in sleep parameters were not associated with improvements in laboratory measurements.


Subject(s)
Obesity/physiopathology , Sleep Apnea Syndromes/physiopathology , Weight Loss , Adolescent , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Body Mass Index , Body Weight , Child , Cholesterol, HDL/blood , Humans , Linear Models , Obesity/therapy , Prevalence , Sleep Apnea Syndromes/therapy
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