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Biomedical subjects

J Gerritsen

Publications and source records attributed to J Gerritsen.

At least 55 records · Page 3Linked to original sources

Risk factors for growth and decline of lung function in asthmatic individuals up to age 42 years. A 30-year follow-up study.

Little is known about factors determining the outcome of childhood asthma. The purpose of this longitudinal study was to assess the factors in childhood that determine the level of FEV(1) in early adulthood in asthmatic individuals, and to examine factors associated with decline in FEV(1) during adulthood. Between 1966 and 1969, 119 allergic asthmatic subjects aged 5 to 14 yr were studied (Visit 1). Of these subjects, 101 (85%) were reinvestigated at ages 22 to 32 yr (Visit 2) and 32 to 42 yr (Visit 3). At the first survey and during follow-up, a standardized questionnaire was used, serum total IgE and peripheral blood eosinophils were measured, and physical examination, skin tests, lung function tests, and histamine challenge (provocative concentration causing a 10% decline in FEV(1); PC(10)) tests were performed according to the same protocol. Multiple linear regression analyses were performed with FEV(1) at Visit 2 and with the change of FEV(1) from Visit 2 to Visit 3 as outcome variables. A low FEV(1)% predicted at Visit 1 and PC(10) </= 16 mg/ml at Visit 1 were significantly associated with a lower level of FEV(1) at Visit 2. Subjects who quit smoking and subjects who continued to use inhaled corticosteroids had a significantly smaller annual decline in FEV(1) from Visit 2 to Visit 3, adjusted for attained level of FEV(1) at Visit 2. In conclusion, bronchial hyperresponsiveness and a low level of lung function in childhood are independent risk factors for a low level of FEV(1) in early adulthood. A smaller decline in FEV(1) after ages 22 to 32 yr occurs in asthmatics who quit smoking and who continue to use inhaled corticosteroids. Our data stress the importance of studying intervention strategies for asthma in young childhood and early adulthood in order to prevent or postpone further lung function deficits.

Adolescent↗

Development of macronutrient composition of very preterm human milk.

The effects of gestational age at delivery (GA), postnatal age (PNA) and post-menstrual age (PMA = PNA + GA, an indicator of autonomous developmental processes not affected by the moment of birth) on macronutrient composition of very preterm milk were studied. Total N, fat, lactose and carbohydrate concentrations, energy density and 24 h volume were determined in 282 24 h milk samples collected at weekly intervals (days 7-55 of lactation) from seventy-nine women delivering their babies between 25 and 29 weeks of gestation. GA related differences were found for carbohydrate concentration only: carbohydrate concentration was lower with increasing GA. PNA was related to a decrease in total N and an increase in lactose concentration. PMA was not related to milk composition. Our data indicate that PNA strongly influences the development of the composition of very preterm human milk, while GA affects carbohydrate content with a negligible effect on the nutritional value of the milk. We conclude that in accordance with current opinion in paediatrics, human milk is the best source of nutrients even for very preterm (< 30 weeks GA) infants.

Analysis of Variance↗

Validation of a screening questionnaire for atopy with serum IgE tests in a population of pregnant Dutch women.

BACKGROUND: We have started a large birth cohort study in which pregnant women with and without atopy are differentially included. In view of the large number of subjects to be screened (12000), a simple questionnaire was developed for the assessment of atopy in pregnant women. OBJECTIVE: The objective of our study was to evaluate the efficacy of a questionnaire using serum IgE tests. METHODS: During a antenatal visit to the midwife clinic, 175 expecting mothers completed a questionnaire and from each subject blood was obtained in which total and specific IgE against house dust mite, cat, dog, birch and grass was determined. RESULTS: When atopy was defined as the presence of a positive test for IgE against at least one allergen, seven questions from the questionnaire had a sensitivity and specificity of 55.0% and 88.7%, respectively. With the use of the questionnaire it was possible to select about 50% of the subjects with specific IgE to one or more common inhalant allergens. The positive predictive value of the screening questions was 71.7%. Taking total IgE into account did not change these results. CONCLUSION: The screening questionnaire is an efficient tool for differential inclusion of subjects with and without atopy in epidemiological studies.

Allergens↗

Eosinophil and mast cell parameters in children with stable moderate asthma.

UNLABELLED: Mast cells and eosinophils are important cells that contribute to the process of inflammation in asthma either by activating other cells or by secreting products which are potentially toxic to the respiratory epithelium. The influx of these cells in the airways and the secretion of toxic products by these cells is abrogated by inhaled corticosteroids. METHODS: In a double blind randomised, placebo controlled, study in children with stable moderate asthma (N = 34, 15 children received fluticasone propionate (FP), an inhaled corticosteroid, and 19 children used a placebo), we investigated the influence of treatment with FP 100 microg b.d. on various parameters of inflammation: number of eosinophils, secretory products of eosinophils i.e. ECP and EDN (in serum and urine) and a secretory product of mast cells, histamine, which is determined as the compound to which histamine is converted and excreted by the human body: NT-methyl-histamine. RESULTS: Previously we reported that lung function increased and bronchial hyperresponsiveness decreased in the 30 children that completed the study during treatment with FP. In these children we found that none of the laboratory parameters of inflammation changed significantly during treatment with either FP or placebo. However, the decrease in urinary EDN almost reached significance (P = 0.07). CONCLUSIONS: Our results indicate that the number of eosinophils, serum ECP and EDN and urinary EDN as well as urinary NT-methyl-histamine do not reflect asthma disease activity in children with stable moderate asthma. Our data on urinary EDN warrant further study of the use of this parameter to monitor asthma in children.

Administration, Inhalation↗

Peak expiratory flow variability, bronchial responsiveness, and susceptibility to ambient air pollution in adults.

Bronchial hyperresponsiveness (BHR) and peak expiratory flow (PEF) variability are associated expressions of airway lability, yet probably reflect different underlying pathophysiologic mechanisms. We investigated whether both measures can be used interchangeably to identify subjects who are susceptible to ambient air pollution. Data on BHR (>= 20% fall in FEV1), PEF variability (ampl%mean PEF > 5% on any day during an 8-d period with low air pollution levels) and diary data on upper and lower respiratory symptoms, cough, and phlegm were collected in 189 subjects (48-73 yr). The acute effects (lag0) of particulate matter with a diameter less than 10 micrometers (PM10), black smoke, SO2 and NO2 on the prevalence of symptoms were estimated with logistic regression. In subjects with airway lability, both when expressed as PEF variability (69%) and BHR (28%), the prevalence of symptoms increased significantly with increasing levels of air pollution, especially in those with the greater PEF variability (n = 55, 29%). We found no such consistent positive associations in adults without airway lability. PEF variability, and to a smaller extent BHR, can be used to identify adults who are susceptible to air pollution. Though odds ratios were rather low (ranging from 1.13 to 1.41), the impact on public health can be substantial because it applies to large populations.

Acute Disease↗

[Lung transplantation in children].

The first lung transplantation in the Netherlands was carried out in 1990. Since, the operation has been performed in over one hundred adults and two children (up to 16 years) with chronic respiratory insufficiency. Most lung transplantations in children are performed because of cystic fibrosis. After referral, the patient is given information about the operation and the pre- and postoperative periods, and the transplantation team advises on the time of screening. Some one-third of the children referred ultimately undergo transplantation; the others refrain from the operation, are rejected or die during the waiting period. Owing to a shortage of donor lungs the waiting period for transplantation may last over one year. A possible but controversial solution is donation of a pulmonary lobe by a close relative. Undergoing lung transplantation places a heavy (psychic) burden on the patient and his parents. Every patient after lung transplantation goes through an average of two or three periods of acute rejection. Chronic rejection occurs in 20-40%. Other complications are connected to medication (infections, renal dysfunction) or to the underlying disease (diabetes mellitus in cystic fibrosis). The percentages of survival for 1, 2 and 4 years are approx. 60-70, 55-60 and 30-50, dependent in part on the type of lung transplantation (unilateral, bilateral or combined heart-lung transplantation). A reasonable condition of the patient owing to timely referral is a positive prognostic factor.

Adolescent↗

[Acetylcysteine in children with lung disorders prescribed by one-third of family physicians: no support in the literature].

OBJECTIVE: To determine whether the use of acetylcysteine in children is supported by literature data and to determine how often and for what indications acetylcysteine is prescribed for children in general practice. DESIGN: Systematic literature review and general practitioners audit. SETTING: Academic Hospital Groningen, the Netherlands. METHODS: A Medline search was performed and the references of the articles found were checked. All 720 general practitioners working in the three northern provinces of the Netherlands were mailed a questionnaire regarding their prescription of acetylcysteine for children. RESULTS: Of the studies on acetylcysteine in children with pulmonary disorders (excluding cystic fibrosis) (n = 15) the majority (n = 12) were uncontrolled clinical observations. Three clinical trials were found, all of which showed considerable methodological shortcomings. The observed benefit of acetylcysteine therapy in these studies was of no clinical relevance. The questionnaire was filled out completely and returned by 70.3% of general practitioners. Almost one-third of the general practitioners (32.6%) prescribed acetylcysteine now and again for children with various pulmonary disorders (such as 'mucus that is difficult to bring up' (73.9%), asthmatic bronchitis (50.3). bronchitis (40.0%), excessive mucus production (40.0%) and dry cough (34.5%)). CONCLUSION: Acetylcysteine is being prescribed frequently for children with various pulmonary disorders by general practitioners whilst the use of this drug is not being supported by literature data.

Acetylcysteine↗

Human uteroglobin gene: structure, subchromosomal localization, and polymorphism.

Human uteroglobin (hUG) or Clara cell 10-kD protein (cc10 kDa) is a steroid-dependent, immunomodulatory, cytokine-like protein. It is secreted by mucosal epithelial cells of all vertebrates studied. The cDNA encoding hUG and the 5' promoter region of the gene have been characterized previously. Here, we report that the structure of the entire hUG gene is virtually identical to those of rabbit, rat, and mouse. It is localized on human chromosome 11q12.3-13.1, a region in which several important candidate disease genes have been mapped by linkage analyses. Our data indicate that candidate genes for atopic (allergic) asthma and Best's vitelliform macular dystrophy are in closest proximity to the hUG gene. To determine whether hUG gene mutation may be involved in the pathogenesis of these diseases, we studied two isolated groups of patients, each afflicted with either atopy or Best's disease, respectively. We detected a single base-pair change in the hUG gene in Best's disease patients and normal controls but no such change was detected in atopy patients. This alteration in hUG gene-sequence in Best disease family appears to be a polymorphism. Although the results of our investigation did not uncover mutations in hUG gene that could be causally related to the pathogenesis of either of these diseases, its conservation throughout vertebrate phyla implies that this gene is of physiological importance. Moreover, the close proximity of this gene to several candidate disease genes makes it an important chromosomal marker in cloning and characterization of those genes.

Animals↗

Community integration of wheelchair-bound athletes: a comparison before and after onset of disability.

OBJECTIVES: (1) To assess to what extent wheelchair-bound athletes living independently in the community were able to return to their premorbid level of functioning in the community; (2) to investigate how they value their current way of functioning in comparison to that before disability; and (3) to examine the factors that hamper their return to their premorbid life in four domains. METHODS: Forty-four wheelchair-bound athletes participated in this study. Data were collected by means of a self-administered semi-structured questionnaire which was divided into four domains: vocational status, leisure time activities, social functioning and relationship with partner. RESULTS: Return to premorbid level of functioning in the community in the long term was reasonably well achieved for the domains 'leisure activities', 'social contacts' and 'relationship with partners', but not for 'vocational situation'. Between 60% and 80% of the participants reported satisfaction with their current level of functioning for all domains. However, about 50% of the respondents reported that they were currently less satisfied with their functioning on the domains 'vocational situation' and 'leisure activities', compared to before the onset of disability. Factors limiting integration were principally access to buildings and physical health problems (pain and fatigue). CONCLUSION: It appeared that wheelchair-bound athletes were able to live a life on a level comparable to that before onset of disability for three of the four domains. It was emphasized that pain treatment in late rehabilitation and improving access for the disabled can contribute to the further integration of wheelchair-bound people into the community.

Adaptation, Psychological↗

Inhibition of PAF-induced expression of CD11b and shedding of L-selectin on human neutrophils and eosinophils by the type IV selective PDE inhibitor, rolipram.

We quantitatively determined whether the selective phosphodiesterase (PDE) inhibitor, rolipram, inhibits changes in the adhesion molecules CD11b and L-selectin on platelet-activating factor (PAF)-stimulated human neutrophils and eosinophils in vitro. Incubations were performed in human whole blood obtained from healthy volunteers, to restrict activation by purification procedures and to simulate in vivo conditions, in which different cell types may interact, more closely. Receptor expression was measured after fixation of cells, using monoclonal antibodies and flow cytometry. Concentration-dependent inhibition of the PAF-induced CD11b expression and L-selectin shedding for neutrophils and eosinophils was observed with rolipram, dibutyryl cyclic adenosine monophosphate (cAMP), prostaglandin E2 (PGE2), and isoproterenol. However, these inhibitions did not exceed 50%. Preincubation with rolipram (10(-8) M) and subsequent incubation with isoproterenol (0.5x10(-8) M) or PGE2 (10(-8) M) induced a cumulative, but not synergistic, effect. Using the combination of rolipram with isoproterenol or PGE2, inhibition of PAF-induced L-selectin shedding from eosinophils was as high as 71+/-28 and 67+/-21%, respectively. Other inhibitions were below 50%. In conclusion, rolipram inhibits CD11b expression and L-selectin shedding of platelet-activating factor-stimulated neutrophils and eosinophils in whole blood in a concentration-dependent fashion. Inhibitions did not exceed 50%, even at high concentrations. The inhibition of platelet-activating factor induced shedding of L-selectin from eosinophils with a combination of rolipram and prostaglandin E2 or isoproterenol, however, was found to be approximately 70%. Inhibition of rolling adhesion of eosinophils may, therefore, be a mode of action of type IV phosphodiesterase inhibitors.

Bucladesine↗

Interleukin-4, interferon-gamma and interleukin-5 in peripheral blood of children with moderate atopic asthma.

BACKGROUND: In asthmatic inflammation, TH2 cells play an important role. TH2 cells specifically secrete cytokines like IL-4 and IL-5. IL-4 stimulates IgE production and IL-5 is involved in hemopoiesis, chemotaxis, priming and activation of eosinophils. IFNgamma, produced by TH1 cells, has an inhibitory action on IgE production. OBJECTIVES: To investigate the TH1/TH2-cell pattern in the cytokine production of peripheral blood of asthmatic children. We determined IL-4, IFNgamma and IL-5 in serum and in supernatants of unstimulated and stimulated (24 h with Concanavaline A) cultures of peripheral blood mononuclear cells (PBMCs) in 22 children with moderate asthma (mean age 9.3 years) and in 17 healthy controls (mean age 10.3 years). All children visited the out-patient department (OPD) where history taking, physical examination and blood sampling took place. Children younger than 8 years of age performed symptom and peak flow registration during 1 week after the visit to the OPD. RESULTS: The number of eosinophils were significantly higher in children with asthma, compared with healthy controls. The concentration of IFNgamma in supernatants of cultures of stimulated PBMCs was significantly lower and the ratio of IL-4/IFNgamma was significantly higher in children with asthma compared with healthy controls. The FEV1 was directly and IgE was inversely related to the concentration of IFNgamma in supernatants of cultures of stimulated PBMCs. CONCLUSION: IFNgamma may play an important role in the pathophysiology of childhood atopic asthma.

Adolescent↗

Partial conservation of the sn-2 position of dietary triglycerides in fasting plasma lipids in humans.

The authors investigated the effect of the position of fatty acids within dietary triglycerides on the composition of plasma lipids. Sixty volunteers consumed two diets of equal fatty acid compositions for 3 weeks each. In the palm oil diet 82% of palmitic acid was attached to the sn-1 and sn-3, and 18% to the sn-2 position of glycerol. In the diet rich in a palm oil analogue, Betapol, these figures were 35% and 65% respectively. Oleic and linoleic acid in palm oil were mainly in the sn-2 position, and in Betapol mainly in the sn-1 and sn-3 position. The proportion of palmitic acid in the 2 position of fasting plasma triglycerides was 10·2 g 100 g-1 on palm oil and 12·3 on Betapol; that of oleic acid was 46·dot 9 vs. 43·6 (P < 0·0001). Overall oleic acid content of triglycerides was 1·4 g 100 g-1 lower on Betapol than on palm oil (P = 0·002). Betapol increased palmitic and palmitoleic acid in cholesteryl esters by 1 g 100 g-1 (P < 0·0001) at the expense of oleic and linoleic acid. The positional configuration of dietary fatty acids has small but consistent effects on lipid metabolism that persist beyond fat absorption and chylomicron clearance.

Adult↗