Biomedical subjects
M O Hoekstra
Publications and source records attributed to M O Hoekstra.
Gastroesophageal reflux in infants with wheezing.
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Life-threatening hemothorax in a child following intrapleural administration of urokinase.
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Sputum induction for the diagnosis of pulmonary tuberculosis.
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Respiratory muscle activity measured with a noninvasive EMG technique: technical aspects and reproducibility.
A new method is being developed to investigate airway obstruction in young children by means of noninvasive electromyography (EMG) of diaphragmatic and intercostal muscles. The purpose of this study was to evaluate the reproducibility of the EMG measurements. Eleven adults, 39 school children (20 healthy, 19 asthmatic), and 16 preschool children were studied during tidal breathing on separate occasions: two for adults with a time interval of 3 wk and three for children with time intervals of 1 and 24 h. Single electrodes were placed on the second intercostal space left and right of the sternum and at the height of the frontal and the dorsal diaphragm. Bipolar electrode pairs were placed on the rectus abdominis muscle. A newly designed digital physiological amplifier without any analog filtering was used to measure the EMG signals. Except for the average dorsal diaphragm EMG derivation in healthy school children on the second occasion, a significant correlation between the mean peak-to-peak inspiratory activity of average diaphragmatic and intercostal EMG was found in the different age groups on the different measurement occasions (P < 0.05). To assess the repeatability, we described the agreement between the repeated measurements within the same subjects. No significant differences were found between the measurements on the separate occasions. Our observations indicate that the EMG signals derived from the diaphragm and intercostal muscles are, in different age groups with and without asthma, reproducible during tidal breathing.
[Clinical thinking and decision-making in practice. A child with dyspnea and excess pleural fluid].
Pleural fluid was diagnosed on an X-ray in a 9-month-old boy with acute dyspnoea without fever. Thoracentesis showed exudate and the patient was diagnosed as having empyema and was treated with continuous chest tube drainage and antibiotics. The culture of the pleural fluid was negative. A month after discharge the boy developed recurrent pleural effusion with dyspnoea. A mass in the right hemithorax was found upon additional diagnostic evaluation. Microscopic evaluation of tumour biopsy specimen showed a malignancy. Infantile fibromatosis was diagnosed in a surgical specimen. The patient died after having developed a recurrent tumour. Infectious causes are not likely in a child with pleural fluid without fever. Pleural fluid has to be analysed in transudate or exudate. Exudate requires a complete diagnostic evaluation.
Can overnight urine collections in children be successful?
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Can eosinophil-derived proteins be used to diagnose or to monitor childhood asthma?
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Is childhood asthma an inflammatory disease?
There is now extensive evidence that asthma results from inflammation in large and small airways, and that the degree of inflammation reflects the clinical severity of the disease. Most of this evidence, however, has come from studies in adult patients. Evidence in children comes largely from indirect studies such as measurements of peripheral blood cells and inflammatory markers, rather than from direct bronchoscopic examination. Studies in adults show that inflammation in asthma is characterized by eosinophilia, epithelial damage, and bronchial hyperresponsiveness, and that activation of allergen-specific T cells plays an important role in orchestrating the inflammatory process. In children, indirect evidence of inflammation comes from the observation that anti-inflammatory agents such as inhaled corticosteroids improve symptoms and bronchial hyperresponsiveness, reduce the number of asthma exacerbations, and limit the progressive decline in lung function. Further evidence comes from measurements of nitric oxide and hydrogen peroxide (potential inflammatory markers) in exhaled air, and of inflammatory mediators in plasma and urine. As in adults, there is evidence that lymphocytes play an important role in orchestrating the inflammatory process. The immunologic profile appears to shift from a Th1-type cytokine profile to an allergen-related Th2-type profile prior to birth. Such a Th2 predominance constitutes a risk factor for the subsequent development of bronchial hyperresponsiveness and asthma in response to allergen.
[Inhalation therapy in children younger than 2 years].
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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.
Bronchial inflammation and hyperresponsiveness.
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[Treatment of asthma in children; revised guidelines by pediatric pneumologists. Section of Pediatric Lung Diseases of the Dutch Association of Pediatric Medicine].
The diagnosis of 'asthma' is still based on anamnesis, physical examination and lung function tests. Supplementary examinations (laboratory or roentgen) are carried out only if indicated. Most young children with recurrent periods of wheezing and coughing prove not to develop asthma in the long run. Oral medication no longer has a place in the treatment of asthma, since inhalation medication is now possible at all ages, among other things because of the current availability of new nozzle attachments. Every child with asthma should have a short-acting beta 2-agonist at hand. Furthermore, inhaled corticosteroids are the maintenance drug of choice in children with moderate or severe asthma. Systemic effects may occur with every inhaled corticosteroid, even with dosages usual for children, but these are rarely relevant. Cromones nowadays play a very limited part. Long-acting beta 2-agonists are indicated in children whose asthma cannot be controlled with standard doses of inhaled corticosteroids. In the prevention of allergic asthma of childhood, prescription of the allergen-tight mattress cover plays a main part. The physician has an important task in discouraging (passive) smoking. Young children who, in spite of treatment with inhaled corticosteroids, have recurrent episodes of wheezing and coughing. and children requiring high doses of inhaled corticosteroids (over 400 micrograms beclomethasone/budesonide or 250 micrograms fluticasone) should be referred to a paediatrician. The asthma nurse has an important task in instructing and advising the asthmatic child and its parents. Self-management programmes may be of great psychological value for the patient and his environment.
[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.
[Diagnosis and treatment of recurrent coughing and wheezing in children younger than 4 years old].
Recurrent coughing and wheezing occur in 10-20% of children younger than 4 years. Forty per cent of these children develop allergic asthma, while in 60% the symptoms are transient. It is difficult to distinguish between persistent and transient symptoms; signs of allergy and lack of symptom-free intervals are suggestive of persistent asthma. In acute wheezing and coughing a trial treatment with beta-2 sympathicomimetic agents is indicated, preferably using an inhalation aerosol with feed container; for cases with pronounced symptoms or strong suspicion of allergic asthma, high-dose oral corticosteroid treatment is recommended. Maintenance treatment with inhalation corticosteroids is valuable in moderately severe complaints of allergic asthma and in severe complaints about recurrent wheezing.
Nebulised antipseudomonal antibiotic therapy in cystic fibrosis.
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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.