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Biomedical subjects

H J Neijens

Publications and source records attributed to H J Neijens.

At least 73 records · Page 4Linked to original sources
PubMed1995

The effect of asphyxia on the pharmacokinetics of ceftazidime in the term newborn.

The multiple-dose pharmacokinetics of ceftazidime (CAZ) (administered twice daily in a 50 mg/kg of body weight i.v. dose) were studied in 10 severely asphyxiated term infants with suspected septicemia on d 3 of life. Nine term infants with suspected septicemia but without asphyxia served as controls. Blood samples were collected from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an i.v. bolus injection. A high performance liquid chromatography method was used to determine CAZ concentrations from serum. CAZ pharmacokinetics followed a one-compartment open model. The GFRs of all infants were simultaneously studied by means of the 24-h continuous inulin infusion technique. Elimination serum half-life (5.86 +/- 1.13 h versus 3.85 +/- 0.40 h) and serum trough concentrations (46 +/- 14 mg/L versus 23 +/- 7 mg/L) of CAZ were significantly (p < 0.001) increased in the asphyxiated newborn, whereas total body clearance of CAZ (128.4 +/- 25.1 mL/h versus 205.7 +/- 55.4 mL/h), CAZ clearance per kg (40.9 +/- 6.1 mL/h/kg versus 60.8 +/- 8.3 mL/h/kg), and the GFR expressed in mL/min (3.14 +/- 0.43 versus 4.73 +/- 0.89) were significantly (p < 0.001) decreased in the asphyxiated newborn. We conclude that twice daily administration of 50 mg/kg of body weight CAZ given to asphyxiated term newborns in the first days of life results in significantly higher serum trough levels in comparison with control infants. The impaired CAZ clearance is a result of a significantly decreased GFR.

Asphyxia Neonatorum↗
PubMed1995

Ceftazidime pharmacokinetics in preterm infants: effect of postnatal age and postnatal exposure to indomethacin.

1. The effects of postnatal age and postnatal exposure to indomethacin on the pharmacokinetic parameters of ceftazidime (CAZ) were investigated in 23 preterm infants (gestational age 28.7 +/- 1.7 weeks; weight 1086 +/- 311 g) on day 3 and day 10 after birth. 2. CAZ (25 mg kg-1) was administered by intravenous bolus injection. Blood samples were drawn from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after the dose and CAZ concentrations in serum were determined by h.p.l.c. CAZ pharmacokinetics followed a one-compartment open model. 3. The glomerular filtration rate (GFR) of all infants was studied by means of the 24 h continuous inulin infusion technique. 4. The total body clearance of CAZ (34.7 +/- 9.2 vs 50.6 +/- 19.6 ml h-1, P < 0.05; 30.7 +/- 5.9 vs 41.6 +/- 9.0 ml h-1 kg-1, P < 0.05) and GFR (0.72 +/- 0.11 vs 0.91 +/- 0.15 ml min-1, P < 0.05) increased, whereas the apparent volume of distribution (425 +/- 147 vs 352 +/- 108 ml, P < 0.05; 363 +/- 59 vs 292 +/- 44 ml kg-1, P < 0.005) and the elimination half-life (8.7 +/- 2.8 vs 5.0 +/- 0.9 h, P < 0.005) decreased significantly between day 3 and day 10 after birth. Clearance of CAZ increased with increasing GFR (r = 0.81, P < 0.001). 5. In infants with postnatal exposure to indomethacin the changes in CAZ pharmacokinetics were markedly reduced. 6. These results indicate that the dosage regimen of CAZ should be adjusted after the first week of life except in infants who were postnatally exposed to indomethacin.

Age Factors↗
PubMed1994

Toxocara seroprevalence in 5-year-old elementary schoolchildren: relation with allergic asthma.

Toxocara seroprevalence and the relation between Toxocara seroprevalence and allergic asthma were investigated in Dutch schoolchildren aged 4-6 years. Data on Toxocara antibodies, allergen-specific immunoglobulin E, allergic manifestations, and risk factors (pets and playgrounds) were obtained from 235 children from The Hague and 477 from Rotterdam, the Netherlands. The surveys were carried out from September 1987 to January 1988 in The Hague and in March and April 1989 in Rotterdam. Logistic regression was used to evaluate putative relations. Toxocara seroprevalence was higher in The Hague (11%) than in Rotterdam (6%), but this difference was not quite significant. Seroprevalences varied widely among schools. No differences between socioeconomic categories or between the sexes were found. Occurrences of asthma/recurrent bronchitis and hospitalization due to asthma/recurrent bronchitis were significantly associated with seroprevalence. Furthermore, a marginally significant relation with eczema was found. Immunoglobulin E specific for inhaled allergens occurred significantly more often in the Toxocara-seropositive group. The risk factors investigated were not related to seroprevalence. It is suggested that Toxocara, among other environmental factors, may stimulate polyclonally immunoglobulin E production, including allergen-specific immunoglobulin E, and thus may contribute to the manifestation of allergic asthma and possibly of eczema in children predisposed to allergy.

Animals↗
PubMed1994

Relation between cytokines and routine laboratory data in children with septic shock and purpura.

OBJECTIVE: To establish the relation between routine laboratory data (lactate, fibrinogen, CRP) and cytokines (TNF,IL-1 and -6) and to estimate their prognostic value in pediatric patients with severe infectious purpura on admission. DESIGN: Prospective study. SETTING: Pediatric intensive care unit (PICU). PATIENTS: 17 children aged 5-172 months (median 46) were hospitalized in our PICU in 1989-90 with severe infectious purpura. Neisseria meningitidis was isolated in 15 children and Haemophilus influenzae in two. The patients were divided into 3 groups: non-shock, shock and severe shock leading to death. Shock was defined by standard criteria. MEASUREMENTS: Arterial blood was sampled for lactate, CRP, fibrinogen, TNF, and IL-1 and -6 on admission. The PRISM (pediatric risk of morality)-score was recorded. METHODS: Statistical analysis was performed with the Student's t-test using the logarithmic values of the cytokine concentration, and Spearman correlation analysis. RESULTS: According to the shock criteria, 9 patients were in shock of whom 4 did not survive. Significant differences existed between the 3 groups concerning lactate, TNF, and IL-6. Fibrinogen, CRP, IL-1, and PRISM-score discriminated only between survivors and non-survivors. A highly significant correlation existed between cytokines, the PRISM-score and lactate (TNF: r = 0.69, IL-1: r = 0.56, IL-6: r = 0.65, PRISM: r = 0.65). A significant inverse correlation existed between cytokines and CRP (TNF: r = -0.55, IL-1: r = -0.64, and IL-6: r = -0.56), and IL-6 and fibrinogen (r = -0.65). CONCLUSION: These results show a significant correlation between cytokines and lactate, and lactate, TNF and IL-6 are closely associated with the severity of septic shock with purpura in children.

Adolescent↗
PubMed1993

Small-cell undifferentiated (neuroendocrine) carcinoma of the cecum in a child with common variable immunodeficiency.

PURPOSE: Patients with primary or secondary immunodeficiencies are known to be at increased risk for the development of malignancies, predominantly of lymphoreticular origin. PATIENTS AND METHODS: We here describe a patient with infant-onset hypogammaglobulinemia due to a common variable immunodeficiency. At the age of 16 a small-cell undifferentiated (neuroendocrine) carcinoma of the cecum (SCUNC) was diagnosed. RESULTS: Neurohormonal analysis showed normal values. CONCLUSIONS: To our knowledge this is the first report in childhood of SCUNC of the gastrointestinal tract, which has also previously not been associated with primary immunodeficiency.

Carcinoma, Small Cell↗
PubMed1991

Abnormal signal transduction in a patient with severe combined immunodeficiency disease.

We have studied an 8-yr-old male patient with adenosine deaminase-positive severe combined immunodeficiency disease with a normal number of peripheral CD3+, T cell receptor-alpha beta+ T cells. The majority of these T cells expressed the CD8 molecule and were oligoclonal in nature as proven by Southern blot analysis of the T cell receptor genes. T cells failed to proliferate in vitro either upon stimulation with T cell mitogens or when stimulated with a combination of the phorbol ester phorbol myristate acetate and the Ca-ionophore ionomycin. High doses of recombinant IL-2, when added to in vitro cultures, were able to restore proliferation induced by phorbol myristate acetate and ionomycin but the response to concanavalin A remained severely defective. However, activation of the patient's T cells with phytohemagglutinin or concanavalin A induced an increase of free cytoplasmic Ca++, which was 2- to 5-fold higher than in normal CD8+ T cells. Furthermore, phorbol myristate acetate or phytohemagglutinin induced the translocation of protein kinase C from cytosol to plasma membrane. Analysis of membrane phospholipid composition of the patient's T cells disclosed that the ratio of phosphatidylcholine to phosphatidylserine was 5-fold higher than in normal T cells. The abnormal Ca++ response after activation with T cell mitogens as well as the high phosphatidylcholine/phosphatidylserine ratio may be causally linked to the defective in vitro T cell proliferation. Because the capacity of T lymphocytes to produce or respond to IL-2 may vary, the oligoclonality of the T cells of the patient should be considered as well in the explanation of defective cell proliferation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1990

Cystic fibrosis, pathophysiological and clinical aspects.

Cystic fibrosis is a lethal, hereditary, until recently little understood disease, which leads to progressive functional disturbances in various organs, including the lungs, liver and pancreas. Knowledge of the genetic and cellular abnormalities is rapidly progressing, but therapy is still symptomatic and based on insufficiently controlled and short-term studies. At present the therapeutic approach aims to combat respiratory infections by optimal antibiotic therapy, combined with techniques to promote sputum evacuation. Additional measures attempt to optimise both nutritional state and physical condition. Median survival has improved from approximately 1 year to about 25 years during the past 3 decades. This article summarises present information on disease mechanisms and treatment.

Cystic Fibrosis↗
PubMed1990

The cystic fibrosis defect approached from different angles--new perspectives on the gene, the chloride channel, diagnosis and therapy.

The search for the basic defect in cystic fibrosis (CF) has reached a decisive stage since the recent identification of the responsible gene. Electrophysiological and biochemical research had defined the CF defect as a dysregulation of epithelial chloride channels. The putative protein product of the now identified gene shares properties with other known transport proteins, but it is not necessarily itself a chloride channel protein. Elucidation of the primary cellular defect will certainly have important aetiological and hopefully therapeutic implications. The identification of the major gene mutation already has significant consequences for genetic counselling and prenatal diagnosis. Heterozygote detection at the population level awaits identification of the probably heterogenous mutations on about 30% of the CF chromosomes. At present, about 50% of CF patients are homozygous for the recently identified major CF mutation.

Chlorides↗
PubMed1990

Determinants and regulating processes in bronchial hyperreactivity.

Bronchial hyperresponsiveness (BHR) can be considered as a feature of asthma, although only a loose relationship is present with symptoms and severity of the disease. Epidemiology of BHR may inform about determining factors in BHR and its role as a risk factor. BHR is found already at a young age, mostly diminishes with age, and increases in many asthmatic patients after midlife. Genetic determinants are suggested by familial segregation and twin studies. Allergy, respiratory infections, and cigarette smoking are found to induce increase in BHR and to modify its degree at the long run. The mechanisms in BHR are being unraveled gradually. A chronic inflammation with an important role for eosinophils, mast cells, and others, is thought to modify bronchial mechanisms, such as smooth muscle, epithelium, and autonomic systems. Growing evidence supports that T lymphocytes are implicated and may determine many of the inflammatory cells, such as eosinophils, neutrophils, and mast cells.

Adolescent↗
PubMed1990

Excessive secretion of antidiuretic hormone in infections with respiratory syncytial virus.

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.

Bronchiolitis, Viral↗
PubMed1990

Relationship between airway obstruction, desaturation during exercise and nocturnal hypoxaemia in cystic fibrosis patients.

We measured pulmonary function, responses to exercise and oxygen saturation (So2) at rest, and also before and during sleep in 24 patients with cystic fibrosis in a varying degree of severity. The pulmonary function indices analysed were forced expiratory volume in one second (FEV1), total lung capacity (TLC), measured by body plethysmography (TLC box) and Helium dilution (TLC He), residual volume measured by body plethysmography (RV) and the amount of trapped air (TA = TLC box-TLC He). The exercise variables included symptom limited maximal oxygen uptake (Vo2max), maximum minute ventilation (VEmax) and So2, at rest in sitting position and during maximal exercise. So2 was measured by ear oximetry. The lowest mean So2 obtained in two consecutive nights over a period of 1 hour was taken as the indicator of nocturnal oxygen saturation. A high correlation existed between resting supine and sitting So2, and the degree of nocturnal hypoxaemia (0.84 and 0.76, respectively). Highly significant correlations existed also for the indices of airway obstruction, Vo2 max and lowest So2 at exercise versus the nocturnal lowest hourly mean So2. From all variables a resting So2 in the sitting position lower than 94% appeared to be most predictive of nocturnal desaturation and indicates a risk of nocturnal hypoxaemia in patients with cystic fibrosis.

Adolescent↗
PubMed1990

[Lung infections with atypical features].

The clinical difference between a lobar pneumonia caused by pneumococci or other bacterial agents and lower respiratory tract infections presenting with atypical symptoms is important. Mycoplasma pneumoniae, chlamydia species, Coxiella burnetii and several viruses amongst others are micro-organisms which cause atypical symptoms. All the time new types of micro-organisms like Ureaplasma urealyticum are found as a cause of pneumonia with atypical symptoms. Special diagnostic tools like cultures, serological or antigen detection are often needed to determine the exact causative agent. Clinical data are important to suspect a specific micro-organism.

Algorithms↗
PubMed1989

[An infant with AIDS].

A four-month-old girl was hospitalized with pneumococcal sepsis from which she recovered. Subsequently she developed various other infectious diseases, including chronic diarrhoea caused by Cryptosporidium. After a period with neurological symptoms, later sagittal sinus thrombosis and cerebral atrophy, she died at age 13 months. It was found that the child suffered from AIDS. The mother was seropositive and the virus had probably been transmitted via the placenta. Rapid recognition of infants and young children with AIDS is necessary, for in the near future more cases of this disease will occur. Antiviral treatment may bring about improvement in children as well.

Acquired Immunodeficiency Syndrome↗