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Biomedical subjects

H J Neijens

Publications and source records attributed to H J Neijens.

At least 55 records · Page 3Linked to original sources
PubMed1997

Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis.

To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis.

Adolescent↗
PubMed1997

Local variability in respiratory syncytial virus disease severity.

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.

Age Distribution↗
PubMed1997

Sample size estimation in studies monitoring exercise-induced bronchoconstriction in asthmatic children.

BACKGROUND: The repeatability of the response to standardised treadmill exercise testing using dry air and monitoring of heart rate in asthmatic children suffering from exercise-induced bronchoconstriction (EIB) has not been well established. METHODS: Twenty seven asthmatic children with known EIB performed standardised exercise testing twice within a period of three weeks. The tests were performed on a treadmill while breathing dry air. During both tests heart rate had to reach 90% of the predicted maximum. Response to exercise was expressed as % fall in forced expiratory volume in one second (FEV1) from baseline and as area under the curve (AUC) of the time-response curve. RESULTS: The intra-class correlation coefficients for % fall and AUC (log-transformed) were 0.57 and 0.67, respectively. From these data, power curves were constructed that allowed estimations to be made of sample sizes required for studies of EIB in children. These indicated that, if a drug is expected to reduce EIB by 50%, as few as 12 patients would be sufficient to demonstrate this effect (90% power) using a parallel design study. CONCLUSIONS: Standardised exercise testing for EIB using dry air and monitoring of heart rate is adequately repeatable for use in research and clinical practice in children with asthma.

Adolescent↗
PubMed1996

Interleukin-10 and soluble tumor necrosis factor receptors in cerebrospinal fluid of children with bacterial meningitis.

The antiinflammatory mediators interleukin (IL)-10 and soluble tumor necrosis factor (TNF) receptors p55 (sTNFR-55) and sTNFR-75 in cerebrospinal fluid (CSF) from 37 children with bacterial meningitis were studied. CSF concentrations of IL-10, sTNFR-55, and sTNFR-75 and of the proinflammatory cytokines TNF-alpha, IL-6, and IL-8 were markedly elevated and were, with the exception of the sTNFRs, significantly higher in CSF than in serum. CSF concentrations of sTNFR- 55 and sTNFR-75 were only associated positively with IL-10 levels. CSF glucose levels correlated highly with levels of IL-10, sTNFR-55, and sTNFR-75 and weakly with TNF-alpha and IL-6. Cytokine levels in CSF decreased rapidly, while sTNFR levels remained elevated for at least 24 h.

Adolescent↗
PubMed1996

The role of nitric oxide in bacterial meningitis in children.

To investigate the role of nitric oxide (NO) in bacterial meningitis, concentrations in serum, cerebrospinal fluid (CSF), or both of the precursor (L-arginine) and degradation products of NO (nitrate, nitrite) and tumor necrosis factor (TNF)-alpha were measured in 35 patients and 30 controls. CSF nitrate levels were significantly elevated, mainly due to increased blood-brain barrier permeability, and are therefore not a good parameter for gauging endogenous NO production in the CSF compartment. CSF NO/nitrite levels were significantly elevated in patients. NO/nitrite levels decreased over time (26%/6 h; P < .001). CSF levels of NO/nitrite correlated with those of TNF-alpha (r = .55; P = .001) and glucose (r = -.43; P = .02). CSF levels of L-arginine were lower in patients than in controls (P < .001). Dexamethasone did not exert a significant effect on NO metabolism. In conclusion, enhanced NO production may contribute to anaerobic glycolysis and neurologic damage in bacterial meningitis.

Adolescent↗
PubMed1996

Occurrence of a late response to exercise in asthmatic children: multiple regression approach using time-matched baseline and histamine control days.

At the present time, there is still controversy concerning the presence of a late asthmatic response (LAR) to exercise challenge in asthma. We have, therefore, investigated the occurrence of a LAR after exercise in asthmatic children visiting an out-patient clinic, using time-matched baseline and histamine control days, and a statistical analysis according to recently published recommendations. After a screening exercise day, 17 children (aged 7-14 yrs) randomly performed, on three subsequent study days, either: a second standardized exercise challenge; or a histamine challenge whilst matching the bronchoconstriction after exercise; or measurement of baseline lung function without any challenge. Measurements of forced expiratory volume in one second (FEV1) were made repeatedly during 8 h. Analysis was performed using multiple regression analysis for each patient, with FEV1 as the dependent, and test day (exercise or control) and clock time as independent variables during the period 2-8 h after exercise. A significant interaction (p < 0.05) between test day and clock time was considered to be indicative of a LAR. Fifteen children completed the study. All children showed an early asthmatic reaction to exercise (range 14-62% fall in FEV1). In two children, a significant interaction (p < 0.05) was found between test day and clock time. However, the difference in FEV1 between exercise and control days for each clock time did not exceed the 99.6% confidence limits of normal diurnal variation in any of the children. We conclude that, in children with mild-to-moderate asthma, a LAR to exercise does not occur. This suggests that exercise is only a symptomatic trigger of asthma. Whether exercise is capable of inducing inflammation needs to be further investigated.

Asthma, Exercise-Induced↗
PubMed1996

Development of immune functions related to allergic mechanisms in young children.

The newborn immune system differs quantitatively and functionally from that of adults. Development of the immune system has important implications for childhood diseases. The immaturity of the immune system in the first years of life may contribute to failure of tolerance induction and in the development of allergic disease. T cell function is diminished, especially the capacity to produce cytokines; production of interferon (IFN)-gamma, and IL-4 is strongly reduced. IFN-gamma has been found to be even lower in cord blood of newborns with a family history of atopy. Differences in other cell types (natural killer cells, antigen-presenting cells, and B cells) could also play a role in the development of allergic disease. Current data suggest that irregularities in IgE synthesis, helper T cell subsets (Th1, Th2, CD45RA, and CD45RO), cytokines (IL-4, IFN-gamma), and possibly other cell types may play a role in the development of allergy in childhood. Moreover, the role of cell surface molecules, like co-stimulatory molecules (CD28, CD40L), activation markers (CD25), and adhesion molecules (LFA-1/ICAM-1, VLA-4/ VCAM-1) is also discussed. These variables are modulated by genetic (relevant loci are identified on chromosome 5q, 11q, and 14) and environmental forces (allergen exposure, viral infections, and smoke). The low sensitivity of current predictive factors for the development of allergic diseases, such as cord blood IgE levels, improves in combination with family history and by measurement of in vitro responses of lymphocytes and skin reactivity to allergens. New therapeutic approaches are being considered on the basis of our current understanding of the immunopathology of allergic disease, for instance cytokine therapy and vaccination with tolerizing doses of allergen or peptides.

Child↗
PubMed1995

Staphylococcal pneumonia in childhood: will early surgical intervention lower mortality?

Staphylococcus aureus pneumonia (SAP) continues to be a serious bacterial infection which is associated with a high incidence of complications. We retrospectively reviewed the case records of 36 infants and children admitted with SAP to the Sophia Children's Hospital between 1970 and 1992 to analyse changes over time in the clinical presentation, diagnostic work-up, management and complications. Fifteen of these 36 children (42%) were less than 1 year old. Fever (97%) and respiratory distress (83%) were the most common symptoms at the initial presentation. Chest X-ray findings on admission or during hospitalisation included pleural effusion (75%), pneumothorax (47%), and abscess and/or pneumatocele (39%). Diagnostic and/or therapeutic thoracentesis of pleural fluid was performed in 17 of the 36 patients (47%). Twenty-one patients (58%) needed chest tube drainage. Twelve had a thoracotomy (33%). Artificial ventilation was needed in 13 of the patients (36%). Extrapulmonary complications included convulsions in 6 patients (17%) and osteomyelitis in 2 children (6%). The mean duration of hospitalization was 36 days. Two of the 36 children died (6%). The low mortality rate in this study may be the result of the relatively high rate of thoracotomy and of improvements in supportive treatment.

Child↗
PubMed1995

Prolonged recovery from exercise-induced asthma with increasing age in childhood.

It has been suggested that children with asthma recover more quickly from exercise-induced bronchoconstriction than adults. On the basis of clinical observation we hypothesized that recovery rate from exercise-induced asthma (EIA) in childhood also decreases with age. In 14 children (aged 7-12 years) with a history of EIA, we measured spontaneous recovery from bronchoconstriction induced by two different stimuli: exercise and histamine. The children visited the laboratory three times. After a screening exercise test on the first visit, standardized bronchoprovocation tests with either exercise or histamine were performed on the following two visits in random order. The degree of bronchoconstriction induced by histamine was matched for that observed after exercise. During recovery, forced expiratory volume in 1 second (FEV1) was measured repeatedly up to 2 hours postchallenge. The recovery rate (% increase in FEV1/min) was calculated from the linear slope of the time-response curve. Differences in recovery rate between the two stimuli were analyzed by paired t-test, and age-related differences were analyzed using multiple regression analysis. For the group as a whole, recovery rate was not different between the two stimuli (mean +/- SD: 1.22 +/- 0.91 for exercise, and 1.46 +/- 0.65, for histamine, P = 0.31). However, the recovery rate for exercise-induced bronchoconstriction decreased significantly with age (r = -0.74, P = 0.003), in contrast to the recovery rate for histamine (r = -0.15, P = 0.60). Consequently, in the oldest age group (11-12 years, n = 5) recovery rate from exercise challenge was significantly slower than in the younger age group (7-10 years, n = 9), i.e., 0.54 +/- 0.17 and 1.60 +/- 0.93, respectively, P = 0.009, and slower than the recovery rate from histamine challenge: 0.54 +/- 0.17 and 1.33 +/- 0.54, respectively, P = 0.03. In the younger age group the recovery rates from exercise and histamine were not different (1.60 +/- 0.93 and 1.54 +/- 0.73, respectively, P = 0.83). We conclude that recovery from EIA in childhood decreases with increasing age. These data suggest that the mechanism of exercise-induced asthma in childhood changes with age. This might be due to changes in mediator production or response to mediator release.

Age Factors↗
PubMed1995

Bacterial meningitis: mechanisms of disease and therapy.

Bacterial meningitis continues to be a serious infectious disease with a high morbidity and mortality in young children. Early recognition and initiation of adequate treatment are the major determinants for a good outcome. Recent advances in our understanding of the host inflammatory response by cytokines may result in the use of new therapeutic strategies. Such modulation of the inflammatory response may reduce the incidence of sequelae and death. The use of steroids as adjunctive therapy in children with bacterial meningitis probably has beneficial effects although the available data are still controversial. Additionally, studies in experimental meningitis models indicate that non-steroidal anti-inflammatory drugs and monoclonal antibodies against bacterial products, cytokines and CD18 on leucocytes reduce the extent of the meningeal inflammation. Human studies to evaluate the efficacy of these immune modulators are expected to start soon. However, prevention of bacterial meningitis by conjugate vaccines against Streptococcus pneumoniae and Neisseria meningitidis will be the most promising development in the next decade.

Humans↗
PubMed1995

Ceftazidime pharmacokinetics in preterm infants: effects of renal function and gestational age.

OBJECTIVE: The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life. METHODS: Multiple-dose pharmacokinetics of ceftazidime (administered twice daily in a 25 or 50 mg/kg body weight intravenous dose) were evaluated in 136 preterm infants on day 3 of life. Blood samples were collected from an arterial catheter 0, 1/2, 1, 2, 4, 8, and 12 hours after the intravenous dose. An HPLC method was used to determine ceftazidime concentrations in serum. The GFR was studied simultaneously by means of the 24-hour continuous inulin infusion technique. RESULTS: The total body clearance, volume of distribution, and elimination serum half-life of ceftazidime (mean +/- SD) were 55.7 +/- 34.4 ml/hr (37.3 +/- 11.9 ml/hr/kg), 496 +/- 228 ml (350 +/- 96 ml/kg), and 6.95 +/- 2.32 hours, respectively. The mean +/- SD peak and trough levels were 114.9 +/- 39.4 and 33.9 +/- 17.8 mg/L. All infants had a serum trough level above 5 mg/L. Clearance and volume of distribution of ceftazidime and GFR increased significantly with increasing gestational age, whereas serum trough levels and serum half-life of ceftazidime decreased significantly with increasing gestational age. Ceftazidime clearance increased significantly with increasing GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values and ceftazidime clearances. CONCLUSIONS: Dosage recommendations for ceftazidime administration in preterm infants during the first week of life should be based on gestational age and GFR. Additional adjustments in dosage are indicated in preterm infants who are exposed prenatally to indomethacin.

Ceftazidime↗
PubMed1995

The treatment of chronic sinusitis: a controversial issue.

The persistence of sinusitis after upper respiratory tract infection is influenced by a range of aetiological factors such as anatomical variation which may be surgically corrected, mucociliary abnormalities and immune deficiency. The latter is more common than previously realised, encompassing IgG subclass deficiency, reduced opsonization and Fc gamma receptor polymorphism. This has therapeutic implications, with the possibility of IgG replacement therapy and vaccination. CT scanning suggests that the age of the patient and anatomical abnormalities are important aetiological factors in chronic rhinosinusitis. Only when medical therapy fails, is surgery considered. Although a range of surgical procedures are available, an endoscopic approach may be directed at the ostiomeatal complex and is generally very conservative. Scanning is a prerequisite to this surgery, demonstrating both the extent of disease and the anatomy but requires careful interpretation. Furthermore, an endoscopic technique can be employed for a number of other sinus conditions though this should only be undertaken by an experienced surgeon. A long-term prospective study of children undergoing radical sinus surgery for neoplasia strongly suggests that concerns that surgery in the middle meatus might disturb subsequent facial development are unfounded.

Adolescent↗
PubMed1995

Pneumococcal meningitis in children: prognostic indicators and outcome.

We studied the outcome of pneumococcal meningitis in 83 children who were admitted to a referral hospital and whose meningitis was diagnosed between 1970 and 1994. The median age of the children was 8 months. The most frequently isolated capsular serotypes and/or serogroups of Streptococcus pneumoniae were 6, 14, 18, 19, and 23. Twenty-nine children (35%) were referred by other hospitals. A mortality rate of 17% (primary referrals, 7%; secondary referrals, 35%) was observed. At discharge, 25 survivors (36%) had sequelae: hearing loss (> or = 30 dB) in 19% and neurological sequelae in 25%. During admission, the presence of coma, respiratory distress, shock, a cerebrospinal fluid (CSF) protein level of > or = 2.5 g/L, a peripheral white blood cell count of < 5 x 10(9)/L, and a serum sodium level of < 135 mmol/L were associated with mortality. Sequelae were associated with the presence of coma and a CSF glucose level of < 0.6 mmol/L. We conclude that the mortality rate of pneumococcal meningitis is lower among children than among adults. Children often die of neurological sequelae, while adults frequently die of cardiorespiratory failure due to underlying diseases. For children, coma, respiratory distress, and shock during admission were the clinical findings with the strongest predictive value for sequelae or death.

Age Factors↗
PubMed1995

Density of eosinophils reflects activity of disease in allergic asthmatic children.

BACKGROUND: Low density eosinophils are more prominent in asthmatic patients compared with healthy subjects. LDE are metabolically more active and produce more tissue-injuring and spasmogenic proteins than normal eosinophils. OBJECTIVE AND METHODS: With a method providing information about eosinophils of 12 different densities we were able to study eosinophil density characteristics in 24 young patients in detail with allergic asthma in a stable phase, and in 21 patients after a bronchial allergen challenge. RESULTS: Study of the eosinophil density profile of patients and healthy controls revealed two density populations. Patients had more low density eosinophils than controls. In the patients eosinophil density characteristics and in particular the number of low density eosinophils correlated strongly with both FEV1% predicted (p = -0.66, P < 0.001) and FEV1/FVC (p = -0.47, P < 0.01) as well as with bronchial responsiveness to histamine (p = -0.68, P < 0.001) and house dust mite (p = -0.37, P < 0.05). Allergen induced bronchial reactions were associated with an increase in the number (P < 0.001) and percentage (P < 0.05) of low density eosinophils. A selective rise in the number of eosinophils collected from fractions with a low density accounted for the observed rise in the total number of eosinophils. Density changes did not differ between patients with an isolated early reaction and patients with both an early and a late reaction, nor was there a relation between the severity of the late reaction and the shift in eosinophil density. CONCLUSION: In conclusion, peripheral blood eosinophil density characteristics and in particular numbers of low density eosinophils are closely related with indicators of the asthma severity under stable conditions. Allergen inhalation induces a further shift towards lower density suggesting additional activation of the eosinophils.

Adolescent↗
PubMed1995

Once-daily versus twice-daily administration of ceftazidime in the preterm infant.

Ceftazidime pharmacokinetics in 28 preterm infants (gestational ages, 25.6 to 31.9 weeks) were studied on day 3 of life. Patients with suspected septicemia were randomized on day 1 of life in two groups. One group (n = 13) was administered 25 mg of ceftazidime per kg of body weight once daily, and the other (n = 15) was given 25 mg of ceftazidime per kg twice daily. Both groups also received 25 mg of amoxicillin per kg twice daily. Blood samples were collected on day 3 of life with an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an intravenous bolus injection. An additional blood sample was taken at 24 h from the group dosed once a day. High-performance liquid chromatography was used to determine serum ceftazidime concentrations. The pharmacokinetics of ceftazidime were best described by using a one-compartment model. The half-life for the elimination of the drug from serum, apparent volume of distribution, total body clearance of ceftazidime, and inulin clearance were not significantly different for both groups. The ceftazidime/inulin clearance ratio was 0.72 for both groups. However, trough concentrations in serum for the twice-daily group were significantly (P < 0.001) higher (42.0 +/- 13.4 mg/liter) than those for the once-daily group (13.1 +/- 4.7 mg/liter). The latter concentrations were all still substantially higher than the MIC of ceftazidime for major neonatal pathogens. We conclude that the currently recommended dosage of 25 mg of ceftazidime per kg twice daily for preterm infants with gestational ages below 32 weeks may be adjusted during the first days of life to one daily dose at 25 mg/kg, provided that for the empirical treatment of septicemia, amoxicillin at 25 mg/kg is also given twice daily.

Ceftazidime↗