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Biomedical subjects

J L Kimpen

Publications and source records attributed to J L Kimpen.

At least 19 recordsLinked to original sources
PubMed2001

Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity.

To investigate the role of cell-mediated immunity during respiratory syncytial virus (RSV) infection, interferon (IFN)-gamma and interleukin (IL)-10 levels in nasopharyngeal secretions were measured in infants with lower respiratory tract infection (LRTI) caused by RSV. A novel technique was used to measure in vivo cytokine levels in nasopharyngeal aspirates (NPAs). Cytokine levels in the NPAs of 17 mechanically ventilated infants and 43 nonventilated hospitalized infants were compared. As expected, mechanically ventilated infants were significantly younger than nonventilated infants (7 vs. 14 weeks). IFN-gamma levels were above the limit of detection in the NPAs of 3 (18%) mechanically ventilated infants and in the NPAs of 26 (60%) nonventilated infants. IL-10 levels in the NPAs of mechanically ventilated and nonventilated infants were comparable. It is hypothesized that maturation-related mechanisms have a key role in the development of RSV LRTI that results in mechanical ventilation.

Age Factors↗
PubMed2001

Management of respiratory syncytial virus infection.

Although bronchiolitis is the most common viral lower respiratory tract infection in infancy and childhood, and the virus responsible (respiratory syncytial virus) was discovered half a century ago, there is no effective treatment available. The antiviral agent ribavirin has not lived up to expectations and should be reserved for selected cases. Corticosteroids have not been shown to be effective in individual trials, although a recent meta-analysis suggested a mild beneficial short-term effect. Bronchodilators can be used on a trial-and-error basis. Prophylaxis with intravenous immunoglobulins enriched for anti-respiratory syncytial virus antibodies or humanized monoclonal antibodies can reduce the rates of related hospitalization by 50% when used in high-risk patients. However, logistical problems with the administration of intravenous immunoglobulins and the cost of both products preclude their widespread use.

Adrenal Cortex Hormones↗
PubMed2001

Medical consumption and socioeconomic effects of infection with respiratory syncytial virus in The Netherlands.

OBJECTIVE: To calculate both medical consumption and socioeconomic effects related to hospitalization for respiratory syncytial virus (RSV) infection in the Netherlands. METHODS: During the winter seasons of 1998 to 2000, parents of all patients hospitalized for RSV in three secondary care hospitals were asked to fill out questionnaires focusing on the 2 weeks before hospitalization, the period in hospital and the 2 weeks after discharge. The questions concerned workdays lost, level of education and current profession, extra childcare needed, consultation by the family physician and drugs prescribed and costs of travelling. RESULTS: Seventy-three children were hospitalized. Median age was 79 days (range, 9 to 537 days), and median weight was 5,295 g (range, 3130 to 10,600 g). Three children were born preterm. Parents had 2 (range, 0 to 6) telephone contacts with the family doctor; the child was seen 2 (range, 0 to 4) times before hospitalization. Parents lost 0.5 workday before hospitalization. Duration of hospitalization was 5 days median (range, 1 to 12 days). Parents lost 1.5 (range, 0 to 9) workdays during hospitalization and drove 118 (range, 6 to 550) miles to visit their child. In the period after discharge expenses were negligible. Calculation of all parameters into currency resulted in a total amount of $2,200 per child hospitalized for RSV. Workdays lost, costs for travelling and consultation of family doctors resulted in $295 per child. CONCLUSIONS: RSV infections necessitating hospitalization in a secondary care hospital have remarkable effects on parental expenses, parental absence from work and medical consumption. On top of the hospital-related costs 15% should be added for parental expenses and socioeconomic costs.

Absenteeism↗
PubMed2001

Does the empiric use of vancomycin in pediatrics increase the risk for Gram-negative bacteremia?

BACKGROUND: Gram-negative bacteremia in children, a major cause of morbidity and mortality, may in part be induced by intensive treatment procedures and nonspecific use of antibiotics. Our primary objective was to study the causal relationship between the use of vancomycin and Gram-negative bacteremia, for which this antibiotic is not specifically indicated. METHODS: The study was conducted in a 105-bed tertiary care children's hospital in the period of 1994 to 1997. The study pertains to a cohort of children with suspected bacteremia, in whom a blood culture was performed during hospital stay. Using the bacteriologic laboratory registration system, we selected all pediatric cases with bacteriologically proved Gram-negative bacteremia (n = 105) and a random sample of 225 pediatric controls with negative blood cultures. Using logistic regression analysis we examined associations between Gram-negative bacteremia and the following factors: preceding use of antibiotics, antacids, corticosteroids, surgery, mechanical ventilation, parenteral nutrition, and invasive instrumentation; and the intensity of care assessed with the Therapeutic Intensity Scoring System (TISS 28). RESULTS: Gram-negative bacteremia was positively associated with the use of aminoglycosides, cephalosporins, surgical interventions, central venous catheters, parenteral nutrition, antacids and dexamethasone. The strongest association was with the use of vancomycin (odds ratio, 8.1; 95% confidence interval, 3.1 to 20.9). In a multiple logistic regression model containing all above-mentioned variables, the use of vancomycin remained positively and strongly associated with Gram-negative bacteremia (odds ratio, 3.88; 95% confidence interval, 1.34 to 11.21). Further adjustments and restrictions in the analysis did not materially change these findings concerning vancomycin. CONCLUSIONS: Among children suspected of bacteremia there are several drugs and clinical procedures influencing the risk for Gram-negative bacteremia. Empiric use of vancomycin is strongly and independently associated with Gram-negative bacteremia. The safety of using vancomycin solely on the basis of suspicion of bacteremia in children may not be warranted.

Adrenal Cortex Hormones↗
PubMed2001

Airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing.

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to RSV LRTI. OBJECTIVE: To determine clinical predictors for airway morbidity after RSV LRTI. METHODS: In a 1-year follow-up study we investigated the predictive value of auscultatory findings characteristic of airflow limitation (wheezing) during RSV LRTI for subsequent airway morbidity. Clinical characteristics, including the presence or absence of signs of airflow limitation, of hospitalized infants with RSV LRTI were prospectively recorded during 2 winter epidemics. During a 1-year follow-up period parents of 130 infants recorded daily airway symptoms. OUTCOME MEASURE: Recurrent wheezing defined as > or = 2 episodes of wheezing. RESULTS: Signs of airflow limitation during RSV LRTI were absent in 47 (36%) infants and present in 83 (64%) infants. Recurrent wheezing was recorded in 10 (21%) infants without signs of airflow limitation and in 51 (61%) with signs of airflow limitation during initial RSV LRTI (relative risk, 0.29, P < 0.001). In a multiple logistic regression model, airflow limitation during initial RSV LRTI proved independent from other clinical parameters, including age, parental history of asthma and smoke exposure. CONCLUSIONS: A sign of airflow limitation during RSV LRTI is the first useful clinical predictor for subsequent recurrent wheezing.

Auscultation↗
PubMed2001

Once-daily versus multiple-daily gentamicin in infants and children.

In this prospective randomized trial, the efficacy and safety of once-daily administration of gentamicin were compared with multiple-daily administration in infants and children. In addition, pharmacokinetic variables were calculated. Gentamicin therapy was started at a dose of 5 mg/kg per day under individual dose or dosage interval adjustments to achieve target levels. Fifty-two infants and children aged 1 month (postterm) to 16 years were enrolled. The duration of fever from the start of therapy, the percentage decline of C-reactive protein (CRP) on day 3 of treatment, and the clinical outcome were used as efficacy parameters. Nephrotoxicity was evaluated using creatinine serum levels. Basic characteristics in both groups were comparable. A good clinical response was observed in both groups. Fever may have resolved faster with multiple-daily administration, but this was not statistically significant. The percentage of decline of CRP was also comparable in both groups. Nephrotoxicity occurred in six patients, three per group. Many patients were too ill or too young to perform hearing tests, but no clinical signs of ototoxicity were observed. Mean doses of 6.8 mg/kg per day (multiple-daily administration) and 7.3 mg/kg per day (once-daily administration) were necessary to meet the target gentamicin levels. Triple-daily doses had to be reduced to a twice-daily regimen in 17 of 26 children. Dose and dosage interval adaptations can be performed by Bayesian forecasting using a one-compartment model with one set of K(e) and V(d) parameters. The authors consider both regimens equally effective, with a comparable incidence of nephrotoxicity. A starting dose of 6.5 mg/kg once daily is advised.

Adolescent↗
PubMed2001

Respiratory tract infections caused by respiratory syncytial virus in children. Diagnosis and treatment.

Respiratory syncytial virus (RSV) is the most common viral cause of lower respiratory tract infection in infancy and young children. No effective treatment for RSV lower respiratory tract infection (RSV-LRTI) exists. Ribavirine initially was reported to be an effective anti-viral drug for RSV-LRTI. However, subsequently performed trials could not reproduce these positive results and based on the current available evidence there is no place of ribavirin in the routine treatment of RSV-LRTI. The use of nebulised bronchodilator therapy in RSV-LRTI has been subject of many trials, with conflicting RESULTS. Although the individual patient may have some short term benefit of nebulised bronchodilators there does not seem to be a sufficient scientific base for the standard use of bronchodilator therapy in infants and children with RSV-LRTI. There is increasing evidence that RSV-LRTI is an immune-mediated disease and therefore corticosteroids may be an effective treatment. The results from efficacy trials have demonstrated that corticosteroids are not effective for patients with mild RSV infection. In contrast, there is some evidence suggesting that it may be beneficial in patients with more severe RSV-LRTI. Immunoprofylaxis with hyperimmune immunoglobulins and monoclonal antibody against the viral F-protein have been shown to be effective in the prevention of severe RSV-LRTI. From the results of the therapeutic efficacy trials, however, it is evident that immunoglobulins have no place in the treatment of RSV-LRTI. In conclusion, although RSV infections each year have a considerable socio-economic impact attempts to find an effective therapy have been quite unsuccessful so far.

Adrenal Cortex Hormones↗
PubMed2000

Vascular endothelial growth factor in bacterial meningitis: detection in cerebrospinal fluid and localization in postmortem brain.

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of VEGF during bacterial meningitis, VEGF was measured in cerebrospinal fluid (CSF) and blood of 37 patients with bacterial meningitis and 51 control patients, including 16 patients with viral meningitis. Circulating VEGF levels were similar in bacterial meningitis patients and control patients. VEGF(CSF) was detected in 11 (30%) of 37 of bacterial meningitis patients (range, <25-633 pg/mL) but in none of the control patients. The median VEGF index was 6.2 (range, 0.6-42), indicating intrathecal production. Median CSF cell counts, protein levels, and CSF: serum albumin ratios were higher for patients with detectable VEGF(CSF), although the difference was not statistically significant. VEGF immunoreactivity in autopsy brain specimens was found in the inflammatory infiltrate of patients with bacterial meningitis. These results indicate that inflammatory cells secrete VEGF during bacterial meningitis and that VEGF may contribute to blood-brain barrier disruption.

Adolescent↗
PubMed2000

Monocyte interleukin-12 production is inversely related to duration of respiratory failure in respiratory syncytial virus bronchiolitis.

The correlation of clinical and immunological parameters with the duration of respiratory failure was investigated to identify factors determining the clinical outcome of respiratory syncytial virus (RSV) bronchiolitis necessitating mechanical ventilation. At initiation of mechanical ventilation in 30 patients with RSV, production of interleukin (IL)-12 and IL-10 was measured in 48-h peripheral blood cell cultures that were stimulated with lipopolysaccharide and interferon-gamma. The ventilation index (VI)-an indicator of respiratory dysfunction that includes partial pressure of arterial CO2, peak airway pressure, and respiratory rate-correlated with the duration of mechanical ventilation (r=.47; P=.013). Age was not associated with the duration of mechanical ventilation. A highly significant inverse correlation was found between the duration of mechanical ventilation and the production of IL-12 at admission (r=-.62; P<.001). This correlation was independent of VI. No correlation was found between IL-10 production and the duration of mechanical ventilation. It is hypothesized that low monocyte IL-12 response during initial RSV infection adversely affects clinical outcome of patients with severe RSV bronchiolitis.

Bronchiolitis↗
PubMed2000

[Respiratory syncytial virus infections and preventive options].

Respiratory syncytial virus (RSV) is the most prominent pathogen found in respiratory tract infections in children and the most important cause of bronchiolitis in the first two years of life. In the Netherlands approximately 2000 children are admitted each winter season. A serious course is mostly seen in children younger than 3 months, (ex-)prematures, children with bronchopulmonary dysplasia or congenital cardiac anomalies, children with cystic fibrosis younger then 2 years and children with impaired T cell immunity; such cases not rarely require intensive care. Treatment (fluid, nutrition, bronchodilator agents, corticosteroids, oxygen and ventilation) is usually symptomatic. Antiviral therapy is only indicated in immunodeficient patients. For prevention by passive immunization palivizumab was recently registered in the Netherlands, a monoclonal antibody against RSV that has to be administered intramuscularly from the start of the RSV season (15 mg per kg bodyweight once a month during five months). In a number of large-scale American multicenter studies both the number of hospital admissions related to RSV infection and the mean duration of hospital stay showed a statistically significant reduction in high-risk children who had been treated with palivizumab. Palivizumab appears to be indicated in children from the categories with an increased risk for serious RSV disease.

Antibodies, Monoclonal↗
PubMed2000

Novel pathways in the pathogenesis of respiratory syncytial virus disease.

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory infections in infants and children. Extensive research in past decades has expanded our knowledge regarding the specific mechanisms involved in the pathogenesis of RSV bronchiolitis and subsequent chronic obstructive airway disease. Studies of RSV infection are performed in humans, cell culture models, and animal models, each with their own specific limitations. A recently developed murine model in which pulmonary dysfunction can be monitored and quantified appears to add a powerful tool for the study of specific pathogenic mechanisms of experimental RSV infections. Both immunologic and nonimmunologic factors have been implicated in the pathogenesis of RSV-induced diseases. Recently, a hypothesis that RSV bronchiolitis may be the result of production of Th2-type cytokines has become popular. There are, however, studies in human infants with RSV as well as in RSV-infected mice that suggest this theory is incorrect, or at least an oversimplification. There is compelling evidence that cells producing interferon gamma may contribute to RSV-induced wheezing, possibly through induction of leukotriene release. Among the nonimmunologic factors, pulmonary surfactant has recently attracted attention, especially because of the therapeutic implications for infants with severe bronchiolitis. A better understanding of the pathogenesis of RSV-induced diseases will be of considerable help in developing specific therapeutic strategies and in vaccine development.

Animals↗
PubMed2000

Long-term effects of prednisolone in the acute phase of bronchiolitis caused by respiratory syncytial virus.

Follow-up studies have demonstrated that bronchiolitis caused by respiratory syncytial virus (RSV) is strongly associated with wheezing in the ensuing years. During the acute infection the immune response may induce long-lasting detrimental effects, thereby contributing to post-bronchiolitis wheezing (PBW). Therefore, immune-modulating drugs like corticosteroids, administered in the acute phase of RSV bronchiolitis, may prevent PBW and asthma. To evaluate this, we performed a controlled prospective follow-up study after a randomized double-blind placebo-controlled intervention in the acute phase with oral prednisolone. Fifty-four patients under 2 years of age and hospitalized for RSV bronchiolitis between 1992 and 1995 were randomly assigned to prednisolone 1 mg/kg/day for 7 days or placebo. At the mean age of 5 years, 47 patients had completed their follow-up. Patients were divided into four groups: no wheezing, transient wheezing (wheezing during the first year of life); persistent wheezing (wheezing during the first year of life and asthma at the age of 5); and late-onset wheezing (no wheezing during the first year of life but asthma at the age of 5). Prevalence of wheezing and asthma were investigated through an interview by telephone, using a standardized questionnaire. We found no significant differences between the prednisolone- and the placebo-treated group in the number of patients with transient wheezing (8% vs. 17%), persistent wheezing (42% vs. 31%), or late-onset wheezing (17% vs. 13%). We conclude that oral prednisolone during the acute phase of RSV bronchiolitis is not effective in preventing PBW or asthma at the mean age of 5 years. Pediatr Pulmonol. 2000; 30: 92-96.

Acute Disease↗
PubMed2000

Intrinsic capacity of monocytes to produce cytokines ex vivo in patients with acute lymphoblastic leukaemia.

Monocytic cytokine profiles of fifteen children with acute lymphoblastic leukaemia (ALL) were included to determine whether malignancy per se contributes to impaired cytokine profiles in vivo and ex vivo. The ex vivo tumour necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta) production was positively correlated with the monocyte number and with the number of intracellular TNF-alpha or IL-1beta positive cells in lipopolysaccharide (LPS)-stimulated MNC cultures. The mean ex vivo TNF-alpha and IL-1beta production per 1x10(4)monocytes in these cultures was not significantly different in children at diagnosis of ALL, at remission or in controls. High IL-10 plasma levels at diagnosis of ALL had no effect on the ex vivo TNF-alpha and IL-1beta production of monocytes in LPS stimulated MNC cultures. These results show that monocytes of ALL patients have a normal intrinsic capacity to produce cytokines ex vivo. However, the decreased monocyte number is responsible for the lower TNF-alpha and IL-1beta concentrations ex vivo upon LPS stimulation.

Adolescent↗