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Biomedical subjects

R de Groot

Publications and source records attributed to R de Groot.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interleukin 12 levels during the initial phase of septic shock with purpura in children: relation to severity of disease.

Plasma levels of interleukin 12 (IL-12), a cytokine consisting of two different polypeptide subunits (p40 and p35), were measured together with interferon gamma (IFN-gamma) and other cytokines in 46 children with septic shock and purpura. The median (range) plasma IL-12 p40 level on admission was 457 (244-2677) pg/ml in non-survivors vs 189 (< 40-521) pg/ml in survivors (P = < 0.001). IL-12 p70 levels were elevated in only nine patients. IL-12 p40 plasma levels were positively correlated with tumour necrosis factor alpha (TNF-alpha), IL-6, IL-8, IL-10 and PRISM-score, whereas they were negatively correlated with C-reactive protein (CRP), whole blood cell (WBC) and serum glucose levels. Twelve (29%) of the patients had detectable levels of IFN-gamma. Thus, circulating levels of IL-12 p40 and to a lesser extent those of IL-12 p70, are elevated in children with septic shock and purpura, and correlate with severity of disease and outcome.

Adolescent↗
PubMed1997

Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations.

OBJECTIVE: Immunophenotyping of blood lymphocytes is an important tool in the diagnosis of hematologic and immunologic disorders. Because of maturation and expansion of the immune system in the first years of life, the relative and the absolute size of lymphocyte subpopulations vary during childhood. Therefore we wished to obtain reference values for the relative and the absolute size of all relevant blood lymphocyte subpopulations in childhood. STUDY DESIGN: We used the lysed whole blood method for analysis of lymphocyte subpopulations in 429 blood samples from neonates (n = 20), healthy children (n = 358), and adults (n = 51). The following age groups were used: 1 week to 2 months (n = 13), 2 to 5 months (n = 46), 5 to 9 months (n = 105), 9 to 15 months (n = 70), 15 to 24 months (n = 33), 2 to 5 years (n = 33), 5 to 10 years (n = 35), and 10 to 16 years (n = 23). RESULTS: Our results show that the absolute number of CD19+ B lymphocytes increases twofold immediately after birth, remains stable until 2 years of age, and subsequently gradually decreases 6.5-fold from 2 years to adult age. The CD3+ T lymphocytes increase 1.5-fold immediately after birth and decrease threefold from 2 years to adult age. The absolute size of the CD3+/CD4+ T-lymphocyte subpopulation follows the same pattern as the total CD3+ population, but the CD3+/CD8+ T lymphocytes remain stable from birth up to 2 years of age, followed by a gradual threefold decrease toward adult levels. In contrast to B and T lymphocytes, the absolute number of natural killer cells decreases almost threefold in the first 2 months of life and remains stable thereafter. Our study also showed that changes in the absolute size of lymphocyte subpopulations are not always consistent with changes in their relative size. This demonstrates that the relative counts of lymphocyte subsets do not reflect their actual size and are therefore of limited value. CONCLUSION: On the basis of this study we strongly recommend that immunophenotyping of blood lymphocytes for the diagnosis of hematologic and immunologic disorders be based on the absolute rather than on the relative size of lymphocyte subpopulations. Our data can be used as age-matched reference values for blood lymphocyte immunophenotyping.

Adolescent↗
PubMed1997

Meningococcal septic shock in children: clinical and laboratory features, outcome, and development of a prognostic score.

The clinical characteristics of and outcome for 75 children with meningococcal septic shock were studied. In addition, a new prognostic scoring system was developed. The median age of the patients was 3.2 years (range, 3 weeks to 17.9 years). The most common phenotype of Neisseria meningitidis was B:4:P1.4 (27%). A mortality rate of 21% was observed. Ten (17%) of the 59 survivors had serious sequelae. Calcium levels were significantly lower in patients with seizures. Disseminated intravascular coagulation occurred in 58% of the patients who were tested. Logistic regression analysis identified four laboratory features independently associated with mortality: serum C-reactive protein level, base excess, serum potassium level, and platelet count. These features were used to develop a novel scoring system with a predictive value for death and survival of 71% and 90%, respectively. The outcome was predicted correctly for 86% of the patients, which is higher than rates previously reported for scoring systems.

Adolescent↗
PubMed1997

Penicillin-resistant Streptococcus pneumoniae in the Netherlands: results of a 1-year molecular epidemiologic survey.

The molecular epidemiologic characteristics of penicillin-resistant pneumococci in the Netherlands were investigated in 1995. Dutch electronic surveillance data showed that 0.7% of all pneumococci were intermediately resistant and 0.4% were highly resistant to penicillin. From March 1995 to March 1996, 89 penicillin-resistant isolates were collected by 39 medical microbiology laboratories. Thirty different genotypes were observed by restriction fragment end labeling. Twenty-one DNA types were unique, whereas 9 distinct genotypes were shared by > or = 2 isolates. Different serogroups were found within 6 of the 9 genetically identical clusters of penicillin-resistant isolates, suggesting that horizontal transfer of capsular genes is common. Finally, nosocomial transmission of penicillin-resistant pneumococci was observed among 21 elderly adults with chronic obstructive pulmonary disease. This study demonstrates that multiple clones of penicillin-resistant pneumococci have been introduced in the Netherlands, a country with a low prevalence of pneumococcal infection. Some clones spread among the population in and outside hospitals.

Aged↗
PubMed1997

Molecular epidemiology of drug-resistant pneumococci: toward an international approach.

An international multicenter study was undertaken to investigate the epidemiological dynamics of penicillin-resistant pneumococci. We compared the molecular epidemiological characteristics of 205 penicillin-resistant isolates originating from The Netherlands, Thailand, United States, Spain, Greece, Poland, Cuba, Germany, Finland, United Kingdom, South Africa, Hungary, Portugal, Croatia, and the Czech Republic. Eighty-four distinct restriction fragment end labeling (RFEL) types were observed. Twenty-eight genetic types were shared by two or more strains. Five genetic clusters consisted of strains originating from different countries, illustrating dissemination of penicillin-resistant pneumococci among countries. The strains displaying the two predominant RFEL types corresponding with the pandemic clones 23F and 9V were found in 10 and 6 different countries, respectively. This clearly demonstrates the pandemic behavior of these two clones. Twelve out of the 28 genetic clusters contained two or more serotypes. This finding indicates frequent horizontal transfer of capsular genes. Within distinct RFEL types, identical penicillin binding protein (PBP) genotypes were often observed, suggesting a high frequency of horizontal transfer of penicillin resistance genes. The most predominant PBP type was found in 15 distinct RFEL types, comprised 44% of the entire collection, and was observed in 11 countries. The vast majority of the strains belonging to the pandemic clones 23F and 9V shared this predominant PBP type. We hypothesize that the clones 23F and 9V are responsible for the worldwide increase of penicillin-resistance, because they serve as a genetic reservoir for susceptible pneumococci to acquire penicillin resistance.

Genotype↗
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↗
PubMed1996

Molecular epidemiological characteristics of pneumococcal meningitis in children.

The molecular epidemiological characteristics of pneumococcal meningitis in children were studied. Pneumococcal isolates were characterized by serotyping and two genotyping methods, BOX fingerprinting and restriction fragment end labeling, to evaluate whether clonal strains were present within the serotypes or serogroups. During a 17-year period, 68 children admitted to the Sophia Children's Hospital were diagnosed with meningitis due to Streptococcus pneumoniae. Pneumococcal isolates from 44 patients were still available for analysis. All strains were susceptible to penicillin. Serotypes/ serogroups 14, 19, 6, and 18 represented 56% of all isolates. The results of the molecular typing methods demonstrate the absence of clonal relatedness between isolates from patients with pneumococcal meningitis.

Child↗
PubMed1996

The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock.

Proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6 and -8), counterinflammatory compounds (IL-10 and soluble TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%) died. Serum levels of pro- and counterinflammatory compounds and plasma levels of plasminogen activator inhibitor (PAI)-1 were significantly higher in nonsurvivors. The interval between appearance of petechiae and blood sampling was shorter in nonsurvivors than in survivors (3.6 +/- 2.4 vs. 6.1 +/- 3.3 h; P = 0.4). This interval correlated strongly with the levels of TNF-alpha, IL-6, -8, and -10, sTNFR-55 and -75, and PAI-1. However, with the exception of PAI-1, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-1 levels correlated with TNF-alpha concentrations (r = .75; P < .001) and were 1.9 (P = .01) times higher in nonsurvivors at a similar TNF-alpha concentration. Thus, an increased PAI-1 response to TNF-alpha may be associated with fatality, probably because of polymorphism of the PAI-1 gene.

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

Influence of maturation and growth on cefetamet pivoxil pharmacokinetics: rational dosing for infants.

The pharmacokinetics of intravenous (i.v.) cefetamet and the bioavailability of oral cefetamet pivoxil in infants aged 3.5 to 17.3 months who were hospitalized for urological surgery were characterized. The absorption of cefetamet pivoxil administered in a syrup formulation was 38 +/- 19% (n = 5) for infants, which was comparable to values observed for children and adults. The plasma half-life of i.v. cefetamet was 3.03 +/- 0.96 h (mean +/- standard deviation; n = 20) in the infants. This was not different from the value observed for normal adult subjects but was longer than that reported for children aged 3 to 12 years. Urinary recovery of cefetamet after i.v. administration to infants was 63.4 +/- 17.7% (n = 16), which was less than the 80% recovery found in older children and adults. The steady-state volume of distribution was 399 +/- 116 ml/kg of body weight. It was comparable in size and showed the same dependence on body weight as it did in children and adults. The mean systemic clearance per kilogram of body weight in the infants was lower than that in children and adults, apparently because of immaturity of clearance processes. A model that accounted for maturation and growth with increasing age was developed for the clearance. On the basis of this model, the clearance capacity increased from birth to 5 years by a factor of 4.5 because of maturation. Maturation progressed exponentially, with a half-life of 14 months. This model was used to develop dosing regimen guidelines for pediatric patients aged 3.5 months and older.

Administration, Oral↗
PubMed1996

Genetic characterization of trimethoprim resistance in Haemophilus influenzae.

We previously demonstrated that trimethoprim (Tmp) resistance in Haemophilus influenzae is mediated by chromosomally encoded dihydrofolate reductase (DHFR) with a modified primary structure and distinct kinetic properties. To gain insight into the relationship of the DHFR structure and the level of Tmp resistance that it confers on the host bacterium, we cloned and characterized the folH genes of one Tmp-susceptible and two Tmp-resistant H. influenzae strains. Differences were observed between Tmp-susceptible and Tmp-resistant isolates both in the promoter region and in the coding sequences. The effect of differences between H. influenzae folH genes on Tmp susceptibility was investigated in Escherichia coli. Various folH gene hybrids were constructed, and their influence on Tmp susceptibility was determined. Resistance in E. coli mediated by folH from H. influenzae strain R1047 was associated with alterations in the promoter and the central part of folH. In contrast, the E. coli Tmp resistance phenotype associated with the folH gene of H. influenzae R1042 was characterized by alterations in one or more of three amino acid residues at the C-terminal part of the protein. These data indicate that Tmp resistance is not only related to alterations in the promoter region of the folH gene and the Tmp binding domains at the N-terminal and central part of DHFR. Alterations in the C-terminal part may also cause Tmp resistance, probably as a result of a change in secondary structure and the subsequent loss of Tmp binding affinity.

Amino Acid Sequence↗
PubMed1996

Novel BOX repeat PCR assay for high-resolution typing of Streptococcus pneumoniae strains.

Typing data obtained by specifically targeting a single, high-stringency PCR at the pneumococcal BOX repeat element for 28 strains of Streptococcus pneumoniae completely corroborated the resolutions attained by five genotypic procedures as described by Hermans et al. (P.W.M. Hermans, M. Sluijter, T. Hoogenboezem, H. Heersma, A. van Belkum, and R. de Groot, J. Clin. Microbiol. 33:1606-1612, 1995). All pairs of strains, except one, derived from both the cerebrospinal fluid and blood of the same individual were shown to be identical. Moreover, other, epidemiologically unrelated isolates were demonstrated to be unique. Considering the combined data from the five typing techniques applied previously as the "gold standard," the single BOX PCR test demonstrated excellent resolving powers while maintaining epidemiological linkage.

Bacterial Typing Techniques↗
PubMed1996

Relationship between clinical severity of respiratory syncytial virus infection and subtype.

The relationship between clinical severity of respiratory syncytial virus (RSV) infection and distribution of subtype A or B was investigated. The data of 232 children, who were admitted with RSV infection or diagnosed in the outpatient department of the Sophia Children's Hospital, Rotterdam between 1992 and 1995, were studied. The diagnosis of RSV was confirmed by a direct immunofluorescence assay. Subtyping was performed by an indirect immunofluorescence assay using specific monoclonal antibodies. Gender, age at diagnosis, gestational age and birth weight, the presence of underlying diseases, feeding difficulties, the presence of wheezing and retractions, respiratory rate, temperature, clinical diagnosis at presentation, oxygen saturation (SaO2), carbon dioxide tension (PCO2), and pH, characteristics of hospitalisation, and the need for mechanical ventilation were observed. Analysis was performed on data from all patients diagnosed with RSV infection in the period between 1992 and 1995 spanning three RSV seasons, and separately on the RSV season 1993-4. The outcome of the three year analysis (150 (64.7%) subtype A v 82 (35.3%) subtype B) was compared with the outcome of the season 1993-4, a mixed epidemic with 37 (60.7%) subtype A and 24 (39.3%) subtype B isolates. None of the variables observed in the season 1993-4 differed significantly between RSV subtype A and B. Similar results were obtained from the analysis in the period 1992 until 1995, with the exception of PCO2 (a higher PCO2 was found in subtype A, p < 0.001) and retractions (more retractions were noted in patients with subtype A, p = 0.03). After correcting for possible confounders using regression analysis, these differences were not significant anymore. The data indicate that there is no relationship between clinical severity of RSV infection and subtype.

Carbon Dioxide↗
PubMed1996

Age-related differences in outcome and severity of DIC in children with septic shock and purpura.

We studied the influence of age on mortality and severity of clotting abnormalities in 79 children (median age: 3.1 years) with meningococcal sepsis. Parameters of coagulation and fibrinolysis and plasma levels of cytokines were prospectively measured on admission. The mortality rate was 27%. The age of survivors was significantly different from that of non-survivors (p = 0.013). With the exception of FVII, vWF and t-PA, parameters of coagulation and fibrinolysis, as well as plasma cytokine levels were related to outcome. Patients were divided in two groups: younger and older than median age. The mortality in children < or = 3.1 years was 40% versus 13% in children > 3.1 years (p = 0.006). In contrast to cytokine levels, which were not different between the two age groups, fibrinogen, prothrombin, factors V, VII, VIII, vWF, protein C, antithrombin, FDP, and the ratio PA1-1/t-PA were related to age, indicating a more severe coagulopathy in children < or = 3.1 years despite a similar degree of inflammatory response. A relative deficiency of coagulation factors due to an immature state of the clotting system, as well as an inadequate fibrinolytic response, both related to age may have caused this more severe coagulative response in younger children, and may have contributed to the higher mortality rate.

Adolescent↗
PubMed1995

[Osteomyelitis as a complication following BCG vaccination].

Osteomyelitis of the proximal femur was diagnosed in a 5-month-old girl after BCG vaccination at the age of 2 weeks. The diagnosis was confirmed by biochemical and molecular techniques (DNA fingerprinting). The girl responded well to antituberculous treatment.

Antitubercular Agents↗