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R de Groot

Publications and source records attributed to R de Groot.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Fever of unknown origin in a young child: diagnosis and treatment].

In children with fever without focus, evaluation should be aimed at recognition of children with an increased risk of bacteraemia or of major bacterial infections, while young children in particular will show few typical symptoms of bacterial infections. A child younger than 1 month with fever (> or = 38.0 degrees C) or hypothermia (< 36.0 degrees C) needs clinical evaluation and additional diagnostic investigations. In children aged from 1 to 36 months referral to hospital should be based on presence of age specific clinical characteristics, i.e. toxic appearance, high fever, diarrhoea, decreased urine production, tachypnoea, or bulging fontanelle. Presence of clinical characteristics as judged by a paediatrician or abnormal laboratory findings indicates hospitalisation and treatment with parenteral antibiotics. Absence of alarming clinical characteristics with normal laboratory values justifies outpatient follow-up without treatment or additional diagnostic procedures. Careful instructions to parents regarding observation, parents' ability to detect clinical changes and facilities for rapid medical re-evaluation are crucial.

Algorithms↗
PubMed1999

Analysing the developing lymphocyte system of neonates and infants.

UNLABELLED: Technical developments in immunophenotyping and function testing have greatly facilitated studies on the developing lymphocyte system in the past decade and contributed to a better interpretation of the data obtained in these studies. This is important for the correct interpretation of data obtained in paediatric patients with possible immunological diseases. The age-related differences in lymphocyte subpopulations and function imply that the available adult reference values cannot be used in children. CONCLUSION: In this review we give an outline of the technical developments, their influence upon the interpretation of data, and the available literature about age-related changes in the developing lymphocyte system.

Humans↗
PubMed1999

Influenza virus serology--a comparative study.

Virus isolation or influenza virus antigen detection are the most rapid tests for diagnosis in the acute stage of influenza virus infection. As serology is easier to carry out, the synthesis of serum IgM, IgA and IgG was studied in two well-defined patient groups, infected with influenza B virus (cohort 1, n = 37) and influenza A virus (cohort 2, n = 40), diagnosed by antigen detection and/or virus isolation within 36 h after onset of symptoms. IgM was found in 13 influenza B patients (35%), IgA in 12 patients (32%), whereas a significant antibody rise was found in 33 patients (92%) by enzyme-linked immunosorbent assay (ELISA) and 74% by haemagglutination inhibition assay (HAI). For the influenza A cohort these numbers were respectively 18 (45%), 27 (68%) and 24 (62%) HAI (72%). In age-matched controls, who were bled on the first day of illness of the enrolled patient low prevalence was found for IgA and IgG, for influenza B respectively in 2 and 18%, and for influenza A in 4 and 39%. Studying the kinetics of the antibody response, we found that virus specific IgA and the bulk of IgG is synthesised within the first week of the infection. It is concluded that the finding of a specific serum IgA is highly indicative of an acute influenza infection.

Adolescent↗
PubMed1999

Hospital-related outbreak of infection with multidrug-resistant Streptococcus pneumoniae in the Netherlands.

Multidrug-resistant strains of Streptococcus pneumoniae were isolated over a two-year period (July 1995 until August 1997) from the sputum of 36 patients who were hospitalized in a Dutch medical centre. Nosocomial transmission was confirmed by typing of the bacterial isolates: all 36 multidrug-resistant isolates shared the same genotype, serotype, and displayed overlapping drug resistance profiles. Thirty-two of the 36 (89%) patients had chronic obstructive pulmonary disease (COPD). The outbreak was initiated by a 76-year old patient, who had been colonized with the same strain since 1993. Because staff screening of the hospital and pulmonary function department was negative, patient-to-patient spread was the most likely cause of this outbreak. The epidemic ceased following the commencement of barrier nursing, a treatment course of ceftriaxone, and a five-day rifampicin eradication therapy for the positive patients. The outbreak resulted from failure to recognize quickly the rapid transmission of this multidrug-resistant pneumococcal clone. We conclude that patients with COPD are at high risk of acquiring multidrug resistant pneumococci, and suggest that COPD patients who are colonized or infected with multidrug-resistant pneumococci should be isolated to prevent future transmission.

Aged↗
PubMed1999

Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections.

The efficacy and safety of zanamivir, administered 2x or 4x daily over 5 days, was evaluated in the treatment of influenza infections. A total of 1256 patients entered the study; 57% of those randomized had laboratory-confirmed influenza infection. The primary end point, "alleviation of major symptoms," was created to evaluate differences in clinical impact. In the overall population with or without influenza infection, zanamivir reduced the median number of days to reach this end point by 1 day (P=.012 2x daily vs. placebo; P=.014 4x daily vs. placebo). The reduction was greater in patients treated within 30 h of symptom onset, febrile at study entry, and in defined high-risk groups. Zanamivir reduced nights of disturbed sleep, time to resumption of normal activities, and use of symptom relief medications. It was well tolerated. These results suggest that zanamivir can significantly reduce the duration and overall symptomatic effect of influenza.

Adult↗
PubMed1999

Multidrug-resistant Streptococcus pneumoniae in Poland: identification of emerging clones.

Penicillin resistance among Streptococcus pneumoniae isolates has rapidly emerged in Poland during the last decade and has reached prevalence levels of up to 14.4% in 1997. In order to investigate the nature of this increase, a molecular epidemiological analysis of non-penicillin-susceptible multidrug-resistant pneumococci isolated in 1995 and 1996 was conducted. Thirty-seven patients who suffered mainly from upper respiratory tract infections and pneumococcal pneumonia were enrolled in this study. The medical centers to which the patients were admitted were located in 16 Polish towns across the country. Eight distinct BOX PCR types were observed, representing 14 subtypes. Restriction fragment end labeling (RFEL) analysis divided the pneumococcal strains into 16 distinct types. By combining the BOX PCR and RFEL data, four genetically distinct clusters of strains were identified. Two clusters represented the genetic clones 23F and 9V, which have recently emerged all over the world. The two other genetic clusters, which represented serotypes 23F and 6B, clearly predominated in the analyzed collection of Polish non-penicillin-susceptible pneumococcal strains. Since the latter clusters did not match any of the 133 RFEL types of non-penicillin-susceptible pneumococci collected in 15 other countries, their Polish clonal origin is most likely.

Adolescent↗
PubMed1999

Correction for erythroid cell contamination in microassay for immunophenotyping of neonatal lymphocytes.

Immunophenotyping of blood lymphocyte subpopulations in neonates and young infants is hampered by the limited amount of blood that can be collected. Contamination of the flow cytometric "lympho-gate" by normoblasts and analysed erythrocytes, and therefore the underestimation of the relative frequencies of lymphocyte subpopulations, interferes with the precise calculation of absolute counts. A microassay was developed by adapting the lysed whole blood technique. Triple immunostaining in a single antibody staining step was used to reduce washing steps and cell loss. Introduction of a triple staining for CD71 (expressed by erythroid precursors), glycophorin A (GpA, expressed by all erythroid cells), and CD45 (expressed by all leucocytes) permitted the relative frequencies of normoblasts (CD71(+)/GpA+/CD45(-) population) and unlysed erythrocytes (CD71(-)/GpA+/CD45(-) population)to be identified and measured within the "lympho-gate" of neonatal cord blood samples. Particularly high frequencies were found (median: 31%) in cord blood samples from preterm neonates. These erythroid cells disappear rapidly by 1 week of age The relative frequencies of erythroid cells can be used to calculate correct lymphocyte subpopulation values. Using only 0.5-0.8 ml of blood, this micro- assay would also be suitable for rapid prenatal immunodiagnosis of congenital immunodeficiencies.

Antigens, CD↗
PubMed1998

Early recovery of CD4+ T lymphocytes in children on highly active antiretroviral therapy. Dutch study group for children with HIV infections.

INTRODUCTION: Regeneration of CD4+ T lymphocytes has been shown to be thymus-dependent in bone marrow transplant recipients and after intensive chemotherapy. The rate of CD4+ T cell regeneration is correlated positively with enlargement of the thymus, as shown on radiographs, and higher rates of CD4+ T lymphocyte regeneration were observed in children as compared with adults, consistent with thymic function diminishing with age. We hypothesized that in HIV infected patients CD4+ T cell recovery during highly active antiretroviral therapy (HAART) may also be thymus dependent. Therefore, repopulation of naive (CD45RA+), memory (CD45RO+) and total CD4+ T lymphocytes and total CD8+ T lymphocytes in peripheral blood was assessed in 13 HIV infected children during the initial 3 months of HAART. RESULTS: Significantly higher recovery rates of naive, memory and total CD4+ T cells were observed in children below the age of 3 years as compared with older children. Kinetics of total CD8+ T cells showed no relation to age. Moreover, recovery rates of naive CD4+ T cells in patients below 3 years of age were 10-40 fold higher as compared with previously reported naive CD4+ T cell recovery rates in adults on HAART. CONCLUSIONS: High recovery rates of naive, memory and total CD4+ T cells can be achieved in children below 3 years of age. Changes in CD8 counts did not correlate with age. These results indicate that regeneration of CD4+ T cells during HAART may be a thymus-dependent process.

Adolescent↗
PubMed1998

Risk factors for respiratory syncytial virus associated apnoea.

UNLABELLED: Respiratory syncytial virus (RSV) infections are characterized by upper or lower respiratory tract symptoms including bronchiolitis and pneumonia. Apnoea may be the first sign of disease in children with RSV infection. The aims of this study were the identification of independent risk factors for RSV associated apnoea and the prediction of the risk for mechanical ventilation in children with RSV associated apnoea. Medical records of children younger than 12 months of age admitted with RSV infection between 1992 and 1995 to the Sophia Children's Hospital, were reviewed. Demographic parameters, clinical features and laboratory parameters (SaO2, pCO2 and pH) were obtained upon admission and during hospitalization. Children with and without apnoea were compared using univariate and multivariate logistic and linear regression analysis. One hundred and eighty-five patients with RSV infection were admitted of whom 38 (21%) presented with apnoea. Patients with apnoea were significantly younger, had a significantly lower temperature, higher pCO2 and lower pH and had on chest radiographs also more signs of atelectasis. The number of patients admitted to the ICU because of mechanical ventilation and oxygen administration was significantly higher in children with RSV associated apnoea. Apnoea at admission was a strong predictor for recurrent apnoea. The relative risk for mechanical ventilation increased with the number of episodes of apnoea: 2.4 (95% CI 0.8-6.6) in children with one episode of apnoea (at admission) versus 6.5 (95% CI 3.3-12.9) in children with recurrent episodes of apnoea. CONCLUSIONS: Age below 2 months is the strongest independent risk factor for RSV associated apnoea. Apnoea at admission increases the risk for recurrent apnoea. The risk for mechanical ventilation significantly increases in children who suffer from recurrent apnoea.

Acid-Base Equilibrium↗
PubMed1998

Pathophysiology of meningococcal sepsis in children.

UNLABELLED: Septic shock with purpura is a syndrome frequently diagnosed in children and predominantly caused by Neisseria meningitidis. Despite improvements in management and therapy the mortality and morbidity in these patients are still high. During the last few years much effort has been put into understanding of the systemic host response during this acute infectious disease. This host response can be divided into the process of recognition of endotoxin, the cascade of pro- and counter inflammatory mediators, the endothelial damage resulting in capillary leakage and inappropriate vascular tone, and the procoagulant state. CONCLUSION: This paper reviews the recent insights in the pathophysiology of the host response and their possible consequences for novel therapies in meningococcal sepsis.

Blood Coagulation Disorders↗
PubMed1998

Localization of the ICF syndrome to chromosome 20 by homozygosity mapping.

Immunodeficiency in association with centromere instability of chromosomes 1, 9, and 16 and facial anomalies (ICF syndrome) is a rare autosomal recessive disorder. ICF patients show marked hypomethylation of their DNA; undermethylation of classical satellites II and III is thought to be associated with the centromere instability. We used DNA from three consanguineous families with a total of four ICF patients and performed a total genome screen, to localize the ICF syndrome gene by homozygosity mapping. One chromosomal region (20q11-q13) was consistently found to be homozygous in ICF patients, whereas all healthy sibs showed a heterozygous pattern. Comparison of the regions of homozygosity in the four ICF patients localized the ICF locus to a 9-cM region between the markers D20S477 and D20S850. Analysis of more families will be required, to refine the map location further. Isolation of the gene associated with the ICF syndrome not only will give insight into the etiology of the ICF syndrome but will also broaden our understanding of DNA methylation processes.

Chromosome Mapping↗
PubMed1998

Differences in N-acetylmuramyl-L-alanine amidase and lysozyme in serum and cerebrospinal fluid of patients with bacterial meningitis.

N-acetylmuramyl-L-alanine amidase (NAMLAA) specifically degrades peptidoglycan, a major component of bacterial cell walls. Lysozyme degrades peptidoglycan differently by hydrolyzing the aminosugar backbone of peptidoglycan. In another study, it was shown that the two enzymes act synergistically to inactivate the inflammatory properties of peptidoglycan. The presence of lysozyme and NAMLAA was determined in serum and cerebrospinal fluid (CSF) of patients with bacterial meningitis. High concentrations of lysozyme were found in CSF while, surprisingly, NAMLAA was not present. To explain this phenomenon, the degranulation pattern of neutrophils in CSF was compared with that of neutrophils from blood. Specific granules contain lysozyme and the azurophil granules contain both lysozyme and NAMLAA. CD66b expression on the cell surface, indicative for fusion of the specific granules with the cell membrane, was higher in CSF than in blood, while the marker for the azurophil granules was lower.

Adolescent↗
PubMed1998

Complement activation in relation to capillary leakage in children with septic shock and purpura.

To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.

Adolescent↗
PubMed1998

Use of recombinant nucleoproteins in enzyme-linked immunosorbent assays for detection of virus-specific immunoglobulin A (IgA) and IgG antibodies in influenza virus A- or B-infected patients.

The nucleoprotein genes of influenza virus A/Netherlands/018/94 (H3N2) and influenza virus B/Harbin/7/94 were cloned into the bacterial expression vector pMalC to yield highly purified recombinant influenza virus A and B nucleoproteins. With these recombinant influenza nucleoproteins, enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of influenza virus A- and B-specific immunoglobulin A (IgA) and IgG serum antibodies. Serum samples were collected at consecutive time points after the onset of clinical symptoms from patients with confirmed influenza virus A or B infections. Nucleoprotein-specific IgA antibodies were detected in 41.2% of influenza virus A-infected patients and in 66. 7% of influenza virus B-infected patients on day 6 after the onset of clinical symptoms. In serum samples taken on day 21 (influenza virus A-infected patients) or day 28 (influenza virus B-infected patients), nucleoprotein-specific IgA antibodies could be detected in 58.8 and 58.3% of influenza virus A- and B-infected patients, respectively. At the same time, IgG antibody rises were detected in 88.2% of influenza virus A-infected patients and in 95.8% of influenza virus B-infected patients. On comparison, hemagglutination inhibition assays detected antibody titer rises in 81.3 and 72.7% of patients infected with influenza viruses A and B, respectively. In contrast to the detection of nucleoprotein-specific IgG antibodies or hemagglutination-inhibiting antibodies, the detection of nucleoprotein-specific IgA antibodies does not require paired serum samples and therefore can be considered an attractive alternative for the rapid serological diagnosis of influenza.

Animals↗
PubMed1998

Molecular characterization of pneumococcal nasopharynx isolates collected from children during their first 2 years of life.

Pneumococcal colonization was studied in 19 children monitored from birth through the age of 2 years. For this purpose, pneumococcal isolates were characterized by capsular typing, restriction fragment end labeling (RFEL), and penicillin-binding protein (PBP) genotyping. Fifty-eight isolates were collected and were found to belong to 10 capsular types, 31 RFEL types, and 7 PBP genotypes. Thirty-nine percent of the isolates had reduced susceptibility to penicillin. All seven highly resistant strains (MICs, > 1 microgram/ml) were identical to the pandemic clone 23F. Children were culture positive between one and eight times at 13 scheduled visits. Although the infants were frequently recolonized with different strains, colonization with one particular strain often persisted for several months. Isolation of a previously detected capsular type was common, and the chromosomal homogeneity tended to be high when it occurred. Horizontal transfer of capsular genes between strains of different RFEL types was demonstrated in one child. The ecological advantage of transfer of capsular genes is unclear unless survival of the organism on a mucosal surface may be linked to immunoprotective pressure against particular capsular types.

Anti-Bacterial Agents↗
PubMed1998

Persistence of clones of coagulase-negative staphylococci among premature neonates in neonatal intensive care units: two-center study of bacterial genotyping and patient risk factors.

From 1 January 1995 until 1 January 1996, we studied the molecular epidemiology of blood isolates of coagulase-negative staphylococci (CoNS) in the Neonatal Intensive Care Units (NICUs) of the Sophia Children's Hospital (SCH; Rotterdam, The Netherlands) and the Wilhelmina Children's Hospital (WCH; Utrecht, The Netherlands). The main goal of the present study was to detect putatively endemic clones of CoNS persisting in these NICUs. Pulsed-field gel electrophoresis was used to detect the possible presence of endemic clones of clinical significance. In addition, clinical data of patients in the SCH were analyzed retrospectively to identify risk factors for the acquisition of positive blood cultures. In both centers, endemic CoNS clones were persistently present. Thirty-three percent of the bacterial isolates derived from blood cultures in the SCH belonged to a single genotype. In the WCH, 45% of all bacterial strains belonged to a single clone. These clones were clearly different from each other, which implies that site specificity is involved. Interestingly, we observe that the clonal type in the SCH differed significantly from the incidentally occurring strains with respect to both the average pH and partial CO2 pressure of the patient's blood at the time of bacterial culture. We found that the use of intravascular catheters, low gestational age, and a long hospital stay were important risk factors for the development of a putative CoNS infection. When the antibiotic susceptibility of the bacterial isolates was assessed, a clear correlation between the nature of the antibiotics most frequently used as a first line of defense versus the resistance profile was observed. We conclude that the intensive use of antibiotics in an NICU setting with highly susceptible patients causes selection of multiresistant clones of CoNS which subsequently become endemic.

Anti-Bacterial Agents↗