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N Nagelkerke

Publications and source records attributed to N Nagelkerke.

At least 19 recordsLinked to original sources

Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: tiapride vs. pyridostigmine.

Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoxime reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 microMol paraoxon (approximately LD75) groups 2-6 received in addition: G(2)50 microMol tiapride 30 min before paraoxonG(3)50 microMol tiapride 30 min before paraoxon and 50 microMol pralidoxime 1 min after paraoxon G41 microMol pyridostigmine 30 min before paraoxon G(5)1 microMol pyridostigmine 30 min before paraoxon and 50 microMol pralidoxime 1 min after paraoxon G(6)50 microMol pralidoxime 1 min after paraoxon. Mortality data were compared using Kaplan-Meier plots and logrank tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G3) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G5). Tiapride pretreatment only (G2) is inferior to pyridostigmine pretreatment only (G4). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G4 and G6).

Acute Disease↗

Effect of maternal exposure to homocystine on sodium valproate-induced neural tube defects in the mouse embryos.

BACKGROUND: Neural tube defects (NTD) are mainly of multifactorial origin. Maternal treatment with valproic acid (VPA) during pregnancy induces NTD in susceptible fetuses. Elevated levels of homocysteine are observed in pregnancies with NTD. The mechanism by which homocysteine might cause NTD is unknown. AIM OF THE STUDY: The aim of this study was to determine if homocystine would augment VPA-induced exencephaly in an experimental model. METHODS: Groups of mice were injected (IP) on gestational day 8 (GD) with a single dose of 75 mg/kg of L: -Homocystine (HC) or a proportionate volume of saline, followed by a single dose of 600 mg/kg of VPA or an equal volume of saline. In a second experiment, mice were treated with a daily dose of 75 mg/kg of HC or an equal volume of saline (IP) from GD 5 and continued through GD 10. These animals had a single exposure to 600 mg/kg of VPA or saline (IP) on GD 8. All animals were killed by cervical dislocation on GD 18. Plasma homocysteine, folate and vitamin B12 were determined on GD 8 and GD 10 from single and multiple dose groups of mice, respectively, from additional experiments. RESULTS: The VPA and HC+VPA induced significantly higher rates of embryonic resorption and intrauterine growth retardation (IUGR) than HC or saline alone. HC + VPA groups had significantly more numerous fetuses with severe IUGR than HC alone or VPA alone groups. Both single and multiple doses of HC augmented VPA-induced reduction in fetal body weight. Successive doses of HC did not augment the rate of IUGR more significantly than a single dose of HC. Incidence of exencephaly was significantly enhanced in the HC + VPA groups compared to that in the HC or VPA alone groups. HC alone was not teratogenic. Plasma homocysteine levels increased several fold both in HC and HC + VPA groups and the increase was not particularly more marked in multiple dose groups than in the single dose groups. VPA did not elevate homocysteine concentration. Both FA and vitamin B12 concentrations were reduced by VPA, HC and HC + VPA, but HC and VPA when combined did not produce an additive effect on vitamin levels. CONCLUSION: These data indicate that HC and VPA interact in neurulation stage embryos, affect fundamental processes of closure of the neural tube and lead to enhanced incidence of NTD.

Abnormalities, Drug-Induced↗

No epidemiological evidence for infant vaccinations to cause allergic disease.

CONTEXT: The prevalence of allergic diseases has increased considerably over the last decades. The hygiene hypothesis has emerged, linking reduced microbial exposure and infections early in life with the development of allergic diseases. Especially some of currently available non-replicating infant vaccines are unlikely to mimic a natural infection-mediated immune response that protects against the development of allergic diseases. Moreover, several studies suggested infant vaccinations to increase the risk of allergic diseases. OBJECTIVE: To determine whether infant vaccinations increase the risk of developing allergic disease. DATA SOURCES: We searched MEDLINE from 1966 to March 2003 and bibliography lists from retrieved articles, and consulted experts in the field to identify all articles relating vaccination to allergy. STUDY SELECTION AND DATA EXTRACTION: We selected epidemiological studies with original data on the correlation between vaccination with diphtheria, pertussis, tetanus (DPT), measles, mumps, rubella (MMR) and Bacillus Calmette-Guérin (BCG) vaccine in infancy and the development of allergic diseases, and assessed their quality and validity. DATA SYNTHESIS: Methodological design and quality varied considerably between the studies we reviewed. Many studies did not address possible confounders, such as the presence of lifestyle factors, leaving them prone to bias. The studies that offer the stronger evidence, including the only randomized controlled trial at issue published to date, indicate that the infant vaccinations we investigated do not increase the risk of developing allergic disease. Furthermore, BCG does not seem to reduce the risk of allergies. CONCLUSIONS: The reviewed epidemiological evidence indicates that, although possibly not contributing to optimal stimulation of the immune system in infancy, current infant vaccines do not cause allergic diseases.

BCG Vaccine↗

Analysing collaborative trials for qualitative microbiological methods: accordance and concordance.

In qualitative (detection) food microbiology, the usual measures of repeatability and reproducibility are inapplicable. For such studies, we introduce two new measures: accordance for within laboratory agreement and concordance for between laboratory agreement, and discuss their properties. These measures are based on the probability of finding the same test results for identical test materials within and between laboratories, respectively. The concordance odds ratio is introduced to present their relationship. A method to test whether accordance differs from concordance is discussed.

Food Microbiology↗

Validation of ISO method 11290 part 2. Enumeration of Listeria monocytogenes in foods.

The European and International Standard method for the enumeration of Listeria monocytogenes, described in EN ISO 11290 Part 2: 1998 [EN ISO 11290-2 Microbiology of Food and Animal Feedingstuffs-Horizontal Method for the Detection and Enumeration of L. monocytogenes: Part 2. Enumeration; International Organisation for Standardisation, Geneva.] was validated by order of the European Commission (Standards, Measurement and Testing Fourth Framework Programme Project SMT4-CT96-2098). The objective was to determine the precision of the method in terms of repeatability (r) and reproducibility (R) using three different food types inoculated with various levels of L. monocytogenes and a typical background flora. The results are intended for publication in the associated standards. Cheese, meat, dried egg powder and reference materials were examined by 21 laboratories in 16 countries in Europe. Each participant received eight test materials per food type: blind duplicates at four inoculum levels (0, 10(2), 10(3), 10(4) cfu/g). In addition, two reference materials containing L. monocytogenes were included in the study. All test materials were subjected to stringent homogeneity and stability testing before being used in the collaborative trial. Participants were required to use only PALCAM agar for enumeration of L. monocytogenes, as prescribed by the reference method. Statistical analyses has been performed using a newly introduced approach for food microbiology (draft standard prEN ISO 16140 [prEN ISO 16140 Microbiology of Food and Animal Feedingstuffs-Protocol for the Validation of Alternative Methods, International Organisation for Standardisation, Geneva.], the precision data being calculated using robust estimates. Overall values for repeatability (r) of EN ISO 11290-2 when used with food test materials were r = log10 0.58 (expressed as an absolute difference between log10-transformed test results) or r = 3.8 (expressed as an absolute ratio between test results on the normal scale). For the reference materials (capsules containing approximately 5000 cfu), r = log10 0.34 (expressed as an absolute difference between log10-transformed test results) or r = 2.2 (expressed as an absolute ratio between test results on the normal scale). Overall values for reproducibility (R) of EN ISO 11290-2 when used with food test materials were R = log10 0.81 (expressed as a difference between log10-transformed test results) or R = 6.5 (expressed as an absolute ratio between test results on the normal scale). For the reference materials, R = log10 0.51 (expressed as a difference between log10-transformed test results) or R = 3.2 (expressed as an absolute ratio between test results on the normal scale). Further studies have been initiated by ISO TC34/SC9 to try to enhance the isolation of L. monocytogenes from foods and improve the confirmation procedures.

Animals↗

Validation of ISO method 11290 part 1--detection of Listeria monocytogenes in foods.

The European and International Standard method for the detection of Listeria monocytogenes, described in EN ISO 11290 Part 1: 1997 (International Organisation for Standardisation, Geneva) was validated by order of the European Commission (Standards, Measurement and Testing Fourth Framework Programme Project SMT4-CT96-2098). Nineteen laboratories in 14 countries in Europe participated in a collaborative trial to determine the performance characteristics of the method, which are intended for publication in the corresponding standard. An additional objective of this project was to devise a new series of parameters to indicate the 'precision' of microbiological qualitative methods. The method was challenged with three food types, namely fresh cheese, minced beef and dried egg powder and a reference material. Inoculation levels ranged from 5 to 100 cfu/25 g. Each participant examined five replicates of each food type at three inoculum levels and five reference materials. Both PALCAM and Oxford media were assessed. All test materials were subjected to stringent homogeneity and stability testing before being used in the collaborative trial. The results demonstrated that the method prescribed in EN ISO 11290-1 had an overall sensitivity of 85.6% and a specificity of 97.4%. L. monocytogenes was detected in most cases after primary enrichment, although secondary enrichment often yielded further positives. However, a significant number of false-negative results were obtained with all food types when large numbers of L. innocua were present in the test materials. L. innocua tended to dominate L. monocytogenes during the selective enrichment stages and thus masked small numbers of colonies of L. monocytogenes on the isolation media. There was no evidence from this collaborative study to demonstrate a significant difference in performance between Oxford and PALCAM media. Due to the problem of false-negative results with this method as highlighted in this trial, recommendations have been made to ISO to launch a revision of the standard to improve the detection of low numbers of L. monocytogenes in foods. New statistical methods devised to advance the measurement of the performance of qualitative microbiological methods are also described.

Animals↗

Lymphocyte subsets in human immunodeficiency virus type 1-infected and uninfected children in Nairobi.

BACKGROUND: Reference lymphocyte subset values for African children are lacking. This study documents these values as well as their alterations associated with perinatal and postnatal HIV-1 transmission and with protection from HIV-1 infection. METHODS: Lymphocyte subsets were determined for HIV-1-seronegative nonpregnant women and their children (controls) and for uninfected, perinatally infected and postnatally infected children born to HIV-1-seropositive mothers in Nairobi, Kenya. The mean, median and 5th and 95th percentile values for CD4+ and CD8+ lymphocyte counts and percentages were determined and compared at the age ranges birth to 3 months, 4 months to 1 year, yearly from 1 to 5 years and from 6 to 10 years of age. RESULTS: Among control children counts differed from published values of other populations. In all age ranges, whereas the absolute values were significantly higher than adult values, the percentages were significantly lower. Children perinatally infected with HIV-1 had clearly distinguishable differences in lymphocyte subset percentages by 3 months of age, when the median CD4+ percentage was 27.9% (5th to 95th percentile, 25.7 to 30.1%) for infected vs. 35.9% (33.3 to 38.7%) for uninfected and 39.9% (37.8 to 42.2%) for control children, P < 0.001; whereas the median CD8+ percentage was 37.0% (33.1 to 41.0%) for infected vs. 27.5% (24.2 to 30.8%) for uninfected and 27.5% (24.2 to 30.8%) for control children, P = 0.001. Differences between uninfected and control children disappeared after 1 year of age. CONCLUSIONS: Normal lymphocyte subset values among African children differ from those in other populations. Significant differences are detectable by 3 months of age in CD4+ and CD8+ lymphocyte percentages among perinatally infected infants, which may be useful as an adjunct in diagnosis. Transient differences observed among HIV-1-exposed but uninfected infants could reflect a successful immune response to HIV-1 challenge.

CD4 Lymphocyte Count↗

The effect of age and study duration on the relationship between 'clustering' of DNA fingerprint patterns and the proportion of tuberculosis disease attributable to recent transmission.

Though it is recognized that the extent of 'clustering' of isolates from tuberculosis cases in a given population is related to the amount of disease attributable to recent transmission, the relationship between the two statistics is poorly understood. Given age-dependent risks of disease and the fact that a long study (e.g. spanning several years) is more likely to identify transmission-linked cases than a shorter study, both measures, and thus the relationship between them, probably depend strongly on the ages of the cases ascertained and study duration. The contribution of these factors is explored in this paper using an age-structured model which describes the introduction and transmission of M. tuberculosis strains with different DNA fingerprint patterns in The Netherlands during this century, assuming that the number of individuals contacted by each case varies between cases and that DNA fingerprint patterns change over time through random mutations, as observed in several studies. Model predictions of clustering in different age groups and over different time periods between 1993 and 1997 compare well against those observed. According to the model, the proportion of young cases with onset in a given time period who were 'clustered' underestimated the proportion of disease attributable to recent transmission in this age group (by up to 25% in males); for older individuals, clustering overestimated this proportion. These under- and overestimates decreased and increased respectively as the time period over which the cases were ascertained increased. These results have important implications for the interpretation of estimates of the proportion of disease attributable to recent transmission, based on 'clustering' statistics, as are being derived from studies of the molecular epidemiology of tuberculosis in many populations.

Adolescent↗

Estimating treatment effects in randomized clinical trials in the presence of non-compliance.

In clinical trials where patients are randomized between two treatment arms, not all patients comply with the treatment they were randomly assigned to. The reasons for (non)compliance may be associated with the outcome variable and thereby act as confounders. The standard way of analysing such trials is by the 'intention-to-treat' principle, which allows the use of permutation tests. Conclusions drawn from such tests do not depend on untested assumptions such as absence of confounding. However, this approach may yield biased estimators for the causal effects of treatments. We consider the estimation of such effects for clinical trials where non-compliers can be considered to have switched to the other trial arm. The most important example of this is the placebo-controlled clinical trial where no substantial placebo effects are anticipated. We consider the situation where the relationship between compliance, and thus treatment received, and outcome is influenced by unobserved confounders. The residual of the regression of the actual treatment indicator variable on the randomization arm indicator variable is shown to 'intercept' the effect of such confounders. Inclusion of this residual in a multivariate analysis, in conjunction with the treatment indicator variable, should thus adjust for confounding. Examples are given. In those examples, the results are similar to those obtained by more complex methods.

Anticholesteremic Agents↗

Tuberculosis screening among immigrants in The Netherlands: what is its contribution to public health?

Understanding the epidemiology of tuberculosis in migrant communities and designing adequate and comprehensive control strategies is a major challenge facing public health authorities in many low-prevalence countries. In The Netherlands, screening immigrants from tuberculosis high prevalence countries has been conducted since 1966. In this paper, we review risk factors for tuberculosis in migrant populations, the public health importance of tuberculosis and the current screening policy in The Netherlands. TB treatment outcome in migrant populations and operational considerations that ought to be taken into account to optimize current screening practices are also reviewed. The article recommends the setting-up of an information system to evaluate the effectiveness of screening immigrants in The Netherlands, and adjustment of screening policies where needed.

Emigration and Immigration↗

Increasing resistance to fluoroquinolones in escherichia coli from urinary tract infections in the netherlands.

In continuous surveillance of routine samples from five Dutch laboratories, we studied resistance to the antibiotics most commonly prescribed for urinary tract infections (UTI) in The Netherlands, namely norfloxacin, amoxycillin, trimethoprim and nitrofurantoin, from 1989 to 1998 in >90000 Escherichia coli isolates. Resistance to norfloxacin increased from 1.3% in 1989 to 5.8% in 1998. Multiresistance, defined as resistance to norfloxacin and at least two of the other three antibiotics, increased from 0.5% in 1989 to 4. 0% in 1998. Multivariate analysis of the norfloxacin resistance demonstrated that this yearly increase (the odds ratio was 1.0 in 1989, 1.6 in 1992, 2.9 in 1995 and 6.1 in 1998) was independent of other determinants of resistance to norfloxacin, such as age, gender and origin of the isolate. Analysis of strata, classified by year, age and gender, demonstrated an association between prescription of fluoroquinolones (defined daily doses per case of UTI) and resistance to norfloxacin in E. coli (P < 0.001). There was no significant association with the prescription of nitrofuran derivatives (nitrofurantoin) and trimethoprim with or without sulphamethoxazole. The yearly increase of resistance to fluoroquinolones in E. coli from UTI may stem from increased prescription of fluoroquinolones for UTI. Resistance of E. coli to these agents is likely to increase further as fluoroquinolone use increases in future.

Adolescent↗

Baseline and previous physical activity in relation to mortality in elderly men: the Zutphen Elderly Study.

Understanding the effect of changes in physical activity on mortality risk may help researchers clarify intervention strategies. This study investigated associations of physical activity at baseline and 5 years previously with all-cause mortality risk in a cohort of 472 elderly Dutch men. Relative risks were estimated for relations between mortality in 1990-1995 and physical activity levels in 1990 and 1985. Adjustments were made for baseline age, chronic diseases, functional status, and lifestyle factors. In contrast to previous levels of physical activity (adjusted p-trend = 0.39), baseline total time spent in physical activity was inversely associated with mortality risk (p-trend = 0.004; for the most active tertile vs. the least active, relative risk = 0.44; 95% confidence interval: 0.25, 0.80). No consistent associations were observed after fractionating total physical activity into activities of differing intensity or into four different types of activity. Relative to maintaining a physically active lifestyle (i.e., walking or bicycling for 20 minutes at least three times per week) in both survey years, a gradient of increasing risk was observed from adopting an active lifestyle to becoming sedentary to remaining sedentary (p-trend = 0.004). Recent levels of physical activity were more important for mortality risk among elderly men than activity 5 years previously. Becoming or remaining sedentary was significantly associated with increased mortality risk in comparison with remaining physically active.

Activities of Daily Living↗

Semi-parametric estimation of age-time specific infection incidence from serial prevalence data.

Many infections cause lasting detectable immune responses, whose prevalence can be estimated from cross-sectional surveys. However, such surveys do not provide direct information on the incidence of infection. We address the issue of estimating age and time specific incidence from a series of prevalence surveys under the assumption that incidence changes exponentially with time, but make no assumption about the age specific incidence. We show that these assumptions lead to a proportional hazards model and estimate its parameters using semi-parametric maximum likelihood methods. The method is applied to tuberculin surveys in The Netherlands to explore age dependence of the risk of tuberculous infection in the presence of a strong secular decline in this risk.

Adolescent↗

Comparison of five methods of malaria detection in the outpatient setting.

In eastern Africa where 90% of the malaria is due to Plasmodium falciparum, the accuracy of malaria diagnosis at the outpatient level is becoming increasingly important due to problems of drug resistance and use of alternative, costly antimalarial drugs. The quantitative buffy coat (QBC) technique, acridine orange staining with an interference filter system, and the ParaSight-F test have been introduced as alternative methods to conventional microscopy for the diagnosis of malaria. Two hundred thirteen outpatients were tested using these alternative methods and conventional microscopy by five experienced technologists; two were randomly allocated to read the results of each test. Paired results showed the highest level of agreement with the ParaSight-F test (99%), followed by Field stain (92%). The results of the QBC technique showed the least agreement (73%). Using conventional microscopy as the reference standard, the ParaSight-F test had a sensitivity range of 90-92% and a specificity of 99%, staining with acridine orange had a sensitivity range of 77-96% and a specificity range of 81-98% and the QBC technique had a sensitivity range of 88-98% and a specificity range of 58-90%. All microscopic tests showed lower sensitivities (as low as 20% using staining with acridine orange) in detecting low parasitemias (< or = 320/microl) than the ParaSight-F test (70%). Due to the high cost of the ParaSight-F test, Field-stained blood films remain the most appropriate method for diagnosis of P. falciparum in eastern Africa. The ParaSight-F test may be used in situations where no trained microscopists are available, or where malaria is strongly suspected and the results of microscopy are negative.

Acridine Orange↗

Analysis of tuberculosis transmission between nationalities in the Netherlands in the period 1993-1995 using DNA fingerprinting.

Immigration from high prevalence areas may contribute to an increased risk of tuberculosis in Europe. This study aimed at quantifying transmission of tuberculosis between and within nationalities among residents of the Netherlands. DNA "fingerprints," on the basis of restriction fragment length polymorphism using marker IS6110, were made of all Mycobacterium tuberculosis isolates in the Netherlands from January 1993 through June 1995. Clusters were defined as groups of patients that had isolates with identical fingerprints. It was assumed that the probability of a patient being the source of a cluster was proportional to the incidence rate of potential sources times the probability that a potential source would give rise to a cluster. The transmission index was defined as the average number of secondary cases of infectious tuberculosis caused directly or indirectly through recent transmission by a single potential source case and was used to estimate the effective reproductive rate associated with recent transmission, ReFAST. Among a total of 623 Dutch tuberculosis cases, 17% (95% confidence interval 9-25%) of cases were attributable to recent transmission from a non-Dutch source. The transmission index varied strongly by nationality, and was highest among the Surinamese (1.3), Moroccan (0.8), and Turkish (0.8) populations; ReFAST was 0.26. Aggregation of tuberculosis cases of given nationalities within clusters was most pronounced among recent immigrants from Somalia and (ex-)Yugoslavia. The authors conclude that differences in transmission between subpopulations can be quantified and may be used to evaluate and direct tuberculosis control.

Adolescent↗

Occurrence of verocytotoxin-producing Escherichia coli O157 on Dutch dairy farms.

During the period from September 1996 through November 1996, 10 Dutch dairy farms were visited to collect fecal samples from all cattle present. The samples were examined for the presence of verocytotoxin (VT)-producing Escherichia coli (VTEC) of serogroup O157 (O157 VTEC) by immunomagnetic separation following selective enrichment. Cattle on 7 of the 10 dairy farms tested positive for O157 VTEC, with the proportion of cattle infected varying from 0.8 to 22.4%. On the seven farms positive for O157 VTEC, the excretion rate was highest in calves ages 4 to 12 months (21.2%). In a follow-up study, two O157 VTEC-positive farms and two O157 VTEC-negative farms identified in the prevalence study were revisited five times at intervals of approximately 3 months. Cattle on each farm tested positive at least once. The proportion of cattle infected varied from 0 to 61.0%. Excretion rates peaked in summer and were lowest in winter. Again, the highest prevalence was observed in calves ages 4 to 12 months (11.8%). O157 VTEC strains were also isolated from fecal samples from horses, ponies, and sheep and from milk filters and stable flies. O157 VTEC isolates were characterized by VT production and type, the presence of the E. coli attaching-and-effacing gene, phage type, and pulsed-field gel electrophoretic genotype. No overlapping strain types were identified among isolates from different farms except one. The predominance of a single type at each sampling suggests that horizontal transmission is an important factor in dissemination of O157 VTEC within a farm. The presence of more than one strain type, both simultaneously and over time, suggests that there was more than one source of O157 VTEC on the farms. Furthermore, this study demonstrated that the O157 VTEC status of a farm cannot be ascertained from a single visit testing a small number of cattle.

Age Factors↗

Mortality among tuberculosis patients in The Netherlands in the period 1993-1995.

This study aimed to estimate excess mortality among tuberculosis patients in The Netherlands and identify risk factors for tuberculosis-associated mortality. The national tuberculosis register provided data on patients diagnosed in the period 1993-1995. Excess mortality in tuberculosis cases, according to age and sex, was determined by comparison with national mortality rates. Risk factors were identified and adjustment for confounders was carried out using Cox's proportional hazard analysis. Of 4,340 patients alive at diagnosis, 258 died within 1 yr while on treatment. The Kaplan-Meier survival probability after 1 yr was 93%. Tuberculosis patients had a standardized mortality ratio of 8.3. Independent risk factors for mortality were: gender; age; presence of a malignancy or human immunodeficiency virus (HIV) infection; addiction to alcohol or drugs; localization of tuberculosis; and the type of medical officer having made the diagnosis. Of all deaths, 83% occurred in two risk groups comprising 21% of tuberculosis patients: those aged > or =65 yrs and those having HIV infection or a malignancy. Tuberculosis patients in The Netherlands are at a considerably increased risk of death. However, the prognosis is very good for those aged less than 65 yrs and without human immunodeficiency virus infection or a malignancy.

Adult↗