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Biomedical subjects

E Bakker

Publications and source records attributed to E Bakker.

At least 37 records · Page 2Linked to original sources

Voiding habits and wetting in a population of 4,332 Belgian schoolchildren aged between 10 and 14 years.

OBJECTIVE: To determine the prevalence of daytime- with/without night-time wetting, in Belgium, in a group of 10 to 14 year old schoolchildren, and to study the voiding habits. SUBJECTS AND METHODS: A questionnaire of 41 questions was developed and completed by 4,332 parents at home. RESULTS: Wetting or soiling episodes were reported by a total of 528 (12%) of the children: monosymptomatic nocturnal enuresis by 62 (1%), daytime wetting with/without night-time wetting by 343 (8%), and faecal soiling by 123 (3%). We found significantly more girls in the wetting group, and the capacity to regularly postpone the voiding was significantly lower in this group. Significantly more children had nocturia in the group with wetting. CONCLUSIONS: Children with daytime wetting with/without night-time wetting have very often bladder-sphincter dysfunctions, which is in turn correlated with recurrent urinary tract infections. Eight percent of the 10 to 12 year old schoolchildren report daytime wetting with/without night-time wetting with some frequency. Surprisingly few parents, especially in the daytime wetting group, searched for medical help. Physicians and paediatricians should be encouraged to be more attentive to wetting in children and initiate discussion about urinary en faecal problems with parents and children.

Adolescent↗

Monodisperse plasticized poly(vinyl chloride) fluorescent microspheres for selective ionophore-based sensing and extraction.

A convenient method for the preparation of monodisperse, plasticized poly(vinyl chloride) particles based on an automated particle casting technique is described. The particles are made highly selective for a number of ions by doping them with ionophores and other active components, in complete analogy to thin-film or fiber-optic chemical sensors. The approach used here produces spheres of high monodispersity at a rate of approximately 20000 particles/s. The casting process is based on a reproducible polymer drop formation and precipitation process, and the particles are formed under very mild, nonreactive conditions. This allows one to conveniently incorporate known amounts of different active components into the polymers. As an initial example, the particles are doped with three optical sensing components, the sodium ionophore tert-butylcalix[4]arene tetraethyl ester, the H+-chromoionophore ETH 5294, and the anionic additive sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate. The particles are found to be of spherical shape with a diameter of approximately 10 microm. They respond individually and selectively to sodium according to classical optode theory, as determined by fluorescence microscopy. With a RSD of 1.6%, sensing reproducibility from particle to particle is excellent. This technique may allow the development of mass-produced chemically selective microspheres on the basis of bulk extraction processes.

Algorithms↗

Effect of lipophilic ion-exchanger leaching on the detection limit of carrier-based ion-selective electrodes.

The equilibrium partitioning of lipophilic ion-exchanger salts from ion-selective polymeric membrane electrodes (ISEs) and its possible effect on the lower detection limit of these sensors is described. Predictions are made on the basis of various parameters, including the knowledge of tetraphenylborate potassium salt partitioning constants, the selectivity of ionophore-free ion-exchanger membranes, and ionophore stability constants in the membrane. Ion-exchanger lipophilicities are significantly increased if the membrane contains an ionophore that strongly binds the primary ion. Predicted detection limits are on the order of 10(-5)-10(-8) M for ionophore-free membranes, and may reach levels as low as 10(-18) M with adequate ionophores in the membrane. Experiments are performed for well-described lead-selective membranes containing different tetraphenylborate derivatives, and detection limits appear to be independent of the ion-exchanger used. However, they are much higher if a more hydrophilic carborane cation-exchanger is incorporated in the membrane. The first finding confirms recent theory, which states that transmembrane ion fluxes, given by a small level of ion-exchange at the sample side by interfering ions, normally dictate the detection limit of these sensing systems. Predicted detection limits on the basis of ion-exchanger leaching alone are here listed for a number of analytically relevant cases. For potassium-selective electrodes containing BME-44 and tetraphenylborate as ion-exchanger, the experimental detection limits are in agreement with predicted values. These results suggest that the detection limit of many current ISEs for ultratrace level analysis are, in optimal cases, dictated by transmembrane ion fluxes; however, because improved chemical solutions are being developed to reduce such effects, simple ion-exchanger partitioning may indeed become an important mechanism that can give higher detection limits than practically desired, and should not be ruled out.

Biosensing Techniques↗

Cerebral microbleeds in CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy leading to recurrent cerebral infarcts and dementia. Intracerebral hemorrhage (ICH) has been described sporadically in patients with CADASIL, suggesting that the affected arteries in CADASIL are not bleed-prone. However, the presence of cerebral microbleeds, which often remain undetected on conventional MRI, has not been determined in CADASIL. OBJECTIVE: To determine whether cerebral vessels in patients with CADASIL are prone to microbleeding. METHODS: T2*-weighted gradient echo MRI, which is highly sensitive for visualizing microbleeds, was performed in patients with CADASIL and their family members (n = 63). Known risk factors for ICH were determined for all individuals. On an exploratory basis, the presence of cerebral microbleeds was correlated with demographic variables, vascular risk factors, disease progression, ischemic MR lesions, and genotype. RESULTS: Cerebral microbleeds were present in 31% of symptomatic CADASIL mutation carriers, predominantly in the thalamus. Vascular risk factors such as hypertension did not account for the microbleeds in these patients. Factors associated with microbleeds were age (p = 0.008), Rankin disability score (p = 0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and the Arg153Cys Notch3 mutation (p = 0.017). After correction for age, only the Arg153Cys mutation remained significantly associated with the presence of microbleeds. CONCLUSION: Patients with CADASIL have an age-related increased risk of intracerebral microbleeds. This implies that they may have an increased risk for ICH, which should be taken into account in CADASIL diagnosis and patient management.

Adult↗

Quantification of the concentration of ionic impurities in polymeric sensing membranes with the segmented sandwich technique.

Ionic impurities in solvent polymeric membranes have been the main reason early ion-selective electrodes (ISEs) without added ion exchanger exhibited a functional potentiometric response. Today, knowledge of such impurities and their elimination becomes important in view of designing ISEs with low detection limits and voltammetric ion-selective electrodes, to increase operational lifetime, and to optimize sensing selectivity. Here, a potentiometric segmented sandwich membrane technique is used to study the amount and properties of impurities in situ directly in the membrane phase. This technique can be used with a number of ionophores and with different membrane matrixes and does not require specialized equipment. The concentration of anionic impurities in PVC-DOS (bis(2-ethylhexyl) sebacate) and PVC-NPOE (o-nitrophenyloctyl ether) was found to be on the order of 100 micromol/kg with membranes containing weakly binding potassium ionophores. The concentration of cation-exchanger sites of carboxylated PVC-NPOE was found to be higher (1.62 mmol/kg). Addition of the neutral lipophilic salt ETH 500 to both membrane segments had only a marginal effect on the results for PVC-NPOE membranes but had a large impact on the observed membrane potential for PVC-DOS membranes. Theory explains that the addition of such salt to membranes where ion pairing is predominant is essential for the accurate assessment of ionic impurities with this technique.

Algorithms↗

[From gene to disease; amyloid-beta precursor protein gene instrumental in hereditary cerebral amyloid angiopathies].

Hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant disease caused by a mutation in the amyloid precursor protein gene on chromosome 21. The disease is characterised by amyloid deposition in cerebral blood vessels, which results in cerebral haemorrhages, leucencephalopathy, dementia and death. In the same gene, mutations have also been found for other rare diseases which also result in dementia and haemorrhages, as well as familial Alzheimer's disease (different mutations in different families). The majority of familial Alzheimer cases, however, are associated with mutations in the PS1 gene (more than 70 different mutations) or the PS2 gene (4 mutations).

Alzheimer Disease↗

Improved detection limits and sensitivities of potentiometric titrations.

Zero-current ion fluxes through polymer membranes of ion-selective electrodes (ISEs) may lead to biased endpoints of potentiometric titrations. The bias is eliminated, and the sensitivity of the end-point detection is improved through reducing transmembrane ion fluxes by an appropriate choice of the inner solution. Surprisingly, ISE membranes that have a significant primary ion flux toward the inner solution show much larger sensitivities than expected by titration theory; however, depending on the experimental conditions, their application may bias the endpoint. With the optimal systems, endpoint detection is now possible with total sample concentrations below 10(-6) M, as demonstrated by the titration of EDTA with a Pb2+ solution.

Edetic Acid↗

An extensive analysis of Y-chromosomal microsatellite haplotypes in globally dispersed human populations.

The genetic variance at seven Y-chromosomal microsatellite loci (or short tandem repeats [STRs]) was studied among 986 male individuals from 20 globally dispersed human populations. A total of 598 different haplotypes were observed, of which 437 (73.1%) were each found in a single male only. Population-specific haplotype-diversity values were.86-.99. Analyses of haplotype diversity and population-specific haplotypes revealed marked population-structure differences between more-isolated indigenous populations (e.g., Central African Pygmies or Greenland Inuit) and more-admixed populations (e.g., Europeans or Surinamese). Furthermore, male individuals from isolated indigenous populations shared haplotypes mainly with male individuals from their own population. By analysis of molecular variance, we found that 76.8% of the total genetic variance present among these male individuals could be attributed to genetic differences between male individuals who were members of the same population. Haplotype sharing between populations, phi(ST) statistics, and phylogenetic analysis identified close genetic affinities among European populations and among New Guinean populations. Our data illustrate that Y-chromosomal STR haplotypes are an ideal tool for the study of the genetic affinities between groups of male subjects and for detection of population structure.

Africa↗

Spatial and spectral imaging of single micrometer-sized solvent cast fluorescent plasticized poly(vinyl chloride) sensing particles.

Microscale plasticized PVC particles doped with hydrophobic ionophores are prepared by solvent evaporation of aqueous suspensions of sensing cocktails (poly(vinyl chloride), plasticizer, active sensing components, and tetrahydrofuran) and tested as particulate microoptical sensors. The particles contain either only the chromoionophore ETH 2458 as active reagent or the potassium ionophore BME-44, chromoionophore ETH 5294, and lipophilic anionic sites NaTFPB. The former system functions according to an anion-hydrogen ion coextraction mechanism and shows a Hofmeister anion selectivity pattern, while the latter sensor containing additional ionophores represents the more complex, truly selective optical sensors based on ion-exchange equilibria. Single microspheres are simultaneously characterized spatially and spectrally by fluorescence microscopy, coupled to a spectrometer equipped with a CCD detector. The results indicate that these microspheres respond in complete analogy to traditional thin-film-based optodes previously reported in the literature. The introduction of small, spherical ionophore-based sensing particles that operate on the basis of bulk extraction principles holds the promise of significantly expanding the available chemical palette of microsphere-based analytical assays.

Indicators and Reagents↗

Potentiometric polymeric membrane electrodes for measurement of environmental samples at trace levels: new requirements for selectivities and measuring protocols, and comparison with ICPMS.

It is here established that potentiometric polymeric membrane electrodes based on electrically neutral ionophores are useful analytical tools for heavy metal ion determinations in drinking water at nanomolar total concentrations. This means that they can compete with the most sophisticated techniques of instrumental analysis. With optimized ion-selective membranes based on the lead-selective ionophore 4-tert-butylcalix[4]arenetetrakis(thioacetic acid dimethylamide) as model example, a number of native and spiked drinking water samples are potentiometrically assessed for lead, and the results compared with ICPMS measurements. The goal of this work is to demonstrate that detection limits in real world samples are routinely achieved that are, with 1.5 ppb, at least 10-fold lower than the lead action limit imposed by the U.S. Environmental Protection Agency (15 ppb). In contrast to earlier reports, different conditioning and measuring protocols are followed, and membranes and inner filling solution of optimized composition are used. The sensors are shown to be useful for the speciation analysis of lead in water as well. Typical water samples are acidified to pH 4 to assess total lead rather than free, uncomplexed lead. For lead concentrations above 2 ppb, the values compare very well with ICPMS. Main interferences are found to be H+ and Cu2+, although Cu2+ only shows significant interference at levels around or above its own action limit (1.3 ppm), in which case the water sample would anyway show quality problems. An explicit, simplified flux model targeted to the practical use of these sensors explains the extent of expected interference. Sensors are shown to require a higher selectivity than predicted by models not considering ion fluxes, since in dilute samples, the counterdiffusion flux of lead from the membrane into the sample becomes potential determining. The model and experiments shown here are a foundation for future trace level applications of potentiometric polymeric membrane electrodes.

Algorithms↗

Selectivity behavior and multianalyte detection capability of voltammetric ionophore-based plasticized polymeric membrane sensors.

The current response features ofvoltammetric ion-selective polymeric membranes doped with neutral ionophores in view of practical sensor development are elucidated. The membranes are designed to extract ions only under applied external potentials and interrogated by normal-pulse voltammetry and pulsed amperometry. They contain two polarizable interfaces to avoid loss of lipophilic ions at the sample side and to maximize the available potential window. A simple theoretical model is developed that describes the observed current at the end of an uptake pulse to the applied membrane potential, which is the sum of both boundary potentials (at the sample and inner electrolyte side) and the membrane internal iR drop. The results describe how the selectivity of the resulting sensor must be dependent on the applied potential. Evidently, the role of the applied potential is akin to incorporating lipophilic cationic and anionic sites with potentiometric ionophore-based membranes, which are well known to considerably affect membrane selectivity and to define the charge type of the assessed ions. This has important implications for sensor design, as the applied cell potential can be used to tune sensor selectivity. Theory also explains the role of the inner electrolyte on sensor behavior. A maximum measuring range is expected with ions in the inner electrolyte that are difficult to extract into the membrane. This corresponds to Kihara's experimental results and contrasts to common ion-selective electrode practice, where a salt of the analyte ion is normally present in the inner electrolyte. Separate and mixed solution experiments with membranes containing the sodium-selective ionophore tert-butyl calix[4]arene tetramethyl ester and the lithium ionophore ETH 1810 agree very well with theoretical expectations. Multianalyte detection capability with a single sensing membrane is demonstrated in a selectivity-modifying pulsed amperometric detection mode, where each applied voltage yields a different practical selectivity of the sensor. The sensor is altered from being sodium to potassium selective as the magnitude of the applied potential is repetitively varied within the pulse sequence. The sensors show high long-term stability under continuous measuring conditions over 15 h.

Algorithms↗

Complete allele information in the diagnosis of facioscapulohumeral muscular dystrophy by triple DNA analysis.

Facioscapulohumeral muscular dystrophy is caused by partial deletion of the D4Z4 repeat array on chromosome 4q35. Genetic diagnosis is based on sizing of this repeat array, which is complicated by cross-hybridization of a homologous polymorphic repeat array on chromosome 10 and by the frequent exchanges between these chromosomal regions. The restriction enzyme XapI optimizes the diagnosis of facioscapulohumeral muscular dystrophy by uniquely digesting 4-derived repeat units and leaving 10-derived repeat units undigested, thus complementing BlnI, which uniquely digests 10-derived repeat units. A triple analysis with EcoRI, EcoRI/BlnI, and XapI unequivocally allows characterization of each of the four alleles, whether homogeneous or hybrid. This is particularly useful in the case of identical sized 4-derived and 10-derived arrays, in situations of suspected facioscapulohumeral muscular dystrophy with nonstandard allele configurations, and for assignment of hybrid fragments to their original alleles.

Aged↗

Results of a questionnaire evaluating different aspects of personal and familial situation, and the methods of potty-training in two groups of children with a different outcome of bladder control.

OBJECTIVE: This study aimed to investigate the family situation, personal behaviour and current micturition habits, the time of beginning and the method of potty-training in two groups of children with different outcomes of bladder control. MATERIAL AND METHODS: Parents of 140 children, between 7 and 15 years old, filled in a questionnaire comprising 43 questions. They were divided into a symptom group (n = 73) and a symptom-free group (n = 67) according to the outcome of bladder control. RESULTS: Parents remembered clearly the method of training and the time of starting the potty-training to achieve continence in their child, and the exact age at which these objectives were achieved. There was some confusion regarding the term incontinence: the majority of the parents (70%) considered their child to be continent in spite of day-wetting several times a week. All children with urge syndrome who had undergone a urodynamic investigation (n = 50) had an objective functional bladder disorder. CONCLUSIONS: Methods of training differed between the groups with and without lasting problems. The symptom group started training at a later age, had more tendency to punish and were more demanding when micturition did not start readily. The findings from the questionnaire strengthen the hypothesis that urge syndrome can be due to poor methods of potty-training. Very few parents searched spontaneously for help, which should prompt practitioners and paediatricians to be more alert to this problem.

Child↗

[From gene to disease; basic concepts].

The twenty-three pairs of chromosomes in the nuclei of human cells consist of four different components: the nucleotides adenosine, cytidine, guanosine and thymidine. Of this chromosomal DNA, 5% of the nucleotides owing to their sequence code for proteins. This involves first transcription of DNA to messenger RNA (mRNA) following which the coding part is spliced and transported from the nucleus. Translation of mRNA to amino acids takes place in the endoplasmatic reticulum. Mutations in the nucleotide sequence (deletion, insertion, duplication or substitution) lead to a change in the reading of the sequence resulting in the production of no or of different proteins (gain of function and loss of function, respectively) with possibly a disease as the consequence.

DNA↗

[From gene to disease; marenostrine and familial Mediterranean fever].

Familial mediterranean fever (FMF) is an autosomal recessive hereditary disorder associated with mutations in the gene on chromosome 16 encoding the protein pyrine (marenostrine). Marenostrine is thought to stimulate the production of an inactivator of a chemotactic factor (possibly C5a). The mutations result in ongoing inflammation, a hallmark of FMF. DNA diagnosis of FMF is operational in Leiden University, the Netherlands, for one year now.

Complement C5a↗

Direct potentiometric information on total ionic concentrations.

Polymeric membrane ion-selective electrodes exhibit an apparently super-Nernstian response at low sample activities if inner solutions are used that induce strong zero-current fluxes of primary ions toward the inner compartment. This is due to the limited ion fluxes in the aqueous boundary layer near the membrane. In the presence of labile complexes, the effective flux rate is increased and the emf depends on the total concentration of the ions. The concept is illustrated experimentally with calcium-selective electrodes based on the ionophore N,N-dicyclohexyl-N',N'-dioctadecyl-3-oxapentanediamide (ETH 5234) that either respond to total or free ion concentrations. Samples can be distinguished that contain varying levels of total calcium but are all buffered with EDTA to the same free calcium concentration of 5 x 10(-8) M.

Electrodes↗