Showing papers by "Radboud University Nijmegen published in 2000"

The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide.

Abstract: Objective Since modern treatment of rheumatoid arthritis (RA) is shifting toward aggressive antirheumatic therapy in an early phase of the disease, diagnostic tests with high specificity are desirable. A new serologic test (anti–cyclic citrullinated peptide [anti-CCP] enzyme-linked immunosorbent assay [ELISA]) was developed to determine the presence of antibodies directed toward citrullinated peptides, using a synthetic peptide designed for this purpose. Methods A cyclic peptide variant that contains deiminated arginine (citrulline) was designed and used as antigenic substrate in ELISA. Test parameters and diagnostic characteristics of the test were studied in patients with and without RA, in patients with various infectious diseases, and in a group of patients from an early arthritis clinic (EAC). Results Using prevalent RA and non-RA sera, the anti-CCP ELISA proved to be extremely specific (98%), with a reasonable sensitivity (68%). Also, in the EAC study group, the anti-CCP ELISA appeared to be highly specific for RA (96%). In comparison with the IgM rheumatoid factor (IgM-RF) ELISA, the anti-CCP ELISA had a significantly higher specificity (96% for CCP versus 91% for IgM-RF; P = 0.016) at optimal cut-off values. The sensitivity of both tests for RA was moderate: 48% and 54% for the anti-CCP ELISA and the IgM-RF ELISA, respectively (P = 0.36). Combination of the anti-CCP and the IgM-RF ELISAs resulted in a significantly higher positive predictive value of 91% (P = 0.013) and a slightly lower negative predictive value of 78% (P = 0.35) as compared with the use of the IgM-RF ELISA alone. The ability of the 2 tests performed at the first visit to predict erosive disease at 2 years of followup in RA patients was comparable (positive predictive value 91%). Conclusion The anti-CCP ELISA might be very useful for diagnostic and therapeutic strategies in RA of recent onset.

Effects of mechanical forces on maintenance and adaptation of form in trabecular bone

Abstract: The architecture of trabecular bone, the porous bone found in the spine and at articulating joints, provides the requirements for optimal load transfer, by pairing suitable strength and stiffness to minimal weight according to rules of mathematical design1,2,3,4,5,6. But, as it is unlikely that the architecture is fully pre-programmed in the genes7, how are the bone cells informed about these rules, which so obviously dictate architecture? A relationship exists between bone architecture and mechanical usage8—while strenuous exercise increases bone mass9, disuse, as in microgravity and inactivity, reduces it10. Bone resorption cells (osteoclasts) and bone formation cells (osteoblasts) normally balance bone mass in a coupled homeostatic process of remodelling, which renews some 25% of trabecular bone volume per year. Here we present a computational model of the metabolic process in bone that confirms that cell coupling is governed by feedback from mechanical load transfer11,12,13.This model can explain the emergence and maintenance of trabecular architecture as an optimal mechanical structure, as well as its adaptation to alternative external loads.

Biting and Chewing in Overdentures, Full Dentures, and Natural Dentitions

Abstract: It has been suggested that the provision of dental implants can improve the oral function of subjects with severely resorbed mandibles, possibly restoring function to the level experienced by satisfied wearers of conventional complete dentures. Nevertheless, a quantitative comparison has never been made and can be drawn from the literature only with difficulty, since studies differ greatly in methodology. To make such a comparison, we measured bite force and chewing efficiency by using identical methods in subjects with overdentures, complete full dentures, and natural dentitions. Our results indicated that bite forces achieved with overdentures on dental implants were between those achieved with artificial and natural dentitions. Chewing efficiency was significantly greater than that of subjects with full dentures (low mandible), but was still lower than that of subjects with full dentures (high mandible) and overdentures on bare roots. Differences in the height of the mandible revealed significant differences in chewing efficiency between the two full-denture groups. Furthermore, subjects with a shortened dental arch exerted bite forces similar to those of subjects with a complete-natural dentition, but their chewing efficiency was limited due to the reduced occlusal area. For all groups combined, a significant correlation was found between maximum bite force and chewing efficiency. Nearly half of the variation in chewing efficiency was explained by bite force alone.

The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis.

Abstract: Objective To study the predictive value of anti–cyclic citrullinated peptide antibody (anti-CCP) in patients with recent-onset rheumatoid arthritis (RA). Methods Outcome in terms of physical disability (Health Assessment Questionnaire) and radiologic damage (modified Sharp method) over 3-year and 6-year periods was determined in an inception cohort of 273 RA patients who had had disease symptoms for >1 year at study entry. Anti-CCP titers were determined at baseline and considered positive as recently described. Their prognostic value was studied by means of multiple regression analysis, in which anti-CCP positivity, sex, age at study entry, IgM rheumatoid factor (IgM-RF) status, Disease Activity Score (DAS), HLA–DR4 status, and (in a separate group of patients) shared epitope status were used as independent variables, and radiologic damage and functional disability as dependent variables. Results Patients with anti-CCP had developed significantly more severe radiologic damage after 6 years of followup. In multiple regression analysis, radiologic damage after 6 years followup was significantly predicted by IgM-RF status, radiologic score at entry, and anti-CCP status. Functional disability was significantly predicted by sex, age at entry, IgM-RF status, and DAS. Conclusion Our data show that in almost 70% of RA patients, anti-CCP antibody is present at the early stages of disease. Anti-CCP–positive patients developed significantly more severe radiologic damage than patients who were anti-CCP negative, although in multiple regression analysis the additional predictive value was rather moderate.

Importance of Mangroves, Seagrass Beds and the Shallow Coral Reef as a Nursery for Important Coral Reef Fishes, Using a Visual Census Technique

Abstract: The nursery function of various biotopes for coral reef fishes was investigated on Bonaire, Netherlands Antilles. Length and abundance of 16 commercially important reef fish species were determined by means of visual censuses during the day in six different biotopes: mangrove prop-roots ( Rhizophora mangle ) and seagrass beds ( Thalassia testudinum ) in Lac Bay, and four depth zones on the coral reef (0 to 3 m, 3 to 5 m, 10 to 15 m and 15 to 20 m). The mangroves, seagrass beds and shallow coral reef (0 to 3 m) appeared to be the main nursery biotopes for the juveniles of the selected species. Mutual comparison between biotopes showed that the seagrass beds were the most important nursery biotope for juvenile Haemulon flavolineatum , H. sciurus , Ocyurus chrysurus , Acanthurus chirurgus and Sparisoma viride , the mangroves for juvenile Lutjanus apodus , L. griseus , Sphyraena barracuda and Chaetodon capistratus , and the shallow coral reef for juvenile H. chrysargyreum , L. mahogoni , A. bahianus and Abudefduf saxatilis . Juvenile Acanthurus coeruleus utilized all six biotopes, while juvenile H. carbonarium and Anisotremus surinamensis were not observed in any of the six biotopes. Although fishes showed a clear preference for a specific nursery biotope, most fish species utilized multiple nursery biotopes simultaneously. The almost complete absence of juveniles on the deeper reef zones indicates the high dependence of juveniles on the shallow water biotopes as a nursery. For most fish species an (partial) ontogenetic shift was observed at a particular life stage from their (shallow) nursery biotopes to the (deeper) coral reef. Cluster analyses showed that closely related species within the families Haemulidae, Lutjanidae and Acanthuridae, and the different size classes within species in most cases had a spatial separation in biotope utilization.

Elasticities: a review of methods and model limitations

Abstract: Elasticity is a perturbation measure in matrix projection models that quantifies the proportional change in population growth rate as a function of a proportional change in a demographic transition (growth, survival, reproduction, etc.). Elasticities thus indicate the relative “importance” of life cycle transitions for population growth and maintenance. In this paper, we discuss the applications of elasticity analysis, and its extension, loop analysis, in life history studies and conservation. Elasticity can be interpreted as the relative contribution of a demographic parameter to population growth rate. Loop analysis reveals the underlying pathway structure of the life cycle graph. The different kinds of results of the two analyses in studies of life histories are emphasized. Because elasticities quantify the relative importance of life cycle transitions to population growth rate, it is generally inferred that management should focus on the transitions with the largest elasticities. Such predictions based on elasticities seem robust, but we do identify three situations where problems may arise. The mathematical properties and biological constraints that underlie these pitfalls are explained. Examples illustrate the additional information that needs to be taken into account for a sensible use of elasticities in population management. We conclude by indicating topics that are in need of research.

Electrostatic trapping of ammonia molecules

Abstract: The ability to cool and slow atoms with light for subsequent trapping allows investigations of the properties and interactions of the trapped atoms in unprecedented detail. By contrast, the complex structure of molecules prohibits this type of manipulation, but magnetic trapping of calcium hydride molecules thermalized in ultra-cold buffer gas and optical trapping of caesium dimers generated from ultra-cold caesium atoms have been reported. However, these methods depend on the target molecules being paramagnetic or able to form through the association of atoms amenable to laser cooling, respectively, thus restricting the range of species that can be studied. Here we describe the slowing of an adiabatically cooled beam of deuterated ammonia molecules by time-varying inhomogeneous electric fields and subsequent loading into an electrostatic trap. We are able to trap state-selected ammonia molecules with a density of 10(6) cm(-3) in a volume of 0.25 cm3 at temperatures below 0.35 K. We observe pronounced density oscillations caused by the rapid switching of the electric fields during loading of the trap. Our findings illustrate that polar molecules can be efficiently cooled and trapped, thus providing an opportunity to study collisions and collective quantum effects in a wide range of ultra-cold molecular systems.

A test of crystal structure prediction of small organic molecules

Abstract: A collaborative workshop was held in May 1999 at the Cambridge Crystallographic Data Centre to test how well currently available methods of crystal structure prediction perform when given only the atomic connectivity for an organic compound. A blind test was conducted on a selection of four compounds and a wide range of methodologies representing the principal computer programs currently available were used. There were 11 participants who were allowed to propose at most three structures for each compound. No program gave consistently reliable results. However, seven proposed structures were close to an experimental one and were classified as `correct'. One compound occurred in two polymorphs, but only one form was predicted correctly among the calculated structures. The basic problem with lattice energy based methods of crystal structure prediction is that many structures are found within a few kJ mol−1 of the global minimum. The fine detail of the force-field methodology and parametrization influences the energy ranking within each method. Nevertheless, present methods may be useful in providing a set of structures as possible polymorphs for a given molecular structure.

Mutations in ARHGEF6 , encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation

Abstract: X-linked forms of mental retardation (XLMR) include a variety of different disorders and may account for up to 25% of all inherited cases of mental retardation1. So far, seven X-chromosomal genes mutated in nonspecific mental retardation (MRX) have been identified: FMR2, GDI1, RPS6KA3, IL1RAPL, TM4SF2, OPHN1 and PAK3 (refs 2–9). The products of the latter two have been implicated in regulation of neural plasticity by controlling the activity of small GTPases of the Rho family. Here we report the identification of a new MRX gene, ARHGEF6 (also known as αPIX or Cool-2), encoding a protein with homology to guanine nucleotide exchange factors for Rho GTPases (Rho GEF). Molecular analysis of a reciprocal X/21 translocation in a male with mental retardation showed that this gene in Xq26 was disrupted by the rearrangement. Mutation screening of 119 patients with nonspecific mental retardation revealed a mutation in the first intron of ARHGEF6 (IVS1-11T→C) in all affected males in a large Dutch family10. The mutation resulted in preferential skipping of exon 2, predicting a protein lacking 28 amino acids. ARHGEF6 is the eighth MRX gene identified so far and the third such gene to encode a protein that interacts with Rho GTPases.

Selection of antiepileptic drug polytherapy based on mechanisms of action: the evidence reviewed

Abstract: Summary: Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried in an attempt to improve effectiveness by improving efficacy, tolerability, or both. We reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be selected for combination therapy based on their mechanisms of action, and if so, which combinations are associated with increased effectiveness. Because various designs and methods of analysis were used in these studies, it was also necessary to evaluate the appropriateness of these approaches. Methods: Published papers reporting on AED polytherapy in animals or humans were identified by Medline search and by checking references cited in these papers. Results: Thirty-nine papers were identified reporting on two-drug AED combinations. Several combinations were reported to offer improved effectiveness, but no uniform approach was used in either animal or human studies for the evaluation of pharmacodynamic drug interactions; efficacy was often the only end point. Conclusions: There is evidence that AED polytherapy based on mechanisms of action may enhance effectiveness. In particular, combining a sodium channel blocker with a drug enhancing GABAergic inhibition appears to be advantageous. Combining two GABA mimetic drugs or combining an AMPA antagonist with an NMDA antagonist may enhance efficacy, but tolerability is sometimes reduced. Combining two sodium channel blockers seems less promising. However, given the incomplete knowledge of the pathophysiology of seizures and indeed of the exact mechanisms of action of AEDs, an empirical but rational approach for evaluating AED combinations is of fundamental importance. This would involve appropriate testing of all possible combinations in animal models and subsequent evaluation of advantageous combinations in clinical trials. Testing procedures in animals should include the isobologram method, and the concept of drug load should be the basis of studies in patients with epilepsy.

Couples dealing with cancer : Role and gender differences regarding psychological distress and quality of life

Abstract: The goal of the present study was to further knowledge on gender and role (i.e. patient versus partner) differences in psychological distress and quality of life as a consequence of dealing with cancer. There is some evidence that being the patient or the caregiver makes more difference for men than for women. In total, 173 couples facing various forms of cancer (two samples) and a control group of 80 couples completed the CES-D and Cantril's Ladder. Analyses of variance revealed that both female patients and female partners of patients perceived more psychological distress and a lower quality of life than women in healthy couples. In contrast, role did have an effect on men. Specifically, male patients scored as high on psychological distress and as low on quality of life as female patients and female partners, but psychological distress and quality of life did not differ between male partners of patients and their healthy controls. However, this effect was found in only one patient sample. The finding that female partners perceived more psychological distress and a lower quality of life than male partners could not be accounted for by differences in the physical condition of the patient or the partner.

Importance of shallow-water biotopes of a Caribbean bay for juvenile coral reef fishes: patterns in biotope association, community structure and spatial distribution

Abstract: Fish community structure of a non-estuarine inland bay on the Caribbean island of Curacao was determined in the mangroves, seagrass beds, algal beds, channel, fossil reef boulders, notches in fossil reef rock, and on the adjacent coral reef, using visual censuses in belt transects. Fish communities varied among biotopes, but some overlap was present. Fish density and species richness were highest at the boulders and on the coral reef, and extremely low on the algal beds, whereas the total number of individuals calculated for the entire bay was highest on the seagrass beds. Differ- ences in fish densities between biotopes were related to differences in structural complexity and amount of shelter. Fishes in the bay largely consisted of 17 (mainly commercially important) reef fish species, which used the bay biotopes only as a nursery during the juvenile part of their life cycle. Small juveniles of these species were most often found in the mangroves, whereas at intermediate sizes some were found in the channel. Large individuals and adults were found on the reef, and den- sities of several of these species were higher on the reef near the bay than on reefs located farther down-current. Fishes which spent their entire life cycles in either the bay or on the coral reef were also found, and the latter group showed a strong decrease in abundance with increasing distance into the bay. The density distribution of individual fish species was not homogeneous within the bay. In the mangroves and seagrass beds, spatial distribution of fishes was correlated with distance to the mouth of the bay, water transparency, amount of shelter, and the structural complexity of the biotope. Juveniles of 3 reef species showed an increase in size on the seagrass beds with distance from the mouth into the bay, whereas 1 bay species showed a decrease in size with this distance.

National Adaptation to European Integration: The Importance of Institutional Veto Points

Abstract: The repercussions of European integration on national policymaking have increasingly drawn scholarly attention, yet, the determinants of national adaptation to the European Union are still poorly understood. This article takes issue with evolving arguments which grant crucial importance to the "goodness of fit" between European provisions and national rules and practices for explaining the degree of national adjustment to European requirements. In the case of the implementation of the Packaging and Packaging Waste Directive in Germany, the Netherlands and the United Kingdom, the country with the greatest misfit, the United Kingdom, adapted more successfully than the country which only needed incremental adjustments, Germany. The German record was also worse than the Dutch, despite the higher adaptation pressure of the latter. The case study suggests that the number of institutional veto points that central governments has to face when imposing European provisions on their constituencies, ultimately tend to shape the pace and quality of implementation, regardless of differential degrees in the goodness of fit.

Patients in Europe evaluate general practice care: an international comparison.

Abstract: BACKGROUND: Patients' evaluations can be used to improve health care and compare general practice in different health systems. AIM: To identify aspects of general practice that are generally evaluated positively by patients and to compare opinions of patients in different European countries on actual care provision. METHOD: An internationally-validated questionnaire was distributed to and completed by patients in 10 European countries. A stratified sample of 36 practices per country, with at least 1080 patients per country, was included. A set of 23 validated questions on evaluations of different aspects of care was used, as well as questions on age, sex, overall health status, and frequency of visiting the GP. RESULTS: The patient sample included 17,391 patients in 10 different countries; the average response rate was 79% (range = 67% to 89%). In general, patients visiting their general practitioner (GP) were very positive about the care provided. For most of the 23 selected aspects of care more than 80% viewed care as good or excellent; in particular, keeping records confidential, GP listening to patients, time during consultations, and quick services in case of urgent problems were evaluated positively. Patients were relatively negative about organisational aspects of care. The evaluations in different countries were largely similar, with some interesting differences; for instance, service and organisational aspects were evaluated more positively in fee-for-service health systems. CONCLUSIONS: Patients in Europe are positive about general practice but improvements in practice management in some countries are requested. More research is needed to study the complex field of differences in expectations and evaluations between countries with different health systems.

Changes in growth, porosity, and radial oxygen loss from adventitious roots of selected mono- and dicotyledonous wetland species with contrasting types of aerenchyma

Abstract: Growth in stagnant, oxygen-deficient nutrient solution increased porosity in adventitious roots of two monocotyledonous (Carex acuta and Juncus effusus) and three dicotyledonous species (Caltha palustris, Ranunculus sceleratus and Rumex palustris) wetland species from 10 to 30% under aerated conditions to 20‐45%. The spatial patterns of radial oxygen loss (ROL), determined with rootsleeving oxygen electrodes, indicated a strong constitutive ‘barrier’ to ROL in the basal root zones of the two monocotyledonous species. In contrast, roots of the dicotyledonous species showed no significant ‘barrier’ to ROL when grown in aerated solution, and only a partial ‘barrier’ when grown in stagnant conditions. This partial ‘barrier’ was strongest in C. palustris, so that ROL from basal zones of roots of R. sceleratus and R. palustris was substantial when compared to the monocotyledonous species. ROL from the basal zones would decrease longitudinal diffusion of oxygen to the root apex, and therefore limit the maximum penetration depth of these roots into anaerobic soil. Further studies of a larger number of dicotyledonous wetland species from a range of substrates are required to elucidate the ecophysiological consequences of developing a partial, rather than a strong, ‘barrier’ to ROL.

ROD: a program for surface X-ray crystallography

Abstract: A brief description is given of the C-program ROD with which surface structures can be refined on the basis of X-ray data. All main features one encounters on surfaces, like roughness, relaxations, reconstructions and multiple domains, are taken into account. The program has proven to be a useful tool over the past ten years.

If bone is the answer, then what is the question?

Abstract: In the 19th century, several scientists attempted to relate bone trabecular morphology to its mechanical, load-bearing function. It was suggested that bone architecture was an answer to requirements of optimal stress transfer, pairing maximal strength to minimal weight, according to particular mathematical design rules. Using contemporary methods of analysis, stress transfer in bones was studied and compared with anatomical specimens, from which it was hypothesised that trabecular architecture is associated with stress trajectories. Others focused on the biological processes by which trabecular architectures are formed and on the question of how bone could maintain the relationship between external load and architecture in a variable functional environment. Wilhelm Roux introduced the principle of functional adaptation as a self-organising process based in the tissues. Julius Wolff, anatomist and orthopaedic surgeon, entwined these 3 issues in his book The Law of Bone Remodeling (translation), which set the stage for biomechanical research goals in our day. 'Wolff's Law' is a question rather than a law, asking for the requirements of structural optimisation. In this article, based on finite element analysis (FEA) results of stress transfer in bones, it is argued that it was the wrong question, putting us on the wrong foot. The maximal strength/minimal weight principle does not provide a rationale for architectural formation or adaptation; the similarity between trabecular orientation and stress trajectories is circumstantial, not causal. Based on computer simulations of bone remodelling as a regulatory process, governed by mechanical usage and orchestrated by osteocyte mechanosensitivity, it is shown that Roux's paradigm, conversely, is a realistic proposition. Put in a quantitative regulatory context, it can predict both trabecular formation and adaptation. Hence, trabecular architecture is not an answer to Wolff's question, in the sense of this article's title. There are no mathematical optimisation rules for bone architecture; there is just a biological regulatory process, producing a structure adapted to mechanical demands by the nature of its characteristics, adequate for evolutionary endurance. It is predicted that computer simulation of this process can help us to unravel its secrets.

Antiferromagnetism and d -wave superconductivity in cuprates: A cluster dynamical mean-field theory

Abstract: We present an approach to investigate the interplay of antiferromagnetism and d-wave superconductivity in the two-dimensional Hubbard model within a numerically exact cluster dynamical mean-field approximation. Self-consistent solutions with two nonzero order parameters exist in a wide range of doping level and temperatures. A linearized equation for the energy spectrum near the Fermi level has been solved. The resulting d-wave gap has the correct magnitude and k dependence, but some distortion compared to the pure ${d}_{{x}^{2}\ensuremath{-}{y}^{2}}$ superconducting order parameter due to the presence of underlying antiferromagnetic ordering.

Citrullination: a small change for a protein with great consequences for rheumatoid arthritis.

Abstract: A new autoantibody activity, which is almost 100% specific for rheumatoid arthritis (RA), has been found. The essential part of the B-cell epitope is a modified form of arginine (ie citrulline). The conversion of protein-contained arginine to citrulline is an enzymatic process that is carried out by peptidylarginine deiminase (PAD), an enzyme that appears to be hormonally controlled. Because of its remarkable specificity, citrullination and related processes might open new possibilities for studying the aetiology of RA.

Neonatal end-of-life decision making: Physicians' attitudes and relationship with self-reported practices in 10 European countries.

Abstract: ContextThe ethical issues surrounding end-of-life decision making for infants with adverse prognoses are controversial. Little empirical evidence is available on the attitudes and values that underlie such decisions in different countries and cultures.ObjectiveTo explore the variability of neonatal physicians' attitudes among 10 European countries and the relationship between such attitudes and self-reported practice of end-of-life decisions.Design and SettingSurvey conducted during 1996-1997 in 10 European countries (France, Germany, Italy, the Netherlands, Spain, Sweden, the United Kingdom, Estonia, Hungary, and Lithuania).ParticipantsA total of 1391 physicians (response rate, 89%) regularly employed in 142 neonatal intensive care units (NICUs).Main Outcome MeasuresScores on an attitude scale, which measured views regarding absolute value of life (score of 0) vs value of quality of life (score of 10); self-report of having ever set limits to intensive neonatal interventions in cases of poor neurological prognosis.ResultsPhysicians more likely to agree with statements consistent with preserving life at any cost were from Hungary (mean attitude scores, 5.2 [95% confidence interval {CI}, 4.9-5.5]), Estonia (4.9 [95% CI, 4.3-5.5]), Lithuania (5.5 [95% CI, 4.8-6.1]), and Italy (5.7 [95% CI, 5.3-6.0]), while physicians more likely to agree with the idea that quality of life must be taken into account were from the United Kingdom (attitude scores, 7.4 [95% CI, 7.1-7.7]), the Netherlands (7.3 [95% CI, 7.1-7.5]), and Sweden (6.8 [95% CI, 6.4-7.3]). Other factors associated with having a pro–quality-of-life view were being female, having had no children, being Protestant or having no religious background, considering religion as not important, and working in an NICU with a high number of very low-birth-weight newborns. Physicians with scores reflecting a more quality-of-life view were more likely to report that in their practice, they had set limits to intensive interventions in cases of poor neurological prognosis, with an adjusted odds ratio of 1.5 (95% CI, 1.3-1.7) per unit change in attitude score.ConclusionsIn our study, physicians' likelihood of reporting setting limits to intensive neonatal interventions in cases of poor neurological prognosis is related to their attitudes. After adjusting for potential confounders, country remained the most important predictor of physicians' attitudes and practices.