Showing papers by "University of Antwerp published in 2001"

Patient adherence to treatment: three decades of research: a comprehensive review

Abstract: Low compliance to prescribed medical interventions is an ever present and complex problem, especially for patients with a chronic illness With increasing numbers of medications shown to do more good than harm when taken as prescibed, low compliance is a major problem in health care Relevant studies were retrieved through comprehensive searches of different database systems to enable a thorough assessment of the major issues in compliance to prescribed medical interventions The term compliance is the main term used in this review because the majority of papers reviewed used this term Three decades have passed since the first workshop on compliance research It is timely to pause and to reflect on the accumulated knowledge The enormous amount of quantitative research undertaken is of variable methodological quality, with no gold standard for the measurement of compliance and it is often not clear which type of non-compliance is being studied Many authors do not even feel the need to define adherence Often absent in the research on compliance is the patient, although the concordance model points at the importance of the patient's agreement and harmony in the doctor-patient relationship The backbone of the concordance model is the patient as a decision maker and a cornerstone is professional empathy Recently, some qualitative research has identified important issues such as the quality of the doctor-patient relationship and patient health beliefs in this context Because non-compliance remains a major health problem, more high quality studies are needed to assess these aspects and systematic reviews/meta-analyses are required to study the effects of compliance in enhancing the effects of interventions

Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)

Abstract: Sclerosteosis is a progressive sclerosing bone dysplasia with an autosomal recessive mode of inheritance. Radiologically, it is characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened and sclerotic skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. By linkage analysis in one extended van Buchem family and two consanguineous sclerosteosis families we previously mapped both disease genes to the same chromosomal 17q12-q21 region, supporting the hypothesis that both conditions are caused by mutations in the same gene. After reducing the disease critical region to approximately 1 Mb, we used the positional cloning strategy to identify the SOST gene, which is mutated in sclerosteosis patients. This new gene encodes a protein with a signal peptide for secretion and a cysteine-knot motif. Two nonsense mutations and one splice site mutation were identified in sclerosteosis patients, but no mutations were found in a fourth sclerosteosis patient nor in the patients from the van Buchem family. As the three disease-causing mutations lead to loss of function of the SOST protein resulting in the formation of massive amounts of normal bone throughout life, the physiological role of SOST is most likely the suppression of bone formation. Therefore, this gene might become an important tool in the development of therapeutic strategies for osteoporosis.

De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy.

Abstract: Severe myoclonic epilepsy of infancy (SMEI) is a rare disorder that occurs in isolated patients. The disease is characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, andsimple and complex partial seizures. Psychomotor development stagnates around the second year of life. Missense mutations in the gene that codes for a neuronal voltage-gated sodium-channel α-subunit (SCN1A) were identified in families with generalized epilepsy with febrile seizures plus (GEFS+). GEFS+ is a mild type of epilepsy associated with febrile and afebrile seizures. Because both GEFS+ and SMEI involve fever-associated seizures, we screened seven unrelated patients with SMEI for mutations in SCN1A. We identified a mutation in each patient: four had frameshift mutations, one had a nonsense mutation, one had a splice-donor mutation, and one had a missense mutation. All mutations are de novo mutations and were not observed in 184 control chromosomes.

Productivity overshadows temperature in determining soil and ecosystem respiration across European forests

Abstract: Summary This paper presents CO2 flux data from 18 forest ecosystems, studied in the European Union funded EUROFLUX project. Overall, mean annual gross primary productivity (GPP, the total amount of carbon (C) fixed during photosynthesis) of these forests was 1380 ± 330 gC m−2 y−1 (mean ±SD). On average, 80% of GPP was respired by autotrophs and heterotrophs and released back into the atmosphere (total ecosystem respiration, TER = 1100 ± 260 gC m−2 y−1). Mean annual soil respiration (SR) was 760 ± 340 gC m−2 y−1 (55% of GPP and 69% of TER). Among the investigated forests, large differences were observed in annual SR and TER that were not correlated with mean annual temperature. However, a significant correlation was observed between annual SR and TER and GPP among the relatively undisturbed forests. On the assumption that (i) root respiration is constrained by the allocation of photosynthates to the roots, which is coupled to productivity, and that (ii) the largest fraction of heterotrophic soil respiration originates from decomposition of young organic matter (leaves, fine roots), whose availability also depends on primary productivity, it is hypothesized that differences in SR among forests are likely to depend more on productivity than on temperature. At sites where soil disturbance has occurred (e.g. ploughing, drainage), soil espiration was a larger component of the ecosystem C budget and deviated from the relationship between annual SR (and TER) and GPP observed among the less-disturbed forests. At one particular forest, carbon losses from the soil were so large, that in some years the site became a net source of carbon to the atmosphere. Excluding the disturbed sites from the present analysis reduced mean SR to 660 ± 290 gC m−2 y−1, representing 49% of GPP and 63% of TER in the relatively undisturbed forest ecosystems.

Oceanic 18S rDNA sequences from picoplankton reveal unsuspected eukaryotic diversity

Abstract: Picoplankton—cells with a diameter of less than 3 µm—are the dominant contributors to both primary production and biomass in open oceanic regions1,2. However, compared with the prokaryotes3, the eukaryotic component of picoplankton is still poorly known. Recent discoveries of new eukaryotic algal taxa based on picoplankton cultures4,5 suggest the existence of many undiscovered taxa. Conventional approaches based on phenotypic criteria have limitations in depicting picoplankton composition due to their tiny size and lack of distinctive taxonomic characters6. Here we analyse, using an approach that has been very successful for prokaryotes7 but has so far seldom been applied to eukaryotes8, 35 full sequences of the small-subunit (18S) ribosomal RNA gene derived from a picoplanktonic assemblage collected at a depth of 75 m in the equatorial Pacific Ocean, and show that there is a high diversity of picoeukaryotes. Most of the sequences were previously unknown but could still be assigned to important marine phyla including prasinophytes, haptophytes, dinoflagellates, stramenopiles, choanoflagellates and acantharians. We also found a novel lineage, closely related to dinoflagellates and not previously described.

Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions

Abstract: Progressive external ophthalmoplegias (PEO) characterized by accumulation of large-scale mitochondrial DNA (mtDNA) deletions are rare human diseases. We mapped a new locus for dominant PEO at 15q22-q26 in a Belgian pedigree and identified a heterozygous mutation (Y955C) in the polymerase motif B of the mtDNA polymerase gamma (POLG). We identified three additional POLG missense mutations compatible with recessive PEO In two nuclear families. POLG is the only DNA polymerase responsible for mtDNA replication.

Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination

Abstract: Fragile-X syndrome is a common form of mental retardation resulting from the inability to produce the fragile-X mental retardation protein. Qualitative examination of human brain autopsy material has shown that fragile-X patients exhibit abnormal dendritic spine lengths and shapes on parieto-occipital neocortical pyramidal cells. Similar quantitative results have been obtained in fragile-X knockout mice, that have been engineered to lack the fragile-X mental retardation protein. Dendritic spines on layer V pyramidal cells of human temporal and visual cortices stained using the Golgi-Kopsch method were investigated. Quantitative analysis of dendritic spine length, morphology, and number was carried out on patients with fragile-X syndrome and normal age-matched controls. Fragile-X patients exhibited significantly more long dendritic spines and fewer short dendritic spines than did control subjects in both temporal and visual cortical areas. Similarly, fragile-X patients exhibited significantly more dendritic spines with an immature morphology and fewer with a more mature type morphology in both cortical areas. In addition, fragile-X patients had a higher density of dendritic spines than did controls on distal segments of apical and basilar dendrites in both cortical areas. Long dendritic spines with immature morphologies and elevated spine numbers are characteristic of early development or a lack of sensory experience. The fact that these characteristics are found in fragile-X patients throughout multiple cortical areas may suggest a global failure of normal dendritic spine maturation and or pruning during development that persists throughout adulthood.

Stomatal conductance of forest species after long‐term exposure to elevated CO2 concentration: a synthesis

Abstract: • Data from 13 long-term (> 1 yr), field-based studies of the effects of elevated CO2 concentration ([CO2]) on European forest tree species were analysed using meta-analysis and modelling. Meta-analysis was used to determine mean responses across the data sets, and data were fitted to two commonly used models of stomatal conductance in order to explore response to environmental conditions and the relationship with assimilation. • Meta-analysis indicated a significant decrease (21%) in stomatal conductance in response to growth in elevated [CO2] across all studies. The response to [CO2] was significantly stronger in young trees than old trees, in deciduous compared to coniferous trees, and in water stressed compared to nutrient stressed trees. No evidence of acclimation of stomatal conductance to elevated [CO2] was found. • Fits of data to the first model showed that growth in elevated [CO2] did not alter the response of stomatal conductance to vapour pressure deficit, soil water content or atmospheric [CO2]. Fits of data to the second model indicated that conductance and assimilation responded in parallel to elevated [CO2] except when water was limiting. • Data were compared to a previous meta-analysis and it was found that the response of gs to elevated [CO2] was much more consistent in long-term (> 1 yr) studies, emphasising the need for long-term elevated [CO2] studies. By interpreting data in terms of models, the synthesis will aid future modelling studies of responses of forest trees to elevated [CO2].

Structural changes in logistics: how will port authorities face the challenge?

Abstract: The market environment in which ports operate has changed dramatically, and this continuous process of change raises questions on the role of port authorities. This paper discusses the impact of some structural changes in international trade, transport and shipping on strategic and operational issues in the framework of port management. The central hypothesis put forward is that a successful port (authority), like a successful actor, must be prepared to constantly adopt new roles in order to cope with the changing market environment. The content and strategic scope of these new roles are highlighted, especially with regard to the European container port system.

Epistemic Modality, Language, and Conceptualization: A cognitive-pragmatic perspective

Abstract: The relationship between language and conceptualization remains one of the major puzzles in language research. This monograph addresses this issue by means of an in depth corpus based and experimental investigation of the major types of expressions of epistemic modality in Dutch, German and English. By adopting a systematic functional orientation, the book explains a whole range of peculiarities of epistemic expression forms (synchronically and diachronically), and it offers a clear perspective on which cognitive systems are needed to get from the concept of epistemic modality to its linguistic expression. On that basis the author postulates a sophisticated, layered view of human conceptualization. This book is of interest both to scholars working on modality and related semantic dimensions, and to the interdisciplinary field of researchers concerned with the cognitive systems involved in language use.

Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene

Abstract: Albers-Schonberg disease, or autosomal dominant osteopetrosis, type II (ADO II), is the most common form of osteopetrosis, a group of conditions characterized by an increased skeletal mass due to impaired bone and cartilage resorption. Following the assignment of the gene causing ADO II to chromosome 16p13.3, we now report seven different mutations in the gene encoding the ClCN7 chloride channel in all 12 ADO II families analysed. Additionally, a patient with the severe, autosomal recessive, infantile form of osteopetrosis (ARO) was identified as being homozygous for a ClCN7 mutation. From genotype-phenotype correlations, it seems that ADO II reflects a dominant negative effect, whereas loss-of-function mutations in ClCN7 do not cause abnormalities in heterozygous individuals. Because some ARO patients have mutations in both copies of the ClCN7 gene, ADO II is allelic with a subset of ARO cases.

Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep apnea

Abstract: Background Hypoglossal nerve stimulation has been demonstrated to relieve upper airway obstruction acutely, but its effect on obstructive sleep apnea is not known. Objective To determine the response in obstructive sleep apnea to electrical stimulation of the hypoglossal nerve. Methods Eight patients with obstructive sleep apnea were implanted with a device that stimulated the hypoglossal nerve unilaterally during inspiration. Sleep and breathing patterns were examined at baseline before implantation and after implantation at 1, 3, and 6 months and last follow-up. Results Unilateral hypoglossal nerve stimulation decreased the severity of obstructive sleep apnea throughout the entire study period. Specifically, stimulation significantly reduced the mean apnea-hypopnea indices in non–rapid eye movement (mean ± SD episodes per hour, 52.0 ± 20.4 for baseline nights and 22.6 ± 12.1 for stimulation nights; P P Conclusion The findings demonstrate the feasibility and therapeutic potential for hypoglossal nerve stimulation in obstructive sleep apnea.

Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F

Abstract: We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function

Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia.

Abstract: The liver is a highly vascularized organ which frequently hosts metastases in patients with colorectal adenocarcinomas. The hypothesis of this study is that the hypoxic drive of angiogenesis might be minimal or absent in those growing liver metastases which are capable of preserving the stromal structure, including the numerous sinusoidal blood vessels. Representative paraffin sections of liver metastases from 26 patients with colorectal adenocarcinoma were investigated. Three different growth patterns were found. In the desmoplastic and in the pushing growth patterns (42% and 46% of all metastases, respectively), the architecture of the liver parenchyma was not preserved. In the replacement growth pattern (12% of all cases), the reticulin pattern of the liver parenchyma was conserved within the metastases at the tumour-liver parenchyma interface. The endothelial cells of the blood vessels near the interface in the metastases of the replacement type did not express CD34, nor were they surrounded by alpha-smooth muscle actin-positive mural cells. In the desmoplastic and in the pushing growth patterns, 23% and 52% of all blood vessels in this area were covered by pericytes. The fraction of proliferating endothelial cells was low in the metastases with a desmoplastic or a replacement growth pattern (about 3%), compared with metastases with a pushing growth pattern (11%). Tumour cell apoptosis was highest in the pushing-type metastases and was inversely correlated with microvessel density in liver metastases. The ratio of the proliferating tumour cell fraction and the proliferating endothelial cell fraction, roughly representing the degree of angiogenesis-dependent growth, was three- to four-fold higher in the replacement-type metastases compared with the other metastases. In summary, the present study has demonstrated that liver metastases are a heterogeneous group, with different growth patterns which predict the fraction of immature blood vessels, the fraction of proliferating endothelial cells, and the fraction of apoptotic tumour cells. The replacement growth pattern expands with minimal angiogenesis by co-opting the stroma with the sinusoidal blood vessels of the liver.

Apoptotic versus autophagic cell death in heart failure.

Abstract: Objective: Progressive loss of cardiomyocytes is one of the most important pathogenic characteristics of heart failure. Apoptosis may be an important mode of cell death in heart failure but it must be demonstrated by multiple criteria and not just TUNEL staining alone. Previously, we and others have demonstrated that besides apoptosis other phenomena like active gene transcription can result in TUNEL positivity. Moreover, other types of cell death that are caspase-independent could be important in heart failure. This study examined the hypothesis whether TUNEL labeling parallels caspase activation. Methods: Cardiac tissue of patients in the terminal stage of heart failure as a consequence of ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) were studied. Embryonic mice hearts were used for positive control for detection of the classical apoptosis. Results: In mice embryonic hearts we could clearly find apoptotic cell death detected by TUNEL labeling and immunohistochemistry for activated caspase-3. In heart failure, TUNEL-positive cardiomyocytes were negative for active caspase-3 but showed signs of active gene transcription (SC-35). However, autophagic cell death could be found in 0.3% of the cardiomyocytes. Autophagic cell death was demonstrated by granular cytoplasmic ubiquitin inclusions, an established marker of autophagocytosis in neurons. Interestingly, these autophagic cardiomyocytes were TUNEL and activated caspase-3 negative but were also negative for C9, a marker for necrosis. Western blot analysis confirmed that in cardiomyopathies no cleavage of caspase-3 and caspase-7 occurred. Conclusion: The present study demonstrates two fundamentally different situations of cell death in cardiac tissue. In embryonic mice, cardiomyocytes undergo caspase-dependent cell death. However, cardiomyocytes in heart failure show caspase-independent autophagic cell death rather than apoptotic cell death.

Who is that (wo)man in the street? From the normalisation of protest to the normalisation of the protester

Abstract: The time has long since passed that protests and demonstrations were regarded as the possible beginning of violent revolutionary ferment. Venting dissatisfaction or making demands in the streets has become commonplace in our 'demonstration-democracy'. In this article we examine whether this normalisation of street protest also means that more het- erogeneous groups of people take to the streets. Have citizens become potentially peaceful protesters or is protest politics still the domain of union militants, progressive intellectuals, and committed students? In answering these questions we will use the three research methods most commonly used for studying collective action: population surveys, protest event-analysis and interviews with protesters at demonstrations.

A comparison of microsatellite-based pairwise relatedness estimators.

Abstract: Studies of inbreeding depression or kin selection require knowledge of relatedness between individuals. If pedigree information is lacking, one has to rely on genotypic information to infer relatedness. In this study we investigated the performance (absolute and relative) of 10 marker-based relatedness estimators using allele frequencies at microsatellite loci obtained from natural populations of two bird species and one mammal species. Using Monte Carlo simulations we show that many factors affect the performance of estimators and that different sets of loci promote the use of different estimators: in general, there is no single best-performing estimator. The use of locus-specific weights turns out to greatly improve the performance of estimators when marker loci are used that differ strongly in allele frequency distribution. Microsatellite-based estimates are expected to explain between 25 and 79% of variation in true relatedness depending on the microsatellite dataset and on the population composition (i.e. the frequency distribution of relationship in the population). We recommend performing Monte Carlo simulations to decide which estimator to use in studies of pairwise relatedness.