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Biomedical subjects

A Visser

Publications and source records attributed to A Visser.

At least 19 recordsLinked to original sources

Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an inherited neurologic disorder with macrocephaly before the age of one and slowly progressive deterioration of motor functions. Magnetic resonance imaging shows diffusely abnormal and swollen white matter of the cerebral hemispheres and the presence of subcortical cysts in the anterior-temporal region and often also in the frontoparietal region. Mutations in the MLC1 gene, encoding a putative membrane protein, have been recently identified as a cause for MLC. Here, we describe 14 new mutations in 18 patients. Two identified polymorphisms lead to alterations of amino acid residues. The role, suggested by others, of a mutation in the MLC1gene in catatonic schizophrenia and the possible function of the MLC1 protein as a cation channel are discussed.

Amino Acid Sequence↗

Differentiation of murine preosteoblastic KS483 cells depends on autocrine bone morphogenetic protein signaling during all phases of osteoblast formation.

In this study, we examine the role of bone morphogenetic protein (BMP) signaling during differentiation of the murine preosteoblastic KS483 cell line, which formed alkaline phosphatase (ALP)-positive and mineralized nodules during a 3 week culture period. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) demonstrated the presence of various BMPs (BMP-2, -3, -4, -6, -7, and -8A and -8B), BMP type I and II receptors (ALK2, ALK3, ALK4, BMPR-II, and ActR-IIA and -IIB), BMP antagonists (DAN, gremlin, chordin, cerberus, noggin, and tsg), and Smads 1-8. mRNA expression of these genes did not change during differentiation, except for BMP-3, BMP-8a, and noggin. BMP-3 increased gradually, particularly in the matrix formation phase; BMP-8a was induced from the onset of matrix maturation and mineralization, in parallel to the expression of osteocalcin; and noggin tended to decline during the mineralization phase. Treatment of KS483 cells with the BMP antagonists noggin or soluble truncated BMPR-IA, either continuously or during distinct periods of osteoblast differentiation; that is, matrix formation or matrix maturation and mineralization phase, decreased ALP-positive and mineralized nodule area independent of the phase of osteoblast differentiation. Notably, the antagonists inhibited mineralization of already existing nodules. Similarly, BMP-4 stimulated differentiation not only at the beginning of the culture period, but also at late stages of differentiation. These data indicate that autocrine BMP signaling is involved in KS483 osteoblastic differentiation not only during the early phase of differentiation, but also during matrix maturation and mineralization. The different expression patterns of components of BMP signaling in the KS483 cells suggest distinct functions of individual BMPs during osteoblast differentiation. In summary, our data suggest that BMP activity is required not only for initiation of osteoblast differentiation and further development of early osteoblasts, but is also involved in late-stage osteoblast differentiation and matrix mineralization.

Activin Receptors, Type I↗

Five years of aftercare of implant-retained mandibular overdentures and conventional dentures.

The purpose of this multicentre randomized clinical trial was to analyse surgical and prosthetic aftercare and clinical implant performance of edentulous patients with implant-retained mandibular overdentures and of patients with conventional dentures, either or not after pre-prosthetic vestibuloplasty and deepening of the floor of the mouth. The evaluation period was 5 years. The implant systems evaluated were the IMZ implant system, the Brånemark implant system and the Transmandibular Implant system. The centre in Groningen had five groups (n=149) and the centre in Nijmegen had three groups (n=86). The evaluation comprised of surgical and prosthetic aftercare, together with clinical implant performance (CIP). The highest implant loss (29%) is found in the Transmandibular Implant group. All groups had prosthetic revisions and complications according to the CIP-scale. The majority of the patients in the endosseous implant groups were subject to minor complications. The CIP-score of the Transmandibular Implant group is significantly higher than the scores of the other groups, because of the high number of lost posts. In 26;1% of the patients in this group score 4 is given, which means failure of the implant system. From this study it can be concluded that the endosseous implant systems used in this study have less surgical aftercare and a better clinical implant performance than the Transmandibular Implant system and are therefore the systems of choice for the edentulous mandible.

Aftercare↗

Radiation-induced changes in gene expression and distribution of atrial natriuretic peptide (ANP) in different anatomical regions of the rat heart.

PURPOSE: To examine the effects of whole-heart irradiation on gene expression and distribution of atrial natriuretic peptide (ANP) in atrial appendages and left ventricles of the rat heart. MATERIAL AND METHODS: Female Sprague-Dawley rats were irradiated with a single dose of 0, 15 or 20 Gy locally to the heart. At intervals up to 16 months post-irradiation, the localization of ANP was examined using immunohistochemical techniques. Absolute mRNA concentrations were determined using the competitive PCR assay. RESULTS: Histological and immunohistochemical studies demonstrated that whole-heart irradiation caused a reduction of atrial ANP, which is due to a substantial loss of ANP-producing atrial myocytes and accumulation of collagen (replacement fibrosis). On the other hand, ANP became detectable in the subendocardium of the irradiated left ventricles. Positive staining of ANP was mainly found in the proximity of injured areas consisting of degeneration of myocytes and fibrosis. At the transcriptional level, reduction of atrial ANP expression at 1 month post-irradiation was followed by recovery at 3 months. Thereafter, ANP mRNA concentrations followed the mRNA pattern of controls and even appeared to increase at 16 months. In the left ventricle, dose-dependent and progressive elevation of ANP gene expression could be observed during the observation period and reached a 20-fold increase as compared with sham-irradiated age-matched controls. CONCLUSIONS: The distribution of ANP after local irradiation of the rat heart depends on the severity of the pathological/structural changes (i.e. myocyte degeneration and fibrosis). In radiation-induced heart disease, elevated ANP expression in the left ventricle is most probably involved in the observed chronic elevation of plasma ANP levels.

Animals↗

Bulking sludge solved?!

At present there is still no final theory explaining the bulking of activated sludge. Previous investigations showed that the sludge settling properties become better and more stable when more plug flow conditions are implemented in wastewater treatment plants for biological nutrient removal. In this research the effect of the process configuration (4 wwtp with fully biological nutrient removal) on the sludge settling properties has been investigated. The results show that a separate anoxic reactor can not avoid the presence of LCFA for the growth of M. parvicella in the anaerobic reactor. A SVI < 120 ml/g could be achieved by: of a separate anoxic reactor with plug flow conditions, introducing of a strictly anaerobic reactor (UCT-modification), implementation of an extra anoxic/aerobic reactor, maintaining a high oxygen concentration (> 1.5 mg/l) and creating a low ammonium concentration (< 1 mg/l) in the aerobic reactor.

Actinobacteria↗

Effectiveness of couch height-based patient set-up and an off-line correction protocol in prostate cancer radiotherapy.

PURPOSE: To investigate set-up improvement caused by applying a couch height-based patient set-up method in combination with a technologist-driven off-line correction protocol in nonimmobilized radiotherapy of prostate patients. METHODS AND MATERIALS: A three-dimensional shrinking action level correction protocol is applied in two consecutive patient cohorts with different set-up methods: the traditional "laser set-up" group (n = 43) and the "couch height set-up" group (n = 112). For all directions, left-right, ventro-dorsal, and cranio-caudal, random and systematic set-up deviations were measured. RESULTS: The couch height set-up method improves the patient positioning compared to the laser set-up method. Without application of the correction protocol, both systematic and random errors reduced to 2.2-2.4 mm (1 SD) and 1.7-2.2 mm (1 SD), respectively. By using the correction protocol, systematic errors reduced further to 1.3-1.6 mm (1 SD). One-dimensional deviations were within 5 mm for >90% of the measured fractions. The required number of corrections per patient in the off-line correction protocol was reduced significantly during the course of treatment from 1.1 to 0.6 by the couch height set-up method. The treatment time was not prolonged by application of the correction protocol. CONCLUSIONS: The couch height set-up method improves the set-up significantly, especially in the ventro-dorsal direction. Combination of this set-up method with an off-line correction strategy, executed by technologists, reduces the number of set-up corrections required.

Humans↗

Reduction of irradiated small bowel volume and accurate patient positioning by use of a bellyboard device in pelvic radiotherapy of gynecological cancer patients.

PURPOSE: To reduce the volume of small bowel within pelvic treatment fields for gynecological cancer using a bellyboard device and to determine the accuracy of the prone treatment position. MATERIALS AND METHODS: Fifteen consecutive patients with a gynecologic malignancy who were treated with postoperative pelvic radiotherapy were selected for this study. The volume of small bowel within the treatment fields was calculated for both the supine and prone treatment positions. The patients were treated in the prone position in a so-called bellyboard device. During treatment sessions electronic portal images were obtained. An off-line setup verification and correction protocol was used and the setup accuracy of the positioning in the bellyboard was determined. RESULTS: The average volume of small bowel within the treatment fields was 229 cm(3) and 66 cm(3) in the supine and prone treatment, respectively, which means an average volume reduction in the prone position of 64% (95% CI 56-72%), as compared with the supine position. For the position of the patient in the field, the systematic error defined by the standard deviation (SD) of the mean difference per patient between simulation and treatment images was 1.7 mm in the lateral direction, 2.1 mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On average, only 0.4 setup correction per patient was required to achieve this accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm, respectively. Standard deviations of the systematic differences between patient positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1 mm in craniocaudal direction. CONCLUSIONS: Treatment of gynecological cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. An off-line verification and correction protocol ensures accurate patient positioning. Daily setup variations using the bellyboard were small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a gynecological malignancy, the use of a bellyboard is recommended.

Aged↗

Patient education in The Netherlands.

This article presents the development of patient education (PE) in The Netherlands from a historical perspective. A description is given of the first pioneering years from the 70s till the late 80s, in which early topics like the organization of PE, the orchestration of PE between different disciplines, the role of the social environment, the provision of PE in difficult patient groups and--most of all--the technical development of educational materials took the time and attention of the growing group of professionals that were engaged in patient education. Recent developments concern the legal aspects of PE, national policy, the role of health insurance, the position of patient organizations and the development of patient education in specific professional groups, e.g. general practitioners, nurses, physiotherapists, pharmacists, and dentists. There is no doubt that patient education has been professionalized considerably during the last decades. Nevertheless, new issues emerge and some old issues still need to be solved. The effective use of information material, the need for counseling as part of PE, and the relevance of coordination of care are longtime, but still actual problems in PE. More recent issues are the pressures on PE because of capacity restraints, the influence of the media and perhaps most of all: the apparent need for a patient-centered attitude and a more two-sided way of communication. Finally, the future policy topics in the Dutch patient education are discussed.

Health Plan Implementation↗

Patient education in Europe: united differences.

This issue of Patient Education and Counseling presents the state of the art of patient education in several European countries. It is based on papers presented at a meeting in Paris on the evolution and development of patient education in western, central and eastern Europe (May 1999). Also patient education in the US is presented in this issue. Patient education is defined as all the educational activities directed to patients, including aspects of therapeutic education, health education and clinical health promotion. Five important factors are identified in the development of patient education: (1) research and evidence based standards; (2) the organization of care; (3) training and methodological support; (4) professional values; and (5) acknowledgment, funding and place of patient education in health policy. Several of the discussed common orientations and priorities in the patient education in the reviewed countries are highlighted in this issue. And finally, an example of the possible integrated international practice in patient education in the field of diabetes is described in this issue. Several conclusions are drawn concerning future development of communication in health care within the framework of patient education in Europe.

Communication↗

Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter.

Leukoencephalopathy with vanishing white matter (VWM) is an inherited brain disease that occurs mainly in children. The course is chronic-progressive with additional episodes of rapid deterioration following febrile infection or minor head trauma. We have identified mutations in EIF2B5 and EIF2B2, encoding the epsilon- and beta-subunits of the translation initiation factor eIF2B and located on chromosomes 3q27 and 14q24, respectively, as causing VWM. We found 16 different mutations in EIF2B5 in 29 patients from 23 families. We also found two distantly related individuals who were homozygous with respect to a missense mutation in EIF2B2, affecting a conserved amino acid. Three other patients also had mutations in EIF2B2. As eIF2B has an essential role in the regulation of translation under different conditions, including stress, this may explain the rapid deterioration of people with VWM under stress. Mutant translation initiation factors have not previously been implicated in disease.

Base Sequence↗

Most marginal zone B cells in rat express germline encoded Ig VH genes and are ligand selected.

The present study was performed to analyze whether marginal zone B (MZ-B) cells in nondeliberately immunized adult rats are selected on basis of the specificity of their B cell receptor, and to determine to what extent memory B cells contribute to the MZ-B cell subset. To this end, the Ig PC7183 V(H) gene repertoire was studied among V(H)DJ(H)-mu transcripts expressed in four sequential stages of B cell development, of two individual untreated adult rats. B cell subsets, i.e., pro/pre-B cells and newly formed B (NF-B) cells from bone marrow, and recirculating follicular B cells and MZ-B cells from spleen were sorted by flow cytometry. In addition, from one these rats, cells were microdissected from follicular and MZ areas of the spleen and productive PC7183 V(H) gene rearrangements were analyzed for the presence of somatic mutations. Sequence analysis reveals that most MZ-B cells in the adult rat, either defined by flow cytometry or by their anatomical location in the spleen, express germline encoded V(H) genes (naive MZ-B cells) and a minor fraction (about 20%) of the MZ-B cells carry somatic mutations (memory MZ-B cells). In addition, we show that naive MZ-B cells are a selected population of cells, both based on PC7183 V(H) gene repertoire and on the length of the Ig heavy (H) chain complementarity-determining region 3 (H-CDR3) region, i.e., PC7183 V(H)DJ(H)-mu transcripts of MZ-B cells carry significantly shorter H-CDR3 regions than other B cell subsets.

Amino Acid Sequence↗

EST sequencing of the parasitic nematode Haemonchus contortus suggests a shift in gene expression during transition to the parasitic stages.

Expressed sequence tags from the parasitic nematode Haemonchus contortus were generated in order to identify anchor loci for comparative mapping between nematode genomes and candidate targets for future control measures. In total, 370 SL1 trans-spliced cDNAs from different developmental stages representing 195 different genes were partially sequenced. From these expressed sequence tags 50% were similar to genes with a known or predicted function and 19% were similar to nematode sequences with no ascribed function. From the first, free-living L1 and L3 stages relatively many cDNAs matched to housekeeping genes, and 11% (L1) or 23% (L3) of the encoded proteins were predicted to contain signal peptides. In contrast, no function could be ascribed to most of the cDNAs from the early L5 and adult parasitic stages, but for 30% (L5) or 55% (adult) of the encoded proteins a signal sequence was predicted. This limited analysis suggests that during the transition from the free-living to parasitic stages gene expression shifts towards the synthesis of less conserved extracellular proteins. These proteins offer the best perspectives for vaccine development and the development of anthelmintic drugs. In contrast, cDNAs from the first larval stages may be most suitable for comparative mapping with the free-living nematode Caenorhabditis elegans.

Animals↗

Caring for caregivers: experiences and evaluation of interventions for a palliative care team.

Palliative care is a fairly recent development in The Netherlands. The first palliative unit in a hospital setting was the Palliative Care Unit (PCU) in the Dr Daniel den Hoed Clinic, a specialized oncology hospital, now part of the Academic Hospital Rotterdam (AZR-Daniel). This PCU was designed to function as an academic laboratory, where palliative care concepts are being developed, put into practice, and evaluated. It's mission was to put the patient first in mind, heart and soul. Right from the start, special attention was paid to the implementation a system of 'care for caregivers' in order to support the staff of the PCU in caring for the terminally ill and to prevent burnout. A process evaluation has been carried out with a special focus on the effects of the implementation of the new unit on the wellbeing of the interdisciplinary team of caregivers during the first year of its existence and on the experiences with a residential training preceding the start of patient care activities and the weekly staff support meetings. In the second half of the first year, the PCU staff experienced increased levels of job-related stress. Most stress was attributed to organizational factors, related to management issues but also to lack of institutional support. Teamwork also contributed to stress within the interdisciplinary team. Direct patient care activities also had some impact on experienced stress levels, through a heavy work-load of complex care, a shortage of staff and an experienced lack of competence. While the staff support activities were designed to give emotional support and deal with death and bereavement, these issues did not arise as major problems. As a consequence, the staff support in the PCU was perhaps less successful than it could have been. However, the high stress levels of this innovative palliative team warrant attention. We discuss how support meetings could be a more effective way of caring for staff. They should be accompanied by adequate resources, a supportive management structure, and an extensive educational program.

Adult↗

Issues in Dutch palliative care: readjusting a distorted image.

This issue presents a review of several issues in Dutch palliative care, paying attention to readjusting a distorted image due to the euthanasia practice in the Netherlands. A few articles stress the evolution of palliative care (especially in the UK and the Netherlands), developed palliative care services in the Netherlands, and new developments in the Netherlands concerning the prevention of euthanasia through palliative care. Also the needs concerning palliative care for children as well as for chronic psycho-geriatrics patients are presented. Further attention is paid to the organisation of palliative care, focusing at evaluative research on palliative support teams, caring for caregivers (experiences and evaluation of interventions for palliative care teams), and effects of transmural care on coordination and continuity of care. Finally, some articles focus on ethical considerations in the treatment of pain in hospice movement, ethical evaluation of clinical trials in palliative care, and the role of informed consent in palliative radiotherapy, stressing the participation of patients and proxies in treatment decisions. Conclusions are presented on the consequences for educational and counselling aspects of palliative care.

Ethics, Medical↗