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Biomedical subjects

A Visser

Publications and source records attributed to A Visser.

At least 19 recordsLinked to original sources

RNA interference in parasitic helminths: current situation, potential pitfalls and future prospects.

RNA interference (RNAi) has become an invaluable tool for the functional analysis of genes in a wide variety of organisms including the free-living nematode Caenorhabditis elegans. Recently, attempts have been made to apply this technology to parasitic helminths of animals and plants with variable success. Gene knockdown has been reported for Schistosoma mansoni by soaking or electroporating different life-stages in dsRNA. Similar approaches have been tested on parasitic nematodes which clearly showed that, under certain conditions, it was possible to interfere with gene expression. However, despite these successes, the current utility of this technology in parasite research is questionable. First, problems have arisen with the specificity of RNAi. Treatment of the parasites with dsRNA resulted, in many cases, in non-specific effects. Second, the current RNAi methods have a limited efficiency and effects are sometimes difficult to reproduce. This was especially the case in strongylid parasites where only a small number of genes were susceptible to RNAi-mediated gene knockdown. The future application of RNAi in parasite functional genomics will greatly depend on how we can overcome these difficulties. Optimization of the dsRNA delivery methods and in vitro culture conditions will be the major challenges.

Animals↗

C21ORF105, A chromosome 21-encoded mRNA, is not a discriminative marker gene for prediction of Down syndrome in maternal plasma.

OBJECTIVES: The presence and detectability of placental mRNA in maternal plasma opens possibilities for the development of non-invasive prenatal diagnostic tests. In this study, we tested C21orf105, a chromosome 21-encoded, placentally expressed gene, in maternal plasma of women carrying a fetus with or without trisomy 21. METHODS: Using real-time RT-PCR, we determined transcript levels of target (C21orf105) and reference (hPL) genes in first-trimester plasma samples. Plasma was obtained from first-trimester EDTA blood after two sequential centrifugation steps and stored at -70 degrees C. After RNA extraction, quantitative RT-PCR was performed using Taqman probes. RESULTS: From the 51 samples, 43 samples were conclusive. Comparison of transcript levels of C21orf105 in both groups showed no significant differences. When expressed as ratios of hPL/C21orf105, the differences between trisomy 21 and normal pregnancies remained non-significant. CONCLUSIONS: The amount of C21orf105 mRNA in maternal plasma, although situated in the Down syndrome critical region on chromosome 21 and up regulated in trisomy 21 placentas, is not higher in women carrying a fetus with trisomy 21.

Adult↗

Efficacy and specificity of RNA interference in larval life-stages of Ostertagia ostertagi.

RNA interference (RNAi) on parasitic nematodes has been described as successful and useful for the identification of novel drug and vaccine candidates. In this study we have evaluated this technology on the cattle parasite Ostertagia ostertagi. Eight different genes were targeted in L1 and L3 O. ostertagi larvae, by electroporation and soaking in dsRNA respectively. Down-regulation of target transcript levels was evaluated by semi-quantitative reverse transcriptase (RT) PCR. In L3 larvae, variable decreases in mRNA levels were observed for 5 genes, ranging from a complete knock down (tropomyosin, beta-tubulin) to a minor decrease (ATPsynthase, superoxide dismutase, polyprotein allergen). However, repeated experiments indicated that effects were sometimes difficult to reproduce. RNAi for ubiquitin, a transthyretin-like protein and a 17 kDa excretion secretion (ES) protein never resulted in a knock down of the transcript. The mRNA levels of 7 non-target genes showed no difference between larvae soaked in C. elegans control dsRNA versus O. ostertagi tropomyosin dsRNA, supporting that the observed reductions are specific for the target gene. Electroporation of L1 larvae proved to be less effective. Reductions in mRNA levels were only noticed for 2 genes and were not reproducible. In conclusion, the results indicate that the RNAi pathway is probably present in O. ostertagi but that the current RNAi techniques can not be used as a reliable screening method.

Animals↗

Wax encapsulation of water-soluble compounds for application in foods.

Water-soluble ingredients have been successfully encapsulated in wax using two preparation techniques. The first technique ('solid preparation') leads to relatively large wax particles. The second technique ('liquid preparation') leads to relatively small wax particles immersed in vegetable oil. On the first technique: stable encapsulation of water-soluble colourants (dissolved at low concentration in water) has been achieved making use of beeswax and PGPR. The leakage from the capsules, for instance of size 2 mm, is about 30% after 16 weeks storage in water at room temperature. To form such capsules a minimum wax mass of 40% relative to the total mass is needed. High amounts of salt or acids at the inside water phase causes more leaking, probably because of the osmotic pressure difference. Osmotic matching of inner and outer phase can lead to a dramatic reduction in leakage. Fat capsules are less suitable to incorporate water soluble colourants. The reason for this could be a difference in crystal structure (fat is less ductile and more brittle). On the second technique: stable encapsulation of water-soluble colourants (encapsulated in solid wax particles) has been achieved making use of carnauba wax. The leakage from the capsules, for instance of size 250 mm, is about 40% after 1 weeks storage in water at room temperature.

Capsules↗

[A schizophrenic patient with loss of teeth].

A 53-year-old woman, known with a schizophrenic disorder and a history of drug addiction, was referred because of progressive hematomas of the lower extremities and fatigue. Her medical history included hyperplastic gums, tooth hypermobility and anaemia. Scurvy was diagnosed as a result of an insufficient diet due to drug addiction and a paranoid psychosis. After suppletion of vitamin C and starting highly nutritious food a rapid amelioration of the scurvy related complaints was observed. While dreaded and often fatal in earlier eras, in the 21st century scurvy is easily treatable if this diagnosis is recognised.

Anemia↗

The quality of communication between parents and adolescent children in the case of parental cancer.

BACKGROUND: This study was designed to investigate: (i) parent-adolescent communication in families of cancer patients; (ii) relationships between parent-adolescent communication and posttraumatic stress symptoms (PTSS) in adolescent children; and (iii) associations between parents' illness characteristics and parent-adolescent communication. PATIENTS AND METHODS: A total of 212 adolescents completed the Impact of Event Scale and Parent-Adolescent Communication Scale. RESULTS: Adolescents communicated less openly with mothers with cancer than controls with mothers; this was the only significant difference with the reference group. Daughters communicated more openly with ill parents than with healthy parents. More open communication with healthy parents was related to fewer PTSS in daughters. More problem communication with both parents was related to more PTSS in both sons and daughters. Sons reported more problems in communication with ill parents in case of more intensive treatment or recurrent disease. Daughters experienced less open communication with both parents when ill parents received more intensive treatment. Time since diagnosis was not related to parent-adolescent communication. Multivariate analyses showed that communication patterns specifically affected PTSS of daughters. Problem communication with the healthy parent was the strongest predictor of intrusion while problem communication with the ill parents was the strongest predictor of avoidance. CONCLUSIONS: Parent-adolescent communication in families of cancer patients differs little from that in families not confronted with parental cancer. Problem communication outweighed lack of openness with respect to development of PTSS. Recurrent disease and intensive treatment regimens affected parent-adolescent communication negatively.

Adolescent↗

Elimination of viruses, bacteria and protozoan oocysts by slow sand filtration.

The decimal elimination capacity (DEC) of slow sand filters (SSF) for viruses, bacteria and oocysts of Cryptosporidium has been assessed from full-scale data and pilot plant and laboratory experiments. DEC for viruses calculated from experimental data with MS2-bacteriophages in the pilot plant filters was 1.5-2 log10. E. coli and thermotolerant coliforms (Coli44) were removed at full-scale and in the pilot plant with 2-3 log10. At full-scale, Campylobacter bacteria removal was 1 log10 more than removal of Coli44, which indicated that Coli44 was a conservative surrogate for these pathogenic bacteria. Laboratory experiments with sand columns showed 2-3 and >5-6 log10 removal of spiked spores of sulphite-reducing clostridia (SSRC; C. perfringens) and oocysts of Cryptosporidium respectively. Consequently, SSRC was not a good surrogate to quantify oocyst removal by SSF. Removal of indigenous SSRC by full-scale filters was less efficient than observed in the laboratory columns, probably due to continuous loading of these filter beds with spores, accumulation and retarded transport. It remains to be investigated if this also applies to oocyst removal by SSF. The results additionally showed that the schmutzdecke and accumulation of (in)organic charged compounds in the sand increased the elimination of microorganisms. Removal of the schmutzdecke reduced DEC for bacteria by +/-2 log10, but did not affect removal of phages. This clearly indicated that, besides biological activity, both straining and adsorption were important removal mechanisms in the filter bed for microorganisms larger than viruses.

Animals↗

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↗