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Biomedical subjects

A Wagenaar

Publications and source records attributed to A Wagenaar.

13 recordsLinked to original sources

The importance of active involvement in learning: a qualitative study on learning results and learning processes in different traineeships.

INTRODUCTION: In order to gain more insight into learning in different traineeships we sought students' opinions on their experiences. METHOD: 24 students of Maastricht University, the Netherlands, were interviewed: 8 medical students, and 16 students in the mental health science programme of the Faculty of Health Sciences (8 research trainees (MHS-res.) and 8 trainees in mental health care practice (MHS-prac.). Students' perceptions about instructive, difficult and less instructive learning experiences were recorded on audiotape. The literal transcripts of the interviews were analysed and categorised. RESULTS: The most frequently mentioned learning process was "learning by doing" followed by "actively overcoming gaps in knowledge and skills". These processes occurred with instructive and difficult experiences. Other processes were "learning by seeing things in practice" and "preparation and evaluation". Learning outcomes were categorised as learning about: working, professional competences and personal growth. Most frequently mentioned - in most cases with difficult experiences - were "professional knowledge and skills", "learning about personal growth" and "learning about working". The latter was mentioned most often by MHS-res. students. Medical students' responses suggested that they occasionally perceived the clerkship environment as stressful. DISCUSSION AND CONCLUSIONS: Although the small sample size precludes any firm conclusions, the overwhelming impression is that students prefer being actively involved in their learning process. In addition, traineeships appear to introduce students to professional working life the hard way. Investigating how teachers and supervisors can stimulate active learning and facilitate the introduction to professional practice might be subjects for fruitful further investigation.

Adult↗

Molecular shape of the cationic lipid controls the structure of cationic lipid/dioleylphosphatidylethanolamine-DNA complexes and the efficiency of gene delivery.

Pyridinium amphiphiles, abbreviated as SAINT, are highly efficient vectors for delivery of DNA into cells. Within a group of structurally related compounds that differ in transfection capacity, we have investigated the role of the shape and structure of the pyridinium molecule on the stability of bilayers formed from a given SAINT and dioleoylphosphatidylethanolamine (DOPE) and on the polymorphism of SAINT/DOPE-DNA complexes. Using electron microscopy and small angle x-ray scattering, a relationship was established between the structure, stability, and morphology of the lipoplexes and their transfection efficiency. The structure with the lowest ratio of the cross-sectional area occupied by polar over hydrophobic domains (SAINT-2) formed the most unstable bilayers when mixed with DOPE and tended to convert into the hexagonal structure. In SAINT-2-containing lipoplexes, a hexagonal topology was apparent, provided that DOPE was present and complex assembly occurred in 150 mm NaCl. If not, a lamellar phase was obtained, as for lipoplexes prepared from geometrically more balanced SAINT structures. The hexagonal topology strongly promotes transfection efficiency, whereas a strongly reduced activity is seen for complexes displaying the lamellar topology. We conclude that in the DOPE-containing complexes the molecular shape and the nonbilayer preferences of the cationic lipid control the topology of the lipoplex and thereby the transfection efficiency.

Animals↗

Effectiveness of the ascomycin macrolactam SDZ ASM 981 in the topical treatment of atopic dermatitis.

OBJECTIVE: To compare the safety and efficacy of 1% SDZ ASM 981 cream and a matching placebo cream in the treatment of patients with moderate atopic dermatitis. DESIGN: A randomized, double-blind, placebo-controlled, right-and-left comparison study. SETTING: Academic referral center. PATIENTS: Thirty-four adult patients with moderate atopic dermatitis. INTERVENTION: Topical 1% SDZ ASM 981 cream was applied twice daily (n=16) or once daily (n=18) and compared with a corresponding placebo cream base. MAIN OUTCOME MEASURES: Efficacy was measured using a 4-point (0-3) scale for erythema, pruritus, exudation, excoriation, and lichenification (Atopic Dermatitis Severity Index [ADSI]). The ADSI score was defined as the sum of these 5 ratings (range, 0-15) and was determined on the pretreatment day (1 to 14 days before day 0) and on days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. The percentage change from baseline (day 0) in the ADSI score was calculated on each of these days. Safety was evaluated by monitoring of adverse events, physical examination, hematologic examination, clinical chemistry studies, urinalysis, and measurement of blood levels of SDZ ASM 981. RESULTS: Of the 38 patients recruited, 34 started and 28 completed treatment according to the protocol. Sixteen patients used the cream twice daily, with significant improvement after 2 days of treatment. Within 3 weeks of topical therapy with 1% SDZ ASM 981 cream twice daily, a mean reduction of 71.9% in the ADSI score was observed at the actively treated test sites compared with a mean reduction of 10.3% at the placebo-treated test sites (P<.001). Efficacy was significantly less in the group treated once daily (n=18), with mean reductions of 37.7% and 6.2%, respectively. The efficacy was especially apparent for pruritus and excoriation. There were no clinically relevant drug-related adverse effects. CONCLUSIONS: Treatment with 1% SDZ ASM 981 cream was well tolerated. Twice-daily application of 1% SDZ ASM 981 cream was significantly more effective than use of the corresponding placebo and more effective than once-daily treatment. The new macrolactam ascomycin derivative SDZ ASM 981 is a promising agent for the treatment of patients with atopic dermatitis. More elaborate phase 2 and 3 trials are under way to fully investigate the potential of this medication.

Administration, Topical↗

Evaluation of two dose-volume histogram reduction models for the prediction of radiation pneumonitis.

PURPOSE: To evaluate the similarities between the mean lung dose and two dose-volume histogram (DVH) reduction techniques of 3D dose distributions of the lung. PATIENTS AND METHODS: DVHs of the lungs were calculated from 3D dose distributions of patients treated for malignant lymphoma (44), breast cancer (42) and lung cancer (20). With a DVH reduction technique, a DVH is summarized by the equivalent uniform dose (EUD), a quantity which is directly related to the normal tissue complication probability (NTCP). Two DVH reduction techniques were used. The first was based on an empirical model proposed by Kutcher et al. (Kutcher, G.J., Burman, C., Brewster, M.S., Goitein, M. and Mohan, R. Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int. J. Radiat. Oncol. Biol. Phys. 21: 137-146, 1991), which needs a volume exponent n. Several values for n were tested. The second technique was based on a radiobiological model, the parallel functional subunit model developed by Niemierko et al. (Niemierko, A. and Goitein, M. Modeling of normal tissue response to radiation: the critical volume model. Int. J. Radiat. Oncol. Biol. Phys. 25: 135-145, 1993) and Jackson et al. (Jackson, A., Kutcher, G.J. and Yorke, E.D. Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation. Med. Phys. 20: 613-625, 1993), for which a local dose-effect relation needed to be specified. This relation was obtained from an analysis of perfusion and ventilation SPECT data. RESULTS: It can be shown analytically that the two DVH reduction techniques are identical, if the local dose-effect relation obeys a power-law relationship in the clinical dose range. Local dose-effect relations based on perfusion and ventilation SPECT data can indeed be fitted with a power-law relationship in the range 0-80 Gy, from which values of n = 0.8-0.9 were deduced. These correspond to the commonly used value of n = 0.87 for lung tissue and yielded EUDn=0.87 values which were almost identical to the mean lung doses. For other n values, for which no experimental data are present, differences exist between EUD and mean dose values. Six patients with malignant lymphoma (6/44) and none of the breast cancer patients (0/42) developed radiation pneumonitis. These cases occurred only at high values for the mean lung dose. CONCLUSION: The two DVH reduction techniques are identical for lung and are very similar to mean dose calculations. The two techniques are also relatively similar for other model parameter values.

Breast Neoplasms↗

The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion.

Topical SDZ ASM 981 has been found to be highly effective in preclinical models of T-cell-mediated skin disease. T cell activation is crucial in the pathogenesis of psoriasis. It has been hypothesized that SDZ ASM 981 may prove to be an effective treatment for chronic plaque psoriasis. Therefore, the study objective was to determine the efficacy, tolerability and safety of the new topical macrolactam, SDZ ASM 981, for chronic plaque psoriasis. Ten patients with chronic plaque-type psoriasis were treated with SDZ ASM 981 (0.3% and 1.0%), the corresponding ointment base (placebo) and open-labelled clobetasol-17-propionate ointment (0.05%) in a randomized, double-blind, within-subject comparison for 2 weeks using the microplaque assay. Evaluation was performed by daily determination of clinical scores for erythema and induration. The results of the study showed that, after 2 weeks of treatment, total scores described by 92% for clobetasol, by 82% for 1 SDZ ASM 981, by 63% for 0.3% SDZ ASM 981 and by 18% for the ointment base (placebo). No adverse drug effects were seen in any patient throughout the study. We conclude from our results that the new macrolactam SDZ ASM 981 (1%) is similar to clobetasol-17-propionate (0.05%) in plaque-type psoriasis when applied topically under occlusion for 2 weeks using the microplaque assay.

Administration, Topical↗

Novel pyridinium surfactants for efficient, nontoxic in vitro gene delivery.

Novel, double-chained pyridinium compounds have been developed that display highly efficient DNA transfection properties. The transfection efficiency of several of these compounds is enhanced by an order of magnitude, when compared with the transfection efficiency accomplished with the widely used cationic lipid system, lipofectin. Most importantly, the pyridinium compounds were found to be essentially nontoxic toward cells. Using various reporter genes, such as beta-galactosidase and pNEO (a gene construct that renders cells resistent to antibiotic derivatives of neomycin like G418), we demonstrate that the enhanced efficiency relates to the fact that a relative higher number of cells in the population is transfected (approximately 50% in the case of COS cells) by the pyridinium derivatives, whereas the delivery of DNA per cell is also enhanced. Furthermore, application of the pyridinium derivatives shows little cellular preference in their ability to transfect cells. By systematically modifying the structure of the pyridinium amphiphile, i.e., by changing either the headgroup structure or the alkyl chains, some insight was obtained that may lead to unraveling the mechanism of amphiphile-mediated transfection, and thus to protocols that further optimize the carrier properties of the amphiphile. Our results reveal that unsaturated alkyl chains enhance the transfection properties of the pyridinium-based amphiphiles. Preliminary experiments suggest that the structure-dependent improvement of transfection efficiency, when comparing pyridinium derivatives with lipofectin, likely relates to the mechanism of delivery rather than the packaging of the amphiphile/DNA complex.

Animals↗

Viewpoints of Minnesota students on school-based sexuality education.

This study gathered information on the perceptions of high school students with regard to human sexuality education. Six focus groups were conducted with 9th-12th grade students at public high schools in the Minneapolis and St. Paul, Minnesota, area. Students described the content of effective sexuality education as covering a variety of human sexuality topics as well as emotional/social aspects of sexuality and relationships. They advocated starting such education in early elementary school and covering all topics by eighth grade. Students strongly favored a presentation style that was open, honest, comfortable, and nonjudgmental, and they believed teachers should be specially trained in this area. Relating material to students' lives and using a discussion format were also considered essential to effective sexuality education. The students' viewpoints have significant implications for teachers, school administrators, and policy makers.

Adolescent↗

Environmental predictors of drinking and drinking-related problems in young adults.

We examined relationships among drinking norms, peer alcohol use, alcohol availability, drinking location, alcohol consumption, and drinking-related problems among young adult drinkers. The specific objectives of our study were to assess the relative contribution of normative and physical environmental factors to drinking and drinking consequences. Subjects were 3,095 young adults, aged eighteen to twenty years old who participated in the Communities Mobilizing for Change on Alcohol Project baseline survey. Alcohol consumption (i.e., number of drinks on the last occasion) and drinking consequences served as dependent variables. Multiple linear regression was used to identify predictors of alcohol consumption, and logistic regression was employed to identify predictors of drinking consequences. Drinking norms and peer alcohol use were positively related to alcohol consumption and to drinking consequences. Drinking in a public setting was positively related to alcohol consumption, but not to drinking-related problems. Findings suggest that policies and programs that alter the normative and physical environment surrounding drinking may reduce alcohol consumption and subsequent problems in young adults.

Adolescent↗

Relationships among alcohol availability, drinking location, alcohol consumption, and drinking problems in adolescents.

We examined relationships among perceived alcohol availability, drinking location, alcohol consumption, and drinking problems. Subjects were 3,372 adolescent drinkers, ages 16-18, who participated in the Communities Mobilizing for Change on Alcohol Project baseline survey. Mixed-model regression was employed to identify predictors of alcohol consumption and drinking consequences. Perceived alcohol availability was significantly associated with higher levels of alcohol consumption for males. Drinking in a public location with higher levels of alcohol consumption for females. Results underscore the importance of youth alcohol assessibility.

Adolescent↗

Parameters influencing the introduction of plasmid DNA into cells by the use of synthetic amphiphiles as a carrier system.

Parameters that affect cellular transfection as accomplished by introducing DNA via carriers composed of cationic synthetic amphiphiles, have been investigated, with the aim to obtain insight into the mechanism of DNA translocation. Such insight may be exploited in optimizing carrier properties of synthetic amphiphiles for molecules other than nucleic acids. In the present work, the interaction of vesicles composed of the cationic amphiphile dioleyloxy-propyl-trimethylammonium chloride (DOTMA) with cultured cells was examined. The results show that optimal transfection is dependent on the concentration of lipid, which determines the efficiency of vesicle interaction with the target cell membrane, as well as the toxicity of the amphiphiles towards the cell. A low lipid/DNA ratio prevents the complex from interacting with the cell surface, whereas at a relatively high amphiphile concentration the complex becomes toxic. Translocation efficiency is independent of the initial vesicle size but is affected by the size of the DNA. An incubation time of the DNA/amphiphile complex and cells of approx. 2-4 h is required for obtaining efficient transfection. In conjunction with observations on DNA/amphiphile complex-induced hemolysis of erythrocytes, a mechanism of DNA-entry is proposed which involves translocation of the nucleic acids through pores across the membranes rather than delivery via fusion or endocytosis. Dioleoylphosphatidylethanolamine, a phospholipid frequently used in a mixture with DOTMA ('lipofectin') strongly facilitates this pore formation. Translocation of the DNA is effectively prevented when the cells are pretreated with Ca2+ or pronase. These observations suggest that Ca(2+)-sensitive cell surface proteins play a role in amphiphile-mediated DNA translocation.

Animals↗

Licit and illicit drug policies: a typology.

To foster comparison of policy interventions across the various categories of licit and illicit drugs, we develop a typology of policies intended to address drug abuse problems. The principal dimensions of the typology are policy type and intervention channel. While the typology has important limitations, as a mechanism to organize information and stimulate thought it holds the potential to improve understanding of commonalities and distinctions among policies applying to widely discrepant drug problems, both within and across cultures. As such, it could contribute to the development of more effective approaches to grappling with a diverse set of drug policy issues.

Alcoholism↗