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PubMed1995

Medical, physical and psychological status related to early rheumatoid arthritis.

As part of an international European research project, a longitudinal study was started by the end of 1990 in the northern part of The Netherlands. The study concentrated on recently diagnosed RA patients (N = 292), i.e., incident cases up to four years. According to the duration of the disease, five groups of patients had been formed. The early influence of rheumatoid arthritis on medical parameters, on functional status, on physical condition and on psychological well-being was evaluated. From the results, an overall statistically significant pattern related to the duration of the disease could not be distinguished. However, patients recently diagnosed did face activity restrictions, a decline in physical condition and social functioning. On medical parameters this deterioration is less profound. Furthermore, across and within the five patient groups, it seems that males and females respond differently to the influence of early RA. Based on cross-sectional data from the five onset cohorts, the present findings do not significantly suggest a steady worsening in medical, physical and psychological condition.

Activities of Daily Living↗
PubMed2003

Creating a saturated reference map for the apple (Malus x domestica Borkh.) genome.

The availability of a high quality linkage map is essential for the detection and the analysis of quantitative traits. Such a map should cover a significant part of the genome, should be densely populated with markers, and in order to gain the maximum advantage should be transferable to populations or cultivars other than the ones on which it has been constructed. An apple genetic linkage map has been constructed on the basis of a segregating population of the cross between the cultivars Fiesta and Discovery. A total of 840 molecular markers, 475 AFLPs, 235 RAPDs, 129 SSRs and 1 SCAR, were used for the two parental maps constructed with JoinMap and spanning 1,140 cM and 1,450 cM, respectively. Large numbers of codominant markers, like SSRs, enable a rapid transfer of the map to other populations or cultivars, allowing the investigation of any chosen trait in another genetic background. This map is currently the most advanced linkage map in apple with regard to genome coverage and marker density. It represents an ideal starting point for future mapping projects in Malus since the stable and transferable SSR frame of the map can be saturated quickly with dominant AFLP markers.

Automation↗
PubMed2006

Forensic mass screening using mtDNA.

At the forensic autopsy of a sexual murder victim, some trace hairs, possibly belonging to the perpetrator, were saved. Initially, the analysis of a pubic hair shaft only revealed the presence of the mitochondrial (mt) DNA haplotype profile consisting of the (CA)(6) allele and the complete hypervariable region 1 (HV1) and 2 (HV2) sequence. Later, typing of some further telogene trace hairs, which had been stored for several years, yielded a nuclear short tandem repeat (STR) profile. We used both the mtDNA haplotype and the STR profile to start a DNA mass screening project involving 2,335 male citizens of the relevant communities. MtDNA screening was carried out by using the CA repeat amplification in combination with an SNP typing procedure based on the restriction site analysis of amplified d-loop sequences. The aim of our paper is to put mass screening with mtDNA up for discussion.

Alleles↗
PubMed1990

Response of prepubertal Bos taurus and Bos indicus x Bos taurus heifers to melengestrol acetate with or without gonadotropin-releasing hormone.

The effectiveness of treatments to induce estrus in prepubertal beef heifers was evaluated. Angus x Hereford (n = 148) and Brahman x Hereford (n = 148) heifers were sorted after weaning by body weight into light and heavy weight blocks. Heifers were assigned to diets, calculated to reach a target weight of 55% or 65% of their projected mature weight by the start of breeding. Cyclicity was determined after a 160-d observation period and from concentrations of progesterone in serum determined 10 d before and on the day that treatments began to induce puberty. The remaining nonpubertal heifers, with concentrations of progesterone in serum of less than 1 ng/ml (0 or 10 d before treatment), were assigned randomly within breed and nutrition group to either a melengestrol acetate + saline (MGA+S) or MGA + gonadotropin-releasing hormone (MGA+GnRH) treatment. Prepubertal Angus x Hereford heifers (n = 11) and Brahman x Hereford heifers (n = 49) were fed 0.5 mg MGA for 7 d. Forty-eight hours after MGA, heifers were injected with 500 ug s.c. GnRH or 5 ml of saline. Blood samples were collected from all prepubertal heifers every 3 d after GnRH or saline for 30 d. There was no difference between treatments in the proportion of heifers that exhibited estrus by Day 7 after treatment. However, a larger (P<0.05) proportion of MGA+S-treated heifers exhibited estrus within 14 d after treatment than MGA+GnRH-treated heifers (87 vs 63%). Among heifers that exhibited estrus during that time period, the proportion with increased progesterone was higher (P<0.10) for the MGA+GnRH group than for the MGA+S group (71 vs 41%, Day 7; 79 vs 54%, Day 14). There was no difference in conception rate at first service between treatment groups. Thirty-seven and 53%, respectively, of the MGA+S and MGA+GnRH-treated heifers had short estrous cycles after treatment, and 44 and 50%, respectively, of those short cycles were repeated. Pregnancy rates at the end of 45 d were numerically higher for MGA+S heifers than for MGA+GnRH treated counterparts (63 vs 53%).

Journal Article↗
PubMed2004

Genome analysis of marine photosynthetic microbes and their global role.

Four recently completed genome projects on marine Cyanobacteria have started the age of comparative genomics for marine microbes. Cyanobacteria are a group of photoautotrophic bacteria that have traditionally been under-represented in studies of complete genome sequences, as have microbes from the marine environment in general. The new genome information is of crucial importance to understanding their role in oceanic primary production, global carbon cycling and functioning of the biosphere. Marine microbes are a still almost untapped resource for the identification of novel beneficial metabolites and activities. The availability of an increasing number of genome sequences will eventually lead to a sustained development of marine biotechnology.

Bacteriophages↗
PubMed2006

Factors influencing the acceptance of nature conservation measures--a qualitative study in Switzerland.

Landscapes fulfil a multitude of ecological and social functions. Due to the fact that both traditional and everyday landscapes today face many different threats, regulatory measures have been undertaken in many countries to protect and further sustainable landscape development. They include legislation as well as economic incentives. In recent years, however, it has become clear that just to have a few laws and to spend money on subsidies is not enough. Factors other than legislation are also essential to further the sustainable development of landscapes. One of the basic factors affecting the success or failure of landscape conservation measures is public acceptance of these measures. Our project took this as its starting point. The objective was to determine which conditions and factors influence acceptance positively or negatively. To this end 22 Swiss who are directly affected by nature conservation measures, in particular by mire landscape and dry meadow conservation measures, were interviewed using qualitative interview techniques. It is shown that perception, communication, and possibilities to participate are the most decisive driving factors influencing the formation of a long-lasting acceptance. Furthermore, acceptance may be based mainly on economic criteria, on usefulness, on ecological or even aesthetic aspects. It can be shown that not all of these motivations lead to a long-lasting acceptance. Ecologically based acceptance seems the most promising because it is founded on general convictions. Economic incentives--though important--seem to generate only superficial acceptance and do not seem to be as important as is usually assumed.

Agriculture↗
PubMed2001

Evidence for involvement of the neural pathway containing the peripheral vagus nerve, medullary visceral zone and central amygdaloid nucleus in neuroimmunomodulation.

It is now evident that a bidirectional communication network exists between the central nervous system (CNS) and immune system (IS). However, the way in which the IS passes inform to the brain is not quite clear.In the present study, one of the neural pathways involved in the cytokine-to-brain communication was investigated in the rat. This pathway starts at the vagal nerve projecting to the medullary visceral zone (MVZ), an arc-shape band from the dorsomedial to ventrolateral area in the middle-caudal segment of the medulla oblongata, and terminates at the central amygdaloid nucleus (Ce) which receives projections from large catecholaminergic neurons in the MVZ. Animals were randomly divided into two experimental groups. Triple-labeling was used in Group I animals to combine wheat germ aggulutinin-conjugated horseradish peroxidase (WGA-HRP) retrograde tracing with anti-Fos and anti-tyrosine hydroxylase (TH) immunostaining. WGA-RP was stereotaxically injected into the unilateral Ce of the animals and, after a survival period of 48 h, intraperitoneal (IP) injection of lipopolysaccharide (LPS) was performed. Seven kinds of labeled neurons were observed in the MVZ, namely, HRP-, Fos- or TH-singly-labeled neurons; Fos/HRP-, Fos/TH- or HRP/TH-doubly-labeled neurons; and Fos/HRP/TH-triply-labeled neurons. As for Group II animals, bilateral subdiaphragmatic vagotomy (SDV) or sham operation was performed, followed 4 weeks later by IP injection of LPS. The number of Fos-positive neurons within the Ce and MVZ was significantly lower (P<0.01) in rats having SDV when compared with those receiving sham operation. Our results suggest that part of the peripheral immune information can be conveyed through the vagus to the catecholaminergic neurons in the MVZ, where it is transported to the Ce. The MVZ is a neural relay station in the immune-to-brain communication and might play a significant role in neuroimmuno-modulation via the vagus-MVZ-Ce pathway.

Amygdala↗
PubMed1982

The use of antithymocyte globulin in the treatment of severe aplastic anemia in children.

The benefit of antithymocyte globulin in severe aplastic anemia in the pediatric age group was assessed. Four children received ten alternate-day courses of ATG (horse antihuman thymocyte globulin) as well as antihistamines and corticosteroids to minimize allergic reactions. The outcome of 19 other children with severe aplastic anemia who received ATG was also summarized. Combined data reveal that 12 of 23 have had a complete or partial response with residual thrombocytopenia and a probability of 48% survival one year from the start of ATG therapy as projected by life table analysis. Only one death has been recorded in the responding group. Response rate did not appear to be influenced by age, sex, etiology, initial blood count, interval prior to ATG therapy, or dose of ATG employed. Complications were minimal and included minor urticarial reactions and intermittent fever. Therapy with ATG should be considered in childhood severe aplastic anemia when bone marrow transplantation is not possible.

Actuarial Analysis↗
PubMed1998

Hyperforin as a possible antidepressant component of hypericum extracts.

We demonstrate that the phloroglucinol derivative hyperforin is not only the major lipophilic chemical constituent of the medicinal plant Hypericum perforatum (St. John's wort) but also a potent uptake inhibitor of serotonin (5-HT), dopamine (DA), noradrenaline (NA), GABA and L-Glutamate with IC50 values of about 0.05-0.10 microg/ml (5-HT, NA, DA, GABA) and about 0.5 microg/ml (L-glutamate) in synaptosomal preparations. Furthermore, potencies of two different hypericum extracts in two conventional pharmacological paradigms useful for the detection of antidepressants (behavioral despair, learned helplessness), closely correlate with their hyperforin contents. In addition, most till now known neuropharmacological properties of the clinically used hypericum extracts can also be demonstrated with pure hyperforin. It appears, therefore, that this non-nitrogenous constituent is a possible major active principle responsible for the observed clinical efficacies of the extract as an antidepressant and that it could also be a starting point for drug discovery projects engaged in the search of psychoactive drugs with novel mode of action.

Animals↗
PubMed2003

TBE vaccination and the Austrian experience.

In the pre-vaccination era, Austria had the highest recorded morbidity of tick-borne encephalitis (TBE) in Europe. The disease accounted for more than 50% of all viral meningoencephalitides in the eastern and southern parts of the country. This prompted us to start a cooperative vaccine development project in 1971 with J. Keppie from the Microbiological Research Establishment, Porton Down, England. After very satisfactory results of field studies, conducted in individuals for whom TBE was classified as occupational disease (forest workers, farmers, etc.), the killed virus vaccine (see chapter by N. Barrett in this issue), was made commercially available by Immuno AG Vienna (now Baxter Health-Care). The vaccine proved to be highly immunogenic and very well tolerated in both adults and children. After completing the series of three vaccinations seroconversion rates of >99% were recorded. In Austria, as in other European countries, TBE is now acquired for the most part during leisure activities. In view of this fact a mass vaccination campaign was initiated in 1981. Subsequently, the vaccination coverage of the Austrian population increased from 6% in 1980 to 86% in 2001, exceeding 90% in some of the high-risk areas. Data annually collected by our surveillance system show that the clinical effectiveness of the vaccine is excellent. Based on the assumption that the whole Austrian population is at risk of infection the calculated rate of protection after three doses of the vaccine is 96-98.7%. Breakthrough disease is rare and affects mainly higher age groups. Since the advent of TBE vaccination only one single case has been observed in the age group up to 20. The increasing vaccination coverage led to a more or less steady decline of TBE, drastically reducing the public health problem that the disease poses in Austria, especially in the provinces, where formerly the highest morbidity rates were observed. For example, in Carinthia, in the years 1973-1982 an average annual incidence of 155 was recorded, compared with only four annual cases in the last 4 years. The Austrian experience shows that containment of a tick-borne viral disease is feasible, provided a well-tolerated and effective vaccine is available that is widely accepted by the general population.

Austria↗
PubMed2006

Computational chemistry-driven decision making in lead generation.

Novel starting points for drug discovery projects are generally found either by screening large collections of compounds or smaller more-focused libraries. Ideally, hundreds or even thousands of actives are initially found, and these need to be reduced to a handful of promising lead series. In several sequential steps, many actives are dropped and only some are followed up. Computational chemistry tools are used in this context to predict properties, cluster hits, design focused libraries and search for close analogues to explore the potential of hit series. At the end of hit-to-lead, the project must commit to one, or preferably a few, lead series that will be refined during lead optimization and hopefully produce a drug candidate. Striving for the best possible decision is crucial because choosing the wrong series is a costly one-way street.

Combinatorial Chemistry Techniques↗
PubMed2001

Fungal genomics and pathogenicity.

The filamentous fungal genetics community has enthusiastically embraced the utilization of genomics technologies to resolve long-standing issues in fungal biology. For example, such technologies have been proposed to study the mechanics of tip growth, photoreception, gene silencing, the molecular basis of conidiation, the pathway leading to sexual reproduction, and mechanisms of pathogenesis. These studies have provided a refreshing change of pace in research on filamentous fungi, which has lagged behind that on other eukaryotes in the exploitation of genome-wide methodologies. Despite the late start, several fungal genome sequencing projects are underway. The resulting databases will allow the comprehensive analysis of developmental processes that are characteristic of fungi, including the molecular nature of pathogenicity. DNA databases underpin analyses of the fungal transcriptome, proteome, and metabolome. This combined information will contribute to our basic understanding of not only the mechanics of infection but also the evolution of pathogenicity.

Calcium-Binding Proteins↗
PubMed1998

Standardizations of clinical laboratory examinations in Japan.

In this paper we introduce Japanese activities concerning laboratory examinations by illustrating three major categories. The first is the contribution of JCCLS to ISO/TC212 clinical laboratory testing and in vitro diagnostic test systems, with NCCLS and CEN TC140. The second is the establishment and promotion of JLAC Classification and Coding for Clinical Laboratory Tests by The Japan Society of Clinical Pathology. The third is a clinical data exchange format between healthcare facilities using MML/MERIT-9 standard, started as a Ministry research project.

Clinical Laboratory Information Systems↗
PubMed1995

Dissecting titin into its structural motifs: identification of an alpha-helix motif near the titin N-terminus.

Titin, also known as connectin, is a giant modular protein specifically found in vertebrate striated muscle. Since the huge size of titin does not allow a direct structure determination, we have started a long-term project to characterize the protein by cutting it into smaller domains or structural units. The major part of the titin sequence is assembled by modules approximately 100 amino acids long that belong to two major protein superfamilies. Most of these modules are linked together by stretches of variable length with unique sequence. No direct structural characterization has been achieved so far for any of these linkers. We present here a study of a stretch located in the titin N-terminus and part of a linker between two modules. Our attention was drawn toward this region because it shows 100% probability to form a coiled coil when analyzed by a prediction program. A synthetic 38 amino acid peptide spanning such a sequence was studied in aqueous solution by circular dichroism, nuclear magnetic resonance, and analytical ultracentrifugation at various pH, salt, and peptide concentrations. Under all conditions, it shows a strong tendency to form alpha-helical structures. In the presence of salt, this conformation is associated with the formation of helical bundles below pH 5. Above pH 5, any aggregate breaks, and the titin peptide is a monomeric helix in equilibrium with its random coil conformation. We discuss the factors which stabilize the helical conformation and the possible role of this stretch in vivo.

Amino Acid Sequence↗
PubMed2000

Efficient lung scintigraphy.

Lung scintigraphy is a first-choice method to diagnose lung embolism. The clinical routine in most centres is a perfusion study complemented with a ventilation study when judged necessary. We describe a routine with ventilation scintigraphy preceding perfusion scintigraphy, which is completed within one hour. Furthermore, the data acquired allow the determination of lung clearance of the tracer 99mTc-DTPA (diethylene triamine penta-acetate) used for the ventilation scintigraphy. An aerosol generator charged once a day with 99mTc-DTPA solution is used for all inhalations during the day. Inhalation is monitored with a counter and interrupted when the count rate corresponds to about 20 MBq. The ventilation imaging starts and ends with posterior projections. This allows calculation of lung clearance of 99mTc-DTPA. Perfusion scintigraphy is performed in a standard fashion with 100 MBq of 99mTc-MAA (macro-aggregated albumin). The ventilation study was considered to give some diagnostic information in the majority of the patients. The clearance determination allows detection of inflammatory lung disease. The background activity caused by the ventilation study comprised only 13% of the activity in the perfusion scintigraphy and did not significantly interfere with interpretation of the perfusion scan. The cost for the investigation is low because of the rational system for aerosol administration and the short time for a complete study.

Humans↗
PubMed1998

Teaching of communication skills in Spanish nursing schools: an overview.

The main objective of this study is to review the teaching of communication skills in Spain as part of the nursing curriculum. A survey was carried out to identify the practical and theoretical issues pertinent to this question. Forty Spanish Nursing Schools took part. Our survey discovered that communication skills are not generally considered in the selection process of the students because personal interviews are rarely used. Communication skills are taught in the first and second years, mainly in Fundamentals of Nursing and subjects related to Psychology and Mental Health. Nursing and psychology were the predominant professional background of the teachers. Lectures, discussion groups and workshops were the main teaching methods. The assessment, when it existed, was often theoretical and, occasionally, using a real patient or a written case report. The authors propose that the knowledge of the teaching situation in Spain is the starting point for any future projects on communication.

Clinical Competence↗
PubMed2001

[Development of a questionnaire for assessing motivational conditions for prediction of therapy cooperation of LVA insured patients during inpatient medical rehabilitation--initial results of scale development].

Medical staff working in rehabilitation often criticize their in-patients' lack of motivation to cooperate in therapy. Consequently, very often the aims of the therapy would not be reached. That, again, causes expenses that could be avoided and it also causes frustration on both sides. On the basis of Schwarzer's Health Action Process Approach (HAPA) we designed a questionnaire on motivation to predict the degree of the in-patients' cooperation in therapy during rehabilitation. The results presented here are based on an interim analysis of 508 questionnaires answered by LVA insurees (Landesversicherungsanstalten, wage earners' pension insurance funds) who had applied for rehabilitation in a clinic. The applicants suffered from illness of the back and spine as well as degenerative illness of the joints. A first examination of the scales Specific Outcome Expectancies, Specific Self-efficacy and Intention of the questionnaire showed very good statistical results as well as correlations between these variables that correspond to HAPA. It also turned out that there is a direct connection between the scores of the motivation variables (e.g. Specific Self-efficacy) and that of cooperation in therapy. These initial test results indicate a generic character of the instruments used in this research project. They also point out starting points for interventions to increase motivation that are to be developed.

Adult↗
PubMed2002

[Execution and quality of attention paid to medical doctoral theses at the faculty of medicine at the University of Würzburg as seen by the doctoral candidates in their 5th and 6th year of study].

BACKGROUND AND OBJECTIVE: The significance of a doctoral thesis in medicine has been discussed controversially among medical students and faculty members. We examined in a brief but comprehensive study how medical students evaluate their research activities and whether or not alternative thesis models should be implemented. METHODS: A questionnaire comprising 50 questions was evaluated from 160 5th and 6th year medical students at the University of Wuerzburg. RESULTS: Almost two-thirds of our interviewees started working on a thesis project at the beginning of the 4th year of study. 59 % of our participants reported to have neglected the regular study and 56 % said to have prolonged the regular study due to the work on a thesis. Despite considerable variation, the median time spent weekly on a thesis project was 10 hours, independent of where the students worked. The median grade of satisfaction during the whole thesis was rated at 6.5 as assessed on an analogous scale from 1-10 (very satisfied). The research results from 94 students contributed to 164 articles (already published or in press) and the results of 110 students were presented at scientific meetings. Only 50 % of our interviewees were pleased with their published output and the importance of student research activities for the overall German biomedical research was rated 4.4 as assessed on an analogous scale from 1-10 (very important). 70 % of our interviewees preferred defined research periods and 47 % would apply for dual-degree research programmes. The scientific significance of a MD thesis in comparison to a PhD thesis was rated at 2.1 on an analogous scale from 1-5 (5 = equally significant). CONCLUSION: The current German research model might be modified and defined research periods and dual-degree research programmes as a one possible alternative should be considered.

Academic Dissertations as Topic↗