Biomedical subjects

Thomas Becker

Publications and source records attributed to Thomas Becker.

At least 37 records · Page 2Linked to original sources

PubMed2006

Adherence to medication and quality of life in people with schizophrenia: results of a European multicenter study.

Quality of life is often severely impaired in people with schizophrenia, and adherence to antipsychotic medication has been consistently found to be low in this population. Although there is a considerable amount of evidence on these two variables in schizophrenia research, there is only limited knowledge on how they relate to one another. The aim of this study is to develop a meaningful model of the relationship between quality of life and adherence that includes mediating variables. A multicenter randomized controlled trial recruited 409 subjects in London, Verona, Amsterdam, and Leipzig. Baseline interviews obtained data on adherence, quality of life, and other variables. We used graphical modeling to investigate the relationships between the variables. No direct relation could be discerned between subjective quality of life and adherence to medication. Mediating variables, most importantly symptomatic impairment, global functioning, and medication side effects, were identified by the model. It can be concluded that, when aiming at the improvement of quality of life in people with schizophrenia, variables other than adherence, i.e., symptomatic impairment, global functioning, and medication side effects, should be targeted.

Antipsychotic Agents↗

PubMed2006

Determinants of first- and second-generation antipsychotic drug use in clinically unstable patients with schizophrenia treated in four European countries.

The present study investigated the use of antipsychotics in a sample of clinically unstable patients with schizophrenia who were recruited in four European sites. The study aimed: (i) to test whether the length of previous antipsychotic exposure was associated with the choice of antipsychotic medication; (ii) to test whether the severity of illness was associated with the use of second-generation antipsychotic agents (SGAs) or with the concomitant use of both first-generation antipsychotics (FGAs) and SGAs; and (iii) to investigate differences between study sites. Participants were recruited from patients under the care of psychiatric services serving geographical catchment areas in Croydon (UK), Verona (Italy), Amsterdam (The Netherlands) and Leipzig (Germany). Clinically unstable patients with a clinical diagnosis of schizophrenia and a research diagnosis of schizophrenia, established using the Item Group Checklist of the Schedule for Clinical Assessment in Neuropsychiatry, were enrolled. Sociodemographic and clinical data, including current antipsychotic drug therapy, psychopathology, adherence, insight, side-effects, attitudes towards medication and quality of life, were gathered. Three hundred and ninety patients were analysed in total. Almost 60% received SGAs, less than one-third FGAs, and less than 15% received both drug classes. Those receiving SGAs were younger and with a shorter length of antipsychotic drug therapy, whereas those receiving both drug classes were more often separated or widowed, unemployed and with a long history of antipsychotic drug therapy. The distribution of patients receiving FGAs, SGAs and both drug classes by illness-related variables showed that patients receiving both drug classes were more severely ill and complained of more side-effects. Using patients receiving FGAs as the reference category, multinomial logistic regression analysis showed that the length of antipsychotic treatment was negatively correlated with receiving SGAs, and that the severity of illness and being separated/widowed were positively correlated with receiving both drug classes. Compared with patients in Leipzig, patients in Amsterdam, Croydon and Verona were less frequently treated with SGAs and with combinations of both drug classes. Consistent with current clinical uncertainty with respect to what pharmacological treatment should be provided, patients with a long history of antipsychotic exposure were receiving FGAs, SGAs and combinations of both drug classes. Physicians tended to reserve polypharmacy for difficult-to-treat patients (i.e. for managing situations where, despite the lack of an evidence base, there is a pressing need to provide clinical answers).

Adolescent↗

PubMed2006

Persistence with polypharmacy and excessive dosing in patients with schizophrenia treated in four European countries.

The purpose of this study was to calculate the proportion of patients with schizophrenia receiving persistent antipsychotic polypharmacy and excessive dosing in four European countries; to test the hypothesis that excessive dosing and/or antipsychotic polypharmacy is associated with higher levels of psychopathology; and to establish whether use of second-generation antipsychotics is a protective or a risk factor for polypharmacy and excessive dosing. Participants with schizophrenia were recruited from patients under the care of psychiatric services serving geographical catchment areas in Croydon (UK), Verona (Italy), Amsterdam (Netherlands), and Leipzig (Germany). We defined patients persistently receiving high antipsychotic dose (i.e. excessive dosing) as those with a prescribed daily dose/defined daily dose ratio of >1.5 both at initial assessment and after 1 year of follow-up. Similarly, we defined patients persistently receiving polypharmacy as those being prescribed two or more antipsychotic drugs both at baseline and at follow-up. A sample of 375 participants with schizophrenia was analyzed. A proportion of 28% of patients persistently received high-dose antipsychotic drugs, and a proportion of 13% of patients persistently received antipsychotic polypharmacy. In the multivariate analysis, psychopathology was not a predictor of persistent polypharmacy and excessive dosing; similarly, use of second-generation antipsychotics was not associated with polypharmacy and excessive dosing; however, persistence with high antipsychotic doses was predicted by baseline use of first-generation antipsychotics and second-generation antipsychotics concurrently. Antipsychotic drug use for patients with schizophrenia is only sometimes satisfactory and offers the opportunity of improvement. Clinicians should consider that dose reduction strategies have been shown to be a feasible intervention in patients with schizophrenia.

Adolescent↗

PubMed2006

Living kidney donors >60 years of age: is it acceptable for the donor and the recipient?

Donors >60 years are now frequently accepted for living kidney transplantation (LKT). We asked whether a donor age >60 years may result in a higher risk for donor and recipient. All adult LKT from May 1996 to June 2005 were included. Long-term outcome was analysed, and results were compared for donors >60 and 60 (group A) and 158 from donors 60 years, we suggest that age should no longer be considered as a contra-indication for living donation.

Age Factors↗

PubMed2006

Paediatric kidney transplantation in small children-- a single centre experience.

Kidney transplantation (KTx) remains a challenging procedure in small children. This study presents our centre results. From 1983 to 2004, 40 of 442 paediatric KTx were performed in children with a body weight <11 kg. Median body weight was 9.2 kg (range: 7.2-10.9), median age was 2.7 years (range: 0.9-5.9). Preoperative dialysis was performed in 87.5%. In 24 cases (60%) grafts came from cadaveric (CAD) and in 16 cases (40%) from living related donors (LRD). Median donor age of CAD was 8 years (range: 1-40). The overall 1-, 5-, 10-, 15-year patient survival was 93%, 90%, 90% and 87% respectively. The overall 1-, 5-, 10-, 15-year graft survival was 90%, 80%, 66% and 56% respectively. There was no significant difference in survival of CAD or LRD grafts. Median follow-up was 13.7 years. Initial graft function rate was 100% for LRD and 79% for CAD. The relative glomerular filtration rate (GFR) showed no statistical difference between CAD and LRD. Main reasons for graft loss were chronic transplant nephropathy. Paediatric KTx is the treatment of choice even in very small children. Living donor KTx is the preferable donor source in terms of primary graft function and timing to transplantation.

Age Factors↗

PubMed2006

Interleukin-2 receptor antagonist induction in modern immunosuppression regimens for renal transplant recipients.

Addition of interleukin-2 receptor antagonist (IL-2RA) induction to calcineurin inhibitor (CNI)-based regimens reduces biopsy-proven acute rejection by 30-40%. IL-2RA induction facilitates early withdrawal of steroids, and supports the safe use of reduced-exposure CNI or delayed CNI introduction. IL-2RAs and rabbit antithymocyte globulin (Thymoglobulin) show comparable efficacy in patients at standard or low immunologic risk, but the adverse event profiles of lymphocyte-depleting agents are less favorable. IL-2RAs, uniquely, provide effective immunosuppression with similar tolerability to placebo.

Animals↗

PubMed2006

Adherence therapy for people with schizophrenia. European multicentre randomised controlled trial.

BACKGROUND: There is equivocal evidence of the effectiveness of adherence therapy in improving treatment adherence and clinical outcomes for people with schizophrenia. AIMS: To evaluate the effectiveness of adherence therapy in improving quality of life for people with schizophrenia. METHOD: A 52-week, single-blind, multicentre randomised controlled trial of the effectiveness of adherence therapy. Participants were individually randomised to receive eight sessions of adherence therapy or health education. Assessments were undertaken at baseline and at 52-week follow-up. RESULTS: Adherence therapy was no more effective than health education in improving quality of life. CONCLUSIONS: This effectiveness trial provides evidence for the lack of effect of adherence therapy in people with schizophrenia with recent clinical instability, treated in ordinary clinical settings.

Adult↗

PubMed2005

Evolution of myelin proteolipid proteins: gene duplication in teleosts and expression pattern divergence.

The coevolution of neurons and their supporting glia to the highly specialized axon-myelin unit included the recruitment of proteolipids as neuronal glycoproteins (DMbeta, DMgamma) or myelin proteins (DMalpha/PLP/DM20). Consistent with a genome duplication at the root of teleosts, we identified three proteolipid pairs in zebrafish, termed DMalpha1 and DMalpha2, DMbeta1 and DMbeta2, DMgamma1 and DMgamma2. The paralogous amino acid sequences diverged remarkably after gene duplication, indicating functional specialization. Each proteolipid has adopted a distinct spatio-temporal expression pattern in neural progenitors, neurons, and in glia. DMalpha2, the closest homolog to mammalian PLP/DM20, is coexpressed with P0 in oligodendrocytes and upregulated after optic nerve lesion. DMgamma2 is expressed in multipotential stem cells, and the other four proteolipids are confined to subsets of CNS neurons. Comparing protein sequences and gene structures from birds, teleosts, one urochordate species, and four invertebrates, we have reconstructed major steps in the evolution of proteolipids.

Amino Acid Sequence↗

PubMed2005

Photosystem II core phosphorylation and photosynthetic acclimation require two different protein kinases.

Illumination changes elicit modifications of thylakoid proteins and reorganization of the photosynthetic machinery. This involves, in the short term, phosphorylation of photosystem II (PSII) and light-harvesting (LHCII) proteins. PSII phosphorylation is thought to be relevant for PSII turnover, whereas LHCII phosphorylation is associated with the relocation of LHCII and the redistribution of excitation energy (state transitions) between photosystems. In the long term, imbalances in energy distribution between photosystems are counteracted by adjusting photosystem stoichiometry. In the green alga Chlamydomonas and the plant Arabidopsis, state transitions require the orthologous protein kinases STT7 and STN7, respectively. Here we show that in Arabidopsis a second protein kinase, STN8, is required for the quantitative phosphorylation of PSII core proteins. However, PSII activity under high-intensity light is affected only slightly in stn8 mutants, and D1 turnover is indistinguishable from the wild type, implying that reversible protein phosphorylation is not essential for PSII repair. Acclimation to changes in light quality is defective in stn7 but not in stn8 mutants, indicating that short-term and long-term photosynthetic adaptations are coupled. Therefore the phosphorylation of LHCII, or of an unknown substrate of STN7, is also crucial for the control of photosynthetic gene expression.

Acclimatization↗

PubMed2005

Quality of life following living donor nephrectomy comparing classical flank incision and anterior vertical mini-incision.

In this study we focused on the quality of life and satisfaction of living kidney donors comparing traditional lumbar (LDN) and mini-incision donor nephrectomy (MIDN). From May 1996 to December 2002, 174 donor nephrectomies including 127 cases of LDN and 47 cases of MIDN were performed. Donors were evaluated using the SF-36 quality-of-life survey as well as a questionnaire dealing with donors' attitude towards kidney donation, financial burdens, pain, cosmetic satisfaction and duration of sick leave. Our donors achieved comparable or even higher scores in all the SF-36 categories in comparison to the general US population. Following MIDN, quality of life tended to be superior compared to that of LDN donors; however, statistical significance was reached only in one of the eight categories. Duration of sick leave following surgery was in favor of MIDN compared to LDN donors. Statistically significant differences favoring MIDN were observed regarding postoperative hospital stay and cosmetic satisfaction. The procedure would be again undergone by 94 of LDN and 97% of MIDN donors. Open-donor nephrectomy is a safe and cost-effective procedure. Introduction of the here-described MIDN has led to comparable or even improved results compared to LDN.

Female↗

PubMed2005

Attitudes towards patient gender among psychiatric hospital staff: results of a case study with focus groups.

There is an increasing awareness of gender-related issues in psychiatry. However, empirical findings on attitudes of psychiatric staff towards patient gender are limited. Gender-related issues are particularly relevant in the debate about mixed versus segregated sex wards, yet while the appropriateness of mixed-sex wards is questioned in Great Britain this is not the case in Germany. To investigate attitudes of psychiatric staff towards both patient gender and mixed versus segregated sex wards, we conducted a case study using focus groups with members of professional teams. We evaluated the transition process from two single-sex wards to two mixed-sex wards in a 330-bed psychiatric hospital in a rural area in south Germany. Staff described female patients as more externally oriented, motivating of others, demanding, and even sexually aggressive. Male patients, on the other hand, were described as more quiet, modest, or lazy. Furthermore, participants described the mixing process as a positive development whereas they did not see a need for gender-separated wards in order to protect vulnerable female patients. Some gender descriptions by professionals are "reversed" in comparison with gender stereotypes supposed to be present in wider society. The perception of crossed gender norms may affect staff attitudes towards the vulnerability of female patients in psychiatric settings and the provision of single-sex wards in in-patient psychiatric care. Practical implications are discussed against the background of a high rate of female patients with sexual abuse histories.

Attitude of Health Personnel↗

PubMed2005

Needs and quality of life among patients with schizophrenia in five European centres: what is the impact of global functioning scores?

BACKGROUND: Global assessment of functioning, quality of life (QOL) and patient needs have been discussed as inter-related domains important for care planning and outcome assessment in care for the severely mentally ill. The study was conducted to investigate relationships of functioning level, subjective QOL and unmet needs in a cross-sectional study of 404 patients with schizophrenia spectrum disorders in five European centres with a focus on the patient group with low function scores. METHODS: Patient groups with low, medium and high function scores were compared with regard to subjective QOL and unmet needs. QOL variability was assessed in subgroups according to function scores. Regression analyses were used to examine the impact of illness-related and other unmet patient needs on QOL. The influence of individual needs in the low and medium/high function score subgroup was compared. RESULTS: QOL increased and unmet needs decreased from the low to high function score subgroup. There was greater QOL variability in patients with low function scores compared to those with medium and high function scores, with some low-function score patients having relatively high QOL. In the low function score subgroup, both illness-related and other needs had an impact on QOL, whereas non-illness needs influenced QOL in medium and high function score patients. CONCLUSION: Scores of functioning level, in people with schizophrenia spectrum disorders, are related to QOL in a complex way, and types of unmet need impinge on the relationship. In order to improve QOL in people with low function scores, both illness-related and other needs should be met.

Adult↗

PubMed2005

Surgical experience in splitting donor liver into left lateral and right extended lobes.

AIM: To outline the surgical experience with donor liver splitting in split liver transplantation. METHODS: From March 1 to September 1 in 2004, 10 donor livers were split ex situ into a left lateral lobe (segments II and III) and a right extended lobe (segments I, IV-VIII) in Medical School of Hannover, and thereafter split liver transplantation was performed successfully in 19 cases. The average age, weight and ICU staying period of the donors were 32.7 years (15-51 years), 64.5 kg (45-75 kg) and 2.4 d (1-8 d) respectively. RESULTS: The average weight of the whole graft and the left lateral lobe was 1,322.6 g (956-1,665 g) and 281.8 g (198-373 g) respectively, and the average ratio of left lateral lobe to the whole graft was 0.215 (0.178-0.274). The average graft to recipient weight ratio (GRWR) of the left lateral lobe and the right extended lobe reached 2.44% (1.22-5.41%) and 1.73% (1.31-2.30%) respectively. On average it took approximately 105 min (85-135 min) to split the donor liver. Five donor organs showed anatomic variation including the left hepatic vein variation in two cases, the left hepatic artery variation in two cases and the bile duct variation in one case. CONCLUSION: Split liver transplantation has become a mature surgical technique to expand the donor pool with promising results. In the process of graft splitting, close attention needs to be paid to potential anatomic variations, especially to variations of the left hepatic vein, the left hepatic artery, and the bile duct.

Adolescent↗

PubMed2005

The evolutionarily related beta-barrel polypeptide transporters from Pisum sativum and Nostoc PCC7120 contain two distinct functional domains.

Several beta-barrel-type channels are involved in the translocation or assembly of outer membrane proteins of bacteria or endosymbiotically derived organelles. Here we analyzed the functional units of the beta-barrel polypeptide transporter Toc75 (translocon in outer envelope of chloroplasts) of the outer envelope of chloroplasts and of a protein, alr2269, from Nostoc PCC7120 with homology to Toc75, both proteins having a similar domain organization. We demonstrated that the N-terminal region functions as a recognition and complex assembly unit, whereas the C terminus forms the beta-barrel-type pore. The pore region is, in turn, modulated by the N terminus of the proteins. The protein from Nostoc PCC7120, which shares a common ancestor with Toc75, is able to recognize precursor proteins destined for chloroplasts. In contrast, the recognition of peripheral translocon subunits by Toc75 is a novel feature acquired through evolution.

Amino Acid Sequence↗

PubMed2005

Factor solution of the BPRS-expanded version in schizophrenic outpatients living in five European countries.

RATIONALE: The expanded version of the Brief Psychiatric Rating Scale (BPRS-E) has improved the instrument's coverage and interrater reliability, but there is little knowledge on its subsyndromes. OBJECTIVES: To assess: (1) whether there are common underlying BPRS-E subscales in patients living in different countries and (2) if this is the case, whether these subscales behave the same in all populations and, if not, what are the differences over these populations. METHODS: Data are part of the EPSILON study, a collaborative project carried out in Denmark, England, Holland, Italy and Spain. A random representative sample of 404 adult patients with a ICD-10 diagnosis of schizophrenia who have been in contact with mental health services of a defined catchment area in each site were assessed. Simultaneous component analysis (SCA) was used to find component weights that optimally explain the variance of the variables in different populations simultaneously. RESULTS: Symptom severity differed significantly among the five EPSILON sites in 12 out of 24 BPRS-E items, but a common component solution could be found. It explained 48.8% of the variance and gave four well-interpretable components: manic excitement/disorganization, depression/anxiety, negative and positive symptoms. Each component's internal consistency and intercomponent correlation matrix differed significantly among sites. The four components mean score differed significantly among sites for negative symptoms and depression/anxiety. CONCLUSIONS: In spite of the heterogeneity of symptom's severity in the various countries, the way symptoms cluster in schizophrenia is rather stable cross-culturally. Data demonstrate that to explore schizophrenia a third component, including mania/disorganization items, is necessary beside the positive-negative symptom dimensions. The subscales derived from these analyses can be readily used in clinical trials and epidemiological studies.

Adult↗

PubMed2005

Distinct methylation patterns of benign and malignant liver tumors revealed by quantitative methylation profiling.

PURPOSE: A comparative quantitative methylation profiling of hepatocellular carcinoma and the most frequent benign liver tumor, hepatocellular adenoma, was set up for the identification of tumor-specific methylation patterns. EXPERIMENTAL DESIGN: The quantitative methylation levels of nine genes (RASSF1A, cyclinD2, p16INK4a, DAP-K, APC, RIZ-1, HIN-1, GSTpi1, SOCS-1) were analyzed in hepatocellular carcinoma and adjacent normal tissue (n = 41), hepatocellular adenoma and adjacent normal tissue (n = 26), focal nodular hyperplasia (n = 10), and unrelated normal liver tissue (n = 28). Accumulated methylation data were analyzed using various statistical algorithms, including hierarchical clustering, to detect tumor-specific methylation patterns. RESULTS: Cluster analysis revealed that hepatocellular adenoma displays a methylation profile much more similar to that found in normal liver tissue and focal nodular hyperplasia than to that found in hepatocellular carcinoma. Many characteristic differences were not detected when using mere qualitative methylation assays. The cyclinD2 gene was identified as a new and frequent target for aberrant hypermethylation in hepatocellular carcinoma (68%). In the control group of 28 liver specimens from healthy donors, a clear correlation between age of patient and frequency and level of aberrant methylation was seen, which could not be detected in the group of hepatocellular carcinoma specimens. CONCLUSIONS: Methylation profiling can clearly contribute to the unequivocal classification of suspicious lesions, but only if done in a quantitative manner applying cell type and gene-specific thresholds. In hepatocellular carcinoma, the altered methylation patterns accompanying malignant transformation override the age-dependent increase in gene methylation.

Adenoma, Liver Cell↗

PubMed2005

Localization and dynamic behavior of ribosomal protein L30e.

The ribosomal protein L30e is an indispensable component of the eukaryotic 80S ribosome, where it is part of the large (60S) ribosomal subunit. Here, we determined the localization of L30e in the cryo-EM map of the 80S wheat germ (wg) ribosome at a resolution of 9.5 A. L30e is part of the interface between large and small subunits, where it dynamically participates in the formation of the two intersubunit bridges eB9 and B4.

Amino Acid Sequence↗

PubMed2005

Neuropilin-1a is involved in trunk motor axon outgrowth in embryonic zebrafish.

Neuropilin-1, a receptor for axon-repellent semaphorins and vascular endothelial growth factor (VEGF), functions both in angiogenesis and axon growth. Here, we show strong expression of neuropilin-1a in primary motor neurons in the trunk of embryonic zebrafish. Reducing the expression of neuropilin-1a using antisense morpholino oligonucleotides induced aberrant branching of motor nerves, additional exit points of motor nerves from the spinal cord, and migration of neurons out of the spinal cord along the motor axon pathway in a dose-dependent manner. These phenotypes could be partially rescued by co-injecting neuropilin-1a mRNA. Other axons in the spinal cord and head appeared unaffected by the morpholino treatment. In addition, neuropilin-1a morpholino treatment disturbed normal formation of blood vessels in the trunk of 24 hours postfertilization embryos, as shown by microangiography. Morpholinos to VEGF also disturbed formation of blood vessels but did not affect motor axons, indicating that correct formation of blood vessels is not needed for the growth of primary motor axons. Morpholinos to the semaphorin 3A homologs semaphorin 3A1 and semaphorin 3A2 also had no effect on motor axon growth. However, combined injections of neuropilin-1a morpholino, at a concentration that did not elicit axonal aberrations when injected alone, with VEGF, semaphorin 3A1, or semaphorin 3A2 morpholinos synergistically increased the proportion of embryos showing aberrant motor axon growth. Thus, neuropilin-1a in primary motor neurons may integrate signals from several ligands and is needed for proper segmental growth of primary motor nerves in zebrafish.

Animals↗