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Biomedical subjects

Ulrich Mansmann

Publications and source records attributed to Ulrich Mansmann.

13 recordsLinked to original sources

Automated Deep Learning-Based Detection of Early Atherosclerotic Plaques in Carotid Ultrasound Imaging.

BACKGROUND: Carotid plaque presence is associated with cardiovascular risk, even among asymptomatic individuals. While deep learning has shown promise for carotid plaque phenotyping in patients with advanced atherosclerosis, its application in population-based settings of asymptomatic individuals remains unexplored. METHODS: We developed a YOLOv8-based model for plaque detection using carotid ultrasound images from 19,499 participants of the population-based UK Biobank (UKB) and fine-tuned it for external validation in the BiDirect study (N = 2,105). Cox regression was used to estimate the impact of plaque presence and count on major cardiovascular events. To explore the genetic architecture of carotid atherosclerosis, we conducted a genome-wide association study (GWAS) meta-analysis of the UKB and CHARGE cohorts. Mendelian randomization (MR) assessed the effect of genetic predisposition to vascular risk factors on carotid atherosclerosis. RESULTS: Our model demonstrated high performance with accuracy, sensitivity, and specificity exceeding 85%, enabling identification of carotid plaques in 45% of the UKB population (aged 47-83 years). In the external BiDirect cohort, a fine-tuned model achieved 86% accuracy, 78% sensitivity, and 90% specificity. Plaque presence and count were associated with risk of major adverse cardiovascular events (MACE) over a follow-up of up to seven years, improving risk reclassification beyond the Pooled Cohort Equations. A GWAS meta-analysis of carotid plaques uncovered two novel genomic loci, with downstream analyses implicating targets of investigational drugs in advanced clinical development. Observational and MR analyses showed associations between smoking, LDL cholesterol, hypertension, and odds of carotid atherosclerosis. CONCLUSIONS: Our model offers a scalable solution for early carotid plaque detection, potentially enabling automated screening in asymptomatic individuals and improving plaque phenotyping in population-based cohorts. This approach could advance large-scale atherosclerosis research.

atherosclerosis↗

The variable number of tandem repeat polymorphism in the P-selectin glycoprotein ligand-1 gene is not associated with coronary heart disease.

Genes involved in inflammatory processes are candidates for predisposition to prothrombotic syndromes. The variable number of tandem repeat (VNTR) polymorphism in the P-selectin glycoprotein ligand (PSGL)-1 gene has been associated with ischemic cerebrovascular disease but not with coronary heart disease (CHD). We assessed the effect of the VNTR polymorphism on CHD in two independent case/control studies. In the first study 281 CHD patients and 397 healthy blood donors were genotyped for the VNTR alleles in PSGL-1. The prevalence of homozygous carriers of the PSGL-1 VNTR allele with 15 repeat units was significantly higher in the CHD patients (5.3% vs. 1.5%) than in controls, suggesting an effect of this marker in CHD. To validate the findings genotyping was performed in a second study including 2,578 CHD patients, 731 patients without CHD, and 1084 healthy blood donors. The larger case control study had a power of 99.9% to detect the initially observed difference but failed to confirm the putative role of PSGL-1 VNTR polymorphism in CHD. Frequencies of the PSGL-1 VNTR 15 repeats for homozygous carriers were 2.2% in healthy blood donors, 2.3% in patients without CHD and 2.7%, in CHD cases, respectively. These results demonstrate that the PSGL-1 VNTR polymorphism is not a genetic risk factor for CHD. Adequately powered studies are prerequisites to obtain reliable results about genotype-phenotype relationships of new candidate genes in complex diseases.

Adult↗

Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group.

PURPOSE: Somatostatin analogs and interferon alfa control hormone-active/functional neuroendocrine gastroenteropancreatic tumors. In addition to hormonal control, variable degrees of antiproliferative effects for both agents have been reported. Until now, however, no prospective, randomized studies in therapy-naive patients have compared somatostatin analogs or interferon alfa alone with a combination of the two. METHODS: Eighty therapy-naive patients with histologically verified neuroendocrine tumor disease (primary localization: foregut, n = 36; midgut, n = 30; hindgut, n = 3; unknown, n = 11; functional, n = 29; nonfunctional, n = 51) were randomly treated either with lanreotide (1 mg three times a day administered subcutaneously [SC]) or interferon alfa (5 x 106 U three times a week SC) or both. All patients had disease progression in the 3 months before study entry, verified with imaging procedures. RESULTS: Twenty-five patients were treated with lanreotide, 27 patients were treated with interferon alfa, and 28 patients were treated with the combination. Partial tumor remission was seen in four patients (one patient who received lanreotide, one patient who received interferon alfa, and two patients who received the combination). During the 12 months of therapy, stable disease was observed in 19 patients (seven patients who received lanreotide, seven patients who received interferon alfa, and five patients who received the combination), whereas tumor progression occurred in 14 of 25 patients (lanreotide), 15 of 27 patients (interferon alfa), and 14 of 28 patients (combination). Side effects leading to an interruption of therapy were more frequent in the combination group than in the monotherapy arms. CONCLUSION: This prospective, randomized, multicenter study shows for the first time that somatostatin analogs, interferon alfa, or the combination of the two had comparable antiproliferative effects in the treatment of metastatic neuroendocrine gastroenteropancreatic tumors. Response rates were lower compared with those published in previous, nonrandomized studies. The antiproliferative effect of the tested substances was similar for functional and nonfunctional neuroendocrine tumors.

Adult↗

Multiple levels of regulation of the interleukin-6 system in stroke.

BACKGROUND AND PURPOSE: Serum levels of the cytokine interleukin-6 (IL-6) rise markedly in stroke. IL-6 is a key regulator of inflammatory mechanisms that play an important part in stroke pathophysiology. The action of IL-6 is modified by its soluble receptor subunits sgp130 and sIL-6R. The purpose of this study was to investigate whether serum levels of the receptor subunits are changed after ischemic stroke and to define the role of genetic influences on IL-6 expression in acute stroke. METHODS: In 48 patients with acute stroke and 48 age- and sex-matched control subjects, serum concentrations of IL-6, sgp130, and sIL-6R were measured by enzyme-linked immunosorbent assay. Furthermore, IL-6 promoter haplotypes comprising 4 different polymorphisms (-597G-->A, -572G-->C, -373A(n)T(n), -174G-->C) were determined by DNA sequencing and allele-specific oligonucleotide polymerase chain reaction. The effect of the common haplotypes on IL-6 gene transcription was tested by transfecting reporter fusion genes in the astrocytelike cell line U373. RESULTS: Whereas serum concentrations of IL-6 significantly rose (P<0.001), sgp130 levels were transiently reduced after stroke (P<0.05), and sIL-6R levels remained unchanged. IL-6 levels depended on the infarct size and the haplotype of the promoter region. The common haplotype A-G-8/12-C was associated with low IL-6 levels after stroke and a reduced induction of IL-6 transcription on stimulation with an adenosine analog in vitro. CONCLUSIONS: The data demonstrate genetic variation in the expression of IL-6 in stroke. Induction of the inflammatory response by IL-6 might be enhanced by a transient downregulation of the potential IL-6 antagonist sgp130.

Acute Disease↗

A new epitope-based HLA-DPB matching approach for cadaver kidney retransplants.

BACKGROUND: Several years ago a significant impact of matching for HLA-DPB1 alleles on the survival of cadaver kidney retransplants was shown. Here we report the results of a new approach, based on matching for HLA-DPB1 epitopes. METHODS: The analysis is based on 1,478 patients who received a cadaver kidney retransplant between 1988 and 1998. DNA methodology (polymerase chain reaction, sequence-specific oligonucleotides) was used to perform HLA-DPB1 typing. Epitope matching was facilitated with the aid of sequence databases and computer calculations. RESULTS: Matching for the HLA-DP epitopes A, B, E, and F, corresponding to the homonymous hypervariable regions of the second exon of the DPB1 gene, seems to have a greater influence on graft survival than matching for the epitopes C and D. Within a group of 529 retransplants with exactly one allelic HLA-DPB1 mismatch, a significantly better graft outcome was observed when less than two epitope mismatches were found, compared with the group with more than three epitope mismatches (at 2 years: 77.8% vs. 65.8%, P=0.0112). Importantly, patients with two DPB1 allele mismatches who had less than or equal to two epitope mismatches exhibited a significantly better graft outcome than recipients who had one HLA-DPB1 allelic mismatch but more than three epitope mismatches (at 2 years: 77.1% vs. 65.8%, P=0.0488). CONCLUSIONS: The findings indicate that the impact of HLA-DPB1 matching on the outcome of kidney retransplants is a result of the predominant immunogenicity of certain epitopes of the HLA-DP molecule. Matching for immunogenic HLA-DPB1 epitopes seems to be functionally more relevant than classical matching at the allelic level.

Cadaver↗

The effect of hydrotherapy on the incidence of common cold episodes in children: a randomised clinical trial.

UNLABELLED: Few interventions have proved to be effective in the prevention and treatment of common colds. Anecdotal reports suggest the possible beneficial effect of hydrotherapy (stimulation of the body surface with warm and cold water). This study's objective was to evaluate the clinical effect of hydrotherapy on common colds in children. Children aged 3-7 years with six or more common cold episodes during the preceding 12 months were randomised to receive either daily inhalation of normal saline in the control group or daily inhalation plus daily hydrotherapy in the experimental group for 12 months. The main outcome measurements were incidence, duration and severity of common cold episodes as reported by the children's parents in a daily symptom diary. Groups did not differ at baseline with regard to age, gender, or number of cold episodes in the year before the study. Diaries were available from 81 patients in the control group and 65 patients in the experimental group. In the study period, there were no significant differences in the incidence of colds (control vs. experimental group, mean +/- SD, 4.8+/-3.5 vs. 4.1+/-3.3 episodes) or the average duration of episodes (7.7+/-3.5 vs. 7.6+/-3.8 days). CONCLUSION: This study does not demonstrate any beneficial effect of hydrotherapy on preschool children with frequent common colds.

Administration, Inhalation↗

Can evaluation studies benefit from triangulation? A case study.

BACKGROUND: Information and communication technologies (ICTs) are increasingly being used in health care. Rigorous evaluations of ICT applications during both introduction and routine use are of great importance for decision makers and users. Within evaluation research, two main (and often rather distinct) traditions can be found: the objectivistic and the subjectivistic tradition. METHODS: The theory of triangulation deals with the integration of methods and approaches as to conduct better evaluation studies. In evaluation research, triangulation in general means the multiple employment of various sources of data, observers, methods, and/or theories in investigations of the same phenomenon. We applied triangulation aspects in the analysis of the effects of a computer-based nursing documentation system. RESULTS: We discuss, based on this case study, what benefits can be obtained from applying triangulation in an evaluation study. We show how both the validation of results and the completeness of results can be supported by triangulation. DISCUSSION: The decision whether triangulation may be useful for a given research question, and how it may be correctly applied, requires-like other evaluation methods-intensive training and methodological experience. Medical informatics evaluation research may profit from this well-established theory.

Documentation↗

Decrease of elastic tissue fibres in stem villus blood vessels of the human placenta during IUGR and IUGR with concomitant pre-eclampsia.

In a recent study we described an increase of elastic tissue fibres in blood vessel walls of placental stem villi during pre-eclampsia when compared to uncomplicated pregnancies. Furthermore, the thickness of these blood vessel walls was enhanced in pre-eclampsia. Since it is known that elastic tissue fibres increase in systemic hypertension, it may be assumed that the enhancement of elastic tissue fibres in placental stem villi during pre-eclampsia may be induced by the hypertension. To get further insight into this assumption, we examined the amount of elastic tissue fibres in stem villus blood vessels of placentae of pregnancies complicated by intrauterine growth retardation (isolated IUGR, fourteen cases), a disease without hypertension of the mother and such with pre-eclampsia and concomitant IUGR (IUGR+PE, nine cases). Each study group was compared with uncomplicated pregnancies (twenty-six cases). Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant lower intensities of orcein staining were calculated for blood vessel walls of placentae of isolated IUGR (P=0.0007) and IUGR+PE (P=0.0039) when compared to uncomplicated pregnancies each. Additionally, the blood vessel wall thickness of stem villi of isolated IUGR (P=0.0081) and IUGR+PE (P=0.0007) was significantly reduced. In comparison to the above mentioned investigation, our results show that, in contrast to isolated pre-eclampsia, elastic tissue fibres are decreased during pregnancies complicated by IUGR, independently of the occurrence of concomitant pre-eclampsia when compared to uncomplicated pregnancies. From our studies it may be considered that the increase of elastic tissue fibres in placentae of patients with isolated pre-eclampsia may be induced by systemic hypertension. Furthermore, our study underline arguments that IUGR may be an independent disease of the fetus.

Adult↗

Course of platelet activation markers after ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the time course of platelet activation after ischemic stroke and to investigate whether platelet activation and inflammation are correlated with each other. METHODS: We serially determined expression of p-selectin (CD62p) and lysosome-associated membrane protein (CD63) by platelets using flow cytometry at 10 time points between days 1 and 90 in patients after ischemic stroke (n=50), in healthy subjects (n=30), and in risk factor control subjects (n=20). Furthermore, we correlated leukocyte count, C-reactive protein, and fibrinogen levels with platelet activation markers. RESULTS: CD62p and CD63 expression was higher on day 1 after stroke than in both control groups (P<0.005 for both). CD62p expression rapidly declined, whereas CD63 expression remained significantly elevated until day 90. Stroke severity and different medication for secondary stroke prevention did not influence CD62p or CD63 expression. Platelet activation markers and inflammatory parameters were not correlated with each other at any time point after stroke. CONCLUSIONS: The initial increase in both CD62p and CD63 expression by platelets is followed by a differential regulation of both parameters after stroke. The rapid decrease in CD62p expression may be caused by shedding from the cell surface. Its persistent elevation makes CD63 a good candidate for studies on predictors for stroke recurrence. Our findings suggest that the expression of CD62p and CD63 by platelets is regulated independently from inflammatory indexes.

Aged↗

Factors affecting and affected by user acceptance of computer-based nursing documentation: results of a two-year study.

OBJECTIVES: The documentation of the nursing process is an important but often neglected part of clinical documentation. Paper-based systems have been introduced to support nursing process documentation. Frequently, however, problems such as low quality of documentation are reported. It is unclear whether computer-based documentation systems can reduce these problems and which factors influence their acceptance by users. DESIGN: We introduced a computer-based nursing documentation system on four wards of the University Hospitals of Heidelberg and systematically evaluated its preconditions and its effects in a pretest-posttest intervention study. For the analysis of user acceptance, we concentrated on subjective data drawn from questionnaires and interviews. MEASUREMENTS: A questionnaire was developed using items from published questionnaires and items that had to be developed for the special purpose of this study. RESULTS: The quantitative results point to two factors influencing the acceptance of a new computer-based documentation system: the previous acceptance of the nursing process and the previous amount of self-confidence when using computers. On one ward, the diverse acceptance scores heavily declined after the introduction of the nursing documentation system. Explorative qualitative analysis on this ward points to further success factors of computer-based nursing documentation systems. CONCLUSION: Our results can be used to assist the planning and introduction of computer-based nursing documentation systems. They demonstrate the importance of computer experience and acceptance of the nursing process on a ward but also point to other factors such as the fit between nursing workflow and the functionality of a nursing documentation system.

Attitude of Health Personnel↗