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Background: Bioinformatics is fundamental to biomedical sciences, but its mastery presents a steep learning curve for bench biologists and clinicians. Learning to code while analyzing data is difficult. The curve may be flattened by separating these two aspects and providing intermediate steps for budding bioinformaticians. Single-cell analysis is in great demand from biologists and biomedical scientists, as evidenced by the proliferation of training events, materials, and collaborative global efforts like the Human Cell Atlas. However, iterative analyses lacking reinstantiation, coupled with unstandardized pipelines, have made effective single-cell training a moving target., Findings: To address these challenges, we present a Multi-Interface Galaxy Hands-on Training Suite (MIGHTS) for single-cell RNA sequencing (scRNA-seq) analysis, which offers parallel analytical methods using a graphical interface (buttons) or code. With clear, interoperable materials, MIGHTS facilitates smooth transitions between environments. Bridging the biologist-programmer gap, MIGHTS emphasizes interdisciplinary communication for effective learning at all levels. Real-world data analysis in MIGHTS promotes critical thinking and best practices, while FAIR data principles ensure validation of results. MIGHTS is freely available, hosted on the Galaxy Training Network, and leverages Galaxy interfaces for analyses in both settings. Given the ongoing popularity of Python-based (Scanpy) and R-based (Seurat & Monocle) scRNA-seq analyses, MIGHTS enables analyses using both., Conclusions: MIGHTS consists of 11 tutorials, including recordings, slide decks, and interactive visualizations, and a demonstrated track record of sustainability via regular updates and community collaborations. Parallel pathways in MIGHTS enable concurrent training of scientists at any programming level, addressing the heterogeneous needs of novice bioinformaticians., (© The Author(s) 2025. Published by Oxford University Press GigaScience.)

Background: In clinical research, data have to be accessible and reproducible, but the generated data are becoming larger and analysis complex. Here we propose a platform for Findable, Accessible, Interoperable, and Reusable (FAIR) data access and creating reproducible findings. Standardized access to a major genomic repository, the European Genome-Phenome Archive (EGA), has been achieved with API services like PyEGA3. We aim to provide a FAIR data analysis service in Galaxy by retrieving genomic data from the EGA and provide a generalized "omics" platform for FAIR data analysis., Results: To demonstrate this, we implemented an end-to-end Galaxy workflow to replicate the findings from an RD-Connect synthetic dataset Beyond the 1 Million Genomes (synB1MG) available from the EGA. We developed the PyEGA3 connector within Galaxy to easily download multiple datasets from the EGA. We added the gene.iobio tool, a diagnostic environment for precision genomics, to Galaxy and demonstrate that it provides a more dynamic and interpretable view for trio analysis results. We developed a Galaxy trio analysis workflow to determine the pathogenic variants from the synB1MG trios using the GEMINI and gene.iobio tool. The complete workflow is available at WorkflowHub, and an associated tutorial was created in the Galaxy Training Network, which helps researchers unfamiliar with Galaxy to run the workflow., Conclusions: We showed the feasibility of reusing data from the EGA in Galaxy via PyEGA3 and validated the workflow by rediscovering spiked-in variants in synthetic data. Finally, we improved existing tools in Galaxy and created a workflow for trio analysis to demonstrate the value of FAIR genomics analysis in Galaxy., (© The Author(s) 2024. Published by Oxford University Press GigaScience.)

There are thousands of well-maintained high-quality open-source software utilities for all aspects of scientific data analysis. For more than a decade, the Galaxy Project has been providing computational infrastructure and a unified user interface for these tools to make them accessible to a wide range of researchers. To streamline the process of integrating tools and constructing workflows as much as possible, we have developed Planemo, a software development kit for tool and workflow developers and Galaxy power users. Here we outline Planemo's implementation and describe its broad range of functionality for designing, testing, and executing Galaxy tools, workflows, and training material. In addition, we discuss the philosophy underlying Galaxy tool and workflow development, and how Planemo encourages the use of development best practices, such as test-driven development, by its users, including those who are not professional software developers., (© 2023 Bray et al.; Published by Cold Spring Harbor Laboratory Press.)

There is an ongoing explosion of scientific datasets being generated, brought on by recent technological advances in many areas of the natural sciences. As a result, the life sciences have become increasingly computational in nature, and bioinformatics has taken on a central role in research studies. However, basic computational skills, data analysis, and stewardship are still rarely taught in life science educational programs, resulting in a skills gap in many of the researchers tasked with analysing these big datasets. In order to address this skills gap and empower researchers to perform their own data analyses, the Galaxy Training Network (GTN) has previously developed the Galaxy Training Platform (https://training.galaxyproject.org), an open access, community-driven framework for the collection of FAIR (Findable, Accessible, Interoperable, Reusable) training materials for data analysis utilizing the user-friendly Galaxy framework as its primary data analysis platform. Since its inception, this training platform has thrived, with the number of tutorials and contributors growing rapidly, and the range of topics extending beyond life sciences to include topics such as climatology, cheminformatics, and machine learning. While initially aimed at supporting researchers directly, the GTN framework has proven to be an invaluable resource for educators as well. We have focused our efforts in recent years on adding increased support for this growing community of instructors. New features have been added to facilitate the use of the materials in a classroom setting, simplifying the contribution flow for new materials, and have added a set of train-the-trainer lessons. Here, we present the latest developments in the GTN project, aimed at facilitating the use of the Galaxy Training materials by educators, and its usage in different learning environments., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: DB has a significant financial interest in GalaxyWorks, a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and is managed by the Cleveland Clinic. This does not alter our adherence to all the PLOS Computational Biology policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Hands-on training, whether in bioinformatics or other domains, often requires significant technical resources and knowledge to set up and run. Instructors must have access to powerful compute infrastructure that can support resource-intensive jobs running efficiently. Often this is achieved using a private server where there is no contention for the queue. However, this places a significant prerequisite knowledge or labor barrier for instructors, who must spend time coordinating deployment and management of compute resources. Furthermore, with the increase of virtual and hybrid teaching, where learners are located in separate physical locations, it is difficult to track student progress as efficiently as during in-person courses., Findings: Originally developed by Galaxy Europe and the Gallantries project, together with the Galaxy community, we have created Training Infrastructure-as-a-Service (TIaaS), aimed at providing user-friendly training infrastructure to the global training community. TIaaS provides dedicated training resources for Galaxy-based courses and events. Event organizers register their course, after which trainees are transparently placed in a private queue on the compute infrastructure, which ensures jobs complete quickly, even when the main queue is experiencing high wait times. A built-in dashboard allows instructors to monitor student progress., Conclusions: TIaaS provides a significant improvement for instructors and learners, as well as infrastructure administrators. The instructor dashboard makes remote events not only possible but also easy. Students experience continuity of learning, as all training happens on Galaxy, which they can continue to use after the event. In the past 60 months, 504 training events with over 24,000 learners have used this infrastructure for Galaxy training., (© The Author(s) 2023. Published by Oxford University Press GigaScience.)

Summary: Properly and effectively managing reference datasets is an important task for many bioinformatics analyses. Refgenie is a reference asset management system that allows users to easily organize, retrieve and share such datasets. Here, we describe the integration of refgenie into the Galaxy platform. Server administrators are able to configure Galaxy to make use of reference datasets made available on a refgenie instance. In addition, a Galaxy Data Manager tool has been developed to provide a graphical interface to refgenie's remote reference retrieval functionality. A large collection of reference datasets has also been made available using the CVMFS (CernVM File System) repository from GalaxyProject.org, with mirrors across the USA, Canada, Europe and Australia, enabling easy use outside of Galaxy., Availability and Implementation: The ability of Galaxy to use refgenie assets was added to the core Galaxy framework in version 22.01, which is available from https://github.com/galaxyproject/galaxy under the Academic Free License version 3.0. The refgenie Data Manager tool can be installed via the Galaxy ToolShed, with source code managed at https://github.com/BlankenbergLab/galaxy-tools-blankenberg/tree/main/data_managers/data_manager_refgenie_pull and released using an MIT license. Access to existing data is also available through CVMFS, with instructions at https://galaxyproject.org/admin/reference-data-repo/. No new data were generated or analyzed in support of this research., (© The Author(s) 2022. Published by Oxford University Press.)

The COVID-19 pandemic is shifting teaching to an online setting all over the world. The Galaxy framework facilitates the online learning process and makes it accessible by providing a library of high-quality community-curated training materials, enabling easy access to data and tools, and facilitates sharing achievements and progress between students and instructors. By combining Galaxy with robust communication channels, effective instruction can be designed inclusively, regardless of the students' environments., Competing Interests: The authors have declared that no competing interests exist.

Background: Galaxy is a web-based and open-source scientific data-processing platform. Researchers compose pipelines in Galaxy to analyse scientific data. These pipelines, also known as workflows, can be complex and difficult to create from thousands of tools, especially for researchers new to Galaxy. To help researchers with creating workflows, a system is developed to recommend tools that can facilitate further data analysis., Findings: A model is developed to recommend tools using a deep learning approach by analysing workflows composed by researchers on the European Galaxy server. The higher-order dependencies in workflows, represented as directed acyclic graphs, are learned by training a gated recurrent units neural network, a variant of a recurrent neural network. In the neural network training, the weights of tools used are derived from their usage frequencies over time and the sequences of tools are uniformly sampled from training data. Hyperparameters of the neural network are optimized using Bayesian optimization. Mean accuracy of 98% in recommending tools is achieved for the top-1 metric., Conclusions: The model is accessed by a Galaxy API to provide researchers with recommended tools in an interactive manner using multiple user interface integrations on the European Galaxy server. High-quality and highly used tools are shown at the top of the recommendations. The scripts and data to create the recommendation system are available under MIT license at https://github.com/anuprulez/galaxy_tool_recommendation., (© The Author(s) 2021. Published by Oxford University Press GigaScience.)

In the modern genomic era, scientists without extensive bioinformatic training need to apply high-power computational analyses to critical tasks like phage genome annotation. At the Center for Phage Technology (CPT), we developed a suite of phage-oriented tools housed in open, user-friendly web-based interfaces. A Galaxy platform conducts computationally intensive analyses and Apollo, a collaborative genome annotation editor, visualizes the results of these analyses. The collection includes open source applications such as the BLAST+ suite, InterProScan, and several gene callers, as well as unique tools developed at the CPT that allow maximum user flexibility. We describe in detail programs for finding Shine-Dalgarno sequences, resources used for confident identification of lysis genes such as spanins, and methods used for identifying interrupted genes that contain frameshifts or introns. At the CPT, genome annotation is separated into two robust segments that are facilitated through the automated execution of many tools chained together in an operation called a workflow. First, the structural annotation workflow results in gene and other feature calls. This is followed by a functional annotation workflow that combines sequence comparisons and conserved domain searching, which is contextualized to allow integrated evidence assessment in functional prediction. Finally, we describe a workflow used for comparative genomics. Using this multi-purpose platform enables researchers to easily and accurately annotate an entire phage genome. The portal can be accessed at https://cpt.tamu.edu/galaxy-pub with accompanying user training material., Competing Interests: The authors have declared that no competing interests exist.

The academic de.NBI Cloud offers compute resources for life science research in Germany.  At the beginning of 2017, de.NBI Cloud started to implement a federated cloud consisting of five compute centers, with the aim of acting as one resource to their users. A federated cloud introduces multiple challenges, such as a central access and project management point, a unified account across all cloud sites and an interchangeable project setup across the federation. In order to implement the federation concept, de.NBI Cloud integrated with the ELIXIR authentication and authorization infrastructure system (ELIXIR AAI) and in particular Perun, the identity and access management system of ELIXIR. The integration solves the mentioned challenges and represents a backbone, connecting five compute centers which are based on OpenStack and a web portal for accessing the federation.This article explains the steps taken and software components implemented for setting up a federated cloud based on the collaboration between de.NBI Cloud and ELIXIR AAI. Furthermore, the setup and components that are described are generic and can therefore be used for other upcoming or existing federated OpenStack clouds in Europe., Competing Interests: No competing interests were disclosed.

Genome annotation is the process of identifying the location and function of a genome's encoded features. Improving the biological accuracy of annotation is a complex and iterative process requiring researchers to review and incorporate multiple sources of information such as transcriptome alignments, predictive models based on sequence profiles, and comparisons to features found in related organisms. Because rapidly decreasing costs are enabling an ever-growing number of scientists to incorporate sequencing as a routine laboratory technique, there is widespread demand for tools that can assist in the deliberative analytical review of genomic information. To this end, we present Apollo, an open source software package that enables researchers to efficiently inspect and refine the precise structure and role of genomic features in a graphical browser-based platform. Some of Apollo's newer user interface features include support for real-time collaboration, allowing distributed users to simultaneously edit the same encoded features while also instantly seeing the updates made by other researchers on the same region in a manner similar to Google Docs. Its technical architecture enables Apollo to be integrated into multiple existing genomic analysis pipelines and heterogeneous laboratory workflow platforms. Finally, we consider the implications that Apollo and related applications may have on how the results of genome research are published and made accessible., Competing Interests: The authors have declared that no competing interests exist.

Community biological databases provide an important online resource for both public and private data, analysis tools and community engagement. These sites house genomic, transcriptomic, genetic, breeding and ancillary data for specific species, families or clades. Due to the complexity and increasing quantities of these data, construction of online resources is increasingly difficult especially with limited funding and access to technical expertise. Furthermore, online repositories are expected to promote FAIR data principles (findable, accessible, interoperable and reusable) that presents additional challenges. The open-source Tripal database toolkit seeks to mitigate these challenges by creating both the software and an interactive community of developers for construction of online community databases. Additionally, through coordinated, distributed co-development, Tripal sites encourage community-wide sustainability. Here, we report the release of Tripal version 3 that improves data accessibility and data sharing through systematic use of controlled vocabularies (CVs). Tripal uses the community-developed Chado database as a default data store, but now provides tools to support other data stores, while ensuring that CVs remain the central organizational structure for the data. A new site developer can use Tripal to develop a basic site with little to no programming, with the ability to integrate other data types using extension modules and the Tripal application programming interface. A thorough online User's Guide and Developer's Handbook are available at http://tripal.info, providing download, installation and step-by-step setup instructions., (© The Author(s) 2019. Published by Oxford University Press.)

Galaxy (homepage: https://galaxyproject.org, main public server: https://usegalaxy.org) is a web-based scientific analysis platform used by tens of thousands of scientists across the world to analyze large biomedical datasets such as those found in genomics, proteomics, metabolomics and imaging. Started in 2005, Galaxy continues to focus on three key challenges of data-driven biomedical science: making analyses accessible to all researchers, ensuring analyses are completely reproducible, and making it simple to communicate analyses so that they can be reused and extended. During the last two years, the Galaxy team and the open-source community around Galaxy have made substantial improvements to Galaxy's core framework, user interface, tools, and training materials. Framework and user interface improvements now enable Galaxy to be used for analyzing tens of thousands of datasets, and >5500 tools are now available from the Galaxy ToolShed. The Galaxy community has led an effort to create numerous high-quality tutorials focused on common types of genomic analyses. The Galaxy developer and user communities continue to grow and be integral to Galaxy's development. The number of Galaxy public servers, developers contributing to the Galaxy framework and its tools, and users of the main Galaxy server have all increased substantially.

Undertreatment of the older patients with AML can explain, in part, their inferior outcome when compared with that in younger patients. In analogy to the benefit of patients under the age of 60 years from high-dose AraC there are dosage related therapeutic effects in the patients over 60 years in particular for daunorubicin in the induction treatment, and for maintenance versus no maintenance in the post-remission treatment. Utilizing these effects can partly overcome the mostly unfavorable disease biology in older age AML, whereas the role of risk factors involved is not completely understood and the concept of dose-response needs to be requestioned. We recommend an adequate dosage of 60 mg/(m2day) daunorubicin for 3 days in a combination with standard dose AraC and 6-thioguanine given for induction and consolidation and followed by a prolonged monthly maintenance chemotherapy. Further improvements in supportive care may help delivering additional anti-leukemic cytotoxicity. As a novel approach, reduced toxicity preparative regimens may open up allogeneic transplantation for older patients with AML. Other new options like MDR modulators, antibody targeted therapies and tyrosine kinase inhibitors are under clinical investigation. A questionnaire study in patients with AML showed that according to patients' self-assessment intensive and prolonged treatment did not result in decreasing quality of life. This finding did not vary by age under or above 60 years. Given the actual median age in this disease being more than 60 years the adequate management of older age AML remains as the major challenge.

Undertreatment of older patients with acute myeloid leukemia (AML) can explain, in part, their inferior outcome when compared to that of younger patients. In agreement with the benefit seen by patients under age 60 from high-dose cytosine arabinoside (Ara-C), there are dose effects in the over 60s, in particular for daunorubicin, in induction treatment and for the duration of postremission treatment. The use of these effects can partly overcome the mostly unfavorable disease biology in older age AML, as expressed by the absence of favorable and the over-representation of adverse chromosomal abnormalities as well as the expression of drug resistance. We recommend an adequate dosage of 60 mg/m2 daunorubicin on 3 days in combination with standard dose Ara-C and 6-thioguanine given for induction and consolidation, and followed by a prolonged monthly maintenance chemotherapy for at least 1 year's duration. Further improvements in supportive care may help to deliver additional antileukemic cytotoxicity. As a novel approach, nonmyeloablative preparative regimens may open up the possibility of allogeneic transplantation for older patients with AML. Other new options like multidrug resistance modulators, antibody targeted therapies and molecular targeting are under clinical investigation. A questionnaire study in patients with AML showed that, according to patients' self-assessment, intensive and prolonged treatment did not result in a diminished quality of life. This finding did not vary by age, under or over 60 years. As the median age in this disease is more than 60 years, the adequate management of AML in older patients remains the major challenge.

Intensive induction therapy in acute myeloid leukemia (AML) as in some other systemic malignancies is a strategy fundamentally different from post-remission strategies. Approaches such as consolidation treatment, prolonged maintenance, and autologous or allogeneic transplantation in first remission are directed against the minimal residual disease in which a malignant cell population has survived induction treatment and shows resistance due to special genetic or kinetic features. In contrast, induction therapy deals with naive tumor cells possibly different from their counterparts in remission in terms of their kinetic status and sensitivity. Therefore, in AML the introduction of intensification strategies into the induction phase of treatment has been suggested as a new step in addition to intensification in the postremission phase. As expected from the dose effects observed in post-remission treatment with high-dose cytarabine (AraC) or longer treatment, similar dose effects have been found in induction treatment both from the incorporation of high-dose AraC and from the double-induction strategy used in patients up to 60 years of age. As a particular effect, patients with poor-risk AML according to an unfavorable karyotype, high LDH in serum, or a delayed response show longer survival following double induction containing high-dose AraC as compared to standard-dose AraC. A corresponding dose effect in the induction treatment of patients aged 60 years and older has been found with daunorubicin 60 vs 30 mg/m2 as part of the thioguanine/ AraC/daunorubicin (TAD) regimen with the higher dosage significantly increasing the response rate and survival in these older patients who represent a poor-risk group as a whole. Thus we have been able to demonstrate both in younger and older patients that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits cumulative toxicity in that repeated courses containing high-dose AraC in the post-remission period lead to long-lasting aplasias of about 6 weeks. Thus after intensive induction treatment, high-dose chemotherapy in remission may be practicable using stem-cell rescue and may contribute to a further improvement in the outcome in poor-risk as well as average-risk patients with AML. These approaches are currently under investigation by the German AML Cooperative Group (AMLCG). "The more intensive the better" is certainly not the way to go in the management of AML and other systemic malignancies but some increase in intensity may be possible and better.

Maintenance treatment for patients with acute myeloid leukemia (AML) in remission has recently been controversially discussed and even abandoned by several groups. An analysis of 14 recently published multicenter trials, however, revealed the highest probabilities of relapse-free survival (RFS), in the range of 35% to 42% at 4 to 5 years, only in patients assigned to maintenance treatment as far as adult age and intent-to-treat conditions were considered. After having demonstrated a superior RFS rate from 3 years of maintenance after standard-dose consolidation compared with that from consolidation alone (P = .00004), the German AMLCG requestioned the effect of maintenance randomly compared with sequential high-dose cytosine arabinoside (Ara-C) and mitoxantrone in patients who received intensified induction treatment. The results show an advantage for maintenance treatment (RFS rate of 32%) versus the sequential Ara-C and mitoxantrone treatment (RFS rate of 25%) (P = .021). We conclude that maintenance treatment continues to substantially contribute to the management of adult patients with AML, even as part of recent strategies using intensified induction treatment, and thus appears necessary in these settings.

Background: Direct thrombin inhibitors belong to a new class of antithrombotic drugs whose effects on blood coagulation in vivo in patients suffering from acute thrombotic conditions have not yet been fully explored., Methods and Results: One hundred and five patients with acute proximal deep-vein thrombosis were randomized to receive a continuous intravenous infusion of napsagatran, a novel synthetic thrombin inhibitor, at a fixed dose of 5 mg/h (n = 36) or 9 mg/h (n = 25) for five days, or APTT-adjusted unfractionated heparin (UFH, n = 44) for the same time. In these patients, thrombin activity and thrombin generation could be assessed by measuring thrombin-antithrombin III complexes (TAT) and prothrombin fragment 1+2 (F1+2), respectively, on three occasions. At baseline, TAT and F1+2 did not differ among the three groups. On Day 2 (steady state), TAT significantly decreased in all groups, and the decrease was significantly more pronounced in the patients given higher-dose napsagatran. F1+2 decreased significantly only in UFH-treated patients. Two hours after cessation of the infusion, the TAT levels increased in the two napsagatran groups but not in the UFH group, whilst F1+2 went back to the baseline levels in the napsagatran-treated patients but remained low in the UFH-treated patients. There was no rebound effect., Conclusions: The data presented suggest that direct thrombin inhibition with napsagatran at 9 mg/h is more potent than UFH in attenuating thrombin activity, but is less potent than UFH in inhibiting thrombin generation. The real significance of these findings will have to be substantiated in further trials with clinically relevant endpoints.

One hundred and ten patients with acute proximal deep-vein thrombosis were randomized in a sequential dose-finding design, to receive continuous intravenous infusion of napsagatran, a novel synthetic thrombin-inhibitor, at a fixed dose of 5 mg/h (n = 37) or 9 mg/h (n = 26), or APTT-adjusted unfractionated heparin (n = 47). Oral anticoagulants were started on the 2nd day and the study drug was discontinued from the 5th treatment day, as soon as the International Normalized Ratio was above 2. Control venogram (97 venogram pairs evaluable) after 5-8 days of treatment showed improvement in 3 napsagatran-treated patients (versus none in heparin-treated patients) and worsening in 4 napsagatran-treated patients (versus 2 in heparin-treated patients). The venographic Marder's score did not change among the treatment groups. New lung scan perfusion defects (99 scintigram pairs evaluable) occurred in 4 (11%), 4 (21%), and 4 (10%) patients in the napsagatran (5 mg/h) group, in the napsagatran (9 mg/h) group, and in the heparin control group, respectively. There was no statistically significant difference in any of these endpoints between the 3 groups. No major bleeding was observed and the rare minor bleedings occurred at a similar rate in the three treatment groups. In conclusion, the ADVENT trial has shown data that suggest comparable efficacy and safety of a synthetic, direct thrombin inhibitor (napsagatran) and conventional heparin therapy for treatment of proximal DVT. These results suggest that synthetic direct thrombin inhibitors are a promising class of antithrombotic agents which deserves further development in this field.

In the present study, 28 hemophiliacs substituted continuously and 5 hemophiliacs who had received almost no blood products were investigated. Cells of OKT 3+, OKT 4+, and OKT 8+ subsets were counted. Percoll separated fractions of peripheral blood mononuclear cells were examined by morphological criteria and were tested for NK cell activity. We found that the NK cell activity of both groups of hemophiliacs was decreased on testing Ficoll separated cells or low density Percoll separated cells. Normal NK cell activity was found in medium density cells of hemophiliacs. Two possible explanations are discussed: first, the NK cell activity may be suppressed in hemophiliacs and secondly, there may be a block in maturation of NK cell activity. It is unlikely that chronic substitution by blood products counts for these alterations. The possible role of chronic infections is discussed.

During the last 3 years, 306 membrane plasma separations (MPS) were performed on 40 patients. Activated partial thromboplastin time (APTT), oncotic pressure (OP), blood count, free hemoglobin, prothrombin time, fibrinogen, and factors II, V, VII, VIII, IX, X, XI, and XIII were determined. The complication rate was evaluated. Mild complications were observed in 4.2% of the cases (extracorporeal coagulation 1.5%, hypotensive episodes 2%, allergic reactions 0.7%). Severe complications were not observed. A flexible heparinization schedule dependent on the APTT values is necessary. In general, 4,500-7,000 IU/MPS is required. The serum OP is maintained within the normal range using a 3-6% human albumin solution to prevent circulatory complications. A marked loss of fibrinogen occurs with short intervals between successive treatments. The remaining coagulation factors are reduced by an average of 32% and the prothrombin time by 28%. Control of the heparinization and OP is essential for monitoring plasma exchange therapy.

The influence of somatostatin on platelets was studied in healthy volunteers. After a bolus injection of 250 microgram somatostatin followed by a three hour infusion at a rate of 250 microgram somatostatin/hr a statistically significant fall of platelet count and impairment of platelet aggregation was observed. The aggregation inhibiting effect of somatostatin at the end of the three hour infusion is clinically unimportant as compared to the effect of aspirin. In vitro concentrations up to 10.0 microgram somatostatin per ml do not show any effect on platelet aggregation and platelet stickiness. Endocrinologically active doses of somatostatin in short term infusions are very unlikely to cause bleeding disorders.

40 patients with acute leukaemia and severe granulocytopenia were treated with granulocyte transfusions for bacteriologically documented or clinically suspected septicaemia. The patients received an average of 5 transfusions each with 2.1 X 10(10) granulocytes per m2 body surface area per day. 26 patients showed clinical benefit from transfusion therapy as documented by the course of blood cultures, local lesions and fever. Only patients with regeneration of granulopoiesis had definite benefit from granulocyte transfusions. All other patients died ultimately from septicaemia.

Thirty-three patients with Addison's disease were studied. Twenty-two had idiopathic Addison's disease; within this group, 14 patients had clinical or subclinical hypothyroidism, and 16 had increased titres of thyroid autoantibodies. Five patients had tuberculous, and eight had unclassifiable Addison's disease; only one patient in the latter group had evidence of thyroid autoimmunity. A stimulation test with 15 mU bTSH/kg was performed in three patients with Schmidt's syndrome (coexisting Addison's disease and manifest primary hypothyroidism), 15 patients with either subclinical hypothyroidism or increased titres of thyroid autoantibodies, 10 patients without thyroid involvement, and 10 normal controls. There was no detectable increase of 'free' and total thyroid hormones in Schmidt's syndrome. The mean increases after 3-4 h of T4, fT4, T3 and fT3 were 22, 35, 63 and 66%, respectively, in patients without thyroid involvement, and 13, 24, 46 and 45% in patients with subclinical hypothyroidism. 'Free' but not total thyroid hormones rose significantly (P less than 0.01) higher in patients without signs of thyroid involvement than in patients with subclinical hypothyroidism and/or thyroid autoantibodies. Thyroid hormone response to bTSH in Addison's disease with apparently healthy thyroid glands was not different from normal controls. Serum diiodotyrosine rose in all groups except in hypothyroidism; hypothyroid patients had, however, basal levels well within the normal range. Thus, thyroid hormone synthesis appears to be blocked at a point distal to diiodotyrosine formation in this particular situation. These results support the assumption that TSH elevation in idiopathic Addison's disease is due to coexisting thyroid autoimmunity and that it reflects incipient thyroid failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Eight human spleens were perfused for up to 65 h at normothermia and the coagulant Factor VIII activity measured in the perfusate. In addition, in three experiments Factor VIII-related antigen was determined in the perfusate. Although the spleens were pathologically enlarged and the normal structure involved by different diseases, all spleens released Factor VIII coagulant activity and Factor VIII-related antigen. On average the total amount of Factor VIII coagulant activity released was equivalent to that of 3.5 l of human plasma.