Biomedical subjects

P Nykänen

Publications and source records attributed to P Nykänen.

At least 19 recordsLinked to original sources

PubMed2006

Success and failure factors in the regional health information system design process--results from a constructive evaluation study.

OBJECTIVES: To identify success and failure factors in the design process of a regional health information system. METHODS: A constructive evaluation study including interviews, observations, usability study and document analysis. RESULTS: Modelling was found to be a key element for the successful implementation of a health information system. The developed service chain model helped to define use cases and to implement seamless service chains. User participation in the design process was a success factor resulting in good user acceptance and signs of positive impacts on work practices. Evaluation study also helped system developers to guide the system's further development. An important failure factor identified was the lack of semantic interoperability of the system components. CONCLUSIONS: The results emphasize the socio-technical nature of health information systems. The starting point for development should be thorough insight into the health care work practices where the information systems are to be used. Successful system design should start from modelling of work processes, data and information flows and definition of concepts and their relations. Health informatics as a scientific discipline provides theories and models for the design and development process.

Attitude to Computers↗

PubMed2006

Factors influencing success and failure of health informatics systems--a pilot Delphi study.

OBJECTIVES: The aim is to gain information on factors influencing success and failure for Health Informatics applications from a group of medical informaticians. METHODS: Based on the presentations at a special topic conference on success and failure in Health ICT and analysis of the proceedings, we conducted a Delphi study on success and failure aspects. RESULTS: A total of 110 success factors and 27 failure criteria were identified, distributed on categories like functional, organizational, behavioral, technical, managerial, political, cultural, legal, strategy, economy, education and user acceptance. These factors and criteria were rated for six different system types. Unanimously it was agreed that "collaboration and co-operation" and "setting goals and courses" are "essential for the success" of clinical systems, and "user acceptance" for educational systems. Similarly, the score "essential in order to avoid a failure" were given unanimously on clinical systems for "response rate and other performance measures" and on administrative systems for "not understanding the organizational context" with "not understanding or foreseeing the extent to which the new IT-system affects the organization, its structure and/or work procedures" as the highest scoring sub-item. CONCLUSIONS: All success factors and failure criteria were considered relevant by the Delphi expert panel. There is no small set of relevant factors or indicators, but success or failure of a Health ICT depends on a large set of issues. Further, clinical systems and decision support systems depend on more factors than other systems.

Delphi Technique↗

PubMed2004

Citric acid as a pH-regulating additive in granules and the tablet matrix in enteric-coated formulations for colon-specific drug delivery.

Colon-specific drug-delivery systems have been extensively investigated over the last decade. The aim of the study reported here was to investigate whether times of commencement of drug liberation and absorption could be controlled by varying the amount of citric acid in granule cores or in the tablet matrix in enteric-coated multiple-unit tablets. One of the most important aims was to determine the optimal amounts and locations of citric acid in formulations intended as drugs targeted at the colon. Ibuprofen was used as the model drug. Drug release rates were studied in phosphate buffer at pH 6.8 and 7.4. A gradient dissolution study at pH 1.2, 6.8 and 7.4 was undertaken with two formulations. Drug absorption was studied by means of bioavailability tests. We concluded that the drug release rate could be controlled in vitro by changing the amount of citric acid in granule cores or the tablet matrix. In vivo tests confirmed that between 10 and 15% citric acid in the tablet matrix delayed the commencement of drug absorption most. This kind of formulations could be suitable for preparation of colon-specific dosage forms. It is probably unnecessary to include citric acid in granule cores. No logical correlation between in vitro and in vivo results was obtained.

Adult↗

PubMed2001

Citric acid as excipient in multiple-unit enteric-coated tablets for targeting drugs on the colon.

Delivery of drugs to the large bowel has been extensively investigated during the last decade. The aim of this study was to investigate whether enteric-coated tablets could be made from enteric-coated matrix granules and drug release targeted to the colon. Whether in vitro drug release rate and in vivo absorption could be delayed by adding citric acid to the granules and/or to the tablet matrix was also studied. Ibuprofen was used as model drug because it is absorbed throughout the gastrointestinal tract. Eudragit S and Aqoat AS-HF were used as enteric polymers. Drug release rates were studied at different pH levels and drug absorption was studied in bioavailability tests. The conclusion was that citric acid retarded in vitro drug release when used in multiple-unit tablets. In vivo absorption of ibuprofen was markedly delayed when citric acid was included in both granules and tablet matrix. Further studies are needed to determine the optimal amount of citric acid in formulations.

Adult↗

PubMed2001

Roles of the heat shock transcription factors in regulation of the heat shock response and beyond.

The heat shock response, characterized by increased expression of heat shock proteins (Hsps) is induced by exposure of cells and tissues to extreme conditions that cause acute or chronic stress. Hsps function as molecular chaperones in regulating cellular homeostasis and promoting survival. If the stress is too severe, a signal that leads to programmed cell death, apoptosis, is activated, thereby providing a finely tuned balance between survival and death. In addition to extracellular stimuli, several nonstressful conditions induce Hsps during normal cellular growth and development. The enhanced heat shock gene expression in response to various stimuli is regulated by heat shock transcription factors (HSFs). After the discovery of the family of HSFs (i.e., murine and human HSF1, 2, and 4 and a unique avian HSF3), the functional relevance of distinct HSFs is now emerging. HSF1, an HSF prototype, and HSF3 are responsible for heat-induced Hsp expression, whereas HSF2 is refractory to classical stressors. HSF4 is expressed in a tissue-specific manner; similar to HSF1 and HSF2, alternatively spliced isoforms add further complexity to its regulation. Recently developed powerful genetic models have provided evidence for both cooperative and specific functions of HSFs that expand beyond the heat shock response. Certain specialized functions of HSFs may even include regulation of novel target genes in response to distinct stimuli.

Amino Acid Sequence↗

PubMed2001

Genomic organization and promoter analysis of the human heat shock factor 2 gene.

Heat shock factor 2 (HSF2) is a member of the heat shock transcription factor family, which appears to be activated during differentiation and development rather than on cellular stress. Here we report the isolation and characterization of the human hsf2 gene and its 5'-flanking region. The transcription unit of the human hsf2 gene consists of 13 exons dispersed over 33 kbp of genomic DNA on chromosome 6. The hsf2 mRNA is transcribed from multiple start sites, and initiation from the major site results in a transcript of 2.45 kb. A functional promoter, as determined by the ability to direct expression of a transiently transfected luciferase reporter gene, resides in a 950-bp upstream region of the human hsf2 gene. Examination of the core promoter sequence revealed a high GC content and lack of a canonical TATA box. This feature seems to be common among various species, as comparison of the hsf2 proximal promoter sequences from human, mouse, and rat showed distinct conserved regions. Moreover, the overall architecture of the human hsf2 gene is similar to its mouse counterpart. A comparison between human hsf2 gene and other hsf genes showed striking similarities in exon size. However, the exons are assembled in an hsf-specific manner.

5' Flanking Region↗

PubMed2001

On conceptualization of a decision support system in health informatics.

A decision support system can be approached from two major disciplinary perspectives, those of information systems science (IS) and artificial intelligence (AI). We present in this study an extended ontology for a decision support system in health informatics, which is founded on experience from related research fields as well as being informed by our case studies. The ontology emphasises the need to cover environmental and contextual variables as an integral part of a decision support systems development methodology. With the addition of these variables, the focus in decision support systems development shifts from a task ontology towards a domain ontology. The results of this study help the system developers to take the system's context into account through the set of defined variables that are linked to the application domain. These variables explicate relevant constructs and present a vocabulary for a decision support system. However, applying the ontology requires a more thorough analysis of the domain and therefore more qualified resources for systems development. This indicates the need to focus more on education and training in health informatics.

Artificial Intelligence↗

PubMed1999

Organic acids as excipients in matrix granules for colon-specific drug delivery.

Interest exists in developing site-specific systems for release of a drug in the lower part of the small intestine or in the colon. The aim of this study was to investigate whether drug release rates from enteric matrix granules could be influenced by using organic acids as excipients. Ibuprofen was used as a model drug and Eudragit S and Aqoat AS-HF as enteric polymers. The dissolution rates of the drug were investigated at different levels of pH (5.8, 6.8 and 7. 4). Drug absorption was studied in bioavailability tests in healthy volunteers. In vitro/in vivo correlation was also investigated. It was concluded that although inclusion of an organic acid in a formulation retarded in vitro release of the model drug, no corresponding effect was evident in in vivo studies. Bioavailability tests are therefore important early on during development of new dosage forms or formulations. Although no correlation between in vitro and in vivo results was generally evident correlation could be demonstrated for individual formulations following mathematical transformation of data.

Acids↗

PubMed1999

Enteric polymers as binders and coating materials in multiple-unit site-specific drug delivery systems.

The aim of this study was to develop a multiple-unit, site-specific drug formulation allowing targeting of drug release in the colon. Initially, characteristics of matrix pellets containing various enteric polymers as binders were tested. An enteric coating was then added to the formulations. Ibuprofen and furosemide were used as model drugs. The former is absorbed throughout the gastrointestinal tract, the latter only from upper parts. Methacrylate copolymers, hydroxypropyl methylcellulose acetate succinates and cellulose acetate phthalate were used as enteric polymers. The properties of the products were initially tested via dissolution studies at different pHs, then via bioavailability studies in healthy volunteers. The main conclusion was that drug release can be targeted on the distal part of the small intestine and the colon by preparing film-coated matrix pellets in which enteric polymers dissolving at pH approximately 7 have been used both as binders in the pellets and as coating material. This conclusion is based on the finding that absorption of ibuprofen from the formulations developed was adequate, with a lag-time of about 2 h and tmax values at 4-5 h, where as absorption of furosemide from the analogous products was negligible. It was also found that uncoated pellets as such could represent a slow-release formulation for furosemide, a problem drug as far as modified-release products are concerned.

Adult↗

PubMed1999

The VATAM guidelines.

Evaluation and assessment of the impact of information and communication technology in medicine is gaining interest. Unfortunately, till now there were no agreed upon approaches. The objective of the VATAM project is to develop guidelines that will assist assessors to set-up and execute studies. This paper describes the background of the VATAM project and provides an account of the current state of the guidelines. It concludes with an indication of the developments that will take place in the short term to further elaborate the guidelines and some considerations for consolidation of VATAM's results.

Databases, Factual↗

PubMed1999

Inventory of validation approaches in selected health telematics projects.

This paper presents the results from an inventory of validation approaches and methodologies which have been used in selected health telematics projects. The inventory was performed in the VATAM Validation of Telematic Applications in Medicine project, HC1115HC. The purpose of the inventory was to analyse the methodologies and their application assumptions in order to identify possibilities for harmonization and consolidation. The inventory was performed using five validation dimensions: IT-development; quality; user; technology assessment and marketing. The inventory results show that possibilities exist to synthesise methodologies and to provide practical guidance and support for projects that are developing health telematics applications. All stakeholders in health telematics projects, i.e. users, health care decision-makers, developers, suppliers and IT-industries, can benefit from practical validation guidelines and support for validation when guidelines are represented in a usable, easy to access and informative way.

Humans↗

PubMed1999

Comparison between low- and standard-dose ACTH tests in premature infants at risk for chronic lung disease.

In order to find a sensitive method to evaluate adrenocortical function in premature infants, we compared low- (0.5 microg/1.73 m(2)) and standard-dose (250 microg/1.73 m(2)) adrenocorticotropin tests (LD- and SD-ACTH) in 12 very-low-birth-weight infants before and 2 days after the end of dexamethasone therapy (duration 9-14 days) for chronic lung disease. Basal serum cortisol levels were inappropriately low in several infants already before dexamethasone therapy (median 190, range 60-357 nmol/l). The 95% confidence intervals of mean serum cortisol levels at 20 min were equal in LD- and SD-ACTH, while at 60 min, the low-dose gave a clearly lower response than the standard-dose test. The LD-ACTH can be used in premature infants as in older children and adults, but the criteria for adrenocortical insufficiency need to be defined.

Adrenocorticotropic Hormone↗

PubMed1997

VATAM: developing consensus in validation of health telematics applications.

VATAM (Validation of Telematics Applications in Medicine) is an EU supported project in the Health care sector of the Telematics Application Programme. Its objective is to assist other health telematics projects by providing a platform for discussion on validation, eventually resulting in 'guidelines for validation of telematics applications in medicine'. The VATAM work can be subdivided into three phases: the inventory phase (1996) in which information is collected on validation approaches in the Telematics Application Programme, previous efforts and expertise. The dissemination phase (1997) will be used to extend and adapt the framework developed in the inventory phase, through cooperation with other projects The experiences phase (1998) in which the projects are actually applying validation, will be used by VATAM to validate the VATAM methodology. VATAM has finished the inventory phase successfully and is now working on the dissemination phase by--among others--establishing contacts with other projects, and providing information on the inventory through the World Wide Web (URL: http:(/)/www-vatam.unimaas.nl). This paper discusses the approach adopted and the proposed VATAM framework to structure the large variety of validation approaches.

Computer Communication Networks↗

PubMed1994

KAVAS-2: Knowledge Acquisition, Visualization and Assessment System.

The objective of KAVAS-2 is the development of a tool, named KAVIAR, with which domain experts can make their knowledge explicit. It contains components for (computer assisted) knowledge elicitation and for machine learning. A key issue in KAVAS is the assessment of the quality of the classification and domain models built. Various quality measures are available and implemented in KAVIAR to assess the quality of models, specifically those developed from data bases by machine learning techniques.

Computer Simulation↗

PubMed1994

OpenLabs: the application of advanced informatics and telematics for optimization of clinical laboratory services.

OpenLabs has four major objectives: to improve the efficiency and effectiveness of clinical laboratory services by the integration of Knowledge Based Systems (KBSs) with Laboratory Information Systems (LISs) and equipment; to provide and implement standard solutions for Electronic Data Interchange (EDI) between laboratories and other medical systems; to specify a fully Open architecture for an integrated Clinical LIS and demonstrate the integration of various KBS modules on the open architecture platform; and to demonstrate the integration of OpenLabs modules with existing LISs.

Clinical Laboratory Information Systems↗

PubMed1993

Interpretative reporting and alarming based on laboratory data.

The utilisation of laboratory services for patient diagnosis and management involves many steps with both clinical and laboratory components. The clinical components include the decision to order a test, interpretation of the test results and actions taken on the basis of the results. The laboratory components on the other hand include receipt of the request, specimen collection, preparation and analysis, result entry, test result validation and verification and reporting of the results. In this paper, which is part of the OpenLabs project, we concentrate on the post-analytical applications which include interpretation and reporting of the laboratory results to the users in primary care and in high dependency care units. The final objective of the work described is to develop generic modules which can be integrated both with an Open laboratory information system architecture and existing laboratory information processing environment.

Acid-Base Imbalance↗

PubMed1989

DNA synthesis in prolyl 4-hydroxylase positive fibroblasts in situ in synovial tissue. An autoradiography-immunoperoxidase double labeling study.

DNA synthesis in prolyl 4-hydroxylase (PH; EC 1.14.11.2) positive fibroblasts in situ in synovial tissue was studied using an autoradiography-avidin-biotin-peroxidase complex (ABC) double labeling. Fibroblasts in monolayer culture and in situ in synovial tissue were PH positive, whereas freshly isolated peripheral blood lymphocytes, monocytes, dendritic cells and granulocytes were PH negative. In rheumatoid arthritis (RA) 37 +/- 3 (22-56)% of all DNA synthesizing cells in situ were PH containing fibroblasts, whereas all DNA synthesizing cells in patients with meniscus lesion were PH positive. In both conditions, more than half of the self-replicating fibroblasts were located in the lining cell layer. This is probably not an artifact caused by insufficient penetration of 3H-thymidine because most of the DNA synthesizing lymphocytes were deep down in the synovial stroma. In RA 51 +/- 8 (17-88) PH positive fibroblasts in the S phase of the cell cycle were observed/3 mm2 synovial tissue, whereas the corresponding figure in meniscus patients was only 1 +/- 1 (0-5) (p less than 0.01). This suggests that the local fibroblasts in RA are activated, probably as a result of various fibroblast growth factors produced locally as a result of the inflammatory synovitis. In RA however, less than 1% of all local fibroblasts were self-replicating in situ, whereas labeling indices over 5% were not uncommon in RA synovial fibroblast cultures. This finding suggests that uncontrolled fibroblast proliferation is regulated in vivo by negative feedback mechanisms.

Arthritis, Rheumatoid↗

PubMed1988

A cytochemical study on the effects of energy deprivation on autophagocytosis in Ehrlich ascites tumor cells.

The effect of energy deprivation on autophagocytosis in Ehrlich ascites tumor cells was studied using cytochemical techniques. Autophagocytosis was induced with vinblastine incubation (0.1 mM) and the cellular ATP-level was lowered with 2-deoxy-D-glucose (0.35 mM). Acid phosphatase was used as a marker for lysosomal enzymes and imidazole-buffered osmium tetroxide impregnation in order to study the effects of energy deprivation on the maturation of autophagic vacuole (AV) membranes. Control and vinblastine treated cells maintained their ATP-levels throughout the incubation period tested (120 min). 2-Deoxy-D-glucose alone and with vinblastine decreased the intracellular ATP-level significantly after only 3 min incubation. Most of the AV's in control and vinblastine treated cells contained degraded material and acid phosphatase activity. Their membranes were stained only slightly or not at all with imidazole-buffered osmium tetroxide. 2-Deoxy-D-glucose alone as well as with vinblastine induced in particular an accumulation of early stages of AV's. These vacuoles contained undegraded cytoplasmic material and no acid phosphatase activity and their membranes were stained usually partly with imidazole-buffered osmium tetroxide. The membranes of some early AV's resembled endoplasmic reticulum and still had attached ribosomes. It was concluded that the inhibition of cellular energy production used in the present study did not inhibit autophagic sequestration but retarded the maturation of AV membranes and impaired the functioning of lysosomal hydrolases.

Acid Phosphatase↗