Bile duct stones, strictures and iatrogenic lesions: studies on early diagnosis and treatment.

Aims: This study was carried out to investigate the role of common liver function tests, and the degree of common bile duct dilatation in the differential diagnosis of extrahepatic cholestasis, as well as the occurrence, diagnosis and treatment of iatrogenic bile duct injuries. In bile duct injuries, special attention was paid to gender and severity distribution and long-term results. Patients and methods: All consecutive patients with diagnosed common bile duct stones or malignant strictures in ERCP between August 2000 and November 2003. Common liver function tests were measured in the morning before ERCP on all of these 212 patients, and their common bile duct diameter was measured from ERCP films. Between January 1995 and April 2002, 3736 laparoscopic cholecystectomies were performed and a total of 32 bile duct injuries were diagnosed. All pre-, per-, and postoperative data were collected retrospectively; and the patients were also interviewed by phone. Results: Plasma bilirubin proved to be the best discriminator between CBD stones and malignant strictures (p≤0.001 compared to other liver function tests and degree of common bile duct dilatation). The same effect was seen in Receiver Operating Characteristics curves (AUC 0.867). With a plasma bilirubin cut-off value of 145 μmol/l, four out of five patients could be classified correctly. The degree of common bile duct dilatation proved to be worthless in differential diagnostics. After laparoscopic cholecystectomy the total risk for bile duct injury was 0.86%, including cystic duct leaks. 86% of severe injuries and 88% of injuries requiring operative treatment were diagnosed in females. All the cystic duct leakages and 87% of the strictures were treated endoscopically. Good long-term results were seen in 84% of the whole study population. Conclusions: Plasma bilirubin is the most effective liver function test in differential diagnosis between CBD stones and malignant strictures. The only value of common bile duct dilatation is its ability to verify the presence of extrahepatic cholestasis. Female gender was associated with higher number of iatrogenic bile duct injuries, and in particular, most of the major complications occur in females. Most of the cystic duct leaks and common bile duct strictures can be treated endoscopically. The long-term results in our institution are at an internationally acceptable level.

Pencil grip : a descriptive model and four empirical studies

Previous studies on pencil grip have typically dealt with the developmental aspects in young children while handwriting research is mainly concerned with speed and legibility. Studies linking these areas are few. Evaluation of the existing pencil grip studies is hampered by methodological inconsistencies. The operational definitions of pencil grip arerational but tend to be oversimplified while detailed descriptors tend to be impractical due to their multiplicity. The present study introduces a descriptive two-dimensional model for the categorisation of pencil grip suitable for research applications in a classroom setting. The model is used in four empirical studies of children during the first six years of writing instruction. Study 1 describes the pencil grips observed in a large group of pupils in Finland (n = 504). The results indicate that in Finland the majority of grips resemble the traditional dynamic tripod grip. Significant genderrelated differences in pencil grip were observed. Study 2 is a longitudinal exploration of grip stability vs. change (n = 117). Both expected and unexpected changes were observed in about 25 per cent of the children's grips over four years. A new finding emerged using the present model for categorisation: whereas pencil grips would change, either in terms of ease of grip manipulation or grip configuration, no instances were found where a grip would have changed concurrently on both dimensions. Study 3 is a cross-cultural comparison of grips observed in Finland and the USA (n = 793). The distribution of the pencil grips observed in the American pupils was significantly different from those found in Finland. The cross-cultural disparity is most likely related to the differences in the onset of writing instruction. The differences between the boys' and girls' grips in the American group were non-significant.An implication of Studies 2 and 3 is that the initial pencil grip is of foremost importance since pencil grips are largely stable over time. Study 4 connects the pencil grips to assessment of the mechanics of writing (n = 61). It seems that certain previously not recommended pencil grips might nevertheless be includedamong those accepted since they did not appear to hamper either fluency or legibility.

Wood as a model material for medical biomaterials. In vivo and in vitro studies with bone and Betula pubescens Ehrh

Novel biomaterials are needed to fill the demand of tailored bone substitutes required by an ever‐expanding array of surgical procedures and techniques. Wood, a natural fiber composite, modified with heat treatment to alter its composition, may provide a novel approach to the further development of hierarchically structured biomaterials. The suitability of wood as a model biomaterial as well as the effects of heat treatment on the osteoconductivity of wood was studied by placing untreated and heat‐treated (at 220 C , 200 degrees and 140 degrees for 2 h) birch implants (size 4 x 7mm) into drill cavities in the distal femur of rabbits. The follow‐up period was 4, 8 and 20 weeks in all in vivo experiments. The flexural properties of wood as well as dimensional changes and hydroxyl apatite formation on the surface of wood (untreated, 140 degrees C and 200 degrees C heat‐treated wood) were tested using 3‐point bending and compression tests and immersion in simulated body fluid. The effect of premeasurement grinding and the effect of heat treatment on the surface roughness and contour of wood were tested with contact stylus and non‐contact profilometry. The effects of heat treatment of wood on its interactions with biological fluids was assessed using two different test media and real human blood in liquid penetration tests. The results of the in vivo experiments showed implanted wood to be well tolerated, with no implants rejected due to foreign body reactions. Heat treatment had significant effects on the biocompatibility of wood, allowing host bone to grow into tight contact with the implant, with occasional bone ingrowth into the channels of the wood implant. The results of the liquid immersion experiments showed hydroxyl apatite formation only in the most extensively heat‐treated wood specimens, which supported the results of the in vivo experiments. Parallel conclusions could be drawn based on the results of the liquid penetration test where human blood had the most favorable interaction with the most extensively heat‐treated wood of the compared materials (untreated, 140 degrees C and 200 degrees C heat‐treated wood). The increasing biocompatibility was inferred to result mainly from changes in the chemical composition of wood induced by the heat treatment, namely the altered arrangement and concentrations of functional chemical groups. However, the influence of microscopic changes in the cell walls, surface roughness and contour cannot be totally excluded. The heat treatment was hypothesized to produce a functional change in the liquid distribution within wood, which could have biological relevance. It was concluded that the highly evolved hierarchical anatomy of wood could yield information for the future development of bulk bone substitutes according to the ideology of bioinspiration. Furthermore, the results of the biomechanical tests established that heat treatment alters various biologically relevant mechanical properties of wood, thus expanding the possibilities of wood as a model material, which could include e.g. scaffold applications, bulk bone applications and serving as a tool for both mechanical testing and for further development of synthetic fiber reinforced composites.

Understanding the bioactivity of plant tannins: developments in analysis methods and structure-activity studies

Tannins, typically segregated into two major groups, the hydrolyzable tannins (HTs) and the proanthocyanidins (PAs), are plant polyphenolic secondary metabolites found throughout the plant kingdom. On one hand, tannins may cause harmful nutritional effects on herbivores, for example insects, and hence they work as plants’ defense against plant-eating animals. On the other hand, they may affect positively some herbivores, such as mammals, for example by their antioxidant, antimicrobial, anti-inflammatory or anticarcinogenic activities. This thesis focuses on understanding the bioactivity of plant tannins, their anthelmintic properties and the tools used for the qualitative and quantitative analysis of this endless source of structural diversity. The first part of the experimental work focused on the development of ultra-high performance liquid chromatography−tandem mass spectrometry (UHPLC-MS/MS) based methods for the rapid fingerprint analysis of bioactive polyphenols, especially tannins. In the second part of the experimental work the in vitro activity of isolated and purified HTs and their hydrolysis product, gallic acid, was tested against egg hatching and larval motility of two larval developmental stages, L1 and L2, of a common ruminant gastrointestinal parasite, Haemonchus contortus. The results indicated clear relationships between the HT structure and the anthelmintic activity. The activity of the studied compounds depended on many structural features, including size, functional groups present in the structure, and the structural rigidness. To further understand tannin bioactivity on a molecular level, the interaction between bovine serum albumin (BSA), and seven HTs and epigallocatechin gallate was examined. The objective was to define the effect of pH on the formation on tannin–protein complexes and to evaluate the stability of the formed complexes by gel electrophoresis and MALDI-TOF-MS. The results indicated that more basic pH values had a stabilizing effect on the tannin–protein complexes and that the tannin oxidative activity was directly linked with their tendency to form covalently stabilized complexes with BSA at increased pH.

Minimization of the experimental workload for the prediction of pollutants propagation in rivers. Mathematical modelling and knowledge re-use

The present thesis in focused on the minimization of experimental efforts for the prediction of pollutant propagation in rivers by mathematical modelling and knowledge re-use. Mathematical modelling is based on the well known advection-dispersion equation, while the knowledge re-use approach employs the methods of case based reasoning, graphical analysis and text mining. The thesis contribution to the pollutant transport research field consists of: (1) analytical and numerical models for pollutant transport prediction; (2) two novel techniques which enable the use of variable parameters along rivers in analytical models; (3) models for the estimation of pollutant transport characteristic parameters (velocity, dispersion coefficient and nutrient transformation rates) as functions of water flow, channel characteristics and/or seasonality; (4) the graphical analysis method to be used for the identification of pollution sources along rivers; (5) a case based reasoning tool for the identification of crucial information related to the pollutant transport modelling; (6) and the application of a software tool for the reuse of information during pollutants transport modelling research. These support tools are applicable in the water quality research field and in practice as well, as they can be involved in multiple activities. The models are capable of predicting pollutant propagation along rivers in case of both ordinary pollution and accidents. They can also be applied for other similar rivers in modelling of pollutant transport in rivers with low availability of experimental data concerning concentration. This is because models for parameter estimation developed in the present thesis enable the calculation of transport characteristic parameters as functions of river hydraulic parameters and/or seasonality. The similarity between rivers is assessed using case based reasoning tools, and additional necessary information can be identified by using the software for the information reuse. Such systems represent support for users and open up possibilities for new modelling methods, monitoring facilities and for better river water quality management tools. They are useful also for the estimation of environmental impact of possible technological changes and can be applied in the pre-design stage or/and in the practical use of processes as well.

PV-1: Leukocyte trafficking molecule and vascular marker

The distinction between lymphatic vessels and blood vessels is a crucial factor in many studies in immunology, vascular biology and cancer biology. They both share several characteristics and perform related, though different functions. They are equally important for the performance of the human immune system with the continuous recirculation of leukocytes from the tissues via lymphatics to the blood vessels and back into the tissue presenting the link between both systems. This study was undertaken to elucidate the differences in the gene expression between primary blood- and lymphatic endothelial cells as well as the two immortalized cell lines HMEC-1 (human microvascular endothelial cell line 1) and TIME (telomerase immortalized microvascular endothelial cell line). Furthermore, we wanted to investigate the mystery surrounding the identity of the antigen recognized by the prototype blood vascular marker PAL-E. In the last step we wanted to study whether the PAL-E antigen would be involved in the process of leukocyte migration from the bloodstream into the surrounding tissue. Our results clearly show that the gene expression in primary blood endothelial cells (BEC), lymphatic endothelial cells (LEC) and the cell lines HMEC-1 and TIME is plastic. Comparison of a large set of BEC- and LEC datasets allowed us to assemble a catalog of new, stable BEC- or LEC specific markers, which we verified in independent experiments. Additionally, several lines of evidence demonstrated that PAL-E recognizes plasmalemma vesicle associated protein 1 (PV-1), which can form complexes with vimentin and neuropilin-1. Finally, numerous in vitro and in vivo experiments identify the first function of the protein PV-1 during leukocyte trafficking, where it acts as regulatory molecule.

Fluvio-morphological processes of meander bends - Combining conventional field measurements, close-range remote sensing and computational modelling

Meandering rivers have been perceived to evolve rather similarly around the world independently of the location or size of the river. Despite the many consistent processes and characteristics they have also been noted to show complex and unique sets of fluviomorphological processes in which local factors play important role. These complex interactions of flow and morphology affect notably the development of the river. Comprehensive and fundamental field, flume and theoretically based studies of fluviomorphological processes in meandering rivers have been carried out especially during the latter part of the 20th century. However, as these studies have been carried out with traditional field measurements techniques their spatial and temporal resolution is not competitive to the level achievable today. The hypothesis of this study is that, by exploiting e increased spatial and temporal resolution of the data, achieved by combining conventional field measurements with a range of modern technologies, will provide new insights to the spatial patterns of the flow-sediment interaction in meandering streams, which have perceived to show notable variation in space and time. This thesis shows how the modern technologies can be combined to derive very high spatial and temporal resolution data on fluvio-morphological processes over meander bends. The flow structure over the bends is recorded in situ using acoustic Doppler current profiler (ADCP) and the spatial and temporal resolution of the flow data is enhanced using 2D and 3D CFD over various meander bends. The CFD are also exploited to simulate sediment transport. Multi-temporal terrestrial laser scanning (TLS), mobile laser scanning (MLS) and echo sounding data are used to measure the flow-based changes and formations over meander bends and to build the computational models. The spatial patterns of erosion and deposition over meander bends are analysed relative to the measured and modelled flow field and sediment transport. The results are compared with the classic theories of the processes in meander bends. Mainly, the results of this study follow well the existing theories and results of previous studies. However, some new insights regarding to the spatial and temporal patterns of the flow-sediment interaction in a natural sand-bed meander bend are provided. The results of this study show the advantages of the rapid and detailed measurements techniques and the achieved spatial and temporal resolution provided by CFD, unachievable with field measurements. The thesis also discusses the limitations which remain in the measurement and modelling methods and in understanding of fluvial geomorphology of meander bends. Further, the hydro- and morphodynamic models’ sensitivity to user-defined parameters is tested, and the modelling results are assessed against detailed field measurement. The study is implemented in the meandering sub-Arctic Pulmanki River in Finland. The river is unregulated and sand-bed and major morphological changes occur annually on the meander point bars, which are inundated only during the snow-melt-induced spring floods. The outcome of this study applies to sandbed meandering rivers in regions where normally one significant flood event occurs annually, such as Arctic areas with snow-melt induced spring floods, and where the point bars of the meander bends are inundated only during the flood events.