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Considerable demand for the repair of bone defects cannot be met solely by using biological donor materials. Hence, the use of biocomposites will most likely be increased in reconstructive surgery in future. Metallic implants cannot be used in all cases, because the defects in the skeleton vary greatly, differing from each other in their shape, size, anatomic location, and physiological weight-bearing in the anatomic location. Therefore, more sophisticated orthopaedic materials (e.g. non-metallic fibre-reinforced composites and particulate filler composites) should be available for clinical practice. Our studies have focused on the development of injectable composites of biostable bone cements, i.e. in situ curable resin systems containing impregnated calcium ceramics particles. The properties of the bone cement composites aspire to simulate as closely as possible the mechanical and structural properties of bone. The purpose of this study was to evaluate the in vitro cell proliferation on the experimental injectable biostable polymer modified with calcium ceramics. In the course of proliferation, the cell activity on the calcium ceramics containing biostable polymer composite increased throughout the experiment. As a conclusion, this cell proliferation study indicated that the studied biocomposite has a good potential to promote cell interaction.

BACKGROUND Wood has been used as a model material for the development of novel fiber-reinforced composite bone substitute biomaterials. In previous studies heat treatment of wood was perceived to significantly increase the osteoconductivity of implanted wood material. AIM The objective of this study was to examine some of the changing attributes of wood materials that may contribute to improved biological responses gained with heat treatment. METHODS Untreated and 140°C and 200°C heat-treated downy birch (Betula pubescens Ehrh.) were used as the wood materials. Surface roughness and the effect of pre-measurement grinding were measured with contact and non-contact profilometry. Liquid interaction was assessed with a dipping test using two manufactured liquids (simulated blood) as well as human blood. SEM was used to visualize possible heat treatment-induced changes in the hierarchical structure of wood. RESULTS The surface roughness was observed to significantly decrease with heat treatment. Grinding methods had more influence on the surface contour and roughness than heat treatment. The penetration of the human blood in the 200°C heat-treated exceeded that in the untreated and 140°C heat-treated materials. SEM showed no significant change due to heat treatment in the dry-state morphology of the wood. DISCUSSION The results of the liquid penetration test support previous findings in literature concerning the effects of heat treatment on the biological response to implanted wood. Heat-treatment has only a marginal effect on the surface contour of wood. The highly specialized liquid conveyance system of wood may serve as a biomimetic model for the further development of tailored fiber-composite materials.

The diagnosis of erythema migrans (EM) is not always easy, and reports of culture- or PCR-confirmed diagnosis as well as reports of EM with simultaneous disseminated disease are few. Characteristics and incidence of EM in addition to frequency of early dissemination of B. burgdorferi were studied in the archipelago of South-Western Finland prospectively using questionnaires, skin biopsies and blood samples. Clinical EM was recognized in 82 patients (incidence 148/100,000 inhabitants/year). Of skin biopsy samples, 35.5% were positive by PCR (the majority B. garinii), and 21.5% by cultivation (all B. garinii). Of blood samples, 3.8% were positive by PCR, and 7.7% by cultivation. Of the patients, 30.9% were seropositive at the first visit, and 52.9% 3 weeks later. Of the patients with laboratory confirmed diagnosis, the EM lesion was ring-like in 31.8% and homogeneous in 65.9%. Dissemination of B. burgdorferi, based on culture or PCR positivity of blood samples, was detected in 11.0% of the patients. The frequency of generalized symptoms was nearly the same in patients with as in those without dissemination (22.2% vs 27.4%). Only 21.4% of the patients with culture-positive EM recalled a previous tick bite at the site of the EM lesion. We conclude that EM lesions are more often homogeneous than ring-like. B. burgdorferi may disseminate early without generalized symptoms.

The aim of the present study was to characterise the ability of malignant chondrosarcomas to invade normal bone by analysing their production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, and for immunohistochemical localisation of the proteins. A characteristic finding of these analyses was increased expression of MMP-13, MMP-14 and TIMP-2 mRNAs in chondrosarcomas when compared with nonmalignant control samples. Individual chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive or have a probability of recurrence. Another finding of the present study was a marked heterogeneity in histologic appearance and gene expression of the chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that analysis of MMPs could be a useful diagnostic indicator in patients with cartilaginous tumours and could help in differentiating between a low-grade malignant chondrosarcoma and a benign growing enchondroma.

To investigate the pulmonary effects of steroid treatment in neonates with meconium aspiration, 25 10- to 12-d-old piglets were studied for 6 h after an intratracheal bolus of human meconium. Dexamethasone (0.5 mg/kg) was given in two treatment schedules, either 1 h before (n = 6) or 1 h after meconium instillation (n = 8). Eight piglets served as controls. Three additional piglets were given dexamethasone without meconium instillation. Pulmonary hemodynamics and oxygenation were followed, and lung tissue samples investigated for signs of inflammation and ultrastructural injury, including apoptosis. Pulmonary artery pressure and vascular resistance increased after meconium instillation, but this rise was significantly prevented after prophylactic dexamethasone. This treatment also improved the acutely deteriorated oxygenation of the piglets after meconium insufflation. Prophylactic, but not early, dexamethasone treatment further protected the lungs from the ultrastructural changes caused by meconium instillation. Additionally, the increase of apoptotic epithelial cell deaths was significantly prevented by both dexamethasone treatments. These results show that prophylactic dexamethasone treatment significantly attenuates the early pulmonary hemodynamic deterioration and structural lung damage caused by meconium aspiration. Further studies on the apoptosis-inhibiting effect of dexamethasone administration in neonatal lungs exposed to heavy meconium are warranted.

The presence of bone morphogenetic proteins (BMPs) in 13 primary bone neoplasms was investigated with conventional bioassay method and immunohistochemically using antiserum against highly purified mixture of bovine BMPs as antibody. In conventional bioassay after implantation of lyophilized bone tumor tissues into mouse muscle pouches 9/13 samples turned out positive by radiography and 10/13 histologically. By immunohistochemical staining, using the avidin-biotin-peroxidase method, signs of BMPs could be verified in all cases investigated. Microscopical scoring showed the local concentration of BMPs to be especially high in sections from giant cell tumors when compared to other bone neoplasms.

Purpose: to investigate magnetization transfer (MT) parameters and rotating frame relaxation time T1ρ in patellar cartilage at different levels of degeneration Material and Methods: Thirty cadaveric patellae were examined at 0.1 T using the time-dependent saturation-transfer MT technique and the spin lock (SL) technique. in an SL experiment, nuclear spins are locked with a radiofrequency (RF) field, and the locked nuclear magnetization relaxes along the magnetic component of the locking RF field. the specimens were divided into three groups according to the level of cartilage degeneration. MT parameters and T1ρ were measured Results: the MT effect was greater in degenerated cartilage than in normal cartilage. T1ρ was longer in advanced cartilage degeneration than in intermediate cartilage degeneration Conclusion: the results suggest that more studies are needed to fully establish the value of SL imaging in cartilage degeneration

Summary. Bone morphogenetic protein (BMP) has been shown to be one of the significant factors in the prognosis of bone tumours. In normal development BMP induces new bone formation and later takes part in fracture healing, but its function in malignant tumours is not known. In this study the concentration of bone morphogenetic protein was measured in primary bone tumours by two methods. Local staining intensity was detected immunohistologically by the avidin-biotin-peroxidase method determining the highest dilution of anti-serum against bovine bone morphogenetic protein. The total amount of BMP in a tumour sample was measured by an enzyme-linked immunosorbent assay technique after digesting the tissue with collagenase to remove proteins from the connective tissue. Immunohistochemical staining showed that bone morphogenetic protein was present in the cytoplasm and in reactive bone formed by malignant cells. The local concentration was highest in the tissue of giant cell tumours compared to chondrosarcoma, osteosarcoma and benign bone tumours. The total amount in malignant bone tumours was 2.4 times higher compared to benign bone tumours.

Crucian carp Carassius carassius show great phenotypic plasticity in individual morphology and physiology, and strong variation in population density in different fish communities. Small fish with shallow bodies and large heads are typical in overcrowded monospecific fish communities in small ponds, whereas deep-bodied, large fish are found in larger, multispecies lakes. Crucian carp are especially vulnerable to predation by piscivorous fish and their greater relative body depth in multispecies fish communities has been proposed to be an induced defence against size-limited predation, and hence to be an adaptive feature. Data are presented here on the two divergent body forms in field populations in eastern Finland, together with results of laboratory experiments on predator effects on morphology and physiology (growth, respiration, heart rate). The deep body can be achieved in a few months by introducing a low population density of shallow-bodied fish into a food-rich environment with no piscivores. In the laboratory, both the presence of piscivores (chemical cues) and enhanced food availability increased the relative depth of crucian carp, but only to a modest extent when compared to natural variation. It is concluded that the deep-body form of crucian carp in the low density populations of multispecies fish communities is the normal condition. Reproduction in monospecific ponds results in high intraspecific competition, low growth rate and a stunted morphology. According to pilot tests, the mechanism behind the predator effect in the laboratory might be a behavioural reaction to chemical cues (alarm substances/predator odour) causing changes in energy allocation: predator-exposed crucian carp adopt a ‘hiding’ mode with decreased activity (less swimming, lower respiration and heart rate) and with higher overall growth. Whether, and to what extent, this predator-induced mechanism works in nature is unclear.

Histological re-evaluation revealed 36 osteogenic sarcoma (OS) patients for analysis in South-Western Finland treated between 1958 and 1987. In 21 cases (58%) the tumour was located in the knee region. The mean age at diagnosis was 28 years (range: 5-62 years) and the follow-up time of the patients was at least 5 years or until death. In 29 patients without metastases at the time of diagnosis, the extent of the primary tumour was T2 in 37% and T3 in 63% of the patients. There were no differences regarding the extent of the primary tumour, delay of the diagnosis, mean age of the patients, or duration of the symptoms while comparing the three decades of the study. Before the 1970s the treatment consisted of surgery with or without radiotherapy in most cases. Since the 1970s the combination of surgical treatment (amputation or wide excision) and adjuvant chemotherapy was the most common treatment modality. Since the late 1970s limb-salvage surgery has been applied in selected cases, and it seems to be justified. None of the patients treated before 1970 survived for 5 years. The 5- and 10-year survival of all 36 patients was 44.4% and 33.6%, respectively. In non-metastatic patients both the 5- and 10-year disease-free survival was 46.7%. A certain group exhibiting a good prognosis was found; the 10-year survival of the 10 patients with OS in extremities, treated with combined chemotherapy and surgery, was 70%. The median survival time was significantly longer for the patients with an intracompartmental tumour extent of T2 (112 months) compared with an extracompartmental extent of T3 (23 months), and for the patients with the primary tumour in the knee region (112 months) compared with other locations (18 months). The long-term survival of the OS patients has improved concomitantly with the multimodality of the treatment.

The main objective of this study was to characterize the cellular phenotypes in the repair tissue of full-thickness defects of articular cartilage by histologic and molecular biologic techniques. Healing of the defects in the articular cartilage of the knee joints of 12 rabbits was analyzed at days 3, 7, 14, 28 and 50 using histology and Northern analysis of mRNA levels for type I, II and III collagens and osteonectin. The cellular source of each mRNAs was determined by in situ hybridization. Two novel cDNA clones for rabbit type II and III collagen mRNA were constructed to obtain species-specific hybridization probes. The repair tissue of full-thickness defects consisted of two types of tissue. At the bottom of the defect, bone-derived cells with high levels of type I collagen and osteonectin mRNA were actively producing new osteoid, while superficially a slow transition from a fibrin clot into undifferentiated mesenchyme with cells containing type III collagen mRNA was observed. This tissue subsequently became fibrocartilaginous, with small groups of cells turning on the transcription of the type II collagen gene and acquiring a phenotype typical for hyaline cartilage. The data suggest that small clusters of cells in the repair tissue of full-thickness articular cartilage defects are capable of turning on an apparently correct chondrocytic phenotype. The low transcription level of the type II collagen gene suggests, however, that insufficient amounts of fundamentally important regulatory factors or progenitor cells are present in the repair tissue. In the future, such factors should be administrable into the joint by novel therapeutic means.

In orthopedics, traumatology, and craniofacial surgery, biomaterials should meet the clinical demands of bone that include shape, size and anatomical location of the defect, as well as the physiological load-bearing stresses. Biomaterials are metals, ceramics, plastics or materials of biological origin. In the treatment of large defects, metallic endoprostheses or bone grafts are employed, whereas ceramics in the case of small defects. Plastics are employed on the artificial joint surfaces, in the treatment of vertebral compression fractures, and as biodegradable screws and plates. Porosity, bioactivity, and identical biomechanics to bone are fundamental for achieving a durable, well-bonded, interface between biomaterial and bone. In the case of severe bone treatments, biomaterials should also imply an option to add biologically active substances.

This paper analyzes the performance and power losses of 2.1 MVA conventional STATCOMs and STATCOMs with energy storage (ESTATCOM), in electric arc furnace applications. The research was conducted by computer simulations with Matlab Simulink software. According to the simulation results load compensation reduces the required current rating of the supply grid transformer and cables by approximately 30 %, and the maximum drop of the reference point (RP) voltage to 2 % compared to 15 % caused by the non-compensated case. The conventional STATCOM attenuates the RP voltage flicker by a factor of 5.9 and the ESTATCOM by a factor of 11.7. The voltage source converters (VSC) of both compensators could be designed for the same rated current, despite the active power compensation capabilities of the ESTATCOM. The system losses are minimized when a 3-level VSC is used instead of a 2-level VSC, and the compensating device is connected to the lowest studied network voltage of 690 V. The energy storage system losses are minimized when the energy storage is connected to the dc link using two separate DC/DC converters instead of a large single converter. This occurs because the system converters can be implemented with IGBTs of lowest rated voltage.

The aim of this study was to compare the osteoconductivity and suitability of three biomaterials used as particulate fillers; S53P4 bioactive glass, allogeneic fresh frozen bone and coral-derived calcium carbonate.Materials were implanted into drill-holes in the femoral condyles of adult rabbits. Follow-ups were performed at 3, 6, 12 and 24 weeks. Host-response, osteoconductivity, bonding and filler-effect were evaluated by SEM, EDXA and histology and histomorphometry to evaluate.All three materials were found to be biocompatible and osteoconductive. Defects filled with allograft seemed to have more bone at 24 weeks, although no statistically significant difference in new bone growth was found. In earlier time points, coral, however, was observed to degrade more quickly, leaving more empty space in the defects, thus making it a less suitable filler for cavitary defects.At all time points there was less filler material (i.e. biomaterial and new bone) in coral-filled defects than in BAG or allograft filled defects (p0.05).

Dynamic power quality improvement and reactive power compensation are typically done either using SVC or STATCOM system depending on performance requirement. Installation and operational costs of a STATCOM are clearly higher compared to the costs of SVC. The benefit of using STATCOM is 2..3 times higher flicker reduction performance compared to SVC. This paper describes a concept and real time simulation results of the concept, where SVC is combined with SVC to do the power quality improvement and reactive power compensation tasks. The target is to optimise the compensation system in terms of costs, performance and availability. (4 pages)

The purpose of this study was to investigate the effect of fiber orientation of a fiber-reinforced composite (FRC) made of poly-methyl-methacrylate (PMMA) and E-glass to the surface fabrication process by solvent dissolution. Intention of the dissolution process was to expose the fibers and create a macroporous surface onto the FRC to enhance bone bonding of the material. The effect of dissolution and fiber direction to the bone bonding capability of the FRC material was also tested. Three groups of FRC specimens (n = 18/group) were made of PMMA and E-glass fiber reinforcement: (a) group with continuous fibers parallel to the surface of the specimen, (b) continuous fibers oriented perpendicularly to the surface, (c) randomly oriented short (discontinuous) fibers. Fourth specimen group (n = 18) made of plain PMMA served as controls. The specimens were subjected to a solvent treatment by tetrahydrofuran (THF) of either 5, 15 or 30 min of time (n = 6/time point), and the advancement of the dissolution (front) was measured. The solvent treatment also exposed the fibers and created a surface roughness on to the specimens. The solvent treated specimens were embedded into plaster of Paris to simulate bone bonding by mechanical locking and a pull-out test was undertaken to determine the strength of the attachment. All the FRC specimens dissolved as function of time, as the control group showed no marked dissolution during the study period. The specimens with fibers along the direction of long axis of specimen began to dissolve significantly faster than specimens in other groups, but the test specimens with randomly oriented short fibers showed the greatest depth of dissolution after 30 min. The pull-out test showed that the PMMA specimens with fibers were retained better by the plaster of Paris than specimens without fibers. However, direction of the fibers considerably influenced the force of attachment. The fiber reinforcement increases significantly the dissolution speed, and the orientation of the glass fibers has great effect on the dissolving depth of the polymer matrix of the composite, and thus on the exposure of fibers. The glass fibers exposed by the solvent treatment enhanced effectively the attachment of the specimen to the bone modeling material.

Lysinuric protein intolerance is an autosomal recessive disease caused by defective transport of cationic amino acids. Of the 38 lysinuric protein intolerance patients diagnosed in Finland since 1965, four pediatric patients have died. We describe the clinical courses and autopsy findings for these patients. All patients developed acute respiratory insufficiency. In addition to pulmonary hemorrhages, three of the patients had pulmonary alveolar proteinosis and one had cholesterol granulomas. Three patients had a clinically obvious renal insufficiency, but all four showed histologic signs of immune complex-mediated glomerulonephritis. The patients also developed hepatic insufficiency with fatty degeneration or cirrhosis. All patients showed anemia, thrombocytopenia, and a severe bleeding tendency. The bone marrow of three patients was hypercellular, but the amount of megakaryocytes was decreased in two cases. Amyloid was present in the lymph nodes and the spleen. Bone specimens showed osteoporosis. We conclude that pediatric patients with lysinuric protein intolerance are predisposed to develop pulmonary alveolar proteinosis and glomerulonephritis. They are also at risk of protein malnutrition in the active growth phase, probably due to higher requirements for total nitrogen and amino acids.

Sugammadex is designed to antagonize neuromuscular blockade (NMB) induced by rocuronium or vecuronium. In clinical practice, we have noticed a rise in the numerical values of bispectral index (BIS) and Entropy, two electroencephalogram (EEG) - based depth of anesthesia monitors, during the reversal of the NMB with sugammadex. The aim of this prospective, randomized, double-blind study was to test this impression and to compare the effects of sugammadex and neostigmine on the BIS and Entropy values during the reversal of the NMB.Thirty patients undergoing gynecological operations were studied. Patients were anesthetized with target-controlled infusions of propofol and remifentanil, and rocuronium was used to induce NMB. After operation, during light propofol-remifentanil anesthesia, NMB was antagonized with sugammadex or neostigmine. During the following 5 min, the numerical values of BIS, BIS electromyographic (BIS EMG) and Entropy were recorded on a laptop computer, as well as the biosignal recorded by the Entropy strip. The Entropy biosignal was studied off-line both in time and frequency domain to see if NMB reversal causes changes in EEG.In some patients, administration of sugammadex or neostigmine caused a significant rise in the numerical values of BIS, BIS EMG and Entropy. This phenomenon was most likely caused by increased electromyographic (EMG) activity. The administration of sugammadex or neostigmine appeared to have only minimal effect on EEG.The EMG contamination of EEG causes BIS and Entropy values to rise during reversal of rocuronium-induced NMB in light propofol-remifentanil anesthesia.

The clinical and radiological outcomes of bioactive glass (BAG)-S53P4 and autograft bone (AB) used as bone-graft substitutes in depressed tibial plateau fractures were evaluated in a prospective randomized 11-year follow-up study. All patients (n = 29) had sustained tibial plateau fractures with a joint-line depression of >3 mm. Fifteen patients (5 patients the BAG group, 10 patients in the AB group) participated in this long-term follow-up. X-rays were taken preoperatively, postoperatively, and at the long-term follow-up, and computed tomography (CT) scans were made at the long-term follow-up for evaluation of the bone substitute, osteoarthritis, the tibial-femoral angle, and deviation of mechanical axes. No material-dependent adverse effects were seen in any patient. The means of the articular surface depression on X-rays at the long-term follow-up were 1.4 mm (range: 0-2 mm) in the BAG group and 1.4 mm (range: 0-4 mm) in the AB group, and on CT scans the means were 2.2 mm (range: 2-3 mm), and 2.1 mm (range: 0-3), respectively. No significant difference in the tibial-femoral angle or deviation of mechanical axes was observed between the two groups. BAG-S53P4 can be used as a bone substitute in depressed lateral tibial plateau fractures with good functional and radiological long-term results.

The need for reconstructive surgery of bones is continuously increasing along with the ageing of the population as well as the increase of traumatologic injuries. In the United States, the number of bone grafts was 350,000 in 2001. Nowadays, over 500,000 bone graft procedures are performed annually, and approximately 2.2 million worldwide (Giannoudis et al., 2005). The estimated cost of these procedures approaches US$2.5 billion per year. Hence, the considerable demand for these replacement procedures cannot be met solely by using donor material. Therefore, superior synthetic orthopaedic materials and techniques should be available on the market for clinical practice. Adjustable porosity, bioactivity, identical biomechanics, as well as all the other tissue-friendly properties to bone are central for achieving a durable, bonding-like, interface between the synthetic material and bone (Aho et al., 2004). Actually, modern material technology would have all the know-how for preparing excellent synthetic orthopaedic materials. Autografts are still regarded as optimal reconstruction material, because of the lack of good enough synthetic materials. However, in orthopaedics, the demands for synthetic materials could be fulfilled by using composite structures. In fact, it is possible to mimic better the structures of living materials, like bone, cartilage or teeth using composite structures. Therefore, there is still a constant need to search for better synthetic bone substitute materials for tissue engineering (Chung et al., 2007).

We studied osseointegration of a bioactive glass (BG) and hydroxylapatite (HA) in rabbit femur epiphyseal and metaphyseal regions. 17 BG and 24 HA cones implanted in defects through arthrotomy were analyzed. The holes for implants were drilled through distal femur joint surfaces. The cartilage wound repaired generally by fibrous tissue. Histomorphometry showed that 61, 78, and 79 percent of BG surface was covered by bone at 3, 6, and 12 weeks, respectively. The corresponding figures for HA were 47, 67, and 78 percent. Chemical bonding between bone and implants of both types was confirmed by scanning electron microscopy (SEM) and energy-dispersive x-ray analysis (EDXA). Formation of a calcium phosphate-rich layer on the surface BG implant was demonstrated by EDXA. Our results indicate that the osseointegration rate of bioactive glass does not differ from that of hydroxylapatite.

Bioactive glass (BAG) and polymethyl methacrylate (PMMA) have been used in clinical applications. Antimicrobial BAG has the ability to attach chemically to surrounding bone, but it is not possible to bend, drill or shape BAG during the operation. PMMA has advantages in terms of shaping during the operation, but it does not attach chemically to the bone and is an exothermic material. To increase the usefulness of BAG and PMMA in skull bone defect reconstructions, a new composite implant containing BAG and PMMA in craniofacial reconstructions is presented. Three patients had pre-existing large defects in the calvarial and one in the midface area. An additive manufacturing (AM) model was used preoperatively for treatment planning and custom-made implant production. The trunk of the PMMA implant was coated with BAG granules. Clinical and radiological follow-up was performed postoperatively at 1 week, and 3, 6 and 12 months, and thereafter annually up to 5 years. Computer tomography (CT) and positron emission tomography (PET-CT) were performed at 12 and 24 months postoperatively. Uneventful clinical recovery with good esthetic and functional outcome was seen. CT and PET-CT findings supported good clinical outcome. The BAG–PMMA implant seems to be a promising craniofacial reconstruction alternative. However, more clinical experience is needed.

Since Distributed Generation (DG) often involves renewable energy, it is important to facilitate integration of DG into existing networks. This is the aim of the EU FP6 demonstration project ADINE. It is based on the Active Network Management (ANM) concept, where automation, ICT and power electronics are used to integrate more DG by exploiting active resources instead of just reinforcing the network. The resources are mobilized through ancillary services or requirements. Five enabling solutions within ANM are pushed forward in the project: Protection relay and fault location applications, coordinated protection planning, voltage control with microturbine, centralized voltage control with SCADA/DMS and a new STATCOM. All these are demonstrated in real-life. Finally the performance of each technical solution during conditions with large amounts of DG are analyzed using a real-time simulation environment with RTDS/dSPACE. Introducing appropriate parts of the ANM concept will permit connection of more DG in distribution networks.

Background Understanding the dynamic cellular behaviors and underlying molecular mechanisms that drive morphogenesis is an ongoing challenge in biology. Live imaging provides the necessary methodology to unravel the synergistic and stereotypical cell and molecular events that shape the embryo. Genetically-encoded reporters represent an essential tool for live imaging. Reporter strains can be engineered by placing cis-regulatory elements of interest to direct the expression of a desired reporter gene. In the case of canonical Wnt signaling, also referred to as Wnt/β-catenin signaling, since the downstream transcriptional response is well understood, reporters can be designed that reflect sites of active Wnt signaling, as opposed to sites of gene transcription, as is the case with many fluorescent reporters. However, even though several transgenic Wnt/β-catenin reporter strains have been generated, to date, none provides the single-cell resolution favored for live imaging studies. Results We have placed six copies of a TCF/Lef responsive element and an hsp68 minimal promoter in front of a fluorescent protein fusion comprising human histone H2B to GFP and used it to generate a strain of mice that would report Wnt/β-catenin signaling activity. Characterization of developmental and adult stages of the resulting TCF/Lef:H2B-GFP strain revealed discrete and specific expression of the transgene at previously characterized sites of Wnt/β-catenin signaling. In support of the increased sensitivity of the TCF/Lef:H2B-GFP reporter, additional sites of Wnt/β-catenin signaling not documented with other reporters but identified through genetic and embryological analysis were observed. Furthermore, the sub-cellular localization of the reporter minimized reporter perdurance, and allowed visualization and tracking of individual cells within a cohort, so facilitating the detailed analysis of cell behaviors and signaling activity during morphogenesis. Conclusion By combining the Wnt activity read-out efficiency of multimerized TCF/Lef DNA binding sites, together with the high-resolution imaging afforded by subcellularly-localized fluorescent fusion proteins such as H2B-GFP, we have created a mouse transgenic line that faithfully recapitulates Wnt signaling activity at single-cell resolution. The TCF/Lef:H2B-GFP reporter represents a unique tool for live imaging the in vivo processes triggered by Wnt/β-catenin signaling, and thus should help the formulation of a high-resolution understanding of the serial events that define the morphogenetic process regulated by this signaling pathway.

A prospective randomized long-term follow-up study of bioactive glass (BG)-S53P4 and autogenous bone (AB) used as bone graft substitutes in benign bone tumor surgery during 1993-1997 was conducted. Twenty-one patients (11 in the BG group, 10 in the AB group) participated in a 14-year follow-up. X-rays and MRI scans were obtained, and in the BG group, CT scans were also performed. In the BG group, the filled cavity had a dense appearance on X-ray. MRI showed a mainly or partly fatty bone marrow, and in the large bone tumor group, remnants of glass granules were also observed. Increased cortical thickness was seen in nonossifying fibromas and enchondromas. BG-S53P4 is a safe and well-tolerated bone substitute with good long-term results. BG-S53P4 does not disturb the growth of bone in children.

An 84-year-old woman suffered for 1 year from intermittent vaginal bleeding. Clinical examination revealed a large ulcerative cervical tumor that was histologically classified as well-differentiated squamous cell carcinoma. Acantholytic areas, apoptotic cell death, and pronounced amyloid deposition characterized the tumor. No evidence of papilloma virus infection was found in immunohistochemical examination or in nucleic acid in situ hybridization. Amyloid formed globular structures surrounded by neoplastic cells that reacted with cytokeratin antibodies. Although the amyloid itself was not labeled, electron microscopy showed filamentous degeneration of the squamous cells analogous to that described in different types of cutaneous keratin-derived amyloidoses. It was concluded that similar pathogenetic mechanisms are involved both in the cutaneous amyloidosis and in the amyloid deposition of squamous cell carcinoma.

Acute pancreatitis is characterized morphologically by edema, hemorrhages, parenchymal necrosis and fat necrosis. The inflammation is accompanied by infiltration of polymorpho-nuclear leukocytes. According to the absence or presence of necrosis the disease can be divided into interstitial (or edematous) pancreatitis and hemorrhagic-necrotizing pancreatitis. The severity of disease can be graded in the histological sections either by giving scores to the different types of morphological alterations or by determining the proportion of necrotic tissue of the total lobular parenchyma. The former method is based on subjective assessment of histological slides and is suitable for the evaluation of both edematous and necrotizing pancreatitis. Histometric measurement of necrotic parenchyma can be used only in the necrotizing forms of experimental pancreatitis, e.g. in those induced by intra-ductal injection of bile, bile salts or digestive enzymes, and in the dietary ethionine-induced pancreatitis. Grading of the tissue damage is essential when the effects of different therapies are evaluated.

Chronic alcohol intake interferes especially with the two main pathways regulating exocrine pancreatic secretion: the cholinergic and the pancreozymin pathway. Recently, a new theory of the pathogenesis of alcoholic pancreatitis was proposed emphasizing disordered agonist-receptor interaction at the level of pancreatic acinar cells. Accordingly, alcohol-induced alterations in the control of exocrine pancreatic secretion result in hyperstimulation of pancreatic acinar cells and their muscarinic receptors, mimicking the mechanism of acute pancreatitis caused by scorpion sting, intoxication with an anti-acetylcholinesterase-containing insecticide or supramaximal doses of secretagogues. The present review emphasizes the role of these alcohol-induced secretory alterations in the pathogenesis of alcoholic pancreatitis.

Wood is a natural fiber reinforced composite. It structurally resembles bone tissue to some extent. Specially heat-treated birch wood has been used as a model material for further development of synthetic fiber reinforced composites (FRC) for medical and dental use. In previous studies it has been shown, that heat treatment has a positive effect on the osteoconductivity of an implanted wood. In this study the effects of two different heat treatment temperatures (140 and 200 degrees C) on wood were studied in vitro. Untreated wood was used as a control material. Heat treatment induced biomechanical changes were studied with flexural and compressive tests on dry birch wood as well as on wood after 63 days of simulated body fluid (SBF) immersion. Dimensional changes, SBF sorption and hydroxylapatite type mineral formation were also assessed. The results showed that SBF immersion decreases the biomechanical performance of wood and that the heat treatment diminishes the effect of SBF immersion on biomechanical properties. With scanning electron microscopy and energy dispersive X-ray analysis it was shown that hydroxylapatite type mineral precipitation formed on the 200 degrees C heat-treated wood. An increased weight gain of the same material during SBF immersion supported this finding. The results of this study give more detailed insight of the biologically relevant changes that heat treatment induces in wood material. Furthermore the findings in this study are in line with previous in vivo studies.

MR imaging with a 0.02 T resistive magnet was used to establish the correlation between the histologic grading of patellar cartilage degeneration and fat water separation images or T1- and T2-relaxation times. We examined 23 cadaveric patellae. There was a positive correlation between histologically graded cartilage degeneration and T1-relaxation time. Patellar cartilage was well differentiated from surrounding structures on chemical shift water proton images, and an evaluation of cartilage degeneration was possible. No correlation was found between cartilage damage and T2-relaxation time. Chemical shift imaging at 0.02 T is easy to perform and gives further information of cartilage disorders.

The integrity of rat pancreatic acinar cells under the influence of human phospholipase A2 (PLA2) was studied. Isolated pancreatic acini showed no increased discharge of aspartylaminotransferase (ASAT) when incubated either in solutions containing human pancreatic PLA2 or the bile salt sodium deoxycholate (DEC), the latter in concentrations that augment PLA2 activity but have no destructive detergent effect. When human pancreatic PLA2 was injected into the rat pancreatic duct, uneven distribution was observed at 15 min and 3 h in immunohistochemical sections. Edema and a mild inflammatory reaction were the main changes in the pancreas. The necrotic areas seen by light and electron microscopy were quite small and located mostly at the periphery of lobules corresponding the spread of the injected material. Necrosis was of the coagulation type and showed equal extent after the injection of PLA2 with or without DEC. Internalized human pancreatic PLA2 was present already 15 min after the injection in the cytoplasm of some intact acinar cells, indicating a functioning protective mechanism. It was concluded that pancreatic acinar cells are quite resistant to PLA2-catalyzed hydrolysis of membrane phospholipids in vitro, but additional trauma, e.g., pressure caused by intraductal injection, and tissue related factors, such as the mediators of the inflammatory reaction, make acinar cells susceptible to the effect of PLA2.

Dewatering of peat slurry has been carried out using a versatile, computer-controlled piston press. The effects of five operating variables on pressing were investigated. The collected data were subjected to multivariate data analysis (PLS2) in which the dewatering parameters were related to the operating variables via an empirical mathematical model. The goal of peat dewatering studies is to obtain a dry solids content of 35 per cent with an economically viable production capacity. The results proved that this goal is some way to being achieved. Peat could be dewatered to a solids content of over 35 per cent in less than 60 s under optimal conditions. Pressure is a dominant factor in the process and should be 3 to 5 MPa. The DS-load of the experiment can exceed 2 kg/m2; dosage of anionic polyelectrolyte can be as low as 0.5 – 0.6 kg/tDS and the pH level must be below 3.7. pH-lowering with H2SO4 does not increase markedly the sulphur content in the cake if a pH value greater than 3 is used. Chemical costs are 4 – 5 USD/tDS and are no longer preventing the process from becoming economic. Problems remain with the pressing technique, although new press types entering the market will probably in time permit economic dewatering of peat.

The basic cellular mechanisms of different forms of myositis ossificans are poorly known. In the current experiment the nature of the early (24-168 h) inflammatory cell reaction preceding trauma-induced myositis ossificans was studied. New bone formation was induced in the vastus intermedius region of the rabbit quadriceps muscle by means of immobilization and daily passive mobilization. Before the start of treatment, a cell harvesting device (viscose cellulose sponge in a silastic tube) was implanted in the region of interest. The opposite intermedius muscle and a standardized surgical skin wound served as the control sites. The results showed a significantly prolonged invasion of macrophages into the ossifying intermedius muscle as compared with the control intermedius muscle. It is hypothesized that microinjury and subsequent muscle necrosis cause the invasion of macrophages, and these cells respond to the conditions of the traumatized muscle under passive mobilization by releasing osteogenic growth factors.

In a prospective randomized study, 25 patients with benign bone tumors were surgically treated with either bioactive glass S53P4 (BG) or autogenous bone (AB) as bone graft material. X-rays were taken preoperatively and postoperatively at 2 weeks and at 3, 8, 12, 18, 24, and 36 months. In addition, for most of the patients, CT scans were performed at the same time-points. No infections or material-related adverse reactions occurred in any patient. The filled cavity was replaced faster by new bone in the AB group than in the BG group (p = 0.0001). However, at 36 months, no statistical difference in cavity volume between the two groups was observed on X-rays (p = 0.7881) or on CT scans (p = 0.9117). In the BG group at 3 years, the filled cavity appeared, however, dense on X-rays, and glass granules on CT scans were observed. During the follow-up period, the cortical thickness seemed to increase more in the BG group than in the AB group (p < 0.0001).

Wood is a natural porous fibre composite, which has some structural similarities to bone. Recently, it has been used as a modelling material in developing synthetic fibre-reinforced composite to be used as load-bearing non-metallic artificial bone material. In this study, the behaviour of wood implanted into bone was studied in vivo in the femur bone of the rabbit. Wood was pre-treated by heat, which altered its chemical composition and structure, as well as the biomechanical properties. In the heat treatment, wood's dimensional stability is enhanced, equilibrium moisture content reduces and the biological durability increases. Cone-shaped implants were manufactured from heat-treated (at 200 and 140 degrees C) birch wood (Betula pubescens) and from untreated birch. A total of 62 implants were placed in the distal femur of 50 white New Zealand rabbits. The behaviour of the implants was studied at 4, 8 and 20 weeks with histological and histometrical analysis. Osteoconductive contact line and the presence of fibrous tissue and foreign body reaction were determined. The amount of fibrous tissue diminished with time, and the absence of foreign body reaction was found to be in correlation to the amount of heat treatment. Histologically found contact between the implant and the host bone at the interface was significantly more abundant in the 200 degrees C group (avg. 12.8%) vs. the 140 degrees C (avg. 2.7%) and the untreated groups (avg. 0.6%). It was observed that the heat treatment significantly modified the biological behaviour of the implanted wood. The changes of the wood by heat treatment showed a positive outcome concerning osteoconductivity of the material.

The presence of the 43 kDa papain inhibitor protein in the skin of 40 fetuses with the gestational age varying from 9 to 40 weeks was studied. Immunohistochemistry showed the first evidence of the 43 kDa papain inhibitor in the acral parts, mostly in the nail bed, at the 14th week when the epidermis in all other sites was not stained. Staining of the follicular infundibulumes well as some parts of the uppermost epidermis and keratin layer was observed from 17 to 40 weeks. The staining was most intensive at 20–30 weeks gestational age, and later the intensity gradually decreased so that in the full-term newborn the 43 kDa papain inhibitor was hardly detectable or absent. It was concluded that the 43 kDa papain inhibitor is present in fetal skin at the stage of stratification (9–14 weeks) only in the nail region and its volar surroundings. It appears at the stage of interfolicular keratinization (14–24 weeks) in the uppermost epidermis, especially in the appendical openings and its amount seems the decrease during the stage of interfollicular keratinization (24 weeks-full-term). The expression of 43 kDa inhibitor protein is temporally related to that of filaggrin.

The authors have previously shown that passive daily mobilization of the rabbit hind limb immobilized with the knee in extension leads to necrosis of the deep thigh muscles and myositis ossificans-like periosteal bone formation. In this study the effect of immobilization alone on the rabbit hind limb muscles was examined similarly to that of immobilized limbs. Serum creatine kinase activities increased significantly and intravenously administered Evans blue albumin showed increased vascular permeability in the deep vastus intermedius muscle even on day 1. Necrotic fibers were clearly present in the deep part of the vastus intermedius muscle on day 5 in light and electron microscopy and in enzyme histochemistry. Fibrosis and atrophy were found later. The superficial portion of the vastus intermedius and the deep contralateral nonimmobilized vastus intermedius showed degenerative changes. Bone formation was not noted. The conclusion was that the deep vastus intermedius muscle composed almost exclusively of type I fibers is exceptionally prone to damage when immobilized in a shortened position. Contact of the necrotic muscle with the underlying periosteum is not alone sufficient to induce heterotopic ossification. The additional trauma caused by daily mobilization is needed for the myositis ossificans-like bone formation.

Deciduous wood, birch, pretreated by a technique combining heat and water vapor was applied for the reconstruction of bone defects in the knee joint of rabbits. It was observed that wood showed characteristic properties to be incorporated by the host bone during observation time of 4, 8, and 20 weeks. The natural channel structure of wood served as a porous scaffold, allowing host bone growth as small islets into the wood implants. The other properties of heat-treated wood, such as bioactivity, good handling properties, and sufficient biomechanical properties, might be additional favorable factors for the application of wood as a natural composite material for bone and cartilage repair. At the interface of the surfaces of wood and living bone, bonding occurred. The Chemical Interface Model for bonding bone to wood consists of the reactive ions, such as hydroxyl groups --OH, and covalent bonding as well as hydrogen bonding, which originate from both wood and bone. The bone tissue trauma, with its reactive Ca(2+) and PO(4) (3-) ions, proteins, and collagen, available for interaction at ionic and nanolevel, are associated with the complicated chemistry in the cellular response of the early bone healing process. It was concluded that heat-treated wood acted like a porous biomaterial scaffold, allowing ongrowth and ingrowth of bone and cartilage differentiation on its surface, and demonstrating osteoconductive contact, bonding at the interface.

We studied how well electronic patient record (EPR) systems meet the needs of general practitioners (GPs) and other health-care professionals for specific information. GPs in eight health centres in the South-Ostrobothnia region of Finland were invited to participate. They used three types of EPR system. They were asked to access EPRs to obtain 20 types of information for patients receiving anticoagulant treatment. In total 2,389 patient cases were studied. All of the information requested was available for 73% of the cases (range 55-93%). There was a significant difference between the type of EPR system and the percentage of patients for whom information was available through the EPR. However, further analysis showed that differences in performance between EPR systems probably reflected differences in the way EPRs were used by different organizations. Great care should be taken in attempts to rank EPR systems based on their performance.

The aim of this study is to determine the peak temperature of polymerization, the setting time and the release of residual monomers of a modified acrylic bone cement. Palacos®R, a commercial bone cement, is used as the main component. The cement is modified by adding short glass fibers and resorbable oligomer fillers, and an additional cross-linking monomer. The test specimens are classified according to the composition of the bone cement matrix (i.e., oligomer-filler, glass-fiber reinforcement, and/or cross-linking monomer). The exothermal characteristics during autopolymerization are analyzed using a transducer connected with a computer. The quantities of residual monomers were analyzed from different test groups using high performance liquid chromatography (HPLC). The Δ T value for the oligomer filler and the glass-fiber-containing acrylic bone cement is lower than that for the unmodified bone cement (2.1±0.8 vs. 23.5±4.2°C). The addition of a cross-linking monomer, EGDMA, shortens the setting time of the autopolymerization of the unmodified bone cement (7.1±0.9min vs. 3.3 ±0.3min). The quantity of the residual monomers released is higher in the modified bone cement than that in the unmodified cement. The cement that contains glass fibers and oligomer fillers has a considerably lower exothermal peak, whereas the total quantity of residual monomers released is increased.

Object. Microscopic Rathke cleft cysts are a common incidental autopsy finding, but some Rathke cleft cysts can become sufficiently large to cause visual impairment, hypothalamic—pituitary dysfunction, and headaches. In this study patients were evaluated pre- and postoperatively to ascertain the clinical significance of surgical intervention on endocrine and visual improvement. Factors correlated with cyst recurrence were also evaluated. Methods. A retrospective analysis was conducted in 160 patients with Rathke cleft cysts who were treated between 1984 and 1995 and completed at least a 5-year follow-up period. Of these 160 patients, 118 initially exhibited symptoms of visual impairment or endocrine dysfunction, became symptomatic during the follow-up period, or were found to have cyst enlargement. These 118 patients underwent transsphenoidal surgery. Forty-two patients with incidental lesions that demonstrated no growth on magnetic resonance (MR) images were followed up without an operation. Complete resection, as observed on MR images 3 months postoperatively, was obtained in 114 (97%) of 118 patients. Vision improved postoperatively in 57 (98%) of 58 patients. Hypogonadism improved in 11 (18%) of 62 patients, growth hormone deficiency resolved in 14 (18%) of 78 patients, and hypocortisolemia resolved in one (14%) of seven patients. Twenty-two patients (19%) began to exhibit symptoms of diabetes insipidus, which had not been present preoperatively. The total 5-year recurrence rate was 18% (21 of 118 patients), with 12 patients requiring a repeated operation. Surgical and pathological factors that were found to be statistically associated with recurrence were the use of a fat and/or fascial graft for closure (p < 0.01) and the presence of squamous metaplasia in the cyst wall (p < 0.01). The extent of resection of the cyst wall was not associated with an increased rate of recurrence. In 42 (69%) of 61 patients the incidental cysts did not progress on imaging studies or clinically. Conclusions. This is the largest series of patients with symptomatic Rathke cleft cysts who received operative intervention and participated in the longest postoperative follow up reported in the literature. The high recurrence rate (18%) supports the theory that a relationship exists between a symptomatic Rathke cleft cyst and craniopharyngioma. Improvements in visual and endocrine dysfunction can be expected after surgical decompression of the optic apparatus and the hypothalamic—pituitary axis.

Injectable composites (Glepron) of particulate bioactive glass S53P4 (BAG) and Poly(epsilon-caprolactone-co-D,L-lactide) as thermoplastic carrier matrix were investigated as bone fillers in cancellous and cartilagineous subchondral bone defects in rabbits. Composites were injected as viscous liquid or mouldable paste. The glass granules of the composites resulted in good osteoconductivity and bone bonding that occurred initially at the interface between the glass and the host bone. The bone bioactivity index (BBI) indicating bone contacts between BAG and bone, as well as the bone coverage index (BCI) indicating bone ongrowth, correlated with the amount of glass in the composites. The indices were highest with 70 wt % of BAG, granule size 90-315 microm and did not improve by the addition of sucrose as in situ porosity creating agent in the composite or by using smaller (45 microm) glass granules. The percentage of new bone ingrowth into the composite with 70 wt % of BAG was 6-8% at 23 weeks. At the articular surface cartilage regeneration with chondroblasts and mature chondrocytes was often evident. The composites were osteoconductive and easy to handle with short setting time. They were biocompatible with low foreign body cellular reaction. Results indicate a suitable working concept as a filler bone substitute for subchondral cancellous bone defects.

The flexural properties of oligomer-modified bone cement with various quantities of crosslinking monomer with or without glass fibre reinforcement were studied. The flexural strength and modulus of acrylic bone cement-based test specimens (N=6), including crosslinked and oligomer-modified structures with or without glass fibres, were measured in dry conditions and after immersion in simulated body fluid (SBF) for seven days (analysis with ANOVA). One test specimen from the acrylic bone cement group containing 30 wt % crosslinking monomer of its total monomer content was examined with scanning electron microscope (SEM) to evaluate signs of the semi-interpenetrating polymer network (semi-IPN). The highest dry mean flexural strength (130 MPa) was achieved with the bone cement/crosslinking monomer/glass fibre combination containing 5 wt % crosslinking monomer of its monomer content. The highest flexural modulus (11.5 GPa) was achieved with the bone cement/crosslinking monomer/glass fibre combination containing 30 wt % crosslinking monomer of its monomer content. SBF storage decreased the flexural properties of the test specimens, as did the addition of the oligomer filler. Nevertheless, the addition of crosslinking monomer and chopped glass fibres improves considerably the mechanical properties of oligomer-modified (i.e. porosity-producing filler containing) acrylic bone cement. In addition, some signs of the semi-IPN structure were observed by SEM examination.

Bioactive glass granules of three different compositions, regarding particularly Si- and Al- content (S53P4, S59.7P2.5, S52P3) and of two different granule sizes (200-250 microm and 630-800 microm) were implanted for 4 and 8 weeks in the distal part of rabbit femur. The effect of glass composition and granule size on bone formation was studied. The results were evaluated using histology, computerized histomorphometry, scanning electron microscopy and energy dispersive X-ray analysis, and used for mathematical description of bone formation. The results showed that both the composition of the glass and the granule size of the granules, have influence on bone growth from the surrounding tissue. Glass S53P4, which from previous observations is known to be an effective bioactive glass and widely used in the Biomaterial Project of Turku, Finland, showed bone bonding and increasing bone growth between the granules. Glass S59.7P2.5 which due to its high Si-content should be inert, showed bone bonding. At 4 weeks the bone growth was significantly more abundant in bone defects filled with large granules (630-800 microm) than in defects filled with small granules (200-250 microm). Glass S52P3 with an alumina content of 3 wt %, showed good bone conduction, possibly even bone bonding for granules of 630-800 microm size. Granules of 200-250 microm with a high alumina content at the surface of the reaction layer, showed hardly any bone contact at all. This data, therefore, gives new information concerning bone bonding and osteoconduction of bioactive glasses with a high silica or alumina content.