A Quantitative method for the characterization of lytic metastases of the bone from radiographic images

The aim of our study was to assess the diagnostic usefulness of the gray level parameters to distinguish osteolytic lesions using radiological images. Materials and Methods: A retrospective study was carried out. A total of 76 skeletal radiographs of osteolytic metastases and 67 radiographs of multiple myeloma were used. The cases were classified into nonflat (MM1 and OL1) and flat bones (MM2 and OL2). These radiological images were analyzed by using a computerized method. The parameters calculated were mean, standard deviation, and coefficient of variation (MGL, SDGL, and CVGL) based on gray level histogram analysis of a region-of-interest.Diagnostic utility was quantified bymeasurement of parameters on osteolyticmetastases andmultiplemyeloma, yielding quantification of area under the receiver operating characteristic (ROC) curve (AUC). Results: Flat bone groups (MM2 and OL2) showed significant differences in mean values of MGL ( = 0.048) and SDGL ( = 0.003). Their corresponding values of AUC were 0.758 for MGL and 0.883 for SDGL in flat bones. In nonflat bones these gray level parameters do not show diagnostic ability. Conclusion: The gray level parametersMGL and SDGL show a good discriminatory diagnostic ability to distinguish between multiple myeloma and lytic metastases in flat bones.

Application of cholesterol determination method to indirectly detect meat and bone meals in ruminant feeds

The aim of this study was to verify the presence of meat and bone meal (MBM) in ruminant feed, by identifying the cholesterol using gas chromatography with a flame ionization detector. The proposed method demonstrated precision, trueness, and capability to detect MBM in the ruminant feed.

Effects of Silica Based Biomaterials on Bone Marrow Derived Cells - Material Aspects of Bone Regeneration

Silica based biomaterials, such as melt-derived bioactive glasses and sol-gel glasses, have been used for a long time in bone healing applications because of their ability to form hydroxyapatite and to stimulate stem cell proliferation and differentiation. In this study, bone marrow derived cells were cultured with bioactive glass and sol-gel silica, and seeded into porous polymer composite scaffolds that were then implanted femorally and subcutaneously in rats to monitor their migration inside host tissue. Bone marrow derived cells were also injected intraperitoneally. Transplanted cells migrated to various tissues inside the host, including the lung, liver spleen, thymus and bone marrow. The method of transplantation affected the time frame of cell migration, with intraperitoneal injection being the fastest and femoral implantation the slowest, but not the target tissues of migration. Transplanted donor cells had a limited lifetime in the host and were later eliminated from all tested tissues. Bioactive glass, however, affected the implanted cells negatively. When it was present in the scaffold no donor cells were found in any of the tested host tissues. Bioactive glass S53P4 was found to support both osteoblastic and osteoclastic phenotype of bone marrow derived cells, but it was resistant to the resorbing effect of osteoclastic bone marrow derived cells, showing that bioactive glass is rather dissolved through physicochemical reactions than resorbed by cells. Fast-dissolving silica sol gel in microparticulate form was found to increase collagen formation by bone marrow derived cells, while slow dissolving silica microparticles enhanced their proliferation, suggesting that the dissolution rate of silica controls the response of bone marrow derived cells.

First-Line Chemotherapy with Anthracycline and Taxane Combination in Metastatic Breast Cancer. Detection of bone metastases with TRACP 5b

Background: In Finland, breast cancer (BC) is the most common cancer among women, and prostate cancer (PC) that among men. At the metastatic stage both cancers remain essentially incurable. The goals of therapy include palliation of symptoms, improvement or maintenance of quality of life (QoL), delay of disease progression, and prolongation of survival. Balancing between efficacy and toxicity is the major challenge. With increasing costs of new treatments, appropriate use of resources is paramount. When new treatment regimes are introduced into clinical practice a comprehensive assessment of clinical benefit, adverse effects and cost is necessary. Both BC and PC show a predilection to metastasize to bone. Bone metastases cause significant morbidity impairing the patients´ QoL. Diagnosis of bone metastases relies mainly on radiological methods, which however lack optimal sensitivity and specificity. New tools are needed for detection and follow-up of bone metastases. Aims: Anthracyclines and taxanes are effective chemotherapeutic agents in the treatment of metastatic breast cancer (MBC) with different mechanisms of action. Therefore, evaluation of the combination of anthracyclines with taxanes was a justifiable approach in the treatment of MBC patients. We assessed the efficacy, toxicity, cost of treatment and QoL of BC patients treated with first-line chemotherapy for metastatic disease with the combination epirubicin and docetaxel. We also evaluated the diagnostic potential of tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal telopeptides of type I collagen (ICTP) in the diagnosis of bone metastases in BC and TRACP 5b in PC patients. Results: The combination of epirubicin and docetaxel was effective in this phase II study, but required individual dose adjustment to avoid neutropenic infections, and the use of growth factors to maintain a feasible dose level. The response rate was 54 % (95 % CI 37-71) and the median overall survival (OS) was 26 months. Of the patients, 87 % were treated for infections. The treatment of adverse events required additional use of health resources mainly due to neutropenic infections, thereby raising direct treatment costs by 20 %. Despite adverse events, the global QoL was not significantly compromised during the treatment. Clinically evident acute cardiac toxicity was not observed. The combination of serum TRACP 5b and ICTP was at least equally sensitive and specific in detection of of bone metastases as commonly used total alkaline phosphatise (tALP) in BC patients. In contrast, TRACP 5b was less specific and sensitive than tALP as a marker of skeletal changes in PC patients. Conclusions: Treatment with epirubicin and docetaxel showed high efficacy in first-line chemotherapy of MBC. The relatively high incidence of neutropenic infections requiring hospitalization increased the treatment costs. Despite adverse events, the global QoL of the patients was not significantly compromised. The combination of TRACP 5b and ICTP showed similar activity as tALP in detecting bone metastases in MBC. In contrast, TRACP 5b was less specific and sensitive than tALP as a marker of skeletal changes in PC.

Utilization of Meat and bone meal for energy production

At the end of the 1990s the stock breeding in the Europe was suffering from the animal disease epidemics such as Bovine spongiform encephalopathy (BSE) and foot –and mouth disease. The European Union (EU) tackled to this problem by tightening the legislation of animal by-products. At this point, rendering and fat producing industries faces new challenges, which they have to cope with in a way of trying to find alternatives to their products (animal fats and meat and bone meal). One of the most promising alternatives to utilize these products was to use them in energy production purposes. The purpose of the Thesis was to examine the utilization possibilities of Meat and bone meal (MBM) for energy production. The first part of the Thesis consists of theory part. The theory part includes evaluation of basic properties of MBM as a fertilizer and as a fuel, legislative evaluation and evaluation of different burning techniques. The second part of the Thesis consists of burning tests in Energy laboratory of LUT with different mixtures of peat and MBM. The purpose of the burning tests was to identify co-firing possibilities of peat and MBM and emission- and ash properties for peat and MBM.

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.

Dissecting the molecular mechanisms of breast cancer bone metastasis for therapeutic targeting

Breast cancer that has metastasized to bone is currently an incurable disease, causing significant morbidity and mortality. The aim of this thesis work was to elucidate molecular mechanisms of bone metastasis and thereby gain insights into novel therapeutic approaches. First, we found that L‐serine biosynthesis genes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH), were up‐regulated in highly bone metastatic MDA‐MB‐231(SA) cells as compared with the parental breast cancer cell line. Knockdown of serine biosynthesis inhibited proliferation of MDA‐MB‐231(SA) cells, and L‐serine was essential for the formation of bone resorbing osteoclasts. Clinical data demonstrated that high expression of PHGDH and PSAT1 was associated with decreased relapse‐free and overall survival and with features typical of poor outcome in breast cancer. Second, RNA interference screening pointed out heparan sulfate 6‐O‐sulfotransferase 2 (HS6ST2) as a critical gene for transforming growth factor β (TGF‐β)‐induced interleukin 11 (IL‐11) production in MDA‐MB‐231(SA) cells. Exogenous heparan sulfate glycosaminoglycans heparin and K5‐NSOS also inhibited TGF‐β‐induced IL‐11 production in MDA‐MB‐231(SA) cells. Furthermore, K5‐NSOS decreased osteolytic lesion area and tumor burden in bone in mice. Third, we discovered that the microRNAs miR‐204, ‐211 and ‐379 inhibited IL‐11 expression in MDA‐MB‐231(SA) cells through direct targeting of the IL‐11 mRNA. MiR‐379 also inhibited Smad‐mediated signaling. Gene expression profiling of miR‐204 and ‐379 transfected cells indicated that these microRNAs down‐regulate several bone metastasis‐relevant genes, including prostaglandin‐endoperoxide synthase 2 (PTGS2). Taken together, this study identified three potential treatment strategies for bone metastatic breast cancer: inhibition of serine biosynthesis, heparan sulfate glycosaminoglycans and restoration of miR‐204/‐211/‐379.

Emprego do saco herniário no reforço parietal nas hérnias inguinais indiretas do adulto

O estudo prospectivo de oitenta pacientes com hérnia inguinal indireta primária teve como objetivo determinar as possíveis vantagens e desvantagens do uso do saco herniário próprio como um reforço adicional da fáscia transversal e do anel interno, no reparo cirúrgico da hérnia inguinal indireta, num período de acompanhamento de 24 meses após a operação. Todos os pacientes eram do sexo masculino, na faixa etária de 18 a 65 anos, com o diâmetro do anel inguinal variando de 1,0cm a 3,5cm, correspondente ao tipo 2 da classificação de Nyhus para hérnias ínguino-femorais. Foram divididos em dois grupos de quarenta cada e operados pelo mesmo cirurgião, de março de 1993 a março de 1995. No grupo A, o reforço parietal posterior foi feito pela sutura do arco do transverso ao ligamento iliopúbico. No grupo B, acrescentou-se o saco herniário próprio, aberto e livre, fixado sobre o citado reforço às estruturas músculo-aponeuróticas do triângulo inguinal. A preparação e sutura do saco herniário foi de fácil execução, acrescentando um tempo médio de nove minutos à operação. Na comparação entre os grupos A e B, os testes estatísticos demonstraram não haver diferença significativa entre as médias de idade, peso, altura e de diâmetro do anel inguinal interno. As complicações pós-operatórias foram semelhantes nos dois grupos, sendo estas de fácil resolução. A diferença na recidiva precoce de dois casos (5%) no grupo A para um caso (2,5%) no grupo B não é estatisticamente significativa. No exame histopatológico dos sacos herniários, verificou-se que suas paredes constituem-se de tecido conjuntivo, vasos sangüíneos, células adiposas e, em 25% dos casos, de fibras musculares lisas. Na reoperação do paciente número 12, do grupo B, observou-se que o saco herniário suturado, há 19 meses na região inguinal, apresentava-se como uma camada espessa e resistente, firmemente aderida à fáscia transversal. A proposta de utilização do saco herniário, como um reforço da hérnia inguinal, mostrou-se um recurso de fácil e rápida execução, com custo operacional baixo, não expondo o paciente ao aumento do número de complicações.

Histopatologia do saco herniário da hérnia inguinal indireta e do peritônio parietal em adultos e crianças: estudo qualitativo da sua musculatura lisa

Estudo prospectivo, realizado entre abril de 1993 e julho de 1995, com o objetivo de estudar a histopatologia do saco herniário de hérnias inguinais indiretas do adulto e criança, no sentido de verificar a existência de musculatura lisa, sua incidência, apresentação morfológica e comparar com biópsias aleatórias do peritônio parietal. Os pacientes foram divididos em Grupo (1) com 123 pacientes, nos quais foram estudados os sacos herniários, e Grupo (2) constituído de 63 pacientes, nos quais foram realizadas biópsias da serosa peritoneal da cavidade abdominal. Verificou-se que fibras de músculo liso (FML) estiveram presentes em 65,4% dos 133 sacos herniários (dez pacientes com hérnia bilateral), estando presentes, também, em 19,04% dos espécimes da cavidade abdominal. Através dos testes do Qui-quadrado e t de Student, foi avaliada a associação entre a presença de FML com as variáveis categóricas (sexo, cor e lado da hérnia) e as variáveis contínuas (idade dos pacientes, comprimento e espessura do saco herniário). Os resultados mostraram que o sexo feminino apresenta uma maior incidência de FML (p=0,004) e a razão das chances (O.R.) demonstra que os pacientes desse mesmo sexo têm 5,46 vezes mais possibilidades de possuir FML nos sacos herniários. Assim, concluem que as FML são predominantes no peritônio parietal do abdome inferior e que existe, também, uma quantidade maior de FML no peritônio do saco herniário inguinal quando comparado com o peritônio parietal.

Bone Health, Osteoporosis and Fracture Risk in Neurofibromatosis 1 - An Emphasis on Osteoclasts

Neurofibromatosis 1 (NF1) is an autosomal dominant hereditary syndrome, affecting skin, neural tissues and skeleton. Hallmarks of NF1 include benign cutaneous neurofibroma tumors, pigmentation lesions on the skin and in the iris, learning disabilities and predisposition to selected malignancies. Low bone mineral density (BMD) and osteopenia/osteoporosis are common in NF1. Osteoporosis is a systemic disorder characterized by low bone mineral density and increased fracture risk. Treatment of osteoporosis aims to prevent falls and decrease fracture risk. Osteoporosis is diagnosed in adults by measuring BMD and evaluating clinical risk factors of the patient. Bone turnover is a process of old bone resorbed by osteoclasts and new bone formed by osteoblasts. Multinuclear osteoclasts are derived from osteoclast progenitors, which can be isolated from peripheral blood. Osteoclast progenitors were isolated from 17 NF1 patients and healthy controls, and cultured in vitro to osteoclasts. NF1 osteoclasts are hyperactive, displaying increased differentiation and resorption capacity, abnormal morphology and tolerance to serum deprivation compared to control osteoclasts. These findings expanded the study to evaluate the effects of bisphosphonates, drugs designed to treat osteoporosis, in osteoclasts derived from blood samples of 20 NF1 and control persons. The number of control osteoclasts was expectedly reduced after bisphosphonate treatment. However, NF1 osteoclasts tolerated the apoptotic effect of alendronate, zoledronic acid and clodronate in vitro compared to controls. NF1-related osteoporosis was found in ~20 % of the patients, and selected laboratory parameters were measured. Patients with NF1 have increased levels of serum CTX and PINP, reflecting increased bone turnover in vivo. BMD decreases progressively in NF1 as evaluated in 19 NF1 patients 12 years after their initial BMD measurement. Patients with NF1-related osteopenia often progress to osteoporosis. This was found in patients aged 37-76.

Flexible multibody approach in bone strain estimation during physical activity:

Bone strain plays a major role as the activation signal for the bone (re)modeling process, which is vital for keeping bones healthy. Maintaining high bone mineral density reduces the chances of fracture in the event of an accident. Numerous studies have shown that bones can be strengthened with physical exercise. Several hypotheses have asserted that a stronger osteogenic (bone producing) effect results from dynamic exercise than from static exercise. These previous studies are based on short-term empirical research, which provide the motivation for justifying the experimental results with a solid mathematical background. The computer simulation techniques utilized in this work allow for non-invasive bone strain estimation during physical activity at any bone site within the human skeleton. All models presented in the study are threedimensional and actuated by muscle models to replicate the real conditions accurately. The objective of this work is to determine and present loading-induced bone strain values resulting from physical activity. It includes a comparison of strain resulting from four different gym exercises (knee flexion, knee extension, leg press, and squat) and walking, with the results reported for walking and jogging obtained from in-vivo measurements described in the literature. The objective is realized primarily by carrying out flexible multibody dynamics computer simulations. The dissertation combines the knowledge of finite element analysis and multibody simulations with experimental data and information available from medical field literature. Measured subject-specific motion data was coupled with forward dynamics simulation to provide natural skeletal movement. Bone geometries were defined using a reverse engineering approach based on medical imaging techniques. Both computed tomography and magnetic resonance imaging were utilized to explore modeling differences. The predicted tibia bone strains during walking show good agreement with invivo studies found in the literature. Strain measurements were not available for gym exercises; therefore, the strain results could not be validated. However, the values seem reasonable when compared to available walking and running invivo strain measurements. The results can be used for exercise equipment design aimed at strengthening the bones as well as the muscles during workout. Clinical applications in post fracture recovery exercising programs could also be the target. In addition, the methodology introduced in this study, can be applied to investigate the effect of weightlessness on astronauts, who often suffer bone loss after long time spent in the outer space.

Surgical techniques for maxillary bone grafting - literature review

For oral rehabilitation with implant-supported prostheses, there are required procedures to create the bone volume needed for installation of the implants. Thus, bone grafts from intraoral or extraoral donor sites represent a very favorable opportunity. This study aimed to review the literature on the subject, seeking to discuss parameters for the indications, advantages and complications of techniques for autogenous bone grafts.

Use of local muscle flaps to cover leg bone exposures

Objective: To evaluate the use of the medial gastrocnemius muscle and/or soleus muscle flaps as surgical treatment of the leg bone exposure.Methods: We retrospectively analyzed the medical records of patients undergoing transposition of the medial gastrocnemius and / or soleus for treating exposed bone in the leg, from January 1976 to July 2009, gathering information on epidemiological data, the etiology the lesion, the time between the initial injury and muscle transposition, the muscle used to cover the lesion, the healing evolution of the skin coverage and the function of the gastrocnemius-soleus unit.Results: 53 patients were operated, the ages varying between nine and 84 years (mean age 41); 42 were male and 11 female. The main initial injury was trauma (84.8%), consisting of tibia and / or fibula fracture. The most frequently used muscle was the soleus, in 40 cases (75.5%). The rank of 49 patients (92.5%) was excellent or good outcome, of three (5.6%) as regular and of one (1.9%) as unsatisfactory.Conclusion: the treatment of bone exposure with local muscle flaps (gastrocnemius and/or soleus) enables obtaining satisfactory results in covering of exposed structures, favoring local vascularization and improving the initial injury. It offers the advantage of providing a treatment in only one surgical procedure, an earlier recovery and reduced hospital stay.

Importance of bone assessment and prevention of osteoporotic fracture in patients with prostate cancer in the gonadotropic hormone analogues use

The antiandrogenic therapy (ADT) for prostate cancer represents an additional risk factor for the development of osteoporosis and fragility fractures. Still, bone health of patients on ADT is often not evaluated. After literature research we found that simple preventive measures can prevent bone loss in these patients, resulting in more cost-effective solutions to the public health system and family when compared to the treatment of fractures.

Obtention of injectable platelets rich-fibrin (i-PRF) and its polymerization with bone graft: technical note

The use of autologous platelet concentrates, represent a promising and innovator tools in the medicine and dentistry today. The goal is to accelerate hard and soft tissue healing. Among them, the platelet-rich plasma (PRP) is the main alternative for use in liquid form (injectable). These injectable form ofplatelet concentrates are often used in regenerative procedures and demonstrate good results. The aim of this study is to present an alternative to these platelet concentrates using the platelet-rich fibrin in liquid form (injectable) and its use with particulated bone graft materials in the polymerized form.