| 1. |
- Aardal-Eriksson, Elisabeth
(författare)
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Salivary cortisol and posttraumatic stress reactions : methodological and applied studies before and after trauma
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.
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| 2. |
- Aarsand, Pål André, 1970-
(författare)
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Around the Screen : Computer activities in children’s everyday lives
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present ethnography documents computer activities in everyday life. The data consist of video recordings, interviews and field notes, documenting (i) 16 students in a seventh grade class in a computer room and other school settings and (ii) 22 children, interacting with siblings, friends and parents in home settings. The thesis is inspired by discourse analytical as well as ethnographic approaches, including notions from Goffman (1974, 1981), e.g. those of activity frame and participation framework, which are applied and discussed.The thesis consists of four empirical studies. The first study focuses on students’ illegitimate use, from the school’s point of view, of online chatting in a classroom situation. It is shown that the distinction offline/online is not a static one, rather it is made relevant as part of switches between activity frames, indicating the problems of applying Goffman’s (1981) notions of sideplay, byplay and crossplay to analyses of interactions in which several activity frames are present, rather than one main activity. Moreover, it is shown that online identities, in terms of what is here called tags, that is, visual-textual nicknames, are related to offline phenomena, including local identities as well as contemporary aesthetics. The second study focuses on placement of game consoles as part of family life politics. It is shown that game consoles were mainly located in communal places in the homes. The distinction private/communal was also actualized in the participants’ negotiations about access to game consoles as well as negotiations about what to play, when, and for how long. It is shown that two strategies were used, inclusion and exclusion, for appropriating communal places for computer game activities. The third study focuses on a digital divide in terms of a generational divide with respect to ascribed computer competence, documenting how the children and adults positioned each other as people ‘in the know’ (the children) versus people in apprentice-like positions (the adults). It is shown that this generation gap was deployed as a resource in social interaction by both the children and the adults. The forth study focuses on gaming in family life, showing that gaming was recurrently marked by response cries (Goffman, 1981) and other forms of blurted talk. These forms of communication worked as parts of the architecture of intersubjectivity in gaming (cf. Heritage, 1984), indexing the distinction virtual/‘real’. It is shown how response cries, sound making, singing along and animated talk extended the virtual in that elements of the game became parts of the children’s social interaction around the screen, forming something of an action aesthetic, a type of performative action for securing and displaying joint involvement and collaboration. As a whole, the present studies show how the distinctions master/apprentice, public/private, virtual/real and subject/object are indexicalized and negotiated in computer activities.
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| 3. |
- Abate, Ebba
(författare)
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The impact of helminth infection in patients with active tuberculosis
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The geographic distribution of helminth infection and tuberculosis (TB) overlap substantially. Experimental animal models and limited data from humans have shown that intestinal helminths could subvert the host immune response towards a T-helper 2 (Th2)-type immune response and an increased regulatory T-cell activity (Tregs). This in turn affects the host's ability to mount an effective Th1 immune-mediated protection against Mycobacterium tuberculosis. However, evidence for this hypothesis in the human setting from helminth infected TB patients is limited. This thesis primarily focuses on the immunological and clinical impact of helminth infection on pulmonary TB. The kinetics of the Quantiferon-Gold (QFN) assay, which measures IFN-³ response to TB-specific antigens in whole blood was assessed and showed a modest decline during TB treatment to the level observed for healthy blood donors. We further assessed another clinical monitoring tool, the-TB-score, composed of clinical signs and symptoms of TB, and found an early decline two weeks after initiation of TB- treatment where a failure of decline correlated with increased mortality. Overall, the helminth co-infection rate was significantly higher in TB patients compared to healthy controls. Helminth co-infection was associated to a significantly higher rate of eosinophilia and IgE-levels in healthy controls and patients with tuberculosis. During the first weeks of anti-TB treatment, a marked decrease in the rate of helminth infection was observed in HIV co-infected compared to HIV-negative TB patients. However, helminth co-infection was more common in HIV negative than HIV positive TB patients. There was no detectable impact of helminth infection on the clinical presentation of pulmonary tuberculosis. At baseline, helminth co-infected TB patients showed an increased frequency of Tregs compared to helminth negative TB patients and healthy controls. This was accompanied by an increased rate of PPD stimulated IL-5 and spontaneous production of IL-10 by peripheral blood mononuclear cells among helminth co-infected TB patients. A placebo controlled randomized trial was conducted in order to test the hypothesis that albendazole treatment of helminth positive TB patients may improve the clinical response of TB by reducing the immunmodulatory effect of helminthes on TB immunity. A total of 140 helminth co-infected TB patients were randomized to albendazole (400 mg per os for three consecutive days) or placebo. No significant difference was observed between the albendazole and placebo group in terms of the primary outcome (TB score change between baseline and week 8). Among the secondary outcomes, a significant decline of peripheral eosinophil cells was observed in the albendazole treated group, but no effect on other outcome variables (changes in chest x-ray findings, IgE level and sputum smear conversion). Regarding the immunological assessment no significant difference was observed for changes in Tregs, and PPD-induced production of IFN- ³ or IL-5 although a non-significant trend of a decrease in IL-10 expressing PBMCs were observed in the albendazole group. Taken together, the burden of helminth infection was higher in TB patients than in a healthy control group. Helminth co-infection during pulmonary TB in the human setting induces an immune response characterized by increased IgE production, eosinophilia as well as increased levels of Tregs and spontaneous IL-10 production. Thus, the immunological impact of helminth infection on the outcome and risk for developing TB merits further investigation.
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| 4. |
- Abbas, Muhammad
(författare)
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On the Implementation of Integer and Non-Integer Sampling Rate Conversion
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main focus in this thesis is on the aspects related to the implementation of integer and non-integer sampling rate conversion (SRC). SRC is used in many communication and signal processing applications where two signals or systems having different sampling rates need to be interconnected. There are two basic approaches to deal with this problem. The first is to convert the signal to analog and then re-sample it at the desired rate. In the second approach, digital signal processing techniques are utilized to compute values of the new samples from the existing ones. The former approach is hardly used since the latter one introduces less noise and distortion. However, the implementation complexity for the second approach varies for different types of conversion factors. In this work, the second approach for SRC is considered and its implementation details are explored. The conversion factor in general can be an integer, a ratio of two integers, or an irrational number. The SRC by an irrational numbers is impractical and is generally stated for the completeness. They are usually approximated by some rational factor.The performance of decimators and interpolators is mainly determined by the filters, which are there to suppress aliasing effects or removing unwanted images. There are many approaches for the implementation of decimation and interpolation filters, and cascaded integrator comb (CIC) filters are one of them. CIC filters are most commonly used in the case of integer sampling rate conversions and often preferred due to their simplicity, hardware efficiency, and relatively good anti-aliasing (anti-imaging) characteristics for the first (last) stage of a decimation (interpolation). The multiplierless nature, which generally yields to low power consumption, makes CIC filters well suited for performing conversion at higher rate. Since these filters operate at the maximum sampling frequency, therefore, are critical with respect to power consumption. It is therefore necessary to have an accurate and efficient ways and approaches that could be utilized to estimate the power consumption and the important factors that are contributing to it. Switching activity is one such factor. To have a high-level estimate of dynamic power consumption, switching activity equations in CIC filters are derived, which may then be used to have an estimate of the dynamic power consumption. The modeling of leakage power is also included, which is an important parameter to consider since the input sampling rate may differ several orders of magnitude. These power estimates at higher level can then be used as a feed-back while exploring multiple alternatives.Sampling rate conversion is a typical example where it is required to determine the values between existing samples. The computation of a value between existing samples can alternatively be regarded as delaying the underlying signal by a fractional sampling period. The fractional-delay filters are used in this context to provide a fractional-delay adjustable to any desired value and are therefore suitable for both integer and non-integer factors. The structure that is used in the efficient implementation of a fractional-delay filter is know as Farrow structure or its modifications. The main advantage of the Farrow structure lies in the fact that it consists of fixed finite-impulse response (FIR) filters and there is only one adjustable fractional-delay parameter, used to evaluate a polynomial with the filter outputs as coefficients. This characteristic of the Farrow structure makes it a very attractive structure for the implementation. In the considered fixed-point implementation of the Farrow structure, closed-form expressions for suitable word lengths are derived based on scaling and round-off noise. Since multipliers share major portion of the total power consumption, a matrix-vector multiple constant multiplication approach is proposed to improve the multiplierless implementation of FIR sub-filters.The implementation of the polynomial part of the Farrow structure is investigated by considering the computational complexity of different polynomial evaluation schemes. By considering the number of operations of different types, critical path, pipelining complexity, and latency after pipelining, high-level comparisons are obtained and used to short list the suitable candidates. Most of these evaluation schemes require the explicit computation of higher order power terms. In the parallel evaluation of powers, redundancy in computations is removed by exploiting any possible sharing at word level and also at bit level. As a part of this, since exponents are additive under multiplication, an ILP formulation for the minimum addition sequence problem is proposed.
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| 5. |
- Abbas, Qaisar, 1975-
(författare)
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Weak Boundary and Interface Procedures for Wave and Flow Problems
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, we have analyzed the accuracy and stability aspects of weak boundary and interface conditions (WBCs) for high order finite difference methods on Summations-By-Parts (SBP) form. The numerical technique has been applied to wave propagation and flow problems.The advantage of WBCs over strong boundary conditions is that stability of the numerical scheme can be proven. The boundary procedures in the advection-diffusion equation for a boundary layer problem is analyzed. By performing Navier-Stokes calculations, it is shown that most of the conclusions from the model problem carries over to the fully nonlinear case.The work was complemented to include the new idea of using WBCs on multiple grid points in a region, where the data is known, instead of at a single point. It was shown that we can achieve high accuracy, an increased rate of convergence to steady-state and non-reflecting boundary conditions by using this approach.Using the SBP technique and WBCs, we have worked out how to construct conservative and energy stable hybrid schemes for shocks using two different approaches. In the first method, we combine a high order finite difference scheme with a second order MUSCL scheme. In the second method, a procedure to locally change the order of accuracy of the finite difference schemes is developed. The main purpose is to obtain a higher order accurate scheme in smooth regions and a low order non-oscillatory scheme in the vicinity of shocks.Furthermore, we have analyzed the energy stability of the MUSCL scheme, by reformulating the scheme in the framework of SBP and artificial dissipation operators. It was found that many of the standard slope limiters in the MUSCL scheme do not lead to a negative semi-definite dissipation matrix, as required to get pointwise stability.Finally, high order simulations of shock diffracting over a convex wall with two facets were performed. The numerical study is done for a range of Reynolds numbers. By monitoring the velocities at the solid wall, it was shown that the computations were resolved in the boundary layer. Schlieren images from the computational results were obtained which displayed new interesting flow features.
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| 6. |
- Abbasi, Mazhar Ali
(författare)
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The synthesis, characterization and device fabrication of ZnO, NiO and their composite nanostructures
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Electronics industry has been revolutionized since last few decades because of the fabrication of electronic devices by using nanoscale based materials. But the more innovative feature in the electronic devices is the use of transparent materials, which makes the transparent electronic devices as one of the most interesting research field in nanoscience and nano-technology now a days. In order to have high performance electronic devices based on the wide band gap compound semiconductors, a selection of right transparent material is crucial step. Among all the transparent metal oxides, ZnO is one of the potential candidates due to the ease in the synthesis process, wide bandgap of 3.37 eV, a high exciton binding energy of 60 meV and diverse morphologies. Since p-type ZnO based nanodevices are still difficult to fabricate due to the instability and unreliability of p-type ZnO nanomaterial, therefore several p-type semiconductors are used for the development of p-n junctions. Among those NiO is suitable p-type compound semiconductor to make p-n junction with ZnO because of its wide band gap of 3.7 eV and environment friendly conditions for its synthesis. Keeping these attractive properties of n-type ZnO and p-type NiO, the synthesis of composite nanostructures of these two transparent oxides and fabrication of their electronic devices is presented in this dissertation work.I started my work with the synthesis of ZnO nanostructures focusing on the effect of different anions of zinc salts on the morphology and crystallinity of ZnO nanostructures. Then I grow honey-comb like NiO nanostructures on 3D nickel foam and used these nanostructures for the detection of Zinc ion. After that synthesized NiO and ZnO based composite nanostructures and characterized them, having main focus on the luminescence properties of ZnO when decorated with NiO nanostructures. The composite nanostructures of p-type NiO and n-type ZnO showed enhancement in the luminescence properties. Since pn junction is the back bone of electronic devices so working on the designing of band alignment along with the current transport properties of p-type NiO/n-type ZnO composite structures, an attempt was put forwarded to explain the phenomenon of these compound semiconducting materials. Different devices based on these two compound semiconducting materials are fabricated and designed in the present dissertation work, however still more work is required to improve the efficiency of devices like LEDs and UV detectors.
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| 7. |
- Abbott, Allan, 1978-
(författare)
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Physiotherapeutic rehabilitation and lumbar fusion surgery
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Over the last two decades, the economic costs and rates of lumbar fusion surgery for chronic low back pain has risen dramatically in western industrialized countries. Data from the Swedish National Spine Register suggest that 25% of patients experience unimproved pain and up to 40% are not satisfied with the outcome of lumbar fusion surgery. Thus, there is a definite need to optimize the selection and management of patients to improve lumbar fusion outcomes. Aim: To investigate the role of biopsychosocial factors in explaining disability and health related quality of life in chronic low back pain patients before and after lumbar fusion surgery and to evaluate the effectiveness of post-operative rehabilitation regimes. Methods: At total of 107 patients were recruited, aged 18 to 65 years, selected for lumbar fusion due to 12 months of symptomatic back and/or leg pain due to spinal stenosis, degenerative/isthmic spondylolisthesis or degenerative disc disease. Measures of disability, health related quality of life, pain, mental health, fear of movement/(re)injury, self-efficacy, outcome expectancy, pain coping styles, work status, health care use, analgesic use and sickness leave were collected with self-rated questionnaires at baseline (Studies I-IV), 3, 6, 12 months (Study II) and 2-3 years after surgery (Studies II-III). In Studies II-IV, patients were randomised to psychomotor therapy (N=53) or exercise therapy (N=54) implemented during the first 3 post-operative months. Semi-structured interviews were conducted 3-6 months after surgery on 20 patients including 10 from each rehabilitation group to investigate experiences of back problems before and after surgery, post-operative recovery and expectations of rehabilitation analysed in terms of the International Classification of Functioning, Disability and Health (Study IV). Results: Approximately 50% of the variability in baseline disability and 40% of the variability in baseline health related quality of life could be explained by psychological variables. In particular, catastrophizing, control over pain, self-efficacy and outcome expectancy had significant mediation roles (Study I). For the short and long term outcome of lumbar fusion surgery, post-operative psychomotor therapy is significantly more effective than exercise therapy with approximately 10-20% better outcome in measures of disability, fear of movement/(re)injury, pain catastrophizing, self-efficacy, outcome expectancy sickness leave, health care utilization and return to work (Study II). A model with good outcome predictive performance which significantly predicts disability, back pain and health related quality of life outcomes 2-3 year after lumbar fusion surgery, was shown to involve pre-operative screening of disability, leg pain intensity, mental health, fear of movement/(re)injury, outcome expectations, catastrophizing, control over pain and the implementation of post-operative psychomotor therapy (Study III). Lumbar fusion patient s experiences of back problems before and after the operation as well as experiences of recovery and outcome expectations correspond well with the content of outcomes measures used in the study suggesting good content validity (Study IV). Conclusion: Psychological factors strongly influence levels of disability and health related quality of life in lumbar fusion candidates as well as predicts post-operative outcomes. Early post-operative rehabilitation focusing on cognition, behaviour and motor control is recommended for improved lumbar fusion outcomes.
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| 8. |
- Abdalla, Hassan, 1987-
(författare)
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Charge and Energy Transport in Disordered Organic Semiconductors
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Improvement of the performance of organic disordered semiconductors (OSC) is driven by the understanding of the underlying charge transport mechanisms and systematic exploitation thereof. There exists a multitude of materials and material systems based on polymers and small molecules with promising performance for use in organic light emitting diodes, photovoltaics, organic field-effect transistors and thermoelectrics. However, universal understanding of many classes of these materials has eluded researchers, due to their broad spectrum of morphologies, molecular structures and electrical properties. Building on the large body of existing models, this thesis deals with charge transport phenomena from the perspective of transport energetics, by studying the interplay between a few but important concepts commonly accepted to play a crucial role in all OSC materials; energetic disorder, charge carrier hopping and Coulomb interactions. The influence of these concepts on the energetic landscape through which charge carriers move and how this translates to experimentally observed transport phenomena are studied by a combination of experimental work, kinetic Monte Carlo (MC) simulations and empirical and analytical models.The universal scaling and collapse of the temperature and electric field dependence of the conductivity of PEDOT:PSS to a single curve is shown to be functionally equivalent to the scaling of the effective temperature, which describes the effect of field heating as a broadening of the charge carrier distribution. From numerical investigation of the energy relaxation, an empirical model is developed that relates the physical meaning behind both concepts to the heat balance between Joule heating of the carrier distribution via the effective temperature and energy loss to the lattice. For this universal description to be applicable a strongly energy- dependent density of states (DOS) as well as Coulomb interactions and large carrier concentrations are needed.Chemical doping is a common way of improving charge transport in OSC and is also beneficial for energy transport, which combined leads to an increased thermoelectric power factor. The ensuing thermoelectric investigations not only showed the potential of these materials for use in thermoelectric generators, but are also helpful in unraveling charge transport mechanism as they give direct insight into the energetics of a material. Interestingly, doped OSC exhibit the same universal power-law relationship between thermopower and conductivity, independent of material system or doping method, pointing towards a common energy and charge transport mechanism. In this thesis an analytical model is presented, which reproduces said universal power-law behavior and is able to attribute it to Variable Range Hopping (VRH) or a transition between Nearest Neighbour Hopping (NNH) and VRH at higher concentrations. This model builds on an existing three- dimensional hopping formalism that includes the effect of the attractive Coulomb potential of ionized dopants that leads to a broadening of the DOS. Here, this model is extended by including the energy offset between host and dopant material and is positively tested against MC simulations and a set of thermoelectric measurements covering different material groups and doping mechanisms.Organic field effect transistors (OFETs) have become increasingly comparable in electrical mobility to their inorganic (silicon) counterparts. The spatial extent of charge transport in OFETs has been subject to debate since their inception with many experimental, numerical and analytical studies having been undertaken. Here it is shown that the common way of analyzing the dimensionality of charge transport in OFETs may be prone to misinterpretations. Instead, the results in this thesis suggest that charge transport in OFETs is, in fact, quasi- two-dimensional (2D) due to the confinement of the gate field in addition to a morphology-induced preferred in-plane direction of the transport. The inherently large charge carrier concentrations in OFETs in addition to the quasi-2D confinement leads to increased Coulomb interaction between charge carriers as compared to bulk material, leading to a thermoelectric behavior that deviates from doped organic systems. At very large concentrations interesting charge transport phenomena are observed, including an unexpected simultaneous increase of the concentration dependence and the magnitude of the mobility, the appearance of a negative transconductance, indicating a transition to an insulating Mott-Hubbard phase. The experimental and numerical results in this thesis relate these phenomena the intricacies of the interplay between Coulomb interactions, energetic disorder and charge carrier hopping.
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| 9. |
- Abdalla, Maie
(författare)
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Cancer and reconstructive surgery in Inflammatory bowel disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon. According to the literature, some thirty percent of UC patients may require a subtotal colectomy and ileostomy due to failure of medical treatment, acute toxic colitis or dysplasia/cancer diagnosis. Some patients choose to get continence restored with either an ileorectal anastomosis (IRA) or an ileal pouch-anal anastomosis (IPAA). Worldwide most surgeons prefer an IPAA to an IRA, despite reports of pouchitis, impaired fertility and fecundity. Fear of recurring proctitis and fear of rectal cancer in the remaining rectum is contributing to the choice of an IPAA. Little is known regarding the outcomes of IRA compared with IPAA in UC patients. We aimed to investigate the anorectal function, quality of life (QoL), risk of failure and rectal cancer in patients with UC restored with IRA and IPAA respectively. Methods: Data about all Inflammatory bowel disease (IBD) patients was obtained from the Swedish National Patient Register (NPR) between 1964-2014 and in one study from the Linköping University Hospital medical records 2006-2012. Patients who developed cancer were identified from the Swedish National Cancer Register. We investigated the risk of cancer and inflammation, functional outcome and failure as well as the quality of life for IRA and IPAA patients. Investigation of risk for cancer in IRA and IPAA compared with the background population was performed using survival analytic techniques: uni-and multivariate regression, Kaplan Meier curves and standardized incidence ratio. Results: Twelve percent (7,889 /63,795) of UC patients required colectomy according to the NPR. The relative risk for rectal cancer among patients with an IRA was increased (SIR 8.7). However, the absolute risk was 1.8% after a mean follow up of 8.6 years and the cumulative risk 10- and 20-years after IRA was 1.6% and 5.6%, respectively. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio 6.12), and severe dysplasia or cancer of the colon prior to subtotal colectomy in patients with a diverted rectum in place (hazard ratio 3.67). Regarding IPAA, the relative risk to develop rectal cancer was (SIR 0.4) compared with the background population and the absolute risk was only 0.06% after a mean of 12.2 years of follow up. Among patients operated at the Linköping University Hospital: IRA patients reported better overall continence according to the Öresland score with in median3 (IQR 2–5) for IRA (n=38) and 10 (IQR 5–15) for IPAA (n=39, p<0.001). There were no major differences regarding the QoL. According to the NPR, after a median follow up of 12.4 years failure occurred in 265(32%) out of 1112 patients, of which 76 were secondarily reconstructed with an IPAA. Failure of the IPAA occurred in 103 (6%) patients with primary and in 6 (8%) patients after secondary IPAA (log-rank p=0.38). Conclusion: IRA is a safe restorative procedure for selected UC patients. Patients should be aware of the annual postoperative endoscopic evaluation with biopsies as well as the need to the use of local anti-inflammatory preparations. However, IRA should not be offered for UC patients with an associated primary sclerosing cholangitis diagnosis due to the increased risk to develop rectal cancer in their rectal mucosa. In such case, IPAA is probably the treatment of choice.
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| 10. |
- Abdiu, Avni, 1963-
(författare)
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Growth regulation in sarcomas : studies in vivo and in cell culture
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sarcomas are malignant tumors of mesenchymal origin, and can arise in soft-tissue and in bones. It has been suggested that the abnormal growth regulation in sarcoma cells may be due to an autocrine mechanism, in which the cells are stimulated by an endogenous production of growth factors. Platelet-derived growth factor (PDGF) has been detected in sarcomas, and may be one of the growth factors important for sarcoma growth.PDGF, originally discovered in platelets, is produced by, and binds to, a variety of cells. PDGF plays several roles both in normal conditions and in disease.Suramin is a polyanionic drug with antineoplastic activities, and is known to dissociate growth factors from their receptors. Suramin has been shown to inhibit growth in several tumors and tumor cell lines; however, some tumor cells have been unaffected, or even stimulated, by suramin.The present work was performed in order to a) examine the effects of suramin on sarcoma growth in vivo; b) investigate the kinetics of extravascularly administered PDGF in vivo; c) establish and characterize human sarcoma cells in vitro, including their relation to PDGF; d) evaluate the effects of suramin on sarcoma growth in vitro; e) compare the effects of PDGF on sarcoma growth in vivo and in vitro.Suramin was shown to inhibit growth of two different human osteosarcoma xenografts grown in nude mice. The action is believed to be mainly cytostatic, as the tumors continued to grow, albeit at a lower pace: the tumors of the suramin treated mice had a volume of one-third or less than the untreated ones. The percentage of cells in S and G2-M cell cycle phases was increased by suramin treatment, suggesting a selective effect of the drug in the S and G2 period.Blood and serum levels of 125I, after extravascular administration of 125I-PDGF-AB by intraperitoneal, intramuscular or subcutaneous injection in mice, were found to rise to a maximum 2-4 hours after injection. The levels of radioactivity persisted over several hours. Precipitiation of serum with 10% trichloracetic acid revealed that more than 50% of the radioactivity was in a macromolecular form. Gel chromatography of the serum showed that a major portion of the radioactive material in the circulation had the same molecular size as the original 125I-PDGF-AB.Eight cell lines derived from malignant fibrous histiocytomas (MFH) were established and characterized. A heterogeneity in the morphology of the MFH cell lines was noted. This heterogeneity was also reflected in the expression of mRNA for PDGF, transforming growth factor-alpha (TGF-/alpha/) and their receptors, ability to grow in serumfree media and secretion of PDGF into growth media. Two cell lines, able to grow in serum-free medium, coexpressed MRNA for PDGF, TGF-/aplpha/ and their receptors, suggesting that they may be regulated in an autocrine manner. However, other cell lines, unable to grow in a serum-free medium, also displayed this coexpression of mRNA. The simultaneous expression of a growth factor and its receptor is therefore not generally indicative of an autocrine mechanism.All cell lines, unable to grow in a serum-free medium, were growth inhibited by high-dose suramin (200 ug/ml). The two cell lines, previously noted to grow under serum-free conditions, were not affected by the high-dose suramin treatment. The finding that only serum-dependent human MFH cell lines were inhibited by high doses of suramin indicates that serum dependence in vitro may predict sensitivity of sarcoma cells to suramin.Two human sarcoma xenografts, one osteosarcoma and one malignant fibrous histiocytoma, were treated with human PDGF-AB when grown in nude mice. No effects on tumor growth were noted, although immunohistochemical studies revealed an expression of PDGF receptors. Furthermore, both sarcomas were markedly stimulated by PDGF-AB in vitro. It is concluded that mechanisms or factors other than available PDGF were limiting the growth of the examined tumors in vivo.
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