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The aim of this thesis was to investigate whether a structured and systematic approach on improving pharmacotherapy in the elderly (the LIMM-model) would lead to a more appropriate and accurate drug use in the elderly. The elderly use many drugs and are more prone to suffer from adverse drug reaction. It is therefore important to address the quality of their drug therapy. The first study presente
In radioimmunotherapy, monoclonal antibodies (mAbs) are used as a targeting agent carrying a toxic payload consisting of radionuclides. This treatment allows the irradiation of small lesions, even on the microscopic level. In the present work, two radionuclides with different properties were used. Lutetium-177 (177Lu) is a beta-particle-emitting radionuclide (t½=6.7 days) and astatine-211 (211At)
This thesis focuses on developing stem cell targeted gene therapy for the severe hereditary disorder Infantile Malignant Osteopetrosis (IMO) as well as increasing the understanding of how the genetic defect present in IMO affects the hematopoietic stem cells and hematopoiesis in general. IMO is a rare congenital disorder associated with an increased number of non-functional osteoclasts and the a
Stroke is a major cause of death and disability around the world. Stroke leads to loss of neurons and also other cells in the brain due to lack of blood supply. Currently no therapies are available to treat stroke-related disability. It has been shown that stroke leads to increased neurogenesis, birth of new neurons, within the brain. This increased neurogenesis is not sufficient to restore lost f
The treatment for head and neck squamous cell carcinoma (HNSCC) is surgery or (chemo)radiotherapy +/- surgery. Side effects related to therapy are long lasting and adversely affects quality of life. The incidence of oropharyngeal cancer is increasing and patients commonly present an advanced tumour stage with neck metastases at the time of diagnosis. The treatment protocol previously comprised rad
Over 100 million people around the world are exposed to high concentrations of arsenic (As) in drinking water, associated with a number of adverse health effects such as skin, lung and bladder cancer, vascular diseases and diabetes. In humans, As is metabolized via alternating reduction and methylation reactions, from inorganic As (iAs) into monomethylated (MMA) and dimethylated As (DMA). The most
Intraventricular haemorrhage (IVH) is the most common brain lesion in preterm infants and is most commonly seen in the sickest children, with 15-20% of very preterm infants developing IVH. The mortality of infants with severe IVH is 20-50 % in the neonatal period and over 50 % of surviving infants develop post-haemorrhagic ventricular dilatation (PHVD) and 40-80 % develop severe neurological impai
There were two principal objectives for this thesis. The first was to develop a methodology and evaluation model of moisture redistribution in order to make the future relative humidity in a screeded concrete slab predictable. The second objective was to develop a method to determine the critical humidity for ion transport in concrete. Residual moisture in screeded concrete slabs may be redistrib
Silicon (Si) is ubiqutious in natural waters as dissolved silica (DSi) and is used as a nutrient by many plant and animal species. DSi ultimately derives from the weathering of silicate minerals, a process which also consumes atmospheric CO2 and couples the silicon and carbon cycles. These processes, among others, impart observable fractionations to the stable isotopes of silicon, which makes the
In the event of a radiation accident, it is crucial to make rapid estimates of the absorbed dose received by both emergency workers, so-called first responders, and members of the public. Today, only personnel in rescue teams responding to nuclear emergencies have access to individual dosemeters. To make accurate assessments of the radiological consequences of an emergency situation, methods of re
In obesity and several other disease scenarios, the measurement of fat accumulation in various organs and tissues has become a sought-after technique in clinical diagnostics and research. Especially, quantitative and non-invasive techniques which also provide images of accumulated fat throughout the body would be valuable. In the typical hospital, magnetic resonance imaging (MRI) is the only techn
Neuroblastoma is a childhood tumor of the developing sympathetic nervous system (SNS) and is the most commonly diagnosed form of cancer in children before one year of age. Although survival curves have improved for these patients during the past decades, the conventional regimen of neuroblastoma treatment has clearly reached a plateau of efficiency with regard to increasing the survival rates of h
Hormone refractory prostate cancer occurs when androgen-deprivation therapy (ADT) fails to stop the growth of prostate cancer for any longer. Recent studies point towards a role for neuroendocrine (NE) differentiation in the development of hormone refractory disease. It has been hypothesized that NE-differentiated malignant tumor cells survive during ADT and promote development of androgen-indepen
Parkinson's disease and L-DOPA-induced dyskinesia (LID) does not merely involve the dopamine (DA) system but also include non-dopaminergic systems such as glutamate and serotonin (5-HT). An aberrant glutamate transmission at the corticostriatal synapse, has been linked to LID. Pharmacological agents to glutamate receptors at this synapse, (of which some are already clinically tested), could preve
This thesis is about the regulation of hematopoietic stem cells (HSCs) that represent rare cells residing in the bone marrow (BM) of adults. They are multipotent cells that have the capacity to differentiate to all mature cells of the blood system and have the capacity to self-renew, i.e. generate new HSCs. These cells have tremendous therapeutic potential to treat a variety of hematopoietic disor
The aim of this thesis was to investigate the effects of cortical reorganisational changes following experimental deafferentation and peripheral nerve injury and apply the concept of brain plasticity to enhance sensory re-education following peripheral nerve injury and repair in the hand. In the first two papers the effects on hand function of contralateral deafferentation was investigated. Tourn
Parkinson's disease (PD) is a neurodegenerative disorder where the midbrain dopaminergic neurons are lost. Presently there is no cure for PD, and the most common treatment is to replace the lost dopamine pharmacologically by administration of the dopamine precursor L-DOPA. This works very well during the initial treatment period, but unfortunately a majority of the patients develop abnormal involu
Hindered diffusion occurs in the most different processes, as has been described in this thesis. It is very important to have an understanding of the influence of hindered diffusion on the mass transfer rate, especially when competing rate processes are acting simultaneously. Using mathematical modeling and simulation makes it possible to predict the effects of hindered diffusion. The systems that
Glioblastoma multiforme (GBM) is the most malignant and also the most common form of brain tumour in humans. The overall aim of this thesis was to investigate morphological and diagnostics features in human GBM that may be of importance for prognosis and treatment. Immunohistochemically stained tissue sections have been microscopically analysed regarding immuno-reactive cells, cell proliferation,
Dizziness is a common reason for visits to primary health care, especially among elderly patients. From a physiotherapeutic perspective, this thesis aims to study the assessment and treatment of dizzy patients in primary health care. Interventions in papers I, III and IV comprised a vestibular rehabilitation programme. In paper I, patients with multisensory dizziness were randomized to interventi
