| 1. |
- Alvehus, Malin, 1975-
(författare)
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Obesity-associated inflammation in adipose tissue
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Excess body fat, particularly in the visceral depot, is linked to increased mortality and morbidity, including the development of diseases such as type 2 diabetes, cardiovascular disease, and cancer. Chronic low-grade inflammation in adipose tissue may be a key mediator of obesity-associated diseases. Importantly, specific pro-inflammatory cytokines have been shown to influence adipose tissue function and could therefore be a link to metabolic disorders. Circulating cytokine levels may also be increased in obesity and metabolic diseases. However, although fat distribution and inflammation are clearly linked to metabolic disorders, inflammatory gene expression in the different abdominal adipose depots has not been investigated in detail. The menopausal transition is followed by a centralization of body fat and increased adiposity. Notably, inflammatory changes in fat during the menopausal transition have not been characterized. Finally, there is a lack of studies investigating the long-term effects of weight loss on low-grade inflammation. The aim of this thesis was to characterize differences between fat depots and investigate putative changes in low-grade inflammation in adipose tissue and circulation following menopause or weight loss. Materials & Methods: The expression of inflammation-related genes was investigated in abdominal adipose tissue depots obtained from women with varying adiposity, before and after menopause or weight loss induced by surgery or dietary intervention. Circulating cytokine levels were analyzed using immunoassays. Results: Visceral fat displayed a distinct and adverse inflammatory profile compared with subcutaneous adipose tissues, and the higher gene expression in visceral fat was associated with adiposity. Postmenopausal women exhibited a higher expression of pro-inflammatory genes than premenopausal women that associated with central fat accumulation. There was also a menopause-related increase in circulating cytokine levels in postmenopausal women. After surgery-induced weight loss, there was a dramatic reduction in inflammatory gene expression followed by increased insulin sensitivity. We observed no alterations in circulating cytokine levels. Long-term dietary intervention, associated with weight loss, had favorable effects on inflammation in both adipose tissue and serum. Conclusion: Fat accumulation is linked to low-grade inflammation in abdominal adipose tissue. The unique inflammatory pattern of visceral fat suggests a distinct role in adipose tissue inflammation that is aggravated with increasing adiposity. In postmenopausal women, the adverse adipose inflammatory profile was associated with central fat accumulation, while higher circulating cytokine levels correlated with menopausal state/age. Our data from severely obese women undergoing surgery-induced weight loss clearly supports a link between adipose inflammation and insulin resistance. The long-term beneficial effects of weight loss were also demonstrated by the improved inflammatory profile after dietary intervention. In summary, excess body fat is clearly linked to adipose tissue inflammation. Long-term weight loss is accompanied by improved metabolic profile and reduced low-grade inflammation in fat.
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| 2. |
- Anticona Huaynate, Cynthia, 1983-
(författare)
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Lead exposure in indigenous children of the Peruvian Amazon : seeking the hidden source,venturing into participatory research
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction. In 2006, a Peruvian environmental agency reported the presence of elevated blood lead levels (BLLs) in indigenous communities of the Corrientes river basin. This is a territory in the Peruvian Amazon where oil activity has been associated with serious environmental effects, with impact on an ongoing social conflict. This PhD project aimed to determine the lead sources, risk factors and pathways in children of these communities and to suggest control and prevention strategies. Given the arguments attributing the lead source to the oil activity pollution, the second objective was to clarify any potential connection between the two. This project was conducted by a collaborative research partnership with the regional health authorities and the community-based organization. The third objective was to characterize the challenges, facilitating factors and the lessons learned from the research process.Methods. Two epidemiological studies were conducted. Study I (2009) was carried out in three communities and study II (2010) in six communities with different levels of exposure to oil activity. The participants were children 0–17 years old. Data collection included: determination of BLLs, hemoglobin levels and anthropometric indicators, a risk factor questionnaire, an environmental assessment and a risk map. Data analysis included univariate, bivariate and multivariate logistic regression. Data for the third objective came from field notes, documents, interviews and a process of collective reflection.Results. Study I (n= 221) found no significant difference in the geometric mean(GM) BLLs between the communities exposed and not exposed to oil activity. Older age and being a boy were found as risk factors for BLLs ≥ 10 μg/dL. In study II (n= 346), age stratified logistic regression models indicated that children 0–3 years whose mothers had BLLs ≥ 10 μg/dL, children 0–6 years who played with pieces of lead and children 7–17 years who fished 3 times or more per weekor chewed pieces of lead to manufacture fishing sinkers had a significant increased risk of having BLLs ≥ 10 μg/dL. Children who lived in communities near oil battery facilities also had a significant increased risk of having BLLs ≥ 10 μg/dL. In both studies, environmental samples showed lead concentrations below reference levels. The challenges and facilitating factors identified focused on five interrelated themes: i) mutual trust, ii) multiple agendas, iii) equal participation, iv) competing research paradigms and v) complex and unexpected findings.Conclusions. Metal lead appeared to be the main source of exposure. Playing with pieces of lead and chewing pieces of lead to construct fishing sinkers appeared to be pathways of exposure for children aged 0–6 years and 7–17 years, respectively. Mothers’ BLLs > 10 μg/dL was a risk factor for BLLs > 10 μg/dL in children aged 0–3 years. Living in a community with high exposure to oil activity was a risk factor for BLLs > 10 μg/dL. The identified connection with oil activity was the proximity of communities to oil battery facilities and thus greater access to lead from cables and other industrial waste. Despite the numerous challenges, participatory research appears to be the most appropriate approach for this type of context. The study findings led us to recommend:i) a comprehensive community-based lead control and prevention plan,ii) the introduction of substitute non-harmful material(s) for fishing sinkers and iii) secure containment of the oil company’s waste deposits.
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| 3. |
- Bergh Drott, Johanna
(författare)
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The role of microorganisms in prostate cancer development
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer is the most common cancer among Swedish men, but the aetiology of this disease is largely unknown. There is evidence for a linkage between chronic inflammation and prostate cancer. The mechanisms causing prostate inflammation and how this could promote tumour development and progression are however largely unknown. Chronic inflammatory infiltrates are common findings in prostate tissue samples and infection is proposed to be one possible cause for this inflammation. Inflammatory cells release free radicals, cytokines, and growth factors that facilitate increased cell proliferation, DNA damage, mutations, and angiogenesis. However, the present literature on the presence of microbes in prostate tissue and their possible linkage to inflammation and cancer development is limited. Therefore, the aim of this thesis was to investigate if microorganisms are present in prostate tissue and to evaluate their role in inducing prostatitis and prostate epithelial neoplasia.The presence of microorganisms (virus, bacteria and fungi) was studied in clinical prostate tissue samples to evaluate whether or not the occurrences of microorganisms were different in patients that later developed cancer compared with matched controls that did not. Viruses, bacteria and fungi were found in prostate tissues. Out of eight different viruses investigated, EBV and JC virus were detected, but there were no differences in occurrence in the case group compared to the control group. The fungus Candida albicans was present in a very small proportion of the prostate tissue samples. The predominant bacterium was Propionibacterium acnes and the second most prevalent was Escherichia coli. The presence of Propionibacterium acnes was associated with inflammation and subsequent prostate cancer development. Propionibacterium acnes was further evaluated for its capacity to induce an inflammatory response both in vitro and in vivo. Live Propionibacterium acnes induced a strong immune reaction in prostate epithelial cells in vitro with up-regulation of inflammatory genes and secretion of pro-inflammatory cytokines. Infection with Propionibacterium acnes in rat prostate resulted in a lobe specific inflammation with the most intense inflammation in the dorso-lateral prostate, lasting up to 3 months post-inoculation. Propionibacterium acnes inflammation was also associated with altered epithelial cell morphology, signs of DNA damage and increased cell proliferation.Taken together, this thesis shows that different viruses and bacteria can be found in prostate tissue. Propionibacterium acnes, the most abundant among the bacteria detected and more prevalent in the cancer than in the control group, exhibits strong prostatitis promoting properties both in vitro and in vivo. In addition, Propionibacterium acnes can induce some of the epithelial changes known to occur during prostate neoplasia formation. This thesis therefore suggests that Propionibacterium acnes induced chronic prostatitis could promote prostate cancer development. Further studies are needed to elucidate the molecular interplay linking Propionibacterium acnes induced inflammation and the formation of a pre-neoplastic state that could evolve into prostate cancer.
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| 4. |
- Berglund, Staffan, 1975-
(författare)
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Effects of iron supplementation on iron status, health and neurological development in marginally low birth weight infants.
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Due to small iron stores and rapid growth during the first months of life, infants with low birth weight (LBW) are at risk of iron deficiency (ID). ID in infancy is associated with irreversible impaired neurodevelopment. Preventive iron supplementation may reduce the risk of ID and benefit neurodevelopment, but there is also a possible risk of adverse effects. More than 50% of all LBW infants are born with marginally LBW (MLBW, 2000-2500g), and it is not known if they benefit from iron supplementation. Methods We randomized 285 healthy, Swedish, MLBW infants to receive 3 different doses of oral iron supplements; 0 (Placebo), 1, and 2 mg/kg/day from six weeks to six months of age. Iron status, during and after the intervention was assessed and so was the prevalence of ID and ID anemia (IDA), growth, morbidity and the interplay with iron and the erythropoetic hormones hepcidin and erythropoietin (EPO). As a proxy for conduction speed in the developing brain, auditory brainstem response (ABR) was analyzed at six months. In a follow up at 3.5 years of age, the children were assessed with a cognitive test (WPPSI-III) and a validated parental checklist of behavioral problems (CBCL), and compared to a matched reference group of 95 children born with normal birth weight. Results At six months of age, the prevalence of ID and IDA was significantly higher in the placebo group compared to the iron supplemented infants. 36% had ID in the placebo group, compared to 8% and 4 % in the 1 and 2mg/kg/day-groups, respectively. The prevalence of IDA was 10%, 3% and 0%, respectively. ABR-latencies did not correlate with the iron intake and was not increased in infants with ID or IDA. ABR wave V latencies were similar in all three groups. Hepcidin correlated to ferritin and increased in supplemented infants while EPO, which was negatively correlated to iron status indicators, decreased. At follow up there were no differences in cognitive scores between the groups but the prevalence of behavioral problems was significantly higher in the placebo group compared to those supplemented and to controls. The relative risk increase of CBCL-scores above a validated cutoff was 4.5 (1.4 – 14.2) in the placebo-group compared to supplemented children. There was no detected difference in growth or morbidity at any age. Conclusion MLBW infants are at risk of ID in infancy and behavioral problems at 3 years of age. Iron supplementation at a dose of 1-2 mg/kg/day from six weeks to six months of age reduces the risks with no adverse effects, suggesting both short and long term benefit. MLBW infants should be included in general iron supplementation programs during their first six months of life.
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| 5. |
- Birkeland, Anna-Lena, 1955-
(författare)
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Psychosocial aspects of living with congenital heart disease : child, family, and professional perspectives
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The vast majority of infants born with congenital heart disease (CHD) reach adulthood because of the developments in cardiology in recent decades. This thesis aims to describe the psychosocial situation of child/adolescent cardiac patients and their families, investigate the situation faced by parents and siblings initially and over time, investigate the approaches paediatric cardiologists use in encountering the family, and describe the teamwork occurring in paediatric cardiology teams (PCTs) in Sweden.Theoretical framework: The theoretical framework was based on a quality of life model applied to children, a stress-coping model, and a psychosocial approach including support, profession, and teamwork.Methods: The research combines quantitative data collection/analysis and qualitative research interviews/content analysis.Results: Complexity: The three grades of medical complexity differed regarding the number and severity of psychosocial symptoms, the children with the most complex CHD having the most severe symptoms. The most frequent symptoms in the whole patient group regarding various spheres were: healthcare and treatment-related needs in the external sphere, family symptoms in the interpersonal sphere, and mental/psychosomatic symptoms in the personal sphere.Coping: Being informed of a child’s/sibling’s heart disease has emotional consequences, so information, communication, and support are essential. Breaking the news of a child’s disease can be described as a turning point still significant after ten years. The professionalism of the doctor’s approach in breaking the news is crucial.Profession: Among paediatric cardiologists, how to break bad news to a family is an important concern, evident in findings regarding the significance of trust and confidence and the use of various emotional positions. Paediatric cardiologists commonly wish to be skilled at handling this situation, and attaining the needed skills calls for reflection, education, and sharing experience.Team: PCTs in Sweden aim and try to work in a structured way. In PCTs, there is a need for leadership, resource coordination, coaching, and a forum for joint reflection. Dependence on the physician on the team was identified in all PCTs. The challenge of managing increasing complexity at both the family and system levels requires interprofessional teams.Conclusions: These studies illustrate the psychosocial complexity and the need of psychosocial support. Emotional consequences, communication, information and support are essential both for the children, parents/families and for the professionals. To manage this complexity organizational alteration action plans are required. There is a need for a forum to stimulate dialogue and common reflection in the local PCT and at the regional and national centres.
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| 6. |
- Björklund, Fredrik, 1968-
(författare)
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Platelet reactivity and comorbidities in acute coronary syndrome
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background In the event of an acute coronary syndrome (ACS), the risk of death and complications such as stroke and re-infarction is high during the first month. Diabetes, impaired kidney function, elevated markers of systemic inflammation and high level of platelet reactivity have all been associated with worsened prognosis in ACS patients. Impaired kidney function is a condition with high cardiovascular morbidity and there is an established association between level of kidney function and outcome in the event of an ACS. Aims We sought to investigate the level of platelet reactivity during the first days of an ACS and specifically the level of platelet reactivity in patients with different conditions associated with worsened prognosis in the event of an ACS. We also wanted to investigate the prognostic impact of baseline levels of cystatin C as well as the importance of decreasing kidney function during the first days of an ACS. Methods We included 1028 unselected patients with ACS or suspected ACS during the years 2002 and 2003, of which 534 were diagnosed with an acute myocardial infarction (AMI). Blood samples for measuring platelet aggregation, cystatin C levels and other clinically important biomarkers were collected day 1, 2, 3 and 5 following admission. Platelet reactivity was measured using 2 different methods. Platelet aggregation was measured using Pa-200, a particle count method, based on scattering of laser light. PFA 100 is a method of measuring primary hemostasis in whole blood. Results Platelet aggregation and comorbidities. We found an increase in platelet aggregation when an ACS was complicated by an infection and there was an increased frequency of aspirin non-responsiveness in patients suffering from pneumonia during the first days of an ACS. Furthermore, we found an independent association between levels of C-reactive protein and platelet aggregation. During the first 3 days following an acute myocardial infarction, platelet aggregation increased despite treatment with anti-platelet agents. Platelet aggregation was found to be more pronounced in patients with diabetes. Patients with impaired kidney function, showed increased platelet aggregation compared to patients with normal renal function, however, this difference was explained by older age, higher prevalence of DM and levels of inflammatory biomarkers. We found no independent association between chronic kidney disease (CKD) and levels of platelet aggregation. Kidney function and outcome Serum levels of cystatin C on admission had an independent association with outcome following an acute myocardial infarction. With a mean follow-up time of 2.9 years, the adjusted HR for death was 1.62 (95% CI 1.28-2.03; p<0.001) for each unit of increase in cystatin C on admission. The level of dynamic changes in cystatin C during admission for an acute myocardial infarction was independently associated with prognosis in patients with normal or mild impairment of renal function. The adjusted HR for death was 10.1 (95% CI 3.4-29.9; p<0.001). Conclusion In patients suffering from an AMI platelet aggregation increases during the first days, despite anti-platelet treatment. Diabetes, age and biomarkers of inflammation are independently associated with platelet aggregation. Admission levels of cystatin C as well as changes in cystatin C levels during hospitalisation are independently associated with outcome.
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| 7. |
- Brändström, Helge, 1953-
(författare)
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Accidental hypothermia and local cold injury : physiological and epidemiological studies on risk
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: (Papers I and II) The objectives were to first determine incidence and contributing factors to cold-related injuries in northern Sweden, both those that led to hospitalization and those that led to fatality. (Papers III and IV) A further aim was to assess post-cooling hand-rewarming responses and effects of training in a cold environment, both on fingertip rewarming and on function of the autonomic nervous system, to evaluate if there was adaptation related to prolonged occupational cold exposure.Methods: In a retrospective analysis, cases of accidental cold-related injury with hospital admission in northern Sweden during 2000-2007 were analyzed (Paper I). Cases of fatal hypothermia in the same region during 1992-2008 were analyzed (Paper II). A cohort of volunteers was studied before and after many months of occupational cold exposure. Subject hand rewarming response was measured after a cold hand immersion provocation and categorized as slow, moderate or normal in rewarming speed. This cold provocation and rewarming assessment was performed before and after their winter training. (Paper III). Heart rate variability (HRV) was analyzed from the same cold provocation/recovery sequences (Paper IV).Results: (Paper I) For the 379 cases of hospitalization for cold-related injury, annual incidences for hypothermia, frostbite, and drowning were 3.4/100,000, 1.5/100,000, and 1.0/100,000 inhabitants, respectively. Male gender was more frequent for all categories. Annual frequencies for hypothermia hospitalizations increased during the study period. Hypothermia degree and distribution of cases were 20 % mild (between 32 and 35ºC), 40% moderate (31.9 to 28ºC), and 24% severe (< 28ºC), while 12% had temperatures over 35.0ºC. (Paper II) The 207 cases of fatal hypothermia showed an annual incidence of 1.35 per 100,000 inhabitants, 72% in rural areas, 93% outdoors, 40% found within 100 meters of a building. Paradoxical undressing was documented in 30%. Ethanol was detected in femoral vein blood in 43%. Contributing co-morbidity was common including heart disease, previous stroke, dementia, psychiatric disease, alcoholism, and recent trauma. (Paper III) Post-training, baseline fingertip temperatures and cold recovery variables in terms of final rewarming fingertip temperature and vasodilation time increased significantly in moderate and slow rewarmers. Cold-related injury (frostbite) during winter training occured disproportionately more often in slow rewarmers (4 of the 5 injuries). (Paper IV) At ‘pre- winter-training’, normal rewarmers had higher power for low frequency and high frequency heart rate variability. After cold acclimatization (post-training), normal rewarmers showed lower resting power values for the low frequency and high frequency heart rate variability components. Conclusions: Hypothermia and cold injury continues to cause injury and hospitalization in the northern region of Sweden. Assessment and management is not standardized across hospitals. With the identification of groups at high risk for fatal hypothermia, it should be possible to reduce the incidence, particularly for highest risk subjects; rural, living alone, alcohol-imbibing, and psychiatric diagnosis-carrying citizens. Long-term cold-weather training may affect hand rewarming patters after a cold provocation, and a warmer baseline hand temperature with faster rewarming after a cold provocation may be associated with less general risk for frostbite. Heart rate variability results support the conclusion that cold adaptation in the autonomic nervous system occurred in both groups, though the biological significance of this is not yet clear.
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| 8. |
- Conradsson, Mia, 1981-
(författare)
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Physical exercise and mental health among older people : measurement methods and exercise effects focusing on people living in residential care facilities
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to study the effects of exercise on mental health among older people living in residential care facilities. The aim was also to study the reliability of an assessment scale for balance function and the usefulness of an assessment scale for depressive symptoms among older people, including people with cognitive impairments. The Berg Balance Scale (BBS) is frequently used to assess balance in older people, but knowledge is lacking about its absolute reliability. The BBS (0-56 points) was assessed twice among older people living in residential care facilities by the same assessor, at approximately the same time of day, and with 1-3 days in between. The absolute reliability was calculated as being 7.7 points, using 95% confidence level, and the Intra Class Correlation coefficient (ICC) was calculated to 0.97. Depression is common among older people and is often not detected and not treated adequately. The Geriatric Depression Scale 15-item version (GDS-15) was designed to assess depressive symptoms among older people, but there is limited knowledge about the usefulness of the scale among people with varying degree of cognitive impairment. A sample of people aged 85 years and over was divided into groups according to cognitive function using their Mini-Mental State Examination (MMSE) scores; 0-4, 5-9, 10-14, 15-19, 20-24, 25-27, and 28-30. In total, 650 (78%) of the 834 participants completed the GDS-15. The lower the cognitive function, the smaller the proportion who completed the GDS-15 assessment; for the two MMSE groups with scores of < 10, the proportions who completed the GDS-15 were 1% and 42%, respectively, compared to 64–95% in people with MMSE scores of ≥ 10. The level of correlation between the GDS-15 and a scale of psychological wellbeing, the Philadelphia Geriatric Center Morale Scale (PGCMS), did not differ between MMSE groups with scores of ≥5 compared to people in the group with the highest scores (MMSE 28–30). Exercise has been suggested as effective in influencing mental health among community-dwelling older people, but there is a need for a well-designed study to establish the effects among older people living in residential care facilities. A high-intensity functional exercise programme was evaluated for effects on depressive symptoms and psychological wellbeing among older people dependent in activities of daily living (ADL) and living in residential care facilities. The study was a cluster-randomised controlled study. Participants were randomised to either a high-intensity functional weight-bearing exercise program (HIFE Program) or a control activity. Sessions were held in groups, for approximately 45 minutes, five times over each two-week period for three months, a total of 29 times. The outcome measures, the GDS-15 and the PGCMS, were blindly assessed at baseline, 3- and 6-month follow-up. There were no differences between the groups at the 3- or 6-month follow-ups in the total sample. However, sub-groups analyses showed a difference in PGCMS scores in favor of the exercise group among people with dementia at the 3-month follow-up. Regarding older people living in residential care facilities, including people with cognitive impairments, there is a lack of evidence showing that exercise has a positive influence on mental health. This may either be due to a lack of effect, or an insufficient amount of effect of exercise on physical capacity or dependence in ADL, which could be two important mediating factors for influencing mental health. The association between changes in physical capacity (BBS) or dependence in ADL (Barthel ADL Index) and changes in mental health (GDS-15 and PGCMS) was evaluated. The results showed no significant associations between change in physical capacity or dependence in ADL, and change in depressive symptoms or psychological well-being. Further, interaction analyses showed no moderating effects for dementia disorder. In conclusion, despite a high ICC value, the result of the absolute reliability evaluation shows that a change of 8 BBS points is required to reveal a genuine change in function among older people who are dependent in ADL and living in residential care facilities. This knowledge is important in the clinical setting when evaluations are made of an individual’s change in balance function over time in this group of older people. The GDS-15 seems useful in assessing depressive symptoms among very old people with MMSE scores of ten or above. More studies are needed to strengthen the validity among people with MMSE scores of 10-14, and for people with lower MMSE scores than ten there may be a need to develop and validate other measurements. Furthermore, a high-intensity exercise programme offered 2-3 times/week seems not to generally influence mental health among older people living in residential care facilities. However, the exercise programme may have a short-term effect on well-being among people with dementia. A change in physical capacity or dependence in ADL does not appear to be associated with a change in depressive symptoms or psychological well-being among older people who are living in residential care facilities. These results may explain why studies of using exercise to influence mental health have not shown effects in this group of older people. In future research, there is a need for studies that evaluate whether exercise offered more frequently, or interventions that aim to increase the level of physical activity in daily life, can influence mental health among older people living in residential care facilities.
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| 9. |
- Crnalic, Sead, 1960-
(författare)
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Metastatic spinal cord compression in prostate cancer : clinical and morphological studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Bone metastases occur in most patients with advanced hormone-refractory prostate cancer causing pain, pathologic fractures, and spinal cord compression. Few studies specifically address surgical treatment of metastatic spinal cord compression (MSCC) in prostate cancer. Criteria for identifying patients who may benefit from surgery are poorly defined. Most of the current knowledge regarding tumor biology in prostate cancer is based on studies of primary tumors or soft tissue metastases. The mechanisms regulating growth of bone metastases are not fully established. Aims: a) to evaluate outcome after surgery for MSCC in prostate cancer and to identify prognostic factors for survival and functional recovery; b) to evaluate current practice for referral of prostate cancer patients with MSCC; c) to analyze expression of androgen receptor (AR), cell proliferation, apoptosis, and prostate-specific antigen (PSA) in bone metastases with regard to survival after surgery for complications of bone metastases. Patients and Methods: We retrospectively evaluated the hospital records of 68 consecutive patients operated for metastatic spinal cord compression. Tumor tissue from bone metastases was obtained on spinal surgery (54 patients), fracture surgery (4 patients) and biopsy (2 patients), and analyzed by immunohistochemistry. Results: Study I: Mortality and complication rate after surgery was high. Patients with hormone-naïve disease and those with hormone-refractory disease with good performance status and without visceral metastases had more favorable survival. The ability to walk after surgery was related to better survival. Study II: A new score for prognosis of survival after surgery for spinal cord compression includes: hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum PSA. The score is simple, tumor specific, and easy to apply in clinical practice. Study III: Our results suggest that delays in diagnosis and treatment may have negative impact on functional outcome. Pretreatment ability to walk, hormone status of prostate cancer, and time from loss of ambulation influenced neurological recovery after surgery for spinal cord compression. Study IV: High nuclear AR immunostaining in bone metastases and high preoperative serum PSA were associated with a poor outcome after metastasis surgery in patients with hormone-refractory prostate cancer. Short-term effect of castration therapy disclosed that nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected. Conclusion: Prostate cancer patients with metastatic spinal cord compression represent a heterogeneous group. We identified prognostic factors for survival and functional outcome, which may help clinicians in making decisions about treatment. Our results also implicate the need for development of local and regional guidelines for treatment of patients with spinal cord compression, as well as the importance of information to patients at risk.
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| 10. |
- Elcadi, Guilherme H.
(författare)
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Near infrared spectroscopy for assessing oxygenation and hemodynamics in the upper extremities of healthy subjects and patients with work-related muscle pain
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of work-related muscle pain (WRMP) is large in the general population in the industrialized world. Despite significant advances over recent years in some research areas, the mechanisms of why WRMP occurs and the pathophysiological mechanisms behind the disorders are still unclear. One suggested explanation is that WRMP is caused initially by a limitation of the local muscle circulation and oxidative metabolism. There is a lack of objective methods to gauge the development and diagnosis of WRMP. Near infrared spectroscopy (NIRS) is a non-invasive technique that allows for determinations of oxygenation and blood flow. The purpose of this thesis was to evaluate NIRS (1) as a method for measuring muscle oxygenation and hemodynamics for the extensor carpi radialis (ECR) and trapezius descendens muscles (TD), and (2) to investigate whether variables measured by NIRS differed between patients diagnosed with WRMP and healthy subjects. Several variables of NIRS were produced and investigated. These included muscle oxygenation (StO2%), changes during contractions (∆StO2%) and StO2% recovery (Rslope), total hemoglobin (HbT) as an indication of blood volume and its changes during contractions (∆HbT). In addition, for the ECR, by applying an upper arm venous occlusion (VO) HbTslope increase as a surrogate of blood flow, and for both VO and arterial occlusion (AO) HHbslope increase (i.e. deoxyhemoglobin slope) as a surrogate of oxygen consumption were variables of interest. A first objective was to determine how StO2% and HbT responded to various contraction forces and how it related to muscle activation measured by electromyography (EMG). For both muscles isometric contractions of 10, 30, 50 and 70% of maximal voluntary contraction (MVC) were maintained for 20 s each by healthy males and females; additionally a 10% MVC contraction was sustained for 5 min. For the different contraction levels, predictable relationships were seen between ∆StO2% and force, and between ∆StO2% and EMG RMS amplitude. The general trend was a decrease in ∆StO2% with increasing force and increasing EMG. Females showed a tendency for a higher oxygen use (i.e., drop in StO2%) for the ECR over force levels than males and a higher RMS% MVC for the TD. For the 10% MVC contraction sustained for 5 min gender specific changes over time for HbT and RMS for the ECR, and for StO2% for the TD muscle were seen. A second objective was to determine the day-to-day reliability of NIRS variables for the ECR and TD muscles at group level (Pooled data) and at gender level (males and females). Measurements were performed on two occasions separated by 4-6 days and intraclass correlation coefficients (ICC) and limits of agreement (LOA) were determined as reliability and reproducibility indicators, respectively. Variables tested were ∆StO2% during submaximal isometric contractions of 10, 30, 50 and 70% MVC and StO2% recovery (Rslope) after contractions and after AO. For the ECR, HbTslope as an indication of blood flow (using VO) and HHbslope as a surrogate of oxygen consumption for both VO and AO were computed. For ∆StO2% for the ECR the highest ICC was at 30% MVC for both the pooled data and at gender level. For the TD ICCs were comparably high for 30, 50, 70 % MVC (for both muscles the ∆StO2% at 10% MVC showed the lowest ICC). Further, females showed a higher ICC than males for contraction levels of 50 and 70% MVC. For both muscles, LOA for ∆StO2% was lowest at 10% and highest at 50 and 70% MVC. For the ECR Rslope ICCs were high for all contraction levels, but was lower for AO; LOA was lowest at 70% MVC. For the TD, Rslope ICCs were also high for all contraction levels and LOA was lowest at 30 % MVC. ICC for HbTslope was the lowest of all variables tested. For HHbslope ICC was higher for AO than for VO, and LOA was lower for AO. A third objective was to determine if there were differences between healthy subjects and patients diagnosed with WRMP in ∆StO2% and ∆HbT responses during varying submaximal contractions (10, 30, 50 and 70% MVC), and StO2% recovery (Rslope) immediately after contractions and AO. Additional variables tested in the ECR at rest were HHbslope to indicate oxygen consumption (using AO) and HbTslope as an indication of blood flow. There were no differences between groups in ∆StO2% and ∆HbT variables during the contractions or Rslope in the recovery after contractions or AO. Furthermore, HbTslope was not different between groups However, oxygen consumption for the ECR and StO2% for the TD at rest were significantly greater for healthy subjects compared to patients. A fourth objective was to determine if there were differences in StO2% and HbT between healthy subjects and WRMP patients during a 12 min sustained contraction of 15 % MVC. In addition, the protocol included a recovery period of 30 min. Prior to contraction, as well as during the recovery period, HbTslope as a surrogate of blood flow was determined for the ECR. Neither the ECR nor the TD exhibited significant differences between groups for StO2% and HbT during the contraction. For the TD patients showed a lower StO2% value at rest and throughout the contraction than healthy subjects. For the ECR HbT during the sustained contraction the general trend was an initial decrease with gradual increase throughout the contraction for both groups. For HbTslope no differences were seen between patients and healthy subjects before the sustained contraction and during the recovery period for both muscles.NIRS is deemed a suitable technique for assessing physiological measurements of the upper extremity, including for day-to-day testing.NIRS was not able to distinguish between the patients with WRMP and controls. A concern in the thesis is the characteristics of the patient group in being equally active in recreational sports, actively working, and similar in muscle strength as controls. Thus, applying NIRS for studying a more severe patient group could yield different results.
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