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  • Salerud, Göran, 1954- (författare)
  • Laser doppler tissue flowmetry : fiberoptic methods in microvascular research
  • 1986
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Laser Doppler flowmetry (LDF) constitutes a method for measuring the flux of blood cells in the microcirculatory bed. Photons are scattered in the moving blood cells, where they undergo a frequency shift according to the Doppler principle. Light is brought to the tissue under study by one optical fiber and transmitted back to photodetectors by two separate fibers. LDF is a particulary useful method to study blood flow patterns and vascular regulatory mechanisms, since it is non-invasive and assesses blood flow in a very small volume of tissue (1 mm3).Blood flow recordings from skin areas, such as forearm and forehead, have revealed large spatial and temporal variations in microvascular blood flow. If the flowmeter probe is moved as little as 2.5 mm, the spatial heterogeneity of the vasculature result in a significant (p<0.001) difference in flowmeter output signal.Spontaneous rhythmical blood flow patterns (vasomotion) with different amplitudes, appeared in all of the 8 subjects studied. Some subjects had a continuous vasomotion pattern, while others showed only "bursts" of the pattern. Recorded blood flow in two juxtaposed skin sites sometimes demonstrated simultaneous variations in both sites, while in other instances the rhythmical flow patterns were out of phase or of different frequencies. To overcome the problem with a large spatial variation in skin blood flow in relation to the geometrical dimension of the probe, a multifiber probe was developed. It was designed to integrate the blood flow over an area enlarged approximately seven times compared to the standard probe. Measurements with this probe reduced the spatial differences as theoretically expected. No averaging effect was found, however, on the temporal variations.In skin, the capillary bed is located superficially, while in other tissues, such as the intestine, the inner wall (mucosa) is the most perfused. In an experiment on cat small intestine, the blood flow was measured both from the mucosal and serosal side. The results showed that it was possible to record the total blood flow of the intestinal wall, irrespective of whether the probe was placed on the mucosal or serosal side of the bowel wall.For tissues like muscle, liver and brain it may be of interest to assess the deep tissue perfusion. The LDF standard probes are, however, too large and blunt to be inserted into the tissue, without disturbing the flow. Therefore a single fiber LDF was developed, with oneoptical diber (Ø =0.5 mm) guiding the light to and from the tissue under study. In a flow model resembling tissue perfusion, the usefulness of the single fiber LDF based on the differential technique was evaluated. When a mathematical model was used to evaluate the single versus the differential channel operation, the differential technique was found most powerful if the laser broadband noise has a substantial rms-value or if many coherence areas are detected. The dynamic responses of the single fiber LDF were studied in a pig experimental model under different physiological conditions. The results agreed well with known reference blood flow patterns
  • Stål, Olle, 1952- (författare)
  • Static and flow cytometry for tumor DNA analysis
  • 1989
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The analysis of cellular DNA content in human tumors has shown to be of prognostic importance. The techniques used involve measurements in slide preparations by absorption cytophotometry and static cytofluorometry as well as the analysis of cell suspensions by flow cytometry. The aim of this work has been to improve these techniques by the development of computer aided systems in order to facilitate the use in a larger scale for clinical purposes. Another aim has been to study the prognostic significance of DNA analysis in breast cancer.Software for determination of DNA content and nuclear area by scanning absorption cytophotometry was developed. The system, HISTOSCAN, is insensitive to light scattering and may therefore be used in tissue sections. Thus, measurements in morphologically well-defined areas may be performed, but the method is less suitable for extensive use due to the slow procedure of the mechanical scanning.More rapid analyses are achieved by the system developed for static cytofluorometry in cytocentrifuged specimens. Cells to be measured are not positioned in the ordinary way, but are just passed through the excitation light beam as the specimen is visually scanned. DNA content and nuclear size are estimated simultaneously from the fluorescence recorded. For estimation of proliferative activity a sufficient number of cells may be analysed within a reasonable time.Similar results were obtained by static cytofluorometry and flow cytometry in a series of primary breast cancers. A close correlation was found for DNA index and, if 200 cells or more were measured, the same was true for S-phase fraction.Tumors from 472 women with primary breast cancer were analysed by flow cytometry. DNA ploidy showed significant association with disease recurrence and mortality but did not show a prognostic value in addition to that of traditional factors. The prognostic significance of S-phase fraction was independent of nodal status, tumor size and estrogen receptor content concerning early relapse and mortality. The survival of 116 women with recurrent breast cancer was correlated with both DNA ploidy and S-phase fraction in a multivariate analysis including nodal status, tumor size, ER content and site of recurrence.
  • Sundqvist, Tommy, 1949- (författare)
  • Probing intestinal permeability in man using different-sized, low-molecular-weight polyethyleneglycols and mathematical modelling
  • 1981
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Selective intestinal permeability as reflected by the urinary recovery of low-molecular-weight polyethylene glycols (PEG 400) of dlfferentsizes after oral administration was characterized with a mathematical filter-function. There was relative loss of both large and small PEG molecules on their way from the intestine to the urine. The reduced recovery of the large molecules is explained by selective intestinal absorption, since intravenous instillation abolished the effect. After curve-fitting to the experimental data, the mathematical procedure gives a quantitative measure of the fraction of selective and non-selective passage, and of filter-efficiency at different molecular weights. When applied to patients treated by bypass surgery for morbid obesity the method indicated a less permeable intestine with a reduced effective absorbtive surface area. In patients with rheumatoid arthritis a fasting diet gave a similar effect, which was accompanied by a reduction in disease activity. However, after changing to lactovegetarian diet the intestinal selectivity returned towards the control values, as did the inflammatory indices. Finally, to evaluate the importance of different physiological criteria for the outcome of the PEG 400 absorption test, a mathematical multi-compartment model was constructed and simulated on a computer.
  • Tenland, Torsten, 1952- (författare)
  • On laser Doppler flowmetry : methods and microvascular applications
  • 1982
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • A laser Doppler flowmeter for non-invasive microcirculatory blood flow studies has been developed. The tissue under study is illuminated by laser light (helium-neon laser, output power 2 mW) via an optical fibre and the Doppler shift oflight scattered in moving red cells is analysed. By the use of two photodetectors for detection of the backscattered light, the influences of mode interference and broadband noise from the laser and noise from surrounding light sources have been suppressed. The instrument is designed to give a continuous, stable and linear real-time measure of the flux of red cells (i.e. the number of red cells times their velocity) in the outermost layer (1 mm) of tissue, in which the red cell volume fractions are low or moderate. Linearity, measuring depth and the influence of blood oxygen tension were evaluated in a flow model with optical properties similar to those of human skin. Laser Dopplerflowmetry was found to be versatile for measurements of blood flow in human skin and rat testis and did not influence the flow under study.An extensive study of spatial and temporal variations of human skin blood flow was performed. As it was found that skin blood flow shows wide day-to-day variations and significant differences between adjacent probe sites, earlier reported "normal" values of skin blood flow were seriously questioned. It is proposed that this study can serve as a base for further functional studies.Testicular blood flow in rats was studied in order to evaluate acute effects of stress-linked substances such as adrenaline and noradrenaline. Both substances lowered the blood flow at high doses.Rhythmical variations of blood flow (frequency 5-12 min-1) in human skin and rat testis were observed and found to be in agreement with earlier findings in microscopic studies on other types of tissue. The nature and origin of this rhythmicity point towards a local regulatory mechanism operating also under "steady state" conditions.
  • Åhlfeldt, Hans, 1955- (författare)
  • Computer-based modeling and simulation in the analysis of cardiac arrhythmias and cardiac pacing
  • 1989
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Most systems for ECG analysis deal with QRS classification and arrhythmia detection but do not address the problem of finding the underlying mechanism responsible for the manifest arrhythmia. Although it is possible to distinguish among different arrhythmogenic mechanisms on the cellular level, it is far more difficult in the clinic based on ECG recordings. A computer model which is well suited for rhythm studies has been developed. The heart is modeled as a network of finite elements in which the impulse propagation is described mathematically, as well as several arrhythmogenic mechanisms. These include modulated parasystole, macro and micro reentry and different kinds of block. Since modulated parasystole provides a unified explanation of a variety of different arrhythmias, a stepwise procedure is presented by which this mechanism can be detected. Modulated parasystole can be described mathematically with a phase response curve, and the model has proven valuable for deduction of biand triphasic phase response curves from clinical cases with frequent ventricular premature complexes.Cardiac pacing is a very important therapy for rhythm disorders and since modern pacemakers interact with the heart in a complex way, the problem of cardiac pacing and pacemaker follow-up has also been studied. An ambulatory recording system has been developed, including a pacemaker spike detector and a computer program which can detect possible events of pacemaker malfunction. The computer model has been used to analyse the interaction between the heart and different types of pacemakers. The model has also been integrated with a hypertext system, allowing the system to be used for computer-aided education of cardiac pacing and cardiac arrhythmias.
  • Jonasson, Lise-Lotte, 1956- (författare)
  • A comprehensive picture of ethical values in caring encounters, based on experiences of those involved Analysis of concepts developed from empirical studies
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Older people should have a life with a sense of value and should feel confident. These ethical values, which are expressed in normative ethics, are expected to prevail in empirical ethics. Central components of nursing are the ethical issues of autonomy, beneficence, non-maleficence and the principles of justice. The general aim of this thesis is to identify and describe the ethical values that are apparent in the caring encounter and their influence on the people involved. This is done from the perspective of the older person in study (I), next of kin in study (II) and nurses in study (III). In study (IV) the aim was to synthesize the concepts from empirical studies (I- III) and analyze, compare and interrelate them with normative ethics. Studies (I, III) were empirical observational studies including follow-up interviews. Twenty-two older people participated voluntarily in study (I), and in study (III) 20 nurses participated voluntarily. In study (II) fourteen next of kin were interviewed. In studies (I- III) constant comparative analysis, the core foundation of grounded theory, was used. Five concepts were used in the analysis in study (IV); three from the grounded theory studies (I- III) and two from the theoretical framework on normative ethics i.e. the ICN code and SFS law. Five categories; being addressed, receiving respect, desiring to participate, increasing self-determination and gaining self-confidence formed the basis for the core category ‚Approaching‛ in study (I). ‘Approaching’ indicates the ethical values that guide nurses in their caring encounters with older people. These ethical values are noted by the older people and are greatly appreciated by them, and also lead to improved quality of care. Four categories were identified in study (II): Receiving, showing respect, facilitating participation and showing professionalism. These categories formed the basis of the core category ‚Being amenable‛, a concept identified in the next of kin’s description of the ethical values that they and the older patients perceive in the caring encounter. In study (III), three categories were identified: showing consideration, connecting, and caring for. These categories formed the basis of the core category ‚Corroborating‛. Corroborating deals with support and interaction. Empirical ethics and normative ethics are intertwined, according to the findings of this study (IV). Normative ethics influence the nurse’s practical performance and could have a greater influence in supporting nurses as professionals. Criteria of good ethical care according to this thesis are: showing respect, invitation to participation, allowing self-determination, and providing safe and secure care. These criteria are elements of the concept of being professional. Professionalism of nurses is shown by: the approach nurses adapt to the performance of their duties, and their competence and knowledge, but also how they apply laws and professional codes
  • Ziegert, Kristina (författare)
  • Everyday Life among Next of Kin of Haemodialysis Patients
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Everyday life can be complex when next of kin of haemodialysis patients are preoccupied with taking care of the patient and his/her health, which implies the difficulties and requirements needed. The general aim of this thesis was to explore and describe everyday life among next of kin of haemodialysis patients with focus on the life situation, health, time and professional support. Two perspectives of the thesis was applied: a holistic perspective on the everyday life of next of haemodialysis patient and a social perspective with focus on human communication and understanding of next of kin’s experience of everyday life. A qualitative descriptive and explorative design, comprising a phenomenographic and content analysis was used in Studies I-IV. The data collected in the studies consisted of interviews with next of kin to haemodialysis patient and analysis of professional support for next of kin to chronic haemodialysis patients in nursing documentation from two hospitals in Sweden. The experience of time in everyday life among next of kin of haemodialysis patients demonstrated that time for them is minimised and life space contracted. Next of kin experienced ambivalence towards their own health, especially in cases of patients’ spouses When next of kin of haemodialysis patient’s became involved in the patients’ care, they experienced arduousness in relation to their own health as well as less uninterrupted time for themselves in everyday life, and their life situation was characterised by confinement and social isolation. They were aware of the prognosis of renal disease and the fact that haemodialysis is a life-sustaining treatment, which forced them to live for the moment. The everyday life among the next of kin changed when the family became involved in the care, which in turn lead to a changed life situation and restrictions in everyday life. Lack of knowledge in nursing documentation of professional support revealed necessity of the readiness of next of kin. It is therefore important to be familiar with this in the nursing process, especially when the patient and their next of kin need support and attention in everyday life.Original papers not included.
  • Aardal-Eriksson, Elisabeth (författare)
  • Salivary cortisol and posttraumatic stress reactions : methodological and applied studies before and after trauma
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)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.
  • Abate, Ebba (författare)
  • The impact of helminth infection in patients with active tuberculosis
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt)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.
  • Abdalla, Maie (författare)
  • Cancer and reconstructive surgery in Inflammatory bowel disease
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt)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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