| 1. |
- Ask, Per, 1950-
(författare)
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Oesophageal manometry : design and evaluation of measurement systems
- 1978
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to investigate the technical characteristics of oesophageal manometry systems and to improve the performance of these systems.The investigation of the characteristics of oesophageal manometry systems with non-perfused catheters or catheters perfused with a flow generated by a syringe pump did not show properties which fullfilled the requirements for accurate pressure measurements. The bandwidth of the pressure mesurement system was limited by the high compliance of the syringe perfusion pump. The characteristics of perfused systems were improved by the design of a low-compliance perfusion pump. The frequency characteristics of a pressure measurement system utilizing the low-compliance perfusion pump seemed to be determined by the properties of the cathetermanometer system. The frequency content of oesophageal peristaltic pressure was studied by use of a measurement system including the low-compliance perfusion pump. This investigation showed that a bandwidth of about 8 Hz or more is necessary for accurate measurements, which bandwidth can only be obtained with a low-compliance system. In a clinical study a non-perfused system and a system perfused with a syringe pump were compared simultaneously to a system with the low-compliance perfusion pump. The non-perfused system and the system perfused with the syringe pump gave lower peristaltic and sphincter pressure amplitudes than the system with the low-compliance perfusion pump. Since the oesophageal sphincter pressure varies in different radial directions, a pressure transducer has been devised, the mechanical design of which gives an integration of a radial pressure profile. The transducer has a linear static and dynamic transfer function.
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| 2. |
- Hellgren, Johan, 1966-
(författare)
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Compensation for hearing loss and cancellation of acoustic feedback indigital hearing aids
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of integrated circuits during the last decades has made it possible to incorporate digital signal processing in hearing aids that fit into the ear canal and are powered by small zink-air batteries. The digital signal processing provides new possibilities for the hearing aid to modify the signal to fit the impaired ear. A linear phase filter bank that is intended as a basic building block of the signal processing in digital hearing aids is introduced in this dissertation. The filterbank is computationally very efficient and divides the input signal into a number of narrow band signals for further signal processing. The filter bank was combined with band specific gains and two compressors to form the signal processing of a hearing aid. The compressors allow leveldependent gain. Three alternative fitting strategies used to adjust the characteristics of this hearing aid to the individual hearing impaired listener were evaluated. The three fitting strategies differed mainly in the characteristics of the compressors. The strategies were evaluated by hearing impaired subjects in a field test and in laboratory tests. When the subjects were grouped according to their preference among the fitting strategies, the results showed significant differences in the hearing loss configuration between the groups.One of the main tasks of a hearing aid is to amplify the signal to make it audible for the hearing impaired user. The maximum gain that can be used in a hearing aid will be controlled by the feedback from the output to the microphone, as the hearing aid will be a part of a closed loop system. The feedback path depends on several factors such as the position of the microphone (differs between hearing aid categories), size of vent, and the acoustics around the hearing aid. The feedback, and thus the maximum gain that can be used in a hearing aid, has been identified with a number of different hearing aids in a number of conditions that can be expected when the hearing aid is used under real-life conditions.Feedback cancellation can be used to reduce the negative effects of feedback on the performance of the hearing aid. An internal feedback in the hearing aid that is an estimate of the external feedback is then used to cancel the feedback signal. The external feedback path will vary as the hearing aid is used ( e.g. when a telephone set is placed by the ear). It is thus desirable to continuously identify the feedback path. One approach to do this is to utilize closed loop identification with the direct method and some recursive identification method. The output and input signals of the hearing aid are then considered as input and output signal of the system to be identified, i.e. the feedback path. An advantage with this method is that the identification can be done without modifying the output signal. A drawback is that the estimate may be biased, depending on the characteristics of the input signal. A difference from many other closed loop identification problems is that the data used for identification will depend on previous estimates of the system. A feedback cancellation algorithm where Filtered-X LMS is used with the direct method has been analyzed. Filtered-XLMS is computationally efficient and gives a possibility to incorporate known characteristics of the feedback path in the model set used. Prefiltering was also used in the algorithm as it can provide an unbiased estimate if the spectrum of the input signal is known.
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| 3. |
- Hällgren, Mathias, 1972-
(författare)
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Hearing and cognition in speech comprehension. Methods and applications
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Central auditory processing is complex and can not be evaluated by a single method. This thesis focuses on assessment of some aspects of central auditory functions by the use of dichotic speech tests and cognitive tests that tax functions important for speech processing.Paper A deals with the cognitive effects in dichotic speech testing in elderly hearing-impaired subjects. It was found that different listening tasks in the dichotic tests put different demands on cognitive ability, shown by a varying degree of correlation between cognitive functions and dichotic test parameters. Age-related cognitive decline was strongly connected with problems to perceive stimuli presented to the left ear.Paper B presents a new cognitive test battery sensitive for functions important for speech processing and understanding, performed in text, auditory and audiovisual modalities. The test battery was evaluated in four groups, differing in age and hearing status, and has proven to be useful in assessing the relative contribution of different input-modalities and the effect of age, hearingimpairment and visual contribution on functions important for speech processing.In Paper C the test battery developed in Paper B was used to study listening situations with different kinds of background noise. Interfering noise at +10 dB signal-to-noise ratio has significant negative effects on performance in speech processing tasks and on the effort perceived. Hearing-impaired subjects showed poorer results in noise with temporal variations, and elderly subjects were more distracted by noise with temporal variations, especially by noise with meaningful content. In noise, all subjects, particularly those with impaired hearing, were more dependent upon visual cues than in the quiet condition.Hearing aid benefit in speech processing with and without background noise was studied in Paper D. The test battery developed in Paper B was used together with a standard measure of speech recognition. With hearing aids, speech recognition was improved in the background condition without noise and in the background condition of ordinary speech. Significantly less effort was perceived in the cognitive tests when hearing aids were used, although only minor benefits of hearing aid amplification were seen. This underlines the importance of considering perceived effort as a dimension when evaluating hearing aid benefit, in further research as well as in clinical practice.The results from the studies contribute to the knowledge about speech processing but also to the search for more specific evaluation of speech understanding, incorporating both sensory and cognitive factors.
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| 4. |
- Johansson, Magnus, 1973-
(författare)
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On noise and hearing loss : Prevalence and reference data
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Noise exposure is one of the most prevalent causes of irreversible occupational disease in Sweden and in many other countries. In hearing conservation programs, aimed at preventing noise-induced hearing loss, audiometry is an important instrument to highlight the risks and to assess the effectiveness of the program. A hazardous working environment and persons affected by it can be identified by monitoring the hearing thresholds of individual employees or groups of employees over time. However, in order to evaluate the prevalence of occupational noise-induced hearing loss, relevant reference data of unexposed subjects is needed.The first part of this dissertation concerns the changes in hearing thresholds over three decades in two occupational environments with high noise levels in the province of Östergötland, Sweden: the mechanical and the wood processing industries. The results show a positive trend, with improving median hearing thresholds from the 1970s into the 1990s. However, the hearing loss present also in the best period, during the 1990s, was probably greater than if the occupational noise exposure had not occurred. This study made clear the need for a valid reference data base, representing the statistical distribution of hearing threshold levels in a population not exposed to occupational noise but otherwise comparable to the group under study.In the second part of the dissertation, reference data for hearing threshold levels in women and men aged from 20 to 79 years are presented, based on measurements of 603 randomly selected individuals in Östergötland. A mathematical model is introduced, based on the hyperbolic tangent function, describing the hearing threshold levels as functions of age. The results show an age-related gender difference, with poorer hearing for men in age groups above 50 years.The prevalence of different degree of hearing loss and tinnitus is described for the same population in the third part of the dissertation. The overall prevalence of mild, moderate, severe or profound hearing loss was 20.9% collectively for women and 25.0% collectively for men. Tinnitus was reported by 8.9% of the women and 17.6% of the men. Approximately 2.4% of the subjects under study had been provided with hearing aids. However, about 7.7% were estimated to potentially benefit from hearing aids as estimated from their degree of hearing loss.Noise-induced hearing loss primarily causes damage to the outer hair cells of the inner ear. The fourth and last part of the dissertation evaluates the outer hair cell function, using otoacoustic emission measurements (OAE). Prevalence results from three different measuring techniques are presented: spontaneous otoacoustic emissions (SOAE), transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). Gender and age effects on the recorded emission levels were also investigated. Women showed higher emission levels compared to men and for both women and men the emission levels decreased with increasing age. The results from the OAE recordings were shown to be somewhat affected by the state of the middle ear. The study included tympanometry, and the relation of the outcome ofthis test to the otoacoustic emissions is described, where high middle ear compliance resulted in low emission level. Reference data for the tympanometric measurements are also presented.The results of this project form an essential part of the important work against noiseinduced hearing loss, which needs continuous monitoring. The reference data presented here will provide a valid and reliable data base for the future assessment of hearing tests performed by occupational health centres in Sweden. This data base will in turn prove useful for comparison studies for Sweden as a responsible fellow EU member country setting high standards for work force safety. The statistical distribution of hearing threshold levels as a function of age for men and women in tabulated form is available on the Swedish Work Environment Authority (Arbetsmiljöverket) web site: http://www.av.se/publikationer/bocker/fysiskt/h293.shtm.
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| 5. |
- Larsby, Birgitta, 1950-
(författare)
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Different neurophysiological methods for studying the vestibular system : evaluation of old methods and development of a new test procedure
- 1980
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Different methods were used to study the physiology and anatomy of the vestibular system. 1) A primary vestibular cortical area in the cat was located and tested for somatosensory inflow by recordings of vestibular evoked potentials and extracellular single unit activity. 2) The enzyme horseradish peroxidase was used as a retrograde anatomical tracer to identify thalamo-cortical vestibular pathways. 3) Vestibular disturbances aused by the industrial solvents methylchloroform and styrene were recorded by electro-oculography. Positional nystagmus was seen above a concentration of 75 ppm of methylchloroform and 40 ppm of styrene in blood. 4) A clinical vestibular rotatory test procedure is described and evaluated in an animal model before and after unilateral labyrinthectomy. A long time reduction in gain is seen at higher rotational frequencies and a trend that serves to define the side of a peripheral lesion is superimposed on the oscillatory eye movements after unilateral vestibular damage.
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| 6. |
- Lövsund, Per, 1948-
(författare)
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Biological effects of alternating magnetic fields with special reference to the visual system
- 1980
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the present investigation were to contribute to more knowledge of the interaction between extremely low frequency magnetic fields and excitable tissue and to widen the basic understanding of the mechanisms behind these effects. The human visual system and the frog retina were used as model systems.In order to ensure that industrial magnetic flux densities and frequencies were employed in the laboratory studies, the magnetic field levels in the welding and electrosteelindustries at the site ordinarily occupied by the operator were first measured. These processes usually generated fields with a frequency of 50 Hz and a magnetic flux density of 01-10 mT. In the laboratory magnetic fields (0-40 mT, 10-50Hz) were used to induce visual light phenomena, so-called magnetophosphenes, in volunteers. The threshold values for these phosphcnes were detennined as functions of magnetic field frequency as well as of colour and intensity of the background illumination. Maximum field sensitivity occurred at a frequency of approximately 20-30 Hz. With broad spectrum light the threshold flux density was about 10-12 mT. The thresholds were found to be dependent upon the intensity and the spectral distribution of the background light. During dark-adaptation the magnetic field sensitivity decreased. In certain respects volunteers with normal colour vision differed from colour defective ones as far as threshold values are concerned. Possible mechanisms for generation of magnetophosphenes are discussed. The threshold values for magnetophosphenes (0-40 mT) and electrophosphenes (0-0.3 mA) were compared under otherwise identical experimental conditions. In both broad spectrum and monochromatic background lighting the two types of phosphenes had a concurring sensitivity maximum at 20Hz. At higher frequencies there were significant differences in the threshold values. Applying electric current stimulation in different directions did not give rise to any great differences with regard to threshold values within the frequency range 10-30Hz. Frog retinas were exposed to magnetic fields (0-80 mT, 20-30 Hz). The electrical activity in the retina induced by the fields was registered from the ganglion cell layer with the aid of microelectrode technique, whereby a threshold value was obtained at approximately 20 mT and a sensitivity maximum was found at 20 Hz. The magnetic field response occurred within approximately 5 ms, while the light stimulus response occurred only after an average of approximately 85 ms. The latency from light stimulus to response in the ganglion cell layer was significantly prolonged if the preparation was simultaneously and continuously exposed to a magnetic field. Magnetic stimuli similar to light stimuli only induced a response upon 'on', 'off or 'on/off and not during continuous stimulation. Cells which were on-cells during light stimulation became off-cells during magnetic stimulation and vice versa. Addition of Na-aspartate or CoCl2 extinguished simultaneously the response both to light and to magnetic field stimuli. The results indicate that magnetophosphenes are generated in the retina and in the same channels that normally propagate signals induced by light.
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| 7. |
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| 8. |
- Nilsson, Gert, 1947-
(författare)
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On the measurement of evaporative water loss : methods and clinical applications
- 1977
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The new method for measurement of water loss by evaporation from the skin described in paper I, offers a high degree of accuracy and improved sensitivity in comparison with devices reported previously. Rapid recordings can be made by technically untrained persons both in clinical departments and in the laboratory.Using this method, the average insensible perspiration from the skin of healthy adult subjects at rest was found to be 381, 526 and 695 gr per day at ambient temperatures of 22°, 27° and 30°C, respectively. On the head, hands and feet the evaporation rate was high, while on other body surface areas more moderate values were recorded,In a clinical study on newborn infants, a linear relationship between the evaporative water loss from the skin and the ambient humidity was found. At an ambient temperature of 34.5°c and an ambient relative humidity of 50% the average transepidermal water loss was calculated to be 8.1 g/m2h.In burned patients high evaporation rates from about 140 g/m2h to over 220 g/m2h were recorded on the injured skin surfaces. Biological dressings were only slightly permeable to water vapour, while the permeability of the artificial dressings tested was generally high.By recording the rate of increase in vapour concentration in a closed measurement chamber placed over the exposed abdominal cavity during surgery, the water loss by evaporation from wounds and exteriorized viscera was determined. At incisions of minor extent the evaporative water loss was low, while at larger incisions with exteriorized viscera the water loss by evaporation from the wound exceeded the basal cutaneous perspiration of healthy adult subjects.
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| 9. |
- Nilsson, Lena, 1950-
(författare)
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Studies on skin blood flow and evaporative water loss : a bioengineering approach
- 1986
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Skin blood flow (SBF), temperature, evaporative water loss (EWL) and skin conductance (SC) measured during stimulus-response experiments reveal valuable information regarding the skin's regulatory capacity. SBF and EWL play powerful roles in keeping the human body within an adequate temperature range. EWL and SC reflect the thermal and mental state of the subject. SBF, EWL and SC were measured using noninvasive laser Doppler flowmetry, vapour pressure gradient estimation and a DC-voltage method, respectively.Short acoustic stimuli evoked responses in both EWL and SC at the palm; their response amplitudes were strongly correlated (r = 0.87). Both latency and time to the peak of EWL responses were delayed by 1.1 sec and 2.3 sec, respectively, in comparison to SC responses.EWL measurements at the forearm revealed rhythmical variations in the recorded signal. The period was approximately 0.74 sec at rest. At a higher evaporation rate, induced by exercise, a longer period (0.84 sec) was detected. The period was independent of the sex of the subject and ambient temperature, and remained unchanged for repeated measurements on the same subject.In the skin temperature range 12 to 38°C, the relationship between SBF and local temperature, at the thigh, palm and fingertip, was best fitted to exponential equations. For a narrower temperature interval (23 to 36°C), palmar SBF and temperature followed linear equations within subjects. However, a large variability in regression coefficients was revealed between subjects. When SBF values were normalized to room climate level, they correlated strongly to skin temperature values (r=0.88).Radiative cooling (17°C) of the palm from room climate conditions doubled local heat loss and left SBF virtually unchanged. When cold convective air currents (19°C, 0.5 or 1.0 m/s) were applied, SBF decreased to 60 and 53% while heat loss dropped to 68 and 70%. Rewarming after local cooling revealed discrepancies'in the restoration of both SBF and skin temperature between the measurement sites.
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| 10. |
- Nygårds, Mats-Erik, 1944-
(författare)
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Computer-based detection of cardiac arrhythmias : methods and systems
- 1983
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to develop methods and systems which could improve the accuracy or arrhythmia monitoring and analysis of long-term ECGs and eliminate or reduce the need for continuous visual ECG screening. The detection of arrhythmias was based on an automatic classification of heart beats, using waveform features obtained from a basis signals representation. Ventricular fibrillation, a condition in which individual QRS complexes cannot be discerned, was diagnosed from a spectral analysis of the ECG.The methods were put into practice in a computer-based system with the capacity for simultaneous monitoring of eight patients. The accuracy of the system with respect to arrhythmia alarms was studied during ten 24-h periods of clinical routine use, with 55 patients. monitored for a total time of about 1000 h. Seventy percent of the time during which an alarm message should have been present (134 h) a correct alarm was given. An incorrect alarm cause was reported 17% of the time, while 13% of the time no alarm at all was given. The ratio between true and false or incorrect alarms was 3:1.The methods for arrhythmia detection were also utilized in a computer program for offline analysis of long-term ECGs from ambulatory patients. Here, the automatic analysis was combined with a subsequent interactive examination of the analysis results for highest accuracy.
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| 11. |
- Rundquist, Ingemar, 1947-
(författare)
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Cytofluorometry : technique and applications
- 1981
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this investigation were to examine the conditions for rapid fluorescence measurements on cellular material, to improve the performance of measurement systems for microscope fluorometry, and to apply this technique in studies on mast cell biology. Fluorescence fading, a general complication of cytofluorometry, was studied during illumination times in the millisecond range, and a new fading phenomenon characterized by short duration and rapid recovery was described. The findings of the study formed the basis for the construction of two instfurnent systems for microscope fluorometry based on Leitz MPV I and MPV II microscope photometers. Rapid fluorescence measurements were performed by a completely automatic measuring sequence, except forselectionandfocusing of the objects to be measured. Automation was mainly achieved by the integration of computers in the measurement systems, which also resulted in easily interchangeable programdetermined measuring routines and proper data processing and presentation of results. The systems were mainly used for rapid analysis of cell populations. The precision of the measurements was improved by different standardization techniques, and the measuring speed, about 500 cells per h on well prepared specimens, was high enough to permit analysis of relatively large cell populations within a reasonable time.The cytofluorometric technique was applied to studies on the biology of the connective tissue mast cell. Rat peritoneal mast cells were used for this purpose. The proliferation of mast cells was estimated by cytofluorometric measurements of DNA in mast cell populations after staining with the fluorescent dye Hoechst 33258. Formaldehyde-induced fluorescence was used to study the uptake and turnover of dopamine in mast cells in vivo. Measurements of the mast cell content of heparin, a constituent of the mast cell granule matrix, were performed by a combination of microscope fluorometry, which permits visual identification of the cells, and flow cytofluorometry, by which rapid measurements of large populations can be made.
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| 12. |
- Salerud, Göran, 1954-
(författare)
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Laser doppler tissue flowmetry : fiberoptic methods in microvascular research
- 1986
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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
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| 13. |
- Stål, Olle, 1952-
(författare)
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Static and flow cytometry for tumor DNA analysis
- 1989
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 14. |
- Sundqvist, Tommy, 1949-
(författare)
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Probing intestinal permeability in man using different-sized, low-molecular-weight polyethyleneglycols and mathematical modelling
- 1981
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 15. |
- Tenland, Torsten, 1952-
(författare)
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On laser Doppler flowmetry : methods and microvascular applications
- 1982
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 16. |
- Åhlfeldt, Hans, 1955-
(författare)
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Computer-based modeling and simulation in the analysis of cardiac arrhythmias and cardiac pacing
- 1989
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 17. |
- Jonasson, Lise-Lotte
(författare)
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A comprehensive picture of ethical values in caring encounters, based on experiences of those involved : Analysis of concepts developed from empirical studies
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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
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| 18. |
- Ziegert, Kristina
(författare)
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Everyday Life among Next of Kin of Haemodialysis Patients
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 19. |
- 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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| 20. |
- 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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| 21. |
- 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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| 22. |
- 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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| 23. |
- Abelius, Martina, 1980-
(författare)
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Immunological interactions between mother and child during pregnancy in relation to the development of allergic diseases in the offspring
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Pregnancy and allergic disease have both been postulated as T-helper 2 (Th2) phenomena. Thus, the increased propensity of allergic mothers to mount Th2-responses might generate favourable effects on the maintenance of pregnancy, but might also be unfavorable, as fetal exposure to a strong Th2 environment could influence the immune development in the offspring to a Th2-like phenotype, favouring IgE production and possibly allergy development later in life. The influence of the intrauterine environment on the immunity and allergy development in the offspring needs to be further investigated.Aim: The aim of this thesis was to explore the Th1/Th2 balance in allergic and non-allergic women during pregnancy and its influence on the shaping of the Th1/Th2 profile in the neonate and the development of allergic diseases in the offspring.Material and methods: The study group included 20 women with and 36 women without allergic symptoms followed during pregnancy (gestational week 10-12, 15-16, 25, 35, 39) and 2 and 12 months postpartum, and their children followed from birth to 6 years of age. The circulating Th1-like chemokines CXCL9, CXCL10, CXCL11, Th2-like chemokines CCL17, CCL18 and CCL22, and the allergen-induced secretion of interleukin-4 (IL-4), IL-5, IL-10, IL-13, Interferon-γ (IFN-γ), CXCL10 and CCL17 were measured by Luminex and ELISA. The allergen-specific and total IgE levels were quantified using ImmunoCAP Technology. mRNA expression of Th1-, Th2-, Treg- and Th17-associated genes were measured by PCR arrays and real-time PCR.Results: We found that sensitised women with allergic symptoms had increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy as compared with postpartum. The non-sensitised women without allergic symptoms had elevated cat-induced IL-5 and IL-13 responses and lower birch- and cat-induced IFN-γ during pregnancy, but similar IgE levels as compared with postpartum.Maternal total IgE levels during and after pregnancy correlated with cord blood (CB) IgE and CCL22 levels (regardless of maternal allergy status). Circulating CXCL11, CCL18 and CCL22 levels during pregnancy and postpartum correlated with the corresponding chemokine levels in the offspring at various time points during childhood. Maternal IL-5 expression in peripheral blood mononuclear cells (PBMC) was associated with neonatal Galectin-1, and placental p35 expression was negatively associated with neonatal Tbx21 expression. Increased mRNA expression of CCL22 in cord blood mononuclear cells (CBMC), and increased CCL17 and CCL22 levels in CB were observed in children later developing allergic symptoms and sensitisation as compared with children who did not. Development of allergic symptoms and sensitisation were associated with increased total IgE, CCL17, CCL18 and CCL22 levels during childhood.Conclusions: Maternal allergy was associated with a pronounced Th2 deviation during pregnancy, shown as increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy, possibly exposing their fetuses to a particular strong Th2 environment during gestation.Correlations were shown between the maternal immunity during pregnancy and the offspring’s immunity at birth and later during childhood, indicating an interplay between the maternal and fetal immunity.Allergy development during the first 6 years of life was associated with a marked Th2 deviation at birth and a delayed down-regulation of this Th2-skewed immunity during childhood.
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| 24. |
- Aboulaich, Nabila, 1976-
(författare)
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Expanding role of caveolae in control of adipocyte metabolism : proteomics of caveolae
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The primary function of adipose tissue is to store energy in the form of triacylglycerol, which is hydrolyzed to fatty acids to supply other tissues with energy. While insulin promotes the storage of triacylglycerol, catecholamines stimulate its hydrolysis. The development of type II diabetes is strongly associated with obesity, indicating a role of triacylglycerol metabolism in the pathogenesis of diabetes. Caveolae are plasma membrane invaginations found in most cells but are highly abundant in adipocytes. Insulin receptors are localized in caveolae and their function depends on intact caveolae structures. In the present thesis work, mass spectrometry-based methodology allowed identification of a number of new proteins and their posttranslational modifications in caveolae of human adipocytes. Variable N-terminal acetylation and phosphorylation of caveolin-1α and caveolin-1β were identified, which might regulate the function of caveolae. The transcription regulator protein PTRF was identified as the major caveolae associated protein. Specific proteolytic modifications of PTRF at the cytosolic surface of caveolae and phosphorylation on nine serine and one threonine residues were identified. Moreover, insulin induced translocation of PTRF from the plasma membrane to the nucleus. PTRF was previously shown to regulate the activity of both RNA polymerase I and polymerase II, thus a role of PTRF in mediating the anabolic action of insulin on protein synthesis and gene transcription is proposed.PTRF was also involved in an extranuclear function in the hormonal regulation of triacylglycerol metabolism in caveolae. PTRF was colocalized with the triacylglycerol regulator proteins perilipin and hormone-sensitive lipase (HSL) in the triacylglycerol-synthesizing caveolae subclass. We showed that, while perilipin was translocated to the plasma membrane, both PTRF and HSL were translocated from the plasma membrane to the cytosol as a complex in response to insulin. The perilipin recruited to the plasma membrane was highly threonine phosphorylated. By mass spectrometry, three phosphorylated threonine residues were identified and were located in an acidic domain in the lipid droplet targeting domain of perilipin. The insulin-induced recruitment of perilipin to the plasma membrane might, therefore be phosphorylation-dependent. Isoproterenol, which stimulates hydrolysis of triacylglycerol, induced a complete depletion of perilipin B from the plasma membrane, suggesting a function of perilipin B to protect newly synthesized triacylglycerol in caveolae from being hydrolyzed by HSL. The location of PTRF and HSL was not affected by isoproterenol, indicating that insulin is acting against a default presence of PTRF and HSL in caveolae.Taken together, this thesis expands our knowledge about caveolae and provided valuable information about their involvement in novel roles, particularly in the hormonal regulation of triacylglycerol metabolism.
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| 25. |
- Abrahamsson, Thomas, 1968-
(författare)
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Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle. Activation of the immune system by microbes early in life is probably required for an accurate maturation of the immune system. Probiotics, live bacteria which are considered to confer health when ingested, have been suggested to prevent eczema and sensitisation infants.Aim: The general aim of this thesis was to assess the effect of oral supplementation with the probiotic bacterium Lactobacillus reuteri (L. reuteri) in infancy on the development of allergic disease and sensitisation during the first 2 years of life and to examine mechanisms possibly underlying eventual effects on allergic manifestations.Subjects: The thesis is based on results obtained from a prospective double-blind placebo-controlled multicenter trial, comprising 232 families with allergic disease, of whom 188 completed the study.Methods: The families were recruited at the antenatal clinic, and the mothers received L. reuteri ATCC 55730 (1 x 108 colony forming units) or placebo daily from gestational week 36 until delivery. Their babies then continued with the same study product from birth until 12 months of age and were followed up for another year. The primary outcomes were allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, employing conventional cultivation methods. Cytokines and IgA antibodies were analysed in colostrum and mature milk from the mothers with ELISA, and Na/K- ratio in breast milk with ion selective electrodes. Circulating Th1/Th2-associated chemokines were analysed in cord and peripheral blood in the infants with Luminex or ELISA technique.Results: The incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L. reuteri group had a lower cumulative incidence of IgE-associated allergic disease, 20% versus 35% (p=0.04), and less IgE-associated eczema during the second year, 8% versus 20% (p=0.02). The prevalence of L. reuteri was higher during the first year of life in stool samples from infants, as well as in colostrum, in the active as compared to the placebo treated group. Colostrum from L. reuteri supplemented mothers had lower levels of TGF-β2, and low levels of this cytokine were associated with less sensitisation. Low Th1- and high Th2-associated chemokine levels preceded allergic disease. The presence of L. reuteri in stool was associated with lower levels of the Th2-associated chemokines CCL17 and CCL22 and higher levels of the Th1-associated CXCL11.Conclusion: Although a preventive effect of probiotics on infant eczema was not confirmed, the L. reuteri treated infants had lower incidence of IgE-associated allergic disease at two years of age, and therefore possibly run a reduced risk to develop later respiratory allergic disease. The mechanisms underlying this effect require further elucidation.
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| 26. |
- Abtahi, Jahan, 1965-
(författare)
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Bisphosphonates and implants in the jaw bone
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention.The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model?In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage.In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption.
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| 27. |
- Abu-Zidan, Fikri M.
(författare)
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Role of platelet-activating factor in sepsis and shock : an experimantal study
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To study the role of platelet-activating factor (PAF) on cardiovascular and pulmonary dysfunction in sepsis and shock.Design: Experimental study. Setting: Trauma research unit, university department of surgery, Sweden.Material: 76 juvenile domestic pigs. Interventions: The effects of a specific PAF receptor antagonist (BB-882) on haemodynamics and on PAF-induced haemodynamic changes were studied (n = 16). BB-882 was given as pretreatment in non-hypotensive Escherichia coli endotoxaemia (n = 9), during resuscitation after severe haemorrhagic shock (n = 7), hefore post-ischaemic shock which was induced by clamping the aorta above the coliac axis for 45 minutes (n = 8), and as pretreatment in post-haemorrhage septic shock: (n = 6). BB~882 groups were compared with controi groups having the same number of animals which received vehicle instead.Major outcome measures: Heart rate, intravascular pressures, cardiac output, pulmonary and systemic vascular resistance, arteriai blood gas tensions, lung thorax compliance, serum lactic acid and blood sugar concentrations, and packed cell volume.Results: BB-882 effectively counleracted the PAF-induced response on the mean systemic and pulmonary arteriai pressures. lt reduced the rise in pulmonary and systemic vascular resistance and improved the cardiac output in non-hypotensive and post-haemorrhage septic shock when given as pretreatment. lt reduced the hypertension in non-hypotensive sepsis and the hypotension in post-haemorrhage septic shock. BB-8B2 did not infiuence the endotoxin-induced hypoxia or reduced lung thorax compliance in non-hypotensive sepsis and post-haemorrhage septic shock. It did not improve the mean arterial pressure or the cardiac output in haemorrhagic shock alone but it reduced the systemic vascular resistanc'e and was associated with tachycardia and acidosis. It did not affect the post-ischaemic shock after clamping the aorta.Conclusion: PAF is a major mediator of the cardiovascular, but not pulmonary dysfunction in sepsis whether associated with shock or not, while its role on the cardiovascular dysfunction in haemorrhagic and post-ischaemic shock is small.
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| 28. |
- Addelyan Rasi, Hamideh, 1975-
(författare)
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Empowering Women in the Middle East by Psychosocial Interventions : Can provision of learning spaces in individual and group sessions and teaching of coping strategies improve women’s quality of life?
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: This study set out to construct a conceptual framework that can be used in social work with women in the Middle East and other settings where women have limited access to resources, which, as a result, limits their decision-making capacity. The framework has both an empirical and a theoretical base. The empirical base comprises data from two intervention projects among Iranian women: single mothers and newly married women. The theoretical base is drawn from relevant psychological and social work theories and is harmonized with the empirical data. Psychosocial intervention projects, based on learning spaces for coping strategies, were organized to assess if Iranian women could use a problemsolving model (i.e. focused on cognition and emotion simultaneously) to effectively and independently meet challenges in their own lives and improve their quality of life.Methods: Descriptive qualitative and quasi-experimental quantitative methods were used for data collection and analysis. Forty-four single mothers and newly married women from social welfare services were allocated to nonrandomized intervention and comparison groups. The intervention groups were invited to participate in a 7-month psychosocial intervention; the comparison groups were provided with treatment as usual by the social welfare services. The WHOQOL-BREF instrument was used to measure quality of life, comparing each intervention groups’ scores before and after the intervention and with respective comparison groups. In addition, content analysis and constant comparative analysis were performed on the qualitative data collected from the participants before, during and after the intervention.Results: The results of the quasi-experimental study show significant and large effect sizes among the women exposed to the intervention. Small and not statistically significant effect sizes were observed in the women provided with traditional social welfare services. Accordingly, teaching coping strategies can be a means to improve the quality of life of women in societies where gender discrimination is prevalent. The qualitative findings from the Iranian projects illustrate a process of change —socio-cognitive empowerment— with regard to thinking, feeling and acting among women during and after the intervention. The women developed a number of mental capacities essential to coping and life management. All women used the model effectively, and consequently, made more deliberate decisions to improve their life situations.Conclusion: The practical lessons from the Iranian projects highlight the possibilities of empowering women through fostering mindfulness and deliberate decision making as well as achieving consciousness. This study provides provisional evidence that psychosocial intervention projects, based on learning spaces for coping strategies, can help many clients to achieve their goals and improve their quality of life, and that this psychosocial intervention project can be a useful model for social work practice with women in the Middle East. The conceptual framework can help social workers to bridge the gap between theory and practice: that is, to draw from existing social work theories and, through the psychosocial intervention model, better apply this knowledge in their practical work with women in challenging social environments.
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| 29. |
- Adell, Gunnar, 1953-
(författare)
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Indicators of colorectal cancer prognosis and response to preoperative radiotherapy
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer is one of the three most common malignant diseases in Sweden, with about 5,000 new cases each year. Thirty-five percent of these are rectal cancer, for which local recurrence after surgery has been a serious problem. The five-year survival rate in colorectal cancer has improved from about 40% in 1960 to 55% in 1995. Adjuvant chemotherapy of colon cancer, preoperative radiotherapy and improved surgical techniques in rectal cancer have contributed to the improved results. To select patients best suited for pre- or postoperative therapy, we need indicators of both prognosis and response to therapy.Using antibodies against cytokeratin, we found that 39% of patients with colorectal carcinoma that had penetrated the muscularis propria but without lymph-node metastases by routine light microscopy, had got micrometastases. Survival among patients with micrometastases was not significantly different from that among patients without such metastases.We also identified subsets of tumour-infiltrating mononuclear cells and studied their pattern of distribution in relation to regressive tumour areas and Dukes class. Our interpretation is that the subsets of tumourinfiltrating mononuclear cells change with advancing Dukes class, indicating gradual deterioration of the local immune control.We also investigated the interaction between p53, Ki-67, apoptosis and the outcome in rectal cancer with and without short-term preoperative radiotherapy. The expression of nuclear p53 protein seemed to be a significant predictive factor for local treatment failure after preoperative radiotherapy. Low tumour cell proliferation measured with Ki-67 in the preoperative biopsy correlated with improved local control and disease-free survival after preoperative radiotherapy.High apoptotic index was associated with improved local control of rectal cancer even without pre-operative radiotherapy, whereas local control of tumours with low and intermediate apoptotic index was significantly improved by preoperative radiotherapy.In conclusion, micrometastases in regional lymph nodes are an interesting phenomenon but with limited prognostic value. The subsets of tumour-infiltrating mononuclear cells change with advancing Dukes class, and its seems that the local immune control is gradually broken down. In rectal cancer, p53 expression, tumour proliferation measured with Ki-67 and apoptotic index seem to be interesting indicators of rectal cancer prognosis and response to preoperative radiotherapy.
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| 30. |
- Adolfsson, Annsofie, 1960-, et al.
(författare)
-
Miscarriage : women’s experience and its cumulative incidence
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many women experience miscarriage every year. Every fourth woman who has given birth reports that she has previous experience of miscarriage. In a study of all women in the Swedish Medical Birth Register 1983-2003, we found that the number of cases of self reported miscarriage had increased in Sweden during this 21 year period. This increase can be explained by the introduction of sensitive pregnancy tests around 1990, as well as an increase in the mean age of the mothers, by approximately 3 years, during the observation period. The risk of miscarriage is 13% with the first child. With subsequent pregnancies, the risk of miscarriage is 8%, 6% and 4% with the second, third and fourth child, respectively.Thirteen of these women who had suffered a recent miscarriage were interviewed four months later, and their feelings of guilt and emptiness were explored. Their experience was that they wanted their questions to be answered, and that they wanted others to treat them as the mothers to be that they felt themselves to be. They also experienced the need for time to grieve their loss.Measurement of grief by means of the Perinatal Grief Scale (PGS) is used in research but has also been proposed for clinical use. We have translated this psychological instrument to Swedish, back-translated and tested it in a small pilot study. In a randomized controlled study, women with early miscarriage were allocated, either to a structured visit (study group) or a regular visit (control group) to a midwife. The structured visit was conducted according to the Swanson caring theory. We could conclude that the structured visit had no significant effect on grief compared to the regular visit, as measured using the PGS. However, women with the sub-diagnosis missed abortion have significantly more grief four months after early miscarriage, regardless of visit type.We also performed a content analysis of the tape-recorded structured follow-up visit. The code-key used was Bonanno and Kaltman’s general grief categorization. Women’s expression of grief after miscarriage was found to be very similar to the grief experienced following the death of a relative. Furthermore, the grief was found to be independent of number of children, women’s age, or earlier experience of miscarriage.Conclusions: Every fourth woman who gives birth reports that she has also experienced early miscarriage. The experience of these women is that they have suffered a substantial loss and their reaction is grief similar to that experienced following the death of a relative.
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| 31. |
- Adolfsson, Emelie, 1985-
(författare)
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Lithium formate EPR dosimetry for accurate measurements of absorbed dose in radiotherapy
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lithium formate has shown to be a material with properties suitable for electron paramagnetic resonance (EPR) dosimetry, among them up to 7 times higher sensitivity compared to alanine, which is a well-established EPR detector material for dose determinations in radiotherapy.The aim of this thesis was to further investigate the properties of lithium formate and develop the dosimetry system towards applications in radiotherapy. The intrinsic efficiency for energies of relevance to brachytherapy and the signal stability were investigated. The dosimetry system was expanded to include a smaller dosimeter model, suitable for measurements in dose gradient regions. An individual sensitivity correction method was applied to the smaller dosimeters to be able to perform dose determinations with the same precision as for the larger ones. EPR dosimetry in general is time consuming and effort was spent to optimize the signal readout procedure regarding measurement time and measurement precision.The system was applied in two clinical applications chosen for their high demands on the dosimetry system: 1) a dosimetry audit for external photon beam therapy and 2) dose verification measurements around a low energy HDR brachytherapy source.The conclusions drawn from this thesis were: dose determinations can be performed with a standard uncertainty of 1.8-2.5% using both the original size dosimeters and the new developed smaller ones. The dosimetry system is robust and useful for applications when high measurement precision and accuracy is prioritized. It is a good candidate for dosimetry audits, both in external beam therapy and brachytherapy.
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| 32. |
- Adolfsson, Lars, 1955-
(författare)
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Arthroscopy in the upper extremity
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This stndy comprising six separate papers, is concerned with the techniques of, and bevaluation of arthroscopy as a diagnostic and therapeutic tool in different pathologic conditions in the upper extremity.Arthroscopy proved to increase diagnostic accuracy in 177 examined patients with anterior shoulder instability or shoulder pain. Previously not well described patterns of pathological morphology in the ventral joint capsule after anterior shoulder dislocations were disclosed. A new classification system of rotator cuff pathology to be used for arthroscopy in the subacromial impingement syndrome is suggested. Different stages of rotator cuff pathology were found to influence the clinical results after arthroscopic acromioplasty in 79 patients.An anatomical stndy on 16 cadaver elbows revealed the close proximity between commonly used arthroscopic portals and important neurovascular structures. The usefulness and potential risks of each portal were demonstrated and a preferred procedure for diagnostic elbow arthroscopy was suggested.Wrist arthroscopy was performed in 30 patients with long-standing post-traumatic pain and resulted in increased diagnostic accuracy. In patients where clinical examination and radiography had shown no abnormality, arthroscopy demonstrated serious carpal ligament injuries and related instability.A technique for arthroscopic wrist synovectomy was described in patients with rheumatoid arthritis. In 18 wrists of 16 patients, a reasonably radical synovectomy could be achieved with this atraumatic method. Primary results showed decreased pain and increased grip-strength in all patients and an increased range of motion in some.
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| 33. |
- Adolfsson, Per, 1967-
(författare)
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Regulatory importance of cyclic nucleotides in smooth muscle growth of the urogenital tract
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Smooth muscle hyperplasia/hypertrophy is, if not responsible for, so at least involved in those diseases, which impair life quality for most people in today's society.This thesis, presents a pharmacological investigation, related to the regulatory role of cyclic nucleotides, of smooth muscle hyperplasia/hypeitrophy in human uterine leiomyoma and benign prostate hyperplasia (BPH).Four main aspects, with cAMP as a connecting thought, have been analyzed, namely expression and characterization of the adrenergic receptors (AR), determination of adenylyl cyclase (AC)- and phosphodiesterase (PDE)-activity, and finally the connection between mentioned issues and proliferation of cultured smooth muscle cells (smc).In the frrst paper, characterization of the a 2-adrenergic receptor (az-AR) subtypes in human myometrium at term pregnancy was examined by combining radioligand binding-studies with reverse transcriptase-polymerase chain reaction (RT-PCR). Results demonstrated a significant eo-expression of α2A and α2B, and a weak indication of the α2C-AR, which however was identified at the mRNA level by the RT-PCR analysis.In the next investigatio~ smooth muscle tissue of human uterine leiomyoma (benign smooth muscle tumor) was compared with surrounding myometrial tissue (control). The expression of AR, AC- and PDE-activity was analyzed, as well as the effect of cAMP with respect to growth regulation of cultured leiomyoma smc. Primarily, a significantly reduced ß2-AR expression and AC-activity was detected in leiomyoma compared to control tissue, whereas the PDE-activity was approximately 100% higher. In addition, the α2-AR population in leiomyoma was slightly increased. When cultured leiomyoma smc was treated with cAMP increasing agents as forskolin, an AC stimulating agent, or papaverin, a general PDE inhibitor, a considerable inhibition of DNA replication and protein synthesis was obtained.In the thh·d paper, a proliferation study was made on cultured benign prostate hyperplasia smc, were the mitogen effect of lysophosphatidic acid (LPA) and cAMP/cGMP increasing agents was investigated. LPA generated a dose-dependent mitogen response, which was efficiently inhibited, both by forskolin, and by papaverin. In addition, sildenafil (Viagra®), which serve as a potent and selective PDE5 inhibitor, also decreased the LPA mediated growth promotion in a dose dependent manner.The last study, demonstrate primarily the expression pattem of LPA receptors (Edg) in BPH smc. Further, the intracellular cAMP changes in LPA stimulated BPH smc and the proliferative effect of the LPA analogue sphingosine 1-phosphate (SIP) was considered. First, all Edg was identified with exception of Edg6. Moreover, the cAMP level was unchanged by LPA per se, whereas co-incubation with forskolin generated a rapid and transient response. Further, SIP generated a divergent response including a LPA equivalent mitogen effect at low concentrations whereas inhibition of DNA replication was obtained at higher concentrations.In summary, this project demonstrates that cyclic nucleotides inhibit smooth muscle hyperplasia/hypertrophy in the luogenital tract. These results also suggest that manipulation of cyclic nucleotide level using tissue specific PDE inhibitors might constitute a new therapeutic approach for hyperplasia/hypertrophy related diseases in the urogenital tract.
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| 34. |
- af Geijerstam, Peder, Doktorand, 1983-
(författare)
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Home Blood Pressure in Health and Disease
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypertension is the most common preventable cause of premature all-cause mortality, primarily from cardiovascular disease (CVD). Individuals with dysglycemia, including prediabetes and diabetes, are at increased risk. Licorice intake raises blood pressure (BP) through the effects of glycyrrhizic acid (GA), but the true limit of safe intake is uncertain. Home BP has several benefits over BP measured at a clinic, including a higher predictive value for CVD. By combining office and home BP, it is possible to diagnose masked hypertension (MH), in which home but not office BP is elevated, and white coat hypertension (WCH), in which office but not home BP is elevated. The aim of this thesis was to advance our knowledge on home BP in relation to dysglycemia, markers of CVD, and licorice intake. The first 3 papers used data from the Linköping cohort of the prospective Swedish CArdioPulmonary bioImage Study (SCAPIS). Study IV was a randomized controlled cross-over study. Data was obtained from questionnaires, blood samples and office and home BP measurements. In studies I-III, pulse wave velocity (PWV), coronary artery calcium score (CACS), and carotid artery plaques as markers of CVD were also included. In Study I, we examined 5025 men and women aged 50-64 years old for the relation between dysglycemia and home BP. Both the systolic office and home BP measurements were positively as-sociated with dysglycemia. Participants with dysglycemia vs normoglycemia more often had MH. The findings were in line with previous research and strengthened the association between dysglycemia and MH. In Study II, we examined the associations between MH and markers of CVD in 4122 individuals without BP-lowering treatment. Of participants, 4.2% had MH, and these were more often men and had higher BMI than those with normotension. Participants with MH also had higher odds for CACS ≥100, an as-sociation which has previously been suggested as a trend.In Study III, we examined the relation between soluble P-se-lectin (sP-selectin) as a measure of thrombotic activity, plasma high-sensitivity C-reactive protein (hsCRP) as a measure of inflammation, and home BP in 4548 participants. Both markers were higher in each hypertension phenotype compared with sustained normotension. The quartile of participants with the highest sP-se-lectin values had higher odds for CACS ≥100 and carotid artery plaques. The association between sP-selectin and sustained hyper-tension was novel and not affected by adjustments for hsCRP. In Study IV, 28 healthy participants aged 18-30 years old were evaluated for the effects of a daily intake of licorice containing 100 mg of GA compared with a control product for 2 weeks. During the licorice intake period, the systolic home BP increased with 3.1 mmHg, and the suppression of serum aldosterone and plasma renin levels indicated that this was due to the licorice intake. In conclusion, this thesis further strengthens the idea that both home and office BP measurements have values beyond that of the other, and that home BP may be most valuable in individuals with dysglycemia and obesity, and in men. Finally, licorice may be more potent than previously known, suggesting the need for increased awareness.
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| 35. |
- af Klercker, Tom
(författare)
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Method for inductive case-based decision support system over the Internet : exemplified by ear, nose and throat diagnostics in primary care
- 1997
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is an example of an ear to loaf process:A Preliminary Essential Data Set (PEDS) for Ear, Nose and Throat (ENT) diagnostics in Primary Health Care (PHC) was established by infologic modelling of existing tractates, between the specialist organisations of ENT and PHC, and four contemporary text-books on the subject (I). The PEDS was then compared to the aggregated data from a sample of case-files from a Swedish PHC centre. The quality of the individual medical record was found to be poor and not sufficient for follow-up and Quality Management (QM) purposes (II). The aggregated data from the case-file sample was processed by an inductive "expert" computer program that generated a decision-tree, based on the total number of decisions (diagnoses) in the data-base. This was nearly identical to the PEDS and somewhat less complicated. Infological modelling of the PEDS and the decision-tree resulted in the proposed Essential Data Set (EDS) for ENT diagnostics in PHC. The decision tree was "pruned" to achieve simplicity and ease of use (III). It was converted into a Computer-aided Decision Support System (CDSS) and put on the Internet using World Wide Web (WWW) tools (IV). This system was then implemented in the Skänninge PHC centre where an Electronic Medical Record System (EMRS) was in everyday use. Due to technical difficulties no integration between the two systems was possible. The CDSS was run on a computer outside the centre and this raised the question of secrecy and security (V). Prior to the implementation, and after a study period of four months attitudes towards, and the acceptance of, new Information Technology (IT) was explored by using focus group methodology (VI). It is important that those who are to use the system are intimately involved in its development. The results showed, that participation of the end-users during implementation is crucial for its acceptance. The need for a uniform and agreed terminology was obvious to facilitate co-operation and QM. The importance of nurses and physicians using the same terminology for documentation, was paramount.
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| 36. |
- Afoke, Anthony Okoro
(författare)
-
Some epidemiological aspects of insulin-dependent diabetes mellitus in Nigeria and Sweden
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the western world diabetes mellitus is one of the most common severe diseases in childhood, but it is rarely seen in black African populations. However, there are very few epidemiological studies of childhood diabetes in Africa and almost nothing is known of the Nigerian population. One aim of this study was therefore to estimate the prevalence of insulin dependent diabetes (IDDM) in children and adolescents and to characterize their type of diabetes.A screening of almost 78,000 school children was performed and beside some already known diabetic patients several new cases were diagnosed. It was found that IDDM is much less common than in Europe but on the other hand more common than in several Asian countries. In addition the prevalence found may be underestimated because of cultural and social factors, health care problems and high mortality in diabetes. Although most patients had a clinical picture of Malnutrition Related Diabetes (MRD) we found in some cases autoantibodies towards islet cells and insulin and furthermore the same HLA-DQ-type-associations as seen to Type 1 diabetes in caucasian diabetics.While we saw no seasonal variation of diagnosis of Nigerian IDDM, there is a pronounced such seasonal variation in Sweden. This study has tried to elucidate whether this seasonal variation is related to any differences in manifestation and clinical course. Patients diagnosed during incidence peaks had more often short duration of symptoms before diagnosis,ketonuria at diagnosis, rapid loss of endogenous insulin secretion but increase of insulin antibodies and of glycosylated haemoglobin. They had also more often infections before diagnosis and high serum immunoglobulins (IgG and IgM) up to 9 months after diagnosis. HLA-DR4 was more common in these patients. The results suggest that IDDM in Swedish children is heterogenous.
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| 37. |
- Afrell, Maria, 1953-
(författare)
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Att leva med en kropp som värker : samtal med fysioterapeuten
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: Physiotherapists in primary care meet, assess and treat patients with long-standing benign musculoskeletal pain. As a clinical condition, long-standing pain is common but nonetheless it is quite complex. The aim of this thesis has been, from a bodily existential perspective, to investigate and conceptualise the experience of living with longstanding benign musculoskeletal pain, and from there, to work out a method for conversation and assessment within non-specialised physiotherapy.Methods: Our first study was an interview study where we applied a phenomenological approach and investigated the ways individuals suffering from long-standing pain experienced their body and their illness. Four aspects of body experience were described, and based on these aspects, four typologies of attitudes to pain were distinguished. In the second study, we made two group interviews with six physiotherapists about their experiences of using, in their clinical work, questions from the interview guide in study I that had given particularly rich responses. Transcripts were analysed using phenomenography. In the third study, patients’ verbal responses to the key questions, directed to them by physiotherapists in clinical situations, were investigated, and the four aspects of body experience from study I formed the concepts of a deductive analysis. In study IV, finally, the key questions and typologies were tried by a larger group (31), and their experiences and the possible applicability of the method were studied by qualitative content analysis combined with the counting of codes.Results: We created four typologies of attitudes to long-standing pain: “Surrendering to one’s fate”, “Accepting by an active process of change”, “Balancing between hope and resignation” and “Rejecting the body”. These typologies, in turn, were based on four aspects of body experience: “The body as an aspect of identity”. “Body reliance”, “Body awareness”, and “Ways of understanding pain”. In study II, by the aid of key questions, patient and physiotherapist managed to have a conversation on bodily existential matters. The physiotherapist learnt to know the patient as a person, a process appeared to be initiated in the patient, and their relation changed. The patient was willing to talk about her body in pain, and had the words to do this. In study III, the key questions opened ways to reflections on body, existence, and biography. The four aspects of body experience were central to the patients’ descriptions. In study IV, the participating physiotherapists reported by large positive experiences from applying key questions and typologies. The patients reflected, emotions were evoked, and the relation and the communication often improved. The typologies helped in giving a comprehensive perspective of the patient’s problem, and to grasp where in the process of rehabilitation the patient was to be found.Conclusions: The method, seven key questions combined with the tentative frame of interpretation of the answers, seemed to be easily applied by interested physiotherapists in non-specialised practice. The application of the method addresses the need of developing the professional role of the physiotherapist. The challenge is to face the whole person, who is her lived body as well as her identity crisis, carried by emotions such as grief and anger. This may inspire the use of the full potential of the physiotherapist’s professional role in the clinical encounter.
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| 38. |
- Agholme, Fredrik
(författare)
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Wnt signaling and metaphyseal bone healing
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis relates to some new aspects on the regulation of bone healing. In the last few years, Wnt-signaling has been shown to play a central role in bone biology. As well as being involved in bone maintenance and repair, Wnt-signaling has been presented as one of the key pathways through which bone responds to mechanical load. Two secreted extracellular inhibitors of Wnt-signaling, sclerostin and dickkopf-1 are potent negative regulators of bone formation.Using a rat fracture model we investigated how metaphyseal bone healing is influenced by changes in Wnt-signaling.Antibodies were used to suppress levels of sclerostin and dickkopf-1, and thereby increase Wnt-signaling. Primarily, we investigated if those antibody treatments lead to improved bone healing. Also, we investigated if the response was coupled to the loading conditions of the bone.Our findings suggest that suppression of either sclerostin or dickkopf-1 leads to increased bone formation and improved bone healing. Apart from just having an effect on healing, the treatment also improved bone formation in other parts of the skeleton. Depending on the loading conditions, the effects were different. Dickkopf-1 appeared to have a stronger effect on bone volume density in unloaded bone, implying a role mainly in mechano-transduction, while sclerostin had similar effect in both loaded and unloaded bone. To confirm these findings, we studied how the expression of several Wnt-related genes changed due to trauma and unloading in metaphyseal bone. We found that trauma led to upregulation of most of the genes with the largest effect seen in the unloaded bone. In untraumatized bone, there was mainly an effect on the sclerostin gene.In conclusion, antibodies against sclerostin and dickkopf-1 appear to be able to improve metaphyseal bone healing. There appear to be some differences in how the effect of the two antibodies manifests itself, especially if the loading conditions of the bone are altered. These findings suggest a potential for clinical use to shorten fracture healing time.
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| 39. |
- Agholme, Lotta
(författare)
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The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although the vast majority of Alzheimer’s disease (AD) cases are of the sporadic type, mutations causing the familial form have been the focus of AD research for decades. The disease is pathologically characterised by β-amyloid (Aβ) and tau protein aggregates in neuritic plaques and neurofibrillary tangles. Furthermore, it is known that AD pathology spreads throughout the brain, most often along the same anatomical pattern. However, so far no cause for the sporadic form of the disease has been found. Accumulation of protein aggregates as well as decreased activity of the protein degradation systems, lysosomes and proteasomes, is found in diseased brains. This indicates that defective degradation contributes to sporadic AD.The aim of this thesis was to develop an improved neuronal model, and study the effects of decreased proteasome function on tau phosphorylation and axonal transport. In addition, the effects on Aβ accumulation and generation upon proteasome inhibition were investigated. Finally, the possibility that intracellularly accumulated Aβ oligomers could be transferred from one neuron to another was tested.Differentiation of human SH-SY5Y neuroblastoma cells in an extracellular matrix gel, using a set of neurotrophic factors, resulted in cells with neuronal phenotype, expressing neuron specific markers and all six adult isoforms of tau. Within this neuronal model, we found that reduced proteasome activity inhibited neuritic transport, and caused tau phosphorylation in a c-Jun and ERK 1/2 dependent manner. Using proteasome inhibition in APP overexpressing cells, we found an autophagy dependent intralysosomal Aβ accumulation, together with elevation of intra- and extracellular concentrations of Aβ. Autophagy inhibition protected the cells from the toxicity induced by decreased proteasome activity. Finally, we could, as the first group, show that Aβ can be directly transferred from one neuron to another through connected neurites. Furthermore, accumulation of Aβ in the endo-lysosomal compartment of receiving cells caused toxicity and neurodegeneration.We believe that cells not able to degrade accumulated Aβ, due to increased generation or reduced degradative capacity, instead tries to clear its content through transfer to connected neurons. If not properly degraded in the receiving cell, this can accelerate AD pathology and cause neuritic and neuronal degeneration spreading throughout the brain. Increasing the activity of the degradative systems, or inhibiting transmission of Aβ between neurons could therefore be novel treatments for AD.
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| 40. |
- Agnafors, Sara, 1981-
(författare)
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A Biopsychosocial and Long Term Perspective on Child Behavioral Problems : Impact of Risk and Resilience
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mental health has become a prominent issue in society. Yet, much remains unknown about the etiology of psychiatric disorders. The aim of the present thesis was to investigate the association between biological, psychological and social factors of risk and resilience and behavioral problems in a birth cohort of Swedish children. 1723 mothers and their children were followed from birth to the age of 12 as part of the South East Sweden Birth Cohort Study (the SESBiC study). Information was gathered through register data, standardized questionnaires and DNA samples.In study I, stability of maternal symptoms of depression and the impact on child behavior at age 12 were investigated. The prevalence of depressive symptoms was found to be 12.0 % postpartum. Symptoms of postpartum depression significantly increased the risk for subsequent depressive symptoms 12 years later in women. Children whose mothers reported concurrent symptoms of depression and anxiety had an increased risk for both internalizing and externalizing problems at age 12, but no long term effect on child behavior was seen for postpartum depressive symptoms. The greatest risk was seen for children whose mothers reported symptoms of depression on both occasions. In study II, the impact of gene-environment interaction of 5-HTTLPR and BDNF Val66Met and experience of life events together with symptoms of maternal depression and anxiety on child behavior at age 12 was studied. A main effect of 5-HTTLPR was noticed, but no geneenvironment effects were shown. Similarly to study I, concurrent symptoms of maternal depression and anxiety were an important predictor of child behavioral problems. A high degree of psychosocial stress around childbirth was found to have long lasting detrimental effects on child behavior, increasing the risk for internalizing problems at age 12. Study III investigated the impact of geneenvironment interactions of 5-HTTLPR and BDNF Val66Met and life events together with symptoms of maternal depression and birth characteristics on behavioral problems at age 3. Symptoms of postpartum depression were found to predict internalizing as well as externalizing problems in children three years later. Child experience of life events was a stable predictor of behavioral problems across the scales similar to sociodemographic factors such as parental immigration status and unemployment. No gene-environment interaction effects of 5-HTTLPR or BDNF Val66Met were shown. Study IV used the risk factors identified in studies I-III to investigate factors of resilience to behavioral problems at age 12. The l/l genotype of 5-HTTLPR was associated with a lower risk for behavioral problems at age 12, especially for children facing low adversity. Good social functioning was found to be a general resource factor, independent of the level of risk, while an easy temperament was associated with resilience for children with a high degree of adversity. However, effect sizes were small.In summary, the results from the present thesis emphasize the importance of maternal mental health and sociodemographic factors for child mental health at ages 3 and 12, which must be taken into account in clinical settings. Moreover, it adds to the null-findings of the gene-environment effect of 5-HTTLPR and BDNF Val66Met on behavioral problems in children, but indicates a main effect of 5-HTTLPR on internalizing symptoms at age 12.
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| 41. |
- Agvall, Björn, 1963-
(författare)
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Heart failure in primary care with special emphasis on costs and benefits of a disease management programme
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim. Heart failure (HF) is a common condition associated with poor quality of life (QoL), high morbidity and mortality and is frequently occurring in primary health care (PHC). It involves a substantial economic burden on the health care expenditure. There are modern pharmacological treatments with evident impact on QoL, morbidity, mortality, and proved to be cost-effective. Despite this knowledge, the treatment of HF is considered somewhat insufficient. There are several HF management programmes (HFMP) showing beneficial effects but these studies is predominantly based in hospital care (HC).The first aim of this thesis was to describe patients with HF in the PHC regarding gender differences, diagnosis, treatment and health related costs (I, II).The second aim was to evaluate whether HFMP have beneficial effects in the PHC regarding cardiac function, quality of life, health care utilization and health care-related costs (III,IV).Methods. The initial study involved retrospective collection of data from 256 patients with symptomatic HF in PHC (I). The data collected were gender, age, diagnostics and ongoing treatment. The second study was an economic calculation performed on 115 patients (II). The economic data was retrospectively retrieved as the number of hospital days, visits to nurses and physicians in HC and PHC, prescribed cardiovascular drugs and performed investigation during retrospectively for one year. The third and fourth study was based on a randomized, prospective, open-label study which was subsequently performed (III,IV). The study enrolled 160 patients with systolic HF who were randomized to either an intervention or a control group. The patients in the intervention group retrieved follow-up of HF qualified nurses and physicians in the PHC, involving education about HF and furthermore, optimizing the treatment according to guidelines if possible. The patients in the control group had a followup performed by their regular general practitioner (GP) receiving customary management according to local routines but there was no contact with HF nurses. The primary endpoint of the study was a composite endpoint consisting of changes in survival, hospitalization, heart function and quality of life (QoL) and to compare differences in resource utilization and costs (III,IV).Results. In the first study, the prevalence was 2% and the average age was 78 years (I). The most frequent cause of HF was IHD followed o hypertension. The diagnosis in the study population was based on clinical criteria and only 31% had been subjected to echocardiography. The most common treatment was diuretics (84%) and angiotensin converting enzyme inhibitors (ACEI) were used in 56% of patients. In the following prospective study, the intervention group had significant improvements in composite endpoints. There were in the intervention group more patients with reduced levels of NTproBNP (p=0.012) and improved cardiac function (p=0.03). No significant changes were found in New York Heart Association (NYHA) functional class or QoL. The intervention involved less health care contacts (p=0.04), less emergency ward visits (p=0.002) and hospitalizations (p=0.03). The total cost for HC and PHC was EUR 4471 in the intervention group and EUR 6638 in the control group which implies a cost reduction of EUR 2167 (33%).Conclusions. HF is common in PHC with a prevalence of 2% the study population had an average age of 78 years. Only 31 % of the HF patients have performed an echocardiographic investigation. Treatment with ACEI occurred in 56 %. Differences were found between genders since women had performed significantly fewer echocardiographic investigations and, had less treatment with ACEI. When implementing HFMP in PHC, beneficial effects were found regarding cardiac function and health care-related costs in patients with systolic HF. These findings indicate that HFMP might be used even in PHC.
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| 42. |
- Ahl, Ing-Marie, 1974-
(författare)
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Protein Engineering of Extracellular Superoxide Dismutase : Characterization of Binding to Heparin and Cellular Surfaces
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Accumulating evidence indicates that oxygen free radicals are involved in many diseases and pathological conditions, such as aging, inflammation, reperfusion damage of ischemic tissue and various cardiovascular diseases. Extracellular superoxide dismutase (ECSOD) thus plays a major role in the maintenance of cells by providing protection against these toxic substances in the extracellular space. Various animal studies have shown that ECSOD has the ability to protect against many of these disorders, and interest has therefore evolved in the potential therapeutic use of the enzyme.However, despite strenuous efforts, large-scale production of the enzyme has not been achieved. To overcome this problem, a mimic of the enzyme, PseudoECSOD, has previouslybeen constructed. This chimera is easy to produce in large amounts and has all the structural, enzymatic and heparin-binding characteristics of ECSOD, making it a potential substitute for ECSOD in therapeutic situations. However, the copper content of PseudoECSOD has been shown to be rather low, and since the copper ion is very important for the catalytic function of the enzyme, a production system that utilizes a copper chaperone for proper insertion of copper into the active site of the enzyme was constructed. The results show that the copper content of PseudoECSOD produced by this system is close to 100 %.In order to use PseudoECSOD therapeutically, further investigations of its binding capability and protective properties are needed. Therefore, the binding of ECSOD and PseudoECSOD to heparin was investigated using isothermal titration calorimetry. The results show that although some purely ionic interactions are important for the binding between ECSOD and heparin, there is also a substantial contribution from non-ionic interactions. The investigation also showed that the C-terminal domain is the only part of ECSOD that contributes to productive binding, and that the binding of PseudoECSOD and ECSOD to heparin is similar.In addition, analysis of mutant proteins strongly indicated that the amino acids R210, K211 and R214 are important for optimal binding of ECSOD to heparin, accounting for about 30 % of the total binding energy. The structural placement of these amino acids in an α-helix also confirms the hypothesis postulated by Margalit et al., that a common structural motif for heparin-binding proteins may be two positively charged amino acids at a distance of approximately 20 Å in the 3D-structure, facing opposite directions of a α-helix. The importance of these residues was also confirmed by analysis of a phage display library of the C-terminal domain of ECSOD.The binding of PseudoECSOD to heparan sulfate on cell surfaces of two different cell types, HepG2 and endothelial cells, was also investigated. The results clearly show that PseudoECSOD binds to these cells in a very similar manner to ECSOD. To investigate the protective properties of PseudoECSOD against ischemia-reperfusion injuries, an isolated rabbit heart model was used. The results indicate that the enzyme has a protective effect. However, more experiments using the rabbit heart and other animal models are needed to identify the optimal dose for protective purposes. The protective properties of PseudoECSOD in human tissue should also be thoroughly investigated.In summary, the findings in these studies, together with earlier results showing the close resemblance of PseudoECSOD to ECSOD in structural, enzymatic and heparin-binding properties, further support the proposition that PseudoECSOD may be a good substitute for ECSOD to use in therapeutic interventions.
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| 43. |
- Ahlander, Britt-Marie, 1954-
(författare)
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Magnetic Resonance Imaging of the Heart : Image quality, measurement accuracy and patient experience
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.Aims: To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.Method: Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.Result: In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).Conclusion: Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.
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| 44. |
- Ahlbeck, Lars, 1964-
(författare)
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Intralymphatic Immunotherapy : A Novel Route to Ameliorate Allergic Rhinitis Due to Pollen
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Allergy to pollen and animal dander is a major public health problem. Close to 30% of the population have symptoms from the upper and/or lower respiratory tract when they meet fur animals or pollen. Whereas symptom-relieving medications have a good to sufficient effect on about 80% of those affected, a large group of 10–20% have severe symptoms, despite medication, with an impact on well-being and ability to work. In Sweden, the annual cost of allergy was calculated at €1.3 billion in 2014.Immunotherapy is effective in treating and preventing pollen allergy and allergic asthma, but is expensive, complicated, requiring 40 injections, and takes more than three years to complete if subcutaneous injections are used. Tablets placed under the tongue are another method, with one tablet taken every day for three years. Only 1.5‰ receive such treatment, yet just over 3% would need it.With intralymphatic immunotherapy, a small dose of allergen is given in a lymph node in the groin on 3 occasions, one month apart. As this method takes only eight weeks, it is a much faster and less costly treatment. However, although several studies have shown that the treatment is safe, its efficacy remains the subject of doubt.Our pilot study in 2012, with a 3-year follow-up to 2015, showed encouraging results, and was followed by a double-blind randomised study with 72 participants from 2014 to 2018. The research subjects then received treatment with birch and grass pollen extract or one extract and a placebo. Regardless of treatment, symptoms, quality of life and medication consumption improved during the birch and grass pollen seasons in the 3 years after treatment. Increased frequencies of T-regulatory lymphocytes may explain the non-specific effects.In 2017 to 2018, we conducted a double-blind study with 38 participants, half of whom received placebo and half, active treatment. In this study, we saw no difference between the treatment groups in the first year after treatment. However, after discontinuation and unblinding in 2019, i.e., two years after treatment, the actively treated group improved in terms of symptoms, and quality of life was improved compared with the placebo group despite less need for medication. T-regulatory lymphocytes increased one year after treatment only in the actively treated group.A long-term follow-up of the research subjects from our two larger studies in 2022, i.e., five to eight years after treatment, showed in the double-blind study without a pure placebo that the scores for symptoms, medication use, and quality of life remained as low as after the first three years. In the placebo-controlled study, a statistically significant improvement in symptoms remained during the grass pollen season. Analysing the two studies together, symptom improvement was significant even during the birch pollen season. Thus, although the effect does not seem to diminish, those who did not receive birch, but only grass, needed to use more medication during the birch pollen season in 2022, seven to eight years after treatment. Moreover, those who did not receive grass but only birch needed more medication during the grass pollen season. This may suggest that the non-specific effect begins to wane after seven to eight years.Allergy to pollen is a major problem for individuals and society, where symptom-relieving treatment with drugs is not enough for many. They can be helped with immunotherapy, which takes at least three years, is expensive and fraught with side effects. In contrast, intralymphatic immunotherapy involves three injections over eight weeks. Our three studies show that the treatment is safe and indicate that it has a clinical effect up to eight years after treatment. T-regulatory cells appear to be important to the immunological mechanism, leading to tolerance to pollen.
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| 45. |
- Ahlberg, Mona, 1966-
(författare)
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Being cared for in an Intensive Care Unit – family functioning and support
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- When COVID-19 came as an uninvited guest into our everyday lives, nursing in intensive care was affected and thus the studies contain data from both before and during the COVID-19 pandemic.Before the pandemic, most intensive care units, which care for patients with critical illness in a technical setting, allowed family members to visit the patient 24 hours a day. The intensive care unit is a stressful and frightening environment for both the patient and their family. They can be affected both mentally and physically, showing symptoms such as difficulty sleeping, stress and depression. The intensive cared patient often does not remember anything from the time they were cared for in the intensive care unit, and the family needs to explain and recount this unconscious time. During the pandemic, this changed, with restrictions and limited opportunities to visit the hospital and patient due to virus outbreaks. Family members received information about the patient's medical condition by phone from a physician. The overall aim of this thesis was to explore and conceptualise the family functioning of families with a family member treated in the intensive care unit. There was also an intention to describe and evaluate how an intervention affects the family and individual family members in families where a family member received intensive care.In these studies, qualitative, quantitative, as well as mixed methods were utilised. Participants were adult intensive cared patients from seven intensive care clinics, and their families. The results examined between families are based on the patient and family characteristics. The results from study I show that families who have experienced COVID-19 and with a family member who was cared for in an intensive care unit, have existential thoughts. Study II shows no major impact on family function between families, but the answers differ within the families who experienced intensive care. In study III, concerning families experiencing intensive care and attending family health conversations, there was an awareness of family function. The conversations brought the family closer together, through improved understanding of each other. In study IV family functioning, hope and sense of coherence were com-pared among the participants in two intervention groups: Family health conversations and support group conversations. Family functioning and hope were higher in the group that participated in the family health conversations and comprehensibility, meaningfulness and vitality were higher among the participants in the support group conversation. By exploring how family function affects the individual family member and the family as a unit during critical illness and intensive care, new ways of working can be strengthened in the care of patients and their families.
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| 46. |
- Ahle, Margareta, 1966-
(författare)
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Necrotising Enterocolitis : epidemiology and imaging
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Necrotising enterocolitis (NEC) is a potentially devastating intestinal inflammation of multifactorial aetiology in premature or otherwise vulnerable neonates. Because of the broad spectrum of presentations, diagnosis and timing of surgical intervention may be challenging, and imaging needs to be an integrated part of management.The first four studies included in this thesis used routinely collected, nationwide register data to describe the incidence of NEC in Sweden 1987‒2009, its variation with time, seasonality, space-time clustering, and associations with maternal, gestational, and perinatal factors, and the risk of intestinal failure in the aftermath of the disease.Early infant survival increased dramatically during the study period. The incidence rate of NEC was 0.34 per 1,000 live births, rising from 0.26 per 1,000 live births in the first six years of the study period to 0.57 in the last five. The incidence rates in the lowest birth weights were 100‒160 times those of the entire birth cohort. Seasonal variation was found, as well as space-time clustering in association with delivery hospitals but not with maternal residential municipalities.Comparing NEC cases with matched controls, some factors, positively associated with NEC, were isoimmunisation, fetal distress, caesarean section, persistent ductus arteriosus, cardiac and gastrointestinal malformations, and chromosomal abnormalities. Negative associations included maternal pre-eclampsia, maternal urinary infection, and premature rupture of the membranes. Intestinal failure occurred in 6% of NEC cases and 0.4% of controls, with the highest incidence towards the end of the study period.The last study investigated current practices and perceptions of imaging in the management of NEC, as reported by involved specialists. There was great consensus on most issues. Areas in need of further study seem mainly related to imaging routines, the use of ultrasound, and indications for surgery.Developing alongside the progress of neonatal care, NEC is a complex, multifactorial disease, with shifting patterns of predisposing and precipitating causes, and potentially serious long-term complications. The findings of seasonal variation, spacetime clustering, and negative associations with antenatal exposure to infectious agents, fit into the growing understanding of the central role of bacteria and immunological processes in normal maturation of the intestinal canal as well as in the pathogenesis of NEC. Imaging in the management of NEC may be developed through future studies combining multiple diagnostic parameters in relation to clinical outcome.
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| 47. |
- Ahlgren, Ewa, 1959-
(författare)
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Cerebral complications after cardiac surgery
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral injuty remains a major cause of morbidity and mortality after cardiac surgery. Previous studies have mainly focused on preoperative risk factors and intraoperative events but cerebral complications may also occur in the postoperative period. Cognitive impairment is common after cardiac surgery but the consequences of this complication for activities of daily life are less known. Safe driving involves a complex set of skills requiring preserved cognitive function. A substantial number of patients with heart disease are active drivers. The impact of postoperative cognitive dysfunction on driving performance, however, has not previously been investigated in this large patient group.In this thesis pre-, intra- and postoperative risk factors for focal cerebral complications were determined and the onset time of cerebral symptoms were evaluated in two cohorts of cardiac surgical patients, comprising 2480 and 3282 patients respectively. Data analysed were drafted from a clinical register and the surgical database of Linköping University Hospital Heart Center. Cerebral complication was delayed, i.e occurred after a free interval, in about one third of patients suggesting causes other than intraoperative events. Different risk factors were found for early and delayed cerebral complications suggesting different mechanisms of cerebral injury. Advanced age, preoperative hypertension, aortic surgery, prolonged cardiopulmonary bypass (CPB) time, intraoperative hypotension after completion of CPB, and arrhytlunia in the early postoperative period increased the risk for early cerebral complication. Female gender, diabetes, previous cerebrovascular disease, combined coronary artery bypass grafting (CABG) and valve surgery and arrhythmia on the thoracic ward increased the risk for delayed cerebral complication. Cognitive function and driving performance were evaluated in 27 patients before and 4-6 weeks after CABG. The patients underwent neuropsychological testing, an on-road driving test and a test in an advanced driving simulator. Twenty patients scheduled for percutaneous coronary intervention (PCI) served as controls. Complete data were obtained in 23 and 19 patients respectively. Furthermore cognitive function and driving performance in on-road driving of the 44 patients with complete tests before intervention were compared with controls of similar age without heart symptoms. Cognitive function and driving performance were already impaired in patients with coronary artery disease before intervention when compared with controls. After surgery 48% of the patients showed cognjtive decline compared to 10% after PCI. These patients also scored less in the on-road driving test to a greater extent than did patients without postoperative cognitive decline.
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| 48. |
- Ahmad, Awais, 1987-
(författare)
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Autoantibodies in healthy blood donors, rheumatic and autoimmune liver diseases
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Autoimmunity is a common phenomenon where the immune system recognises the body's own tissues. Autoimmunity can lead to disease if tissue damage occurs. Autoimmune diseases affect 5–10% of the global population and in many of these autoantibodies can be detected. The autoantibodies can be detected with several different methods. In this thesis, line immunoassays and fluorescence enzyme immunoassay were used to investigate the presence of autoantibodies in blood donors and various disease groups. Line immunoassays use strips while fluorescence enzyme immunoassay uses wells. The strips and wells are coated with proteins that are allowed to react with serum samples from the patient. In the presence of autoantibodies, either a color change (line immunoassay) or a light reaction (fluorescence enzyme immunoassay) occurs.Study I and II: With the EuroLine -Autoimmune Liver Diseases- (IgG) line immunoassay, the presence of autoantibodies associated with autoimmune liver diseases was analysed in blood donors, patients with autoimmune liver diseases and patients with SLE. Autoantibodies could be detected in several blood donors. A very rare autoantibody, anti-LC- 1, was more common in blood donors than in patients with autoimmune liver diseases. Despite the presence of the autoantibodies, no association was seen with abnormal liver values in blood donors or patients with SLE. By raising the cut-off, the number of "false positive" results decreased. However, this could not correct the problem with anti-LC-1, which seems to indicate that there is a problem with the LC-1 antigen so that non-specific reactions are detected. The risk of developing autoimmune liver disease was considered to be low in the SLE patients, as none of these patients developed autoimmune liver disease despite several years of follow-up. Most of the positive findings with the EuroLine immunoassay could not be confirmed with other methods, indicating that this method is very sensitive.Study III: With the EuroLine Systemic Sclerosis (Nucleoli) Profile (IgG) line immunoassay, the rare autoantibodies anti-Th/To and anti-NOR90 could be detected as frequently in blood donors as in patients with systemic sclerosis. Most of the other autoantibodies were more common in patients with systemic sclerosis compared to blood donors and other disease groups. Some of these autoantibodies were associated with specific clinical manifestations, including renal involvement in patients with SLE. These findings need to be verified.Study IV: Autoantibodies that bind the U1-RNP protein (anti-U1-RNP) can be detected in patients with SLE. Patients with anti-U1-RNP can be further analysed for the presence of autoantibodies against the protein RNP 70kDa (anti-RNP70). However, the clinical value of further analysis of anti-RNP70 is uncertain. In this study, fluorescence enzyme immunoassay was used to analyse anti-U1-RNP positive samples for anti-RNP70 to evaluate whether it added anything of clinical value in SLE patients. Presence of anti-U1-RNP was associated with low white blood cell counts and less organ damage. However, analysis of anti-RNP70 in patients with SLE did not add any additional clinical information.Conclusion: Euroline -Autoimmune Liver Diseases- (IgG) and EuroLine Systemic Sclerosis (Nucleoli) Profile (IgG) are tools that are of value in the diagnosis of autoimmune liver diseases and systemic sclerosis, but the methods have high sensitivity which can lead to false positive results. By raising the cut-off, the risk of this can be reduced. Some rare antibodies were found more frequently in blood donors than in patients with the different disease groups, suggesting potential problems with the antigen source. Subtyping of anti-RNP70 in SLE patients with anti-U1-RNP did not add anything of clinical value.
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| 49. |
- Ahmadi, Ahmad, 1964-
(författare)
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Genetic predisposition and risk factors for neurodegenerative diseases with special emphasis on Parkinson's disease and solvent-induced chronic toxic encephalopathy
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The inter-individual variability in biotransformation, may lead to differences in activation and detoxification of both endogenous and exogenous compounds. Polymorphism studies in such genes were applied for Parkinson's disease (PD) and Chronic toxic encephalopathy (CTE), two diseases influenced by both genetic and enviromnental factors.An elevated median age for the onset of PD was found among GS1M1 gene carriers compared to PD patients being GS1M1 null genotypes (68 years versus 57 years). No similar difference was found for GSTT1. mEPHX (113HH) isoform, which has been suggested as a low activity variant, is over represented in PD patients (OR=3.8, CI 95%, 1.2-11.8).Monoamine oxidases (MAO-A and -B) are important in the dopamine metabolism and in the detoxification of neurotoxins and genetic variants in these genes have earlier been assigned to PD. However, no difference was revealed between any of the polymorphisms studied in the MAO-A and -B genes and PD. Smoking displayed an enviromnental exposure with a strong decreased risk for PD in this study (OR=0.40 for men and OR=0.48 for women) but no obvious interaction with the MAO genotypes could be observed.Mitochondrial dysfunction and oxidative stress have been hypothesized to contribute to the pathogenesis of PD. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals in mitochondria. Polymorphisms neither in superoxide dismutase 2 (SOD2) nor mitochondrial complex I subunit, NDUFV2, were associated with PD.An increased risk ratio for CTE was found in smokers with the GSTM1 null genotype (RR=2.5, Cl 95%, 1.4-4.2) or the GSTT1 null genotype (RR=1.4, Ci 95%, 1.02-2.0). In non-smokers GS1M1 null genotype did not confer any risk for CTE. Polymorphisms in mEPHX were not associated with an increased risk for CTE.Thus, various genetic and enviromnental factors most likely influence both PD and solvent-induced CTE. Detoxification pathways may represent important protective mechanisms against reactive intermediates, thus genetic predisposition in these pathways could modify the susceptibility and onset of PD and solvent-induced CTE.
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| 50. |
- Ahnström Waltersson, Marie, 1976-
(författare)
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Cell cycle alterations and 11q13 amplification in breast cancer : prediction of adjuvant treatment response
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The growth and development of the breast is to a large extent regulated by oestrogens through the oestrogen receptor (ER). Activation of the ERα triggers transcription of genes that are important for cell proliferation and stimulates entry into the G1 phase of the cell cycle. In breast cancer the ERα is often upregulated and is therefore a suitable target for adjuvant therapies such as tamoxifen. Although tamoxifen is an effective treatment in most cases, tumours sometimes acquire resistance to the drug. The aim of this thesis was to investigate the impact of G1 phase proteins and 11q13 amplification on prognosis and treatment response in breast cancer. The material used was from a clinical trial in which postmenopausal breast cancer patients were randomised to chemotherapy or radiotherapy and tamoxifen or no adjuvant treatment. We studied the expression of cyclin D1, cyclin E and Rb with immunohisochemistry and amplification of CCND1 and PAK1 with real time PCR. We found that among patients with high tumour expression of cyclin D1, overexpression of ErbB2 was associated with reduced recurrence-free survival. Both cyclin D1 and cyclin E overexpression were associated with reduced tamoxifen response. High expression of cyclin D1 has been found to induce ligand independent activation of ERα in breast cancer cells and might also switch tamoxifen from acting as an antagonist to an agonist. Overexpression of cyclin E has been shown to be associated with expression of low molecular weight isoforms of the protein that possess an increased kinase activity and are insensitive to p21 and p27 inhibition. Furthermore, amplification of 11q13, and in particular the gene PAK1, was a strong predictor of tamoxifen resistance. The pak1 protein is involved in phosphorylation and ligand independent activation of the ERα. We also found that lost expression of either p53 or Rb reduced the patients benefit from radiotherapy compared with patients with normal expression of both proteins. Normally, ionizing radiation upregulates p53 resulting in G1 arrest or apoptosis. If either functional p53 or Rb is missing the cells can proceed from G1 to the S phase despite damaged DNA. The expression of the microRNA, miR-206, was analysed with real time PCR, and the results showed that high expression of miR-206 correlated to low expression of ERα and 11q13 amplification. In vitro studies have shown that miR-206 negatively regulates the expression of ERα. Taken together the G1 regulators and amplification of 11q13 seem to have an important role in predicting the patient’s response to adjuvant therapy.
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