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- Abd El-Gawad, Gamal, 1959
(författare)
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Urologic and metabolic consequences of continent urostomy (Kock reservoir) in children and adolescents
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last decades, urinary diversion using an intestinal segment has been commonly used in children and adolescents. Kock pouch is a feasible alternative for the children in need of a continent diversion where other alternatives such as Mitrofanoff are excluded for various reasons. The present study focused on the evaluation of the urologic and metabolic consequences after continent urinary diversion (Kock reservoir) and the assessment of the quality of life after surgery in children and adolescents. Twenty patients with congenital urinary incontinence were operated and followed for 3-12 years. The reservoir and upper urinary tract were studied through enterocystometry, enterocystoscopy, enterocystography, intravenous urography and clinical history. Acid-base status, serum electrolytes, vitamin B12, folate, methylmalonic acid (MMA) and homocystine were measured. Renal function was assessed by Cr51 EDTA clearance and serum creatinine and the split renal function by (99m) Tc-MAG 3 renoscintigraphy. Patients answered a questionnaire that covered medical, physical, social and body image aspects. The follow-up was divided into different periods: early -EFU (3 months - 2 or 5 years), and late -LFU (2-10 or 5-12 years after surgery).A low reservoir pressure was accompanied by high capacity and compliance. Nipple malfunction (angled nipple, prolapsed or stenosed stoma) occurred in 35% and stones in 40% of patients. Reservoir perforation was observed in 2 patients. An excellent continence was reported in 90% and a good one in the rest of patients. Angled efferent nipple seen on enterocystoscopy or enterocystography coincided with nipple malfunction, reservoir mal-position or infrequent emptying (= 4 times/day). Ureteral dilatation was detected in 84% of patients 3 months after surgery. The dilatation was improved in 56% and unchanged in 25% of patients after one year, and then it continued to improve at the LFU. New focal renal scars were radiologically detected in 2 patients. Three patients had metabolic acidosis and 8 had hyperchloremia. Serum creatinine level was increased in 82% of patients with infrequent emptying at the LFU (P<0.05). GFR was below normal in 4 patients preoperatively, in 6 at the EFU and in 8 at the LFU. Two patients developed low B12 values and 2 had elevated MMA with normal B12 values. Blood folate was low in 5 patients at the EFU and in different 5 at the LFU. There was no correlation between the resected ileal segment length and B12 value.Physical activities were not hampered by the operation in any patient. Instead, some activities as full day outside home and friend at home over night were increased in some patients. More than half of patients had excellent positive self-esteem and body image and the rest had good one. However, some patients were concerned about how they looked and felt that life was unfair to them.Conclusion: Kock reservoir remains a viable alternative to other forms of continent urinary diversion. The stability of the reservoir volume and low internal pressures was achieved early after operation depending on the frequency of the reservoir emptying. Efferent nipple malfunction is common during the first 2 years after surgery. The Kock pouch provided a satisfactory continence to all patients, although a revisional operation was necessary in some patients to get a permanent continence. Urinary tract dilatation is a frequent finding postoperatively, but it subsides in most cases 3-12 months after surgery. Long-term afferent nipple dysfunction may be the result of angulation, reservoir stones, mal-position and/or over-distension. Permanent renal damage may be due to pyelonephritis, stones, infrequent reservoir emptying, urinary obstruction, or metabolic acidosis. A strict regime of reservoir evacuation to decrease the possibility of metabolic alterations and of renal function deterioration is strongly advisable in these patients. Vitamin B12 and folate values should be monitored regularly. B12 deficiency is neither correlated with the time elapsed since surgery, nor with the resected ileal length. Serum MMA and homocystine may offer increased detection of occult B12 deficiency. The patients were physically active and declared a positive perspective regarding self-esteem and body image. The medical problems related to the operation did not have any negative influence on the self-esteem or body image. The choice of the operation can only be determined on the basis of an attentive dialogue between surgeon, child and parents.
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| 2. |
- Abel, Frida, 1974
(författare)
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Genetic studies of neuroblastoma with emphasis on the apoptotic pathway
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The objective of this thesis was to find genes and chromosomal regions involved in neuroblastoma (NB) tumor progression. NB is a childhood tumor of the sympathetic nervous system that generally occurs spontaneously. Biologically, NB has a complex heterogeneity from tumor progression to tumor regression, dependent on clinical stage and age at diagnosis. The main genetic markers, which are also of prognostic value in NB, are amplification of the oncogene MYCN, deletion of chromosome arm 1p and gain of chromosome arm 17q. Results: We have been shown using fluorescence in situ hybridization (FISH) on a Scandinavian tumor material, that 17q gain is present in approximately 65% of all NB stages, is significantly associated with poor prognosis and predicts survival. The gene encoding somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, was not found to be mutated in any NB, when analyzed with PCR-based single stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing. In a tentative effort of defining of the location of a general embryonal tumor suppressor gene (TSG) on 1p, we combined the smallest region of overlap (SRO) of 1p deletions in NB tumors and germ cell tumors (GCTs). We thus delimited the NB/GCT SRO to approximately 5 cM between markers D1S508 and D1S244, and fine-mapped this region by radiation hybrid mapping and construction of a bacterial artificial chromosome (BAC) contig. A homozygously deleted region in an NB cell line was found to partially overlap the proximal part of the 5 cM-SRO defined by us, which further focused our search for a TSG to a 500 kb candidate region in 1p36.22. Two attractive candidate NB TSGs, DFFA and CASP9, are both located in 1p36.2 and encode key apoptotic mediators. In fact, DFFA resides in the 500 kb TSG candidate region. Via sequence analysis of the entire tumor material, we found three different coding alterations in DFFA which all affect the highly conserved N-terminal regulatory domain of DFF45. Using RT-PCR and real-time RT-PCR (TaqMan) studies, we were able to show that both DFFA and CASP9 are preferably expressed in NB tumors with favorable outcome. It has been proposed that lack of apoptosis plays an important role in tumor progression. We therefore screened an array with cDNAs involved in the apoptotic process, to find genes differentially expressed in NB tumors with unfavorable versus favorable biology. Using real-time RT-PCR analysis, we verified the differential expression of several transcripts encoding mitochondrial apoptotic mediators. Conclusions: We have shown that 17q gain is the most frequently detected alteration in NB and that it is associated with established prognostic factors. We narrowed down the TSG candidate region on 1p and found mutations in a gene localized in the region possessing fundamental functions in apoptosis. Our results also suggest that the mitochondrial apoptotic pathway is suppressed at multiple steps in advanced stages of NB tumors, due to imbalance between anti-apoptotic and pro-apoptotic mediators.
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| 4. |
- Abou-Ali, Hala, 1972
(författare)
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Water and Health in Egypt: An Empirical Analysis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is an empirical work dealing with water issues in Egypt where the emphasis is put on the analysis of the relationship: inadequate water quality and health impacts. The first chapter includes a general discussion of water resources in Egypt and other developing countries. This chapter briefly also deals with water tariffs and sustainable water pricing in Cairo. In the second chapter the impacts of water and sanitation on child mortality in Egypt are assessed. The analysis is conducted using a three-part model specification, comprising discrete choice to model the child prospects of dying during the neonatal period. The remaining parts use transition models, in which unobserved heterogeneity is accounted for, to model infant and childhood risk of death. The results show that access to municipal water decreases the risk, and sanitation is found to have a more pronounced impact on mortality than water. The results suggest that increasing the awareness of the Egyptian population relative to health care and hygiene is an important means to decrease the risk of child mortality. Moreover, gender discrimination is found to have an important effect beyond the neonatal period. In the third chapter, controlling for the Egyptian households' choice of health infrastructure (i.e., sanitation facility and water accessibility) is done by means of a discrete choice approach consistent with the random utility model. Evidence of the importance of the indirect effect of the source of drinking water on neonatal mortality is found, but generally the indirect effect is negligible. Furthermore, changes in wealth and educational levels are assessed taking into consideration a priori the choice of health infrastructure. The analysis suggests that wealth and education contribute loosely to the child mortality reduction. The fourth chapter analyzes the impact of better water quality on health improvements using two stated preference methods: choice experiments and the contingent valuation method. These methods were administered to a random sample of 1500 households in metropolitan Cairo, Egypt. The results show that both methods give quite the same welfare measures. Moreover, households in metropolitan Cairo do have a positive willingness to pay for reducing health risks owing to water quality that amounts to roughly double their current water bills. This finding suggests that the willingness to pay is rather small compared to the likely cost.
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| 5. |
- Abrahamsson, Kajsa H., 1956
(författare)
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Dental fear and oral health behavior. Studies on psychological and psychosocial factors
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to study psychological and psychosocial factors in relation to the development, maintenance and expression of dental fear, how individuals cope with their fear, and how dental fear may impact on health and daily life. The study samples consisted of adult dental fear patients seeking treatment at a specialized dental fear clinic. Both quantitative and qualitative research methods were used. The qualitative interview protocols were analyzed using the constant comparative method of grounded theory. It was found that dental fear patients with concomitant high general fear differ in several ways from patients with less frequent and wide-spread fear. These differences concern dental fear reactions and related emotions, as well as general psychological dimensions. The results indicated an overall more negative and complex situation for patients with high dental and general fear. Comparisons between severe dental fear patients reporting different attendance patterns showed a higher education level and more filled teeth among patients with a history of regular dental care, while patients with phobic dental avoidance behavior had more anticipatory dental anxiety, more missing teeth, and reported a stronger negative impact from dental fear/poor oral status on daily life. General fearfulness was not related to phobic dental avoidance. According to the qualitative interviews the onset of dental fear was commonly related to an individual vulnerability and to traumatic dental care experiences, where perceived negative dentist behavior played a significant role. The patient was caught in a "vicious circle" that was difficult to break, and fear and anxiety were maintained by negative expectations about treatment and about the patient's own ability to cope in dental care situations. The interviews brought out the patients' ambivalence in coping with dental fear. The ambivalence was between, on the one hand the tendency to avoid dental care, and on the other hand the need for dental care and their attempt to find active problem-solving strategies. This left patients in a state of conflict with negative consequences for self-respect and well-being. It was obvious that dental fear and deteriorated oral health status resulted for many patients in wide-spread negative life consequences. It was also obvious that several psychological and social factors interact in determining how individuals cope with their dental fear, and demonstrate how dental fear affects their daily lives. Finally, the importance of dental beliefs in dental fear treatment was investigated. The interpretation of the results suggests that the assessment of dental beliefs provides valuable information and that patients' subjective perceptions about how dentists communicate are important for treatment outcome. However, initial dental beliefs were not found to predict clinical treatment outcome, and dental beliefs are one of several factors interacting in dental fear treatment. The results emphasize the complexity of dental fear and oral health behavior, where personality characteristics and environmental factors interact. This further elucidates the need for a broad-spectrum approach in dentistry.
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| 6. |
- Abramsson, Alexandra, 1973
(författare)
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Tumor angiogenesis. Regulation of mural cell recruitment and endothelial sprouting
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The formation of new blood vessels is an inherent part of many physiological and pathological processes. Currently, there is a strong hope pathological situations like stroke, diabetic retinopathy and cancer may be affected by pharmacological regulators of blood vessel formation. This thesis work has mainly been focused on two molecules implicated in blood vessel formation, platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor (VEGF)-A. In vessels, PDGF-B is expressed by endothelial cells (EC) and act as a chemotactic and mitogenic signal via the PDGF receptor (PDGFR)-b on vascular smooth muscle cells (vSMC) and pericytes (PC). Tumor vessels are often abnormal and show a sparse association of vSMC/PC. We addressed the role of PDGF-B in vSMC/PC recruitment to tumor vessels using gain- and loss-of function analyses of PDGF-B. Our results show that vSMC/PC recruitment is dependent on PDGFRb and an EC source of PDGF-B. PDGF-B binds to the extracellular matrix in the close vicinity of EC through its retention motif. This spatial distribution of PDGF-B protein is needed for proper association of the PC with vessels; lack of PDGF-B retention leads to the extension of cellular processes away from the vessel, and to partial or complete PC detachment.VEGF-A stimulates migration and proliferation by binding to VEGF receptor expressed by EC. We have addressed the mechanism by which VEGF stimulate vessel formation by analyzing postnatal retinal vascularization. Our results revealed two functions of VEGF-A; guidance of highly specialized cells, tip-cells, at the tip of sprouting vessels, and proliferation of cells in the trailing cells, stalk-cells. Both these processes are mediated by VEGF receptor (VEGFR)-2. VEGF-A is produced in isoforms of 120, 164 or 188 amino acids where VEGF188 bind to the ECM, VEGF120 is soluble and VEGF164 has intermediate properties. Their spatial distribution creates a gradient sensed by filopodial extensions from the tip-cell. We also describe the existence of tip-cells with filopodia in tumors vessels. The extent of EC filopodia varies between tumors and correlates with vSMC/PC density and VEGF-A expression. Taken together, these results suggest that PDGF-B- and VEGF-A-stimulated processes in the vasculature are analogous. Migration of vSMC and EC seem to depend on the exact spatial distribution of PDGF-B and VEGF-A respectively. Proliferation of these cells on the other hand, appears to be regulated by the concentration of PDGF-B and VEGF-A. Our work also implies that anti-angiogenic therapy targeting VEGFR2 will inhibit the tip-cell and hence guided angiogenesis. The differences in sprouting phenotype in various tumors indicate that the angiogenic process of these tumors might differ. This, and variable vSMC/PC abundance in different tumors may implicate differences in responsiveness to anti-angiogenic therapy.
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| 9. |
- Adermark, Louise, 1974
(författare)
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Ethanol-mediated effects on astroglial cells in primary culture. With a focus on acute changes in intracellular Ca2+, cell volume, actin filaments, and gap junction coupling
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The astroglial cells are abundant in the central nervous system (CNS), where they control and regulate the homeostasis of the extracellular milieu. A change in astroglial cell volume, mediated through activation of neuroactive substances or changes in osmolarity, leads to changes in the size and geometry of the extracellular space volume, which could affect the diffusion and concentration of neuroactive substances. The astroglial cells are connected through gap junctions, which are small pores that allow bidirectional communication. The intercellular coupling through gap junctions has been suggested to allow the astroglial network to function as a unit, and to equalize the concentration of intracellular ions.To enable studies of signal transduction systems involved in astroglial cell swelling and volume regulation, we developed a new method for quantifying changes in cell volume at the single-cell level (Paper I). The method, which was based on optical sectioning in combination with image analysis, was used to study changes in astroglial cell volume mediated by ethanol (10 200 mM) in three dimensions (3D) over time (Papers II and IV). The method was proven to be capable of properly reconstructing and segmenting individual cells. Exposure for 5 min to 25 mM or 150 mM ethanol increased astroglial cell volume in 19% and 36% of analyzed cells, while cell shrinkage was detected in 22% and 35%, respectively (Paper IV). The ethanol-mediated volume changes were partially inhibited during incubation in low extracellular sodium ([Na+]o), during blockage of the Na+/K+/2Cl- cotransporter with furosemide, during blockage of the Na+/K+-adenosine triphosphatase (ATPase) with ouabain, or during blockage of the inward-rectifying potassium channels (K+IR) with BaCl2 (Paper IV). Exposure to ethanol-induced morphological changes and ethanol-mediated transformation in filamentous actin led to a more dispersed appearance of the filaments and an increased number of cells with actin in ring formations (Paper II). Ethanol decreased cell-to-cell communication through gap junctions in astroglial cultures from the cerebral cortex, brain stem, or hippocampus, while cultures from the olfactory bulb or hypothalamus remained unaffected (Paper III). The decrease was not seen during incubation in low [Na+]o, or during blockage with furosemide, and ethanol had no additional effect on the decrease in gap junction coupling mediated by ouabain (Paper III). The results presented in Papers II IV suggest that astroglial cells could be important targets during ethanol exposure, and that possible changes in cell volume and gap junction coupling could be of toxicological relevance.
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| 10. |
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