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2.
  • Abd El-Gawad, Gamal, 1959- (författare)
  • Urologic and metabolic consequences of continent urostomy (Kock reservoir) in children and adolescents
  • 2001
  • Doktorsavhandling (övrigt vetenskapligt)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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3.
  • Abdalrahim, Maysoon S, 1962- (författare)
  • Postoperative Pain Assessment and Management: The Effects of an Educational program on Jordanian nurses’ practice, knowledge, and attitudes
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Aims: The overall aims of this thesis was describe the current nursing postoperative pain assessment and management practices in the surgical wards in Jordan and evaluate the effectiveness of implementing a ostoperative pain management (POPM) program in improving the Jordanian nurses’ POP assessment and management practices in the surgical wards. Lewin’s Force-Field Model for change provided the structure for planning for and implementing the POPM program. Method: Both qualitative and quantitative approaches were used. Qualitative content analysis inspired by the hermeneutic philosophy was used to describe the surgical nurses’ experiences in caring for patients having POP. Data were collected by interviewing 12 registered nurses working in surgical wards at four hospitals in Jordan. A retrospective quantitative design was used to collect data on the documentation system and strategies of the POP assessment and management in the surgical wards. A total of 322 patients’ records obtained from six hospitals in Jordan were audited in six-month period. The records review was performed using three audit instruments. Later, a POPM program for nurses was implemented in two surgical wards at a university hospital in Jordan. The program was evaluated by means of a quasi-experimental design with a nonequivalent control group where the control group (120 patients) and the intervention group (120 patients) were not drawn from the same population. All registered nurses (65 nurses) employed in the two surgical wards participated in the study to implement the program. First, assessment of patients’ communication about pain with nurses and their satisfaction about nurses’ intervention were assessed by means of a questionnaire. Second, the quality of nurses’ pain assessment was evaluated by comparing the attending nurses’ assessment of patients’ pain intensity rating scores with the researcher’s rating scores of the same patients. Third, a questionnaire was used to test the nurses’ knowledge of and their attitudes toward pain. Forth, the records were audited before and after the intervention. The POPM program was implemented for three months. Findings: The findings of the studies I and II formulated the foundation where the researchers can illuminate the main issues and obstacles in the process of change toward better POP management. Findings from these studies draw attention to the fact that there is an urgent need for improving POP assessment, management and documentation. The findings illustrated that the implementation of an educational program for nurses was successful. First of all, the quality communicated information about pain and pain management with patients was significantly improved. Secondly, the nurses developed the habit of assessing POP intensity using numeric rating scales, in addition to the assessment of other pain characteristics. Thirdly, the nurses improved their knowledge about POP, and their attitudes toward it were evidently changed. Finally, the nurses improved their practice in documenting patients’ pain. The patients’ records showed a significant difference in the amount and the quality of nursing documentation which reflected the fact that nurses became more aware about the importance of documentation and might also means that they change their practices toward better POP management. Discussion and Implications: The studies provide several contributions to the knowledge and understanding of the POP current management practices such as the recognition of the surgical patients suffering due to the unsatisfactory pain management routines, the impact of health institutions restraints on nurses that prohibit them from providing quality of care for patients with POP, and the need to change the current practices of nursing documentation of POP. The findings add to a growing body of literature on the benefits of implementing educational programs for nurses to improve their roles in caring for patients with POP. The findings of this thesis provide opportunities for nurses to evaluate themselves in the area of POP knowledge and management practices which may affect their caring abilities. Another implication related to nursing practice is that this study might increase the awareness of the health care professionals and the health institutions administration toward the establishment of team work to induce change with a common purpose in upgrading the quality of pain assessment and management. Managers and supervisors can facilitate the application of educational programs and incorporate with the team to move more quickly in the desired change. Implications of the study may be relevant to nursing education and in continuing education of health care institutions.
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  • Abdul-Hussein, Saba (författare)
  • Cellular studies of neuromuscular disorders related to the sarcomeric proteins
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Sarcomere is the basic unit of cardiac and skeletal muscle contraction and its proper function requires an invariant organization of this structure. Mutations in sarcomeric proteins are known to cause increasing number of different cardiac and skeletal muscle diseases. The front line in research on muscle diseases is at present to define the genetic background and pathogenesis of these diseases. The potential for development of effective therapies depends on elucidation of the molecular and cellular impact of the mutations on morphological abnormalities and muscle weakness that accompany pathogenesis. In paper I we identified an unexpected skeletal muscle myopathy in an infant with fatal cardiomyopathy due to a homozygous mutation in MyBPC3. The ectopic expression of cardiac MyBPC was restricted to abnormal type 1 muscle fibres, indicating that the muscle pathology was caused by a dominate-negative effect of mutant MyBPC3. In paper II we addressed the expression profile of a panel of sarcomeric components during myogenesis, with a focus on proteins associated with a group of congenital disorders. The analyses were performed in cultured human skeletal muscle myoblasts and myotubes. We identified early expression of certain isoforms involved in congenital diseases, suggesting the possibility of an early role for these proteins as constituent of the developing contractile apparatus during myofibrillogenesis. In paper III we used human tissue-culture cells as a model to investigate the primary trigger for β-tropomyosin-related myopathies and the basis for the histological changes seen in muscle biopsies of patients. Protein localization and pathobiology caused by dominant TPM2 mutations were investigated by transfecting human myoblasts and C2C12 with WT and mutant EGFP-fusion β-TM constructs. Abnormal aggregation of β-TM variants and their localization within the thin filaments was observed in myoblasts and differentiated myotubes. We demonstrated that histopathological phenotypes associated with β-TM mutants might be accounted for the variable response to the cellular environment influenced by physiological context, in combination with the time course of expression of mutant protein rather than the alteration of amino acid itself. Our results confirmed that cell cultures of human skeletal muscle are an appropriate tool and environment closer to the reality in human skeletal muscle and more reliably mimic the disease conditions. In paper IV we identified and characterized a new human protein aggregate myopathy and cardiomyopathy associated with combined mutations in isogenes TRIM63 and TRIM54, encoding muscle specific ring finger proteins, MuRF1 and MuRF3, respectively. Our morphological and cellular investigation suggested that the disease is caused through impaired organization of the microtubule network and sarcomeric M-band proteins. The results from this study have deepened the understanding of pathogenesis of a group of sarcomeric
6.
  • Abdulle, Sahra, 1970- (författare)
  • HIV-1 infection of the central nervous system. Markers of pathogenesis and antiretroviral treatment effects
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) early in the course of infection and either directly or through opportunistic infections causes a spectrum of neurological complications. The most severe manifestation of HIV-1 CNS infection is AIDS Dementia Complex (ADC), which occurs in approximately 20% of untreated patients with AIDS. ADC is considered the result of a complex interplay between immune activation effects and viral replication in the brain, which ultimately leads to neuronal injury and death. Reliable markers to diagnose HIV-1 associated CNS injury, track disease progression, and identify patients at risk of developing ADC are lacking. Such markers would also be beneficial in evaluating the efficacy of antiretroviral treatment (ART) in the CNS, as well as to provide insights into the pathogenesis of HIV-1 CNS infection.HIV-1 elicits intrathecal cell-mediated and humoral immune activation. We found that ART effectively decreased the cerebrospinal fluid (CSF) concentrations of neopterin and beta2-microglobulin, but had little effect on the elevated IgG index. However, almost half of the patients still had slightly elevated levels of neopterin after 2 years of follow-up. Phylogenetic analyses have identified 3 distinct HIV-1 genetic groups. Group M, which is responsible for most of the global HIV-1 epidemic is further subdivided into subtypes and circulating recombinant forms (CRFs). Most of the current knowledge of HIV-1 CNS infection is based on studies of subtype B, which is predominant in the western world. However, subtypes other than subtype B are responsible for most of the epidemic outside the western world, and HIV-1 infections due to subtypes other than B are rapidly increasing across Europe. Markers of HIV-1 CNS infection such as HIV-1 RNA, neopterin, and white blood cell (WBC) count in CSF were measured and compared in patients infected with different HIV-1 subtypes. We did not find any significant subtype-specific differences in the neuromarkers evaluated in this study. Thus, subtypes do not appear to influence neuropathogenesis.Although there is no evidence of productive infection of neurons the end-result of HIV-1 CNS infection is neuronal damage and loss. We investigated the potential of CSF neurofilament (NFL), a sensitive indicator of axonal injury, as a marker of HIV-1 associated neurodegeneration. CSF NFL concentrations were higher in patients with ADC than in neuroasymptomatic patients, or patients with primary HIV-1 infection. Patients with severe ADC had higher CSF NFL levels compared to those with milder disease. CSF NFL declined with ART to the limit of detection in parallel with virological response and neurological improvement in patients suffering from ADC.Neurocognitive impairment remains a major concern in HIV-1 infection despite the success of ART. Studies on the pathogenesis, epidemiology, and the effects of ART on HIV-1 CNS infection are important to improve patient management.
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7.
  • Abel, Frida, 1974- (författare)
  • Genetic studies of neuroblastoma with emphasis on the apoptotic pathway
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt)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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8.
  • Abelin, Åsa, 1953- (författare)
  • Studies in Sound Symbolism
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • This thesis investigates how the Swedish lexicon is structured with respect to sound symbolism, the productivity of phonesthemes and cross language similarities in certain areas of sound symbolism. The Swedish lexicon has been analyzed with emphasis on the sound symbolic properties of initial and final consonant clusters, and to a certain extent of vowels. Approximately 1, 000 lexemes were judged to be sound symbolic and the outcome of the analysis are tentative phonesthemes, i.e. motivated connections between meanings and consonant clusters. Almost all Swedish initial consonant clusters and many of the final consonant clusters may carry sound symbolic meanings. Lexically infrequent clusters are utilized to a larger extent than lexically frequent clusters. No two consonant clusters have exactly the same semantic profile. Phonesthemes have different sound symbolic strength, i.e. some are clearly sound symbolic (i.e. a high percentage of the words beginning with a certain cluster are sound symbolic), and carry either one meaning or several meanings. Other (candidates for) phonesthemes are weaker and not so clearly sound symbolic. The meanings of most phonesthemes are relatable to the senses: hearing, vision or tactile sensation, or they are metaphorically or metonymically connected to the senses. The most common semantic features occurring are often related to synaesthesia. The productivity of phonesthemes was tested in experiments of production and understanding. The experiments show that in interpretation no constructed word is interpreted as expected by all subjects, but that all of the constructed words are interpreted correctly by some subjects. The most common semantic features found in the lexical analysis are also often the most successfully interpreted by subjects. For production, the experiments indicate that subjects tend to encode the semantic features in initial clusters rather than in final clusters. Final consonant clusters seem to be of less importance than the initial clusters in new sound symbolic words in Swedish. For the contrastive studies, the general results are that there are both similarities and differences between the expressions in the different languages. The variation is greater for some semantic fields than for others.
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