Thesis (Doctoral)--Department of Internal Medicine, Lund Institute of Technology. / Added t.p. with thesis statement inserted. Includes bibliographical references.

In Chapter 1, the literature relating to rabies virus and the rabies like lyssaviruses is reviewed. In Chapter 2 data are presented from 1170 diagnostic submissions for ABLV testing by fluorescent antibody test (Centocor FAT). All 27 non-bat submissions were ABLV-negative. Of 1143 bat accessions 74 (16%) were ABLV-positive, including 69 of 974 (7.1%) flying foxes (Pteropus spp.), 5 of 7 (71.4%) Saccolaimus flaviventris (Yellow-bellied sheathtail bats), none of 151 other microchiropteran bats, and none of 11 unidentified bats. Statistical analysis of data from 868 wild Black, Grey-headed, Little Red and Spectacled flying foxes (Pteropus alecto, P. poliocephalus, P. scapulatus, and P. conspicillatus) indicated that three factors; species, health status and age were associated with significant (p&lt 0.001) differences in the proportion of ABLV-positive bats. Other factors including sex, whether the bat bit a person or animal, region, year, and season submitted, were not associated with ABLV. Case data for 74 ABLV-positive bats, including the circumstances in which they were found and clinical signs, is presented. In Chapter 3, the aetiological diagnosis was investigated for 100 consecutive flying fox submissions with neurological signs. ABLV (32%), spinal and head injuries (29%), and neuro-angiostrongylosis (18%) accounted for most neurological syndromes in flying foxes. No evidence of lead poisoning was found in unwell (n=16) or healthy flying foxes (n=50). No diagnosis was reached for 16 cases, all of which were negative for ABLV by TaqMan® PCR. The molecular diversity of ABLV was examined in Chapter 4 by sequencing 36 bases of the leader sequence, the entire N gene, and start of the P gene of 28 isolates from pteropid bats and 3 isolates from Yellow-bellied sheathtail (YBST) bats. Phylogenetic analysis indicated all ABLV isolates clustered together as a discrete group within the Lyssavirus genera closely related to rabies virus and European bat lyssavirus-2 isolates. The ABLV lineage consisted of two variants; one (ybst-ABLV) consisted of isolates only from YBST bats, the other (pteropid-ABLV) was common to Black, Grey-headed and Little Red flying foxes. No associations were found between the sequences and either the geographical location or year found, or individual flying fox species. In Chapter 5, 15 inocula prepared from the brains or salivary glands of naturally-infected bats were evaluated by intracerebral (IC) and footpad (FP) inoculation of Quackenbush mice in order to select and characterize a highly virulent inoculum for further use in bats (Inoculum 5). In Chapter 6, nine Grey-headed flying foxes were inoculated with 105.2 to 105.5 MICED50 of Inoculum 5 divided into four sites, left footpad, pectoral muscle, temporal muscle and muzzle. Another bat was inoculated with half this dose divided into the footpad and pectoral muscle only. Seven of 10 bats developed clinical disease of 1 to 4 days duration between PI-days 10 and 19 and were shown to be ABL-positive by FAT, HAM immunoperoxidase staining, virus isolation in v mice, and TaqMan PCR. Five of the seven bats displayed overt aggression, one died during a seizure, and one showed intractable agitation, pacing, tremors, and ataxia. Viral antigen was demonstrated throughout the central and peripheral nervous systems and in the epithelial cells of the submandibular salivary glands (n=4). All affected bats had mild to moderate non-suppurative meningoencephalitis and severe ganglioneuritis. No ABLV was detected in three bats that remained well until the end of the experiment on day 82. One survivor developed a strong but transient antibody response. In Chapter 7, the relative virulence of inocula prepared from the brains and salivary glands of experimentally infected flying foxes was evaluated in mice by IC and FP inoculation and TaqMan assay. The effects in mice were correlated to the TaqMan CT value and indicated a crude association between virulence and CT value that has potential application in the selection of inocula. In Chapter 8, 36 Black and Grey-headed flying foxes were vaccinated with one (day 0) or two (+ day 28) doses of Nobivac rabies vaccine and co-vaccinated with keyhole limpet haemocyanin (KLH). All bats responded to the Nobivac vaccine with a rabies-RFFIT titer &gt 0.5 IU/mL that is nominally indicative of protective immunity. Plasma from bats with rabies titres &gt 2 IU/mL had cross-neutralising ABLV titres &gt 1:154. A specifically developed ELISA detected a strong but transient response to KLH.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 144-167).

No / Starting from the premise that people are essentially narrative beings, I argue that the onset of severe mental illness compromises the narrative enterprise of being able to construct one's Self and one's relationships inmeaningful and coherent ways. This is due to both the curtailment of opportunities for narrative engagement and the dispossession of those whose narratives do not conform to the current conceptualization of narrative and narrativity. In these circumstances, supporting the narrative enterprise is an ethical endeavour that requires that we examine not only which narratives we construct, but also how we construct them. This requires a re-thinking of what might constitute narrative and how we might facilitate or enhance the narrativity of people with severe mental illness. Following this, I suggest four means to support the narrativity of people with severe mental illness: through maintaining narrative continuity, maintaining narrative agency, countering master narratives and attention to small stories.

Introdução: A síndrome Spoan é uma forma de paraplegia espástica complicada de herança recessiva recentemente identificada em indivíduos originários do sudoeste do estado do Rio Grande do Norte. O quadro clínico é caracterizado por atrofia óptica congênita, paraplegia crural espástica de caráter progressivo e neuropatia axonal levando a perda da função motora em membros superiores. A caracterização fenotípica dessa doença não está completa, e não foram realizados estudos quantitativos e funcionais, que poderiam mensurar a intensidade e contribuir para a definição de uma estratégia de reabilitação. Objetivos: caracterizar o desempenho motor e as habilidades funcionais de indivíduos acometidos pela Spoan. Casuística e metodologia: participaram do estudo 61 indivíduos com diagnóstico clínico de Spoan com idade entre 5 e 72 anos. Avaliou-se a força de preensão palmar por meio do dinamômetro hidráulico de Jamar e a sensibilidade a pressão profunda e protetora dos pés e mãos por meio dos monofilamentos de náilon de Semmes-Weinstein. Definiu-se o grau de dependência dos indivíduos afetados por meio do Índice de Barthel modificado. Considerou-se para a descrição do desempenho motor: 1. quantificação da espasticidade, por meio da escala modificada de Ashworth; 2. grau de disfunção, de acordo com a escala ponderada de paraplegia espástica descrita por Schule e a escala funcional de paraplegia espástica hereditária descrita por Fink; 3. grau da capacidade de deambulação, por meio do índice de deambulação 4. grau da capacidade de sentar, por meio da escala de avaliação motora. Resultados: constatou-se fraqueza de preensão manual em todos os indivíduos e os valores obtidos indicam correlação inversa moderada entre a idade e a força manual. A sensibilidade mostrava-se anormal em 100% dos indivíduos avaliados em pelo menos seis pontos dos pés e mãos. O grau de dependência foi mínimo em 3,3%, médio em 23,3%, grave em 46,6% e total em 26,6% dos pacientes. Na escala de Schule, 60% dos indivíduos obtiveram entre 40/52 e 52/52 pontos e na escala de Fink detectou-se grau 5 (máximo) de disfunção em 71% dos pacientes. O grau de espasticidade teve uma distribuição bimodal, em média, de 30,5% com grau 1 e 37,7% grau 4. A capacidade de deambulação mostrou-se reduzida, com 83% dos indivíduos restritos a cadeira de rodas e 11% acamados. A habilidade de sentar-se estava preservada em todos os pacientes, sendo que 53% o faziam apenas com apoio. Conclusão: A síndrome Spoan é uma forma grave de paraplegia espástica hereditária, responsável por incapacidade progressiva e duradoura. / INTRODUCTION: Spoan syndrome is a complex form of spastic paraplegia of recessive inheritance recently identified in individuals from Southwest of Rio Grande do Norte state. Clinical features are characterized by congenital optic atrophy, progressive spastic paraplegia, and axonal neuropathy, resulting in severe handicap. Phenotypic description of this disease is nevertheless not complete; functional and quantitative studies, that would help planning a rehabilitation strategy, have not been undertaken. OBJECTIVES: To evaluate the motor performance and functional abilities of individual with Spoan syndrome. CASUISTIC AND METHODS: 61 individuals with confirmed diagnosis of Spoan, with ages ranging from 5 and 72 years were evaluated. Hand grip strength was measured with a Jamar hydraulic dynamometer and the sensitivity to deep pressure and protective hands and feet with Semmes-Weinstein nylon monofilaments. Functional abilities were verified by the Modified Barthel Index. For motor performance, the following procedures were performed: 1. Spasticity quantification, according to modified Ashworth scale; 2. Dysfunction level, according to the spastic paraplegia rating scale described by Schule and functional scale of hereditary spastic paraplegia described by Fink; 3. Gait ability, verified with deambulation index; 4.Sitting ability, using motor assessment scale. RESULTS: grip hand weakness was reduced in all patients, with a moderate inverse correlation between age and hand strength. Sensibility was abnormal in 100% of evaluated individuals in at least six points of hands and feet. Dependency level was minimum in 3.3%, moderate in 23.3%, severe in 46.6%, and total in 26.6% of individuals. According to Schule s scale , 60% of individuals scored between 40/52 and 52/52 points; in Fink s scale,71% achieved level 5 (maximum) of dysfunction. Spasticity level had a bimodal distribution, with 30,5% achieving level 1 and 37,7% level 4. Gait ability was reduced, with 83% of individuals being wheelchair bound and 11% bedridden. Sitting ability was preserved in all patients, but 53% were able to sit only with support. CONCLUSION: Spoan syndrome is a severe form of hereditary spastic paraplegia that is responsible for progressive and long lasting handicap.

Introdução: A síndrome Spoan é uma forma de paraplegia espástica complicada de herança recessiva recentemente identificada em indivíduos originários do sudoeste do estado do Rio Grande do Norte. O quadro clínico é caracterizado por atrofia óptica congênita, paraplegia crural espástica de caráter progressivo e neuropatia axonal levando a perda da função motora em membros superiores. A caracterização fenotípica dessa doença não está completa, e não foram realizados estudos quantitativos e funcionais, que poderiam mensurar a intensidade e contribuir para a definição de uma estratégia de reabilitação. Objetivos: caracterizar o desempenho motor e as habilidades funcionais de indivíduos acometidos pela Spoan. Casuística e metodologia: participaram do estudo 61 indivíduos com diagnóstico clínico de Spoan com idade entre 5 e 72 anos. Avaliou-se a força de preensão palmar por meio do dinamômetro hidráulico de Jamar e a sensibilidade a pressão profunda e protetora dos pés e mãos por meio dos monofilamentos de náilon de Semmes-Weinstein. Definiu-se o grau de dependência dos indivíduos afetados por meio do Índice de Barthel modificado. Considerou-se para a descrição do desempenho motor: 1. quantificação da espasticidade, por meio da escala modificada de Ashworth; 2. grau de disfunção, de acordo com a escala ponderada de paraplegia espástica descrita por Schule e a escala funcional de paraplegia espástica hereditária descrita por Fink; 3. grau da capacidade de deambulação, por meio do índice de deambulação 4. grau da capacidade de sentar, por meio da escala de avaliação motora. Resultados: constatou-se fraqueza de preensão manual em todos os indivíduos e os valores obtidos indicam correlação inversa moderada entre a idade e a força manual. A sensibilidade mostrava-se anormal em 100% dos indivíduos avaliados em pelo menos seis pontos dos pés e mãos. O grau de dependência foi mínimo em 3,3%, médio em 23,3%, grave em 46,6% e total em 26,6% dos pacientes. Na escala de Schule, 60% dos indivíduos obtiveram entre 40/52 e 52/52 pontos e na escala de Fink detectou-se grau 5 (máximo) de disfunção em 71% dos pacientes. O grau de espasticidade teve uma distribuição bimodal, em média, de 30,5% com grau 1 e 37,7% grau 4. A capacidade de deambulação mostrou-se reduzida, com 83% dos indivíduos restritos a cadeira de rodas e 11% acamados. A habilidade de sentar-se estava preservada em todos os pacientes, sendo que 53% o faziam apenas com apoio. Conclusão: A síndrome Spoan é uma forma grave de paraplegia espástica hereditária, responsável por incapacidade progressiva e duradoura. / INTRODUCTION: Spoan syndrome is a complex form of spastic paraplegia of recessive inheritance recently identified in individuals from Southwest of Rio Grande do Norte state. Clinical features are characterized by congenital optic atrophy, progressive spastic paraplegia, and axonal neuropathy, resulting in severe handicap. Phenotypic description of this disease is nevertheless not complete; functional and quantitative studies, that would help planning a rehabilitation strategy, have not been undertaken. OBJECTIVES: To evaluate the motor performance and functional abilities of individual with Spoan syndrome. CASUISTIC AND METHODS: 61 individuals with confirmed diagnosis of Spoan, with ages ranging from 5 and 72 years were evaluated. Hand grip strength was measured with a Jamar hydraulic dynamometer and the sensitivity to deep pressure and protective hands and feet with Semmes-Weinstein nylon monofilaments. Functional abilities were verified by the Modified Barthel Index. For motor performance, the following procedures were performed: 1. Spasticity quantification, according to modified Ashworth scale; 2. Dysfunction level, according to the spastic paraplegia rating scale described by Schule and functional scale of hereditary spastic paraplegia described by Fink; 3. Gait ability, verified with deambulation index; 4.Sitting ability, using motor assessment scale. RESULTS: grip hand weakness was reduced in all patients, with a moderate inverse correlation between age and hand strength. Sensibility was abnormal in 100% of evaluated individuals in at least six points of hands and feet. Dependency level was minimum in 3.3%, moderate in 23.3%, severe in 46.6%, and total in 26.6% of individuals. According to Schule s scale , 60% of individuals scored between 40/52 and 52/52 points; in Fink s scale,71% achieved level 5 (maximum) of dysfunction. Spasticity level had a bimodal distribution, with 30,5% achieving level 1 and 37,7% level 4. Gait ability was reduced, with 83% of individuals being wheelchair bound and 11% bedridden. Sitting ability was preserved in all patients, but 53% were able to sit only with support. CONCLUSION: Spoan syndrome is a severe form of hereditary spastic paraplegia that is responsible for progressive and long lasting handicap.