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Ziyad, Riyam. "Nervledningsstudie av suralisnerven och dess anatomiska variation." Thesis, Högskolan Kristianstad, Sektionen för lärande och miljö, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-14046.
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Syftet med studien är att studera normala variationer i suralisnervens anatomi och utifrån detfastställa lämpligaste metoden för neurografi i kliniskt bruk. Vidare vill jag genom studien fåsvar på hur ålder och kroppslängd påverkar suralis sensoriska nerv aktion potential (SNAP)amplituden hos män och kvinnor, hur stimuleringslokationen påverka mätvärdena föramplitud och fortledningshastighet samt hur temperaturen påverkar fortledningshastigheten.Suralisnerven (SN) är den mest studerande sensoriska nerven i nedre extremiteterna hospatienter med perifer neuropati. Nervledningsstudier av SN är ett viktigt diagnostiskt verktygvid både axonal och demyeliniserande form av neuropatier. Det finns en stor spridning avnormalvärdena för SN eftersom den påverkas av olika parameter som ålder, kroppslängd ochhudtemperatur. SN är dessutom känd för sin anatomiska variation som gör att resultatetfeltolkas på grund av minskad eller frånvarande (SNAP).Fyrtio friska frivilliga personer deltog i studien. Medelålder för kvinnor var 47 (intervall 22-64) och 42 (intervall 25-54) för män. Nerven stimulerades från ett antal fördefinierade punkterpå distala halvan av vaden: medialt 14,12 och 10 cm från registretingselektroden och 2 cmlateralt från utgångspunkterna. Registrering utfördes från SN vid laterala malleolen.Studien kunde visa att SN amplitud påverkas av parameter som ålder, kön, kroppslängd ochtemperatur. Den största SNAP- amplituden registrerades från stimuleringsavstånd 10 cmmedialt och lateralt. Stimulering medialt gav större svar än stimulering lateralt.Parametrar som temperatur, ålder längd och köns påverkar normala variationer bland normalapatienter i nervledningsstudier. Studien visar att låga temperaturer ger minskadfortledningshastighet medan amplitudsvar ökar. Det är säkrare att stimulera nerven frånavstånd 10 cm medialt då risken för falskt positivt svar minimeras jämfört med avstånd 14cm. Det är viktigt att känna till suralisnervens anatomiska variationer inför mätningar vidundersökning av polyneuropati, eftersom resultaten annars kan misstolkas.
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Oluwole, O. S. A. "Endemic ataxic polyneuropathy in Nigeria /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-165-9/.
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Gross, M. L. P. "The therapeutic modification of inflammatory polyneuropathy." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599754.
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Wigenstam, Veronica. "Behandling av familjär amyloidos med polyneuropati." Thesis, Umeå universitet, Farmakologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-119817.
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Inledning Familjär amyloidos med polyneuropati (FAP) är en genetisk sjukdom som påverkar deperifera nerverna i kroppen. FAP utbryter pga. en mutation i TTR-genen som kodar förtransthyretin (TTR). Den vanligaste TTR-mutationen heter Val30Met. TTR har entetrametrisk struktur, men när TTR-genen är muterad kommer denna tetramer att brytas upp. Till följd av att tetrameren faller sönder, bildas en onormal substans som heter amyloid. Amyloid lagras i kroppens perifera nerver och orsakar skada. Idag finns två etableradebehandlingar: Levertransplantation och behandling med substansen tafamidis. Idag forskasdet på en ny behandling med substansen diflunisal. Diflunisal är ett NSAID och finns inte på marknaden i Sverige. Syfte Syftet med denna litteratur studie är att undersöka hur familjär amyloidos medpolyneuropati behandlas idag. Frågeställningarna är följande: Hur effektiv är levertransplantation vid familjär amyloidos med polyneuropati? Hur effektiv är tafamidis vid familjär amyloidos med polyneuropati? Har behandling med diflunisal någon effekt motFAP? Vilken verkningsmekanism har diflunisal mot FAP? Metod En litteraturstudie gjordes för att få svar på frågeställningarna. Åtta originalartiklar hittades i databasen PubMed. Filter “Clinical trial” , “human” och “5 years” användes för att begränsa antalet träffar. Sökningar gjordes också i web of science där en originalartikel hittades. Tre hemsidor hittades med hjälp av sökord på Google.se, som användes till inledningen. Resultat Kaplan-Meiers analys användes i tre av studierna för att mäta överlevnadsgraden hos patienter med FAP som genomgått en levertransplantation (LTx). Kontrollgrupper togs medför att jämföra med LTx grupperna. En betydligt högre överlevnadsgrad kunde ses i en LTxgrupp jämfört med en kontrollgrupp. Patienter som genomgått en levertransplantation i sendebut (≥50år) har en lägre överlevnadsgrad än patienter som fått sjukdomen tidigt. Studierna som mätt tafamidis effekt vid FAP visade på en minskad neurologisk försämring, bevarande av funktionen hos små- och stora fibrer samt bevarad quality of life (QOL). Behandling med tafamidis hos patienter som har en sen debut av sjukdomen och en mer avancerad sjukdomsbild gav ej någon effekt. Patienter som fick diflunisal jämfört med placebo i 2 år, visade en minskad progression av neurologisk försämring. De hade även en bevarad livskvalitet. Diflunisal binder till T4 på TTR tetramern. Uppbundit TTR stabiliserasoch kommer inte att brytas upp och starta amyloidgenesen. Diskussion/slutsats Levertransplantation är en bra behandlingsmetod då stora skillnader kan ses mellan LTxgrupper och kontrollgrupper. Tafamidis ger bättre effekt vid FAP än diflunisal och tafamidishar färre biverkningar. Både tafamidis och diflunisal kan stabilisera TTR tetramerer, men iolika grad. Tafamidis kunde stabilisera en högre grad (%) tetramerer. Slutsatsen avresultaten från de beskrivna studierna i detta arbete blir att det är tveksamt att ta in diflunisalsom behandling mot FAP eftersom andra behandlingsmetoder är bättre.
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Lindh, Jonas. "Cryptogenic Polyneuropathy : Clinical, Environmental, And Genetic Studies." Doctoral thesis, Linköpings universitet, Neurologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-71215.
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Objectives: The purpose of this medical thesis was to describe the clinical and neurophysiological features and to evaluate the health related quality of life (HR-QoL) in patients with cryptogenic polyneuropathy. We also wanted to investigate different occupational, and leisure time exposures as determinants for cryptogenic polyneuropathy, and to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1), and Theta-1 (GSTT1), and a low activity genetic variation of epoxide hydrolase (EPHX) affect the risk of developing polyneuropathy. These genes were chosen because their enzymes are important in the metabolism of toxic compounds. Methods: The medical records of all patients aged 40–79 years with the diagnosis of cryptogenic polyneuropathy from 1993 to 2000 were analyzed, and data regarding clinical symptoms, laboratory findings, and neurophysiological findings at diagnosis were collected. 255 cases were found. When the medical records were reevaluated assessment to a protocol 168 patients remained as cryptogenic. Two validated instruments (SF-36 and EQ-5D) for measuring HR-QoL were sent to patients, and a reference group from the general population. Additional clinical information, and data on occupational, and leisure time exposure was obtained from postal questionnaires. Crude odds ratios (COR), and logistic regression odds ratios (LOR) were calculated for exposures with five or more exposed cases and referents taken together. We also tested for genetic polymorphisms of GSTM1 and GSTT1, and epoxide hydrolase exon three, EPHX*3. Results: 68% of the patients were men. The mean age at first symptom was 61 years and at diagnosis 64 years. Distal numbness was the most common symptom, but pain, pedal paresthesias, and impairment of balance were also common. The most common clinical findings were decreased or lost proprioception or sense of vibration (80%), and loss of ankle jerks (78%). Neurography showed mixed sensorimotor polyneuropathy of axonal or mixed axonal and demyelinating type. QOL was significantly affected concerning motor functions, with 42% of the patients reporting problems to walk, 3% having problems with daily activities, and 85% were suffering from pain. Mental health was preserved. Mobility was declining with increasing age, but was not affected by disease duration. Increased risks were found in men for occupational exposure to sulphur dioxide, xylene, methyl ethyl ketone, and herbicides and in women for occupational exposure to lead, nitrous oxide, and insecticides. Interaction between occupational and leisure time exposure were seen for several exposures. No significant correlation was found between GSTM1, GSTT1, and EPHX1 polymorphisms in patients with cryptogenic polyneuropathy compared with controls. A tendency, however, was seen for the GSTT1 null phenotype, which was enhanced among smokers compared to controls (OR 3.7). Conclusions: Cryptogenic polyneuropathy is a slowly progressive sensorimotor nerve lesion of mainly axonal type. Patients with cryptogenic polyneuropathy have a lower QOL compared to the general population, although mental health scores did not differ between the groups. Our results show that known determinants could be confirmed, but also some new appeared i.e. sulphur dioxide, hydrogen sulphide, fungicides, and vibrations in the feet. Moreover our results point to a synergistic effect of various exposures. Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances and reactive oxygen that could lead to nerve damage in the peripheral nervous system. Our results are indicating that components in cigarette smoke might increase the risk of axonal neuropathy in genetically predisposed patients.
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Bonifácio, Maria João Macedo da Silva. "Studies on amyloid formation in familial amyloidotic polyneuropathy." Tese, Porto : Edição do Autor, 1996. http://catalogo.up.pt/F?func=find-b&local_base=UPB01&find_code=SYS&request=000084315.
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Bonifácio, Maria João Macedo da Silva. "Studies on amyloid formation in familial amyloidotic polyneuropathy." Doctoral thesis, Porto : Edição do Autor, 1996. http://hdl.handle.net/10216/64551.
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Redondo, Ana Clara Corujas. "Familial amyloidotic polyneuropathy : Study of structural determinants in amyloidogenesis." Tese, Universidade do Porto. Reitoria, 2002. http://hdl.handle.net/10216/9586.
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Azevedo, Ana do Carmo Ramalho Moreira. "Familial amyloid polyneuropathy: TTR sequencing and "in silico" analysis." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/15608.
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Mestrado em Biomedicina MolecularFamilial amyloid polyneuropathy (FAP) or paramiloidosis is an autosomal dominant neurodegenerative disease with onset on adult age that is characterized by mutated protein deposition in the form of amyloid substance. FAP is due to a point alteration in the transthyretin (TTR) gene and until now more than 100 amyloidogenic mutations have been described in TTR gene. FAP shows a wide variation in age-at-onset (AO) (19-82 years, in Portuguese cases) and the V30M mutation often runs through several generation of asymptomatic carriers, before expressing in a proband, but the protective effect disappear in a single generation, with offspring of late-onset cases having early onset. V30M mutation does not explain alone the symptoms and AO variability of the disease observed in the same family. Our aim in this study was to identify genetic factors associated with AO variability and reduced penetrance which can have important clinical implications. To accomplish this we genotyped 230 individuals, using a directautomated sequencing approach in order to identify possible genetic modifiers within the TTR locus. After genotyping, we assessed a putative association of the SNPs found with AO and an intensive in silico analysis was performed in order to understand a possible regulation of gene expression. Although we did not find any significant association between SNPs and AO, we found very interesting and unreported results in the in silico analysis since we observed some alterations in the mechanism of splicing, transcription factors binding and miRNAs binding. All of these mechanisms when altered can lead to dysregulation of gene expression, which can have an impact in AO and phenotypic variability. These putative mechanisms of regulation of gene expression within the TTR gene could be used in the future as potential therapeutical targets, and could improve genetic counselling and follow-up of mutation carriers.
A Polineuropatia amiloidótica familiar (FAP) ou paramiloidose é uma doença neurodegenerativa autossómica dominante com início na vida adulta sendo caracterizada pela deposição da proteína mutada na forma de substância amilóide. A FAP é devida a uma mutação pontual no gene transtirretina (TTR) e até agora mais de 100 mutações amiloidogénicas foram descritas neste gene. A FAP apresenta uma grande variação na idade de início (AO) (19-82 anos, nos casos portugueses) e a mutação V30M pode segregar através de várias gerações de portadores assintomáticos, antes de se expressar num probando. No entanto, este efeito protetor pode desaparecer numa única geração, com os filhos de casos tardios a apresentarem um início precoce. A mutação V30M não explica por si só os sintomas e a variabilidade da AO observada dentro de uma mesma família. O nosso objetivo neste trabalho foi identificar fatores genéticos associados com a variabilidade da AO e a penetrância reduzida. De modo a cumprir este objetivo genotipámos 230 doentes, por sequenciação automática, para identificar possíveis modificadores genéticos dentro do locus da TTR. Após a genotipagem, investigamos uma possível associação dos SNPs encontrados com a AO e realizamos uma intensiva análise in silico de modo a perceber uma possível regulação da expressão génica. Apesar de não termos encontrado nenhuma associação entre os SNPs e a AO, encontrámos resultados não descritos e muito interessantes na análise in silico dado termos observado algumas alterações a nível do mecanismo de splicing, ligação de fatores de transcrição e ligação de miRNAs. Todos estes mecanismos quando alterados podem levar à desregulação da expressão do gene, o que pode ter um impacto na AO e variabilidade fenotípica. Estes mecanismos hipotéticos da regulação da expressão génica no gene da TTR podem ser úteis para no futuro serem aplicados como potenciais alvos terapêuticos, beneficiando o aconselhamento genético e o follow-up dos portadores da mutação.
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Redondo, Ana Clara Corujas. "Familial amyloidotic polyneuropathy : Study of structural determinants in amyloidogenesis." Doctoral thesis, Universidade do Porto. Reitoria, 2002. http://hdl.handle.net/10216/9586.
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Amaral, José Manuel Barbas do. "Insigts in familial amyloidotic polyneuropathy portuguese type (Val30Met)salivary glands." Tese, Instituto de Ciências Biomédicas Abel Salazar, 2011. http://hdl.handle.net/10216/63642.
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Amaral, José Manuel Barbas do. "Insigts in familial amyloidotic polyneuropathy portuguese type (Val30Met)salivary glands." Doctoral thesis, Instituto de Ciências Biomédicas Abel Salazar, 2011. http://hdl.handle.net/10216/63642.
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Monteiro, Filipe Almeida. "Insights on signal transduction pathways involved in familial amyloidotic polyneuropathy neurodegeneration." Tese, Porto : Edição do Autor, 2006. http://catalogo.up.pt/F?func=find-b&local_base=UPB01&find_code=SYS&request=000105409.
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Monteiro, Filipe Almeida. "Insights on signal transduction pathways involved in familial amyloidotic polyneuropathy neurodegeneration." Doctoral thesis, Porto : Edição do Autor, 2006. http://hdl.handle.net/10216/64588.
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Cardoso, Isabel dos Santos. "Dynamics of transthyretin fibrillogenesis : contribution to therapeutic approaches in familial amyloidotic polyneuropathy." Tese, Porto : Edição do Autor, 2002. http://catalogo.up.pt/F?func=find-b&local_base=UPB01&find_code=SYS&request=000090157.
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Soares, Miguel Filipe Tavares da Luz. "Trinucleotide repeat scanning in portuguese familial amyloidotic polyneuropathy kindreds exhibiting genetic anticipation." Dissertação, Universidade do Porto. Reitoria, 1997. http://hdl.handle.net/10216/10329.
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Soares, Miguel Filipe Tavares da Luz. "Trinucleotide repeat scanning in portuguese familial amyloidotic polyneuropathy kindreds exhibiting genetic anticipation." Master's thesis, Universidade do Porto. Reitoria, 1997. http://hdl.handle.net/10216/10329.
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Cardoso, Isabel dos Santos. "Dynamics of transthyretin fibrillogenesis : contribution to therapeutic approaches in familial amyloidotic polyneuropathy." Doctoral thesis, Porto : Edição do Autor, 2002. http://hdl.handle.net/10216/64570.
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Rochette, Amber Denae. "The Relationship between Symptoms of Polyneuropathy and Cognitive Function Pre- and Post-bariatric Surgery." Kent State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1561925069394142.
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Olsson, Malin. "Familial amyloidosis with polyneuropathy : studies of genetic factors modifying the phenotype of the disease." Doctoral thesis, Umeå universitet, Medicin, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-34128.
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Background. Familial Amyloidosis with Polyneuropathy (FAP) is an autosomal dominantly inherited systemic amyloid disease. The disease is caused by mutations in the transthyretin (TTR) gene, where close to 100 different amyloidogenic mutations have been identified. FAP is found worldwide, but endemic areas with a high frequency of patients are found in Portugal, Japan and northern Sweden. Cases from these endemic areas all share the same TTR c.148G>A, p.V50M ("V30M") mutation, but the phenotype of the disease varies between the areas, and also within the endemic areas. The mean onset of the disease is two decades earlier in Portugal and Japan compared to Sweden, but late as well as early age at onset cases occur within all the populations. Interestingly, the different populations all display a maternal anticipation, where an earlier onset is observed for those individuals who inherit the trait from their mother. Since substantial variation in the phenotype is observed for different populations, epigenetic/genetic and/or environmental factors must exert a significant impact on the penetrance of the disease. Amyloid formation is caused by conformational changes of proteins, which facilitates their assembly into fibrils, amyloid. Oxidative stress can mediate conformational changes of proteins and since the mitochondria regulate oxidative processes within the cell, mitochondrial function may affect amyloid formation. The mitochondrial DNA is a non-nuclear DNA, which is entirely maternally inherited, and therefore could be related to the observed maternal anticipation of the disease. In addition, differences within the surrounding regions of the TTR gene may have an impact on the transcription of the gene and thereby on the expression of the different alleles. Material and methods. DNA from early and late onset V30M cases and from non-carriers (the latter utilised as controls) from Swedish, French, Japanese and Portuguese populations were analysed. In addition, DNA from healthy Swedish V30M carriers was analysed. Conventional analytical methods were employed, such as PCR, sequencing and genotyping. Conventional statistical methods used were t-test, Chi-squared test and maximum likelihood. Results. The study of V30M carrier frequency in two counties (Lycksele and Skellefteå) within the Swedish endemic area revealed a carrier frequency of 2.14% and 2.54%, respectively. The mitochondrial haplogroup analysis showed that in populations with generally late onset (French and Swedish), the haplogroup distribution of late onset cases resembled that of the controls derived from the same area, whereas haplogroup distribution for early onset patients was significantly different. The most pronounced difference was for the rare haplogroup K, of which early onset cases had a higher frequency than the controls. Analysis of the Portuguese population, with predominantly early onset, showed that haplogroup distribution for early onset cases were similar to the Portuguese control group, which had a different distribution than the Swedish control group. By analysis of pedigrees from Swedish and Portuguese patients it could be shown that mitochondrial genetic variation entirely could explain maternal anticipation in the Portuguese patients, whereas for Swedish patients, an additional parent of origin effect is present. Our analysis of the TTR gene disclosed a polymorphism (rs62093482) in the 3'UTR region of the Swedish patients. This polymorphism was found in all V30M carriers, irrespective of symptoms. In addition, homozygous TTR V30M carriers were homozygous also for the polymorphism. Since Swedish patients share a common founder this polymorphism thus is localised on the V30M allele. This polymorphism was found in only 4% of the Swedish controls. French controls showed the same frequency, but none of the French V30M patients displayed the polymorphism. In the Japanese population the polymorphism was not present at all. Interestingly, this polymorphism generates a potential binding site for microRNA and thereby possibly could down-regulate the expression of the mutated TTR allele. Conclusions. The carrier frequency in the endemic area is remarkably high, above 2% in the Lycksele and Skellefteå areas. The prevailing haplogroup distributions in the different endemic areas are consistent between the general population and the patient group with the predominant phenotype of that area. Mitochondrial genetic differences may explain maternal anticipation in Portuguese patients, and have an influence in Swedish patients. A polymorphism in the 3'UTR regulatory region of the mutated TTR allele is found in all Swedish patients. This polymorphism may down-regulate TTR V30M expression and thereby contribute to the late onset of the disease noted in the Swedish population.
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Karlström, Sandra. "Förekomst av dyssynkroni hos patienter med förtjockade hjärtväggar." Thesis, Umeå universitet, Biomedicinsk laboratorievetenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-90058.
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Mörner, Stellan. "Hypertrophic cardiomyopathy in Northern Sweden : with special emphasis on molecular genetics." Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-274.
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Hypertrophic cardiomyopathy (HCM) is a heterogeneous, often familial disease, characterized by cardiac hypertrophy, predominantly affecting the interventricular septum. To date, no study has systematically analysed the genetic and phenotypic aspects of the disease in a Swedish population. The aim of this thesis was to identify the genotypes causing HCM in northern Sweden, to characterize the disease phenotypes and correlate these findings. Forty-six patients were recruited for the genetic studies (21 women), 11 familial and 35 sporadic cases. Eight sarcomeric protein genes were screened for mutations. A total of 11 different disease causing mutations were found in four genes. Six of the mutations were previously not described. A novel mutation (a 33 base pair deletion) in the troponin I gene was found in one HCM family. Despite the severe genetic defect, the associated phenotype displayed only mild cardiac hypertrophy and few symptoms. Most mutations (64%) were identified in the myosin binding protein C gene, a gene considered to have a low penetrance. Mutations were identified in 10 of 11 familial HCM cases, but only in three of the 35 sporadic cases. It was found that cardiac amyloidosis can sometimes present itself as HCM. Three HCM patients (7%) carried the ATTR Val30Met mutation, also found in Swedish patients with familial amyloid polyneuropathy (FAP). The patients had no symptoms of polyneuropathy, but cardiac amyloidosis as the cause of hypertrophy was verified by myocardial biopsy in an index case. Amyloid heart disease should therefore be considered as a differential diagnosis in patients with HCM. By studying heart rate variability (HRV), it was found that young patients with HCM had signs of autonomic dysfunction, expressed as a reduced HRV. Treatment with beta-blockade attenuated these effects. Abnormal autonomic function might be a substrate for lethal arrhythmias, most often encountered in younger patients with HCM. The results suggest a possible protective effect of beta-blockade, remaining to be studied further. Ventricular function is frequently abnormal in HCM. In particular, diastolic dysfunction has been demonstrated. The recently described myocardial performance index allows the assessment of cardiac function by combining systolic and diastolic performance. We found that patients with hypertrophic cardiomyopathy had evidence of global and regional right ventricular dysfunction, besides left ventricular dysfunction. Hypertrophic cardiomyopathy is traditionally considered to be a disease of the left ventricle. The results show that hypertrophic cardiomyopathy should more be regarded as a biventricular disease. In conclusion, the myosin binding protein C gene is the most common gene causing familial HCM in northern Sweden. This disease gene is considered to be associated with a mild, late-onset disease with ≈50% penetrance at 30 years of age. The low disease penetrance emphasizes the importance of adequate family screening when evaluating patients with HCM, since the familial nature of the disease might easily be overlooked. These particular disease features in northern Sweden contrast to most previous reports, which indicate another disease gene as the most frequent in HCM, associated with a much higher penetrance. Amyloid heart disease, requiring different treatment than HCM, should be kept in mind as a differential diagnosis in the management of patients with HCM. Key words: Hypertrophic cardiomyopathy, genetics, autonomic nervous system, familial amyloid polyneuropathy, echocardiography.
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Hörnsten, Rolf. "Cardiac arrhythmias and heart rate variability in familial amyloidotic polyneuropathy : A clinical study before and after liver transplantation." Doctoral thesis, Umeå universitet, Kirurgisk och perioperativ vetenskap, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1407.
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Familial amyloidotic polyneuropathy (FAP), found in the northernmost counties in Sweden, is a rare, lethal and inherited amyloidosis. The disease is caused by mutated transthyretin (TTR). The mutation is characterized by an exchange of valine for methionine at position 30 (ATTRVal30Met). FAP is characterised by progressive polyneuropathy affecting both the peripheral and autonomic nervous system (ANS). Cardiac arrhythmia and autonomic disturbances are common as well as gastrointestinal symptoms: such as constipation and diarrhoea. Today, orthotopic liver transplantation (LTx) is the only treatment to stop the progression of FAP. The rationale for this is because 95% of TTR is synthesized by the liver, a liver transplantation should abolish the production of new mutated amyloidogenic TTR. The first liver transplantation for FAP was performed in Sweden 1990. Heart complications and autonomic disturbances are common in FAP patients both before and after liver transplantation. The aim of the present study was three-fold: to determine whether liver transplantation affects the natural course of cardiac arrhythmias and cardiac autonomic function; to predict the risk of ventricular arrhythmias; and to elucidate heart rate variability (HRV) patterns by power spectrum analysis and Poincaré plots. In total, ninety-seven Swedish FAP patients were included in the studies. The patients underwent 24-hours electrocardiography (Holter) recordings, and/or signal averaged electrocardiography (SAECG) and heart rate variability. The study showed that many patients developed cardiac arrhythmias and conduction disturbances after LTx. Approximately 25 percent of patients were pacemaker treated after LTx. The SAECG recordings disclosed that many FAP patients had ventricular late potentials (LP) compared with healthy subjects, and that LP were associated with nonsustained ventricular arrhythmia. Analyses of heart rate variability (HRV) showed reduced autonomic function in the majority of patients. Some patients had high HRV with broadband power spectra and Poincaré graphs with a fan or complex pattern. These novel findings could be an indicator of ECG abnormalities (subtle atrial arrhythmia) in FAP patients instead of reflecting normal cardiac autonomic modulation. The HRV studies also showed that LTx preserves cardiac autonomic function in FAP. In conclusion, cardiac arrhythmias, late potentials and reduced heart rate variability were common in Swedish patients with FAP, whether they underwent liver transplantation or not. The absence of LP may indicate a low risk for ventricular tachycardia in FAP patients.
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Latasiewicz, Marta Joanna. "Familial amyloid polyneuropathy: ocular complications and the use of novel non-invasive imaging techniques to assess retinal involvement." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/670403.
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Familial amyloid polyneuropathy (FAP) is a hereditary condition characterized by systemic deposition of transthyretin (TTR), which causes debilitating peripheral polyneuropathy, cardiopathy, nephropathy and usually after a few years, ophtalmopathy. Occasionally the onset can be atypical and the diagnosis of FAP is reliant on identifying ocular amyloid deposition clinically and histopathologically. However, images of TTR derived from the eye, identified using immunolabeling techniques, have so far not been published.
In ocular tissues FAP can cause sight-threatening complications such as glaucoma and retinal amyloid angiopathy. Glaucoma in FAP often requires surgical treatment. Nonpenetrating deep sclerectomy (NPDS) is a surgical technique with several advantages over the traditional trabeculectomy. It is successfully performed in primary and many types of secondary open-angle glaucoma, but so far with limited reports in FAP.
Retina imaging modalities, such as optic coherence tomography (OCT) and autofluorescence (AF), have significant value in the assessment of retinal pathologies. Fluorescein angiography is the conventional method of evaluating retinal vasculature, but requires injection of fluorescein, which has several side effects and contraindications. Recently a new non-invasive modality, the OCT angiography (OCT-A) has become a useful tool for visualizing posterior pole blood circulation. In patients with FAP the use of OCT-A has so far not been reported and only few cases of AF findings were published.
This doctoral thesis, presented as a compendium of publications, is divided into three parts.
The first part (Paper 1) aims to present the immunostaining images of TTR amyloid derived from the vitreous of a series of patients with FAP, which demonstrates vitreous biopsy as a valid diagnostic tool, especially in clinically challenging cases.
The second part (Paper 2) is a retrospective review of clinical charts of patients with FAP to determine the prevalence and characteristics of open-angle glaucoma secondary to FAP. It reveals the particularly quick progression of glaucoma in FAP and its increased risk in patients with a previous vitrectomy. Surgical management and outcomes of the affected patients are presented, indicating that NPDS is a safe and effective treatment of glaucoma secondary to FAP.
The third part (Paper 3) is an observational cross-sectional study of retinal findings in patients with FAP. It gives a descriptive analysis of retinal images in FAP using novel non-invasive techniques: AF, OCT, OCT-A, and ultra-wide-field (UWF) retinography. These modalities can be used to detect perivascular retinal amyloid deposits, as well as microvascular changes including areas of non-perfusion, allowing better understanding of the pathology, complications and prognosis of patients with FAP. It also shows that amyloid retinopathy is more frequent than previously reported.
The thesis outcomes emphasize glaucoma and retinopathy as the severe irreversible complications of FAP and need for addressing them promptly. This is especially important in establishing adequate regular eye reviews in patients with FAP and identifying those individuals requiring stricter ophthalmological care to prevent vision loss.La polineuropatía amiloidótica familiar (PAF) es una enfermedad hereditaria caracterizada por el depósito sistémico de transtiretina (TTR), que resulta en polineuropatía periférica debilitante, cardiopatía, nefropatía y, habitualmente, después de unos años, oftalmopatía. Ocasionalmente, el inicio puede ser atípico y el diagnóstico de PAF depende de la identificación de depósitos de amiloide en tejidos oculares clínicamente e histopatológicamente. Sin embargo, hasta ahora no se han publicado imágenes de TTR derivadas del ojo, identificadas utilizando técnicas de inmunotinción. En los tejidos oculares, la PAF puede causar complicaciones amenazantes para la vista, como el glaucoma y la angiopatía amiloide de la retina. El glaucoma en la PAF frecuentemente requiere tratamiento quirúrgico. La esclerectomía profunda no penetrante (EPNP) es una técnica quirúrgica con varias ventajas sobre la trabeculectomía tradicional. Se realiza con éxito en glaucoma de ángulo abierto primario y muchos tipos de glaucoma secundario, pero hasta ahora con pocos casos descritos en PAF. Las modalidades de imágen de retina, como la tomografía de coherencia óptica (OCT) y la autofluorescencia (AF), tienen un valor importante en la evaluación de las patologías retinianas. La angiografía con fluoresceína es el método convencional para evaluar la vasculatura retiniana, pero requiere la inyección de fluoresceína, que tiene varios efectos secundarios y contraindicaciones. Recientemente, una nueva modalidad no invasiva, la angiografía OCT (OCT-A) se ha convertido en una herramienta útil para visualizar la circulación sanguínea del polo posterior. En pacientes con PAF, el uso de OCT-A no ha sido publicado hasta ahora, y solo se han descrito dos casos de hallazgos de AF. Esta tesis doctoral, presentada como un compendio de publicaciones, se divide en tres partes. La primera parte (Artículo 1) tiene como objetivo presentar las imágenes de inmunotinción de TTR amiloide derivado del vítreo en una serie de pacientes con PAF, lo que demuestra que la biopsia vítrea es una herramienta de diagnóstico válida, especialmente en casos clínicamente atípicos. La segunda parte (Artículo 2) es una revisión retrospectiva de las historias clínicas de pacientes con PAF para determinar la prevalencia y las características del glaucoma de ángulo abierto secundario a la PAF. Revela la progresión particularmente rápida del glaucoma en la PAF y su mayor riesgo en pacientes con vitrectomía previa. Se ha presentado el tratamiento quirúrgico y los resultados de los pacientes afectados, lo que indica que EPNP es un tratamiento seguro y efectivo para el glaucoma secundario a PAF. La tercera parte (Artículo 3) es un estudio transversal observacional de hallazgos retinianos en pacientes con PAF. Se expone un análisis descriptivo de las imágenes de la retina en PAF utilizando nuevas técnicas no invasivas: AF, OCT, OCT-A y retinografía de campo amplio (UWF). Estas modalidades se pueden utilizar para detectar depósitos amiloides perivasculares de la retina, así como cambios microvasculares que incluyen áreas de no perfusión, lo que permite una mejor comprensión de la patología, las complicaciones y el pronóstico de los pacientes con PAF. También se muestra que la retinopatía amiloidea es más frecuente de lo que se publicó anteriormente. Los resultados de la tesis enfatizan el glaucoma y la retinopatía como las complicaciones irreversibles graves de la PAF y la necesidad de abordarlos precozmente. Esto es especialmente importante para establecer revisiones oculares regulares adecuadas en pacientes con PAF e identificar a aquellas personas que requieren atención oftalmológica más estricta para prevenir la pérdida de visión.
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Hörnsten, Rolf. "Cardiac arrhythmias and heart rate variability in familial amyloidotic polyneuropathy : a clinical study before and after liver transplantation /." Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1407.
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Centner, Chad. "Distal sensory polyneuropathy in HIV/TB co-infection : the role of vitamin B6 and N-acetyltransferase 2 genetic variation." Master's thesis, University of Cape Town, 2012. http://hdl.handle.net/11427/3370.
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Both human immunodeficiency virus (HIV) infection and tuberculosis (TB) are complicated by a painful distal sensory polyneuropathy (DSP) that may be due to virus-related HIV-DSP, antiretroviral toxic neuropathy (ATN) or isoniazid-induced peripheral neuropathy (INH-PN). In co-infection with and co-treatment for HIV/TB, DSP risk is increased. Factors driving this risk may be vitamin B6 deficiency and slow metabolism of INH mediated by N-acetyltransferase 2 (NAT2) acetylation, both known risk
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Maritz, Jean. "Distal sensory polyneuropathy in South Africans infected with human immunodeficiency virus : a cross-sectional analysis of a community cohort." Master's thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/8938.
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Includes bibliographical references (leaves 93-107).Introduction: Distal sensory polyneuropathy (DSP), the most common neurological complication of HIV infection, is related to either HIV or antiretroviral therapy (ART). Dideoxynucleoside reverse transcriptase inhibitors such as stavudine are widely used in resource-poor countries and often associated with neuropathy. The prevalence of DSP in developed countries range from 21% to 63%; little data is available from Africa. We aimed to estimate the prevalence of DSP in a South African community clinic-based population and to investigate associated risk factors. Methods: In a cross-sectional study, DSP status was determined in 598 HIV-infected adults using validated tools (Brief Peripheral Neuropathy Screen and a modified version of the Total Neuropathy Score) to categorize subjects. Symptomatic DSP required the presence of at least two neuropathic signs together with at least one symptom. Asymptomatic DSP required the presence of two neuropathic signs. Clinical, anthropometric, quality of life and laboratory evaluations were prospectively performed. Information about CD4 counts, antiretroviral therapy (ART) and questionnaires regarding previous tuberculosis (TB) and alcohol exposure was retrospectively collected Results: Approximately half (49%) of the study population were diagnosed with DSP (30% symptomatic DSP). In the ART-naïve group 37% had evidence of neuropathy (23% symptomatic) compared to 63% of the ART-exposed subjects (39% symptomatic). Overall, subjects with DSP were older (p<0.001) and had lower CD4 counts (p<0.001) compared to those without neuropathy. Previously treated TB infection (p<0.001) and ART use (p<0.001) showed strong associations with DSP. In multivariate analyses the odds (95% confidence interval) of developing DSP was independently associated with ART use (OR 1.7, 1.0-2.9), age (per 10 year increments) (OR 1.7, 1.4-2.2) and previously treated TB infection (OR 2.0, 1.3-3.0). Although stavudine significantly associated with DSP, the duration of exposure was similar irrespective of neuropathy status. Pain or paresthesia was reported by 69% of those with symptomatic DSP and rated as at least moderate to severe. ART-exposed subjects had a tendency towards lower pain scores compared to ART-naïves (p=0.032). Conclusions: DSP is a clinically significant problem in urban HIV-infected Africans. The findings of this study raise the possibility that with avoidance of stavudine-containing regimens in older subjects, especially those with a history of previously treated TB infection, the prevalence of DSP may be reduced.
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Wähner, Michael. "Klinische Studie zum Vergleich des schmerztherapeutischen Effektes von Mikroreizstrom-Therapie versus Placebo bei schmerzhafter diabetischer Neuropathie." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-90086.
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Diabetes mellitus und seine Folgeerkrankungen haben aufgrund der hohen Prävalenz in der Bevölkerung eine starke medizinsche Relevanz. Dabei stellen die durch eine diabetische Neuropathie ausgelösten Schmerzen ein Herausforderung in der Schmerztherapie dar. Die Behandlung dieser Schmerzen mit TENS ist eine oft angewendete Therapieoption, welche jedoch in ihrer Wirksamkeit nicht ausreichend evidenzbasiert gesichert ist, da es methodenbedingt bei klinischen Studien zur Wirksamkeit der TENS-Therapie oft Zweifel an einer ausreichenden Verblindung gibt. Die vorliegende Studie untersuchte deshalb Mikro-TENS als Therapiealternative zur TENS-Behandlung im Rahmen einer einfach verblindeten, placebokontrollierten, klinischen Studie mit 41 Patienten. Die Placebokontrolle ist bei der Anwendung von Mikroreizstrom möglich, weil dieser unterhalb der Wahrnehmungsschwelle für sensible Nervenfasern liegt. Damit können die Patienten nicht zwischen MENS-Therapie und Placebo-Therapie unterscheiden.
Die Diabetespatienten wurden über 4 Wochen in insgesamt 12 Sitzungen à 30 Minuten mit Mikro-TENS am distalen Fuß beidseits behandelt. Als Messgrößen dienten der PDI, der NPS, der ADS und die durchschnittliche Schmerzintensität auf einer numerischen Ratingskala von 0 bis 10. Diese Variablen wurden jeweils zu Beginn der Studie, direkt am letzten Behandlungstag und einen Monat nach der letzten Behandlung erhoben.
Der PDI Score zeigte nach vierwöchiger Therapie eine durchschnittliche absolute Reduktion von 4,27 \\pm 4,17 in der Verum- und 3,79 \\pm 7,71 in der Placebogruppe. Eine mindestens 30 %ige Verbesserung des NPS- und PDI-Scores wurde als Ansprechen auf die Therapie gewertet. Insgesamt konnte bei circa 30 % der 40 Studienteilnehmer eine Therapieresponse festgestellt werden. Laut NPS sprachen nach vier Wochen Reizstromtherapie 6 von 22 Patienten in der Verumgruppe und 10 von 19 Patienten in der Placebogruppe auf die Therapie an. Die Unterschiede zwischen den Studiengruppen waren statistisch nicht signifikant.
Letztlich konnte die Wirksamkeit von Mikroreizstromtherapie bei diabetischer Polyneuropathie nicht bestätigt werden. Mit einer größeren Fallzahl und damit größerer statistischer Power könnte möglicherweise ein geringer Unterschied im Therapieerfolg zwischen Placebo- und Verumbehandlung statistisch signifikant werden. Dieser Therapieeffekt wäre aber möglicherweise schmerztherapeutisch als nicht relevant einzuschätzen, da es sich mit 80 %iger Wahrscheinlichkeit (Power der vorliegenden Studie) um eine Reduktion von weniger als 15 Punkten im PDI handelt. Daher kann die Mikroreizstromtherapie zur symptomatischen Therapie bei schmerzhafter diabetischer Neuropathie (dPNP) nicht empfohlen werden. Auf die Wirksamkeit von TENS mit höheren Stromstärken zur Behandlung der dPNP kann anhand der vorliegenden Studie kein Rückschluß gezogen werden.
Es profitieren dennoch circa 30 % der insgesamt 40 Studienteilnehmer von der Intervention. Da in der Schmerztherapie Ansprechraten auf eine Placebotherapie von 7 bis 49 % möglich sind, stellt TENS eine Möglichkeit dar, diesen Effekt zusätzlich mit relativ geringem Aufwand auszuschöpfen. Vorteile in der Therapie mit Reizstrom sind außerdem geringe Kosten, nahezu keine unerwünschten Nebenwirkungen und fast kein Vorliegen von Kontraindikationen. Damit ist diese zusätzliche Therapieoptionen der dPNP neben einer optimale Einstellung des Blutzuckers und einer medikamentösen Schmerztherapie nicht außer Acht zu lassen und die Wirksamkeit komplexer Therapieprogramme mit Langzeitreizstromtherapie sollte in weiteren kontrollierten klinischen Studien eruiert werden.
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Andersson, Karin, M. Pokrzywa, Ingrid Dacklin, and Erik Lundgren. "Inhibition of TTR aggregation-induced cell death : a new role for serum amyloid P component." Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-65622.
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BACKGROUND: Serum amyloid P component (SAP) is a glycoprotein that is universally found associated with different types of amyloid deposits. It has been suggested that it stabilizes amyloid fibrils and therefore protects them from proteolytic degradation. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we show that SAP binds not only to mature amyloid fibrils but also to early aggregates of amyloidogenic mutants of the plasma protein transthyretin (TTR). It does not inhibit fibril formation of TTR mutants, which spontaneously form amyloid in vitro at physiological pH. We found that SAP prevents cell death induced by mutant TTR, while several other molecules that are also known to decorate amyloid fibrils do not have such effect. Using a Drosophila model for TTR-associated amyloidosis, we found a new role for SAP as a protective factor in inhibition of TTR-induced toxicity. Overexpression of mutated TTR leads to a neurological phenotype with changes in wing posture. SAP-transgenic flies were crossed with mutated TTR-expressing flies and the results clearly confirmed a protective effect of SAP on TTR-induced phenotype, with an almost complete reduction in abnormal wing posture. Furthermore, we found in vivo that binding of SAP to mutated TTR counteracts the otherwise detrimental effects of aggregation of amyloidogenic TTR on retinal structure. CONCLUSIONS/SIGNIFICANCE: Together, these two approaches firmly establish the protective effect of SAP on TTR-induced cell death and degenerative phenotypes, and suggest a novel role for SAP through which the toxicity of early amyloidogenic aggregates is attenuated.Epub 2013 Feb 4.
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Schmidt, Débora. "Características clínicas do desenvolvimento de polineuromiopatia do doente crítico em uma Unidade de Terapia Intensiva." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/71285.
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Introdução: A polineuromiopatia do doente crítico (PNMDC) é uma freqüente complicação neuromuscular adquirida na Unidade de Terapia Intensiva (UTI). O principal fator de risco está relacionado à sepse e à disfunção de múltiplos órgãos sendo que sua incidência pode variar entre 50 a 100%. A confirmação do diagnóstico é feita pela eletroneuromiografia, porém sugere-se que as características clínicas (fraqueza muscular, alterações sensoriais e de reflexos e dificuldade de desmame da ventilação mecânica) possam ser suficientes para o diagnóstico clínico. Objetivo: Identificar sinais clínicos que possam ser utilizados como marcadores para auxiliar no diagnóstico de PNMDC à beira do leito em pacientes sépticos. Resultados: Cinquenta pacientes foram avaliados e divididos em dois grupos conforme o resultado da eletroneuromiografia (PNMDC e não PNMDC). Os pacientes com PNMDC tinham idade maior e eram mais graves (APACHE IV e SAPS 3), permaneceram maior período hospitalizados e necessitaram de suporte ventilatório por mais tempo. Os pontos de corte: <40 para escore Medical Research Council (MRC); <7 kg para dinamometria em homens e <4 kg em mulheres; <34 cmH2O para pressão expiratória máxima e >-40 cmH2O para pressão inspiratória máxima conseguiram identificar com bons níveis de sensibilidade e de especificidade os pacientes com PNMDC. Conclusões: A força muscular esquelética pelo escore MRC, dinamometria e pressões respiratórias máximas é uma método simples que permite a identificação de PNMDC em uma avaliação clínica à beira do leito.Introduction: Critical illness polyneuromyopathy (CIPNM) is a frequent acquired neuromuscular complication in the Intensive Care Units (ICU). The main risk factor is related to sepsis and multiple organs dysfunction and the incidence of this disorder can reach 50-100%. The diagnosis is made by electromyography, but it is suggested that the clinical features (muscle weakness, sensory and reflexes changes and difficulty in weaning patients from mechanical ventilation) may be sufficient for clinical diagnosis. Objective: To identify clinical signs that may be used as markers to help in the bedside diagnosis of CIPNM in septic patients. Results: Fifty patients were evaluated and divided into two groups according to the results of electromyography (CIPNM and non-CIPNM). The patients with CIPNM were older, showed more severe illness (Apache IV and Saps 3), remained hospitalized for longer period of time, and required longer period of ventilatory support than non-CIPNM. The cutoffs that could identify the patients with CIPNM with good levels of sensitivity and specificity were: Medical Research Council (MRC) score <40; dynamometry <7 kg for men and <4 kg for women, maximal expiratory pressure (MEP) <34 cmH2O and maximal inspiratory pressure (MIP) > -40 cmH2O . Conclusions: The assessment of skeletal muscle strength by MRC score, dynamometry and maximum respiratory pressure is a simple method that allows the diagnosis of CIPNM through a clinical examination at the bedside.
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Campêlo, Maria das Graças Loureiro das Chagas. "Polineuropatia Periférica na Doença de Parkinson Idiopática." Programa de Pós-Graduação em Medicina e Saúde, 2013. http://www.repositorio.ufba.br/ri/handle/ri/13152.
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Palavras-chaves: 1.; 2.; 3.; 4.; 5..1.; 2.; 3.levodopa; 4., 5.homocysteine.
Indivíduos com doença de Parkinson idiopática (DPI) podem apresentar neuropatia periférica, o que pode agravar o desempenho motor. A causa da neuropatia periférica nesses pacientes é controversa. Objetivos- Identificar a prevalência de polineuropatia periférica (PNP) e os fatores que contribuem para seu surgimento na DPI. Métodos- Corte transversal com grupo controle. Foram avaliados 66 indivíduos: 36 com doença de Parkinson e 30 controles quanto à presença de polineuropatia pelos Escores de Toronto (ET), de Sintomas (ESN) e de Comprometimento Neuropáticos (ECN), e pela Eletroneuromiografia (EMG). Investigou-se a possível associação entre níveis séricos aumentados de homocisteína (HCI), hipovitaminose B12 (VB12), e diminuição de ácido fólico no soro, uso da levodopa, a gravidade da doença de Parkinson e a PNP. Resultados- O grupo Parkinson foi composto por 16M/20F [idade 69,4±6,8 anos] e os controles por 12M/18F[idade 70,5±6,1 anos]. A maioria dos participantes apresentou escores clínicos sugestivos de neuropatia, ET [controles 3,8±2,6; DPI 5,3±1,8, p=0,012], ECN [controles 3,0±2,3; DPI 4,2±1,7, p=0,026], alterações neuropáticas no estudo condução nervosa sensitiva e motora dos nervos sural e fibular ocorreu em 3% dos controles e em 8% dos pacientes com DPI. Embora a HCI tenha sido mais alta nos DPI, a diferença não foi significante [DPI 16,01±6,88 mmol/L; controles 14,68±5,77 mmol/L, p=0,403]; níveis baixos de VB12 foram mais frequentes nos controles 30% vs 19,4%, p=0,961. Não houve associação entre as dosagens bioquímicas (coef.associação= 0,30), nem entre o uso de levodopa (Phi= 0,533) e a PNP, que esteve associada a DPI (RC=2,64). Conclusão- Na nossa amostra, os escores neuropáticos foram mais altos entre os portadores de DPI e não esteve associado ao uso da levodopa nem a hiperhomocisteinemia e/ou deficiência da vitamina B12.
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Vilà, Rico Marta. "Transthyretin familial amyloid polyneuropathy: novel therapeutics derived from drug repurposing and new insights in diagnosis through proteomic analysis of clinical samples." Doctoral thesis, Universitat Ramon Llull, 2015. http://hdl.handle.net/10803/299374.
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La transtirretina (TTR) és una proteïna tetramèrica amiloidogènica (55 kDa) present al plasma humà i responsable del transport de la hormona T4 i del retinol a través de la proteïna d’unió a retinol (RBP). La proteïna TTR està associada amb diverses amiloïdosis, concretament la polineuropatia amiloide familiar (FAP), la cardiomiopatia amiloide familiar (FAC) i l’amiloïdosi senil sistèmica (SSA). La variabilitat associada a la TTR es deu tant a mutacions puntuals al gen codificant per aquesta com a modificacions post-traduccionals (PTMs) al residu Cys-10. Les PTMs més comuns associades a la Cys-10 de la TTR són la S-Sulfonació (S-Sulfo), la S-Glicinilcisteinilació (S-CysGly), la S-Cisteinilació (S-Cys) i la S-Glutationilació (S-GSH). Es creu que dites PTMs associades a la Cys-10 podrien jugar un paper biològic important en l’inici i procés patològic de les diferents amiloïdosis lligades a TTR.
Hem tractat les amiloïdosis lligades a TTR des de dues perspectives diferents i) Intervencions terapèutiques i ii) Diagnòstic i monitorització de FAP. Referent a la primera part del projecte, hem portat a terme el cribratge de 41 possibles inhibidors de fibril·logènesis seleccionats mitjançant estratègies bioinformàtiques de repurposing de fàrmacs. Com a resultat de l’estudi, s’han trobat 4 nous estabilitzadors del tetràmer de TTR i, per tant, nous candidats pel tractament d’amiloïdosis lligades a TTR.
Pel que fa a l’aproximació diagnòstica d’aquest treball, hem desenvolupat una metodologia per a la quantificació de PTMs en mostres de sèrum, així com per a la determinació dels nivells de TTR en aquest, tant en individus sans (wt) com en individus portadors de TTR amiloïdogènica (mutació V30M). Dita metodologia consisteix en una primera etapa d’enriquiment en TTR mitjançant immunoprecipitació, seguit de l’anàlisi de la TTR per espectrometria de masses de i) la proteïna intacta i ii) els pèptids de TTR portadors de les PTMs d’interès mitjançant l’anàlisi dirigit per LC-MS. L’anàlisi de les mostres de sèrum per la combinació d’ambdues estratègies aporta informació sobre la quantificació relativa i absoluta de les diferents PTMs presents a la TTR. Ha sigut possible mostrar que els mètodes basats en proteïna intacta es troben esbiaixats per algunes de les PTMs, donat que assumeixen un factor de resposta constant per les diferents isoformes. Contràriament, el nou mètode de LC-MS dirigit permet la quantificació absoluta de les diferents PTMs i els nivells totals de TTR (wt i mutant). La metodologia reportada ha sigut aplicada en l’anàlisi de dos grups de mostres clíniques. Com a resultat de l’estudi de mostres humanes de pacients de FAP en els diferents estadis de la malaltia, suggerim de forma preliminar les isoformes S-GSH i S-CysGly com a biomarcadors de progressió de la malaltia, permetent la diferenciació entre pacients en estadi 0 i 1 i, per tant, indicant l’aparició de la malaltia. Mitjançant l’anàlisi de mostres de pacients de FAP a diferents temps després de sotmetre’s a un transplantament de fetge (LT) i de pacients receptors de transplantament de fetge dominó provinent d’individus portadors de la mutació V30M, hem caracteritzat la progressió de la relació wt:V30M, així com l’evolució dels nivells de PTMs a la Cys-10, des de la intervenció fins a 9 anys després. Addicionalment, hem observat diferències significatives en els nivells de S-GSH i S-CysGly en comparar pacients de LT i DLT, resultats anàlegs als obtinguts en la comparació d’individus wt (sans) i pacients de FAP en estadi 0.La transtirretina (TTR) es una proteína tetramérica amiloidogénica (55 kDa) presente en el plasma humano y la responsable del transporte de la hormona T4 y el retinol, a través de la proteína de unión al retinol (RBP). La proteína TTR está asociada con varias amiloidosis, concretamente la polineuropatía amiloide familiar (FAP), la cardiomiopatía amiloide familiar (FAC) y la amiloidosis senil sistémica (SSA). La variabilidad encontrada en la TTR se debe tanto a mutaciones puntuales encontradas en el gen que codifica para ésta como a modificaciones post-traduccionales (PTMs) en el residuo Cys-10. Las PTMs más comunes asociadas a la Cys-10 de la TTR son la S-Sulfonación (S-Sulfo), la S-Glicinilcisteinilación (S-CysGly), la S-Cisteinilación (S-Cys) y la S-Glutationilación (S-GSH). Se cree que dichas PTMs asociadas a la Cys-10 podrían jugar un papel biológico importante en el inicio y proceso patológico de las distintas amiloidosis ligadas a TTR. Hemos abordado las amiloidosis ligadas a TTR desde dos perspectivas distintas i) Intervenciones terapéuticas y ii) Diagnóstico y monitorización de FAP. Respecto a la primera parte del proyecto, hemos llevado a cabo el cribado de 41 posibles inhibidores de fibrilogenesis seleccionados mediante estrategias bioinformáticas de repurposing de fármacos. De este modo, se han encontrado 4 nuevos estabilizadores del tetrámero de TTR y por tanto, nuevos candidatos para el tratamiento de amiloidosis ligadas a TTR. En relación a la aproximación diagnóstica de este trabajo, hemos desarrollado una metodología para la cuantificación de PTMs en muestras de suero, así como para la determinación de los niveles de TTR en éste, tanto en individuos sanos (wt) como en individuos portadores de TTR amiloidogénica (mutación V30M). Dicha metodología consiste en una primera etapa de enriquecimiento en TTR mediante immunoprecipitación, seguido por el análisis de ésta mediante espectrometría de masas de i) la proteína TTR intacta y ii) de los péptidos de TTR portadores de las PTMs de interés mediante análisis dirigido por LC-MS. El análisis de muestras de suero mediante la combinación de ambas estrategias aporta información sobre la cuantificación relativa y absoluta de las distintas PTMs en TTR. Ha sido posible mostrar que los métodos basados en proteína intacta se encuentran sesgados para algunas de las PTMs, dado que asumen un factor de respuesta constante para las distintas isoformas. Por el contrario, el nuevo método de LC-MS dirigido permite la cuantificación absoluta de las distintas PTMs y los niveles totales de TTR (wt y mutante). La metodología reportada ha sido aplicada en el análisis de dos grupos de muestras clínicas. Como resultado del estudio de muestras humanas de pacientes de FAP en los distintos estadios de la enfermedad, sugerimos de forma preliminar las isoformas S-GSH y S-CysGly como biomarcadores de progresión de la enfermedad, permitiendo la diferenciación entre pacientes en estadio 0 y 1 y, por lo tanto, indicando la aparición de la enfermedad. Mediante el análisis de muestras de pacientes de FAP a distintos tiempos después de someterse a un trasplante de hígado (LT) y de pacientes receptores de trasplante de hígado dominó proveniente de individuos portadores de la mutación V30M, hemos caracterizado la progresión del ratio wt:V30M así como la evolución de los niveles de PTMs en la Cys-10, des de la intervención hasta 9 años después. Adicionalmente, hemos observado diferencias significativas en los niveles de S-GSH y S-CysGly en comparar pacientes de LT y DLT, resultados análogos a los obtenidos en la comparación de individuos wt (sanos) y pacientes de FAP en estadio 0.
Transthyretin (TTR) is an amyloidogenic tetrameric protein (55kDa) present in human plasma, transporting T4 hormone and retinol, through the retinol binding protein (RBP). TTR is associated with several amyloidosis, namely familial amyloidotic polyneuropathy (FAP), familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA). Variability of TTR is not only due to point mutations in the encoding gene but also to post-translational modifications (PTMs) at Cys-10, the most common PTMs being the S-Sulfonation (S-Sulfo), S-Glycinylcysteinylation (S-CysGly), S-Cysteinylation (S-Cys) and S-Glutathionylation (S-GSH). It is thought that PTMs at Cys-10 may play an important biological role in the onset and pathological process of amyloidosis related to TTR. We have aimed TTR amyloidosis from two different perspectives i) Therapeutic interventions and ii) FAP diagnosis and monitoring. Regarding the first branch of the project, we have performed the screening of a library of 41 possible fibrillogenesis inhibitors selected by a bioinformatic repurposing workflow, finding 4 new TTR tetramer stabilizers and thus, new potential candidates for TTR amyloidosis treatment. Concerning the clinical approach of this work, we have developed a methodology for quantification of PTMs in serum samples, as well as for the determination of serum TTR levels, from healthy (wt) and TTR-amyloidotic (V30M mutation) individuals. It involves an enrichment step by immunoprecipitation followed by mass spectrometry analysis of (i) the intact TTR protein and (ii) targeted LC-MS analysis of peptides carrying the PTMs of interest. Analysis of serum samples by the combination of the two methods affords complementary information on the relative and absolute amounts of the selected TTR PTM forms. It is shown that methods based on intact protein are biased for specific PTMs since they assume constant response factors, whereas the novel targeted LC-MS method provides absolute quantification of PTMs and total TTR variants. The reported methodology has been applied to two different sets of clinical samples. As a result of the study of human samples of FAP patients at different disease stages, we preliminary pointed out S-GSH and S-CysGly isoforms as biomarkers of disease progression, allowing the differentiation between FAP stage 0 and 1 and therefore indicating disease onset. Through the analysis of a time series from FAP patients having undergone liver transplantation (LT) and from domino liver transplantation (DLT) recipients from V30M carriers, we have characterized the progression of the wt:V30M ratios, as well as the evolution of the Cys-10 PTMs, from transplantation and up to 9 years after. Additionally, we have observed significant differences in the levels of S-GSH and S-CysGly when comparing liver and domino liver transplanted patients, analogous to the results obtained in the comparison of wt individuals and FAP stage 0 patients.
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Silva, Alex Eduardo da. "Avaliação genotípica de pacientes com polineuropatia inflamatória desmielinizante crônica: estudo da duplicação/deleção do gene PMP22." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/17/17140/tde-25112014-142430/.
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Introdução: Polineuropatias são doenças do sistema nervoso periférico com etiologias variadas. Dentre elas são freqüentes as inflamatórias e as hereditárias, com prevalência de 0,67-7,7/100000 e 7,9-82,3/100000 para polineuropatia inflamatória desmielinizante crônica (PIDC) e Doença de Charcot-Marie-Tooth (CMT), respectivamente. Existem poucas evidências de sobreposição entre estas duas doenças e também algumas dificuldades diagnósticas em situações específicas. Objetivos: Estudar a freqüência de mutações (duplicações e deleções) do gene PMP22 em uma coorte de pacientes inicialmente diagnosticados como PIDC ou suspeitos de apresentarem as duas condições, os sinais e sintomas sugestivos da sobreposição e os fatores implicados em erro de classificação da neuropatia. Métodos: 111 pacientes com diagnóstico de PIDC foram estudados. DNA foi isolado a partir de leucócitos de sangue periférico segundo protocolo padrão. Duplicações e deleções do gene PMP22 foram avaliadas através de marcadores polimórficos do DNA localizados dentro do cromossomo 17p11.2-12, o qual contém o gene PMP22. Achados clínicos e laboratoriais também foram estudados e comparados entre os grupos. Resultados: Dentre os 111 pacientes estudados, mutações no PMP22 foram encontradas em 10 (9%), sendo duplicações em 9 pacientes e deleção em 1 paciente. Concomitância entre PIDC e CMT foi verificada em 4 pacientes (3,6%), todos com duplicação do PMP22. Os outros 6 pacientes foram diagnosticados como CMT puro (5) ou Neuropatia Hereditária Susceptível à Compressão (1), visto que não apresentaram melhora com o uso de tratamento imunomodulador e/ou imunossupressor (5 casos) ou foi estabelecido diagnóstico alternativo associado (1). Os outros 101 pacientes não tiveram duplicação nem deleção deste gene e, portanto, tinham PIDC apenas. Idade média dos pacientes com PIDC/CMT foi de 23,8±18,0 anos e 43,6±19,3 anos para pacientes sem mutações (p=0,04). Houve diferença estatísticamente significativa na resposta ao tratamento entre os grupos PIDC/CMT X CMT (p=0,008) e PIDC X CMT (p=0,00). Ausência de história familiar e presença de doenças e hábitos ligados ao desenvolvimento de neuropatias periféricas, como diabetes mellitus e ingesta de bebidas alcoólicas, por exemplo, bem como achados atípicos na eletroneuromiografia e na biópsia de nervo podem ter contribuído para a confusão diagnóstica nos casos de CMT puro. Conclusões: Alguns pacientes podem desenvolver PIDC em associação com CMT e se beneficiam do tratamento. A neuropatia hereditária poderia predispor à neuropatia inflamatória, uma vez que estes pacientes tendem a apresentar essa condição em idades mais precoces. Cautela deve ser dispensada àqueles pacientes com suspeita diagnóstica de PIDC que não têm os achados clássicos ou não melhoram com o tratamento, uma vez que podem apresentar outras etiologias para a neuropatia, dentre elas uma neuropatia hereditária, como a CMT.Introduction: Polyneuropathies are peripheral nervous system disorders with a wide range of etiologies. Among them, inflammatory and hereditary are frequent with prevalence of 0.67-7.7/100000 and 7.9-82.3/100000, for chronic inflammatory demyelinating polyneuropathy (CIDP) and Charcot-Marie-Tooth disease (CMT), respectively. There are a few evidence of ovelapping between these two conditions and also some diagnostic difficulties in specific situations. Objectives: To study the frequency of mutations in PMP22 gene (duplications and delections) among a cohort of patients initially diagnosed as CIDP or suspected to have both conditions, the signs and symptoms related to this ovelapping and factors implicated in misdiagnose. Methods: 111 patients with an initially CIDP suspected diagnosis were studied. DNA was isolated from peripheral blood leucocytes following a standard salting-out protocol. Duplications and delections in the PMP22 gene were analysed by polymorphic DNA markers located within the chromosome 17p11.2-12, wich contains the PMP22 gene. Clinical and laboratory findings were also studied and compared within groups. Results: Among 111 patients studied, 10 (9%) were found to harbor mutations in PMP22 gene, specifically duplications in nine and delection in one. We therefore diagnosed CIDP plus CMT in four patients (3.6%), all of them with a duplicated PMP22 gene. The other six patients were diagnosed as pure CMT (5) or Hereditary Neuropathy with liability to Pressure Palsy (1), as they did not improved with the use of immunomodulatory and/or immunosupressive treatment (five cases) or were found to have alternative associated diagnosis (one patient). The other 101 patients did not show duplication nor delection in this gene, so they had CIDP. Mean age of patients with CIDP/CMT were 23.8±18.0 years and 43.6±19.3 years for patients without mutations (p=0.04). There were statistically significant difference in treatmet response between groups CIDP/CMT X CMT (p=0.008) and CIDP X CMT (p=0.00). The lack of family history and presence of other diseases and habits linked to the development of peripheral neuropathies, as diabetes mellitus and alcohol intake, for instance, as well as atypical findings in electrodiagnostic studies and nerve biopsy may have contributed to misdiagnose in the pure CMT cases. Conclusions: Some patients may develop CIDP in association with CMT and have benefit from treatment. The hereditary neuropathy may predispose to the inflammatory neuropathy as these patients tend to show this condition at younger ages. Caution should be dispensed to those patients with a suspected diagnose of CIDP who do not have the classical disease findings or do not improve with treatment, as they can have alternative etiologies for the neuropathy, among them a hereditary neuropathy as CMT disease.
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Heldestad, Victoria. "Methodological aspects and usefulness of Quantitative Sensory Testing in early small fiber polyneuropathy : a clinical study in Swedish hereditary transthyretin amyloidosis patients." Doctoral thesis, Umeå universitet, Klinisk neurofysiologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-50617.
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Generalised polyneuropathy (PNP) is a common cause to neurological impairment, and may be an early symptom of a severe systemic disease. One such illness is hereditary transthyretin (TTR) amyloidosis (ATTR), a progressive fatal disorder caused by a mutation on the TTR gene. More than 100 such mutations have been found worldwide, of which Val30Met is the most common neuropathic variant with initial clinical manifestations indicating small fiber impairment. Differences in onset age, penetrance and phenotypes are present between endemic areas. Liver transplantation generally slows the progress of the symptom development, especially in patients with short disease duration. Ongoing research has also shown promising results with drug interventions. In any event, early diagnosis of PNP onset in ATTR patients is crucial to ensure early therapeutic interventions. Nerve conduction studies (NCS) and electromyography (EMG) provide the basis for evaluation of the functional state of the thick myelinated nerve fibres in patients with symptoms of PNP, but no such quantitative methods are available for the thin myelinated or unmyelinated fibers. Instead, a psychophysical method with thermal quantitative sensory testing (QST) can provide indirect information about the overall function in the afferent small fiber systems. The purpose of thesis was to evaluate the applicability of QST by the Method-of-limits (MLI) for early detection of PNP in Swedish ATTR patients with the Val30Met mutation. In healthy subjects the repeatability of the MLI was assessed, and reference values for thermal perception thresholds (TPT) in several body regions were determined. No significant differences in TPT or pain thresholds were found at repeated testing with MLI, indicating that the MLI is a reliable method. However, the results show that the arrangement of the testing order is of importance, as cold (CT) and warm (WT) perception thresholds were significantly elevated when tested after thermal pain assessments, instead of before. I general, the TPT was more elevated at lower parts of the body compared to the upper part, and with higher WT than CT, fully in accordance with the underlying anatomical and physiological prerequisites for QST. In biopsy verified ATTR patients lacking EMG and NCS abnormalities, significantly elevated TPT were found compared to controls. Furthermore, significantly more increased TPT were observed in patients with an early onset of the disease, compared those with a late onset. Finally, a combined detailed evaluation of QST and heart rate variability (HRV) analyses demonstrated correlations between QST and HRV abnormalities in patients with late onset, but not in those with early onset. The present thesis emphasizes the importance of incorporating QST early in the clinical evaluation of ATTR patients with a Val30Met mutation and with symptoms of thin fiber PNP. This is particularly indicated when patients report symptoms, or show signs, of neuropathic small fiber affection, but simultaneously exhibit normal EMG and NCS findings. The results furthermore underline the importance of performing both QST and HRV for a complete evaluation of both the thin somatic and autonomic nerve fibers, as both types of nerves may be affected early in the ATTR disease.
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Presnell, Scott. "Whatever the individual says it is : a phenomenological analysis of chronic pain in people with Human Immunodeficiency Virus-associated distal symmetrical polyneuropathy /." [St. Lucia, Qld.], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18066.pdf.
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Nienov, Otto Henrique. "Polineuropatia periférica em mulheres e homens obesos graves com síndrome metabólica sem diagnóstico de diabetes : prevalência e associações." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/118342.
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Introdução: As polineuropatias periféricas (PNP) relacionadas ao diabetes têm sido descritas em associação com fatores causais como obesidade, hipertrigliceridemia, hipertensão arterial sistêmica (HAS) e síndrome metabólica (SM), alterações que frequentemente precedem o diabetes. Objetivo: Avaliar a prevalência da PNP em indivíduos obesos graus 2 e 3 com SM sem diabetes e buscar possíveis fatores associados. Métodos: Em um estudo transversal, realizado em indivíduos obesos graus 2 e 3 com SM e sem diagnóstico de diabetes, o Michigan Neuropathy Screening Instrument (MNSI) foi utilizado para avaliar a presença de PNP. Resultados: Um total de 46 de 218 pacientes obesos graus 2 e 3 com SM e sem diabetes tinham PNP. Das variáveis estudadas, HAS (p=0.003), pressão arterial média (PAM) (p<0.001), baixo HDL-colesterol (p=0.011), níveis séricos de HDL-colesterol (p=0.048), IMC (p=0.036) e circunferência da cintura (p=0.035) mostraram-se significativamente associados com PNP. Houve uma tendência para os níveis séricos de triglicerídeos (p=0.107) se associarem com a presença de PNP. Após regressão multivariada, HAS, baixo HDLcolesterol, IMC e circunferência da cintura mantiveram-se independentemente associados. Conclusão: Baixos níveis de HDL-colesterol, hipertensão e aumento do IMC e da circunferência da cintura estão associados com PNP definido pelo MNSI em pacientes com obesidade severa e SM mas sem diabetes.Introduction: Peripheral polyneuropathy (PPN) related to diabetes has been reported in association with causal factors such as obesity, hypertriglyceridemia, systemic arterial hypertension (SAH) and metabolic syndrome (MS), changes which frequently precede diabetes. Objective: To evaluate the prevalence of PPN in subjects with grade 2 and 3 obesity with MS without diabetes and to investigate for possible associating factors. Methods: A cross-sectional study performed with grade 2 and 3 obese subjects with MS and without a diagnosis of diabetes using the Michigan Neuropathy Screening Instrument (MNSI) to assess the presence of PPN. Results: A total of 46 of 218 obese patients grade 2 and 3 with MS and without diabetes had PPN. From the variables studied, SAH (p=0.003), mean blood pressure (MBP) (p<0.001), low HDL-cholesterol (p=0.011), serum levels of HDL-cholesterol (p=0.048), BMI (p=0.036) and waist circumference (p=0.035) were significantly associated with PPN. There was a tendency for serum triglyceride levels (p=0.107) to associate with the presence of PPN. After multivariate regression, SAH, low HDL-cholesterol, BMI and waist circumference remained independently associated. Conclusion: Low levels of HDL-cholesterol, hypertension and increase of BMI and waist circumference are associated with PPN defined by the MNSI in patients with severe obesity and MS but without diabetes.
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Abulhaija, Ashraf. "The Relationship Between Total Neuropathy Score-reduced, Neuropathy Symptoms and Function." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6992.
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Chemotherapy Induced Peripheral Neuropathy (CIPN) is a common problem among cancer patients who receive a wide range of chemotherapy. This problem causes a decline in quality of life and increased disabilities. CIPN assessment instruments are either subjective, objective, or a combination of both. So far, there is no agreement on the best way for assessment. The goal of this study was to explore the relationships among subjective and objective CIPN assessment instruments. Specifically, this study aimed to 1) evaluate the relationship between the Total Neuropathy Score-reduced (mainly objective) and patients’ function, as measured by the interference scale of the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (subjective); and 2) evaluate the relationship between the Total Neuropathy Score-reduced and neuropathy symptom experience, as measured by the symptom experience scale of the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (Subjective). To achieve those aims, a secondary data analysis for 56 participants who participated in a study entitled: Group Acupuncture for Treatment of Neuropathy from Chemotherapy was done. After Pearson correlations were calculated, the study found that there is a positive, weak relationship between the TNSr and the symptom experience scale of the CIPNAT(r=0.34). A positive, week relationship was found between the TNSr and the interference with activity scale of the CIPNAT(r=0.28). These results suggest that objective and subjective assessment are not highly correlated, and likely measure different aspects of CIPN. A comprehensive assessment approach is needed for decision making in the clinical oncology setting.
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Ihse, Elisabet. "Two Types of Fibrils in ATTR Amyloidosis : Implications for Clinical Phenotype and Treatment Outcome." Doctoral thesis, Uppsala universitet, Molekylär och morfologisk patologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-160980.
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Systemic amyloidoses are a group of lethal diseases where proteins aggregate into fibrillar structures, called amyloid fibrils, that deposits throughout the body. Transthyretin (TTR) causes one type of amyloidosis, in which the aggregates mainly infiltrate nervous and cardiac tissue. Almost a hundred different mutations in the TTR gene are known to trigger the disease, but wild-type (wt) TTR is also incorporated into the fibrils, and may alone form amyloid. Patients with the TTRV30M mutation show, for unknown reasons, two clinical phenotypes. Some have an early onset of disease without cardiomyopathy while others have a late onset and cardiomyopathy. It has previously been described that amyloid fibrils formed from TTRV30M can have two different compositions; either with truncated molecules beside full-length TTR (type A) or only-full-length molecules (type B). In this thesis, the clinical importance of the two types of amyloid fibrils was investigated. We found that the fibril composition types are correlated to the two clinical phenotypes seen among TTRV30M patients, with type A fibrils present in late onset patients and type B fibrils in early onset patients. The only treatment for hereditary TTR amyloidosis has been liver transplantation, whereby the liver producing the mutant TTR is replaced by an organ only producing wt protein. However, in some patients, cardiac symptoms progress post-transplantationally. We demonstrated that the propensity to incorporate wtTTR differs between fibril types and tissue types in TTRV30M patients, with cardiac amyloid of type A having the highest tendency. This offers an explanation to why particularly cardiac amyloidosis develops after transplantation, and suggests which patients that are at risk for such development. By examining patients with other mutations than TTRV30M, we showed that, in contrast to the general belief, a fibril composition with truncated TTR is very common and might even be the general rule. This may explain why TTRV30M patients often have a better outcome after liver transplantation than patients with other mutations. In conclusion, this thesis has contributed with one piece to the puzzle of understanding the differences in clinical phenotype and treatment response between TTR amyloidosis patients, by demonstrating corresponding differences at a molecular level.
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Granat, Johanna, and Schøn Tanja Lermark. "Hur påverkar en stel ankel och appliceringen av en flexibel ankel-fot-ortos ankeln under gång? : Dynamisk analys av ankelns kinematik och kinetik hos friska människor." Thesis, Högskolan i Jönköping, Hälsohögskolan, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-43347.
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Sammanfattning Bakgrund: Perifer neuropati och polyneuropati är termer för att beskriva ett tillstånd hos individer där nerverna i det perifera nervsystemet är skadade och den motoriska samt somatosensoriska förmågan är förlorad. Ankelns motoriska kontroll är essentiell för förmågan till gång och för att bibehålla dynamisk stabilitet under gången. Vid behandling av individer med perifer neuropati används ofta en AFO för att förbättra gångförmågan. När kunskapen förbättras om vilka faktorer som påverkar gången samt hur kroppen biomekaniskt påverkas av hjälpmedlet är det till hjälp för att välja den mest fördelaktiga behandlingen. Syftet är att utvärdera hur ankelns kinematik samt kinetik i frontal- (Y) och sagittalplan (X) påverkas vid en situation där rörelse i ankeln tillåts samt vid en situation där rörelse i ankeln inte tillåts. Metod: För att studera ankelns kinematik samt kinetik använde vi oss av två interventioner på våra testpersoner. Vid en av interventionerna utförde testpersonerna en gånganalys med en dynamisk AFO (ToeOFF), där ankeln har utrymme för rörlighet. Vid den andra interventionen låstes testpersonernas ankel med gips med avsikt att tillåta så lite rörelse som möjligt i ankeln. Kinematisk samt kinetiska data samlades in från 5 friska unga vuxna individer, som ombads gå med en dynamisk AFO (ToeOFF) samt med en gipsad ankel i självvald hastighet. Datan samlades in med hjälp av gånganalys samt av programmen Visual 3D och Qualisys Track Manager. Den kinematiska datan kvantifierades av: ankelns vinkel i sagittal- (X) samt frontalplan (Y), och den kinetiska datan kvantifierades av: moment i ankeln både i sagittal- (X) och frontalplan (Y). Resultat: Studien visade en signifikant skillnad i den kinematiska samt den kinetiska datan vid jämförelse mellan de två interventionerna. Ankelns RoM var markant större med ToeOFF ortosen än med gips. Under gips interventionen genererades ett signifikant reducerat yttre plantar flekterande moment. Resultatet är menat att användas som en vägvisare för att optimera behandlingen av patienter med stabilitetsproblem i ankeln. Slutsats: Det finns en skillnad mellan gips-interventionen och ToeOFF-interventionen i ankelns kinematiska samt kinetiska data.
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du, Plessis Ronél. "Effect of an exercise training programme on muscular strength, ankle mobility, balance and gait patterns in patients with diabetic peripheral neuropathy in the lower legs." University of the Western Cape, 2021. http://hdl.handle.net/11394/8049.
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>Magister Scientiae - MScBackground: Patients who suffer from diabetic peripheral neuropathy in the leg experience a greater risk of developing gait deviations due to a decrease in strength of the lower extremities, especially the tibialis anterior and triceps surea muscle groups. Aim: The aim of the study was to determine the effect of an exercise training programme on blood pressure, fasting blood glucose, muscle strength, range of motion, balance and gait pattern deviations in patients with diabetic neuropathies. Methods: A total of fourteen participants, who had been diagnosed with diabetic peripheral neuropathy or nocturnal allodynia in either one or both extremities, were asked to participate in this study. Participants were purposively selected from two private Podiatry practices based on their signs and symptoms of diabetic neuropathy, age, gender and doctor’s clearance to participate in any form of physical activity. Dependent variables included isometric strength of the muscles surrounding the hip, knee and ankle, the range of motion of the ankle in plantarflexion and dorsiflexion using goniometry, an assessment of balance using the stork stand test, and a gait pattern analysis, using the modified Tinetti Gait pattern Assessment Scale. Study design: The study was a single-blinded, pre-test and post-test experimental study design using a quantitative approach. Intervention: The researcher (a registered biokineticist) developed a scientifically-based exercise intervention programme to specifically target the entire kinetic chain, and to reduce fall risks, improve quality of life and to assist in developing a standard protocol for patients with DPN. The intervention programme consisted of a combination of ankle, hip and knee rehabilitation, including gait pattern specific rehabilitation. The intervention took place 2-3 times a week for 45 minutes per session and was divided in four categories: Range of motion exercises, strengthening exercises, balance and proprioception and gait pattern training exercises. Results: The Mann-Whitney and Wilcoxon Sign Rank Tests were used to evaluate the differences in dependent variables from pre- to post-intervention. The level of significance was set at p<0.05. An increase in range of motion only in the left ankle dorsiflexion were observed and an increase in balance time for the left leg were observed in the intervention group after a 10-week follow up assessment. Clinical significance was observed in the intervention group, post-intervention, with a decrease in systolic (-9.09%) and diastolic blood pressure (-13.89%) and a decrease in blood glucose levels (-17.89%), however, an increase in these variables was observed in the control group post-intervention. An increase in plantarflexion, 8% (left) and 8% (right) and dorsiflexion 5.26% (left) and an 11.11% (right) increase in range of motion for both left and right ankles, and balance time for both legs, 200% (left) and 159% (right) was observed in the intervention group post-intervention. Although the muscular strength variables showed a mix of an increase and decrease in strength post-intervention in the intervention group, however a clinically significant decreased amount was observed in the control group post-intervention for the majority of muscular strength variables. Conclusions: Although not many findings of this study are statistically significant, clinical significance were observed with most of the variables of this study. The findings of this study can assist future researchers in the development of exercise interventions for patients who suffers from DPN.
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Santos, Mário Sérgio Ferreira. "Neuropatia periférica em pacientes com síndrome antifosfolípide primária." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-22022010-161123/.
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O envolvimento do sistema nervoso periférico em diversas doenças auto-imunes é bem estabelecido. No entanto, não existem estudos, com desenho metodológico apropriado, que tenham investigado a relação entre síndrome antifosfolípide primária (SAFP) e neuropatia periférica. Nosso objetivo nesse trabalho foi investigar a ocorrência de neuropatia periférica em pacientes com SAFP. Vinte e seis pacientes com SAFP (critérios de Sapporo) e vinte controles, saudáveis, pareados por sexo e idade, foram recrutados em dois centros de referência. Foram excluídas as causas secundárias de neuropatia periférica e um exame neurológico completo, seguido de estudo de neurocondução, foi realizado em todos os indivíduos. Parestesias foram observadas em oito pacientes (31%). Leve fraqueza distal e anormalidades nos reflexos tendíneos profundos, foram observados em três (11,5%) pacientes. Evidência eletrofisiológica de neuropatia periférica foi observada em nove (35%) pacientes: quatro (15,5%) pacientes apresentaram neuropatia sensitiva ou sensitivo-motora axonal distais (em dois deles, com a superposição de síndrome do túnel do carpo), um (4%) paciente apresentou neuropatia sensitivo-motora, axonal e desmielinizante, acometendo os membros superiores e inferiores, enquanto que em quatro (15,5%) pacientes, observou-se a presença isolada de síndrome do túnel do carpo. As alterações clínicas e sorológicas dos pacientes com SAFP não guardaram qualquer correlação, com as alterações eletrofisiológicas. Em conclusão, neuropatia periférica, em geral assintomática, é comum na SAFP. Estudo de condução nervosa deve ser considerado na avaliação desses pacientes.The involvement of the peripheral nervous system in diverse autoimmune diseases is well established. However, no appropriately designed studies have been performed in primary antiphospholipid syndrome (PAPS)-related peripheral neuropathy. We aimed to investigate the occurrence of peripheral neuropathy in patients diagnosed with PAPS. Twenty-six consecutive PAPS (Sapporo\'s criteria) patients and twenty age- and gender-matched healthy controls were enrolled at two referral centers. Exclusion criteria were secondary causes of peripheral neuropathy. A complete clinical neurological exam followed by nerve conduction studies (NCSs) were performed. Paresthesias were reported in 8 patients (31%). Objective mild distal weakness and abnormal symmetric deep tendon reflexes were observed in three (11.5%) patients. With regard to the electrophysiological evidence of peripheral neuropathy, nine (35.0%) patients had alterations: four (15.5%) had pure sensory or sensorimotor distal axonal neuropathy (in two of them a carpal tunnel syndrome was also present) and one (4%) had sensorimotor demyelinating and axonal neuropathy involving upper and lower extremities, while four patients (15.5%) showed isolated carpal tunnel syndrome. Clinical and serological results were similar in all PAPS patients, regardless of the presence of electrophysiological alterations. In conclusion, peripheral neuropathy is a common asymptomatic abnormality in PAPS patients. The routine performance of NCS may be considered when evaluating such patients.
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Beckmann, Juliane [Verfasser]. "Systematischer Review zur medikamentösen Prävention und Therapie Chemotherapie-induzierter peripherer Polyneuropathie = Systematic review for the medicinal prevention and treatment of chemotherapy-induced peripheral polyneuropathy / Juliane Beckmann." Halle, 2017. http://d-nb.info/1148425101/34.
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Norgren, Nina. "Hereditary transthyretin amyloidosis (ATTR V30M) : from genes to genealogy." Doctoral thesis, Umeå universitet, Medicin, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84494.
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Background: Hereditary transthyretin amyloidosis is an autosomal dominant disease with a reduced penetrance. The most common mutation in Sweden is the V30M mutation in the transthyretin gene. Clustering areas of the disease can be found in Northern Sweden, Portugal, Brazil and Japan, although sporadic cases exist worldwide. Despite being caused by the same mutation, there are large differences in onset, penetrance and symptoms of the disease. Swedish V30M patients typically have a later onset with a lower penetrance compared to those from the clustering Portuguese V30M areas. The reasons for these differences have not been fully understood. The aim of this thesis is to study mechanisms that may influence onset and symptoms and investigate why patients carrying the same mutation have different phenotypes. Methods: Genealogy studies were performed on all known V30M carriers in Sweden using standard genealogy methods. DNA samples from patients, asymptomatic carriers and controls from different countries were collected and the transthyretin gene was sequenced. Liver biopsies from patients were used for allele specific expression analysis and a cell assay was used for miRNA analysis with the mutated allele. Gene expression analysis was performed on biopsies from liver and fat from patients and controls. Results and conclusions: Genealogic analysis of all known Swedish V30M carriers managed to link together 73% of the Swedish ATTR V30M population to six different ancestors from the 17th and 18th century, thus dating the Swedish V30M mutation to be more than 400 years old. A founder effect was also visible in descendants to one of the ancestors, producing a later age at onset. Sequencing of the transthyretin gene revealed a SNP in the 3’ UTR of all Swedish V30M carriers that was not found in any of the Japanese or French V30M carriers. The SNP was present on the Swedish transthyretin haplotype and defined the Swedish V30M population as separate from others. However, the SNP itself had no effect upon phenotype or onset of disease. Gene expression analysis of liver and fat tissue revealed a change in genetic profile of the patients’ livers, in contrast to the unchanged profile of the fat tissue. A changed genetic profile of the liver could explain why domino liver recipients develop the disease much earlier than expected.
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Bergström, Joakim. "Apolipoprotein A-IV and Transthyretin in Swedish Forms of Systemic Amyloidosis." Doctoral thesis, Uppsala University, Department of Genetics and Pathology, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4535.
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Over 20 different plasma proteins have been shown to have the capacity to undergo conformational changes and self-assemble into highly stable and insoluble amyloid fibrils.
One, transthyretin (TTR), consists of 127 amino acid residues arranged in eight β-strands (named A to H) and is involved in two different clinical forms of amyloidosis. In familial amyloidotic polyneuropathy (FAP), mutated TTR is found in the amyloid deposits while in senile systemic amyloidosis (SSA) only wild type TTR is present in the amyloid deposits.
In this study, we have identified a novel form of amyloidosis that is caused by the deposition of an N-terminal fragment of apolipoprotein A-IV (apoA-IV). Interestingly, apoA-IV amyloid was found deposited in a patient that also suffered from SSA. Thus, this patient had two biochemically distinct and concurrent forms of amyloidosis that were derived from apoA-IV and TTR.
We have also discovered that two different morphological deposition patterns (identified as patterns A and B) exist in TTR-derived amyloidosis. Pattern A, observed in all SSA patients studied and in half of the FAP patients examined contained large homogenous deposits that were composed of short randomly oriented fibrils. In contrast, pattern B was observed in the remaining FAP patients and was represented by smaller-sized deposits that consisted of longer fibrils that were arranged in parallel bundles. The predominant TTR component deposited also differed between the two amyloid patterns. Amyloid pattern A contained mainly C-terminal TTR fragments while pattern B amyloid consisted of full-length TTR. Our findings suggest that two different mechanisms of fibril formation may exist in TTR-derived amyloidosis.
We have found two epitopes, corresponding to strand C and H that are surface-exposed in TTR-derived amyloid fibrils but hidden and part of the hydrophobic core in the native molecular structure. This indicates that TTR undergoes partial unfolding during fibril formation.
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Moreira, Carolina Lavigne. "Epidemiologia mutacional da polineuropatia amiloidótica familiar transtiretina em um serviço brasileiro terciário de neuropatias periféricas." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17140/tde-30032017-142719/.
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Introdução: A amiloidose transtiretina é uma doença autossômica dominante decorrente de uma proteína transtiretina (TTR) variante, que sofre uma mudança conformacional e origina um tetrâmero de TTR instável, passo que é decisivo para o início da formação dos depósitos amilóides em diferentes órgãos e tecidos. Na maioria dos pacientes, o sistema nervoso periférico é o alvo principal, resultando na polineuropatia amiloidótica familiar transtiretina (TTR-FAP), classicamente uma neuropatia sensitivo-motora e autonômica progressiva, evoluindo para o óbito em aproximadamente 10 anos. A mutação de ponto mais frequente no mundo, incluindo o Brasil, é a TTRVal30Met, entretanto mais de 100 mutações de ponto diferentes já foram descritas. Objetivos: descrever a epidemiologia mutacional do gene TTR na polineuropatia amiloidótica familiar e correlacionar estas mutações com seus achados clínicos e eletroneuromiográficos. Métodos: estudo de coorte, descritivo e retrospectivo de um grupo de pacientes brasileiros encaminhados para o serviço de neurogenética do HC da FMRP-USP para investigação de neuropatia periférica, cujo estudo genético identificou uma mutação no gene TTR, com posterior análise transversal dos resultados obtidos entre os subgrupos com as diferentes mutações. Resultados: um total de 128 pacientes tiveram uma mutação de ponto no gene TTR identificada, dos quais 12 (9,4%) pacientes apresentaram uma mutação não TTRVal30Met, incluindo 4 patogênicas (6 pacientes, 4,7%) e 2 não patogênicas (6 pacientes, 4,7%). A mutações não TTRVal30Met patogênicas foram TTRAsp38Tyr (2 pacientes), TTRIle107Val (2 pacientes), TTRVal71Ala (1 paciente) e TTRVal122Ile (1 paciente). Dentre as mutações não patogênicas, foram encontradas TTRGly6Ser (5 pacientes) e TTRThr119Thr (1 paciente). A mutação TTRVal30Met estava presente em 116 (90,6%) pacientes, dos quais 52 possuíam dados clínicos e eletroneuromiográficos completos: 39 (75%) tiveram início precoce e 13 (25%), início tardio. O grupo de início precoce apresentou-se como a forma clássica da PAF-TTR, sem predileção de gênero (homens: 53,8%), manifestação inicial como neuropatia de fibras finas e autonômica (82,1%) e história familiar positiva (90,3%). A ENMG estava normal em 36,7% destes pacientes. O envolvimento cardiovascular foi caracterizado mais frequentemente por alterações da condução cardíaca (84,2%), sendo menos prevalente a cardiomiopatia (11,1%). Por outro lado, o grupo de início tardio mostrou uma predominância do sexo masculino (92,3%), presença de sintomas motores na primeira consulta (38,5%), resultando numa neuropatia sensitivo-motora com acometimento de fibras grossas e história familiar negativa (69,2%). Todos apresentaram neuropatia sensitivo-motora na ENMG. Neste grupo, a cardiomiopatia estava presente em 71,4% dos pacientes. Todos os pacientes, em ambos os grupos, tiveram disautonomia em algum momento do seu seguimento clínico. Conclusões: no nosso estudo aproximadamente 5% dos pacientes com FAP-TTR tinham uma mutação não TTRVal30Met, demonstrando a importância do sequenciamento do gene TTR em pacientes com história clínica sugestiva e screening negativo para a mutação TTR Val30Met. Além disso, os pacientes brasileiros com FAP-TTRVal30Met apresentaram achados clínicos e eletroneuromiográficos similares as populações descritas com esta mutação em outros países.Background: Transthyretin amyloidosis is an autossomal dominant disease caused by variant transthyretin, that is misfolded, originating a unstable transthyretin tetramer, a rate-limiting step in the formation of the amyloid deposits in different organs and tissues. In most patients, the peripheral nervous system is the main target, leading to transtyretin familial amyloid neuropathy (TTR-FAP), classically characterized as a progressive sensory-motor and autonomic neuropathy, that leads to death in about 10 years. TTRVal30Met is the most frequent point mutation worldwide, including Brazil, but more than 100 different point mutations has been described. Objectives: describe the mutational epidemiology of TTR gene in TTR-FAP and characterize its clinical and electrophysiological findings. Methods: a descriptive and retrospective study of a group of Brazilian patients forwarded to the Neurogenetics or Peripheral Nerve Clinics from FMRP-USP whose etiological investigation identified a mutation in the TTR gene. A cross-sectional analysis evaluating the subgroups with different mutations was also carried on. Results: we identified one hundred and twenty eight patients carrying a TTR point mutation, of whom 12 (9,4%) harbored a non-Val30Met mutation, including 4 pathogenic (6 patients, 4,7%) and 2 non-pathogenic abnormalities (6 patients, 4,7%). The non Val30Met pathogenic mutations were TTRAsp38Tyr (2 patients), TTRIle107Val (2 patients), TTRVal71Ala (1 patient) and TTRVal122Ile (1 patient). Among the non-pathogenic mutations, we found the TTRGly6Ser (5 patients) and the TTRThr119Thr (1 patient). The TTRVal30Met mutation was present in 116 (90,6%) patients, of whom 52 had a complete clinical and neurophysiological data: 39 (75%) with early-onset and 13(25%) with late-onset neuropathies. The early-onset group presented as the classic TTRFAP, with no gender predominance (male: 53,8%), the first manifestations were those of a small fiber sensory and autonomic neuropathy (82,1%) and a highly positive family history (90,3%). EMG was normal in 36,7% of these patients. The cardiovascular involvement was characterized by frequent ECG abnormalities (84,2%), less often associated with cardiomayopathy (11,1%). On the other hand, the late-onset TTRVal30Met showed a male predominance (92,3%), presence of motor complaints in the first evaluation (38,5%) resulting in a sensory-motor polyneuropathy with large fiber involvement and a negative family history (69,2%). All patients presented a sensory and motor neuropathy on EMG examination. In this group, cardiomiopathy was frequently associated with the neuropathy (71,4%). All patients, in both groups, had autonomic symptoms at some point in clinical follow up. Conclusions: In our study almost 5% of the patients with TTR-FAP have a non Val30Met pathogenic mutation, highlighting the importance of sequecing the whole TTR gene in patients with a sugestive clinical history and negative screening for TTRVal30Met mutation. In adition, the Brazilian patients we studied with early and late onset TTR-FAP, present similar findings to TTRVal30Met populations from other countries submitted to similar studies.
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Juvenal, Biraguma. "Peripheral neuropathy and quality of life of adults living with HIV/AIDS in Rulindo District in Rwanda." Thesis, University of the Western Cape, 2008. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_3156_1269548496.
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Peripheral neuropathy (PN) is a common neurological complication occurring in the asymptomatic and symptomatic stages of human immune deficiency virus (HIV) infection. The pain and other symptoms caused by PN can impair functional ability and limit physical activity that could affect quality of life (QoL). Additionally, studies done on quality of life of people living with HIV/AIDS have shown that, HIV-related neurological syndromes, including PN, significantly reduce QoL. The aim of this study was to determine the prevalence of peripheral neuropathy amongst and the quality of life of adults living with HIV/AIDS attending the out-patient clinic at Rutongo Hospital in Rulindo District in Rwanda.
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Rodrigues, Daiane. "Comparação da prevalência de neuropatia e dos testes de screening para neuropatia diabética (Neuropathy Disability Score versus Michigan Neuropathy Screening Instrument) em homens e mulheres : diabéticos, obesos pré-diabéticos, obesos com síndrome metabólica, obesos sem pré-diabetes e síndrome metabólica e pós-cirurgia bariátrica." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/179831.
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Introdução: Polineuropatia periférica (PNP) é descrita em diabéticos, porém estudos têm mostrado alterações neuropáticas em pacientes com pré-diabetes (Pre-DM), Síndrome Metabólica (SM), obesos e submetidos à cirurgia bariátrica (post-BS). Objetivo: Avaliar a prevalência de PNP entre pacientes com Diabetes Mellitus (DM), obesos graus II e III e pré-diabetes (OB-PRE-DM), obesidade graus II e III e síndrome metabólica (OB-SM), obesidade sem PREDM e SM (Ob No MS) e pacientes Post-BS e avaliar a sensibilidade e a especificidade da escala Neuropathy Disability Score (NDS) em comparação com Michigan Neuropathy Screening Instrument (MNSI). Método: Foi realizado um estudo transversal onde as prevalências de PNP foram avaliadas através do MNSI e do NDS. O desempenho do NDS foi comparado ao MNSI através de curvas Receiving Operating Characteristics Curves (ROC). Resultados: Considerando os escores MNSI ≥ 2,5 e ≥ 4 sintomas, MNSI ≥ 2,5 e ≥ 7 sintomas e NDS ≥ 3 em combinação com Neuropathy Symptom Score (NSS) score ≥ 3, houve a prevalência maior de PNP em DM e Pre-DM vs Ob-SM e Ob No MS e em todos vs Post-BS quando os grupos foram comparados entre si. As curvas ROC mostraram que o melhor desempenho do NDS foi ≥ 0,5. Conclusão: A prevalência de PNP descrita com o MNSI é maior em relação a com NDS. O baixo valor obtido para o melhor desempenho do NDS sugere que exploremos escores <3 para avaliar alterações neuropáticas com este escore.Introduction: Peripheral polineuropathy (PNP) is seen in diabetics, however, studies have shown neuropathic alterations in patients with pre-diabetes (Pre-DM), Metabolic Syndrome (MS), obese and submitted to bariatric surgery (post-BS). Objective: To evaluate the prevalence of PNP among patients with Diabetes Mellitus (DM), obese grades II and III and pre-diabetes (OB-PRE-DM), obesity grades II and III and metabolic syndrome (OB-SM), obesity without PREDM and Ob No MS and Post-BS patients and to assess the sensitivity and specificity of Neuropathy Disability Score (NDS) compared to the Michigan Neuropathy Screening Instrument (MNSI). Method: A cross-sectional study was carried out in which PNP prevalence were evaluated through the MNSI and the Neuropathy NDS. The performance of the NDS was compared to the MNSI through Receiving Operating Characteristics Curves (ROC curves). Results: Considering MNSI scores ≥ 2.5 and ≥ 4 symptoms, MNSI ≥ 2.5 and ≥ 7 symptoms and NDS ≥ 3 in combination with NSS score ≥ 3, there was a higher prevalence of PNP in DM and Pre-DM vs Ob-SM and Ob No MS and in all vs. Post-BS when groups were compared to each other. The curves ROC showed that the best performance of NDS was ≥ 0.5. Conclusion: The prevalence of PNP described with MNSI is higher in relation to described with NDS. The low value obtained for the best performance of NDS suggest that we explore <3 scores to evaluate neuropathic alterations with this score.
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Sousa, Alexandra Adriana Moreira de. "Vinculação do adulto com Polineuropatia Amiloidotica Familiar." Master's thesis, [s.n.], 2013. http://hdl.handle.net/10284/4298.
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Dissertação apresentada à Universidade Fernando Pessoa como parte dos requisitos para a obtenção do grau de Mestre em Psicologia, ramo de Psicologia Clínica e da SaúdeA Polineuropatia Amiloidótica Familiar (PAF), denominada de forma comum como Doença dos Pezinhos é uma doença incapacitante com implicações físicas e psicológicas. Com este estudo pretende-se analisar e comparar a vinculação do adulto em indivíduos portadores assintomáticos e doentes com PAF; assim como comparar a vinculação do adulto um grupo de doentes com PAF com a de uma amostra da população geral sem diagnóstico conhecido de doenças genéticas e hereditárias ou psicológicas; e identificar correlatos sociodemográficos da vinculação do adulto. Este estudo tem como objetivos: a) caracterizar um grupo de indivíduos com PAF, portadores assintomáticos e doentes, quanto às dimensões da vinculação do adulto; b) caracterizar um grupo de indivíduos com PAF, portadores assintomáticos e doentes, quanto aos estilos de vinculação do adulto; c) verificar se existem diferenças ao nível das dimensões da vinculação do adulto entre portadores assintomáticos e doentes com PAF; d) verificar se existem diferenças significativas entre sexos ao nível das dimensões da vinculação do adulto num grupo de indivíduos com PAF; e) verificar se existem diferenças ao nível das dimensões da vinculação do adulto num grupo de indivíduos com PAF, tendo em conta o progenitor doente (mãe ou pai); f) Verificar se existem diferenças ao nível das dimensões da vinculação do adulto em indivíduos com PAF (doentes e portadores assintomáticos), atendendo à existência de uma relação amorosa significativa; g) verificar se existem diferenças ao nível das dimensões da vinculação do adulto em indivíduos com PAF (doentes e portadores assintomáticos) atendendo à altura em que perdeu o progenitor doente; h) verificar se existem diferenças significativas ao nível das dimensões da vinculação do adulto entre indivíduos doentes com PAF e indivíduos da população geral; e por último, pretende-se verificar se existem diferenças significativas ao nível das dimensões da vinculação do adulto entre indivíduos portadores assintomáticos com PAF e indivíduos da população geral. A amostra é constituída por 124 sujeitos (n=79 doentes com PAF e n=45 indivíduos portadores assintomáticos) com idades compreendidas entre os 20 anos e os 71 anos. A amostra de doentes com PAF (n=31) utilizada para comparar com um grupo da população geral (n=30) tem idades compreendidas entre os 24 anos e 66 anos. A recolha de dados foi efetuada de forma individual na Unidade Clínica de Paramiloidose do Hospital Santo António, do Centro Hospitalar do Porto, sendo oprotocolo de investigação formado por um Questionário sociodemográfico e clínico, um questionário sobre a História Familiar da Doença e a Escala de Vinculação de Adulto (EVA) (Versão Original: Collins & Read, 1990; Versão Portuguesa: Canavarro, 1995). No Grupo PAF, a dimensão com valores mais elevados é Conforto com a Proximidade (M=2,93), verificando-se o mesmo relativamente aos subgrupos Doentes (M=2,98) e Portadores Assintomáticos (M=2,84). Apenas se verificaram diferenças estatisticamente significativas entre os subgrupos na dimensão Confiança nos Outros (t-student=3,43; p=0,001). Atendendo ao subgrupo Doentes (n=31) quando comparado com o grupo da População Geral verificou-se que existem diferenças estatisticamente significativas nas dimensões Conforto com a Proximidade (t-student=3,445; p=0.001) e Confiança nos Outros (t-student=4,187; p<0,001). Quanto ao estilo de vinculação com maior presença no Grupo PAF (n=124) é o Desligado (n=86; 69,4%) e no grupo da população geral (n=30) é o Seguro (n=25; 83,3%).
Familial Amyloidosis Polyneuropathy (FAP) is an incapacitating disease with physical and psychological implications. The present study intends to analyse the adult’s attachment in both asymptomatic FAP carriers and patients. It also intends to compare the FAP patients’ population with a group from the general population that has never been diagnosed with any hereditary and genetic or psychological disease. The objectives of this study are: a) characterize a group of individuals with FAP, asymptomatic carriers and patients, as the dimensions of the adult attachment; b) to characterize a group of individuals with FAP, asymptomatic carriers and patients about styles of adult; c) verify if are differences in the dimensions of the adult attachment between asymptomatic carriers and patients with PAF; d) verify that there are significant differences between genders in terms of dimensions of adult attachment in a group of individuals with FAP; e) verify if are differences in the dimensions of the adult attachment in a group of individuals with FAP, given the ill parent (mother or father); f) verify if are differences in the dimensions of attachment in adult patients with PAF (patients and asymptomatic carriers), given the existence of a significant love relationship; g) check if there are differences in the dimensions of attachment in adult patients with PAF (patients and asymptomatic carriers) because of lost time when the ill parent; h) verify if are significant differences in terms of the dimensions of the linkage between adult patients with FAP individuals and the general population, and finally, we intend to verify that there are significant differences in terms of the dimensions of the adult attachment between adult individuals with asymptomatic PAF and the general population. The study group is composed by a grand total of 124 subjects (n=79 FAP symptomatic carriers and 45 FAP asymptomatic carriers) aged between 20 and 71. The FAP carriers’ study group (n=31) that was compared with the general population (n=30) is aged between 24 and 66. Data collection was individually made at Unidade Clínica de Paramiloidose (FAP Clinical Unit), from Hospital de Santo António, Centro Hospitalar do Porto. The investigation protocol comprised a sociodemographic and clinical questionnaire, a questionnaire about the history of the disease in each family and the Adult Attachment Scale (AAS) (original: Collins & Read, 1990; Portuguese version: Canavarro, 1995). In the FAP group, the parameter with the highest score was Close (M=2,93), with both patients’ (M=2,98) and asymptomatic carriers’ (M=2,84) scoring almost equally. The only statistically significant difference between these subgroups concerns depend (tstudent= 3,43; p=0,001). Comparing the FAP patients’ subgroup (n=31) with the general population subgroup, statistically significant differences were found on the Close (tstudent= 3,445; p=0.001) and Depend parameters (t-student=4,187; p<.001). When attachment categories are at stake, in the FAP group (n=124) Dismissed is the most common (n=96; 69,4%); while in the general population group (n=30) Secure is the most present (n=25; 83,3%).
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Wixner, Jonas. "Gastrointestinal disturbances in hereditary transthyretin amyloidosis." Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88745.
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Background Transthyretin amyloid (ATTR) amyloidosis is a systemic disorder caused by amyloid deposits formed by misfolded transthyretin (TTR) monomers. Two main forms exist – wild-type and hereditary ATTR amyloidosis, the latter associated with TTR gene mutations. Wild-type ATTR amyloidosis has a late onset and primarily cardiac manifestations, whereas hereditary ATTR amyloidosis is a rare autosomal dominant condition with a considerable phenotypic diversity. Both disorders are present all over the world, but endemic areas of the hereditary form are found in Sweden, Portugal, Brazil and Japan. Gastrointestinal (GI) complications are common in hereditary ATTR amyloidosis and play an important role in the patients’ morbidity and mortality. Malfunction of the autonomic and enteric nervous systems has been proposed to contribute to the GI disturbances, but the underlying mechanisms have not been fully elucidated. The aims of this thesis were to assess the prevalence of GI disturbances for different subtypes of ATTR amyloidosis, to further explore the mechanisms behind these disturbances, and to evaluate the outcome of the patients’ GI function after liver transplantation, which currently is the standard treatment for hereditary ATTR amyloidosis. Methods The Transthyretin Amyloidosis Outcomes Survey (THAOS) is the first global, multicenter, longitudinal, observational survey that collects data on patients with ATTR amyloidosis. THAOS enrollment data were used to assess the prevalence of GI symptoms and to evaluate their impact on nutritional status (mBMI) and health-related quality of life (EQ-5D Index Score). Data from routine investigations of heart-rate variability and cardio-vascular response to tilt tests were utilized to evaluate the impact of autonomic neuropathy on the scintigraphically measured gastric emptying half-times in Swedish patients with hereditary ATTR amyloidosis. Gastric wall autopsy specimens from Japanese patients with hereditary ATTR amyloidosis and Japanese non-amyloidosis controls were analyzed with immunohistochemistry and computerized image analysis to assess the densities of interstitial cells of Cajal (ICC) and nervous tissue. Data from gastric emptying scintigraphies and validated questionnaires were used to evaluate the outcome of Swedish patients’ GI function after liver transplantation for hereditary ATTR amyloidosis. Results Sixty-three percent of the patients with TTR mutations and 15 % of those with wild-type ATTR amyloidosis reported GI symptoms at enrollment into THAOS. Subsequent analyses focused on patients with TTR mutations and, among them, unintentional weight loss was the most frequent symptom (32 %) followed by early satiety (26 %). Early-onset patients (<50 years of age) reported GI symptoms more frequently than late-onset cases (70 % vs. 50 %, p <0.01), and GI symptoms were more common in patients with the V30M mutation than in those with non-V30M mutations (69 % vs. 56 %, p <0.01). Both upper and lower GI symptoms were significant negative predictors of nutritional status and health-related quality of life (p <0.01 for both). Weak but significant correlations were found between gastric emptying half-times and the function of both the sympathetic (rs = -0.4, p <0.01) and parasympathetic (rs = -0.3, p <0.01) nervous systems. The densities of c-Kit-immunoreactive ICC were significantly lower in the circular (median density 0.0 vs. 2.6, p <0.01) and longitudinal (median density 0.0 vs. 1.8, p <0.01) muscle layers of the gastric wall in patients compared to controls. Yet, no significant differences in protein gene product 9.5-immunoreactive nervous cells were found between patients and controls either in the circular (median density 3.0 vs. 6.8, p = 0.17) or longitudinal (median density 1.4 vs. 2.5, p = 0.10) muscle layers. Lastly, the patients’ GI symptoms scores had increased slightly from before liver transplantation to the follow-ups performed in median two and nine years after transplantation (median score 7 vs. 10 vs. 13, p <0.01). However, their gastric emptying half-times (median half-time 137 vs. 132 vs. 125 min, p = 0.52) and nutritional statuses (median mBMI 975 vs. 991 vs. 973, p = 0.75) were maintained at follow-ups in median two and five years after transplantation. Conclusion GI disturbances are common in hereditary ATTR amyloidosis and have a negative impact on the patients’ nutritional status and health-related quality of life. Fortunately, a liver transplantation appears to halt the progressive GI involvement of the disease, although the patients’ GI symptoms tend to increase after transplantation. An autonomic neuropathy and a depletion of gastrointestinal ICC seem to contribute to the GI disturbances, but additional factors must be involved.
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Cunha, Zélia Tatiana Silva. "O adoecer na polineuropatia amiloidótica familiar: acontecimentos de vida, vulnerabilidade ao stress e factores psicopatológicos." Master's thesis, [s.n.], 2011. http://hdl.handle.net/10284/2446.
Full textAbstract:
Dissertação apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Psicologia, especialização em Psicologia Clínica e da Saúde.A polineurapatia amiloidótica familiar (PAF) mais conhecida por doença dos pezinhos apresenta um conjunto de repercussões físicas e psicológicas. O objectivo do presente trabalho é analisar a percepção de stress, a vulnerabilidade ao stress e a sintomatologia psicopatológica nos portadores assintomáticos e nos doentes com PAF. A amostra é constituída por 89 indivíduos com idades compreendidas entre os 19 e os 62 anos, divididos em portadores assintomáticos (n=53, 59,6%) e doentes (n=36, 40,4%). Os dados foram recolhidos individualmente na Unidade Clínica de Paramiloidose no Hospital de Santo António, tendo-se utilizado para o efeito um Questionário Sócio- Demográfico e Clínico, Life Experiencies Survey (LES) (Silva, Ribeiro, Cardoso & Ramos, 2003), a Escala de 23 Questões para Avaliar a Vulnerabilidade ao Stress (23 QVS) (Serra, 2000) e o Brief Symptom Inventory (BSI) (Canavarro, 1995). Não foram verificadas diferenças significativas entre o grupo de doentes e portadores assintomáticos ao nível da vulnerabilidade ao stress (t=-1,226; p=0,224). Em termos de sintomatologia psicopatológica, apenas os níveis de depressão (t=-2,215; p=0,023), ansiedade (t=-2,255; p=0,027), somatização (t=-2,403; p=0,018), índice geral de sintomas (t=-2,061; p=0,040) e total de sintomas positivos (t=-2,557; p=0,012) variam significativamente entre os dois grupos, sendo sempre superiores na amostra de doentes. Ao nível da percepção de stress, os resultados revelaram-se significativos apenas para o distress (t= -2,102; p=0,038) entre os grupos. Foram também discutidos os resultados obtidos, analisando-se as limitações apresentadas pelo estudo, as implicações do estudo para a prática, apresentando-se também sugestões para futuros estudos. The familial amyloidotic polyneuropathy (FAP) better known diseases of the feet has a set of physical and psychological repercussions. The purpose of this study is to analyze the perception of stress, vulnerability to stress and psychological symptoms in asymptomatic carriers and patients with FAP. The sample consists of 89 individuals aged between 19 and 62 years were divided into asymptomatic (n=53, 59,6%) and patients (n=36, 40,4%). Data were collected individually in Amyloidosis Clinical Unit at the Hospital de Santo António, having been used for this purpose a questionnaire Socio-Demographic and Clinical, Life Experience Survey (LES) (Silva, Ribeiro, Cardoso & Ramos, 2003), Scale 23 Questions about Vulnerability to Stress (23 QVS) (Serra, 2000) and the Brief Symptom Inventory (BSI) (Canavarro, 1995). No significant differences were found between the group of asymptomatic patients and the level of vulnerability to stress (t=-1,226, p=0,224). In terms of psychological symptoms, only the levels of depression (t=-2.215, p=0,023), anxiety (t=-2,255, p=0,027), somatization (t =-2,403, p=0,018), index of symptoms (t =- 2,061, p=0,040) and total positive symptoms (t=-2,557, p=0,012) varied significantly between the two groups, being always higher in the patient sample. At the level of perceived stress, the results show is only significant for distress (t =-2,102, p=0,038) between groups. We also discussed the results obtained by analyzing the limitations presented by the study, the study's implications for practice, also presenting suggestions for future studies.