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1

Vives, Vilagut Roser. "Design of an exploratory development plan for the assessment of the activity of drugs for the treatment of chronic inflammatory dermatological diseases." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/400199.

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Antecedents: El procés de desenvolupament d'un fàrmac des del descobriment a la comercialització és una seqüència complexa que es pot perllongar més de deu anys. La duració, taxa de fracassos i les fites varien molt depenent del tipus de fàrmac i la seva indicació. Hipòtesis: Durant el desenvolupament de noves entitat moleculars (NEM) pel tractament tòpic de malalties dermatològiques inflamatòries (MDI), l'establiment d'un pla de desenvolupament clínic utilitzant dissenys d'estudis de Prova de Concepte (PdC) eficients portarà a obtenir dades robustes i concloents en un curt període de temps, amb mínims requeriments de dades no-clíniques i clíniques, minimitzant l'exposició al producte en investigació dels subjectes en assajos clínics, assegurant la seva seguretat. Objectiu: Identificar l'aproximació més eficient per explorar l'activitat clínica d'una NEM pel tractament tòpic de les MDI en quant a fiabilitat dels resultats, requeriments de dades no-clíniques i clíniques i subjectes exposats, temps per obtenir dades d'activitat i inversió requerida. Mètodes: S'ha dut a terme una revisió de guies regulatòries de la ICH, l'EMA i la FDA i dels informes d'avaluació públics de productes tòpics dermatològics per tal d'identificar els objectius d'un pla de desenvolupament exploratori i els estudis no-clínics i clínics requerits per a iniciar els estudis de PdC. Es va dur a terme una revisió d'assajos clínics publicats de productes dermatològics tòpics en dermatitis atòpica (DA) i psoriasis publicats durant el període de gener 2003-desembre 2013, per tal de descriure els estudis utilitzats per obtenir una PdC en termes de disseny, nombre de subjectes, duració i tipus de variables i identificar els dissenys de PdC més rellevants en DA i psoriasis. Per cada tipus de disseny identificat s'ha proposat un pla de desenvolupament amb recomanacions, estimant costos i duració, comparant les diferents aproximacions. Resultats: Hi ha molt poca informació sobre com planificar el desenvolupament d'una NEM pel tractament de la DA i la psoriasis per la via tòpica malgrat les diferencies respecte dels productes per via sistèmica en termes de exposició sistèmica i seguretat podrien impactar en els plans de desenvolupament. S'han revisat un total de 59 estudis en DA i 40 en psoriasis i s'han identificat 3 tipus d'estudis principals con a rellevants per a avaluar l'activitat d'un producte aplicat per via tòpica: Estudi aleatoritzat, paral·lel inter-subjecte, Estudi aleatoritzat paral·lel intra-subjecte i estudis farmacodinàmics. Per la DA, s'han proposat dos escenaris, amb els dissenys inter-subjecte i intra-subjecte com a PdC i per la psoriasis s'ha proposat un tercer escenari amb un estudi de placa com a PdC. Després de tenir en compte totes les dades prèvies requerides en cadascun dels escenaris i les seves característiques, s'ha proposat un escenari implementant un estudi intra-subjecte per la DA i un amb un estudi de placa per la psoriasis com les aproximacions més eficients en terme de costos i temps fins a obtenir una prova d'activitat clínica d'una NEM especialment quan es tracta d'un nou mecanisme d'acció. Conclusions: El disseny del estudi de PdC s'hauria d'establir molt aviat quan es planeja el desenvolupament ja que impactarà en tot el pla de desenvolupament. Algunes de les aproximacions s'han identificat com a més eficients, encara que hi ha diferents factors que poden influenciar. Una guia regulatòria amb els requeriments generals pel desenvolupament de productes tòpics dermatològics seria útil per ajustar la quantitat de proves no-clíniques i clíniques de forma que garantissin la seguretat dels subjectes exposats durant els assajos clínics al mateix temps que evitaria l'ús excessiu de recursos, facilitant el desenvolupament, fent-lo més eficient i predictible.
Background: The process of developing a drug from discovery to the market is a complex sequence of milestones that may take more than ten years. The duration, rate of failures and milestones vary greatly depending on the type of drug and the indication. Hypothesis: During the development of new molecular entities (NME) aimed for the topical treatment of inflammatory dermatological diseases (IDD), setting up an exploratory clinical development plan objective using efficient proof of concept (PoC) study designs, leads to obtaining robust and conclusive data in a short period of time, with minimal requirements of non-clinical and clinical data and minimizing the exposure of subjects participating in clinical trials to the investigational product, thus ensuring their safety. Objective: To identify the most efficient approach to explore the clinical activity of a NME for the topical treatment of IDD in terms of reliability of the results, non-clinical and clinical data requirements and in terms of exposed subjects, time to obtain activity data and investment required. Methods: A systematic review of regulatory guidelines issued by the ICH, EMA and FDA, as well as public assessment reports of topical dermatological products was done to identify the objectives of an exploratory development, and non-clinical and clinical studies required to initiate PoC studies. A systematic review of clinical trials of topical dermatological products in Aropic Eczema (AE) and Psoriasis published in the period January 2003-December 2013, to describe the type of designs used to obtain a PoC in terms of designs, number of patients, duration, type of variables and identify the most relevant clinical trial designs for PoC in AE and/or psoriasis was performed and for each type of design identified, a development plan with recommendations was proposed, estimating costs and duration and comparing the different approaches. Results: There is little information on how to plan the development of a NME for the treatment of AE or psoriasis by the topical route despite differences with respect to systemically administered products in terms of systemic exposure and safety issues may impact development plans. A total of 59 studies in AE and 40 in psoriasis were summarized and 3 main types of studies identified as relevant to assess the activity of a product applied topically on the skin: Randomized, parallel inter-subject study, Randomized, parallel, intra-subject comparison and Pharmacodynamic studies. For AE, two scenarios were proposed, where inter-subject and intra-subject studies were the PoC designs and for psoriasis a third scenario was proposed with a psoriasis plaque test as a PoC. After accounting for all previous data needed in each of the scenarios, and the particular features of development, an scenario implementing an intra-subject design for AE and with a psoriasis plaque test for psoriasis were proposed as the most efficient in terms of time and costs till a proof of clinical activity of a NME especially when it has a new mechanism of action. Conclusions: The design of the PoC study should be established early when planning the development as it will impact on the whole plan. Some approaches have been identified as more efficient although this may be influenced by different factors. A general regulatory guidance for early stage development requirements specific for topical dermatological products would be useful to adjust the amount of non-clinical testing to an extent that guaranties the safety of subjects exposed during clinical trials at the same time that avoids excessive use of resources, easing the development process and making it more efficient and predictable.
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2

Badial, Peres Ramos [UNESP]. "Astenia dérmica regional hereditária equina: diagnóstico, ocorrência no Brasil e caracterização clinica." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/108390.

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Este estudo foi realizado para caracterizar os achados dermatológicos, oftalmológicos e morfológicos da pele de cavalos com Astenia Dérmica Regional Hereditária Equina (HERDA) e padronizar um ensaio de “High Resolution Melting” (HRM), para determinar a ocorrência de heterozigotos. As avaliações e a padronização do HRM foram realizadas em cinco cavalos afetados (GA) e cinco não afetados (GC). Adicionalmente, cinco animais heterozigotos (GH) foram utilizados para padronizar o HRM. A ocorrência de heterozigotos foi determinada em 690 animais. Diversas regiões da pele foram mensuradas com cutímetro no GA e GC. Biópsias de pele foram submetidas aos exames histopatológico e ultraestrutural. Avaliação histopatológica foi realizada por dois patologistas. O exame oftalmológico incluiu, além das avaliações rotineiras, aferição dos diâmetros da córnea, paquimetria e biometria. Foi extraído DNA do sangue colhido do GA, GC, GH e de 690 cavalos e o HRM foi validado. Observou-se menor espessura de pele no GA. A sensibilidade e especificidade do diagnóstico histopatológico da pele dependeram do avaliador e da região, respectivamente. Foram observados menor espessura e maior curvatura e diâmetros da córnea no GA. O HRM apresentou elevadas acurácia e precisão. A frequência de heterozigotos foi de 4,7%. Apesar do padrão regional dos sinais dermatológicos, a diminuição da espessura da pele não é regional. Para o diagnóstico histopatológico, recomenda-se realizar biópsia de pele no pescoço, garupa ou dorso. A relevância clínica dos achados oftalmológicos deve ser investigada. O ensaio de HRM padronizado será útil na seleção dos acasalamentos, visando minimizar a ocorrência da doença
The present study was conducted to characterize the dermatological, ophthalmological, and morphological findings from horses affected with Hereditary Equine Regional Dermal Asthenia (HERDA) and to standardize a High Resolution Melting (HRM) genotyping assay to determine the frequency of carriers. The evaluations and HRM standardization were performed in five affected (AG) and five non-affected (CG) horses. Additionally, five heterozygous (HG) horses were used to HRM standardization. The frequency of carriers was determined in 690 horses. Several skin regions of both groups were measured with a cutimeter Skin biopsies were submitted to histopathological and ultrastructural evaluations. Histopathological evaluation was performed by two pathologists. Ophthalmology included, besides the routine evaluations, corneal diameters measurement, pachymetry, and biometry. HRM was validated using purified DNA from blood samples of the AG, CG, HG and 690 horses. Skin thickness decrease was observed in the AG. Histopathological sensitivity and specificity to diagnose HERDA was dependent on the evaluator and region, respectively. HERDA horses exhibited decreased corneal thickness and increased corneal curvature and corneal diameters. The HRM assay resulted in high accuracy and precision. The estimated carrier frequency was 4.7%. Despite of the regional pattern of the dermatological signs, the decrease of skin thickness from HERDA horses is not regional. Skin samples of the neck, croup or back are recommended to diagnose HERDA. The relevance of the ocular findings should be further investigated. The standardized HRM assay will be useful in the management of breeding programs to minimize the occurrence of this disease
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3

Badial, Peres Ramos. "Astenia dérmica regional hereditária equina : diagnóstico, ocorrência no Brasil e caracterização clinica /." Botucatu, 2013. http://hdl.handle.net/11449/108390.

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Orientador: Alexandre Secorun Borges
Banca: Carlos Alberto Hussni
Banca: João Pessoa Araújo Junior
Banca: Luiz Claudio Nogueira Mendes
Banca: Paulo Henrique Jorge da Cunha
Resumo: Este estudo foi realizado para caracterizar os achados dermatológicos, oftalmológicos e morfológicos da pele de cavalos com Astenia Dérmica Regional Hereditária Equina (HERDA) e padronizar um ensaio de "High Resolution Melting" (HRM), para determinar a ocorrência de heterozigotos. As avaliações e a padronização do HRM foram realizadas em cinco cavalos afetados (GA) e cinco não afetados (GC). Adicionalmente, cinco animais heterozigotos (GH) foram utilizados para padronizar o HRM. A ocorrência de heterozigotos foi determinada em 690 animais. Diversas regiões da pele foram mensuradas com cutímetro no GA e GC. Biópsias de pele foram submetidas aos exames histopatológico e ultraestrutural. Avaliação histopatológica foi realizada por dois patologistas. O exame oftalmológico incluiu, além das avaliações rotineiras, aferição dos diâmetros da córnea, paquimetria e biometria. Foi extraído DNA do sangue colhido do GA, GC, GH e de 690 cavalos e o HRM foi validado. Observou-se menor espessura de pele no GA. A sensibilidade e especificidade do diagnóstico histopatológico da pele dependeram do avaliador e da região, respectivamente. Foram observados menor espessura e maior curvatura e diâmetros da córnea no GA. O HRM apresentou elevadas acurácia e precisão. A frequência de heterozigotos foi de 4,7%. Apesar do padrão regional dos sinais dermatológicos, a diminuição da espessura da pele não é regional. Para o diagnóstico histopatológico, recomenda-se realizar biópsia de pele no pescoço, garupa ou dorso. A relevância clínica dos achados oftalmológicos deve ser investigada. O ensaio de HRM padronizado será útil na seleção dos acasalamentos, visando minimizar a ocorrência da doença
Abstract: The present study was conducted to characterize the dermatological, ophthalmological, and morphological findings from horses affected with Hereditary Equine Regional Dermal Asthenia (HERDA) and to standardize a High Resolution Melting (HRM) genotyping assay to determine the frequency of carriers. The evaluations and HRM standardization were performed in five affected (AG) and five non-affected (CG) horses. Additionally, five heterozygous (HG) horses were used to HRM standardization. The frequency of carriers was determined in 690 horses. Several skin regions of both groups were measured with a cutimeter Skin biopsies were submitted to histopathological and ultrastructural evaluations. Histopathological evaluation was performed by two pathologists. Ophthalmology included, besides the routine evaluations, corneal diameters measurement, pachymetry, and biometry. HRM was validated using purified DNA from blood samples of the AG, CG, HG and 690 horses. Skin thickness decrease was observed in the AG. Histopathological sensitivity and specificity to diagnose HERDA was dependent on the evaluator and region, respectively. HERDA horses exhibited decreased corneal thickness and increased corneal curvature and corneal diameters. The HRM assay resulted in high accuracy and precision. The estimated carrier frequency was 4.7%. Despite of the regional pattern of the dermatological signs, the decrease of skin thickness from HERDA horses is not regional. Skin samples of the neck, croup or back are recommended to diagnose HERDA. The relevance of the ocular findings should be further investigated. The standardized HRM assay will be useful in the management of breeding programs to minimize the occurrence of this disease
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4

Casas, Fernando Constantino. "A seborrheic dermatitis in pygmy goats." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385334.

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5

Wäster, Larsson Petra. "UVA/B induced redox alterations and apoptosis in human melanocytes." Doctoral thesis, Linköpings universitet, Dermatologi och venerologi, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-8880.

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Malignant melanoma is one of the most rapidly increasing cancers and accounts for about three-quarter of all skin cancer deaths worldwide. Despite compelling evidence that ultraviolet (UV) irradiation causes melanoma the knowledge how various wavelength spectra affect the balance between proliferation and apoptosis controlling the homeostasis of the melanocyte population is still limited. The aim of this thesis was to elucidate the regulation of UVA/B induced apoptotic signaling in human epidermal melanocytes in vitro in relation to redox alterations and antioxidant photoprotection. UVA irradiation induced changes in plasma membrane stability, decreased cell proliferation and increased apoptosis. In comparison, melanocyte plasma membrane was markedly resistant to UVB irradiation although apoptosis was triggered. Thus, UVA irradiation should not be overlooked as an etiologic factor in melanoma development. Further, after irradiation with UVA/B we found alterations in redox state manifested by a reduction of intracellular GSH levels, translocation of nuclear factor-κB from the cytosol to the nucleus, an increase of γ-glutamylcysteine synthetase, the rate-limiting enzyme in GSH synthesis, and an increased apoptosis frequency. α-Tocopherol provided photoprotection through several modes of action affecting redox alterations and signaling, stabilizing the plasma membrane, and decreased proliferation and apoptosis rate, while β-carotene did not show the same protective capacity. Altogether, α-tocopherol might be a useful substance in protecting melanocytes from UV induced damage. We demonstrate UVA/B irradiation to activate the intrinsic pathway of apoptosis in melanocytes where translocation of Bcl-2 family proteins to the mitochondria modulates the apoptosis signal. Interestingly, the anti-apoptotic Bcl-2 family proteins generally thought to be attached to membranes, were localized in the cytosol before UV irradiation and translocated to the mitochondria in the surviving population, which might be a critical event in preventing apoptotic cell death. Lysosomal cathepsins were released to the cytosol acting as pro-apoptotic mediators upstream of activation and translocation of Bax to the mitochondria. When melanocytes were exposed to UVA, p53 participated in apoptosis regulation through interaction with Bcl-2 family proteins, while UVB induced p53-transcriptional activity and apoptosis involving lysosomal membrane permeabilization. Thus, depending on the UV wavelength p53 mediated apoptosis in melanocytes by transcriptional dependent or independent activity. These results emphasize p53 as an important pro-apoptotic component in the regulation of apoptosis. This thesis gives new insight in the harmful and various effects of different wavelengths within the UV spectrum on human melanocytes in vitro. Improved knowledge of the apoptosis regulatory systems in melanocytes might lead to a better understanding of the formation of pigment nevi and malignant melanoma and, in the future, provide better strategies to prevent and eliminate tumor development and progression.
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6

Venning, Vanessa Ann. "Bullous pemphigoid : clinical and pathogenetic studies." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334938.

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7

Souza, Tatiana Mello de. "Dermatopatias não-tumorais em cães: bases para o diagnóstico e dados de prevalência em Santa Maria, Rio Grande do Sul (2005-2008)." Universidade Federal de Santa Maria, 2009. http://repositorio.ufsm.br/handle/1/4036.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico
The current study stemmed from the interest in improving the diagnostic capabilities of a team consisting of two small animal clinicians and four veterinary pathologists from the Laboratório de Patologia Veterinária of the Universidade Federal de Santa Maria (UFSM), Santa Maria, Rio Grande do Sul (RS), Brazil; it was conducted from March 2005 to December 2008 as part of a doctoral project entitled "Non-tumorous dermatopathies in dogs" and was divided in two parts. The first part consists of an illustrated literature review on the histological aspects of the skin of dogs and cats, aimed to serve as a tool for dermatopathology, and on the methods applied to the dermatological diagnosis in small animals, with emphasis in the laboratory tests that support the diagnosis. The second part consists of the determination of the prevalence of dermatopathies in dogs in the municipality of Santa Maria, Rio Grande do Sul, Brazil. In this second part there is a pictorial collection, in the format of an atlas, of the main gross and histopathological aspects, that, in association with other criteria, allowed the diagnosis of the non-tumorous dermatopathies herein described. To accomplish that, the canine dermathological clinical cases seen at the Hospital Veterinário Universitário of UFSM and at a private practice from Santa Maria were followed up from March 2005 to June 2008. During this period 480 dogs with dermatological problems were examined; in 393 (81.9%) it was possible to establish a definitive diagnosis and in 87 (18.1%) the diagnosis was inconclusive. Four hundred and twenty four primary diagnosis and 78 secondary diagnosis were performed in the 393 dogs with conclusive diagnosis, totaling 502 diagnosis. The distribution of the diagnosis according to the categories of diagnosed dermatopathies was as follows: Allergic (190/502 [37.8%]), bacterial (103/502 [20.5%]), parasitic (97/502 [19.3%]), environmental (28/502 [5.6%]), mycotic (20/502 [4.0%]), endocrine (13/502 [2.6%]), keratinization defects (11/502 [2.2%]), psychogenic (9/502 [1.8%]), acquired alopecias (6/502 [1.2%]), autoimmune (6/502 [1.2%]), inherited (6/502 [1.2%]), pigmentary abnormalities (1/502 [0.2%], nutritional (1/502 [0.2%]), and sundry conditions (11/502 [2.2%]). In general, the ten most frequently diagnosed non-tumorous dermatopathies in decreasing order of frequency were: Atopy, flea bite allergic dermatitis, superficial bacterial folliculitis, demodectic mange, deep bacterial folliculitis/furunculosis, sarcoptic mange, myiasis, food allergy, pyotraumatic dermatitis, and Malassezia dermatitis. These 10 conditions together made up approximately for 75% of all canine skin diseases diagnosed in the current study. Such a result supports the view that a few skin diseases make up for the most part of the dermatological clinical cases seen in dogs from Santa Maria.
Este estudo derivou do interesse no aperfeiçoamento do diagnóstico dermatológico de uma equipe formada por dois clínicos de pequenos animais e por quatro patologistas veterinários vinculados ao Laboratório de Patologia Veterinária da Universidade Federal de Santa Maria (UFSM), Santa Maria, Rio Grande do Sul (RS), Brasil; foi conduzido no período de março de 2005 a dezembro de 2008, faz parte do projeto de doutorado intitulado Dermatopatias não-tumorais em cães e foi dividido em duas partes. A primeira parte consiste de uma revisão de literatura ilustrada sobre os aspectos histológicos da pele de cães e gatos como ferramenta para dermatopatologia e sobre métodos de diagnóstico dermatológico aplicados para pequenos animais, com ênfase em exames laboratoriais que servem de apoio diagnóstico. A segunda parte consiste na determinação da prevalência das dermatopatias nãotumorais em cães do município de Santa Maria, RS, Brasil. Nessa segunda parte há um apanhado fotográfico, no formato de um atlas, dos principais aspectos macroscópicos e microscópicos, que, juntamente com outros critérios, permitiram os diagnósticos das dermatopatias não-tumorais aqui descritas. Para isso, foram acompanhados os atendimentos dermatológicos no Hospital Veterinário Universitário da UFSM e de um consultório veterinário particular no período de março de 2005 a junho de 2008. Durante esse período foram atendidos 480 cães com problemas dermatológicos. Desses, em 393 (81,9%) foi possível estabelecer o diagnóstico definitivo e em 87 (18,1%) o diagnóstico não foi conclusivo. Esses 393 cães com diagnóstico conclusivo totalizaram 502 diagnósticos, 424 diagnósticos primários e 78 diagnósticos secundários. A distribuição dos diagnósticos em relação às categorias de dermatopatias diagnosticadas foi a seguinte: dermatopatias alérgicas (190/502 [37,8%]), dermatopatias bacterianas (103/502 [20,5%]), dermatopatias parasitárias (97/502 [19,3%]), dermatopatias relacionadas ao ambiente (28/502 [5,6%]), dermatopatias fúngicas (20/502 [4,0%]), dermatopatias endócrinas (13/502 [2,6%]), defeitos da ceratinização (11/502 [2,2%]), dermatopatias psicogênicas (9/502 [1,8%]), alopecias adquiridas (6/502 [1,2%]), dermatopatias auto-imunes (6/502 [1,2%]), dermatopatias hereditárias (6/502 [1,2%]), anormalidades pigmentares (1/502 [0,2%], dermatopatias nutricionais (1/502 [0,2%]) e outras dermatopatias (11/502 [2,2%]). No geral, as 10 principais dermatopatias não-tumorais, em ordem decrescente de freqüência, foram: atopia, dermatite alérgica à picada de pulga, foliculite bacteriana superficial, sarna demodécica, foliculite bacteriana profunda/furunculose, sarna sarcóptica, miíase, alergia alimentar, dermatite piotraumática e malassezíase. Essas 10 condições perfizeram juntas aproximadamente 75% de todas as doenças de pele de cães diagnosticadas neste estudo, o que reforça a idéia corrente de que poucas doenças de pele são responsáveis pela maior parte dos atendimentos dermatológicos no município de Santa Maria.
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Winter, Randi P., Lorin Bibb, and Stuart S. Dr Leicht. "Pressure-induced Lipodystrophy from Elbow Compression." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/59.

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Lipodystrophic syndromes encompass a wide range of both inherited and acquired conditions whereby adipose tissue is lost or absent. We report a rare case of acquired localized, pressure-induced lipodystrophy whereby continuous elbow pressure to the distal thighs led to marked tissue disfigurement. Pressure-induced lipodystrophy is a condition that likely results from protracted, localized pressure which ultimately decreases blood flow to the surrounding tissues. Overtime, the decreased perfusion is thought to induce adipocyte degeneration and eventual tissue deformation. Our findings resemble those described in the case reports of leg crossers’ dimples and lipoatrophia semicircularis and support current literature suggesting that prolonged pressure can indeed lead to significant adipose tissue loss and local architectural distortion. Our findings are significant because pressure-induced lipodystrophy represents an avoidable condition that can be circumvented if patients and physicians are knowledgeable of the underlying causes. We highlight a rare case report to educate the public as well as physicians about the causes of pressure-induced lipodystrophy and ultimately prevent future cases of unnecessary and unintended disfigurement.
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Castro, Eneida Lazzarini de 1955. "O conhecimento e o ensino sobre as doenças sexualmente transmissíveis entre os alunos da Unicamp." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311632.

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Orientador: Paulo Eduardo Neves Ferreira Velho
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: O ensino superior deve educar socialmente o cidadão, independente da sua área de conhecimento. As doenças sexualmente transmitidas (DST) são a principal causa global de doença aguda e morte e representam elevado custo socioeconômico. Os universitários são altamente expostos e ter outras infecções aumenta enormemente o risco de contrair o HIV. Objetivos: Avaliar o conhecimento de universitários sobre as DST, desenvolvendo um instrumento didático de autopercepção deste (des)conhecimento sobre o tema. Material e métodos: Um questionário foi enviado aos graduandos da Universidade Estadual de Campinas no final de 2011 e, em 2012, aos alunos recém-ingressos. Resultados e conclusões: Responderam o questionário 1.448 veteranos e 371 calouros. Metade era de cada sexo e houve representatividade de todas as áreas. Não tinham tido atividade sexual 20,0 e 38,0% dos veteranos e calouros, respectivamente. Dos alunos que já haviam tido, 26,9% não tinham parceria fixa e 28,2% mais que 2 parcerias/ano. A bissexualidade foi informada por 9,0% dos alunos, enquanto 5,8% dos homens e 1,1% das mulheres a homossexualidade. O preservativo foi usado por 99% dos alunos, mas menos de 20% deles fazia uso adequado do mesmo. Entre os alunos, 43% entenderam errado um slogan da campanha do governo. Cerca de 80% não sabiam que o preservativo não protege fora da área de barreira; não souberam identificar lesões de herpes simples e que não há cura para este vírus; quando apontadas lesões discretas da infecção pelo HPV, afirmaram que elas poderiam ser confundidas com "pintas"; pretendiam ler mais sobre DST e aprenderam algo sobre o assunto. Quase a metade dos alunos julgou que uma disciplina deveria ser oferecida a todos os graduandos. Vacinação pré-exposição poderia ter sido oferecida a mais de 43% dos calouros. Os dados encontrados serão úteis para definir estratégias de prevenção e o instrumento didático poderá ser utilizado em outros ambientes de ensino
Abstract: Higher education should educate students socially, regardless of their area of expertise. STDs are a global major cause of acute illness and death and represent high socioeconomic cost. Undergraduate students are highly exposed to them. Having other infection greatly increases the risk of contracting HIV. Our goals were to develop a teaching tool to generate perception of (un) knowledge about STDs and quantify that knowledge and the interest of the students in a course about this subject. A questionnaire was sent to students from State University of Campinas in late 2011 and, in 2012, to beginner students. The questionnaire was answered by 1,448 seniors and 371 freshmen. They were half of each gender and were representative of all areas. Twenty percent of seniors and 38,0% of freshmen had no sexual activity. Among the students that already had sexual activity, 26.9% had no regular partner and 28.2% had more than 2 partnerships a year. Bisexuality was reported by 9.0% of students, while 5.8% of men and 1.1% of female referred homosexuality. The condom was used by 99% of students, but less than 20% of them made proper use of it. Among the students, 43% misunderstood a slogan of the government campaign. About 80% of them did not know that condoms do not protect the outside barrier area; were not able to identify herpes simplex lesions and there is no cure for this virus; considered that discrete HPV lesions could be confused with nevus; wanted to read more about STDs; and learned something about the subject. Nearly half of the students felt that a course should be offered to all undergraduates. Pre-exposure vaccination could have been offered to more than 43% of freshmen. Our findings will be useful to help define strategies for prevention and the teaching tool might be used in other learning environments
Mestrado
Ensino em Saúde
Mestra em Clínica Médica
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Schielein, Maximilian [Verfasser], and Alexander [Akademischer Betreuer] Zink. "Mental health in dermatology: addictions in psoriasis and an outlook on the psychosocial burden of chronic skin diseases / Maximilian Schielein ; Betreuer: Alexander Zink." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/1232645427/34.

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11

Correia, Ana Filipa Carvalho. "Nutrição, alimentação e doenças dermatológicas: associação e perspetiva histórica – uma revisão da literatura." Bachelor's thesis, [s.n.], 2020. http://hdl.handle.net/10284/9334.

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Trabalho Complementar apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciada em Ciências da Nutrição
Objetivos: A ligação entre a nutrição e a dermatologia é controversa, no entanto, tem emergido ao longo dos anos podendo ser um complemento ao tratamento convencional. O objetivo do presente trabalho é rever a literatura existente, de forma a analisar o estudo da associação entre alimentação, nutrição e as doenças dermatológicas, numa perspetiva integrada e tendo em conta a evolução histórica. Metodologia: Utilizou-se a plataforma PubMed para a recolha de dados. Resultados: Abordam-se três doenças de pele com uma etiologia inconclusiva: a acne vulgar, a dermatite atópica e a psoríase vulgar. Encontraram-se vários fatores que podem exacerbar os sintomas destas doenças. A acne é uma doença inflamatória crónica que afeta maioritariamente os adolescentes. Uma dieta com alimentos de baixo índice glicémico/carga glicémica parece reduzir a gravidade da acne. A dermatite atópica é uma doença inflamatória crónica que ocorre principalmente na infância. Presume-se que a suplementação com probióticos na infância auxilia no tratamento e, no período pré e pós-natal poderá prevenir a doença. A suplementação com vitamina D parece reduzir a gravidade dos sintomas da doença. A psoríase é uma doença crónica inflamatória e imunomediada. Indivíduos obesos com psoríase beneficiam com a perda de peso, reduzindo a gravidade dos sintomas. Conclusões: A nutrição e alimentação, per se, não apresentam um impacto significativo na terapêutica das doenças dermatológicas analisadas. Contudo, verificou-se que a intervenção nutricional, incluindo alterações dos hábitos alimentares e/ou no aporte de alguns nutrientes, poderá sempre ser considerada como meio coadjuvante da terapêutica.
Aims: The link between nutrition and dermatology is controversial, however, it has emerged over the years and can be a complement to conventional treatment. The aim of this paper is to review the existing literature, in order to analyze the study of the association between food, nutrition and dermatological diseases, in an integrated perspective and taking into account historical evolution. Methodology: The PubMed platform was used for data collection. Results: Three skin diseases with an inconclusive etiology are approached: acne vulgaris, atopic dermatitis and psoriasis vulgaris. Several factors have been found that can exacerbate the symptoms of these diseases. Acne is a chronic inflammatory disease that mostly affects adolescents. A diet with low glycemic index / glycemic load foods seems to reduce the severity of acne. Atopic dermatitis is a chronic inflammatory disease that occurs mainly in childhood. It is assumed that supplementation with probiotics in childhood helps in the treatment and, in the pre and postnatal period, may prevent the disease. Vitamin D supplementation appears to reduce the severity of the disease's symptoms. Psoriasis is a chronic inflammatory and immune-mediated disease. Obese individuals with psoriasis benefit from weight loss by reducing the severity of symptoms. Conclusions: Nutrition and food, per se, have no significant impact on the treatment of the dermatological diseases analyzed. However, it was found that nutritional intervention, including changes in eating habits and / or in the supply of some nutrients, can always be considered as an adjunct to therapy.
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Nie, Yali. "Automatic Melanoma Diagnosis in Dermoscopic Imaging Base on Deep Learning System." Licentiate thesis, Mittuniversitetet, Institutionen för elektronikkonstruktion, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-41751.

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Melanoma is one of the deadliest forms of cancer. Unfortunately, its incidence rates have been increasing all over the world. One of the techniques used by dermatologists to diagnose melanomas is an imaging modality called dermoscopy. The skin lesion is inspected using a magnification device and a light source. This technique makes it possible for the dermatologist to observe subcutaneous structures that would be invisible otherwise. However, the use of dermoscopy is not straightforward, requiring years of practice. Moreover, the diagnosis is many times subjective and challenging to reproduce. Therefore, it is necessary to develop automatic methods that will help dermatologists provide more reliable diagnoses.  Since this cancer is visible on the skin, it is potentially detectable at a very early stage when it is curable. Recent developments have converged to make fully automatic early melanoma detection a real possibility. First, the advent of dermoscopy has enabled a dramatic boost in the clinical diagnostic ability to the point that it can detect melanoma in the clinic at the earliest stages. This technology’s global adoption has allowed the accumulation of extensive collections of dermoscopy images. The development of advanced technologies in image processing and machine learning has given us the ability to distinguish malignant melanoma from the many benign mimics that require no biopsy. These new technologies should allow earlier detection of melanoma and reduce a large number of unnecessary and costly biopsy procedures. Although some of the new systems reported for these technologies have shown promise in preliminary trials, a widespread implementation must await further technical progress in accuracy and reproducibility.  This thesis provides an overview of our deep learning (DL) based methods used in the diagnosis of melanoma in dermoscopy images. First, we introduce the background. Then, this paper gives a brief overview of the state-of-art article on melanoma interpret. After that, a review is provided on the deep learning models for melanoma image analysis and the main popular techniques to improve the diagnose performance. We also made a summary of our research results. Finally, we discuss the challenges and opportunities for automating melanocytic skin lesions’ diagnostic procedures. We end with an overview of a conclusion and directions for the following research plan.
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Amarante, Cristina Fernandes do. "An?lise epidemiol?gica das dermatopatias de uma popula??o canina atendida no per?odo de 2005 a 2010 no Setor de Dermatologia do Hospital Veterin?rio da Universidade Federal Rural do Rio de Janeiro." Universidade Federal Rural do Rio de Janeiro, 2012. https://tede.ufrrj.br/jspui/handle/jspui/1780.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
In Brazil, epidemiological studies on canine dermatopathies are scarce and the literature point out several gaps in knowledge about. The aim of this study was to describe the profile of canine population with dermatopathies attended by the Section of Dermatology, Rural Federal University of Rio de Janeiro, testing associations with variables inherent to animals, eating habits, hygiene and in relation to concurrent dermatopathies. The records of all animals attended between January 2005 and December 2010 were organized in a database using the software Epi Info? version 3.5.1. The Chi-square ?? test or Fisher?s exact test, the prevalence ratios and their confidence intervals, the ?? test for linear trend and the respective Odds ratios were used to evaluate the associations. The level of significance adopted was 5%. We reviewed the records of 2,280 dogs, with a total of 3,433 diagnostics, and 113 types of dermatopathies were identified. The population studied was composed predominantly of females (55.2%), adults (58.3%) and defined breed animals (67.32%). The categories of dermatopathies more prevalent were: allergic (41.35%), bacterial (23.94%) and endocrines (22.41%). The categories not zoonotic (94.12%) predominated over zoonotic diseases (5.88%). The more prevalent dermatitis were: atopic dermatitis - AD (31.67%), hypothyroidism (20.75%), bacterial folliculitis (8.42%), demodicosis (8.29%), flea infestation (7.67%) otitis by M. pachydermatis (6.14%), bacterial otitis (5.92%) and flea allergic dermatitis ? FAD (5.8%). Sex was significantly associated with AD, hepatoid adenoma, acute moist dermatitis - AMD, hypothyroidism, hyperadrenocorticism and demodicosis. Significant differences were observed in relation to age and AD, folliculitis, hypothyroidism, hyperadrenocorticism, scabiosis, demodicosis, dermatophytosis, systemic lupus erythematosus and neoplasms. The prevalence of AD, FAD, contact dermatitis, hypothyroidism, scabiosis, discoid lupus erythematosus, otohematoma and neoplasms varied with significant differences in relation to animal breed. In addition, there are statistical evidences of association between: AD and hypothyroidism, use of perfumes and cleaning products; FAD and AD, food allergic dermatitis and type of food; AMD and neutering, hair type and AD; hypothyroidism and neutering; demodicosis, hair type and neutering; sporotrichosis and contact with injuried animals. The study population is characterised by high prevalence of dermatopathies of the categories allergic, bacterial, endocrines, fungal and parasitic diseases and low prevalence of dermatozoonoses. The nosology of the population studied is consistent with the type of service offered by the Section of Dermatology, which is most seek for solving complex problems and in several occasions by private practitioners. It should be noted that the studied population was examined by a dermatologist from an University Veterinary Hospital where the technology could overcome the private clinics. Therefore, despite the validity of results, these should not be extrapolated without care for other populations. The variety of the diagnostics performed indicates that the diagnosis and management of dermatopathies must receive higher attention from graduates and specialists
No Brasil, estudos epidemiol?gicos sobre dermatopatias caninas s?o escassos e a literatura aponta v?rias lacunas no conhecimento. O objetivo deste estudo foi descrever o perfil da popula??o canina atendida no Setor de Dermatologia da Universidade Federal Rural do Rio de Janeiro, e das dermatopatias, testando-as quanto ?s associa??es com vari?veis inerentes aos animais, seus h?bitos alimentares, higi?nicos e em rela??o ?s dermatopatias concorrentes. Os dados de todos os prontu?rios de animais atendidos no per?odo de janeiro de 2005 a dezembro de 2010 foram armazenados em um banco de dados elaborado no programa Epi Info? vers?o 3.5.1. O teste ?? ou exato de Fisher, as raz?es de preval?ncias e seus respectivos intervalos de confian?a, o ?? de tend?ncia linear e as respectivas odds ratio foram empregados na avalia??o da associa??o. O n?vel de signific?ncia adotado foi de 5%. Foram revisados os prontu?rios de 2.280 c?es, nos quais foram realizados 3.433 diagn?sticos e identificadas 113 dermatopatias diferentes. A popula??o estudada foi composta predominantemente por f?meas (55,2%), adultos (58,3%) e animais com ra?a definida (67,32%). As categorias de dermatopatias mais prevalecentes foram: as al?rgicas (41,35), as bacterianas (23,94%) e as end?crinas (22,41%). As categorias n?o zoon?ticas (94,12%) prevaleceram sobre as zoon?ticas (5,88%). As dermatites mais prevalecentes foram: dermatite at?pica- DA (31,67%), hipotireoidismo (20,75%), foliculite bacteriana (8,42%), demodicose (8,29%), infesta??o por pulga (7,67%) otite por M. pachydermatis (6,14%), otite bacteriana (5,92%) e dermatite al?rgica por picada de pulga- DAPP (5,8%). O sexo esteve associado significativamente a DA, ao adenoma hepat?ide, a dermatite ?mida aguda- DUA, ao hipotireoidismo, ao hiperadrenocorticismo e ? demodicose. Diferen?as significativas foram observadas em rela??o ? idade e a DA, ? foliculite, ao hipotireoidismo, ao hiperadrenocorticismo, ? escabiose, ? demodicose, ? dermatofitose, ao l?pus eritematoso sist?mico, e as neoplasias. As preval?ncias de DA, DAPP, dermatite por contato, hipotireoidismo, escabiose, l?pus eritematoso disc?ide, otohematoma e neoplasias variaram com diferen?as significativas em rela??o ? ra?a. H? evid?ncias estat?sticas de associa??o entre: DA e hipotireoidismo, uso de perfumes e produtos de limpeza; DAPP e DA, dermatite al?rgica alimentar e tipo de alimento; DUA e castra??o, tipo de pelagem e DA; hipotireoidismo e castra??o; demodicose, tipo de pelagem e castra??o; esporotricose e contactantes com les?o. A popula??o estudada caracteriza-se por apresentar altas preval?ncias de dermatopatias nas categorias al?rgicas, bacterianas, end?crinas, parasit?rias e f?ngicas e baixas preval?ncias de dermatozonoses. O quadro nosol?gico da popula??o ? coerente com o tipo de servi?o oferecido pelo setor de dermatologia, que ? mais procurado para resolver problemas complexos e em muitas ocasi?es por indica??o de cl?nicos gerais. Deve-se ressaltar que popula??o estudada foi examinada por dermatologista em Hospital Veterin?rio de uma Universidade onde a capacidade tecnol?gica pode superar a da maioria das clinicas privadas. Portanto, apesar da validade interna dos resultados obtidos, estes n?o devem ser extrapolados sem os devidos cuidados para outras popula??es. A variedade de diagn?sticos realizados indica que o diagn?stico e o manejo das dermatopatias devem receber maior aten??o por parte dos graduandos e especialistas
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Clark, Michael Edward. "Unravelling the potential applications of extracellular vesicles for the clinical management of melanoma patients." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2021. https://ro.ecu.edu.au/theses/2485.

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Metastatic melanoma is the third most common cancer in Australia with global incidence increasing. After decades without effective systemic treatments for advanced melanoma, the advent of targeted and immune therapies has substantially improved patient survival. While this is encouraging, further research is needed as the majority of patients treated with targeted therapy ultimately develop drug resistance. Immunotherapy can achieve durable responses in many patients however, not all patients respond to current single or a combination of immune checkpoint inhibitors. Considering the cost and potential toxicities to patients being treated with these therapies, there is an urgent need to develop biomarkers that can predict patient response to treatment, likelihood of toxicity, and ultimately survival. Extracellular vesicles (EVs) are small particles that contain a diverse array of molecular cargos that represent the cell of origin. EVs have established roles in various hallmarks of cancer, including the mediation of drug resistance and immunosuppression. In addition, EVs have tremendous potential as biomarkers to predict or monitor patient outcomes. This thesis aims to provide a foundation of methodologies to explore the potential of melanoma derived EVs. In turn, this will allow an expansion of our understanding on the role of melanoma derived EVs on therapeutic outcomes. Chapter 1 of the thesis provided a review into the development of melanoma, current treatment strategies, drug resistance and a broad introduction on EVs. Chapter 2 demonstrated the ability to detect the mRNA of BRAF splicing variants in the plasma of melanoma patients who developed resistance to targeted therapy. Further, it showed that these mRNA variants were detected in plasma derived EVs. In Chapter 3, the potential of EVs to transfer resistance to BRAF inhibition was explored utilising a panel of BRAF treatment resistant cell lines. However, no evidence was found that EVs could transfer BRAF resistance. In Chapter 4, the plasma of melanoma patients being treated with pembrolizumab was used to isolate EV-RNA to identify a transcriptional signature predictive of response. Lastly, Chapter 5 provides a general discussion of the studies presented in this thesis. Altogether, the results of these studies underscore the potential of EVs as unique biomarkers to predictive response to treatment in melanoma.
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Silva, Ana Paula da. "Suscetibilidade antimicrobiana de Staphylococcus spp. isolados de cães com pioderma superficial." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/10179.

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Superficial pyoderma is the bacterial infection of the epidermis and hair follicle and is a common skin disease in dogs. The main etiological agents involved are bacteria of the Staphylococcus genus. This skin disease represents one of the main indications for antimicrobial therapy by small animal practitioners, a procedure usually performed empirically. The emergence of multidrug-resistant staphylococci species in skin infections has been reported in many countries and implies difficulties in the treatment. This study aimed to determine the antimicrobial susceptibility and evaluate the presence of multidrug resistance in 154 isolates of Staphylococcus spp. from skin lesions of dogs with superficial pyoderma that were assisted by the Veterinary Dermatology Service at the Hospital Veterinário Universitário (HVU) of the Universidade Federal de Santa Maria (UFSM). After bacterial culture and identification, the isolates were tested for antimicrobial susceptibility, and the results showed high rates of resistance to amoxicillin (60.4%) and penicillin G (60.4%), moderate resistance to potentiated sulfonamides (29.9%), enrofloxacin (20.1%), ciprofloxacin (18.8%) and azithromycin (17.5%), and low percentages of resistance to the amoxicillin and clavulanic acid association (1.9%), cephalexin (1.9 %), cefadroxil (1.9%) and vancomycin (0.6%). The multidrug resistance was detected in 23.4% (11/154) and the methicillin resistance in 5.8% (9/154) of the samples. It may be concluded that the Staphylococcus spp. isolates present high susceptibility to key antimicrobials used in the treatment of superficial pyodermas in dogs at the HVU-UFSM, such as cephalexin and the amoxicillin and clavulanic acid association, confirming the preference for these drugs when treating dogs with this disorder. The susceptibility of the isolates to fluoroquinolones, also recommended in the literature as an alternative in the treatment of pyodermas, allows suggesting that such drugs should not be considered in the empirical selection. The identification of multidrug-resistant Staphylococcus spp. in the studied canine population justifies periodic and regional bacteriological tests of skin lesions in dogs with superficial pyoderma, to minimize bacterial resistance, possible therapeutic failures and also motivates wise use of antimicrobial therapy.
Pioderma superficial é a infecção bacteriana da epiderme e folículo piloso e é considerada uma das doenças de pele mais frequentes em cães. Os principais agentes etiológicos envolvidos são bactérias do gênero Staphylococcus. Essa dermatopatia representa uma das principais indicações de antimicrobianoterapia pelos clínicos de pequenos animais, procedimento habitualmente realizado de forma empírica. A emergência de espécies estafilococos multirresistentes em infecções cutâneas tem sido relatada em diversos países e implica em dificuldades no tratamento. Este estudo teve como objetivo determinar a suscetibilidade antimicrobiana e avaliar a presença de multirresistência em 154 isolados de Staphylococcus spp. oriundos de lesões cutâneas de cães com pioderma superficial atendidos no Serviço de Dermatologia Veterinária do Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria (UFSM). Após cultura e identificação bacteriana, os isolados foram submetidos ao teste de sensibilidade aos antimicrobianos, cujos resultados evidenciaram elevados percentuais de resistência frente à amoxicilina (60,4%) e penicilina G (60,4%), moderada resistência às sulfonamidas potencializadas (29,9%), enrofloxacina (20,1%), ciprofloxacina (18,8%) e azitromicina (17,5%) e baixos percentuais de resistência à associação amoxicilina e ácido clavulânico (1,9%), cefalexina (1,9%), cefadroxil (1,9%) e vancomicina (0,6%). A multirresistência foi detectada em 23,4% e a resistência à meticilina em 5,8% das amostras. Pode-se concluir que os isolados de Staphylococcus spp. apresentam elevada suscetibilidade aos antimicrobianos comumente utilizados no tratamento dos piodermas superficiais em cães no HVU-UFSM, como a cefalexina e a amoxicilina associada ao ácido clavulânico, confirmando a eleição desses fármacos para o tratamento de cães com esta afecção. A suscetibilidade dos isolados frente às fluoroquinolonas, também recomendadas pela literatura como opção terapêutica nos piodermas, permite sugerir que esses fármacos não devem ser considerados na seleção empírica. A identificação de Staphylococcus spp. multirresistentes na população canina estudada justifica análises bacteriológicas periódicas e regionais de lesões cutâneas de cães com pioderma superficial, a fim de minimizar resistência bacteriana, possíveis falhas terapêuticas e também motiva a antimicrobianoterapia prudente.
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Bivik, Cecilia. "Regulation of UV induced apoptosis in human melanocytes." Doctoral thesis, Linköping : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-8749.

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Seifert, (Bock) Oliver. "Keloids - A fibroproliferative disease." Doctoral thesis, Linköpings universitet, Institutionen för klinisk och experimentell medicin, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-10360.

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Keloids are a fibroproliferative disorder of unknown etiology developing in the skin after injury or spontaneously. The aim of this thesis is to gain deeper insight into the role of TGF-β and its signaling pathway proteins, SMADs, in the pathogenesis of keloids and describe the gene expression profile in different keloid sites in the search for potential target genes for future treatment. Further aim is to develop an instrument to describe the quality of life of patients with keloids. We find cultured keloid fibroblasts to express an increased level of TGF-β1 mRNA and a decreased level of TGF-β3 mRNA compared to control skin. Keloid derived fibroblasts exhibit significantly decreased mRNA levels of TGF-β receptor type II (TβRII) and the ratio of TβRI/TβRII mRNA expression is increased. This suggests that a certain expression pattern of TGF-β subtypes and receptors may be important in keloid pathogenesis. Analysis of keloid derived fibroblasts reveal decreased SMAD3 mRNA expression and decreased ratio of SMAD2/SMAD3 mRNA implicating a disturbed SMAD signaling. Keloid fibroblasts up-regulate SMAD4 protein after stimulation with TGF-β1 and display diminished levels of the inhibitory proteins SMAD6 and 7. This may contribute to unlimited and deregulated TGF-β signaling leading to increased extracellular matrix production (ECM). The gene expression pattern is described in fibroblasts from different keloid sites using microarrays covering the whole human genome. This study reveals 105 regulated genes (79 genes are up- and 26 down-regulated) resulting in a unique gene expression profile in different sites of keloids, where progression or regression of the keloid process took place. In cells from the central part of keloids with clinical signs of regression, an up-regulation of apoptosis inducing genes as ADAM12 and ECM degrading genes as MMP19 is found. These genes may contribute to regression of keloids and might be possible future target genes for treatment. Overexpression of apoptosis inhibitors as AVEN and down-regulation of angiogenesis inhibiting genes as PTX3 found at the active margin of keloids may be responsible for the invasive character of the keloid margin. We develop a disease specific questionnaire to measure the quality of life of patients with keloids. We find two scales, psychological and physical impairment, describing the dimensions of quality of life in patients with scars. These two scales are independent of each other and show a high test-retest reliability. Single items which clinically characterize the disease show correlations to these scales. The results of this study demonstrate for the first time a severe impairment of quality of life of patients suffering from keloids and hypertrophic scars. In conclusion the described alteration in TGF-β expression and its receptors, the disrupted SMAD signaling pathway and the unique gene expression patterns in different keloid sites provide new knowledge on ECM formation and degradation in keloids. Regulatory genes in ECM homeostasis may be future target genes for keloid prevention, regression and treatment. The disease specific quality of life instrument of patients with keloids and scars is a useful tool to estimate success in future therapeutic efforts over time.
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Strassner, James P. "The Role of Interferon Gamma in Melanocyte Clearance During Vitiligo." eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1023.

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Vitiligo is an autoimmune disease in which CD8+ T cells selectively destroy melanocytes, leading to a patchy, disfiguring depigmentation of the skin. Our group and others have highlighted the central role of IFN-γ-dependent chemokines in the progression of disease; however, IFN-γ is also reported to have pleiotropic effects on melanocyte biology. We examined whether IFN-γ has a direct role in melanocyte killing. We tested the T-cell effector functions IFN-γ, Fas ligand and perforin by deleting them from autoreactive T cells used to induce vitiligo in mice. We found that disease incidence, disease severity and T cell accumulation in the skin was reduced in mice receiving adoptive transfer of either IFN-γ deficient or Fas ligand deficient gp100-specific T cells; however, perforin was dispensable and led to increased disease scores and T cell accumulation. To determine how melanocytes are affected by IFN-γ signaling during vitiligo, we performed single-cell RNA-sequencing on suction blister biopsies obtained from vitiligo and healthy subjects. We discovered that integrin expression and TGFb2 signaling was decreased only in lesional melanocyte transcriptomes. Moreover, melanocytes appear to participate in their own demise by increasing HLA expression and recruiting effector cells through the chemotactic ligand CCL18. The loss of melanocyte retention factors may explain their clean disappearance from the skin during keratinocyte turnover. Taken together, we believe IFN-γ production by autoreactive T cells in the skin leads to clean loss of melanocytes by downregulation of melanocyte retention factors and by increasing their potential to be detected by effector cells during vitiligo.
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Hjorth-Hansen, Henrik. "Novel cytokines in growth control and bone disease of multiple myeloma." Doctoral thesis, Norwegian University of Science and Technology, Faculty of Medicine, 2001. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-315.

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Myelomatose (benmargskreft) er en blodsyk dom som rammer ca 200 nordmenn årlig. Sykdommen kan ikke kureres og karakteriseres av symptomer som benmargssvikt og infeksjonstendenns, men kanskje først og fremst av sykelig nedbrytning av skjelettet. Pasientene rammes i høy utstrekning av benbrudd, hvirvelsammenfall og skjelettsmerter. Mekanismene for bennedbrytning og vekstkontroll står sentralt i avhandlingsarbeidet som består av fem artikler om cytokiners rolle i myelomatose. Cytokiner er signalsubstanser som benyttes i celle-celle-kommunikasjon. Det er sannsynligvis ubalanse av cytokiner som forårsaker den sykelige nedbrytningen av bensubstansen.

Det første delarbeidet omhandler funnet av hepatocyttvekstfaktor (HGF) som er uttrykt hos nesten alle pasienter med myelomatose Dette påvises med forskjellige teknikker og det benyttes bl a en separasjonsmetode for myelomceller basert på Ugelstadkuler som ble utviklet ved IKM i 1993. Videre påvises forhøyede nivåer av HGF i serum fra pasienter. Et interessant funn er at HGF reseptor også er uttrykt i pasientprøver, hvilket kan tale for at myelomceller kan ha en selvstimulerende (autokrin) funksjon.

I det andre delarbeidet vises en dyremodell for myelomatose i immundefekte mus. Et hovedpoeng er at det lar seg gjøre å få vekst av myelomceller i musebenmarg med påvisbare tegn til patologisk bennedbrytning på røntgen og ved histologisk undersøkelse. Musene har forhøyede nivåer av HGF i serum. Benlesjonene ble karakterisert ved hjelp av histomorfometri. Denne undersøkelse viste 99% reduksjon av de bendannende cellene (osteoblaster) og 33% reduksjon av bennedbrytende celler (osteklaster).

I tredje delarbeidet viser man at HGF induserer interleukin (IL)-11-produksjon i osteoblaster. IL-11 er en kjent påskynder av benresorpsjon og osteoklastaktivator. Et interessant fenomen er at HGF ser ut til å være bundet til heparansulfat på cellemembranen og at slikt membranbundet HGF virker bedre enn løselig HGF. Effekten av HGF potensieres av cytokinene TGF-beta og IL-1. En styrke ved arbeidet er at såvel ferskisolerte pasientceller som cellelinjer viser identiske mønstre. Arbeidet angir en mulig måte som HGF kan befremme bennedbrytning.

I fjerde delarbeid vises at cytokinet IL-15 forhindrer programmert celledød (apoptose) i myelomcellelinjen OH-2. Det var fra før kjent at myelomceller relativt hyppig lar seg stimulere av cytokinet IL-6, som fortsatt er den mest anerkjente myelomvekstfaktoren. IL-15 var tilnærmet like potent antiapoptotisk som IL-6, og befremmet også kortvarig proliferasjon. IL-15s effekt kunne potensieres av TNF-alfa

I femte delarbeid påvises at cytokinet benmorfogent protein (BMP)-4 hemmer vekst av myelomceller. BMP-4 befremmer bendannelse. Effekten av BMP-4 kom fram i IL-6-stimulerte cellelinjer og pasientprøver. Effekten skyldtes såvel induksjon av apoptose som stopp i cellesyklus G1-fase. Dette er et mulig viktig funn siden man kan tenke seg at pasienter med myelomatose kunne behandles med BMP-4 eller lignende substanser. På slik måte ville såvel skjelettnedbrytningen som myelomcellevekst kunne påvirkes gunstig.

Arbeidet bidrar til forståelse av molekylære mekanismer for bendestruksjon og myelomcellevekst og ble veiledet av profesor dr. med. Anders Waage. Henrik Hjorth-Hansen har vært stipendiat i Den norske kreftforening, og undersøkelsen ble dessuten støttet av Kreftfondet ved RiT og Blix’ legat.

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20

Burge, Susan Mary. "Darier's disease." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306219.

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21

Gånemo, Agneta. "Hereditary ichthyosis : Causes, Skin Manifestations, Treatments and Quality of Life." Doctoral thesis, Uppsala University, Dermatology and Venereology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1780.

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Hereditary ichthyosis is a collective name for many dry and scaly skin disorders ranging in frequency from common to very rare. The main groups are autosomal recessive lamellar ichthyosis, autosomal dominant epidermolytic hyperkeratosis and ichthyosis vulgaris, and x-linked recessive ichthyosis. Anhidrosis, ectropion and keratodermia are common symptoms, especially in lamellar ichthyosis, which is often caused by mutations in the transglutaminase 1 (TGM1) gene. The aim of this work was to study patients with different types of ichthyosis regarding (i) the patho-aetiology (TGM1 and electron microscopy [EM] analysis), (ii) skin signs and symptoms (clinical score and subjective measure of disease activity), (iii) quality of life (questionnaires DLQI, SF-36 and NHP and face-to-face interviews) and (iv) a search for new ways of topical treatment. Patients from Sweden and Estonia with autosomal recessive congenital ichthyosis (n=83) had a broader clinical spectrum than anticipated, but a majority carried TGM1 mutations. Based on DNA analysis and clinical examinations the patients were classified into three groups, which could be further subdivided after EM analysis. Our studies indicate that patients with ichthyosis have reduced quality of life as reflected by DLQI and by some domains of SF-36, by NHP and the interviews. All the interviewees reported that their skin disease had affected them negatively to varying degrees during their entire lives and that the most problematic period was childhood. All patients with ichthyosis use topical therapy. In a double-blind study creams containing either 5% urea or 20% propylene glycol were found inferior to a cream formulation containing lactic acid 5% and propylene glycol 20% both regarding clinical improvement and thinning of the skin barrier. Improved topical therapy may reduce the need of more toxic, oral drugs. Future studies should elucidate whether this increases the quality of life of ichthyosis patients, especially if combined with more detailed information about the aetiology and inheritance of the diseases.

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22

Murray, Caroline Siân. "Measuring disease in dermatology : studies of objective and subjective methods." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/23594.

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Itch lies second only to disturbance of body image as a reported symptom in dermatology. This study started by concentrating on improving the measurement of itch. Itch has a paired physical response, scratch. The pairing can be exploited: preliminary work by this unit had validated the use of wrist-worn movement-measuring machines called ‘accelerometers’ to measure itch-related movement (scratch and rub). The first part of this research developed use of these machines. Simple accelerometers (‘Actiwatch Plus’) were used to observe the pattern of variation of itch over clusters of nights and in different conditions. The accelerometer scores were able to identify controls’ scores from those with itchy disease. Considerable variation (56%) was discovered in objective score between subject and considerable variation was noted (46%) even within subject. More complex accelerometers, (‘DigiTrac’) which could potentially specifically identify itch-related movement on the basis of frequency of action derived from Fast Fourier Transform (FFT), were validated against the ‘gold standard’ measurement of itch-related movement, directly observed movement (via infra red video recording). It was necessary to characterise the ‘frequency of action’ of itch on video and, as an aside, the characteristics of human itch-related movement were compared to other mammals’ itch-related movement ‘frequency of action’. The ‘frequency of action’ and video data was used to enrich the DigiTrac readouts to improve specificity of itch-related movement detection. During the accelerometer studies, an unexpected finding came to light: objective score of itch was not related to subjective score. To try to explain the lack of relationship, a 42 day longitudinal study of atopic dermatitis patients’ subjective and objective scores was undertaken. The results demonstrated autocorrelation for subjective scores, but not for the objective scores but still did not fully explain the lack of relationship. In an effort to explain the disconnect between subjective and objective scores a second tranche of experiments and the second part of this research interrogated whether the methods with which we measure disease as a whole in dermatology are robust. One study investigated whether the way patients are asked about subjective symptoms in general was resistant to the effects of focusing and framing bias. The results were reassuring as they suggested that the commonly used and recommended symptom scoring systems were robust in the face of bias. In order to assess whether perspective or perception of disease explained the disconnect, a study was designed in collaboration with the Edinburgh College of Art. A series of computer-generated images of different psoriasis severities were created and used to assess how doctors and patients assessed disease-extent. This study showed that, whilst each group had a naturally divergent opinion of extent of disease, by scoring disease using the models it was possible to unify the perspective and perception of extent. Finally, an exploratory study to reduce recall bias to a minimum, in case this had caused the disconnect between objective and subjective, was undertaken. This employed a novel questionnaire, the Day Reconstruction Method.
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El, Mansori Ibtessam Mustafa. "Thyrotropin receptor signalling links skin and thyroid disease." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/46110/.

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Thyroid dysfunction is frequently associated with skin and hair diseases; however, the underlying pathogenic mechanisms are poorly understood. Pathological activation of the thyroid stimulating hormone receptor (TSHR) is the key feature of both hyper- and hypo-thyrodism. Expression of the (TSHR) has been reported in several extra-thyroidal locations including adipose tissue, bone and skin fibroblasts. TSHR expression may explain the association between the thyroid and skin disease. The TSHR can also be activated by a newly discovered glycoprotein hormone, known as thyrostimulin. This hormone is composed of a dimer of unique α 2 and β 5 subunits. Although thyrostimulin has not been detected in the circulation. However, both subunits have been shown to be expressed in different tissues including the skin. The aim of this study is to examine the expression of the TSHR and thyrostimulin in the skin. In addition, to investigate the expression of a variant form of the TSHR in human and mouse skin and, other mouse tissues. RT-PCR using primers specific for the full length receptor and the truncated variant revealed that although the variant was widely expressed in mouse tissues including skin, it was not found in human skin. The full length receptor and thyrostimulin were found to be co-expressed in eye, testis and skin. Immunohistochemistry of frozen skin and thyroid sections using commercially available antibodies against the extracellular (A9) and transmembrane domains (A7) of TSHR demonstrates that TSHR is not expressed in the epidermis but expressed in dermal fibroblasts and in myoepithelium around sweat glands. A new β5 antibody was characterised by western blotting and immunohistochemistry for future investigation of β5 expression in the skin. These data suggest a functional role for TSHR signalling possibly via thyrostimulin in the skin and that the variant form,although potentially present in some tissues, is unlikely to be important in human skin.
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Rodriguez-Macias, Wallberg Kenny A. "Artery Wall Imaging and Effects of Postmenopausal Estrogen Therapy." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5722.

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25

Dawe, Robert Stewart. "Phototherapy in the treatment of skin disease in Scotland." Thesis, University of Glasgow, 2001. http://theses.gla.ac.uk/5857/.

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This thesis discusses some aspects of the use of ultraviolet rays to treat skin disease. The early history of dermatological phototherapy in Scotland is summarised as an introduction to the more recent developments described in a chapter on the Scottish phototherapy and photochemotherapy audit of 1996/1997 (funded by the Clinical Resource and Audit Group, the Scottish Office). This audit revealed some aspects of the phototherapy service that could be improved, and identified areas of particular importance for future research. Firstly, what type of UVB phototherapy lamp is most effective: the narrow-band (311-313nm) TL-01 lamp, or the broad-band UVB lamp? A meta-analysis conducted as part of this thesis gave a clear answer. TL-01 UVB is much more effective than broad-band UVB. The second included study was a randomised, controlled study that has contributed to deciding the optimal treatment frequency for TL-01 UVB phototherapy of psoriasis. Although 5x weekly treatment cleared psoriasis slightly more quickly than 3x weekly treatment, the difference in speed of clearance was too small to warrant the significantly greater frequency of acute erythema during treatment, and the greater number of exposures and dose required. The final question, answered by a randomised, controlled trial, in conjunction with a systematic review of the previous literature, was: for chronic plaque psoriasis, is TL-01 UVB or psoralen-UVA photochemotherapy to be preferred? The study conducted for this thesis showed TL-01 UVB to be more effective. Heterogeneity in findings of the studies addressing this question highlighted the importance of the particular treatment regimens selected for comparison, but the overall conclusion was that TL-01 UVB is the first choice of these two therapies.
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Khan, Gul Karim. "The measurement of disability caused by skin disease." Thesis, Bangor University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302336.

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27

Pavez, Loriè Elizabeth. "Retinoic Acid Metabolism Blocking Agents and the Skin : In vivo and in vitro Studies of the Effects on Normal and Diseased Human Epidermis." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9325.

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Retinoic Acid Metabolism Blocking Agents (RAMBAs) increase the endogenous levels of all-trans retinoic acid (RA) by inhibiting CYP26 enzymes. Thus they are believed to mimic the effects of retinoid treatment. Their mechanism of action and effects on vitamin A metabolism in keratinocytes are however uncertain. To explore this and the function of CYP26 in human skin was the main purpose of the project. The effects of two RAMBAs (talarozole and liarozole) on the expression of retinoid biomarkers in epidermis were studied in vivo and in vitro. Normal human skin (n=16) exposed to topical talarozole for 9 days showed similar response as previously reported for topical RA, even though no skin inflammation occurred. Lamellar ichthyosis patients (n=11) treated systemically with liarozole showed variable clinical improvement after 4 weeks with only mild effects on the retinoid biomarkers and the expression did not always correlate at the protein and mRNA levels. In these studies the proinflammatory transcripts IL-1α and TNFα were down-regulated by RAMBAs. In vitro, using an organotypic epidermis model we first studied how the RA metabolism was affected by adding RA and/or RAMBAs. We next examined the effects of the same agents on the expression of vitamin A metabolising enzymes in monolayer cultures of proliferating and differentiating keratinocytes. The results show among other things that CYP26 A1 and B1 are both involved in the catabolism of RA, and that talarozole potently increases the level of endogenous RA, primarily by inhibiting CYP26B1. However the drug´s biological effects cannot be solely attributed to increased RA levels. In conclusion, RAMBAs are promising new drugs for treatment of skin disorders, but further studies on their mechanism of action are needed.
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Yell, Jennifer Anne. "The 52 and 60 kD Ro/SS-A : antigens where are they? : do anti-Ro/SS-A autoantibodies cause cutaneous disease?" Doctoral thesis, University of Cape Town, 1998. http://hdl.handle.net/11427/25683.

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Systemic lupus erythematosus, considered a multifactorial autoimmune disease, is a disease affecting many systems, with associated immunological abnormalities. It has a striking diversity of clinical patterns, pathologies and prognoses. Genetic factors determine the inherited baseline, on which environmental, hormonal and infectious triggers act to produce autoantibodies. Ro antibodies have been considered pathogenic in subacute cutaneous and neonatal lupus erythematosus. I affinity-purified antibodies to the 52 kD Ro from immunised rabbits (whole 52 kD protein) and human sera (using two immunodominant regions of the protein). I affinity-purified antibodies to the 60 kD Ro from immunised rabbits (whole 60 kD protein) and human sera (using two immunodominant regions of the protein, as well as the total "native" protein). Using these purified antibodies, with immunofluorescence on normal neonatal human keratinocytes, I showed that the 52 kD Ro is mainly cytoplasmic and the 60 kD Ro is mostly nuclear, with some fine cytoplasmic staining. I looked at the capacity of these purified antibodies to penetrate living keratinocytes under various conditions (hormones, drugs and vitamins). No antibody penetration was found, although one whole serum gave low levels of intracellular fluorescence. I studied the putative membrane translocation of 52 kD and 60 kD Ro under conditions of stress (UV A or UVB with or without hormones, drugs, vitamins and heat shock). I could not identify translocation of the 52 or 60 kD antigens with purified antibodies, although some whole sera showed fluorescence. I can find no evidence that antibodies directed against the 52 and 60 kD Ro antigens cause cutaneous disease.
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29

Armstrong, Angela. "Dermoscopy : An Evidence-Based Approach for the Early Detection of Melanoma." UNF Digital Commons, 2011. http://digitalcommons.unf.edu/etd/382.

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The purpose of this project was to evaluate the effectiveness of a practice-based dermoscopy training program for dermatology healthcare providers in order to improve their technique of performing clinical skin exams for the early detection of melanomas. The overall incidence of melanoma continues to rise. More than 75% of all skin cancer deaths are from melanoma. Advanced melanoma spreads to lymph nodes and internal organs and can result in death. One American dies from melanoma almost every hour (American Cancer Society [ACS], 2009). Early diagnosis and excision are essential to reduce morbidity and to improve patient survival. This one-group before-and-after study design utilized a convenience sample of three dermatology healthcare providers (DHPs). The primary investigator conducted a retrospective review of the pathology logs for each provider. The time frame for the review was a three-month period in 2010, which represented the same time frame that the study was conducted in 2011. The DHPs participated in a four-hour training workshop that included pattern analysis recognition using dermoscopy. Following the workshop, each DHP was given a DermLite 3Gen DL100 to use in practice when performing clinical skin examinations. All DHPs completed a data collection sheet to document their pattern of decision making with and without a DermLite. The outcome of interest was the use of dermoscopy by DHPs to demonstrate an increased detection of melanoma when compared to naked-eye examination. The outcome was evaluated 12 weeks postworkshop training. There were 120 evaluations made with the DermLite as compared to the naked eye. The overall agreement was 0.52, AC1 coefficient (95% CI) was 0.36 (0.30, 0.42), p < .001, and kappa coefficient (95% CI) was 0.27 (0.20, 0.43), p < .001. Overall, the risk of lesion under exam being suspicion for skin cancer was higher on 27.5% (33 out of 120) of the evaluations and lower on 20.8% (25 out of 120) evaluations. The risk of lesion was evaluated the same on 51.7% (62 out of 120) of the evaluations. This is an indication of “Poor” agreement between the two methods. The diagnosis and disposition made using DermLite compared to naked-eye results for both coefficients provided an “Intermediate to Good” agreement between the two methods in assigning diagnosis and disposition. This indicates that there is no difference between DermLite and naked-eye evaluations. More studies are needed in order to provide better evidence on the value of dermoscopy in clinical practice at the Dermatology and Laser Center. Future projects should be more explicit regarding the methods used and lesion selection in order to better understand the benefits of dermoscopy.
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Ahmed, Refat Maggi. "Improving the Success of Melanocyte Keratinocyte Transplantation Surgery in Vitiligo; The Role of JAK Inhibitors, and Ablative Laser Resurfacing." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1143.

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The Melanocyte Keratinocyte Transplantation Procedure (MKTP) is an effective surgical replacement of lost melanocytes in recalcitrant vitiligo and pigmentary skin disorders. However, it is only effective in stable vitiligo lesions because active autoimmunity destroys the newly transplanted melanocytes. Despite careful selection of candidates based on the reported clinical stability, the success of the procedure is still unpredictable. MKTP candidates with non-segmental, segmental, and mixed vitiligo, as well as hypopigmented scars and Piebaldism patients were enrolled to our studies. Our aim was first, to investigate the possible immunological mechanisms responsible for the unpredictable post- transplantation outcomes, including T cell subsets and inflammatory chemokines, by correlating these biomarkers with clinical phenotypes, duration of stability, and surgical outcomes. We used suction blister biopsy, a minimally invasive technique that we developed to sample human skin. Moreover, we quantified transplanted melanocytes in the suspension using flow cytometry. Following MKTP, we corelated these biomarkers to the repigmentation score. We found that CD8+ T cells remain in some clinically stable vitiligo lesions, correlate negatively with the post-surgical score of repigmentation, and inversely impact the durability of the responses. Interestingly, the number of transplanted melanocytes in the suspension and the duration of stability do not have prognostic roles. Based on our findings and in a second group of patients, we suppressed the activity of T cells to enhance the outcomes of MKTP. We used Ruxolitinib, JAK1/2 inhibitor, in a triple blinded randomized controlled within subject study, in comparison with Tacrolimus (a calcineurin inhibitor and the standard of care treatment in vitiligo) as well as placebo control. We found lower T cell infiltrate, lower chemokines, and better skin repigmentation in lesions treated with MKTP plus Ruxolitinib or Tacrolimus than in lesions treated with MKTP plus placebo. Lastly, we compared two different types of laser in preparation of the recipient skin for MKTP - ablative versus fractional Er:YAG laser. We found that the ablative laser is combined with minimal CD8+ T cell epidermal infiltrate and superior repigmentation score in comparison to more infiltrate and lower repigmentation score with the fractional laser. Taken together, these results from our studies provide novel insight to predict the optimal surgical candidates and will improve surgical outcomes. It advances the treatment of vitiligo by uncovering the impact of autoimmunity on the success of repigmentation and discovering new approaches to optimize the surgical treatment options in patients with vitiligo and pigmentary skin disorders.
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31

Simpson, Rosalind C. "Erosive lichen planus affecting the vulva : defining the disease, developing outcome measures and designing a randomised controlled trial." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/28301/.

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Erosive lichen planus affecting the vulvovaginal region (ELPV) is a rare chronic inflammatory condition causing painful raw areas that can lead to scarring, at the vaginal entrance. Symptoms considerably impact upon daily function and quality of life. There is risk of cancerous change in affected skin of 1-3%. A Cochrane Systematic Review, published in 2012, found no randomised controlled trials (RCT) on which to base treatment for ELPV. Retrospective case series suggest that super-potent topical corticosteroids are frequently used as first-line therapy, although one third of patients fail to respond adequately and require escalation of therapy. There is clinical uncertainty regarding which second-line therapies should be used. The following steps were taken to inform the design of an RCT to determine optimal second-line therapy for EVLP resistant to topical steroids: • A multi-centre retrospective review and audit of case notes to assess current clinical management in the UK. • A qualitative investigation with UK clinicians to establish their views and principles of management of ELPV. • An international multi-disciplinary electronic-delphi consensus exercise to agree a set of diagnostic criteria for ELPV. • A systematic review to assess existing outcome measure tools that have been used in randomised controlled trials of vulval skin disorders. • Assessment of patients views through a survey of a national patient group and subsequent focus groups with patients. The resulting multi-centre, four-armed, open-label, pragmatic randomised controlled trial will compare hydroxychloroquine, methotrexate and mycophenolate mofetil against a standard care group of clobetasol propionate 0.05% plus a short course of oral prednisolone. This will be the first RCT to test systemic agents for patients with ELPV and will add to the existing evidence base. The methodologies employed to develop the RCT protocol, and the trial design itself, may act as a template for clinical research into the therapeutic management of other rare inflammatory conditions.
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32

Zethelius, Björn. "Proinsulin and Insulin Sensitivity as Predictors of Type 2 Diabetes Mellitus and Coronary Heart Disease : Clinical Epidemiological Studies with up to 27 Years of Follow-Up." Doctoral thesis, Uppsala University, Geriatrics, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3159.

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Defects in insulin secretion and insulin action are the major abnormalities in the development of Type 2 diabetes. Hyperinsulinemia is a risk marker for Type 2 diabetes and according to some, but not in all studies also for coronary heart disease (CHD). Conventional insulin assays measure immunoreactive insulin including proinsulin-like molecules.

Proinsulin and insulin measured by specific methods, insulin sensitivity measured by the euglycemic insulin clamp and early insulin response after a glucose challenge give more detailed information and may be better estimates of true risk for Type 2 diabetes and CHD.

This study examined relationships between proinsulin, insulin, insulin secretion and insulin sensitivity for the development of Type 2 diabetes and CHD. The investigation of the prognostic significance of proinsulin and insulin for the development of Type 2 diabetes and CHD was performed in prospective studies of 50-year and 70-year-old men in a population-based cohort. The results indicated, that increased proinsulin concentrations, was a marker of increased risk for Type 2 diabetes independent of measurements of insulin secretion and insulin sensitivity whereas insulin was not. Proinsulin was shown to be a predictor for CHD mortality and morbidity, respectively, independent of conventional risk factors, whereas insulin was not. Insulin sensitivity measured by the gold standard euglycemic insulin clamp at age 70 was a predictor of CHD morbidity, independently of established risk factors.

In summary, these data provide evidence that an increased concentration of proinsulin and not an elevated plasma insulin level per se, that constitutes the association with Type 2 diabetes and CHD and that insulin resistance per se, is associated with CHD risk.


Defekter i insulinsekretionen och insulinkänsligheten i målorganen för insulin är de huvudsakliga orsakerna till utvecklandet av typ-2 diabetes. Förhöjd insulinhalt i blodet indikerar nedsatt känslighet för insulin och är en riskmarkör för typ-2 diabetes men också för hjärt-kärlsjukdom enligt vissa studier.

Konventionella insulinmätmetoder är ospecifika och mäter immunoreaktivt insulin som förutom insulin också innehåller ett förstadium till insulin, proinsulin.

Proinsulin och specifikt insulin, insulinkänslighet bestämd med hyperglykemisk insulin clamp teknik och tidigt insulinsvar vid sockerbelastning ger en bättre och mer detaljerad och precis information. Dessa variabler kan därför utgöra en bättre prediktor för typ-2 diabetes och hjärt-kärlsjukdom.

I denna avhandling har proinsulin, specifikt insulin, tidigt insulinsvar vid sockerbelastning och insulinkänslighet jämförts med varandra som prediktorer för utvecklandet av typ-2 diabetes och hjärt-kärlsjukdom. Två studier har omfattat risken för diabetes och två studier risken för hjärt-kärlsjukdom. Män i medelåldern respektive i högre ålder har studerats. Studierna har utförts i en populations-baserad grupp, en kohort som har sitt ursprung i en stor hälsoundersökning som genomfördes i Uppsala 1970 till 1973.

Resultaten visar att proinsulin, i motsats till specifikt insulin, är en riskmarkör för utveckling av typ 2 diabetes, oberoende av insulinkänslighet och tidigt insulinsvar vid sockerbelastning. Vidare har visats att proinsulin i motsats till specifikt insulin är en riskmarkör för död respektive sjuklighet i hjärt-kärlsjukdom, oberoende av de kända riskfaktorerna rökning, högt blodtryck och förhöjt kolesterol. Slutligen har visats att insulinkänsligheten i sig är en riskmarkör för hjärt-kärlsjuklighet oberoende av ovanstående riskfaktorer förutom proinsulin.

Sammanfattningsvis visar resultaten i avhandlingen att det snarare är proinsulinhalten och inte insulinnivån i blodet som står för de observerade sambanden med typ 2 diabetes och hjärt-kärlsjukdom. Nedsatt känslighet för insulin i sig är förenat med ökad risk för hjärt-kärlsjukdom.

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33

Sköldberg, Filip. "Studies of Autoantibodies in Systemic and Organ-Specific Autoimmune Disease." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3421.

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Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease, whereas autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal disorder characterized by combinations of organ-specific autoimmune manifestations including hypoparathyroidism and intestinal dysfunction, and may serve as a model for organ-specific autoimmunity. Autoantibodies directed against proteins expressed in the affected tissues are found in both diseases. From a chondrocyte cDNA expression library, we identified the protein AHNAK as an autoantigen in SLE. Anti-AHNAK antibodies were found in 29.5% (18/61) of patients with SLE, 4.6% (5/109) of patients with rheumatoid arthritis, and 1.2% (2/172) of blood donors. Using a candidate approach, we analyzed the prevalence in APS1 and other organ-specific autoimmune diseases, of autoantibodies against the pyridoxal phosphate-dependent enzymes histidine decarboxylase (HDC) and cysteine sulfinic acid decarboxylase (CSAD), which are structurally closely related to known autoantigens. Anti-HDC and anti-CSAD reactivity was detected exclusively in APS1 patient sera. Anti-HDC antibodies were detected in 37.1% (36/97) of the APS1 sera, did not cross-react with aromatic L-amino acid decarboxylase, and were associated with intestinal dysfunction and loss of histamine-producing gastric enterochromaffin-like cells. In contrast, anti-CSAD reactivity was detected in 3.6% (3/83) of APS1 sera and cross-reacted with recombinant glutamic acid decarboxylase. From a parathyroid cDNA expression library, novel spliced transcripts of the CLLD4 gene on human chromosome 13q14, encoding 26 and 31 kDa isoforms recognized by autoantibodies in 3.4% (3/87) of APS1 patients, were identified and found to be preferentially expressed in lung and ovary. Both isoforms contain an N-terminal BTB/POZ domain, similarly to the TNF-alpha-regulated protein B12, localize both to the cytoplasm and nucleus in transfected COS cells, and form oligomers in vitro. The CLLD4 gene is located in a region frequently deleted in several forms of cancer, including lung and ovarian tumors. In conclusion, we have identified and partially characterized AHNAK and HDC as two common targets of autoantibodies in SLE and APS1, respectively. We have also identified CSAD and CLLD4 as two minor autoantigens in APS1, one of which is a novel protein with unknown function.
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34

Smith, Catherine Claire. "The mouse tail model in dermatology : a histological study on the effects of crude coal tar and isoquinoline." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236062.

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This study involves a morphological and histological investigation of normal mouse tail skin and its response to crude coal tar and isoquinoline (a major constituent of coal tar). Mouse tail skin is unusual in that it undergoes both parakeratotic and orthokeratotic keratinization in adjacent sites. The former develops without a granular layer and resembles psoriasis, while the latter, with a granular layer, resembles normal human skin. Based on this property, mouse tail skin has frequently been used as a model for psoriasis but in spite of this, an integrated, detailed picture of its structure has not previously been described. This was achieved in this study by using a range of complementary techniques: light microscopy of embedded and frozen material, scanning and transmission electron microscopy, quantitative image analysis and autoradiography. Such a study may help to elucidate the mechanism of both orthokeratotic and parakeratotic keratinization. Coal tar has been used extensively in the treatment of psoriasis and is safe and effective. However, it is cosmetically unappealing, its mechanism of action is unknown and its efficacy varies with its composition which is extremely heterogeneous. Isoquinoline may significantly contribute to its anti-psoriatic properties. The mode of action of these substances as modifiers of the keratinization process may be clarified by studying their effects on the model. Both substances induced granular layer formation in previously parakeratotic areas, with concommitant development of an orthokeratotic stratum corneum, a desirable property in a potential anti-psoriatic. However, they also induced epidermal thickening and hyperkeratosis. The effects on the pilosebaceous unit were strikingly different: coal tar caused metaplasia of sebaceous glands with follicular hyperkeratosis and hair loss while isoquinoline caused sebaceous gland hypertrophy. Isoquinoline also caused far more epidermal irritation than coal tar, and caused damage to the basal lamina and dermal collagen. The irritant effects were modified to some extent by hydrocortisone cream but this also reduced granular layer induction. These studies suggest that isoquinoline may act on parakeratotic epidermis in a similar way to coal tar. It has the advantages of being a cleaner substance, with a more consistent action. However, its usefulness may be limited by its irritancy.
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35

Berglin, Ewa. "Predictors of disease onset and progression in early rheumatoid arthritis : A clinical, laboratory and radiological study." Doctoral thesis, Umeå : Public Health and Clinical Medicine, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-669.

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36

Lindqvist, Per. "Right heart function in health and disease : a Doppler echocardiography and Doppler tissue imaging study /." Doctoral thesis, Umeå : Department of Public Health and Clinical Medicine, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-392.

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37

Rauma-Pinola, T. (Tanja). "Adenovirus endocytosis and adenoviral gene transfer in cardiovascular and dermatologic disease models." Doctoral thesis, University of Oulu, 2004. http://urn.fi/urn:isbn:9514274342.

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Abstract Adenoviral gene transfer is a valuable tool in molecular biology research. In order to be an efficient and safe vector, adenovirus structure and infection mechanism as well as molecular biology of the used transgene need to be well studied. The aim of this study was to evaluate the role of adenovirus as a gene transfer vector from several perspectives. Adenovirus uses receptor-mediated endocytosis in order to enter the target cell. The effect of Rab5 GTPase on adenovirus entry and gene transfer efficiency was examined first. Next, adenovirus was used as an investigatory tool in the cardiovascular research, focused on clarifying the role of adrenomedullin (AM) in heart and vascular remodeling. Finally, a model of adenoviral gene transfer into skin fibroblasts was used. The role of Rab5 GTPase in the adenovirus endocytosis was examined in HeLa cells using Cy3-labeled adenovirus, and gene transfer efficiency using β-galactosidase encoding adenovirus. Rab5 increased both adenovirus uptake and gene transfer, whereas dominant negative Rab5S34N decreased both endocytosis and gene transfer. The data indicate that Rab5 is needed in mediating the adenovirus uptake into the target cell. In the rat heart, adenovirus-mediated AM gene transfer transiently improved systolic function both in vivo and in vitro. AM caused activation of translocation of protein kinases C ε and δ, whereas phosphorylation of p38 mitogen activated protein kinase was decreased in the left ventricle. AM significantly attenuated the development of angiotensin II-induced cardiac hypertrophy. In rats with myocardial infarction, AM enhanced dilatation of left ventricle and thinning of anterior wall. The role of AM in neointima formation was evaluated in rat artery after endothelial injury. Intravascular AM gene transfer decreased neointimal growth and increased neointimal myofibroblasts apoptosis. These results show that AM regulates left ventricular systolic function and remodeling in the heart, and plays a role in pathological vascular remodeling. Adenovirus-mediated lysyl hydroxylase (LH) gene transfer into skin fibroblasts of type VI Ehlers-Danlos syndrome patient and rat skin increased functional LH production, elevated LH activity, and human LH mRNA production both in vitro and in vivo. LH gene replacement therapy may thus lead to possibilities to improve skin wound healing in Ehlers-Danlos syndrome patients.
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38

Lindberg, Anne. "Chronic obstructive pulmonary disease (COPD) : prevalence, incidence, decline in lung function and risk factors." Doctoral thesis, Umeå : Public Health and Clinical Medicine, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-347.

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39

Johnston, Nina. "Low-Density Lipoprotein Oxidation and Renal Dysfunction : New Markers of Poor Prognosis in Patients with Unstable Coronary Artery Disease." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6626.

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40

Hönzke, Stefan [Verfasser]. "In vitro Skin Disease Equivalents and their Applications in Basic Dermatologic Research / Stefan Hönzke." Berlin : Freie Universität Berlin, 2018. http://d-nb.info/1159900620/34.

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41

Kristjánsson, Guðjón. "Food Antigen Sensitivity in Coeliac Disease Assessed by the Mucosal Patch Technique." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6020.

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A diagnosis of coeliac disease (CD) in adults relies on the presence of a structurally abnormal intestinal mucosa, followed by a clear clinical remission on a gluten-free diet. There is a clear need for a rapid, simple, safe and sensitive method to determine the type and intensity of inflammation in the gut mucosa in clinical practice. The overall aims of our studies were to develop and evaluate a new technique, “the mucosal patch technique”, to characterize rectal local inflammatory process after rectal food challenge in patients with CD. In study 1 we evaluated the potential of the new technique. The technique was well tolerated and easily applied. Pronounced neutrophil and eosinophil involvement in ulcerative colitis (UC) was demonstrated. With the high sensitivity of the technique, low-degree mucosal neutrophil activation could also be quantified in patients with collagen colitis,UC in clinical remission and in patients with irritable bowel syndrome. In study 2 and 3 the aim was to elucidate the dynamics of the rectal inflammatory response and nitric oxide (NO) production after rectal gluten challenge. We found a pronounced neutrophil activation in coeliac patients after rectal gluten challenge. This activation was apparent 4 hours after challenge and remains for at least 48 hours. A more modest eosinophil activation started 1-2 hours later and remained at least for 48 hours. The biphasic pattern of neutrophil and eosinonphil activation after challenge suggests a biphasic inflammatory reaction. The activation of neutrophils and eosinophils precedes a pronounced enhancement of mucosal NO production. Some of our coeliac patients displayed signs of an inflammatory reaction after rectal corn gluten challenge. In study 4 the aim was to investigate the local inflammatory reaction to gluten and cow’s milk protein in CD patients in remission. The findings indicate that not only gluten sensitivity but also cow’s milk (CM) protein sensitivity is common in CD. The data support the hypothesis that CM sensitivity may contribute to persistent symptoms in coeliac patients on gluten-free diet.

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42

Bukachi, Frederick. "Ventricular Long Axis Function: Amplitudes and Timings : Echocardiographic Studies in Health and Disease." Doctoral thesis, Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-282.

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43

Dinh, Kate H. "Sentinel Lymph Node Biopsy in Elderly Patients with Intermediate Thickness Melanoma: A Masters Thesis." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/778.

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Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes. Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a prospectively-maintained database. Clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, ulceration, receipt and result of SLNB, completion of CLND, OS, and DFS. Results: Ninety-one patients underwent excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (p=0.11). DFS was similar between groups independent of receipt of SLNB. Conclusion: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had similar 5-year OS and DFS compared with those who did not receive SLNB. Routine SLNB for intermediate-thickness melanoma patients may not significantly change outcomes for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care.
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44

Dinh, Kate H. "Sentinel Lymph Node Biopsy in Elderly Patients with Intermediate Thickness Melanoma: A Masters Thesis." eScholarship@UMMS, 2005. http://escholarship.umassmed.edu/gsbs_diss/778.

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Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes. Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a prospectively-maintained database. Clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, ulceration, receipt and result of SLNB, completion of CLND, OS, and DFS. Results: Ninety-one patients underwent excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (p=0.11). DFS was similar between groups independent of receipt of SLNB. Conclusion: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had similar 5-year OS and DFS compared with those who did not receive SLNB. Routine SLNB for intermediate-thickness melanoma patients may not significantly change outcomes for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care.
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45

Schmitt, Jochen, Elisabeth Heese, Gottfried Wozel, and Michael Meurer. "Effectiveness of Inpatient Treatment on Quality of Life and Clinical Disease Severity in Atopic Dermatitis and Psoriasis Vulgaris – A Prospective Study." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135494.

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Background: Financial constraints challenge evidence of the effectiveness of dermatological inpatient management. Objective: To evaluate the effectiveness of hospitalization in atopic dermatitis and psoriasis regarding initial and sustained benefits. Methods: Prospective study on adults with psoriasis vulgaris (n = 22) and atopic dermatitis (n = 14). At admission, discharge, and 3 months after discharge, validated outcomes of objective and subjective disease severity were assessed by trained investigators. Results: Hospitalization resulted in substantial benefit in quality of life and clinical disease severity. Looking at mean scores, the observed benefit appeared stable until 3-month follow-up. The analysis of individual patient data revealed significant changes in disease severity between discharge and 3-month follow-up with some patients relapsing, others further improving. Reasons for hospitalization and treatment performed were not related to sustained benefit. Conclusions: In psoriasis vulgaris and atopic dermatitis, hospitalization effectively improved quality of life and clinical disease severity. Further research should focus on prognostic factors for sustained improvement
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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46

Schmitt, Jochen, Elisabeth Heese, Gottfried Wozel, and Michael Meurer. "Effectiveness of Inpatient Treatment on Quality of Life and Clinical Disease Severity in Atopic Dermatitis and Psoriasis Vulgaris – A Prospective Study." Karger, 2007. https://tud.qucosa.de/id/qucosa%3A27655.

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Background: Financial constraints challenge evidence of the effectiveness of dermatological inpatient management. Objective: To evaluate the effectiveness of hospitalization in atopic dermatitis and psoriasis regarding initial and sustained benefits. Methods: Prospective study on adults with psoriasis vulgaris (n = 22) and atopic dermatitis (n = 14). At admission, discharge, and 3 months after discharge, validated outcomes of objective and subjective disease severity were assessed by trained investigators. Results: Hospitalization resulted in substantial benefit in quality of life and clinical disease severity. Looking at mean scores, the observed benefit appeared stable until 3-month follow-up. The analysis of individual patient data revealed significant changes in disease severity between discharge and 3-month follow-up with some patients relapsing, others further improving. Reasons for hospitalization and treatment performed were not related to sustained benefit. Conclusions: In psoriasis vulgaris and atopic dermatitis, hospitalization effectively improved quality of life and clinical disease severity. Further research should focus on prognostic factors for sustained improvement.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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47

Chamcheu, Jean Christopher. "Disease-causing Keratin Mutations and Cytoskeletal Dysfunction in Human Skin : In vitro Models and new Pharmacologic Strategies for Treating Epidermolytic Genodermatoses." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-123071.

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Epidermolysis bullosa simplex (EBS) and epidermolytic ichthyosis (EI) are rare skin fragility diseases characterized by intra-epidermal blistering due to autosomal dominant-negative mutations in basal (KRT5 or KRT14) and suprabasal (KRT1 or KRT10) keratin genes,  respectively. Despite vast knowledge in the disease pathogenesis, the pathomechanisms are not fully understood, and no effective remedies exist. The purpose of this work was to search for keratin gene mutations in EBS patients, to develop in vitro models for studying EBS and EI, and to investigate novel pharmacological approaches for both diseases. We identified both novel and recurrent KRT5 mutations in all studied EBS patients but one which did not show any pathogenic keratin mutations. Using cultured primary keratinocytes from EBS patients, we reproduced a correlation between clinical severity and cytoskeletal instability in vitro. Immortalized keratinocyte cell lines were established from three EBS and three EI patients with different phenotypes using HPV16-E6E7. Only cell lines derived from severely affected patients exhibited spontaneous keratin aggregates under normal culture conditions. However, heat stress significantly induced keratin aggregates in all patient cell lines. This effect was more dramatic in cells from patients with a severe phenotype. In organotypic cultures, the immortalized cells were able to differentiate and form a multilayered epidermis reminiscent of those observed in vivo. Addition of two molecular chaperones, trimethylamine N-oxide dihydrate (TMAO) and sodium 4-phenylbutyrate (4-PBA), reduced the keratin aggregates in both stressed and unstressed EBS and EI keratinocytes, respectively. The mechanism of action of TMAO and 4-PBA was shown to involve the endogenous chaperone system (Heat shock proteins e.g. Hsp70). Besides, MAPK signaling pathways also seemed to be incriminated in the pathogenesis of EBS. Furthermore, depending on which type of keratin is mutated, 4-PBA up-regulated Hsp70 and KRT4 (possibly compensating for mutated KRT1/5), and down-regulated KRT1 and KRT10, which could further assist in protecting EBS and EI cells against stress. In conclusion, novel and recurrent pathogenic keratin mutations have been identified in EBS. Immortalized EBS and EI cell lines that functionally reflect the disease phenotype were established. Two pharmacologic agents, TMAO and 4-PBA, were shown to be promising candidates as novel treatment of heritable keratinopathies in this in vitro model.
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48

Claesson, Maria. "Women's hearts : ischaemic heart disease and stress management in women." Doctoral thesis, Umeå : Department of Public Health and Clinical Medicine, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-725.

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49

James, Stefan. "Coagulation, Inflammation and Myocardial Dysfunction in Unstable Coronary Artery Disease and the Influence of Glycoprotein IIb/IIIa Inhibition and Low Molecular Weight Heparin." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3372.

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50

Smith, Derek Richard. "Dermatological and musculoskeletal disorders of nursing home workers in Australia, Japan, South Korea and Taiwan." University of Southern Queensland, Faculty of Sciences, 2003. http://eprints.usq.edu.au/archive/00001510/.

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Although skin disease and musculoskeletal disorders are believed to be common among nursing home workers, to date there have been no coordinated international studies of these occupational issues. Therefore, it was considered appropriate to conduct one of the first cross-cultural investigations of occupational dermatology and ergonomic complaints among nursing home workers in Australia, Japan, South Korea and Taiwan using a standardised methodology. This thesis documents a 4-year investigation of skin disease and musculoskeletal disorders conducted among 465 nursing home staff in Australia, Japan, South Korea and Taiwan. Skin diseases were diagnosed by specialist physicians during medical examinations, while information on musculoskeletal disorders was collected by means of a self-reported questionnaire. There were major differences in both the location and type of skin disease between the 4 groups. Overall, the Australian group suffered a generally higher prevalence of skin disease than in the other three countries investigated, most likely due to their significantly higher rate of sun-induced skin damage. The high prevalence of cutaneous fungal disease seen within the Taiwanese subjects most probably arose from the comparatively higher temperature and relative humidity of Taiwan. Other potentially important skin disease risk factors included previous skin disease and a history of allergy, both of which are consistent with current knowledge. Although musculoskeletal disorders were found to be most prevalent among the Japanese nursing home staff at almost all body sites, the reasons for this are not clear. It may have related to a generally higher musculoskeletal rate, or a higher degree of self-reporting on their questionnaires. Individual MSD risk factors included moving patients, washing patients, working as an assistant nurse and daily alcohol consumption. Interestingly, MSD was found to be a co-factor for current skin disease. Overall, this study indicated that certain occupational health issues consistently affect nursing home staff in the 4 countries, but the prevalence and rank order varies from nation to nation. It was also shown that nursing home work incurs a reasonable degree of risk and that skin disease and musculoskeletal disorders are important occupational issues within these facilities.
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