Den här uppsatsens syfte har varit att kartlägga skillnader i representation av individer med dvärgväxt, från antikens Egypten fram till renässansen. Forskning har gjorts på detta utanför Sverige, men de fyra svenska människorna med dvärgväxt har inte tillfogats och jämförts med det utländska materialet innan denna uppsats. Metoden har varit en litterär jämförelse där andra författare har analyserats. De förhistoriska och historiska litterära verken som dessa författare undersökt har bland annat innefattat egyptiska papyrus, grekisk och romersk lagstiftning och medeltida dokument. Konst från dessa tider har också undersökts. Resultatet av uppsatsen har varit att uppfattningen av dvärgväxt har undergått stor variation genom förhistorien och historien. Ju längre tillbaka vi går desto högre tolerans finner vi. Dvärgar var populära i Egypten på ett sätt som återkommer i medeltidens och renässansens Europa, då hovdvärgar är på modet. Hur det har sett ut i Skandinavien är svårt att säga trots de mänskliga kvarlevorna som påträffats av individer med dvärgväxt. I uppsatsen tas även myter och folklore om dvärgar upp för att måla en djupare förståelsebild av acceptansen i samhället och hur legender kan antingen hjälpa eller stjälpa i sammanhanget.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Orientadores: Denise Pontes Cavalcanti, Luciana Cardoso Bonadia / Texto em português e inglês / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T19:05:42Z (GMT). No. of bitstreams: 1 Kanazawa_ThatianeYoshie_M.pdf: 1904408 bytes, checksum: 8b54672e34f366d597d94eb97bfafa4d (MD5) Previous issue date: 2014 / Resumo: Entre as osteocondrodisplasias (OCD) destacam-se as displasias esqueléticas do grupo 1 (FGFR3) devido à sua alta frequência. Nesse grupo, além das displasias com fenótipo característico e considerável correlação genótipo-fenótipo, como a acondroplasia (Ach) e a displasia tanatofórica (DT), está a hipocondroplasia (Hch), cujo fenótipo em geral é mais leve, apresenta grande variabilidade clínico-radiológica e heterogeneidade etiológica. O objetivo desse estudo foi sequenciar o gene FGFR3 numa coorte de pacientes com fenótipo típico ou sugestivo. A análise molecular foi feita por sequenciamento direto, começando pelos hot spots e, seguindo com o sequenciamento completo do gene quando os primeiros foram negativos. Foram incluídos 63 pacientes na casuística: 30 Ach, 7 Hch, 10 Hch?, 13 DT-I e 3 DT-II. Dentre os casos de Ach, todos apresentaram a mutação mais comumente associada à Ach (p.G380R), inclusive um paciente com fenótipo atípico e suspeita de mosaicismo somático, não comprovado, devido à assimetria corporal. Dentre os casos de Hch, todos os sete apresentaram a mutação mais comum para este fenótipo (p.N540K) inclusive dois pacientes com uma Hch grave com manifestações clínicas e radiológicas no período neonatal e dez pacientes, diagnosticados como uma Hch duvidosa (Hch?) por apresentarem baixa estatura com alguns sinais radiológicos, não foi encontrada mutação, sendo que em cinco casos, o sequenciamento não foi concluído. Três mutações diferentes, que ocorrem com maior frequência, foram identificadas entre os casos de DT-I, a p.R248C em sete pacientes, entre eles um paciente atípico por apresentar maior sobrevida, p.S249C em três e a p.Y373C em dois. Em todos os casos de DT-II, como esperado, foi encontrada a única mutação até então descrita para este fenótipo (p.K650E). Os resultados deste estudo permitiram a identificação de casos interessantes, ressaltaram a ótima correlação genótipo-fenótipo do grupo FGFR3 e reforçaram a importância da investigação molecular do gene FGFR3 nos casos com fenótipos duvidosos ou atípicos / Abstract: Among osteochondrodysplasias (OCD) stand out the skeletal dysplasias group 1 (FGFR3) due to its high frequency. In this group, besides the conditions with considerable characteristic phenotype and genotype-phenotype correlation, such as achondroplasia (Ach) and thanatophoric dysplasia (TD), there is hypochondroplasia (HCH), whose phenotype is generally milder, with a large clinical and radiological variability and etiological heterogeneity. The aim of this study was to sequence the FGFR3 gene in a cohort of patients with typical or suggestive phenotype. Molecular analysis was performed by direct sequencing, starting with the hot spots, and following with the complete sequencing of the gene when the first were negative. In this sample, 63 patients were included: 30 Ach, 7 Hch, 10 Hch?, 13 DT-I and 3 DT-II. Among the Ach cases, all exhibit the most common mutation associated with Ach (p.G380R), including one patient with an atypical phenotype, with suspicious of somatic mosaicism, not confirmed, due to body asymmetry. Among the Hch cases, all the seven patients showed the most common mutation for this phenotype (p.N540K) including two patients with severe Hch with clinical and radiological manifestations in the neonatal period and ten patients, diagnosed as a doubtful Hch (Hch?), because of their low stature with some radiological signs, no mutation was found, and in five cases, sequencing was not completed. Three different mutations, which occur more frequently, were identified among the DT-I cases, p.R248C in seven patients, including an atypical patient with a long-term survival, p.S249C in three and p.Y373C in two. In all DT-II cases, as expected, the only mutation described so far for this phenotype (p.K650E) was found. The results of this study allowed the identification of interesting cases, emphasized the great genotype-phenotype correlation of FGFR3 group and reinforced the importance of molecular investigation of the FGFR3 gene in cases with doubtful or atypical phenotypes / Mestrado / Ciencias Biomedicas / Mestra em Ciências Médicas

Introduction: Achondroplasia is the most common bone dysplasia. It is caused by mutations in the FGFR3 gene, which is involved in regulation of proliferation and maturation of chondrocytes on the growth plates. Activating mutation results in impaired endochondral ossification and a wide range of symptoms: severe growth disorder with limb shortening, macrocephaly with risk of hydrocephalus, mid-facial dysplasia, sleep apnea, narrowing of the spinal canal, increased risk of respiratory complications, and airway inflammation. The current rapid technological development has led to a better understanding of the processes of epiphyseal growth cartilage, thus enabling the development of new drugs for the treatment of this disorder (modified CNP, soluble FGFR3, meclozine). Nevertheless, current treatment is primarily symptomatic. It is very important to have a growth patterns of patients with achondroplasia who have not been affected by any growth promoting treatment (prolongation surgery, growth hormone). Objectives: The aim of this study is to evaluate the growth of Czech patients with achondroplasia, to compare our data with the world-wide used data by Horton et al. (1978) and the current data by del Pino et al. (2018). The next aim was to verify the accuracy of the multiplier method of final height...

Introduction Achondroplasia is associated with foramen magnum stenosis (FMS) which can lead to sudden unexpected death in infants. There is no wide consensus regarding the best management of FMS. Aim The study aimed to describe the prevalence of FMS in a population of children with achondroplasia and to evaluate screening and neurosurgical interventions of FMS in regard to its effects and complications. Material and Methods This is a retrospective cohort study including all children with achondroplasia assessed or treated at Karolinska University Hospital between September 2005 to June 2020. Severity of FMS was graded using MRI Achondroplasia Foramen Magnum Score (AFMS). AFMS was correlated to neurological exams and polysomnography results. Results 51 children were included and severe FMS (AFMS3-4) was present in 35%. Sixty-five percent of the children underwent foramen magnum decompression (FMD). Neurological examination had a high specificity (94%), but a low sensitivity (28%) for severe FMS. Signs of central apnea on polysomnography did not correlate to severity of FMS (p=0.735). Surgery improved FMS (p<0.001) and decreased central apnea (p=0.070), but carried a risk of 9% for severe complications. Conclusions This study suggests that severe FMS is common in children with achondroplasia, that neurological symptoms may be absent even in severe FMS, and that FMD improves both FMS and central apnea. In order to limit morbidity and mortality by identifying children with severe FMS in need of FMD, we recommend routine MRI on all children with achondroplasia.

Os cães da raça Dachshund apresentam acondroplasia/hipocondroplasia, considerada uma condição fisiológica da raça, resultando num corpo longo com os membros curtos, arqueados e musculosos, esterno largo e proeminente, caixa torácica oval e ampla. Essas condições podem dificultar a realização e interpretação de alguns exames. A hipótese desse trabalho é que os cães da raça Dachshund tenham valores ecocardiográficos, eletrocardiográficos, radiográficos e pressóricos diferenciados. Para isso, foram estudados 69 cães adultos e sadios da raça Dachshund, sendo 28 (40,6%) machos e 41 (59,4%) fêmeas; com idade variando de 18 meses a 10 anos de idade; e peso médio de 8,4±2,3 kg. Foram realizados exames ecocardiográfico, eletrocardiográfico, radiográfico, bem como determinação de pressão arterial sistêmica em todos os animais. Para a análise dos resultados, os animais foram categorizados, segundo, gênero, presença ou ausência de castração, faixa etária (A: >1 a ≤ 3 anos, B: >3 a ≤ 6 anos e C: >6 a ≤ 10 anos), peso (< 8 kg e ≥ 8 kg) e circunferência torácica (> 45 cm e ≥ 45 cm). Foram estabelecidos, em cães adultos e sadios da raça Dachshund, os valores de ecocardiografia convencional, eletrocardiografia, radiografia e de pressão arterial sistêmica por meio do método Doppler Os resultados ecocardiográficos principais, com a média e intervalo de confiança de 95% foram: septo interventricular em diástole SIVd (6,5 [6,3-6,7] cm), parede livre de ventrículo esquerdo em diástole PLVEd (6,3 [6,1-6,4] cm), diâmetro interno de ventrículo esquerdo na diástole DIVEd (2,5 [2,5-2,6] cm), diâmetro interno de ventrículo esquerdo na sístole DIVEs (1,2 [1,2-1,3] cm), fração de encurtamento - FE -(51,32 [49,79-52,84]%), fração de ejeção do ventrículo esquerdo Fej (0,84 [0,82-0,85]). Não houve diferença estatística para gênero ou castração. Mas quando os cães foram separados pela faixa etária, houve diferença estatística significativa entre os grupos A e B (p = 0,0073) para SIVd e PLVEd; sendo que os valores para o grupo A foram de: SIVd (6,2 [5,9-6,5] cm) e PLVEd (6,0 [5,7-6,2] cm). Os valores para o grupo B foram: SIVd (6,9 [6,5-7,3] cm) and PLVEd (6,5 [6,3-6,8] cm). Não houve diferença entre o grupo C e os grupos A e B; os valores para o grupo C foram: SIVd (6,4 [5,9-6,8] cm) e PLVEd (6,4 [6,1-6,7] cm). Portanto, cães adultos da raça Dachshund possuem espessura maiores de SIVd e PLVEd quando comparados com valores padronizados para outras raças. Quando os animais foram divididos pelo peso (>8 kg e ≥ 8 Kg), houve diferenças significativas para DVEd (2,44±0,26 cm; 2,64±0,27 cm; p>0,001), como também para circunferência torácica (> 45 cm e ≥ 45 cm), com valores de 2,43±0,25 cm e 2,63±0,27 cm (p>0,001). Também foram estabelecidos valores ecocardiográficos para tamanho do átrio esquerdo, nos eixos látero-lateral e ápico-basilar, respectivamente, iguais a 2,24±0,31 cm e 2,17±0,31 cm; bem como os valores de Doppler tecidual do anel valvar mitral lateral: onda E`=0,11±0,02 m/s, onda A´=0,10±0,02 m/s e razões E´/A´=1,12±0,33 m/s e E/E´=5,91±1,21 m/s. Cães adultos e sadios da raça Dachshund podem apresentar prolapso valvar mitral (40,58%). O valor de pressão arterial sistêmica por meio do método Doppler na cauda de cães Dachshund adultos e sadios foi de 134±20 mmHg diferenciando-se estatisticamente (p > 0,0001) dos valores obtidos no membro torácico (155±28 mmHg). / Dachshund dogs present achondroplasia/hypochondroplasia, considered a breed physiological condition, that results in a long body with short, arched and muscular limbs, large sternum, oval and wide ribcage and developed heart and lungs. All this factors can difficult exams realization and interpretation. The hypothesis is that Dachshund dogs have differentiated echocardiographic, electrocardiographic, radiographic, and systolic blood pressure parameters. Therefore, 69 adult and healthy Dachshund dogs were studied (28 [40.6%] males and 41 [59.4%] females); from 18 months to 10 years-old, weighting 8.4±2.3 kg. Echocardiographic, electrocardiographic, radiographic and systemic arterial pressure evaluations were performed. Animals were categorized according to gender, neutered or not, age group (A: >1 a ≤ 3 years, B: >3 a 6 years e C: >6 a ≤ 10 years), weight (< 8 kg e ≥ 8 kg) e thoracic circumference (< 45 cm e ≥ 45 cm). The values of conventional echocardiography, electrocardiography, radiography and systemic arterial pressure were established in Dachshund dogs using the Doppler method. The main echocardiographic results, with a mean and 95% confidence interval were: interventricular septum in diastole IVSd (6.5 [6.3-6.7] cm), left ventricular free wall in diástole - LVFWd (6.3 [6.1-6.4] cm), left ventricular internal diameter in diastole LVIDd (2.5 [2.5-2.6] cm), left ventricular internal diameter LVIDs (1.2 [1.2-1.3] cm), shortening fraction SF (51.32 [49.79-52.84]%), left ventricular ejection fraction LVEF (0.84 [0.82-0.85]). There was no statistical difference for gender or castration. But when dogs were categorized by age, there was a statistically significant difference between groups A and B (p = 0.0073) for IVSd and LVFWd.; and the values for group A were: IVSd (6.2 [5.9-6.5] cm) and LVFWd (6.0 [5.7-6.2] cm). The values for group B were: IVSd (6.9 [6.5-7.3] cm) and LVFWd (6.5 [6.3-6.8] cm). There was no difference between group C and groups A and B; The values for group C were: IVSd (6.4 [5.9-6.8] cm) and LVFWd (6.4 [6.1-6.7] cm). Therefore, adult dogs of the breed Dachshund have thickness of IVSd and LVFWd when compared with values standardized for other breeds. When animals were divided by weight (< 8 kg and ≥ 8 kg), there were significant differences for LVIDd (2.44 ± 0.26 cm, 2.64 ± 0.27 cm, p (< 0.001), as well as for thoracic circumference (< 45 cm and ≥ 45 cm), with values of 2.43 ± 0.25 cm and 2.63 ± 0.27 cm (p < 0.001). Echocardiographic values were also established for left atrial size, on the latero-lateral and apical-basilar axes at 2.24 ± 0.31 cm and 2.17 ± 0.31 cm, respectively. In addition, the tissue Doppler values of the lateral mitral valve ring: E\' wave = 0.11±0.02 m/s, A\' wave = 0.10±0.02 m/s and E\'/A\' ratios = 1,12±0.33 m/s and E/E \'= 5.91±1.21 m/s. Adult and healthy Dachshund dogs may present with mitral valve prolapse (40.58%). The Doppler method in the tail of healthy Dachshund dogs was 134 ± 20 mmHg, statistically different (p < 0.0001) from values obtained in left forelimb (155 ± 28 mmHg).

The role of Indian hedgehog (Ihh) signalling in the regulation of endochondral bone formation is well established. Ihh controls the rate of bone growth by negatively regulating differentiation and positively regulating growth plate chondrocyte proliferation. It has been well documented also that mutations resulting in constitutive activation of signalling through FGFR3 in chondrodysplasia, lead to a significant decrease in this important signalling factor accompanied by reduced proliferation of the chondrocytes and a dwarf phenotype. / In an attempt to rescue the chondrodysplasia phenotype hedgehog agonist Hh-Ag 1.4 was injected subcutaneously into mice with achondroplasia (ACH) or with severe achondroplasia with developmental delay and acanthosis negricans (SADDAN) with mixed results. / Administration of a hedgehog agonist in SADDAN mice led to a significant up-regulation of both Ptch and Gli1, as measured by quantitative PCR, indicating that Hh-Ag 1.4 does indeed stimulate hedgehog signalling in vivo. Also, in situ hybridization for Ihh seems to show a down regulation of native Ihh expression in pre-hypertrophic chondrocytes, possibly due to the activation of the negative PTHrP feedback loop. In our study, Hh-Ag 1.4 treatment resulted in an increased growth plate length and reduced size of the hypertrophic zone. The cortical bone flanking the growth plate in mice injected with Hh-Ag 1.4 was 2-3 times thicker than in control mice, which may be attributed to the positive effect of increased Ihh signalling in osteoblastogenesis. Contrary to our expectations, there was also a noticeable reduction in chondrocyte proliferation in mice treated with the agonist. / Overall, the effect on the growth of long bones was not beneficial and the treatment with high doses of Hh-Ag 1.4 did not result in an amelioration of the chondrodysplastic phenotype.

Os cães da raça Dachshund apresentam acondroplasia/hipocondroplasia, considerada uma condição fisiológica da raça, resultando num corpo longo com os membros curtos, arqueados e musculosos, esterno largo e proeminente, caixa torácica oval e ampla. Essas condições podem dificultar a realização e interpretação de alguns exames. A hipótese desse trabalho é que os cães da raça Dachshund tenham valores ecocardiográficos, eletrocardiográficos, radiográficos e pressóricos diferenciados. Para isso, foram estudados 69 cães adultos e sadios da raça Dachshund, sendo 28 (40,6%) machos e 41 (59,4%) fêmeas; com idade variando de 18 meses a 10 anos de idade; e peso médio de 8,4±2,3 kg. Foram realizados exames ecocardiográfico, eletrocardiográfico, radiográfico, bem como determinação de pressão arterial sistêmica em todos os animais. Para a análise dos resultados, os animais foram categorizados, segundo, gênero, presença ou ausência de castração, faixa etária (A: >1 a ≤ 3 anos, B: >3 a ≤ 6 anos e C: >6 a ≤ 10 anos), peso (< 8 kg e ≥ 8 kg) e circunferência torácica (> 45 cm e ≥ 45 cm). Foram estabelecidos, em cães adultos e sadios da raça Dachshund, os valores de ecocardiografia convencional, eletrocardiografia, radiografia e de pressão arterial sistêmica por meio do método Doppler Os resultados ecocardiográficos principais, com a média e intervalo de confiança de 95% foram: septo interventricular em diástole SIVd (6,5 [6,3-6,7] cm), parede livre de ventrículo esquerdo em diástole PLVEd (6,3 [6,1-6,4] cm), diâmetro interno de ventrículo esquerdo na diástole DIVEd (2,5 [2,5-2,6] cm), diâmetro interno de ventrículo esquerdo na sístole DIVEs (1,2 [1,2-1,3] cm), fração de encurtamento - FE -(51,32 [49,79-52,84]%), fração de ejeção do ventrículo esquerdo Fej (0,84 [0,82-0,85]). Não houve diferença estatística para gênero ou castração. Mas quando os cães foram separados pela faixa etária, houve diferença estatística significativa entre os grupos A e B (p = 0,0073) para SIVd e PLVEd; sendo que os valores para o grupo A foram de: SIVd (6,2 [5,9-6,5] cm) e PLVEd (6,0 [5,7-6,2] cm). Os valores para o grupo B foram: SIVd (6,9 [6,5-7,3] cm) and PLVEd (6,5 [6,3-6,8] cm). Não houve diferença entre o grupo C e os grupos A e B; os valores para o grupo C foram: SIVd (6,4 [5,9-6,8] cm) e PLVEd (6,4 [6,1-6,7] cm). Portanto, cães adultos da raça Dachshund possuem espessura maiores de SIVd e PLVEd quando comparados com valores padronizados para outras raças. Quando os animais foram divididos pelo peso (>8 kg e ≥ 8 Kg), houve diferenças significativas para DVEd (2,44±0,26 cm; 2,64±0,27 cm; p>0,001), como também para circunferência torácica (> 45 cm e ≥ 45 cm), com valores de 2,43±0,25 cm e 2,63±0,27 cm (p>0,001). Também foram estabelecidos valores ecocardiográficos para tamanho do átrio esquerdo, nos eixos látero-lateral e ápico-basilar, respectivamente, iguais a 2,24±0,31 cm e 2,17±0,31 cm; bem como os valores de Doppler tecidual do anel valvar mitral lateral: onda E`=0,11±0,02 m/s, onda A´=0,10±0,02 m/s e razões E´/A´=1,12±0,33 m/s e E/E´=5,91±1,21 m/s. Cães adultos e sadios da raça Dachshund podem apresentar prolapso valvar mitral (40,58%). O valor de pressão arterial sistêmica por meio do método Doppler na cauda de cães Dachshund adultos e sadios foi de 134±20 mmHg diferenciando-se estatisticamente (p > 0,0001) dos valores obtidos no membro torácico (155±28 mmHg). / Dachshund dogs present achondroplasia/hypochondroplasia, considered a breed physiological condition, that results in a long body with short, arched and muscular limbs, large sternum, oval and wide ribcage and developed heart and lungs. All this factors can difficult exams realization and interpretation. The hypothesis is that Dachshund dogs have differentiated echocardiographic, electrocardiographic, radiographic, and systolic blood pressure parameters. Therefore, 69 adult and healthy Dachshund dogs were studied (28 [40.6%] males and 41 [59.4%] females); from 18 months to 10 years-old, weighting 8.4±2.3 kg. Echocardiographic, electrocardiographic, radiographic and systemic arterial pressure evaluations were performed. Animals were categorized according to gender, neutered or not, age group (A: >1 a ≤ 3 years, B: >3 a 6 years e C: >6 a ≤ 10 years), weight (< 8 kg e ≥ 8 kg) e thoracic circumference (< 45 cm e ≥ 45 cm). The values of conventional echocardiography, electrocardiography, radiography and systemic arterial pressure were established in Dachshund dogs using the Doppler method. The main echocardiographic results, with a mean and 95% confidence interval were: interventricular septum in diastole IVSd (6.5 [6.3-6.7] cm), left ventricular free wall in diástole - LVFWd (6.3 [6.1-6.4] cm), left ventricular internal diameter in diastole LVIDd (2.5 [2.5-2.6] cm), left ventricular internal diameter LVIDs (1.2 [1.2-1.3] cm), shortening fraction SF (51.32 [49.79-52.84]%), left ventricular ejection fraction LVEF (0.84 [0.82-0.85]). There was no statistical difference for gender or castration. But when dogs were categorized by age, there was a statistically significant difference between groups A and B (p = 0.0073) for IVSd and LVFWd.; and the values for group A were: IVSd (6.2 [5.9-6.5] cm) and LVFWd (6.0 [5.7-6.2] cm). The values for group B were: IVSd (6.9 [6.5-7.3] cm) and LVFWd (6.5 [6.3-6.8] cm). There was no difference between group C and groups A and B; The values for group C were: IVSd (6.4 [5.9-6.8] cm) and LVFWd (6.4 [6.1-6.7] cm). Therefore, adult dogs of the breed Dachshund have thickness of IVSd and LVFWd when compared with values standardized for other breeds. When animals were divided by weight (< 8 kg and ≥ 8 kg), there were significant differences for LVIDd (2.44 ± 0.26 cm, 2.64 ± 0.27 cm, p (< 0.001), as well as for thoracic circumference (< 45 cm and ≥ 45 cm), with values of 2.43 ± 0.25 cm and 2.63 ± 0.27 cm (p < 0.001). Echocardiographic values were also established for left atrial size, on the latero-lateral and apical-basilar axes at 2.24 ± 0.31 cm and 2.17 ± 0.31 cm, respectively. In addition, the tissue Doppler values of the lateral mitral valve ring: E\' wave = 0.11±0.02 m/s, A\' wave = 0.10±0.02 m/s and E\'/A\' ratios = 1,12±0.33 m/s and E/E \'= 5.91±1.21 m/s. Adult and healthy Dachshund dogs may present with mitral valve prolapse (40.58%). The Doppler method in the tail of healthy Dachshund dogs was 134 ± 20 mmHg, statistically different (p < 0.0001) from values obtained in left forelimb (155 ± 28 mmHg).

No description available.