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1.
Sci Rep ; 7(1): 7975, 2017 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-28801591

RESUMO

YAP1, which encodes the Yes-associated protein 1, is part of the Hippo pathway involved in development, growth, repair and homeostasis. Nonsense YAP1 mutations have been shown to co-segregate with autosomal dominantly inherited coloboma. Therefore, we screened YAP1 for variants in a cohort of 258 undiagnosed UK patients with developmental eye disorders, including anophthalmia, microphthalmia and coloboma. We identified a novel 1 bp deletion in YAP1 in a boy with bilateral microphthalmia and bilateral chorioretinal coloboma. This variant is located in the coding region of all nine YAP1 spliceforms, and results in a frameshift and subsequent premature termination codon in each. The variant is predicted to result in the loss of part of the transactivation domain of YAP1, and sequencing of cDNA from the patient shows it does not result in nonsense mediated decay. To investigate the role of YAP1 in human eye development, we performed in situ hybridisation utilising human embryonic tissue, and observed expression in the developing eye, neural tube, brain and kidney. These findings help confirm the role of YAP1 and the Hippo developmental pathway in human eye development and its associated anomalies and demonstrate its expression during development in affected organ systems.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Coloboma/genética , Microftalmia/genética , Mutação , Fenótipo , Fosfoproteínas/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Criança , Coloboma/patologia , Genótipo , Humanos , Masculino , Microftalmia/patologia , Fosfoproteínas/metabolismo , Fatores de Transcrição , Proteínas de Sinalização YAP
2.
Hum Genet ; 136(1): 119-127, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27844144

RESUMO

Anophthalmia, microphthalmia, and coloboma are a genetically heterogeneous spectrum of developmental eye disorders and affect around 30 per 100,000 live births. OLFM2 encodes a secreted glycoprotein belonging to the noelin family of olfactomedin domain-containing proteins that modulate the timing of neuronal differentiation during development. OLFM2 SNPs have been associated with open angle glaucoma in a case-control study, and knockdown of Olfm2 in zebrafish results in reduced eye size. From a cohort of 258 individuals with developmental eye anomalies, we identified two with heterozygous variants in OLFM2: an individual with bilateral microphthalmia carrying a de novo 19p13.2 microdeletion involving OLFM2 and a second individual with unilateral microphthalmia and contralateral coloboma who had a novel single base change in the 5' untranslated region. Dual luciferase assays demonstrated that the latter variant causes a significant decrease in expression of OLFM2. Furthermore, RNA in situ hybridisation experiments using human developmental tissue revealed expression in relevant structures, including the lens vesicle and optic cup. Our study indicates that OLFM2 is likely to be important in mammalian eye development and disease and should be considered as a gene for human ocular anomalies.


Assuntos
Proteínas da Matriz Extracelular/genética , Anormalidades do Olho/genética , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Polimorfismo de Nucleotídeo Único , Linhagem Celular Tumoral , Estudos de Coortes , Olho/embriologia , Anormalidades do Olho/diagnóstico , Proteínas do Olho/genética , Deleção de Genes , Regulação da Expressão Gênica , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/etiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino
3.
Acta Biomater ; 25: 131-142, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26213371

RESUMO

We provide evidence to show that the standard reactant concentrations used in tissue engineering to cross-link collagen-based scaffolds are up to 100 times higher than required for mechanical integrity in service, and stability against degradation in an aqueous environment. We demonstrate this with a detailed and systematic study by comparing scaffolds made from (a) collagen from two different suppliers, (b) gelatin (a partially denatured collagen) and (c) 50% collagen-50% gelatin mixtures. The materials were processed, using lyophilisation, to produce homogeneous, highly porous scaffolds with isotropic architectures and pore diameters ranging from 130 to 260 µm. Scaffolds were cross-linked using a carbodiimide treatment, to establish the effect of the variations in crosslinking conditions (down to very low concentrations) on the morphology, swelling, degradation and mechanical properties of the scaffolds. Carbodiimide concentration of 11.5mg/ml was defined as the standard (100%) and was progressively diluted down to 0.1%. It was found that 10-fold reduction in the carbodiimide content led to the significant increase (almost 4-fold) in the amount of free amine groups (primarily on collagen lysine residues) without compromising mechanics and stability in water of all resultant scaffolds. The importance of this finding is that, by reducing cross-linking, the corresponding cell-reactive carboxylate anions (collagen glutamate or aspartate residues) that are essential for integrin-mediated binding remain intact. Indeed, a 10-fold reduction in carbodiimide crosslinking resulted in near native-like cell attachment to collagen scaffolds. We have demonstrated that controlling the degree of cross-linking, and hence retaining native scaffold chemistry, offers a major step forward in the biological performance of collagen- and gelatin-based tissue engineering scaffolds. STATEMENT OF SIGNIFICANCE: This work developed collagen and gelatine-based scaffolds with structural, material and biological properties suitable for use in myocardial tissue regeneration. The novelty and significance of this research consist in elucidating the effect of the composition, origin of collagen and crosslinking concentration on the scaffold physical and cell-binding characteristics. We demonstrate that the standard carbodiimide concentrations used to crosslink collagenous scaffolds are up to 100 times higher than required for mechanical integrity in service, and stability against dissolution. The importance of this finding is that, by reducing crosslinking, the corresponding cell-reactive carboxylate anions (essential for integrin-mediated binding) remain intact and the native scaffold chemistry is retained. This offers a major step forward in the biological performance of tissue engineered scaffolds.


Assuntos
Colágeno/química , Reagentes de Ligações Cruzadas/química , Fenômenos Mecânicos , Alicerces Teciduais/química , Aminas/análise , Animais , Carbodi-Imidas/química , Bovinos , Comunicação Celular , Linhagem Celular Tumoral , Humanos , Microscopia Confocal , Microscopia Eletrônica de Varredura , Peptídeos/química , Porosidade , Reologia , Solubilidade , Suspensões , Viscosidade , Água/química
4.
Clin Med (Lond) ; 11(5): 434-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22034700

RESUMO

Significant changes to the structure and entry into specialist training continue to be implemented. This is likely to have had a long-term impact on rheumatology service provision and the proportion of trainees undertaking academic medicine. An online questionnaire was sent to all trainees on the Joint Royal Colleges Postgraduate Training Board (JRCPTB) database. Out of 211 trainees, 141 responded (66.8%). Of these, 33 (23%) were registered for, or had been awarded, an MD or PhD with a wide variety of funding sources. Mainstream funding sources included Arthritis Research UK, the Medical Research Council, the National Institute for Health Research and the Wellcome Trust, but a substantial number of trainees (n = 17, 51.5%) also utilised other sources of funding. The data from this study will be valuable in the planning of future rheumatology training and academic career pathways and provide useful comparative data for other medical specialties.


Assuntos
Educação de Pós-Graduação em Medicina/organização & administração , Reumatologia/educação , Adulto , Feminino , Humanos , Masculino , Apoio à Pesquisa como Assunto , Apoio ao Desenvolvimento de Recursos Humanos , Reino Unido
5.
Ann Rheum Dis ; 69(6): 1191-4, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19713205

RESUMO

OBJECTIVES: To investigate the possible role of a functional polymorphism in the soluble interleukin 6 receptor (sIL-6R) gene in the genetic background of rheumatoid arthritis (RA). METHODS: An association between disease status and the sIL-6R rs8192284 (A358D) variant was tested in 965 patients with RA and 988 unrelated healthy controls. Odds ratios (ORs) for disease were calculated with asymptotic 95% CI; p values <0.05 were considered statistically significant after adjustment for multiple testing. To determine the relationship between protein levels and IL-6R A358D genotype, the protein levels of sIL-6R in 100 plasma samples from healthy controls were measured using an ELISA and compared across the genotype groups. RESULTS: The allele frequency of the C allele (alanine) was lower in cases than in controls (38.4% vs 41.7%, p=0.04, OR 0.9, 95% CI 0.8 to 1.0), as were the CC/AC genotypes compared with AA genotype frequencies (61.0% in RA cases vs 67.5% in controls, p=0.004, OR 0.8, 95% CI 0.6 to 0.9). Plasma levels of sIL-6R differed significantly according to genotype in the controls: 17.00 + or - 2.03 ng/ml for A/A, 20.08 + or - 1.83 ng/ml for A/C and 21.57 + or - 2.10 ng/ml for C/C (p=0.0001). CONCLUSION: These data suggest a role for genetically determined lower sIL-6R levels as a risk factor for RA. The proinflammatory role of the IL6 system in established RA has been highlighted by the use of anti-sIL-6R antibodies. However, the findings of this study suggest a protective effect of IL6 on the risk of developing RA.


Assuntos
Artrite Reumatoide/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-6/genética , Artrite Reumatoide/sangue , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Receptores de Interleucina-6/sangue
6.
Ann Rheum Dis ; 68(9): 1494-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18728048

RESUMO

OBJECTIVE: Selenoprotein-S (SELS) is involved in the stress response within the endoplasmic reticulum (ER) and inflammation. Recently, promoter variants in the SELS gene were shown to be associated with plasma levels of interleukin (IL)6, IL1beta and tumour necrosis factor (TNF). It was hypothesised that these variants could influence rheumatoid arthritis (RA) susceptibility and may interact with functional single nucleotide polymorphisms (SNPs) in the genes for IL1, IL6 and TNF. METHODS: Genotyping was performed in 988 unrelated healthy controls and 965 patients with RA. Stratified analysis was used to test for interactions. Single gene effects and evidence of epistasis were investigated using the Mantel-Haenszel (M-H) test and the linkage disequilibrium (LD)-based statistic. RESULTS: No association of SELS -105 genotype and RA susceptibility was detected. Stratification of SELS -105 genotypes by IL1 -511 genotypes showed that the disease risk (comparing AA/GA to GG at the SELS -105 locus) in individuals with the GG/AG genotype at the IL1beta -511 locus was significantly lower than that in individuals having the AA genotype at the IL1beta -511 locus (odds ratio (OR): 0.9 and 2.3, respectively; p = 0.004 by M-H test). Significant epistasis was also detected using the LD-based statistic (p = <0.001). No interaction was observed between SELS -105 and IL6 or TNF variants. CONCLUSION: Our results reveal evidence of strong epistasis in two genes in the IL1 production pathway and highlight the potential importance of gene-gene interactions in the pathogenesis of RA.


Assuntos
Artrite Reumatoide/genética , Epistasia Genética , Interleucina-1/genética , Proteínas de Membrana/genética , Selenoproteínas/genética , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
7.
Rheumatology (Oxford) ; 47(6): 901-6, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18411218

RESUMO

OBJECTIVES: Against changes to junior doctor career structure under MMC (Modernizing Medical Careers), and uncertainty about the future place of rheumatology, we explored critical factors in choice of rheumatology as a speciality, and asked what factors might govern choices of prospective trainees. Using these data, we developed suggestions to enhance future recruitment. METHODS: A postal survey was sent to rheumatology specialist registrars (SpRs) on the Joint Committee for Higher Medical Training (JCHMT) database between December 2005 and January 2006, and concurrently by e-mail to the Rheumatologists at Training e-mail list. RESULTS: Seventy-three percent (165/227) of trainees responded. Of them, 89.1% had previous senior house officer (SHO) experience in rheumatology and 81.8% made a career decision in favour of rheumatology during their SHO post. The top four ranked factors influencing choice of rheumatology were SHO experience, subject matter, inspirational consultants and lifestyle aspects; 89.1% would still choose rheumatology now. Factors felt to be negatively influencing future trainees came under three key themes: poor student or postgraduate exposure, employment and service delivery issues (including concern over the future place of rheumatology in primary vs secondary care), and perceived poor profile of rheumatology. Factors positively influencing future candidates were subject matter, work/life balance and prior exposure to the speciality. CONCLUSIONS: Early postgraduate experience is key to choice of speciality. An overwhelming majority of trainees decide speciality during SHO experience. With ongoing changes in career structure, it is critical that rheumatology is incorporated into foundation and speciality training programmes and essential that continued measures are taken to improve the image of rheumatology.


Assuntos
Atitude do Pessoal de Saúde , Escolha da Profissão , Seleção de Pessoal/tendências , Reumatologia , Pesquisa Biomédica , Tomada de Decisões , Educação de Pós-Graduação em Medicina , Feminino , Humanos , Estilo de Vida , Masculino , Reumatologia/educação , Reumatologia/tendências , Reino Unido , Recursos Humanos
9.
Aliment Pharmacol Ther ; 24(11-12): 1613-21, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17206949

RESUMO

BACKGROUND: Intestinal metaplasia (Barrett's oesophagus), but not cardiac-type mucosa in columnar-lined oesophagus, is regarded as premalignant. As intestinal metaplasia and cardiac-type mucosa are endoscopically indiscernible, it is difficult to take targeted samples from columnar-lined oesophagus with consequently a risk of having undetected intestinal metaplasia. AIM: To investigate whether the intestinal markers CDX2, MUC2 and villin can predict the presence of undetected intestinal metaplasia in columnar-lined oesophagus. Methods Presence of intestinal metaplasia or cardiac-type mucosa was identified in 122 biopsy sets of columnar-lined oesophagus from 61 patients, collected at two subsequent follow-up upper endoscopies. CDX2, MUC2 and villin expression were determined by immunohistochemistry. RESULTS: All intestinal metaplasia samples (55) were positive for CDX2 and MUC2 and 32 of 55 for villin. CDX2 expression was detected in 23 of 67 (34%) samples with only cardiac-type mucosa. Detection of CDX2 in cardiac-type mucosa increased the likelihood of finding intestinal metaplasia in another biopsy set of columnar-lined oesophagus (odds ratio 3.5, 95% CI = 1.2-10, P = 0.02). MUC2 was positive in 13 of 23 (57%) of CDX2-positive cardiac-type mucosa samples, whereas villin was detected in seven of 23 (30%). CONCLUSIONS: CDX2 expression in cardiac-type mucosa might be able to predict the presence of undetected intestinal metaplasia in columnar-lined oesophagus, and thus may be a putative marker for the presence of intestinal metaplasia in the absence of goblet cells.


Assuntos
Esôfago de Barrett/patologia , Esôfago/patologia , Proteínas de Homeodomínio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia/métodos , Fator de Transcrição CDX2 , Endoscopia Gastrointestinal/métodos , Células Caliciformes/patologia , Humanos , Imuno-Histoquímica/métodos , Metaplasia , Pessoa de Meia-Idade
11.
J Clin Pathol ; 57(12): 1267-72, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15563666

RESUMO

BACKGROUND: Patients with Barrett's oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. AIMS: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. METHODS: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett's epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1-4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. RESULTS: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p<0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. CONCLUSIONS: Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.


Assuntos
Esôfago de Barrett/metabolismo , Carcinoma in Situ/química , Neoplasias Esofágicas/química , Mucinas/análise , Proteínas de Neoplasias/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Adenocarcinoma/química , Apoptose/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos , Mucina-4 , RNA Mensageiro/análise , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteína X Associada a bcl-2
12.
J Clin Pathol ; 57(10): 1063-8, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15452161

RESUMO

BACKGROUND: In Barrett's oesophagus (BO), squamous epithelium is replaced by specialised intestinal epithelium (SIE). Transcription factors associated with intestinal differentiation, such as CDX2, may be involved in BO development. AIM: To investigate CDX2 expression in BO, squamous epithelium, and oesophageal adenocarcinoma (ADC). METHODS: CDX2 expression was assessed in 245 samples-167 biopsies of the columnar lined segment and 38 squamous epithelial biopsies of 39 patients with histologically confirmed BO (10 with ADC). Forty biopsies from 20 patients with reflux oesophagitis (RO) without BO were also evaluated. CDX2 protein was investigated immunohistochemically in 138 biopsies from 16 patients with BO, four with ADC, and 20 with RO. Cdx2 and Muc2 mRNA were detected semiquantitatively using 88 BO biopsies and squamous epithelium from 19 BO patients, and when present from ADC. RESULTS: SIE was present in 53/79 biopsies from the columnar lined segment; CDX2 protein was seen in all epithelial cells, but not in biopsies containing only gastric metaplastic epithelium (26/79), or in squamous epithelium (0/40) of patients with RO. Cdx2 mRNA was detected in all biopsies with goblet cell specific Muc2 transcription-indicative of SIE. Low Cdx2 mRNA expression was seen in 6/19 squamous epithelium samples taken 5 cm above the squamocolumnar junction of BO patients. CONCLUSION: CDX2 protein/mRNA is strongly associated with oesophageal SIE. Cdx2 mRNA was present in the normal appearing squamous epithelium of one third of BO patients, and may precede morphological changes seen in BO. Therefore, pathways that induce Cdx2 transcription in squamous epithelial cells may be important in BO development.


Assuntos
Esôfago de Barrett/patologia , Esôfago/química , Proteínas de Homeodomínio/análise , Adenocarcinoma/química , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/metabolismo , Biomarcadores/análise , Fator de Transcrição CDX2 , Epitélio/química , Epitélio/patologia , Neoplasias Esofágicas/química , Esôfago/patologia , Feminino , Proteínas de Homeodomínio/genética , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Mucina-2 , Mucinas/análise , Mucinas/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas
13.
Clin Exp Rheumatol ; 20(6): 829-32, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12508775

RESUMO

OBJECTIVES: To determine if a tumour necrosis factor (TNF +489) polymorphism is associated with susceptibility to rheumatoid arthritis (RA). METHODS: Two European populations were studied: 217 controls and 238 patients from the north of England and 145 controls and 179 patients from Spain. HLA-DRB1 and TNF +489 markers were typed using polymerase chain reaction based methods. RESULTS: Strong associations were demonstrated with shared epitope (SE) encoding HLA-DRB1 alleles in the English (OR = 2.9 [2.2-3.9]) and Spanish (OR = 2.3 [1.6-3.3]) populations, however no association was found with TNF +489 alleles. Furthermore carriage of TNF +489A was not associated with the presence of radiological erosions, rheumatoid nodules or rheumatoid factor. CONCLUSION: The role of the TNF locus in the genetic background of RA is unclear, however, our data does not support the previous reported association of the TNF +489A allele with RA susceptibility or severity.


Assuntos
Artrite Reumatoide/genética , Predisposição Genética para Doença , Fator de Necrose Tumoral alfa/genética , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Portador Sadio/epidemiologia , Estudos de Casos e Controles , DNA/análise , Inglaterra/epidemiologia , Epitopos , Frequência do Gene , Marcadores Genéticos , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Humanos , Immunoblotting , Repetições de Microssatélites , Sondas de Oligonucleotídeos/química , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Espanha/epidemiologia
14.
Osteoporos Int ; 11(4): 331-7, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10928223

RESUMO

The aim of the study was to assess risedronate's effect on bone mineral density in postmenopausal women with rheumatoid arthritis receiving glucocorticoids. We carried out a two center, 2 year, double-masked, placebo-controlled trial with a third year of nontreatment follow-up. We studied 120 women requiring long-term glucocorticoid therapy at > 2.5 mg/day prednisolone randomized to treatment with daily placebo; daily 2.5 mg risedronate; or cyclical 15 mg risedronate (2 out of 12 weeks). At 97 weeks, bone mineral density was maintained at the lumbar spine (+1.4%) and trochanter (+0.4%) in the daily 2.5 mg risedronate group, while significant bone loss occurred in the placebo group (-1.6%, p = 0.03; and 4.0%, p < 0.005, respectively). At the femoral neck, there was a nonsignificant bone loss in the daily 2.5 mg risedronate group (-1.0%) while in the placebo group bone mass decreased significantly (-3.6%, p < 0.001). The difference between placebo and daily 2.5 mg risedronate groups was significant at the lumbar spine (p = 0.009) and trochanter (p = 0.02) but did not reach statistical significance at the femoral neck. Although not significantly different from placebo at the lumbar spine, the overall effect of the cyclical regimen was similar to that of the daily 2.5 mg risedronate regimen. Treatment withdrawal led to bone loss in the risedronate groups that was significant at the lumbar spine. A similar number of patients experienced adverse events (including upper gastrointestinal events) across treatment groups and risedronate was generally well tolerated. Thus risedronate preserves bone mass in postmenopausal women with rheumatoid arthritis receiving glucocorticoids while patients receiving a placebo have significant bone loss.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ácido Etidrônico/análogos & derivados , Glucocorticoides/efeitos adversos , Osteoporose/prevenção & controle , Prednisolona/efeitos adversos , Administração Oral , Idoso , Densidade Óssea/efeitos dos fármacos , Método Duplo-Cego , Ácido Etidrônico/uso terapêutico , Feminino , Humanos , Osteoporose/induzido quimicamente , Ácido Risedrônico
15.
Ann Rheum Dis ; 54(10): 801-6, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7492217

RESUMO

OBJECTIVES: To determine the prevalence of vertebral fracture in postmenopausal women with steroid treated rheumatoid arthritis (RA), and whether the risk of vertebral fracture could be predicted from measurements of bone mineral density (BMD). METHODS: Vertebral deformities were defined from spine radiographs in 76 postmenopausal women with steroid treated RA (aged 50-79 years) and 347 age matched women from a population based group, using a morphometric technique. Lumbar spine (LS) BMD was measured by dual energy x ray absorptiometry. RESULTS: The odds ratio for vertebral fracture in the women with RA was 6.2 (95% confidence interval 3.2 to 12.3). The decrease in LS-BMD was less than expected for the observed prevalence of vertebral fracture and, among the women with RA, LS-BMD was not lower in those with vertebral fractures. CONCLUSIONS: We conclude that patients with steroid treated RA may have abnormal bone quality, and that LS-BMD cannot be used to predict the risk of vertebral fracture in these patients.


Assuntos
Anti-Inflamatórios/efeitos adversos , Artrite Reumatoide/complicações , Densidade Óssea , Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/etiologia , Idoso , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/etiologia , Fatores de Risco , Esteroides
17.
Arthritis Rheum ; 37(7): 983-91, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8024625

RESUMO

OBJECTIVE: To determine the reproducibility, accuracy, and linearity of hand bone mineral content (BMC) measurements, and to evaluate the influence of hand posture; to determine the relationship of hand bone mineral density (BMD) to generalized osteopenia in rheumatoid arthritis (RA); and to determine the relationship between hand BMD and disease severity in early RA. METHODS: Hand BMD was measured by dual-energy x-ray absorptiometry (DXA). We studied 70 postmenopausal women with steroid-treated RA (established RA), ages 49-79, and 20 age-matched healthy controls to determine the relationship to generalized osteoporosis; we also studied 20 patients aged 23-74 years with early RA to determine the relationship between disease severity and hand BMD. RESULTS: Reproducibility of hand BMD was to within 1%. In established RA, there was a greater decrease in juxtaarticular BMD (23% at the hand) than in generalized BMD (16% at the femoral neck, 11% at the lumbar spine, and 11% total body) compared with that in age-matched controls. Hand BMD correlated with skeletal size and BMD at other skeletal sites. In established RA, there was no effect of disease duration, disability, or steroid therapy. In early RA, hand BMD correlated with age and disease activity. CONCLUSION: Measurement of hand BMD by DXA is accurate and precise. Hand BMD reflects BMD at other skeletal sites in patients with RA, and is a marker of disease severity in patients with early disease. It may be a sensitive marker of disease progression and response to therapeutic intervention.


Assuntos
Artrite Reumatoide/fisiopatologia , Densidade Óssea , Mãos , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Tempo
18.
Br J Rheumatol ; 30(6): 455-8, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1747703

RESUMO

Self-induced disease can be difficult to diagnose and costly of time and money to investigate. The key is to think of the possibility. Five patients in whom the evidence for factitious rheumatological illness was strong are discussed and their histories, physical signs and family backgrounds are explored in relationship to factitious disease presenting in other fields. Young immature individuals seem most at risk and the discrepancy between physical signs and understandable pathological mechanisms may suggest the diagnosis. The outlook seems frequently poor.


Assuntos
Artrite Reumatoide/diagnóstico , Transtornos Autoinduzidos/diagnóstico , Adolescente , Adulto , Artrite Reumatoide/psicologia , Transtornos Autoinduzidos/psicologia , Feminino , Humanos , Masculino , Comportamento Autodestrutivo , Papel do Doente
19.
Br J Rheumatol ; 27(6): 465-8, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2904830

RESUMO

Leucopenia is one of the most worrying of the many toxic effects of second-line drug therapy for rheumatoid arthritis, and much time and energy is expended in screening for it. Sulphasalazine (SASP) is generally claimed to be safer than some alternative second-line drugs but the reported incidence of leucopenia has varied widely. We have examined, retrospectively, all records of blood counts before, during and after treatment in 326 SASP treated patients and in 213 on gold. Leucopenia on at least one occasion occurred in up to 10% of patients on both drugs but usually recovered spontaneously in spite of continued therapy. 'Serious' leucopenia leading directly to drug withdrawal was a rare event occurring in only one SASP patient and in two patients receiving gold treatment. Most episodes of leucopenia do not require drug withdrawal and may not be drug related.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Ouro/efeitos adversos , Leucopenia/induzido quimicamente , Sulfassalazina/efeitos adversos , Adulto , Idoso , Artrite Reumatoide/sangue , Sedimentação Sanguínea , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Contagem de Plaquetas , Estudos Retrospectivos
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