RESUMO
BACKGROUND: There were at least 31,171 metal-on-metal (MoM) hip implants in the UK between 2003 and 2011. Some of these were subject to failure and widescale recalls and revisions followed. METHOD: This is a presentation of ten cases (mean age 60 years) where we evaluated neuropsychiatric morbidity following metal-on-metal hip implant failure and revision. Implants were ASR total hip replacement (acetabular implant, taper sleeve adaptor and unipolar femoral implants) performed between 2005 and 2009. This case series describes, for the first time, neuropsychiatric complications after revision where there has been cobalt and chromium toxicity. RESULTS: Pre-revision surgery, nine patients had toxic levels of chromium and cobalt (mean level chromium 338 nmol/l, mean cobalt 669.4 nmol/l). Depression assessment showed 9 of 9 respondents fulfilled the BDI criteria for depression and 3 of these were being treated. 7 of 9 patients showing short term memory deficit with mean mini mental state examination score of 24.2. The normal population mean MMSE for this group would be expected to be 28 with <25 indicating possible dementia. CONCLUSIONS: We found neurocognitive and depressive deficits after cobalt and chromium metallosis following MoM implant failure. Larger studies of neurocognitive effects are indicated in this group. There may be implications for public health.
Assuntos
Artroplastia de Quadril/efeitos adversos , Cromo/toxicidade , Cobalto/toxicidade , Depressão/induzido quimicamente , Transtornos da Memória/induzido quimicamente , Próteses Articulares Metal-Metal/efeitos adversos , Falha de Prótese/efeitos adversos , Adulto , Idoso , Cromo/sangue , Cobalto/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Bipolar disorder is complex and can be difficult to diagnose. It is often misdiagnosed as recurrent major depressive disorder. AIMS: We had three main aims. To estimate the proportion of primary care patients with a working diagnosis of unipolar depression who satisfy DSM-IV criteria for bipolar disorder. To test two screening instruments for bipolar disorder (the Hypomania Checklist (HCL-32) and Bipolar Spectrum Diagnostic Scale (BSDS)) within a primary care sample. To assess whether individuals with major depressive disorder with subthreshold manic symptoms differ from those individuals with major depressive disorder but with no or little history of manic symptoms in terms of clinical course, psychosocial functioning and quality of life. METHOD: Two-phase screening study in primary care. RESULTS: Three estimates of the prevalence of undiagnosed bipolar disorder were obtained: 21.6%, 9.6% and 3.3%. The HCL-32 and BSDS questionnaires had quite low positive predictive values (50.0 and 30.1% respectively). Participants with major depressive disorder and with a history of subthreshold manic symptoms differed from those participants with no or little history of manic symptoms on several clinical features and on measures of both psychosocial functioning and quality of life. CONCLUSIONS: Between 3.3 and 21.6% of primary care patients with unipolar depression may have an undiagnosed bipolar disorder. The HCL-32 and BSDS screening questionnaires may be more useful for detecting broader definitions of bipolar disorder than DSM-IV-defined bipolar disorder. Subdiagnostic features of bipolar disorder are relatively common in primary care patients with unipolar depression and are associated with a more morbid course of illness. Future classifications of recurrent depression should include dimensional measures of bipolar symptoms.
Assuntos
Transtorno Bipolar/epidemiologia , Transtorno Depressivo/epidemiologia , Programas de Rastreamento , Atenção Primária à Saúde/estatística & dados numéricos , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Reações Falso-Negativas , Medicina de Família e Comunidade , Feminino , Humanos , Masculino , Prevalência , Escalas de Graduação Psiquiátrica/normas , Qualidade de Vida , Curva ROC , Reino Unido/epidemiologiaRESUMO
BACKGROUND: The under-recognition of hypomanic symptoms by both clinicians and patients is a major clinical problem which contributes to misdiagnosis and diagnostic delay in patients with bipolar disorder. The recent development of validated screening instruments for hypomania, such as the Hypomania Checklist (HCL-32), may help to improve the detection of bipolar disorder. In this study, we assess whether it is possible to reduce the number of items on the HCL-32 without any loss in the screening tool's ability to reliably differentiate between bipolar disorder (BD) and major depressive disorder (MDD). METHODS: Using our large samples of patients with DSM-IV defined bipolar I disorder (BD-I) (n=230) and recurrent MDD (n=322), we performed item correlations in order to identify potentially redundant items in the HCL-32. We then tested the performance of a shortened 16-item HCL questionnaire within a separate sample of patients with BD (including BD-I, BD-II and BD-NOS) (n=59) and MDD (n=76). RESULTS: The structure of the 16-item HCL demonstrated two main factors similar to those identified for the HCL-32 (an 'active-elated' factor and a 'risk-taking/irritable' factor). A score of 8 or more on a shortened 16-item version of the HCL had excellent ability to distinguish between BD and MDD. The sensitivity (83%) and specificity (71%) of the 16-item version were very similar to those for the full 32-item HCL. LIMITATIONS: The HCL-16 was derived after subjects had completed the full HCL-32. It will be important to test the validity of a 'stand-alone' 16-item HCL questionnaire. CONCLUSIONS: A shortened 16-item HCL (the HCL-16) is potentially a useful screening tool for hypomania within busy clinical settings.
Assuntos
Transtorno Bipolar/diagnóstico , Lista de Checagem/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Determinação da Personalidade/estatística & dados numéricos , Adulto , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/estatística & dados numéricos , Recidiva , Reprodutibilidade dos Testes , Estatística como AssuntoRESUMO
Cbl family proteins are evolutionarily conserved ubiquitin ligases that negatively regulate signaling from tyrosine kinase-coupled receptors. The mammalian cbl family consists of c-Cbl, Cbl-b, and the recently cloned Cbl-3 (also known as Cbl-c). In this study, we describe the detailed expression pattern of murine Cbl-3 and report the generation and characterization of Cbl-3-deficient mice. Cbl-3 exhibits an expression pattern distinct from those of c-Cbl and Cbl-b, with high levels of Cbl-3 expression in epithelial cells of the gastrointestinal tract and epidermis, as well as the respiratory, urinary, and reproductive systems. Cbl-3 expression was not detected in nonepithelial cells, but within epithelial tissues, the levels of Cbl-3 expression varied from undetectable in the alveoli of the lungs to very strong in the cecum and colon. Despite this restricted expression pattern, Cbl-3-deficient mice were viable, healthy, and fertile and displayed no histological abnormalities up to 18 months of age. Proliferation of epithelial cells in the epidermises and gastrointestinal tracts was unaffected by the loss of Cbl-3. Moreover, Cbl-3 was not required for attenuation of epidermal growth factor-stimulated Erk activation in primary keratinocytes. Thus, Cbl-3 is dispensable for normal epithelial development and function.
Assuntos
Células Epiteliais/metabolismo , Epitélio/crescimento & desenvolvimento , Proteínas Oncogênicas de Retroviridae/metabolismo , Animais , Células Cultivadas , Ativação Enzimática , Células Epiteliais/citologia , Epitélio/anatomia & histologia , Regulação da Expressão Gênica , Marcação de Genes , Humanos , Hibridização In Situ , Queratinócitos/citologia , Queratinócitos/metabolismo , Camundongos , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-cbl , Proteínas Oncogênicas de Retroviridae/genética , Distribuição TecidualRESUMO
Adaptor proteins are essential components of T cell receptor (TCR) signaling cascades regulating gene transcription and cytoskeletal reorganization. The molecular adaptor adhesion- and degranulation-promoting adaptor protein (ADAP), also known as Fyn binding protein (FYB) or Slp-76-associated protein of 130 kilodaltons (SLAP-130), interacts with a number of signaling intermediates including Slp-76, the Src family tyrosine kinase Fyn, vasodilator-stimulated phosphoprotein (VASP), and the actin-nucleating protein WASP. Recently ADAP was shown genetically to positively regulate T cell activation, TCR-induced integrin clustering, and T cell adhesion. The mechanism by which ADAP couples TCR stimulation to integrin clustering remains unclear; however, studies of ADAP, the exchange factor Vav1, and WASP suggest that TCR and integrin clustering may be controlled by distinct signaling pathways.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Integrinas/fisiologia , Receptores de Antígenos de Linfócitos T/fisiologia , Transdução de Sinais/imunologia , Animais , Proteínas de Transporte/metabolismo , Proteínas de Transporte/fisiologia , Adesão Celular/imunologia , Degranulação Celular/imunologia , Humanos , Integrinas/metabolismo , Proteínas Tirosina Quinases/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Proto-Oncogênicas c-fyn , Receptores de Antígenos de Linfócitos T/metabolismoRESUMO
Integrin-mediated adhesion is essential for the formation of stable contacts between T cells and antigen-presenting cells (APCs). We show that Vav1 controls integrin-mediated adhesion of thymocytes and T cells to ECM proteins and ICAM1 following TCR stimulation. In a peptide-specific system, Vav1 is required for T cell adhesion to peptide-loaded APCs. Intriguingly, TCR-induced cell adhesion and aggregation of integrins occurs independent of WASP. Whereas LFA-1 and actin caps colocalize in wasp(-/-) T cells in response to TCR stimulation, loss of WASP uncouples TCR caps from actin patches. Our data reveal a novel role for Vav1 and WASP in the regulation of TCR-induced integrin clustering and cell adhesion and show that integrin and TCR clustering are controlled by distinct pathways.