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1.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33753502

RESUMO

Genetic variation within the factor H-related (FHR) genes is associated with the complement-mediated kidney disease, C3 glomerulopathy (C3G). There is no definitive treatment for C3G, and a significant proportion of patients develop end-stage renal disease. The prototypical example is CFHR5 nephropathy, through which an internal duplication within a single CFHR5 gene generates a mutant FHR5 protein (FHR5mut) that leads to accumulation of complement C3 within glomeruli. To elucidate how abnormal FHR proteins cause C3G, we modeled CFHR5 nephropathy in mice. Animals lacking the murine factor H (FH) and FHR proteins, but coexpressing human FH and FHR5mut (hFH-FHR5mut), developed glomerular C3 deposition, whereas mice coexpressing human FH with the normal FHR5 protein (hFH-FHR5) did not. Like in patients, the FHR5mut had a dominant gain-of-function effect, and when administered in hFH-FHR5 mice, it triggered C3 deposition. Importantly, adeno-associated virus vector-delivered homodimeric mini-FH, a molecule with superior surface C3 binding compared to FH, reduced glomerular C3 deposition in the presence of the FHR5mut. Our data demonstrate that FHR5mut causes C3G by disrupting the homeostatic regulation of complement within the kidney and is directly pathogenic in C3G. These results support the use of FH-derived molecules with enhanced C3 binding for treating C3G associated with abnormal FHR proteins. They also suggest that targeting FHR5 represents a way to treat complement-mediated kidney injury.


Assuntos
Complemento C3/metabolismo , Proteínas do Sistema Complemento/genética , Mutação com Ganho de Função , Glomerulonefrite/genética , Glomerulonefrite/metabolismo , Glomérulos Renais/patologia , Animais , Modelos Animais de Doenças , Feminino , Humanos , Glomérulos Renais/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Fatores Sexuais
2.
Nephrol Dial Transplant ; 38(11): 2576-2588, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37120733

RESUMO

BACKGROUND: Light chain proximal tubulopathy (LCPT) is a rare form of paraprotein-related disease, occurring in two main histopathological forms: crystalline and non-crystalline. The clinicopathological features, treatment strategies and outcomes, especially of the non-crystalline form, are not well described. METHODS: We conducted a single-centre retrospective case series of 12 LCPT patients, 5 crystalline and 7 non-crystalline, between 2005 and 2021. RESULTS: The median age was 69.5 years (range 47-80). Ten patients presented with CKD and significant proteinuria (median estimated glomerular filtration rate of 43.5 ml/min/1.73 m2; urine protein:creatinine ratio 328 mg/mmol). Only six patients had known haematological disease at the time of renal biopsy. Multiple myeloma (MM) was diagnosed in seven patients cases and monoclonal gammopathy of renal significance (MGRS) in five patients. A clone was detected in all cases combining serum/urine electrophoresis and free light chain (LC) assays. Crystalline and non-crystalline variants had similar clinical presentations. For the non-crystalline variant, a diagnosis was reached based on a combination of CKD without another cause, haematological workup, LC restriction on immunofluorescence and abnormalities on electron microscopy (EM). Nine of 12 patients received clone-directed treatment. Patients who achieved haematological response (including all non-crystalline LCPT) had improved renal outcomes over a median follow-up of 79 months. CONCLUSIONS: The non-crystalline variant may go unrecognised because of its subtle histopathological features and requires EM to distinguish it from 'excessive LC resorption without tubular injury'. Clone-directed treatment with good haematological response improves renal outcomes in both variants but limited data exist in MGRS. Multicentre prospective studies are needed to better define the clinicopathological characteristics associated with poor outcomes and optimize treatment strategies in patients with MGRS.


Assuntos
Nefropatias , Mieloma Múltiplo , Paraproteinemias , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Nefropatias/patologia , Rim/patologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/complicações , Cadeias Leves de Imunoglobulina/análise , Insuficiência Renal Crônica/complicações , Paraproteinemias/diagnóstico , Paraproteinemias/complicações , Paraproteinemias/patologia
3.
J Pathol ; 252(4): 346-357, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32918747

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in an urgent need to understand the pathophysiology of SARS-CoV-2 infection, to assist in the identification of treatment strategies. Viral tissue tropism is an active area of investigation, one approach to which is identification of virus within tissues by electron microscopy of post-mortem and surgical specimens. Most diagnostic histopathologists have limited understanding of the ultrastructural features of normal cell trafficking pathways, which can resemble intra- and extracellular coronavirus; in addition, viral replication pathways make use of these trafficking pathways. Herein, we review these pathways and their ultrastructural appearances, with emphasis on structures which may be confused with coronavirus. In particular, we draw attention to the fact that, when using routine fixation and processing, the typical 'crown' that characterises a coronavirus is not readily identified on intracellular virions, which are located in membrane-bound vacuoles. In addition, the viral nucleocapsid is seen as black dots within the virion and is more discriminatory in differentiating virions from other cellular structures. The identification of the viral replication organelle, a collection of membranous structures (convoluted membranes) seen at a relatively low scanning power, may help to draw attention to infected cells, which can be sparse. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
COVID-19/virologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/ultraestrutura , Animais , Humanos , Vírion/ultraestrutura , Replicação Viral/genética
4.
Clin Exp Nephrol ; 23(5): 700-709, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30637591

RESUMO

BACKGROUND: Post-transplant focal segmental glomerulosclerosis (FSGS) is associated with renal allograft loss. Currently, optimal treatment remains controversial. METHODS: The aim of our study was to examine the efficacy and safety of therapeutic plasma exchange (TPE), and rituximab (RTX), in the management of post-transplant FSGS. The treatment protocol consisted of RTX and monthly cycles of 5 plasma exchanges for 6 months. We treated 10 transplant recipients with biopsy-proven post-transplant FSGS. Lastly, we compared the studied group to a historic control group of nine patients with post-transplant FSGS. RESULTS: 9 out of 10 patients achieved remission after the conclusion of treatment (4 complete and 5 partial), while 1 patient did not respond to treatment. During the follow-up period, there was one graft loss and one patient died while in remission from unrelated complications. There was a significant reduction in mean uPCR between diagnosis (517.4 ± 524.2 mg/mmol) and last follow-up (87 ± 121.6 mg/mmol) in the patients with sustained remission (p = 0.026). There was no significant decline in eGFR in the eight relapse-free responders at the end of follow-up. (54.4 ± 16.7 from 49.8 ± 20.4 ml/min) (p = 0.6) An increased response rate to the combined TPE and RTX treatment was demonstrated, when compared to a historic control group of nine patients with post-transplant FSGS, as only five out of nine patients achieved remission (two complete and three partial) in that group. CONCLUSIONS: In this study, treatment with TPE and RTX appears to be safe, well tolerated and effective in the management of patients with post-transplant FSGS.


Assuntos
Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Troca Plasmática , Complicações Pós-Operatórias/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Feminino , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Rim/patologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Adulto Jovem
5.
J Am Soc Nephrol ; 27(7): 2188-95, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26614383

RESUMO

The presence of tubuloreticular inclusions (TRIs) in native glomerular endothelial cells associates with viral infections and lupus nephritis. However, the associations of TRIs in renal transplant biopsy specimens are not known. We analyzed data from 316 patients who had a transplant biopsy with electron microscopy examination; 41 of 316 (13.0%) patients had TRIs. Patients with TRIs had significantly lower allograft survival rates (50.9%) than patients without TRIs (74.3%; P=0.03). Transplant glomerulopathy-free survival was also inferior in the TRI-positive group (57.5%) compared with the TRI-negative group (87.3%; P=0.002). Serologically, hepatitis C associated with the presence of TRIs (P=0.04) along with donor-specific antibodies (P=0.01). Furthermore, patients who were TRI positive were more likely than patients who were TRI negative to have had a previous rejection episode (P=0.02). On multivariate analysis, TRIs associated with prior rejection, viral infections, and class 1 HLA donor-specific antibodies. These results show that the presence of TRIs in renal allograft biopsy specimens associates with poor allograft outcomes and serologic evidence of viral infections and alloimmunity. The association with alloimmunity is a novel finding that warrants additional investigation.


Assuntos
Anticorpos , Glomérulos Renais/patologia , Transplante de Rim , Rim/imunologia , Rim/patologia , Viroses/patologia , Células Endoteliais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos
8.
Curr Opin Organ Transplant ; 20(3): 333-42, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25944229

RESUMO

PURPOSE OF REVIEW: To review and discuss the use of electron microscopy in the examination of renal transplant biopsies, in particular its role in the diagnosis of glomerular disease and antibody-mediated rejection. RECENT FINDINGS: Electron microscopy can detect recurrent and de-novo glomerular disease at early stages, in particular for focal and segmental glomerulosclerosis and thrombotic microangiopathy.Ultrastructural features are an integral part of the Banff definition of chronic, active antibody-mediated rejection, which has been recently modified to include ultrastructural-only glomerular double contours. In addition, the threshold of peritubular capillary basement membrane multilayering diagnostic for chronic, active antibody-mediated rejection has been changed. As an area for further investigation, ultrastructural-only glomerular and peritubular capillary features could become tools in the early detection of antibody-mediated rejection. SUMMARY: Electron microscopy is important in the diagnosis of glomerular disease and chronic, active antibody-mediated rejection, both of which contribute to late graft loss. Early detection and treatment may help prolong graft survival. More data are needed on the early ultrastructural features of antibody-mediated injury, so that the usefulness of this technique can be compared with emerging technologies such as transcript analysis.


Assuntos
Nefropatias/patologia , Transplante de Rim , Rim/ultraestrutura , Biópsia , Humanos , Microscopia Eletrônica , Transplante Homólogo
9.
Virchows Arch ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376618

RESUMO

STK11 adnexal tumour is a recently described female genital tract tumour, usually identified in a paratubal location, often associated with Peutz-Jeghers syndrome (PJS) and with STK11 gene alterations identified in most of the cases. Morphologically, this tumour is composed of cells arranged in a variety of patterns, including cords, trabeculae, tubules and cystic and acinar structures. The cells are only moderately pleomorphic and mitotic activity is variable. As tumour cells express epithelial, sex cord stromal and mesothelial markers, STK11 adnexal tumour may be of sex cord stromal, epithelial or mesothelial origin; a Wolffian origin has also been suggested. We report the ultrastructural features of two STK11 adnexal tumours and compare their ultrastructural features with those of other sex cord stromal tumours, a granulosa cell tumour cell line, as well as the known ultrastructural features of epithelial, mesothelial and Wolffian cells. On ultrastructural examination, two STK11 adnexal tumours showed an admixture of elongated cells with regular elongated nuclei and polygonal cells with nuclei showing markedly irregular outlines and prominent nucleoli. Extracellular collagen fibres were identified. These are common ultrastructural features of sex cord stromal tumours, principally sex cord tumour with annular tubules; no ultrastructural features of epithelial, mesothelial or Wolffian cells were found. These findings in conjunction with the shared clinical and genetic association with PJS and shared molecular changes in STK11 gene suggest that STK11 adnexal tumour represents a poorly differentiated sex cord tumour.

10.
Neurogenetics ; 12(4): 295-305, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21800131

RESUMO

The role of glial cells in Parkinson's disease (PD) is unclear. We have previously reported a striking up-regulation of DnaJB6 heat shock protein in PD substantia nigra astrocytes. Whole genome transcriptome analysis also indicated increased expression of metallothionein genes in substantia nigra and cortex of sporadic PD cases. Metallothioneins are metal-binding proteins in the CNS that are released by astrocytes and associated with neuroprotection. Metallothionein expression was investigated in 18 PD cases and 15 non-PD controls using quantitative real-time polymerase chain reaction (qRT-PCR), in situ hybridisation (ISH) and immunocytochemistry (ICC). We observed a strong increase in the expression of metallothioneins MT1E, MT1F, MT1G, MT1H, MT1M, MT1X and MT2A in both PD nigra and frontal cortex. Expression of LRP2 (megalin), the neuronal metallothionein receptor was also significantly increased. qRT-PCR confirmed metallothionein up-regulation. Astrocytes were found to be the main source of metallothioneins 1 and 2 based on ISH results, and this finding was confirmed by ICC. Our findings demonstrate metallothionein expression by reactive astrocytes in PD nigra and support a neuroprotective role for these cells. The traditional view that nigral astrocytes are non-reactive in PD is clearly incorrect. However, it is possible that astrocytes are themselves affected by the disease process which may explain their comparatively modest and previously overlooked response.


Assuntos
Astrócitos/fisiologia , Metalotioneína/genética , Metalotioneína/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Regulação para Cima/genética , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Astrócitos/citologia , Análise por Conglomerados , Feminino , Humanos , Masculino , Análise em Microsséries , Dados de Sequência Molecular , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Alinhamento de Sequência
11.
Neurogenetics ; 9(1): 1-13, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18196299

RESUMO

We have previously established a first whole genome transcriptomic profile of sporadic Parkinson's disease (PD). After extensive brain tissue-based validation combined with cycles of iterative data analysis and by focusing on the most comparable cases of the cohort, we have refined our analysis and established a list of 892 highly dysregulated priority genes that are considered to form the core of the diseased Parkinsonian metabolic network. The substantia nigra pathways, now under scrutiny, contain more than 100 genes whose association with PD is known from the literature. Of those, more than 40 genes belong to the highly significantly dysregulated group identified in our dataset. Apart from the complete list of 892 priority genes, we present pathways revealing PD 'hub' as well as 'peripheral' network genes. The latter include Lewy body components or interact with known PD genes. Biological associations of PD with cancer, diabetes and inflammation are discussed and interactions of the priority genes with several drugs are provided. Our study illustrates the value of rigorous clinico-pathological correlation when analysing high-throughput data to make optimal use of the histopathological phenome, or morphonome which currently serves as the key diagnostic reference for most human diseases. The need for systematic human tissue banking, following the highest possible professional and ethical standard to enable sustainability, becomes evident.


Assuntos
Doença de Parkinson/genética , Bases de Dados Genéticas , Complicações do Diabetes/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Inflamação/complicações , Inflamação/genética , Modelos Genéticos , Modelos Neurológicos , Neoplasias/complicações , Neoplasias/genética , Rede Nervosa/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia
12.
J Neuroimmunol ; 183(1-2): 1-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17188367

RESUMO

We have analysed the microglial pathway stimulated by interferon-gamma (IFN-gamma) using an in silico approach employing a database of eukaryotic molecular interactions and a microarray dataset validated by quantitative real-time PCR (qRT-PCR). Following IFN-gamma stimulation, production of neuroprotective factors by microglia was found to be reduced while caspase 1 and serping1 which are involved in cell death cascades are up-regulated suggesting a safeguarding mechanism. Extracellular matrix interactions and intracellular protein degradation are altered in concert with these changes. The regulatory network of IFN-gamma responsive microglial genes is outlined in detail and differentially expressed genes are mapped to their respective cellular compartments. A pathway approach to the analysis of microarray data is advocated since overlaying pathway and actual expression data as shown here greatly facilitates understanding the biological meaning of a gene regulatory network. In addition, genes of similar function that are differentially regulated are less likely to be false positives than single unrelated genes.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Interferon gama/farmacologia , Microglia/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Células Cultivadas , Perfilação da Expressão Gênica , Modelos Biológicos , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos Endogâmicos Lew
13.
Transplantation ; 100(4): 889-97, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26413993

RESUMO

BACKGROUND: Severe peritubular capillary basement membrane multilayering (PTCBML) is part of the Banff definition of chronic antibody-mediated rejection. We retrospectively investigated whether assessment of the mean number of layers of basement membrane (BM) around peritubular capillaries (PTC) can be used in a cohort of patients with de novo donor-specific antibodies (dnDSA) as an early marker to predict long-term antibody-mediated injury. METHODS: This is a retrospective cohort study with 151 electron microscopy samples from 54 patients with dnDSA, assessed at around 1 year after transplantation, for a mean number of BM layers around PTC and in serial biopsies. Graft survival and time to transplant glomerulopathy (TG) development were estimated in survival analyses. RESULTS: We found that a mean PTCBML count greater than 2.5 layers assessed in a sample of 25 PTCs around 1 year after transplantation is indicative of the development of TG in patients with dnDSA (P = 0.001). In addition, in patients with serial biopsies available for electron microscopy analysis, we could distinguish 2 groups: patients with a mean PTCBML count of 2.5 or less on all biopsies, and patients who developed greater than 2.5 layers at any time after transplantation. The latter group reflected dnDSA patients at risk for TG development (P < 0.001). In patients with dnDSA, PTCBML score added significantly to the sensitivity and specificity of prediction of TG compared with microcirculation injury score alone. CONCLUSIONS: Our results highlight the potential value of assessing the mean number of BM in PTC for early prediction of progression to chronic antibody-mediated injury.


Assuntos
Capilares/imunologia , Membrana Basal Glomerular/imunologia , Rejeição de Enxerto/imunologia , Isoanticorpos/análise , Transplante de Rim/efeitos adversos , Rim/irrigação sanguínea , Doadores de Tecidos , Adulto , Aloenxertos , Biomarcadores/análise , Biópsia , Capilares/ultraestrutura , Doença Crônica , Progressão da Doença , Feminino , Imunofluorescência , Membrana Basal Glomerular/ultraestrutura , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
14.
J Neuroinflammation ; 2: 14, 2005 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-15935098

RESUMO

BACKGROUND: The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease. METHODS: We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course. RESULTS: While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD. CONCLUSION: While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution.

16.
J Clin Endocrinol Metab ; 100(3): E531-41, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25494863

RESUMO

CONTEXT: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. OBJECTIVE: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. DESIGN: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. SETTING: The study was conducted at university hospitals. PATIENTS: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. OUTCOME: Outcomes included genetic screening and clinical characteristics. RESULTS: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. CONCLUSIONS: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.


Assuntos
Adenoma/genética , Neoplasias das Glândulas Suprarrenais/genética , Heterogeneidade Genética , Predisposição Genética para Doença , Paraganglioma/genética , Feocromocitoma/genética , Neoplasias Hipofisárias/genética , Adenoma/epidemiologia , Neoplasias das Glândulas Suprarrenais/epidemiologia , Adulto , Estudos de Coortes , Feminino , Estudos de Associação Genética , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Paraganglioma/epidemiologia , Feocromocitoma/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Adulto Jovem
17.
Brain Pathol ; 12(3): 385-90, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12146806

RESUMO

Apoptosis has become a most popular concept of cell death. However, the term is now so widely used and employed in such general terms in relation to neurological diseases that its application is very problematic. In addition, with the exception of developmental conditions, there is essentially no evidence of apoptosis fulfilling the criteria of its classical definition in any of the important human neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, Amyotrophic Lateral Sclerosis, and Creutzfeldt-Jakob disease. Importantly, a number of new cell death forms have been described in the literature and there is good reason to pay attention to these emerging concepts as they may provide a rationale for the development of disease-specific therapies.


Assuntos
Apoptose , Doenças Neurodegenerativas/patologia , Doença de Alzheimer/patologia , Esclerose Lateral Amiotrófica/patologia , Isquemia Encefálica/patologia , Morte Celular , Síndrome de Creutzfeldt-Jakob/patologia , Humanos , Doença de Huntington/patologia , Marcação In Situ das Extremidades Cortadas/métodos , Doença de Parkinson/patologia , Terminologia como Assunto
18.
Cochlear Implants Int ; 15(1): 2-12, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23684485

RESUMO

OBJECTIVES: Youth and young adults with cochlear implants are now transitioning from pediatric to adult services in increasing numbers. Research in other areas of health care has indicated that there is a gap in the transition from pediatric services for the young adult, and that it is important to obtain their perspectives to reduce disruption and improve care. Previous research has documented issues from the perspective of cochlear implant professionals. The objectives of this study were to examine current practices from the perspective of young adults and their families and to make recommendations for future practice. METHODS: Interviews were conducted with 11 individuals, including cochlear implant recipients and their parents. All patients were within 4 years of transition between pediatric and adult hospital services: four youths were pediatric patients, and two had been discharged to adult services. Qualitative research methodology was used to identify key themes. RESULTS: All participants indicated that they had not anticipated a change to an adult hospital as part of their plan of care. Key themes from interviews were differences between pediatric and adult hospitals, challenges in establishing new relationships with professionals, specific concerns about new health care settings and procedures, and the need for youth to develop independent health-related skills in the context of parental involvement. DISCUSSION: Themes identified through interviews with young people with cochlear implants and their parents were similar to research in other areas of health care, as well as to themes identified in focus groups with professionals providing cochlear implant services. There were some differences which highlight both needs in the provision of health care and opportunities for providers and patients to collaborate to provide improved service delivery.


Assuntos
Implantes Cocleares , Necessidades e Demandas de Serviços de Saúde/organização & administração , Perda Auditiva/psicologia , Perda Auditiva/terapia , Pais/psicologia , Transição para Assistência do Adulto/organização & administração , Adolescente , Fatores Etários , Audiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hospitais Pediátricos , Humanos , Masculino , Relações Médico-Paciente , Pesquisa Qualitativa , Adulto Jovem
20.
Cochlear Implants Int ; 13(4): 197-205, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22449437

RESUMO

OBJECTIVES: Over the last 20 years, the availability of cochlear implantation has resulted in a pediatric population with different health needs than adults who receive cochlear implants (CIs). These pediatric patients are now transitioning to adult hospital settings in significant numbers. This issue of transition is not unique to cochlear implant services: research in other chronic health conditions has documented a variety of challenges for youth and health care providers. The objectives of this study were to identify factors important in the transition from pediatric to adult CI services from the perspective of service providers and to make recommendations to improve transition practices in the future. METHODS: Focus groups were conducted with professionals providing specialized CI services in pediatric and adult hospitals, and specialized educators in the school setting. Qualitative research methodology was used to identify key themes. Data extracted from patient files allowed comparison of pediatric and adult CI recipients. RESULTS: Youth who had received CIs in the pediatric setting differed from other adult patients in the incidence of prelingual hearing losses, and age at CI surgery. Key focus group themes were related to service delivery models, communication between settings, and skills needed by the patients to effectively meet their own health needs. DISCUSSION: Factors identified by CI professionals were very similar to those identified in research for other health conditions. From the focus groups, as well as other literature, a number of recommendations are proposed to facilitate a positive transition of young people to adult health care.


Assuntos
Implante Coclear/reabilitação , Continuidade da Assistência ao Paciente/normas , Correção de Deficiência Auditiva/normas , Atenção à Saúde/normas , Avaliação das Necessidades , Educação de Pacientes como Assunto/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Comunicação , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Educação de Pacientes como Assunto/normas , Apoio Social , Inquéritos e Questionários , Adulto Jovem
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