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1.
Eur J Neurol ; 27(12): 2415-2421, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32692883

RESUMO

BACKGROUND AND PURPOSE: Dementia disorders predispose for lethal complications and decrease life expectancy. A more profound knowledge regarding end-stage conditions in dementia could therefore ameliorate treatment and care of these patients. METHODS: Autopsy reports on 207 deceased individuals with clinically diagnosed neurocognitive disorder/dementia and on 200 neurocognitively healthy individuals of the same age range were studied. Autopsy results, especially cause of death, were compared between the dementia and the control groups. RESULTS: The two most frequent causes of death in the dementia population were pneumonia (34.3%) and acute myocardial infarction (30.4%). This result differed from that of the control group, in which acute myocardial infarction (42.5%) accounted for most events of deaths, followed by circulatory failure (12.5%). The leading cause of death varied amongst dementia subtypes. Further, in Alzheimer's disease pneumonia was more frequent in severe/advanced cases whilst acute myocardial infarction was more common in milder cases. CONCLUSIONS: Cause of death differed between the demented and the general population of the same age and between subtypes of dementia. Alzheimer's disease severity was reflected in different final conditions. The findings have relevance for the final stage care and treatment in dementia disorders.


Assuntos
Doença de Alzheimer , Pneumonia , Autopsia , Causas de Morte , Humanos , Índice de Gravidade de Doença
2.
Neuropathol Appl Neurobiol ; 45(6): 557-569, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30957900

RESUMO

AIMS: We observed a microvascular structure in the cerebral cortex that has not, to our knowledge, been previously described. We have termed the structure a 'raspberry', referring to its appearance under a bright-field microscope. We hypothesized that raspberries form through angiogenesis due to some form of brain ischaemia or hypoperfusion. The aims of this study were to quantify raspberry frequency within the cerebral cortex according to diagnosis (vascular dementia, Alzheimer's disease, frontotemporal lobar degeneration and nondemented controls) and brain regions (frontal, temporal, parietal and occipital cortices, regardless of diagnosis). MATERIALS AND METHODS: In each of 10 age-matched subjects per group, a 20-mm section of the cerebral cortex was examined in haematoxylin-and-eosin-stained sections of the frontal, temporal and parietal, and/or occipital lobes. Tests were performed to validate the haematoxylin-and-eosin-based identification of relative differences between the groups, and to investigate inter-rater variability. RESULTS: Raspberry frequency was highest in subjects with vascular dementia, followed by those with frontotemporal lobar degeneration, Alzheimer's disease and last, nondemented controls. The frequency of raspberries in subjects with vascular dementia differed from that of all other groups at a statistically significant level. In the cerebral lobes, there was a statistically significant difference between the frontal and occipital cortices. CONCLUSIONS: We believe the results support the hypothesis that raspberries are a sign of angiogenesis in the adult brain. It is pertinent to discuss possible proangiogenic stimuli, including brain ischaemia (such as mild hypoperfusion due to a combination of small vessel disease and transient hypotension), neuroinflammation and protein pathology.


Assuntos
Doença de Alzheimer/patologia , Isquemia Encefálica/patologia , Córtex Cerebral/patologia , Demência Vascular/patologia , Degeneração Lobar Frontotemporal/patologia , Neovascularização Patológica/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino
3.
Neuropathol Appl Neurobiol ; 45(4): 361-379, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30019499

RESUMO

AIMS: Metabolic dysfunction is involved in modulating the disease process in Huntington disease (HD) but the underlying mechanisms are not known. The aim of this study was to investigate if the metabolic regulators sirtuins are affected in HD. METHODS: Quantitative real-time polymerase chain reactions were used to assess levels of SIRT1-3 and downstream targets in post mortem brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin (HTT) using recombinant adeno-associated viral vectors in mice. RESULTS: We show that mRNA levels of the metabolic regulator SIRT1 are increased in the striatum and the cerebral cortex but not in the less affected cerebellum in post mortem HD brains. Levels of SIRT2 are only increased in the striatum and SIRT3 is not affected in HD. Interestingly, mRNA levels of SIRT1 are selectively increased in the lateral hypothalamic area (LHA) and ventromedial hypothalamus (VMH) in HD. Further analyses of the LHA and VMH confirmed pathological changes in these regions including effects on SIRT1 downstream targets and reduced mRNA levels of orexin (hypocretin), prodynorphin and melanin-concentrating hormone (MCH) in the LHA and of brain-derived neurotrophic factor (BDNF) in the VMH. Analyses after selective hypothalamic expression of mutant HTT suggest that effects on BDNF, orexin, dynorphin and MCH are early and direct, whereas changes in SIRT1 require more widespread expression of mutant HTT. CONCLUSIONS: We show that SIRT1 expression is increased in HD-affected brain regions and that metabolic pathways are altered in the HD hypothalamus.


Assuntos
Encéfalo/metabolismo , Doença de Huntington/metabolismo , Hipotálamo/metabolismo , Sirtuína 1/metabolismo , Idoso , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia
4.
Neuropathol Appl Neurobiol ; 39(5): 572-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23346995

RESUMO

BACKGROUND: von Economo neurones (VEN) are bipolar neurones located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI), areas affected early in behavioural variant frontotemporal dementia (bvFTD), in which VEN may constitute a selectively vulnerable cellular population. AIM: A previous study has shown a selective loss of VEN in FTD above other neurones in the ACC of FTD. The aim of this study was to confirm this finding in a larger cohort, using a different methodology, and to examine VEN loss in relation to neuropathological severity and molecular pathology. METHODS: VEN and neighbouring neurones (NN) were quantified in layers Va and Vb of the right dorsal ACC in 21 cases of bvFTD, 10 cases of Alzheimer's disease (AD) and 10 non-demented controls (NDC). RESULTS: A marked VEN reduction was seen in all FTD cases. In the neuropathologically early cases of FTD (n = 13), VEN/10,000 NN was significantly reduced by 53% compared with NDC (P < 0.001) and 41% compared with AD (P = 0.019), whereas AD patients showed a non-significant 30% reduction of VEN/10,000 NN compared with NDC. VEN reduction was present in all protein pathology subgroups. DISCUSSION: In conclusion, this study confirms selective sensitivity of VEN in FTD and suggests that VEN loss is an early event in the neurodegenerative process.


Assuntos
Córtex Cerebral/patologia , Demência Frontotemporal/patologia , Giro do Cíngulo/patologia , Neurônios/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/classificação
5.
Magn Reson Imaging ; 104: 88-96, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37734574

RESUMO

BACKGROUND: Early detection of treatment response is important for the management of patients with malignant brain tumors such as glioblastoma to assure good quality of life in relation to therapeutic efficacy. AIM: To investigate whether parametric response mapping (PRM) with diffusion MRI may provide prognostic information at an early stage of standard therapy for glioblastoma. MATERIALS AND METHODS: This prospective study included 31 patients newly diagnosed with glioblastoma WHO grade IV, planned for primary standard postoperative treatment with radiotherapy 60Gy/30 fractions with concomitant and adjuvant Temozolomide. MRI follow-up including diffusion and perfusion weighting was performed at 3 T at start of postoperative chemoradiotherapy, three weeks into treatment, and then regularly until twelve months postoperatively. Regional mean diffusivity (MD) changes were analyzed voxel-wise using the PRM method (MD-PRM). At eight and twelve months postoperatively, after completion of standard treatment, patients were classified using conventional MRI and clinical evaluation as either having stable disease (SD, including partial response) or progressive disease (PD). It was assessed whether MD-PRM differed between patients having SD versus PD and whether it predicted the risk of disease progression (progression-free survival, PFS) or death (overall survival, OS). A subgroup analysis was performed that compared MD-PRM between SD and PD in patients only undergoing diagnostic biopsy. MGMT-promotor methylation status (O6-methylguanine-DNA methyltransferase) was registered and analyzed with respect to PFS, OS and MD-PRM. RESULTS: Of the 31 patients analyzed: 21 were operated by resection and ten by diagnostic biopsy. At eight months, 19 patients had SD and twelve had PD. At twelve months, ten patients had SD and 20 had PD, out of which ten were deceased within twelve months and one was deceased without known tumor progression. Median PFS was nine months, and median OS was 17 months. Eleven patients had methylated MGMT-promotor, 16 were MGMT unmethylated, and four had unknown MGMT-status. MD-PRM did not significantly predict patients having SD versus PD neither at eight nor at twelve months. Patients with an above median MD-PRM reduction had a slightly longer PFS (P = 0.015) in Kaplan-Maier analysis, as well as a non-significantly longer OS (P = 0.099). In the subgroup of patients only undergoing biopsy, total MD-PRM change at three weeks was generally higher for patients with SD than for patients with PD at eight months, although no tests were performed. MGMT status strongly predicted both PFS and OS but not MD-PRM change. CONCLUSION: MD-PRM at three weeks was not demonstrated to be predictive of treatment response, disease progression, or survival. Preliminary results suggested a higher predictive value in non-resected patients, although this needs to be evaluated in future studies.

6.
Neurobiol Dis ; 41(1): 177-88, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20850531

RESUMO

We show that intranigral lipopolysaccharide (LPS) injection, which provokes specific degeneration of DA neurons, induced caspase-3 activation in the rat ventral mesencephalon, which was mostly associated with glial cells. In contrast, nigral DA neurons exhibited AIF nuclear translocation in response to LPS. A significant decrease of the Bcl-2/Bax ratio in nigral tissue after LPS injection was observed. We next developed an in vitro co-culture system with the microglial BV2 and the DA neuronal MN9D murine cell lines. The silencing of caspase-3 or AIF by small interfering RNAs exclusively in the DA MN9D cells demonstrated the key role of AIF in the LPS-induced death of DA cells. In vivo chemical inhibition of caspases and poly(ADP-ribose)polymerase-1, an upstream regulator of AIF release and calpain, proved the central role of the AIF-dependent pathway in LPS-induced nigral DA cell death. We also observed nuclear translocation of AIF in the ventral mesencephalon of Parkinson's disease subjects.


Assuntos
Fator de Indução de Apoptose/fisiologia , Dopamina/toxicidade , Degeneração Neural/metabolismo , Doença de Parkinson/metabolismo , Transdução de Sinais/fisiologia , Substância Negra/metabolismo , Animais , Fator de Indução de Apoptose/antagonistas & inibidores , Fator de Indução de Apoptose/genética , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular , Técnicas de Cocultura , Modelos Animais de Doenças , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Doença de Parkinson/patologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Substância Negra/patologia
7.
Clin Neuropathol ; 30(2): 56-69, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21329614

RESUMO

OBJECTIVE: There are several neuropathological scales for staging of Alzheimer pathology. The system proposed by Braak and Braak is based on the topographic distribution of neurofibrillary tangles and neuropil threads, while that of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is based on the quantity of neocortical neuritic plaques. A combination of the Braak and CERAD staging scales was recommended by the National Institute on Aging and Reagan Institute (NIA-RI). The Poly-Pathology Alzheimer's Disease assessment, nine areas (PPAD9) is a staging system based on the extent of neuronal degeneration, microvacuolization, cytoarchitectural disorder and gliosis, in addition to neurofibrillary tangles and neuritic plaques, in nine cerebral regions. The aim of the present study was to critically compare these four neuropathological staging scales. METHODS: We assessed the Alzheimer pathology, using the four scales, in 43 patients with various dementia disorders, with focus on concordance and differences between the staging systems. RESULTS: Comparing the staging systems, the Spearman's rho value for PPAD9 vs. Braak was 0.65, for PPAD9 vs. CERAD 0.72, for PPAD9 vs. NIA-RI 0.67, and for Braak vs. CERAD 0.46. CONCLUSION: The correlation between the neuropathological staging systems was suboptimal, and we conclude that the choice of staging system affects the evaluation of Alzheimer pathology, and hence the final diagnosis.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Patologia Clínica/normas , Pesos e Medidas/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Clin Neuropathol ; 30(3): 104-10, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21545773

RESUMO

OBJECTIVE: Neuronal loss in the locus coeruleus (LC) is common in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The aims of the present study were to investigate LC degeneration in different dementia disorders including vascular dementia (VaD) and frontotemporal lobar degeneration (FTLD), to compare LC degeneration with severity of pathology in AD and DLB/PDD, to further evaluate the usefulness of a previously presented scoring system and to examine the predictive value of macroscopic assessment of the LC. METHODS: A horizontal mid-level section of the pons was examined in 200 neuropathologically examined cases with clinical dementia. A previous macroscopic assessment of the LC was performed in 149 of the cases. RESULTS: Cases with DLB/ PDD and AD presented with the highest microscopic LC degeneration scores, with significant differences compared to combined AD + VaD, in turn with a higher score than VaD, FTLD and other dementia disorders. Interrater agreement (weighted kappa;) for LC degeneration scoring was 0.83 - 0.91. DLB/ PDD, AD and AD + VaD were the diagnoses for 85% of the cases with macroscopic LC depigmentation. CONCLUSION: LC degeneration, which may be macroscopically noted, often indicates synuclein and/or Alzheimer pathology among demented. When clinical information is scarce or inconsistent, a macroscopic assessment of the LC may facilitate focusing of the subsequent neuropathological investigation. Also, the semiquantitative scoring system is a reliable tool for histological assessment of LC degeneration.


Assuntos
Demência/patologia , Locus Cerúleo/patologia , Degeneração Neural/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Demência Vascular/patologia , Feminino , Humanos , Doença por Corpos de Lewy/patologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia
9.
Diabet Med ; 26(11): 1120-6, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19929990

RESUMO

AIMS: Myelinated nerve fibre pathology has been demonstrated at wrist level in diabetic patients. We examined if quantification of intra-epidermal nerve fibre density (IENFD) in hairy and glabrous skin at wrist level could detect signs of subclinical small nerve fibre neuropathy. METHODS: In 35 diabetic patients who were age and gender matched with 31 non-diabetic patients, punch biopsies were obtained in conjunction with surgical carpal tunnel release. Biopsies were immunostained with anti-protein gene product (PGP) 9.5. The IENFD was quantified using manual counting by light microscopy. RESULTS: We could not demonstrate significant differences in IENFD between diabetic or non-diabetic patients. Additionally, no differences were found between patients with Type 1 and Type 2 diabetes or in diabetic patients with and without neurophysiologic signs of mild peripheral neuropathy. However, the IENFD was significantly higher in hairy skin compared with glabrous skin. Furthermore, the IENFD was significantly higher in females than in males and correlated with age, but not with duration of diabetes or glycated haemoglobin (HbA(1c)). CONCLUSIONS: In mild neuropathy no difference in IENFD at the wrist level could be detected between diabetic and non-diabetic patients. Independent of diabetes, we found IENFD to be higher in hairy skin compared with glabrous skin and higher in females than in males. These results must be taken into consideration when assessing small nerve fibre pathology in the upper extremity.


Assuntos
Síndrome do Túnel Carpal/patologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/patologia , Epiderme/patologia , Articulação do Punho/patologia , Adulto , Idoso , Síndrome do Túnel Carpal/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/fisiopatologia , Epiderme/inervação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Condução Nervosa/fisiologia , Valores de Referência , Limiar Sensorial/fisiologia
10.
Eur J Neurol ; 16(4): 488-92, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19170740

RESUMO

BACKGROUND: Investigations on cause of death may provide valuable information about life expectancy and on conditions of terminal dementia care, which perhaps can be ameliorated. METHODS: The autopsy reports were studied on all patients (n = 524; 55.3% females; median age 80 years) with a clinically and neuropathologically diagnosed dementia disorder who underwent a complete autopsy at the University Hospital in Lund, Sweden, during 1974-2004. RESULTS: The two most common causes of death were bronchopneumonia (38.4%) and ischaemic heart disease (23.1%), whilst neoplastic diseases were uncommon (3.8%). In a general population of elderly studied for comparison, bronchopneumonia accounted for 2.8%, ischaemic heart disease for 22.0%, and neoplasm for 21.3% of the deaths. Amongst the demented patients, circulatory and respiratory system diseases were the causes of death in 23.2% and 55.5% of the Alzheimer patients, respectively, whilst the corresponding figures were 54.8% and 33.1% for the patients with vascular dementia. CONCLUSIONS: In patients with dementia, pneumonia as the immediate cause of death may reflect a terminal stage in which patient care and feeding is difficult to manage well. Knowledge about what actually causes death is of value in the terminal care of patients with dementia disorders.


Assuntos
Demência/complicações , Demência/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/mortalidade , Broncopneumonia/complicações , Broncopneumonia/mortalidade , Causas de Morte , Demência Vascular/complicações , Demência Vascular/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Neoplasias/complicações , Neoplasias/mortalidade , Doenças Respiratórias/complicações , Doenças Respiratórias/mortalidade , Doenças Vasculares/complicações , Doenças Vasculares/mortalidade
11.
Eur J Vasc Endovasc Surg ; 36(3): 292-6, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18547827

RESUMO

OBJECTIVES: Little is known about the biological processes causing aortic aneurysm rupture. Chronic Chlamydophila pneumoniae infection has been suggested as a possible contributing factor to the development and expansion of abdominal aortic aneurysm (AAA). The importance of infection in AAA may be related to the previous pathogen burden, that is, the number of significant titres of antibodies against infectious pathogens rather than to single infectious agents. The aim of this study was to examine the relationship between infectious burden and AAA rupture. METHODS: In a case-control study, 119 patients with abdominal aortic aneurysm and 36 matched controls without aneurysm were prospectively investigated for specific IgG class antibodies against C. pneumoniae, Helicobacter pylori, Cytomegalovirus, and Herpes simplex virus. RESULTS: Patients with ruptured AAA have similar levels of pathogen burden as patients with nonruptured electively operated AAA, small AAA, and controls without aneurysm. CONCLUSION: The present study fails to demonstrate a connection between infectious burden and abdominal aortic aneurysm rupture.


Assuntos
Aneurisma da Aorta Abdominal/imunologia , Ruptura Aórtica/imunologia , Idoso , Estudos de Casos e Controles , Infecções por Chlamydia/imunologia , Infecções por Citomegalovirus/imunologia , Feminino , Infecções por Helicobacter/imunologia , Herpes Simples/imunologia , Humanos , Imunoglobulina G , Masculino , Estudos Prospectivos
12.
Clin Neuropathol ; 27(4): 224-33, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18666438

RESUMO

OBJECTIVE: To investigate a marker of tumor proliferation, Ki-67, and telomerase expression in glioblastoma multiforme and to compare the results of different mainly quantitative assessments, in relation to age and survival rates. METHODS: Immunohistochemical stainings of Ki-67 and hTERT were evaluated in 39 formaldehyde-fixed, paraffin-embedded surgical samples of glioblastoma multiforme diagnosed during 2004, comprising all specimens with sufficient amount of vital tissue sent to the Department of Pathology during this year. Ki-67 counting and hTERT evaluation was assessed on whole tumor sections and on selected areas within each section. Age and length of survival were analyzed in relation to these parameters. RESULTS: We found that different methods of evaluating the stained sections yielded different results regarding Ki-67, but less marked differences for hTERT. With Ki-67 counting on whole sections (non-selected areas), we found a statistically significant correlation with length of survival. There was no corresponding information in the hTERT assessment. We could also confirm a significant inverse correlation between age and length of survival, as previously published. CONCLUSION: Our data demonstrate that different methods of Ki-67 evaluation may give markedly dissimilar results. The significant correlation found between survival and one but not with two other methods of Ki-67 assessment, implicate the value of standardized quantification methods. Our data indicate a possible prognostic use of immunohistochemical Ki-67 proliferation index in glioblastoma multiforme.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Antígeno Ki-67/biossíntese , Telomerase/biossíntese , Idade de Início , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico
13.
J Environ Radioact ; 99(2): 219-29, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17892902

RESUMO

This study reports the first data of (129)I fallout in Scandinavia, covering the last 80 years. The investigation is based on sediment sections from a lake in central Sweden. In addition to analysis of (129)I, a combination of several radionuclides ((210)Pb, (137)Cs and (14)C) was used to establish an accurate chronology of the sediment profile. The concentration of (129)I exhibits an increasing trend ( approximately 10(7) to approximately 10(9)atoms/g) during the last 40 years, suggesting a significant atmospheric input from the nuclear reprocessing facilities in Sellafield (UK) and La Hague (France). A peak corresponding to fallout from the Chernobyl accident (1986) is clearly distinguishable, whereas the impact of fallout from the nuclear weapons' tests since the early 1950s is not distinguished.


Assuntos
Sedimentos Geológicos/química , Radioisótopos do Iodo/análise , Poluentes Radioativos da Água/análise , França , Reino Unido
14.
J Hand Surg Eur Vol ; 43(2): 131-136, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28758528

RESUMO

Late displacement of distal radius fractures, still in acceptable radiological position after 1-2 weeks, occurs in approximately one-third of cases. The aim of this study was to investigate the influence of late displacement on the functional outcome and quality of life at 1 year in non-operatively treated distal radius fractures. One hundred and seventy five unilateral conservatively treated distal radius fractures with minimal displacement after 10-14 days were finally evaluated in the study. Follow-up included radiographs at 3 months and clinical examination 1 year after the fracture. Final radiographic parameters, grip strength, range of motion, QuickDASH, EQ-5D and pain visual analogue scale were evaluated with multivariate analysis. Late displacement occurred in 28% of the cases and was associated with loss of grip strength and range of motion. No significant differences were seen in the outcome questionnaires. LEVEL OF EVIDENCE: II.


Assuntos
Força da Mão , Qualidade de Vida , Fraturas do Rádio/fisiopatologia , Fraturas do Rádio/terapia , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Radiografia , Fraturas do Rádio/diagnóstico por imagem , Fatores de Tempo , Adulto Jovem
15.
Oncogene ; 35(43): 5585-5596, 2016 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-27065333

RESUMO

Cartilage oligomeric matrix protein (COMP) is a soluble pentameric protein expressed in cartilage and involved in collagen organization. Tissue microarrays derived from two cohorts of patients with breast cancer (n=122 and n=498) were immunostained, revealing varying expression of COMP, both in the tumor cells and surrounding stroma. High levels of COMP in tumor cells correlated, independently of other variables, with poor survival and decreased recurrence-free survival. Breast cancer cells, MDA-MB-231, stably expressing COMP were injected into the mammary fat pad of SCID (CB-17/Icr-Prkdcscid/Rj) mice. Tumors expressing COMP were significantly larger and were more prone to metastasize as compared with control, mock-transfected, tumors. In vitro experiments confirmed that COMP-expressing cells had a more invasive phenotype, which could in part be attributed to an upregulation of matrix metalloprotease-9. Furthermore, microarray analyses of gene expression in tumors formed in vivo showed that COMP expression induced higher expression of genes protecting against endoplasmic reticulum stress. This observation was confirmed in vitro as COMP-expressing cells showed better survival as well as a higher rate of protein synthesis when treated with brefeldin A, compared with control cells. Further, COMP-expressing cells appeared to undergo a metabolic switch, that is, a Warburg effect. Thus, in vitro measurement of cell respiration indicated decreased mitochondrial metabolism. In conclusion, COMP is a novel biomarker in breast cancer, which contributes to the severity of the disease by metabolic switching and increasing invasiveness and tumor cell viability, leading to reduced survival in animal models and human patients.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Transformação Celular Neoplásica/metabolismo , Animais , Apoptose/genética , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Proteína de Matriz Oligomérica de Cartilagem/genética , Adesão Celular/genética , Linhagem Celular , Membrana Celular/metabolismo , Movimento Celular/genética , Modelos Animais de Doenças , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Xenoenxertos , Humanos , Imuno-Histoquímica , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos SCID , Metástase Neoplásica , Fosforilação Oxidativa , Prognóstico , Modelos de Riscos Proporcionais , Recidiva
16.
Clin Neuropathol ; 24(5): 201-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16167543

RESUMO

Glioblastoma multiforme (GBM) is the most common highly malignant brain tumor and is also one among the most therapy-resistant human neoplasias. At the University Hospital in Lund, a group of patients with GBM were treated with a new therapy form attempting immunization by glioma cells transfected to produce interferon-gamma. The purpose of this report was to evaluate tumor material from the first nine patients treated with this therapy, assessing the levels of inflammatory/reactive cells (lymphocytes and macrophages). Tumor biopsies from surgery performed at different time points during treatment were analyzed with conventional histotechnical methods and immunohistochemistry. A post-mortem neuropathological investigation with a whole brain assessment was achieved in 5 immunized patients. The results show that cytotoxic T lymphocytes exhibited a mild increase during immunotreatment. This increase indicates an invoked stimulation of a cytotoxic T cell reaction, which may prove beneficial when immunization is adequately manipulated in dosage and timing.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Glioblastoma/patologia , Glioblastoma/terapia , Imunoterapia Adotiva , Idoso , Neoplasias Encefálicas/imunologia , Ensaios Clínicos como Assunto , Feminino , Glioblastoma/imunologia , Humanos , Imuno-Histoquímica , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Acta Neurol Scand Suppl ; 168: 31-8, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8997417

RESUMO

This review concerns the fundamental cerebral lesions in cases of vascular dementia. Extracerebral vascular alterations are dominated by atherosclerosis with or without thrombosis. In addition, occlusion of extracerebral arteries can be induced by thrombo-embolism and in rare cases by other vascular diseases, chiefly arteritis. Intracerebral microangiopathies are usually of arteriolosclerotic or hyalinotic types in which there is degeneration of smooth muscle cells of the media and deposition of components of extracellular matrix, chiefly collagens. Ageing, chronic hypertension, hyperlipidemias and diabetes are important factors inducing vascular lesions. The vascular lesions, often combined with systemic factors, may produce various ischemic and edematous alterations of the brain parenchyma. Occlusion and obliteration of arteries (macroangiopathy) are associated with large infarcts, whereas microangiopathy may cause lacunar infarcts and some forms of white matter degeneration. Cases of vascular dementia usually present many types of lesions in the brain parenchyma and its arterial supply. The extent and location of the injuries differ considerably from case to case. Location of the lesions, volume of destroyed tissue, multiplicity and bilateral occurrence are most important parameters underlying the clinical manifestations in vascular dementia. A strategic location of a small injury is in some cases of particular importance.


Assuntos
Demência por Múltiplos Infartos/patologia , Demência Vascular/patologia , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Dominância Cerebral/fisiologia , Matriz Extracelular/patologia , Humanos , Arteriosclerose Intracraniana/patologia , Embolia e Trombose Intracraniana/patologia , Túnica Média/patologia
18.
J Gerontol A Biol Sci Med Sci ; 54(9): B363-8, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10536640

RESUMO

Based on the known age-related loss of Purkinje cells (PC) in the cerebellum, this study focuses on whether a marked loss of PC occurs in individuals of very high age. The inferior olive, which is intimately connected with the cerebellum anatomically as well as functionally, was also studied. The study group included 15 nondemented and basically healthy cases aged 32-104 years. Linear neuronal density was expressed as number of PC per millimeter tissue measured in the vermis and as neuronal numbers per square millimeter tissue in the inferior olive. The linear PC density clearly decreased with increasing age, R2 = 0.82 and p < .001. The inferior olive showed a small but insignificant age-related neuronal loss. We conclude that aging results in reduced PC density in the vermis cerebelli, further accentuated in the very late stages of life.


Assuntos
Envelhecimento/patologia , Tronco Encefálico/patologia , Morte Celular/fisiologia , Cerebelo/patologia , Neurônios/patologia , Núcleo Olivar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência
19.
Int J Tuberc Lung Dis ; 3(5): 394-401, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10331728

RESUMO

SETTING: The pilot projects for tuberculosis (TB) control, supported by the World Health Organization (WHO) and based on the WHO recommended control strategy, directly-observed treatment, short-course (DOTS) in the Caucasian countries (Armenia, Azerbaijan, Georgia). OBJECTIVE: To evaluate the results 2 years after the implementation of the pilot projects. METHODS: Analysis of data on case detection, sputum conversion and treatment outcome reported quarterly to the WHO from the Ministries of Health in each country. RESULTS: Since the establishment of the project, 1330, 764 and 4866 new cases and relapses, respectively, of TB have been detected in the pilot areas of Armenia, Azerbaijan and Georgia. In Armenia and Azerbaijan, respectively 46% and 57% of all cases were smear positive, whilst in Georgia, the corresponding figure was only 12%. After 3 months' treatment, 93% of new smear-positive patients had become smear-negative. The sputum conversion rate for relapses and other retreatment cases (failure, treatment interrupted) was 85%. In Armenia, 78.1% of new smear-positive patients were treated successfully (cured or completed treatment). The corresponding percentages for Azerbaijan and Georgia were 87.9% and 59.6%. Treatment success rates among retreatment cases was generally low, at respectively 46%, 64%, and 35%, in Armenia, Azerbaijan, and Georgia. CONCLUSION: The results of the implementation of the WHO TB control pilot projects in Armenia, Azerbaijan and Georgia suggest that the DOTS strategy is feasible in emergency situations in general, and in the Caucasus in particular.


Assuntos
Tuberculose/prevenção & controle , Notificação de Doenças , Humanos , Prevalência , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Transcaucásia/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Organização Mundial da Saúde
20.
Neurosci Lett ; 226(1): 65-7, 1997 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-9153643

RESUMO

The apolipoprotein (apoE) epsilon4 allele was studied in fronto-temporal dementia (FTD), a diagnostic category including the specific disorders Pick's disease and frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases have neuronal and synaptic degeneration in common with Alzheimer's disease (AD), for which the presence of the apoE epsilon4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon4 allele frequency in FTD have been inconclusive. The structural hallmarks of AD, allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily composed of hyperphosphorylated tau, are lacking in FTD. However, tau-positive cytoskeletal pathology is found in Pick's disease, but not in FLD. Resolving whether the epsilon4 frequency is increased in FTD or not may thus give clues to the pathogenetic mechanism of apoE in AD. We therefore studied apoE alleles in a well characterized material of FTD patients. The epsilon4 allele frequency was similar in 25 patients with FTD (14.0%) as compared with 26 healthy controls (13.5%). A post-mortem neuropathological examination was performed in 10 cases (nine had FLD and one Pick's disease). Our finding of a normal epsilon4 allele frequency in our group of FTD, principally consisting of FLD cases, support hypotheses involving differential binding of apoE to beta-amyloid and/or tau, in the development of beta-amyloid deposition and NP formation and/or tau hyperphosphorylation and NFT formation, for the pathogenetic role of apoE in AD. The age at onset was significantly lower (P < 0.01) in FTD patients possessing the epsilon4 allele (48.7 +/- 8.0 years) than in patients not possessing this allele (58.9 +/- 7.6 years). We conclude that, although the apoE epsilon4 allele frequency is not increase in FTD, the epsilon4 allele is not an etiological factor, but may rather be an accelerating factor in the degenerative process of FTD, thereby resulting in an earlier presentation of the disorder in individuals predisposed to develop FTD.


Assuntos
Idade de Início , Apolipoproteínas E/metabolismo , Demência/metabolismo , Lobo Frontal/metabolismo , Lobo Temporal/metabolismo , Adulto , Idoso , Alelos , Apolipoproteína E4 , Demência/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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