884 resultados para 1950 - Sclero Year of Death 20
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<p>PURPOSE: Concerns were raised about the safety of antiplatelet thienopyridine derivatives after a randomized control trial reported increased risks of cancer and cancer deaths in prasugrel users. We investigate whether clopidogrel, a widely used thienopyridine derivative, was associated with increased risk of cancer-specific or all-cause mortality in cancer patients.</p><p>METHODS: Colorectal, breast and prostate cancer patients, newly diagnosed from 1998 to 2009, were identified from the National Cancer Data Repository. Cohorts were linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2012). Unadjusted and adjusted hazard ratios (HRs) for cancer-specific and all-cause mortality in post-diagnostic clopidogrel users were calculated using time-dependent Cox regression models.</p><p>RESULTS: The analysis included 10359 colorectal, 17889 breast and 13155 prostate cancer patients. There was no evidence of an increase in cancer-specific mortality in clopidogrel users with colorectal (HR=0.98 95% confidence interval (CI) 0.77, 1.24) or prostate cancer (HR=1.03 95%CI 0.82, 1.28). There was limited evidence of an increase in breast cancer patients (HR=1.22 95%CI 0.90, 1.65); however, this was attenuated when removing prescriptions in the year prior to death.</p><p>CONCLUSIONS: This novel study of large population-based cohorts of colorectal, breast and prostate cancer patients found no evidence of an increased risk of cancer-specific mortality among colorectal, breast and prostate cancer patients using clopidogrel.</p>
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Introduction Institutionalization in a nursing home restricts autonomy, most notably free will, free choice, and free action. Decreased physical activity and fitness are predictive of disability and dependence (Rikli & Jones, 2013; Tak, Kuiper, Chorus, & Hopman-Rock, 2014); however little is known about the impact of these factors on institutionalization. Thus, this study aimed to analyze the impact of physical activity and fitness and on the risk of elderly people without cognitive impairment become institutionalized. Methods This cross-sectional study involved 195 non-institutionalized (80.14.4yrs) and 186 institutionalized (83.85.2yrs) participants. Cognitive impairment was assessed using Mini-Mental State Examination, physical activity was assessed using the International Physical Activity Questionnaire, and measures of physical fitness were determined by the Senior Fitness Test. Results: Multivariate binary logistic analysis selected 4 main predictors of institutionalization in both genders. The likelihood of becoming institutionalized increased by +18.6% for each additional year of age, while it decreased by -24.8% by each fewer kg/m2 in BMI, by -0.9% for each additional meter performed in the aerobic endurance test and by -2.0% for each additional 100MET-min/wk of physical activity expenditure (p<0.05). Values 50th percentile (age 81yrs, BMI26.7kg/m2, aerobic endurance 367.6m, and physical activity 693MET-min/wk) were computed using Receiver Operating Characteristics analysis as cut-offs discriminating institutionalized from non-institutionalized elderly people. Conclusion The performance of physical activity, allied to an improvement in physical fitness (mainly BMI and aerobic endurance) may prevent the institutionalization of elderly people without cognitive impairment only if they are above the 50th percentile; the following is highly recommend: expending 693MET-min/wk on physical activity, being 26.7kg/m2 on BMI, and being able to walk 367.6m in the aerobic endurance test, especially above the age of 80 years. The discovery of this trigger justifies the development of physical activity programs targeting the pointed cut-offs in old, and very old people. References Rikli, R., & Jones, C. (2013). Development and validation of criterion-referenced clinically relevant fitness standards for maintaining physical independence in later years. Gerontologist, 53, 255-267. Tak, E., Kuiper, R., Chorus, A., & Hopman-Rock, M. (2014). Prevention of onset and progression of basic ADL disability by physical activity in community dwelling older adults: a meta-analysis. Ageing Res Rev, 12, 329-338.
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According to the World Health Organization, around 8.2 million people die each year with cancer. Most patients do not perform routine diagnoses and the symptoms, in most situations, occur when the patient is already at an advanced stage of the disease, consequently resulting in a high cancer mortality. Currently, prostate cancer is the second leading cause of death among males worldwide. In Portugal, this is the most diagnosed type of cancer and the third that causes more deaths. Taking into account that there is no cure for advanced stages of prostate cancer, the main strategy comprises an early diagnosis to increase the successful rate of the treatment. The prostate specific antigen (PSA) is an important biomarker of prostate cancer that can be detected in biological fluids, including blood, urine and semen. However, the commercial kits available are addressed for blood samples and the commonly used analytical methods for their detection and quantification requires specialized staff, specific equipment and extensive sample processing, resulting in an expensive process. Thus, the aim of this MSc thesis consisted on the development of a simple, efficient and less expensive method for the extraction and concentration of PSA from urine samples using aqueous biphasic systems (ABS) composed of ionic liquids. Initially, the phase diagrams of a set of aqueous biphasic systems composed of an organic salt and ionic liquids were determined. Then, their ability to extract PSA was ascertained. The obtained results reveal that in the tested systems the prostate specific antigen is completely extracted to the ionic-liquid-rich phase in a single step. Subsequently, the applicability of the investigated ABS for the concentration of PSA was addressed, either from aqueous solutions or urine samples. The low concentration of this biomarker in urine (clinically significant below 150 ng/mL) usually hinders its detection by conventional analytical techniques. The obtained results showed that it is possible to extract and concentrate PSA, up to 250 times in a single-step, so that it can be identified and quantified using less expensive techniques.
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According to the World Health Organization, around 8.2 million people die each year with cancer. Most patients do not perform routine diagnoses and the symptoms, in most situations, occur when the patient is already at an advanced stage of the disease, consequently resulting in a high cancer mortality. Currently, prostate cancer is the second leading cause of death among males worldwide. In Portugal, this is the most diagnosed type of cancer and the third that causes more deaths. Taking into account that there is no cure for advanced stages of prostate cancer, the main strategy comprises an early diagnosis to increase the successful rate of the treatment. The prostate specific antigen (PSA) is an important biomarker of prostate cancer that can be detected in biological fluids, including blood, urine and semen. However, the commercial kits available are addressed for blood samples and the commonly used analytical methods for their detection and quantification requires specialized staff, specific equipment and extensive sample processing, resulting in an expensive process. Thus, the aim of this MSc thesis consisted on the development of a simple, efficient and less expensive method for the extraction and concentration of PSA from urine samples using aqueous biphasic systems (ABS) composed of ionic liquids. Initially, the phase diagrams of a set of aqueous biphasic systems composed of an organic salt and ionic liquids were determined. Then, their ability to extract PSA was ascertained. The obtained results reveal that in the tested systems the prostate specific antigen is completely extracted to the ionic-liquid-rich phase in a single step. Subsequently, the applicability of the investigated ABS for the concentration of PSA was addressed, either from aqueous solutions or urine samples. The low concentration of this biomarker in urine (clinically significant below 150 ng/mL) usually hinders its detection by conventional analytical techniques. The obtained results showed that it is possible to extract and concentrate PSA, up to 250 times in a single-step, so that it can be identified and quantified using less expensive techniques.
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It is widely recognized that protein restriction in utero may cause metabolic and endocrine adaptations, which may be of benefit to the neonate on a short-term basis but may cause adverse long-term conditions such as obesity, Type 2 diabetes, metabolic syndrome, hypertension and cardiovascular diseases. Adequate foetal and early post natal nutrient and energy supply is therefore essential for adult animal health, performance and life span. In this project it was investigated the progressive adaptations of the hepatic proteome in male mink offspring exposed to either a low protein (FL) or an adequate protein (FA) diet in utero fed either on a low protein (LP) or on an adequate (AP) diet from weaning until sexual maturity. Specifically, the aim was to determine the metabolic adaptations at selected phases of the animals first annual cycle and establish the metabolic priorities occurring during those phases. The three different morphological stages studied during the first year of development included, end of bone growth at 4 months of age, maximal fat accretion at 6 months of age and sexual maturity at 12 months of age. A reference proteome of mink liver coming from these different animal groups were generated using 2D electrophoresis coupled to MALDI-TOF analysis and the way in which dietary treatment affect their proteome was established. Approximately 330 proteins were detected in the mink liver proteome. A total of 27 comparisons were carried out between all different animal groups which resulted in 20 differentially expressed proteins. An extensive survey was conducted towards the characterization of these proteins including their subcellular localization, the biological processes in which they are involved and their molecular functions. This characterization allowed the identification of proteins in various processes including the glycolysis and fatty acid metabolism. The detailed analysis of the different dietary treatment animal groups was indicative of differences in metabolism and also to changes associated with development in mink.
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This study determined annual and monthly fluctuations in concentration of 20 fungal genera. The selection of taxa was made based upon their high frequency in the air as well as their well-known allergenic properties. Air samples were collected using a spore trap of Hirst design at an urban site where the trap continuously worked throughout a 5-year survey. Weather data were acquired from a meteorological station co-located with the air sampler. Influence of several meteorological parameters was then examined to reveal speciesenvironment interactions and the potential location of fungal spore sources within the urban area. The maximum monthly sum of mean daily spore concentration varied between genera, and the earliest peaks were recorded for Pleospora sp. in April and Ustilago sp. in June. However, the majority of investigated spore types occurred in the greatest concentrations between August and September. Out of the 20 studied taxa, the most dominant genus was Cladosporium sp., which exceeded an allergenic threshold of 3000 s m-3 40 times during very rainy years and twice as much during dry years. A Spearmans rank test showed that statistically significant (p B 0.05) relationships between spore concentration and weather parameters were mainly rs B 0.50. Potential sources of spores at Worcester were likely to be localised outside the city area.
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Introduo: As doenas cardiovasculares so a principal causa de morte na Europa e o sedentarismo um dos seus principais fatores de risco. Os programas de reabilitao cardiovascular (RCV) no domiclio parecem ser eficazes na tolerncia ao exerccio. No entanto, torna-se difcil reproduzir um protocolo de exerccios no domiclio, por se tratar de estudos pouco especficos. Objetivo: Avaliar os efeitos de um programa de exerccios especfico realizado no domiclio, na tolerncia ao exerccio em pacientes integrados num programa RCV. Metodologia: Estudo quase experimental composto por 20 indivduos com pelo menos um ano de enfarte agudo do miocrdio, distribudos aleatoriamente em dois grupos: grupo experimental (GE) e grupo de controlo (GC), ambos com 10 indivduos. O programa de RCV no domiclio (constitudo por 10 exerccios) teve a durao de 8 semanas, com uma frequncia de 3 vezes por semana. Avaliou-se a frequncia cardaca (FC), tenso arterial e duplo produto basais e mximos; FC de recuperao; equivalentes metablicos (METs); velocidade; inclinao; tempo de prova e de recuperao; ndice ciftico; equilbrio; e tempo em atividade moderada a vigorosa. Resultados: Ao fim de 8 semanas de exerccio o GE aumentou significativamente os METs (p=0,001), tenso arterial sistlica mxima (p<0,001), duplo produto mximo (p<0,001) e tempo de prova (p=0,037) e diminuiu significativamente o tempo de recuperao (p<0,001), quando comparado com o GC. Concluso: O programa de exerccios no domiclio promoveu uma melhoria na tolerncia ao exerccio e parece ter melhorado o equilbrio, para a amostra em estudo.
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RESUMO - A valorizao econmica de intervenes preventivas pode contribuir para melhorar a afetao de recursos em sade. A hipertenso, primeira causa de morte em Portugal, um grave problema de sade Pblica e o principal fator de risco para a ocorrncia de Acidente Vascular Cerebral (AVC). O presente estudo um primeiro ensaio para quantificar a disposio para pagar (DPP) da sociedade por uma interveno de promoo da adeso teraputica em hipertensos no controlados. Foi aplicado um questionrio presencial a uma amostra de convenincia (n=93), numa perspetiva ex post, sendo o questionrio constitudo por dois formatos de questes e dois cenrios de diferentes redues de presso arterial sistlica (cenrio 1 corresponde reduo de 10 mmHg e cenrio 2 reduo de 20 mmHg). O risco de AVC a 10 anos foi adaptado idade e ao sexo de cada participante. Relativamente ao cenrio 1, a DPP mdia foi de 25,87 e 33,93, dependendo do formato da questo (resposta aberta ou bidding game, respetivamente). Na questo de resposta aberta, 78,3% dos participantes estavam dispostos para pagar pela interveno, no bidding game 75,6% dos participantes referiram estar dispostos para pagar pelo menos 10. No cenrio 2, a DPP mdia foi de 26,81 e 34,79, dependendo se o formato da questo era do tipo resposta aberta ou bidding game, respetivamente. Na questo de resposta aberta, 84,3% dos participantes estavam dispostos para pagar pela interveno, no bidding game 76,1% dos participantes referiram estar dispostos para pagar pelo menos 10. Ao contrrio do bidding game, nas questes de resposta aberta verificou-se 25,8% e 24,7% de respostas no sei, para o cenrio 1 e cenrio 2 respetivamente, diretamente relacionada com a baixa escolaridade dos participantes (p=0,004). Tambm se verificou uma maior tendncia para respostas s questes de bidding game com valores mais elevados, comparativamente s questes de resposta aberta. Identificaram-se duas variveis explicativas para os valores DPP: o rendimento e a ocupao principal. A sensibilidade dos respondentes magnitude dos ganhos em sade foi verificada internamente em cada questionrio (os participantes referiram DPP mais elevadas no cenrio 2 relativamente ao cenrio 1), no entanto, os participantes que beneficiariam mais da interveno no demonstraram DPP superiores aos restantes. Para confirmar os efeitos identificados neste estudo e extrapol-los para a populao portuguesa necessrio realizar um estudo representativo de populao portuguesa.
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Hospital-acquired infections (HAIs) delay healing, prolong Hospital stay, and increase both Hospital costs and risk of death. This study aims to estimate the extra length of stay and mortality rate attributable to each of the following HAIs: wound infection (WI); bloodstream infection (BSI); urinary infections (UI); and Hospital-acquired pneumonia (HAP). The study population consisted of patients discharged in CHLC in 2014. Data was collected to identify demographic information, surgical operations, development of HAIs and its outputs. The study used regressions and a matched strategy to compare cases (infected) and controls (uninfected). The matching criteria were: age, sex, week and type of admission, number of admissions, major diagnostic category and type of discharge. When compared to matched controls, cases with HAI had a higher mortality rate and greater length of stay. WI related to hip or knee surgery, increased mortality rate by 27.27% and the length of stay by 74.97 days. WI due to colorectal surgery caused an extra mortality rate of 10.69% and an excess length of stay of 20.23 days. BSI increased Hospital stay by 28.80 days and mortality rate by 32.27%. UI caused an average additional length of stay of 19.66 days and risk of death of 12.85%. HAP resulted in an extra Hospital stay of 25.06 days and mortality rate of 24.71%. This study confirms the results of the previous literature that patients experiencing HAIs incur in an excess of mortality rates and Hospital stay, and, overall, it presents worse results comparing with other countries.
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RESUMO: Actualmente, a nica possibilidade de cura para doentes com adenocarcinoma do pncreas (PDAC) a resseco cirrgica, no incio deste estudo, perguntamo-nos se os predictores clnico-patolgicos clssicos de prognostico poderiam ser validados em uma grande cohort de doentes com cancro do pncreas ressecvel e se outros predictores clnicos poderiam ter um papel na deciso de que doentes beneficiariam de resseco cirrgica. No captulo 2, observamos que at 30% dos doentes morrem no primeiro ano aps a resseco cirrgica, pelo que o nosso objectivo foi determinar factores pr-operatrios que se correlacionam com mortalidade precoce aps ressecao cirrgica com recurso a um instrumento estatisticamente validado, o Charlson-Age Comorbidity Index (CACI), determinamos que um CACI score superior a 4 foi preditivo de internamentos prolongados (p <0,001), complicaes ps-operatrias (p = 0,042), e mortalidade em 1 ano ps- resseco cirrgica (p <0,001). Um CACI superior a 6 triplicou a mortalidade no primeiro ano ps-cirurgia e estes doentes tm menos de 50% de probabilidade de estarem vivos um ano aps a cirurgia. No captulo 3, o nosso objectivo foi identificar uma protena de superfcie que se correlacionasse estatisticamente com o prognostico de doentes com adenocarcinoma do pncreas e permitisse a distino de subgrupos de doentes de acordo com as suas diferenas moleculares, perguntamo-nos ainda se essa protena poderia ser um marcador de clulas-estaminais. No nosso trabalho anterior observamos que as clulas tumorais na circulao sangunea apresentavam genes com caractersticas bifenotpica epitelial e mesenquimal, enriquecimento para genes de clulas estaminais (ALDH1A1 / ALDH1A2 e KLF4), e uma super-expresso de genes da matriz extracelular (colagnios, SPARC, e DCN) normalmente identificados no estroma de PDAC. Aps a avaliao dos tumores primrios com RNA-ISH, muitos dos genes identificados, foram encontrados co-localizando em uma sub-populao de clulas na regio basal dos ductos pancreticos malignos. Alm disso, observamos que estas clulas expressam o marcador SV2A neuroendcrino, e o marcador de clulas estaminais ALDH1A1/2. Em comparao com tumores negativos para SV2, os doentes com tumores SV2 positivos apresentaram nveis mais baixos de CA 19-9 (69% vs. 52%, p = 0,012), tumores maiores (> 4 cm, 23% vs. 10%, p = 0,0430), menor invaso de gnglios linfticos (69% vs. 86%, p = 0,005) e tumores mais diferenciados (69% vs. 57%, p = 0,047). A presena de SV2A foi associada com uma sobrevida livre de doena mais longa (HR: 0,49 p = 0,009) bem como melhor sobrevida global (HR: 0,54 p = 0,018). Em conjunto, esta informao aponta para dois subtipos diferentes de adenocarcinoma do pncreas, e estes subtipos co-relacionam estatisticamente com o prognostico de doentes, sendo este subgrupo definido pela presena do clone celular SV2A / ALDH1A1/2 positivo com caractersticas neuroendcrinas. No Captulo 4, a expresso de SV2A no cancro do pncreas foi validado em linhas celulares primrias. Demonstramos a heterogeneidade do adenocarcinoma do pncreas de acordo com caractersticas clonais neuroendcrinas. Ao comparar as linhas celulares expressando SV2 com linhas celulares negativas, verificamos que as linhas celulares SV2+ eram mais diferenciadas, diferindo de linhas celulares SV2 negativas no que respeita a mutao KRAS, proliferao e a resposta quimioterapia. No captulo 5, perguntamo-nos se o clone celular SV2 positivo poderia explicar a resistncia a quimioterapia observada em doentes. Observamos um aumento absoluto de clones celulares expressando SV2A, em mltiplas linhas de evidncia - doentes, linhas de clulas primrias e xenotransplantes. Embora, tenhamos sido capazes de demonstrar que o adenocarcinoma do pncreas uma doena heterognea, consideramos que a caracterizao gentica destes clones celulares expressando SV2A de elevada importncia. Pretendemos colmatar esta limitao com as seguintes estratgias: Aps o tratamento com quimioterapia neoadjuvante na nossa coorte, realizamos microdissecao a laser das amostras primarias em parafina, de forma a analisar mutaes genticas observadas no adenocarcinoma pancretico; em segundo lugar, pretendemos determinar consequncias de knockdown da expresso de SV2A em nossas linhas celulares seguindo-se o tratamento com gemicitabina para determinao do papel funcional de SV2A; finalmente, uma vez que os nossos esforos anteriores com um promotor - reprter e SmartFlare falharam, o prximo passo ser realizar RNA-ISH PrimeFlow seguido de FACS e RNA-seq para caracterizao deste clone celular. Em conjunto, conseguimos provar com vrias linhas de evidncia, que o adenocarcinoma pancretico uma doena heterognea, definido por um clone de clulas que expressam SV2A, com caractersticas neuroendcrinas. A presena deste clone no tecido de doentes correlaciona-se estatisticamente com o prognostico da doena, incluindo sobrevida livre de doena e sobrevida global. Juntamente com padres de proliferao e co-expresso de ALDH1A1/2, este clone parece apresentar um comportamento de clulas estaminais e est associado a resistncia a quimioterapia, uma vez que a sua expresso aumenta aps agresso qumica, quer em doentes, quer em linhas de clulas primrias.----------------------------- ABSTRACT: Currently, the only chance of cure for patients with pancreatic adenocarcinoma is surgical resection, at the beginning of my thesis studies, we asked if the classical clinicopathologic predictors of outcome could be validated in a large cohort of patients with early stage pancreatic cancer and if other clinical predictors could have a role on deciding which patients would benefit from surgery. In chapter 2, we found that up to 30% of patients die within the first year after curative intent surgery for pancreatic adenocarcinoma. We aimed at determining pre-operative factors that would correlate with early mortality following resection for pancreatic cancer using a statistically validated tool, the Charlson-Age Comorbidity Index (CACI). We found that a CACI score greater than 4 was predictive of increased length of stay (p<0.001), post-operative complications (p=0.042), and mortality within 1-year of pancreatic resection (p<0.001). A CACI score of 6 or greater increased 3-fold the odds of death within the first year. Patients with a high CACI score have less than 50% likelihood of being alive 1 year after surgery. In chapter 3 we aimed at identifying a surface protein that correlates with patients outcome and distinguishes sub-groups of patients according to their molecular differences and if this protein could be a cancer stem cell marker. The most abundant class of circulating tumor cells identified in our previous work was found to have biphenotypic features of epithelial to mesenchymal transition, enrichment for stem-cell associated genes (ALDH1A1/ALDH1A2 and KLF4), and an overexpression of extracellular matrix genes (Collagens, SPARC, and DCN) normally found in the stromal microenvironment of PDAC primary tumors. Upon evaluation of matched primary tumors with RNA-ISH, many of the genes identified were found to co-localize in a sub-population of cells at the basal region of malignant pancreatic ducts. In addition, these cells expressed the neuroendocrine marker SV2A, and the stem cell marker ALDH1A1/2. Compared to SV2 negative tumors, patients with SV2 positive tumors were more likely to present with lower CA 19-9 (69% vs. 52%, p = 0.012), bigger tumors (size > 4 cm, 23% vs. 10%, p= 0.0430), less nodal involvement (69% vs. 86%, p = 0.005) and lower histologic grade (69% vs. 57%, p = 0.047). The presence of SV2A expressing cells was associated with an improved disease free survival (HR: 0.49 p=0.009) and overall survival (HR: 0.54 p=0.018) and correlated linearly with ALDH1A2. Together, this information points to two different sub-types of pancreatic adenocarcinoma, and these sub-types correlated with patients outcome and were defined by the presence of a SV2A/ ALDH1A1/2 expressing clone with neuroendocrine features. In Chapter 4, SV2A expression in cancer was validated in primary cell lines. We were able to demonstrate pancreatic adenocarcinoma heterogeneity according to neuroendocrine clonal features. When comparing SV2 expressing cell lines with SV2 negative cell lines, we found that SV2+ cell lines were more differentiated and differ from SV2 negative cell lines regarding KRAS mutation, proliferation and response to chemotherapy. In Chapter 5 we aimed at determining if this SV2 positive clone could explain chemoresistance observed in patients. We found an absolute increase in SV2A expressing cells, with multiple lines of evidence, in patients, primary cell lines and xenografts. Although, we have been able to show evidence that pancreatic adenocarcinoma is a heterogeneous disease, our findings warrant further investigation. To further characterize SV2A expressing clones after treatment with neoadjuvant chemotherapy in our cohort, we have performed laser capture microdissection of the paraffin embedded tissue in this study and will analyze the tissue for known genetic mutations in pancreatic adenocarcinoma; secondly, we want to know what will happen after knocking down SV2A expression in our cell lines followed by treatment with gemcitabine to determine if SV2A is functionally important; finally, since our previous efforts with a promoter reporter and SmartFlare have failed, we will utilize a novel PrimeFlow RNA-ISH assay followed by FACS and RNA sequencing to further characterize this cellular clone. Overall our data proves, with multiple lines of evidence, that pancreatic adenocarcinoma is a heterogeneous disease, defined by a clone of SV2A expressing cells, with neuroendocrine features. The presence of this clone in patients tissue correlates with patients disease free survival and overall survival. Together with patterns of proliferation and ALDH1A1/2 co-expression, this clone seems to present a stem-cell-like behavior and is associated with chemoresistance, since it increases after chemotherapy, both in patients and primary cell lines.
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Purpose: To report a novel maculopathy in a patient with SCA1. To describe autofluorescence findings in family with SCA7 and associated cone-rod retinal dysfunction.Methods: 4 affected patients from two families were assessed to investigate a progressive loss of visual acuity (VA). Examinations included fundus photography, autofluorescence (AF) fundus fluorescein angiogragraphy (FFA) and optical coherence tomography. Electroretinogram (full-field) was performed in 2 affected patients. All patients had color vision testing using Ishihara pseudoisochromatic plates. Molecular analysis was performed in family 2.Results: The patient with known diagnosis of SCA1 had a visual acuity of 20/200 bilaterally and dyschromatopsia. He had saccadic pursuit. Fundus examination showed mild retinal pigment epithelium (RPE) changes at the macula. OCT showed bilateral macular serous detachment, which was not obvious at the FFA and explained his VA. AF imaging showed a central hyperfluorescence. The 45 year old proband from family 2 had a visual acuity of 200/20 and dyschromatopsia. ERG testing showed cone type dysfunction of photoreceptors. Her daughter affected at a younger age had the same ERGs findings. Fundus examination showed mild RPE changes in proband, normal findings in her daughter. AF imaging of both patients showed a ring of high density AF around the fovea. The ring was also obvious on near infrared AF. Later onset of gait imbalance led to the diagnosis of SCA7Conclusions: Within the group of spinocerebellar ataxias, only the type 7 is associated with retinal dysfunction. We present the first report of maculopathy associated with SCA1 causing severe vision loss. The ring of high density AF in SCA7 confirmed an early retinal photoreceptor dysfunction in patient with normal fundus.
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Lung transplantation has evolved from an experimental procedure to a viable therapeutic option in many countries. In Switzerland, the first lung transplant was performed in November 1992, more than ten years after the first successful procedure world-wide. Thenceforward, a prospective national lung transplant registry was established, principally to enable quality control. The data of all patients transplanted in the two Swiss Lung Transplant centres Zurich University Hospital and Centre de Romandie (Geneva-Lausanne) were analysed. In 10 years 242 lung transplants have been performed. Underlying lung diseases were cystic fibrosis including bronchiectasis (32%), emphysema (32%), parenchymal disorders (19%), pulmonary hypertension (11%) and lymphangioleiomyomatosis (3%). There were only 3% redo procedures. The 1, 5 and 9 year survival rates were 77% (95% CI 72-82), 64% (95% CI 57-71) and 56% (95% CI 45-67), respectively. The 5 year survival rate of patients transplanted since 1998 was 72% (95% CI 64-80). Multivariate Cox regression analysis revealed that survival was significantly better in this group compared to those transplanted before 1998 (HR 0.44, 0.26-0.75). Patients aged 60 years and older (HR 5.67, 95% CI 2.50-12.89) and those with pulmonary hypertension (HR 2.01, 95% CI 1.10-3.65) had a significantly worse prognosis The most frequent causes of death were infections (29%), bronchiolitis obliterans syndrome (25%) and multiple organ failure (14%). The 10-year Swiss experience of lung transplantation compares favourably with the international data. The best results are obtained in cystic fibrosis, pulmonary emphysema and parenchymal disorders.
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RESUME Objectifs: Etudier la prvalence des troubles lis l'utilisation de substances psychoatives parmi des adolescents suicidaires; valuer l'influence de la prise de substances psychoactives sur le geste suicidaire; analyser l'association entre les troubles lis l'utilisation de substances psychoactives et le risque de rcidive de la conduite suicidaire. Mthode: 186 adolescents, gs de 16 21 ans, hospitaliss pour tentative de suicide ou ides suicidaires envahissantes, ont t inclus. Parmi eux, 148 ont t revus pour valuation 6 et/ou 18 mois. Des diagnostics psychiatriques, bass sur les critres du DSM-IV, ont t poss l'aide d'un questionnaire, le MINI (Mini International Neuropsychiatric Interview). Rsultats: A l'inclusion, 39.2% des sujets avaient un trouble li l'utilisation de substances psychoactives. Parmi eux, une proportion significativement plus leve tait sous l'influence d'alcool ou drogue au moment de la tentative de suicide (44.3% versus 25.4%). Des 148 adolescents suivis et revus 6 ou 18 mois, 2 sont dcds par suicide et il y a eu 30 rcidives de tentative de suicide durant l'tude. Une association significative a t trouve entre les rcidives de suicide et un diagnostic d'abus/dpendance l'alcool l'inclusion (OR=3.3; CI 0.7-15.0; 0R=2.6, CI 0.7-9.3). Des antcdents de plusieurs tentatives de suicide (OR=3.2; CI 1.1-10.0) et un ge suprieur 19 ans (OR=3.2; CI 1.1-9.2) l'inclusion taient associs la probabilit de mort par suicide ou de rcidive de tentative de suicide. Conclusion: Parmi les adolescents hospitaliss pour tentative de suicide ou ides suicidaires envahissantes, le risque de dcs ou de rcidive est important. Ce risque est associ, entre autres, des antcdents suicidaires et au diagnostic de trouble li l'utilisation de substances psychoactives. Le risque suicidaire ainsi que la consommation de substances psychoactives devrait tre valu chez les adolescents. De plus, les sujets jugs risque devraient tre suivis systmatiquement aprs une hospitalisation pour conduite suicidaire. ABSTRACT Aim: To study the prevalence of psychoactive substance use disorder (PSUD) among suicidal adolescents, psychoactive substance intoxication at the moment of the attempt and the association between PSUD at baseline and either occurrence of suicide or repetition of suicide attempt(s). Methods: 186 adolescents aged 16 to 21 hospitalised for suicide attempt or overwhelming suicidal ideation were included (TO); 148 of them were traced again for evaluations after 6 months and/or 18 months. DSM-IV diagnoses were assessed each time using the Mini International Neuropsychiatric Interview. Results: At TO, 39.2% of the subjects were found to have a PSUD. Among them, a significantly higher proportion was intoxicated at the time of the attempt than those without PSUD (44-.3% vs. 25.4%). Among the 148 adolescents who could be traced at either Ti or T2, two died from suicide and 30 repeated suicide attempt once or more time. A marginally significant association was found between death by suicide/repetition of suicide attempt and alcohol abuse/dependence at baseline (0R=3.3; CI 0.7-15.0; 0R=2.6, CI 0.7-9.3). More than one suicide attempt before admission to hospital at TO (OR=3.2; CI 1.1-10.0) and age over 19 at TO (0R=3.2; CI 1.1-9.2) were independently associated with the likelihood of death by suicide or repetition of suicide attempt. Conclusion: Among adolescents hospitalised for suicide attempt or overwhelming suicidal ideation, the risk of death or repetition of attempt is high and is associated with previous suicide attempts - especially among older adolescents - and also marginally associated with PSUD; these adolescents should be carefully evaluated for such risks and followed up once discharged from the hospital.
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The dentate gyrus is one of only two regions of the mammalian brain where substantial neurogenesis occurs postnatally. However, detailed quantitative information about the postnatal structural maturation of the primate dentate gyrus is meager. We performed design-based, stereological studies of neuron number and size, and volume of the dentate gyrus layers in rhesus macaque monkeys (Macaca mulatta) of different postnatal ages. We found that about 40% of the total number of granule cells observed in mature 5-10-year-old macaque monkeys are added to the granule cell layer postnatally; 25% of these neurons are added within the first three postnatal months. Accordingly, cell proliferation and neurogenesis within the dentate gyrus peak within the first 3 months after birth and remain at an intermediate level between 3 months and at least 1 year of age. Although granule cell bodies undergo their largest increase in size during the first year of life, cell size and the volume of the three layers of the dentate gyrus (i.e. the molecular, granule cell and polymorphic layers) continue to increase beyond 1 year of age. Moreover, the different layers of the dentate gyrus exhibit distinct volumetric changes during postnatal development. Finally, we observe significant levels of cell proliferation, neurogenesis and cell death in the context of an overall stable number of granule cells in mature 5-10-year-old monkeys. These data identify an extended developmental period during which neurogenesis might be modulated to significantly impact the structure and function of the dentate gyrus in adulthood.
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The objective of this analysis was to evaluate mortality among a cohort of 24,865 capacitor-manufacturing workers exposed to polychlorinated biphenyls (PCBs) at plants in Indiana, Massachusetts, and New York and followed for mortality through 2008. Cumulative PCB exposure was estimated using plant-specific job-exposure matrices. External comparisons to US and state-specific populations used standardized mortality ratios, adjusted for gender, race, age and calendar year. Among long-term workers employed 3 months or longer, within-cohort comparisons used standardized rate ratios and multivariable Poisson regression modeling. Through 2008, more than one million person-years at risk and 8749 deaths were accrued. Among long-term employees, all-cause and all-cancer mortality were not elevated; of the a priori outcomes assessed only melanoma mortality was elevated. Mortality was elevated for some outcomes of a priori interest among subgroups of long-term workers: all cancer, intestinal cancer and amyotrophic lateral sclerosis (women); melanoma (men); melanoma and brain and nervous system cancer (Indiana plant); and melanoma and multiple myeloma (New York plant). Standardized rates of stomach and uterine cancer and multiple myeloma mortality increased with estimated cumulative PCB exposure. Poisson regression modeling showed significant associations with estimated cumulative PCB exposure for prostate and stomach cancer mortality. For other outcomes of a priori interest--rectal, liver, ovarian, breast, and thyroid cancer, non-Hodgkin lymphoma, Alzheimer disease, and Parkinson disease--neither elevated mortality nor positive associations with PCB exposure were observed. Associations between estimated cumulative PCB exposure and stomach, uterine, and prostate cancer and myeloma mortality confirmed our previous positive findings.
