Qualidade de vida de pacientes submetidos ao transplante cardíaco: aplicação da escala Whoqol-Bref

FUNDAMENTO: O sucesso do transplante cardíaco significa garantir a sobrevida dos pacientes com cardiopatia e permitir-lhes desenvolver suas atividades diárias. O transplante cardíaco apresenta-se como a primeira opção de tratamento na falência cardíaca, representando um aumento de sobrevida e qualidade de vida dos transplantados. OBJETIVO: Avaliar a qualidade de vida de pacientes submetidos ao transplante cardíaco através da aplicação de uma escala padronizada (Whoqol-Bref). MÉTODOS: Estudo exploratório descritivo de abordagem quantitativa, realizado com 55 pacientes submetidos ao transplante cardíaco, em um período entre o terceiro e o 103º mês, que realizam acompanhamento na Unidade de Transplante e Insuficiência Cardíaca em um Hospital de Referência em Cardiologia na cidade de Fortaleza, CE. Os dados foram coletados no período de fevereiro a abril de 2009, por meio da aplicação de um questionário padronizado pela Organização Mundial da Saúde e utilização de dados constantes nos prontuários. RESULTADOS: Com relação ao domínio físico, 62,8% e 58,3% dos pacientes, dos sexos masculino e feminino, respectivamente, estão satisfeitos. No domínio psicológico, dentre pacientes do sexo masculino, 65,1% apresentam satisfação quanto à qualidade de vida e, no sexo feminino, 58,3% encontram-se satisfeitas. No domínio das relações sociais, observou-se que, no sexo masculino, 53,5% estão muito satisfeitos, e apresentou-se um nível de satisfação de 100% no sexo feminino. No domínio do meio ambiente, 65,1% do sexo masculino encontram-se satisfeitos, e no sexo feminino, 83,3% estão satisfeitas. CONCLUSÃO: O transplante cardíaco teve bastante influência na qualidade de vida dos pacientes transplantados, pois os resultados mostram-se estatisticamente significantes no pós-transplante.

Proteína C-Reativa Incrementa o Valor Prognóstico do Escore GRACE em Síndromes Coronarianas Agudas?

Fundamento: O valor prognóstico incremental da dosagem plasmática de Proteína C-reativa (PCR) em relação ao Escore GRACE não está estabelecido em pacientes com síndromes coronarianas agudas sem supradesnivelamento do segmento ST (SCA). Objetivo: Testar a hipótese de que a medida de PCR na admissão incrementa o valor prognóstico do escore GRACE em pacientes com SCA. Métodos: Foram estudados 290 indivíduos, internados consecutivamente por SCA, os quais tiveram material plasmático colhido na admissão para dosagem de PCR por método de alta sensibilidade (nefelometria). Desfechos cardiovasculares durante hospitalização foram definidos pela combinação de óbito, infarto não fatal ou angina refratária não fatal. Resultados: A incidência de eventos cardiovasculares durante hospitalização foi 15% (18 óbitos, 11 infartos, 13 anginas), tendo a PCR apresentado estatística-C de 0,60 (95% IC = 0,51 - 0,70; p = 0,034) na predição desses desfechos. Após ajuste para o Escore GRACE, PCR elevada (definida pelo melhor ponto de corte) apresentou tendência a associação com eventos hospitalares (OR = 1,89; 95% IC = 0,92 - 3,88; p = 0,08). No entanto, a adição da variável PCR elevada no modelo GRACE não promoveu incremento significativo na estatística-C, a qual variou de 0,705 para 0,718 (p = 0,46). Da mesma forma, não houve reclassificação de risco significativa com a adição da PCR no modelo preditor (reclassificação líquida = 5,7%; p = 0,15). Conclusão Embora PCR possua associação com desfechos hospitalares, esse marcador inflamatório não incrementa o valor prognóstico do Escore GRACE.

Prognostic Value of TIMI Score versus GRACE Score in ST-segment Elevation Myocardial Infarction

Background: The TIMI Score for ST-segment elevation myocardial infarction (STEMI) was created and validated specifically for this clinical scenario, while the GRACE score is generic to any type of acute coronary syndrome. Objective: Between TIMI and GRACE scores, identify the one of better prognostic performance in patients with STEMI. Methods: We included 152 individuals consecutively admitted for STEMI. The TIMI and GRACE scores were tested for their discriminatory ability (C-statistics) and calibration (Hosmer-Lemeshow) in relation to hospital death. Results: The TIMI score showed equal distribution of patients in the ranges of low, intermediate and high risk (39 %, 27 % and 34 %, respectively), as opposed to the GRACE Score that showed predominant distribution at low risk (80 %, 13 % and 7%, respectively). Case-fatality was 11%. The C-statistics of the TIMI score was 0.87 (95%CI = 0.76 to 0.98), similar to GRACE (0.87, 95%CI = 0.75 to 0.99) - p = 0.71. The TIMI score showed satisfactory calibration represented by χ2 = 1.4 (p = 0.92), well above the calibration of the GRACE score, which showed χ2 = 14 (p = 0.08). This calibration is reflected in the expected incidence ranges for low, intermediate and high risk, according to the TIMI score (0 %, 4.9 % and 25 %, respectively), differently to GRACE (2.4%, 25% and 73%), which featured middle range incidence inappropriately. Conclusion: Although the scores show similar discriminatory capacity for hospital death, the TIMI score had better calibration than GRACE. These findings need to be validated populations of different risk profiles.

The Sanctified ‘Adultress’ and Her Circumstantial Clause: Bathsheba’s Bath and Self-Consecration in 2 Samuel 11

Bathsheba's actions in 2 Sam. 11.2-4 identify crucial aspects of her character. Past commentators interpret these words in connection with menstrual purification, stressing the certain paternity of David's adulterine child. This article demonstrates that the participles rōheset and mitqaddesšet and the noun mittum'ātāh do not denote menstrual cleansing. Bathsheba's washing is an innocent bath. She is the only individual human to self-sanctify, placing her in the company of the Israelite deity. The syntax of the verse necessitates that her action of self-sanctifying occurs simultaneously as David lies with her. The three focal terms highlight the important legitimacy of Bathsheba before the Israelite deity, her identity as a non-Israelite, her role as queen mother of the Solomonic line, and her full participation in the narrative.

Development of metabolic labeling strategies to study changes in protein expression

Résumé : Les progrès techniques de la spectrométrie de masse (MS) ont contribué au récent développement de la protéomique. Cette technique peut actuellement détecter, identifier et quantifier des milliers de protéines. Toutefois, elle n'est pas encore assez puissante pour fournir une analyse complète des modifications du protéome corrélées à des phénomènes biologiques. Notre objectif était le développement d'une nouvelle stratégie pour la détection spécifique et la quantification des variations du protéome, basée sur la mesure de la synthèse des protéines plutôt que sur celle de la quantité de protéines totale. Pour cela, nous volions associer le marquage pulsé des protéines par des isotopes stables avec une méthode d'acquisition MS basée sur le balayage des ions précurseurs (precursor ion scan, ou PIS), afin de détecter spécifiquement les protéines ayant intégré les isotopes et d'estimer leur abondance par rapport aux protéines non marquées. Une telle approche peut identifier les protéines avec les plus hauts taux de synthèse dans une période de temps donnée, y compris les protéines dont l'expression augmente spécifiquement suite à un événement précis. Nous avons tout d'abord testé différents acides aminés marqués en combinaison avec des méthodes PIS spécifiques. Ces essais ont permis la détection spécifique des protéines marquées. Cependant, en raison des limitations instrumentales du spectromètre de masse utilisé pour les méthodes PIS, la sensibilité de cette approche s'est révélée être inférieure à une analyse non ciblée réalisée sur un instrument plus récent (Chapitre 2.1). Toutefois, pour l'analyse différentielle de deux milieux de culture conditionnés par des cellules cancéreuses humaines, nous avons utilisé le marquage métabolique pour distinguer les protéines d'origine cellulaire des protéines non marquées du sérum présentes dans les milieux de culture (Chapitre 2.2). Parallèlement, nous avons développé une nouvelle méthode de quantification nommée IBIS, qui utilise des paires d'isotopes stables d'acides aminés capables de produire des ions spécifiques qui peuvent être utilisés pour la quantification relative. La méthode IBIS a été appliquée à l'analyse de deux lignées cellulaires cancéreuses complètement marquées, mais de manière différenciée, par des paires d'acides aminés (Chapitre 2.3). Ensuite, conformément à l'objectif initial de cette thèse, nous avons utilisé une variante pulsée de l'IBIS pour détecter des modifications du protéome dans des cellules HeLa infectée par le virus humain Herpes Simplex-1 (Chapitre 2.4). Ce virus réprime la synthèse des protéines des cellules hôtes afin d'exploiter leur mécanisme de traduction pour la production massive de virions. Comme prévu, de hauts taux de synthèse ont été mesurés pour les protéines virales détectées, attestant de leur haut niveau d'expression. Nous avons de plus identifié un certain nombre de protéines humaines dont le rapport de synthèse et de dégradation (S/D) a été modifié par l'infection virale, ce qui peut donner des indications sur les stratégies utilisées par les virus pour détourner la machinerie cellulaire. En conclusion, nous avons montré dans ce travail que le marquage métabolique peut être employé de façon non conventionnelle pour étudier des dimensions peu explorées en protéomique. Summary : In recent years major technical advancements greatly supported the development of mass spectrometry (MS)-based proteomics. Currently, this technique can efficiently detect, identify and quantify thousands of proteins. However, it is not yet sufficiently powerful to provide a comprehensive analysis of the proteome changes correlated with biological phenomena. The aim of our project was the development of ~a new strategy for the specific detection and quantification of proteomé variations based on measurements of protein synthesis rather than total protein amounts. The rationale for this approach was that changes in protein synthesis more closely reflect dynamic cellular responses than changes in total protein concentrations. Our starting idea was to couple "pulsed" stable-isotope labeling of proteins with a specific MS acquisition method based on precursor ion scan (PIS), to specifically detect proteins that incorporated the label and to simultaneously estimate their abundance, relative to the unlabeled protein isoform. Such approach could highlight proteins with the highest synthesis rate in a given time frame, including proteins specifically up-regulated by a given biological stimulus. As a first step, we tested different isotope-labeled amino acids in combination with dedicated PIS methods and showed that this leads to specific detection of labeled proteins. Sensitivity, however, turned out to be lower than an untargeted analysis run on a more recent instrument, due to MS hardware limitations (Chapter 2.1). We next used metabolic labeling to distinguish the proteins of cellular origin from a high background of unlabeled (serum) proteins, for the differential analysis of two serum-containing culture media conditioned by labeled human cancer cells (Chapter 2.2). As a parallel project we developed a new quantification method (named ISIS), which uses pairs of stable-isotope labeled amino acids able to produce specific reporter ions, which can be used for relative quantification. The ISIS method was applied to the analysis of two fully, yet differentially labeled cancer cell lines, as described in Chapter 2.3. Next, in line with the original purpose of this thesis, we used a "pulsed" variant of ISIS to detect proteome changes in HeLa cells after the infection with human Herpes Simplex Virus-1 (Chapter 2.4). This virus is known to repress the synthesis of host cell proteins to exploit the translation machinery for the massive production of virions. As expected, high synthesis rates were measured for the detected viral proteins, confirming their up-regulation. Moreover, we identified a number of human proteins whose synthesis/degradation ratio (S/D) was affected by the viral infection and which could provide clues on the strategies used by the virus to hijack the cellular machinery. Overall, in this work, we showed that metabolic labeling can be employed in alternative ways to investigate poorly explored dimensions in proteomics.

La concepció clàssica de la monarquia egípcia a partir de la documentació literària del Regne Mitjà i la seva pervivència en Època Grecorromana. El cas paradigmàtic d'Alexandre el Gran

Aquest estudi s’insereix en un projecte de tesi. L’estudi versa sobre l’ideal egipci de monarquia durant el Regne Mitjà, a partir de l’anàlisi directa de quatre fonts literàries del període. S’ha constatat que la concepció de monarquia resultant, concebuda com a clàssica o modèlica, és la que es transmet en essència fins a l’etapa final de la història antiga egípcia, encara que readaptant-se a les noves realitats polítiques i culturals. L’anàlisi d’aquest ideal teòric de monarquia ha estat fonamental per afrontar l’objectiu essencial del projecte de tesi: l’estudi de la legitimació d’Alexandre el Gran com a faraó d’Egipte, és a dir, l’examen en profunditat del conjunt de mecanismes mitjançant els quals el macedoni va assumir el rol clàssic dels monarques egipcis i que expliciten el procés segons el qual un nou sobirà, que a més era d’origen estranger, fou inserit en la ideologia faraònica tradicional. Per tal de determinar com això es va produir, es fa necessari l’estudi del període en què Alexandre és el titular del tron del país (332-323 aC), és a dir, del moment de gènesi, formulació i desenvolupament de l’entramat ideològic que proporcionarà base teològica al nou govern i l’adequarà a la tradició. Per a l’examen d’aquest període cronològic, la documentació egípcia s’erigeix com la principal font d’informació, i per tant, durant el projecte s’ha compilat i analitzat el conjunt de la documentació de procedència egípcia disponible fins al moment que, datada o no, s’adscriu cronològicament a aquest període.

On the association between HLA-A1 and B5 and clinical forms of schistosomiasis mansoni

The association between both HLA-A1 and B5 antigens and chronic forms of human schistosomiasis was studied in 64 patients and 26 normal controls from a southern Brazilian hospital. No apparent correlation between the chronic forms of the disease and the expression of those antigens was detected. However, the analysis of these date together with those observed on an Egyptian sample suggests that the presence of either of the antigens and the hepatomegalic forms of schistosomiasis is significant, without heterogeneity. Converseley, the association of histocompatibility antigens with splenogegaly is consistent and significant only for HLA-B5, but not HLA-A1

Microgeographical patterns of schistosomiasis and water contact behavior; examples from Africa and Brazil

This paper examines the results of spatial (microgeographical) water contact/schistosomiasis studies in two African (Egyptian and Kenyan) and one Brazilian communities. All three studies used traditional cartographic and statistical methods but one of them emploeyd also GIS (geographical information systems) tools. The advantage of GIS and their potential role in schistosomiasis control are briefly described. The three cases revealed considerable variation in the spatial distribution of water contact, transmission parameters and infection levels at the household and individual levels. All studies showed considerable variation in the prevalence and intensity of infection between households. They also show a variable influence of distance on water contact behavior associated with type of activity, age, sex, socioeconomic level, perception of water quality, season and availability of water in the home. Water contact behavior and schistosomiasis were evaluated in the Brazilian village of Nova União within the context of water sharing between household and age/sex groups. Recommendations are made for further spatial studies on the transmission and control of schistosomiasis.

Schistosomiasis vaccine development: progress and prospects

The undisputed, worldwide success of chemotherapy notwithstanding, schistosomiasis continues to defy control efforts in as much rapid reinfection demands repeated treatment, sometimes as often as once a year. There is thus a need for a complementary tool with effect for the longer term, notably a vaccine. International efforts in this direction have been ongoing for several decades but, until the recombinant DNA techniques were introduced, antigen production remained an unsurmountable bottleneck. Although animal experiments have been highly productive and are still much needed, they probably do not reflect the human situation adequately and real progress can not be expected until more is known about human immune responses to schistosome infection. It is well-known that irradiated cercariae consistently produce high levels of protection in experimental animals but, for various reasons, this proof of principle cannot be directly exploited. Research has instead been focussed on the identification and testing of specific schistosome antigens. This work has been quite successful and is already at the stage where clinical trials are called for. Preliminary results from coordinated in vitro laboratory and field epidemiological studies regarding the protective potential of several antigens support the initiation of such trials. A series of meetings, organized earlier this year in Cairo, Egypt, reviewed recent progress, selecteded suitable vaccine candidates and made firm recommendations for future action including pledging support for large-scale production according to good manufacturing practice (GMP) and Phase I trials. Scientists at the American Centers for Disease Control and Prevention (CDC) have drawn up a detailed research plan. The major financial support will come from USAID, Cairo, which has established a scientific advisory group of Egyptian scientists and representatives from current and previous international donors such as WHO, NIAID, the European Union and the Edna McConnell Clark Foundation.

Traducció i estudi de documents demòtics datats del regnat d'Alexandre el Gran (332-323 aC)

Projecte de recerca elaborat a partir d’una estada a l’Oriental Institute de la University of Oxford, Regne Unit, entre juliol i octubre de 2007. Durant l’estada s’ha analitzat la documentació demòtica datada del regnat d’Alexandre el Gran com a faraó d’Egipte (332-323 aC). El conjunt de fonts que examinat està constituït per sis papirs (actes notarials que recullen diversos tipus de contractes o acords entre dues parts), un òstrakon fragmentari i una sèrie d’esteles provinents de la Necròpolis d’Animals de Saqqara Nord, en concret de la Catacumba de les Mares d’Apis. Aquesta documentació és fonamental perquè permet extreure conclusions importants sobre diversos aspectes relacionats amb l’administració i la religiositat egípcies en els moments inicials de la dominació grega d'Egipte. Cadascun d’aquests documents ha estat traduït, analitzat en profunditat i degudament contextualitzat històricament. D’una banda, en l’àmbit de l’administració, he pogut constatar la continuïtat existent amb el període històric immediatament anterior, és a dir, amb la Segona Dominació Persa del país; mentre que de l'altra, des del punt de vista religiós, l’anàlisi d’aquestes fonts m’ha permès verificar l'existència de tota una sèrie de canvis substancials, estretament vinculats a la voluntat expressa de la nova elit dirigent d'origen grec de distanciar-se dels seus predecessors aquemènides i de marcar amb força l’obertura d’una nova era que es caracteritzarà pel respecte a les tradicions autòctones i per la potenciació dels cultes nacionals.

Fibrogenesis and collagen resorption in the heart and skeletal muscle of Calomys callosus experimentally infected with Trypanosoma cruzi: immunohistochemical identification of extracellular matrix components

Intense inflammatory lesions and early development of interstitial fibrosis of the myocardium and skeletal muscle with spontaneous regression, have been described in Calomys callosus infected with Trypanosoma cruzi. The genetic types of collagen present in this model were investigated through immunohistochemistry using specific antibodies, combined with histopathology and Picro-Sirius staining of collagen. Thirty-five calomys were infected with the Colombian strain of T. cruzi and sacrificed at 24, 30, 40, 60 and 90 days post-infection. Inflammatory lesions and fibrogenesis were prominent at the early phase of infection and significantly decreased during late infection. Immunoisotyping of the matrix components was performed by indirect immunofluorescence on 5 µm thick cryostat sections using specific antibodies against laminin, fibronectin and isotypes I, III and IV of collagen. In the early phase, positive deposits of all the matrix components were present, with predominance of fibronectin, laminin and collagens types I and III in the myocardium and of types III and IV in the skeletal muscles. From the 40th day, type IV collagen predominates in the heart. At the late phase of infection (60th to 90th day), a clear fragmentation and decrease of all the matrix components were detected. Findings of the present study indicate that a modulation of the inflammatory process occurs in the model of C. callosus, leading to spontaneous regression of fibrosis independent of the genetic types of collagen involved in this process.

Els déus xacals de l'antic egipte i el seu comportament xamànic : un estudi egiptològic i antropològic

El treball consta de dos apartats: una part egiptològica on s?estudia els deus xacals egipcis psicopomps i obridors de camins i els rituals religiosos que els envolten, per una banda, i una part antropològica on s?estudia el fenomen del xamanisme, per una altra, interrelacionant els trets bàsics i establint comparacions entre ambdós apartats.

First paleoparasitological study of an embalming rejects jar found in Saqqara, Egypt

For the first time, a jar of embalming rejects was studied in search for helminth parasite eggs. This kind of jar was used to put discarded material by Egyptian embalmers during mummification process. Ascaris lumbricoides and Tænia saginata eggs were found in the linen and strip fragment contents of the jar, dated of 2,715-2,656 years ago.

Infection of Calomys callosus (Rodentia Cricetidae) with strains of different Trypanosoma cruzi biodemes: pathogenicity, histotropism, and fibrosis induction

The influence of different Trypanosoma cruzi biodemes on the evolution of the infection and on the histopathological lesions of the heart and skeletal muscles, during the experimental infection of Calomys callosus, was investigated. Three groups of C. callosus were infected, respectively, with parasite strains representative of three different Biodemes: Type I (Y strain), Type II (21 SF strain), and Type III (Colombian strain). For each group, normal C. callosus were also used as controls. Marked differences have been detected in the responses of C. callosus to the infection with the three strains in this model. The strains Types I and II (Y and 21 SF) determined moderate lesions, mostly in the myocardium, with low parasitism, a rapid course, and total regression of the lesions by the 60th day of infection. Differently, Type III strain (Colombian), was more pathogenic for C. callosus and induced necrotic-inflammatory lesions in skeletal muscles and myocardium, in correspondence to intracellular parasitism. Proliferation of fibroblasts and amorphous matrix deposits, followed by interstitial fibrosis were present. Progressive regression of the inflammatory changes and collagen deposits occurred spontaneously. The progression and regression of both inflammation and fibrosis induced by the Colombian strain were further submitted to quantitative evaluation by morphometry. Results of the morphometric studies presented good correlation with the histopathological findings. The results confirm the importance of the different biodemes in the determination of tissue lesions and the peculiarities of response of C. callosus to infection with T. cruzi.